metal complexes of amino acids which form tridentate n ... · redox-active aromatic amino acids...

Metal complexes of amino acids which form tridentate

N-chelates

Metallkomplexe mit Dreizähnig Chelatisirenden

Aminosäuren

Den Naturwissenschaftlichen Fakultäten

der Friedrich-Alexander-Universität Erlangen-Nürnberg

zur Erlangung des Doktorgrades

Vorgelegt von

Slobodan Novokmet

aus Kragujevac, Serbien und Montenegro.

Als Dissertation genehmigt von den

Naturwissenschaftlichen Fakultäten der Universität

Erlangen-Nürnberg

Tag der mündlichen Prüfung: 22.12.2005

Vorsitzender der

Promotionskommission: Prof. Dr. D. –P. Häder

Erstberichtstatter: PD Dr. R. Alsfasser

Zweiteberichtstatter: Prof. Dr. Dr. h. c. R. van Eldik

Acknowledgements

This work was carried out from August 2002 until September 2005 at the Institute of

Inorganic Chemistry at the Friedrich–Alexander–University of Erlangen–Nürnberg

under supervision of PD Dr. Ralf Alsfasser to whom I would especially like to thank for

a very productive time in his group, his permanent interest in my work, and his financial

support during my work. Sincere thanks are given to my group co-workers Dipl. Chem.

Christian Schickaneder and Dr. Nicole Niklas for having a good time during the work in

the lab, useful discussions, and advices.

I would like to thank to Prof. Dr. Dr. h. c. Rudi van Eldik for his great support and the

possibility to finish my work in his group.

Special thanks are also given to: Dr. Frank Heinemann for x-ray analyses, Dr. Achim

Zahl for NMR measurements, Susanne Hoffmann for IR measurements, Christina

Wrona for elemental analyses, Dr. Jörg Sutter and Martin Bachmüller for mass

spectrometry measurements, Prof. Dr. Paul Müller and Sahabul Alam (Department of

Physics) for the STM measurements, the people from workshop of the Institute and

glassblower Mr. Zöbelein, for their excellent technical support. Dr. Jürgen Limmer, Dr.

Anton Neubrand, Dr. Carlos Dücker-Benfer, Dr. Ivana Ivanovic-Burmazovic, PD Dr.

Roland Meier, Ariane Brausam, David Sarauli, Hakan Ertürk, Joachim Maigut, Nadine

Summa, Patrick Witte, Peter Illner, Wolfgang Schiessel, Usrula Niegratschka (secretary

of the institute) for their continuous support during my work. Dr. Diana Utz and Dr.

Markus Weitzer for a wonderful time that we spent toghether on lunch-brakes. Prof. Dr.

Živadin Bugarčić (University of Kragujevac) for helping me to get the oportunity to

study in Germany.

City of Erlangen and Germany for hosting me and my family during my PhD studies.

Finally, I would like to thank my familly, wife Danijela and son Aleksa, that supported

me all of this PhD-time.

"Labor praebet quod natúra negat"

I dedicate this thesis to my wife Danijela and son Aleksa.

List of publications

1. Z. Bugarčić, S. Novokmet, Ž. Senić, Ž. Bugarčić, Chem. Mon., 2000, 131(7), 799-802.

2. S. Novokmet, V. Mujović, V. Jakovljević, D. Djurić, Perfusion, 2001, 2, 93-94.

3. Z. Bugarčić, S. Novokmet, V. Kostić, J. Serb. Chem. Soc., 2005, 70(5), 681-686.

4. S. Novokmet, S. Alam, V. Dremov, F. W. Heinemann, P. Müller, R. Alsfasser,

Angew. Chem. Int. Ed. Engl., 2005, 44, 803-806.

5. S. Novokmet, F. W. Heinemann, A. Zahl, R. Alsfasser, Inorg. Chem., 2005, 44(13), 4796-4805.

Conference contributions

1. Annual meeting of the German Atherosclerosis Society, 29.03.-31.03.2001, Blaubeuren, Germany.

2. Annual meeting of the German Chemical Society, 06.10–11.10. 2003, Munich,

Germany.

3. The 2004 Yonger European Chemists’ Conference, Short-talk, 25.08-29.08.2004, Torino, Italy.

4. Joint SFB Workshop, SFB 436, SFB 583, SFB 623, SFB 624, "Advances ion

Molecular Catalysis", 12-14.10.2004, Lauterbad (Schwarzwald), Germany.

5. SFB 583-Minisymposium, February 2005, Erlangen, Germany.

Table of Contents Chapter 1 1. General Introduction 11.1. Aromatic Interactions 11.1.2. π–π Interactions 2

1.1.3. Cation–π Interactions 2

1.1.4. Investigation of aromatic interactions in peptide model systems 31. 2. Coordination Polymers 41.3. Preliminary work done in our research group 61.3.1. Synthesis of peptide type metal complexes: chelating ligand + biomolecule- metal 61.3.2. Helical Coordination Polymers 71.3.3. pH dependent switch of peptidic amide group from oxygen to anionic nitrogen

coordination 81.4. Goals and tasks of this work 91.4.1. Dipeptide Ligands Containing the Amino Acid Dipicolylglycine (Dpg) 91.5. References and Notes 11 Chapter 2 2. The Deposition of Metallopeptide Based Coordination Polymers on Graphite

Substrates: Effects of Side Chain Functional Groups and Local Surface Structure 132.1. Introduction 132.2. Results and Discusion 142.3. Experimental Section 202.4. References and Notes 26 Chapter 3 27 3.

Aromatic Interactions in Unusual Backbone N-Coordinated Zinc Peptide Complexes: A Crystallographic and Spectroscopic Study 27

3.1. Introduction 273.2. Results and discussion 293.3. Conclusions 383.4. Experimental Section 393.4.1. General Methods 39

Table of Contents 3.4.2. Bromoacetylated Amino Acid Esters. 403.4.3. Ligands 433.4.4. [(Dpg-Xaa-OMe)(H2O)Zn](CF3SO3)2 45

3.4.5. Synthesis of [(Dpg-Xaa)-HZn] 47

3.4.6. X-ray crystallography 513.4.7. Apendix 553.5. References and Notes 57 Chapter 4 4.1. Synthesis of chiral quadridentate ligands derived from L-alanine and L-leucine 614.1.1. Bromoacetylated Amino Acid Esters 614.1.2. Ligands 624.2. Synthesis of chiral quadridentate ligands Dpg-Xaa – type 634.3. Synthesis of Zn(II) complexes using chiral quadridentate ligands Dpg-Ala-OMe

and Dpg-Leu-OMe 674.4. Synthesis of Zn(II)peptide based coordination polymer and N-anionic coordinated

monomer derived from leucine 704.5. Synthesis of Cu(II)peptide based coordination polymer derived from leucine 724.6. Synthesis of Ni(II)peptide based coordination dimer derived from phenylalanine 744.7. Synthesis of Cd(II), Co(II) and Mn(II) complexes using chiral quadridentate

ligand Dpg-Phe-OMe 765. Summary 816. Zusammenfassung 827. Curiculum Vitae 83

1

Chapter 1

1. General Introduction

1.1. Aromatic Interactions

Aromatic rings are important structural and functional elements both in biological and

in synthetic supramolecular architectures, and contribute to the intramolecular

stabilization of structures such as enzyme-substrate complexes. Aromatic interactions

play a key role in biomolecular recognition processes1 and protein aggregation. The

redox-active aromatic amino acids tyrosine and tryptophan are known to participate in

metalloenzyme-catalysed substrate oxidations. Recent results demonstrate their

importance for the activation of coordinated ligands.2 In model complexes, aromatic

rings are well known to form close contacts with metal centers in planar complexes.3

They can thereby significantly contribute to the stabilization of ternary amino acid

complexes. Depending on the nature of the rings, aromatic groups can interact in one of

several geometries. Those interactions are expected to be strong in water because of the

hydrophobic component of the interaction, and the interaction should be selective if the

electrostatic component is significant. Several geometries have been proposed on the

basis of the electrostatic component of the interaction (Figure 1).4

Figure 1. Geometries of aromatic interactions:

(a) edge-face; (b) offset stacked; (c) face-to-face stacked.

a b c

2

The edge-face geometry (Figure 1a), which can be considered a CH–π interaction, is

found in benzene in the solid state, and is commonly observed between aromatic

residues in proteins. The face-to-face stacked orientation (Figure 1b) is observed with

donor–acceptor pairs and compounds that have opposite quadrupole moments. The

offset stacked orientation (Figure 1c) represents the geometry of base stacking in DNA,

and is also found in proteins. Two types of aromatic interactions have been described

and characterized.

1.1.2. π–π Interactions

The interaction between two aromatic rings consists of van der Waals, hydrophobic and

electrostatic forces.5 Such aromatic–aromatic interactions, including the edge–face and

offset stacked geometries, are commonly observed in proteins. The interactions between

two aromatic rings may be intra- and intermolecular. π-π-Stacking between aromatic

rings is crucially involved in the stabilization of the double helical structure of DNA,

the packing of aromatic molecules in crystals, and the tertiary structures of proteins.6

1.1.3 Cation–π Interactions

The ion–quadrupole interaction between a positively charged group, such as an

ammonium or guanidinium group, and the electron-rich π-cloud of an aromatic ring,

represents the cation-π interaction.

Figure 2. Cation–π interaction

3

These interactions are important in proteins and in the binding of alkaline earth ions to

aromatic amino acid substituents.7 Cation–π interactions can stabilize the α-helix with a

small molecule that binds through a combination of cation–π interactions and salt

bridges.8 Aromatic interactions, including π–π, cation–π, aryl–sulfur, and carbohydrate–

π interactions, are important contributors to protein structure. The potential significance

of aromatic interactions in protein folding and structure was first discovered by Burley

and Petsko.9, 10 Recently, NH-π interactions became known as an important factor in

molecular recognition processes and the stabilization of molecular structures, e.g. in

metal complexes.11

1.1.4 Investigation of aromatic interactions in peptide model systems

Such investigation provides information about factors that contribute to protein

secondary structure and a context for studying noncovalent interactions in aqueous

solution. Noncovalent interactions have been investigated using NMR as a typical

method which provides information, such that folding can be investigated at each

position in the peptide. α-Protons, side-chain protons, and amide proton chemical shifts,

have been used with reference chemical shifts for the unfolded and fully folded states,

from which ∆Gfold can be determined.12 Structured peptides present excellent model

systems for the study of aromatic interactions. These studies can provide quantitative

information on the magnitude, role and the nature of aromatic interactions and how they

differ from hydrophobic interactions in biologically relevant systems. Utilizing aromatic

interactions in de novo protein design has recently been successfully. Despite their

importance and the multitude of characterized structures it remains a challenge to obtain

quantitative experimental data on the strength of aromatic interactions even in simple

systems. Most of the available data were obtained from theoretical calculations and

from gas phase measurements.13 Only a small number of metal complexes, mostly

copper(II), were investigated with respect to a quantitative description.14 This obvious

lack of experimental data is a stimulation to study aromatic interactions in metal

complexes with amino acid derived ligands.

4

1. 2. Coordination Polymers

In order to design helical coordination polymers, much effort has been devoted to the

preparation of helical coordination polymers with metals in the backbone by using

appropriately designed bridging ligands, with individual building blocks connected

through either coordinate bonds and hydrogen bonds, or both of them. To date, only a

few examples of chiral, nonracemic, helical coordination polymers have been reported

in which the chirality is induced by a stereogenic center, noncovalent, supramolecular

interactions (hydrogen bonds, π–π interactions).15 Coordination polymers exhibit a wide

range of infinite zero-dimensional (0D), one-dimensional (1D), two-dimensional (2D)

or three-dimensional (3D) frameworks16 with different interesting structural features,

resulting from coordinate bonding, hydrogen bonding, aromatic π–π stacking

interactions as well as van der Waals forces (Scheme 1). Aside from coordination

bonding interactions, relatively strong hydrogen bonding and π-π stacking interactions,

the solvent molecules, counterions and templates also influence the formation of the

ultimate architectures.17

Scheme 1. Topologies of some coordination polymers.

5

Coordination polymers built on molecular building-blocks hold great promise for

processability, flexibility, structural diversity, and geometrical (size, shape, and

symmetry) control. As such, supramolecular architectures assembled by coordinate

bonds and/or supramolecular interactions allow for more predictable control over

directional assemblies and packing arrangements in the solid state. In order to design

targets with different structural features and potential functions, an important step is the

selection and synthesis of structural units.18, 19 Different metal ions may exhibit different

coordination geometries.20 Monocarboyxlates and polycarboxylates play an important

role as bridging ligands, in the construction of coordination polymers.

The crystal engineering of coordination polymers and design strategies are now

producing molecular magnets, micro porous solids, heterogeneous catalysts and

materials that show NLO (non-linear optical) activity. Numerous factors involved,

include the solvent effects, guest molecules, counter ions and crystallizing

conditions.21,22

6

1.3. Preliminary work done in our research group

1.3.1. Synthesis of peptide type metal complexes: chelating ligand + biomolecule –

metal

Zn(II), Cu(II), and Ni(II) complexes were synthetised to evaluate the relevance of weak

aromatic interactions between a metal center and an amino acid side chain in square-

pyramidal or octahedral coordination enviroments.23,24 It was found that the

coordination geometry of complexes with amino acid derived ligands is a crucial

determinant for the occurrence of weak non-covalent interactions (Scheme 2). The

aromatic side chain conformation is “locked” in trigonal-bipyramidal Zn2+ complexes

(relatively short distance of 4.5 Å between the zinc ion and the center of the phenyl

ring), whereas it is "flexible" in square-pyramidal Cu2+ and “loose” in octahedral Zn2+

derivatives.25,26

Scheme 2. Aromatic interactions in trigonal-bipyramidal and no aromatic interactions

in octahedral zinc complexes and square-pyramidal copper complexes

Cu

N

N N

L

O

HN

OCH3

O

OZnN

N

H2O

N

HN

OCH3

O

"Locked"

Zn

N

L

OH2

N

N

O

HN

O

OCH3

"Loose"

7

1.3.2. Helical Coordination Polymers

An interesting observation was made when the methyl ester of the trigonal-bipyramidal

phenylalanine derivative shown in Scheme 4 was cleaved in aqueous solution at pH ca.

9. Those complexes turned out to be excellent starting materials for the synthesis of

chiral coordination polymers. The synthesis proceeds with basic ester cleavage of a

methyl ester function. Neutralization of the reaction mixture yielded the coordination

polymer (Scheme ).27 The compound has a homochiral, right-handed helical structure

with three zinc complex fragments per turn and a pitch of ca. 14 Å. Its formation is

reversible.

(S) O Zn

NN

OH2

N

HN

O

O

(S) (S) (S)

(S)

Zn

NN

N

OO

N

O

+pH 8- 2 H+

pH 6+ 2 H+

3+

n

O

Zn

NN

N

HNO

O

O

Zn

NN

N

HNO

O

O

Zn

NN

N

HNO

O

Precipitation DissolutionpH = 6 pH = 8

Scheme 3. Reversible Formation of Coordination Polymer

8

1.3.3. pH dependent switch of peptidic amide group from oxygen to anionic

nitrogen coordination

At high pH the coordination polymer (Scheme 4) redissolves and a complex is formed

which was proposed to contain the secondary amide linkage in an anionic N-bound

fashion. At the beginning of this work there was no proof for this mechanism. The

proposal was rather speculative since zinc(II) ions usually do not bind to the

deprotonated nitrogen atom of a peptide bond.28 No structural evidence for such a

coordination mode was ever observed in the literature. The compounds provide the first

example for a nitrogen bound zinc complex with a peptide ligand and prove the pH

dependent amide switching proposed in Scheme 4. The aromatic ring of the amino acid

side-chain and the parallel pyridine ring are ca. 3 Å apart. This is an indication of

stabilizing π-π -stacking interactions. 1H-NMR measurements provide a sensitive tool to

distinguish between O-coordinated and N-coordinated amide functions in zinc

complexes of our ligands.27 This is shown in Figure 3 for the phenylalanine derivative.

Most interesting is the significant high-field shift of the phenyl resonances in the

nitrogen bound pH 9 derivative. This is further evidence for π-π -stacking interactions

and indicates a solution structure (Figure 3).

Figure 3. 1H-NMR spectra of the [(Dpg-Phe)-HZn] in D2O;

top: pH = 9.00, bottom: pH = 4.00

(ppm)6.57.07.58.08.59.0

(ppm)2.53.03.54.04.5

6py4,4’,6’py

3,3’,5,5’py 2,6Ph 3,5Ph4Ph

αCH + py-CH2 py-CH2 C(O)-CH2

βCH +C(O)-CH2 2

6,6’py4,4’py

3,3’,5,5’py 3,5Ph2,4,6Ph

αCΗ

py-CH2

py-CH2

C(O)-CH2

βCΗ2

βCΗ2

9

1.4. Goals and tasks of this work

1.4.1. Dipeptide Ligands Containing the Amino Acid Dipicolylglycine (Dpg)

For comparative studies aimed at the quantitative evaluation of noncovalent

interactions, a series of quadridentate ligands derived from amino acids (biomolecule)

and the tridentate (chelating) ligand bpa (N,N-bispicolylamine) was synthesized. Their

synthesis followed an earlier described method23, with some small modifications. It is

schematically shown in Scheme 4.

NH

N

N R O

OR'NH

O

Br i-Pr2EtN / DMF or CH3CN

r.t., 12h

N

N N

HN

O

R

OR'O

+

R O

OR'H2N THF / Et3N

0°C - (-80°C), 4h+

R O

OR'NH

O

BrBr

O

Br

Scheme 4. Strategy for the synthesis of quadridentate amino acid ligands

Amino acids are versatile starting materials for the synthesis of bifunctional ligands.

Therefore dipicolylamine incorporated in the amino acid dipicolylglycine (Dpg) was

coupled with the following amino acid building blocks: glycine-methylester (1), L-

alanine-methylester (2), L-leucine-methylester (3), L-phenylalanine-methylester23 (4),

L-tyrosine-methylester (5), L-tryptophane-methylester (6), and 2-H-napththylalanine-

benzylester (7), to form the quadridentate tripodal dipeptide framework N3O -type

(Scheme 5).

10

Scheme 2. Newly synthesized quadridentate amino acid ligands

It would be interesting to apply other metals ions of the first or second transition series

such as Mn2+, Co2+, Cd2+ to see the adaptability of quadridentate N3O ligand depending

to a different metal center. However, only amide O-coordinated compounds have been

studied and no attempt has been made to remove the ester functions.

A well ordered array of aromatic rings is formed which consists of amino acid side

chains and the pyridine rings of the helix-backbone. Thus, a one-dimensional molecular

wire could result. Such systems are exceedingly rare and highly interesting as materials

for the design of nano-electronic devices. However, the derivatives prepared so far

cannot be attached to a surface in a sufficiently tight manner to allow for conductivity

measurements.

HN

N

O

O

O

H3C

N N

1

HN

N

O

O

O

H3C

N N

2

HN

N

O

O

O

H3C

N N

3

HN

N

O

O

O

N N

7

HN

N

O

O

O

H3C OH

N N

5

HN

N

O

O

O

H3C

NH

N N

6

HN

N

O

O

O

H3C

N N

4

11

1.5. References and Notes

1. K. Jitsukawa, A. Katoh, K. Funato, N. Ohata, Y. Funahashi, T. Ozawa and H.

Masuda, Inorg. Chem., 2003, 42, 6163-6155.

2. S. D. Zarić, D. M. Popović and E-W. Knapp, Chem. Eur. J., 2000, 6, 3953-3942.

3. Y. Shimazaki, T. Nogami, F. Tani, A. Odani and O. Yamauchi, Angew. Chem.

Int. Ed., 2001, 40, 3859-3862.

4. W. B. Jennings, B. M. Farrel, J. F. Malones, Acc. Chem. Res., 2001, 34, 885-

894.

5. M. L. Waters, Current Op. Chem. Biol, 2002, 6, 736–741.

6. C. A. Hunter and J. K. M. Sanders, J. Am. Chem. Soc., 1990, 112, 5525-5534

7. a) F. M. Siu, N. L. Ma and C. W. Tsang, J. Am. Chem. Soc., 2001, 123, 3397-

3398; b) J-F. Gal, P-C. Maria, M. Decouzon, O. Mó, M. Yáñez and L. M.

Abboud, J. Am. Chem. Soc., 2003, 125, 10394-10401; c) A. B. Koren, M. D.

Curtis, A. H. Francis and J. W. Kampf, J. Am. Chem. Soc., 2003, 125, 5040-

5050; d) C. D. Andrew; S. Bahattacharjee, N. Kokkoni, J. D. Hirst, G. R. Jones

and A. J. Doig, J. Am. Chem. Soc., 2002, 124, 12706-12714; e) G. B.

McGaughhey, M. Gagné and A. K. Rappé, J. Biol. Chem., 1998, 273, 15458-

15463; f) F. L. Gervasio, R. Chelli, P. Procacci and V. Schettino, PROTEINS:

Structure, Function, and Genetics, 2002, 48, 117-125; g) J. Hu, L. J. Barbour

and G. W. Gokel, PNAS, 2002, 99, 5121-5126; h) M. Nakano, S. Yamada, M.

Takahata and K. Yamaguchi, J. Phys. Chem. A, 2003, 107, 4157-4164.

8. J. C. Ma, D. A. Dougherty, Chem. Rev., 1997, 97, 1303.

9. Burley, S. K.; Petsko, G. A. Science, 1985, 229, 23–28.

10. Burley, S. K.; Petsko, G. A. Adv. Protein Chem., 1988, 39, 125–189.

11. H. Kumita, T. Kato, K. Jitsukawa, H. Einaga and H. Msauda, Inorg. Chem.,

2001, 40, 3936-3942.

12. M. L. Waters, Biopolymers (Peptide Science), 2004, 76, 435–445.

13. J. Sunner, K. Nishizawa, P. Kebarle, J. Phys. Chem., 1981, 85, 1814-1820

14. T. Yajima, M. Okajima, A. Odani, O. Yamauchi, Osamu, Inorg. Chim. Acta,

2002, 339, 445-454.

15. L. Han, M. Hong, Inorg. Chem. Comm., 2005, 8, 406–419.

12

16. A. Erxleben, Coord. Chem. Rev., 2003, 246, 203–228.

17. B-H. Ye, M-L, Tong, X-M. Chen, Coord. Chem. Rev., 2005, 249, 545–565.

18. T. Kaliyappan, P. Kannan, Prog. Polym. Sci., 2000, 25, 343–370.

19. N. R. Champness, M. Schröder, Current Op. Solid State Mat. Science, 1998, 3,

419-424.

20. B. Moulton, M. J. Zaworotko, Current Op. Sol. State Mat. Science, 2002, 6,

117–123.

21. Stuart R. Batten, Current Op. Solid State Mat. Science, 2001, 5, 107–114.

22. Jack Y. Lu, Coord. Chem. Rev., 2003, 246, 327–347.

23. N. Niklas, O. Walter and R. Alsfasser, Eur. J. Inorg. Chem., 2000, 8, 1723-

1731.

24. N. Niklas, S. Wolf, G. Liehr, C. E. Anson, A. K. Powell and R. Alsfasser, Inorg.

Chim. Acta, 2001, 314, 126-132

25. N. Niklas, O. Walter, F. Hampel and R. Alsfasser, J. Chem. Soc., Dalton Trans.,

2002, 17, 3367-3373.

26. N. Niklas, F. Hampel, O. Walter, G. Liehr and R. Alsfasser, Eur. J. Inorg.

Chem., 2002, 7, 1839-1847.

27. N. Niklas, F. Hampel and R. Alsfasser, Chem. Com., 2003, 1586-1587

28. H. Sigel, R. B. Martin, Chem. Rev., 1982, 82, 385-426.

13

Chapter 2

2. The Deposition of Metallopeptide Based Coordination

Polymers on Graphite Substrates: Effects of Side Chain

Functional Groups and Local Surface Structure

This work was published in Agewandte Chemie.

S. Novokmet, S. Alam, V. Dremov, F. W. Heinemann, P. Müller, R. Alsfasser, Angew.

Chem. Int. Ed. Engl., 2005, 44, 803 - 806.

2.1. Introduction

Coordination polymers have attracted much attention in the development of new

functional materials.1 This is due to the many interesting properties of metal-organic

coordination networks such as zeolitic behavior,2 conductivity,3 luminescence,4

magnetism,5 spin-crossover,6 and second harmonic generation (SHG).7 Stimulated by

possible applications impressive progress has been made in the so-called crystal

engineering of solid materials.8 Only at the beginning but equally important is the

controlled assembling of metal-organic polymers on solid surfaces.9 A central focus of

this research must be the investigation of elementary structure formation processes on

substrate surfaces. With a series of structurally similar polymers containing different

aromatic amino acid building blocks we were able to study both the effects of

substituents and local surface properties on the deposition of coordination polymers on

highly ordered pyrolytic graphite (HOPG).

14

2.2. Results and Discusion

(S)O Zn

NN

OH2

N

HN

O

O

(S) (S) (S)

2+

Polymer

3+

n

O

Zn

NN

N

HN

R

O

O

O

Zn

NN

N

HN

R

O

O

O

Zn

NN

N

HN

R

O

O

3 n(S)

O Zn

NN

OH2

N

HN

O

O

2+H3C

R'

3 n

1. NaOH (pH 9)2. HCl (pH 4)

H2, Pd/CCH3OH

R = Ph: 1; R = Ph-OH: 2; R = 2-Naphtyl: 3

R' = H: [(Dpg-Phe-OMe)(H2O)Zn]2+

R' = OH: [(Dpg-Tyr-OMe)(H2O)Zn]2+ [(Dpg-Nal-OMe)(H2O)Zn]2+

Scheme 1. Synthesis of the coordination homochiral helical coordination polymers 1-3

Scheme 1 illustrates our synthetic approach. Cleavage of the methylester or benzylester

protecting groups in zinc complexes of dipicolylglycyl (Dpg) peptides results in the

formation of a free carboxylate function, which binds to the metal ion under slightly

acidic conditions. The coordination polymers that form precipitate from aqueous

solutions. We have already reported on the synthesis and structure of [{Zn(Dpg-Phe-

O)}n](CF3SO3)n, (1; Phe = phenylalanine).10 Here we present two new compounds,

[{Zn(Dpg-Tyr-O)Zn}n](CF3SO3)n (Tyr = Tyrosine, 2) and ({[(Dpg-Nal-

O)Zn]n(CF3SO3)}n (Nal = 2-Naphthylalanine, 3). Ortep plots of structures are given in

Figures 1 and 2. The cationic polymers in 1-3 are very similar. In all cases right-handed

antiparallel-packed helices are found in which three zinc complex fragments make up

each turen. Only the pitch increases from 14.80 Å in 1 to 14.83 Å in 2 and 15.06 Å in 3,

most likely as a consequence of the larger aryl substituents.

15

Zn21

O21

O22

O23

Zn11

O32

O33

N21

N22N23

N24

N34

O24

Figure 1. left: Ortep plots (30 % ellipsoids) of the cationic repetition unit in [{Zn(Dpg-

Tyr-O)}n](CF3SO3)n (2); shown is the second complex in the trimeric asymmetric unit.

right: View along the 100 axis of the helical polymer

Zn21

O22

O23

Zn11

O32N21

N22N23

N24

N34

O33

O21

Figure 2. left: Ortep plots (30 % ellipsoids) of the cationic repetition unit in

{[(Dpg-Nal-O)Zn](CF3SO3)}n (3); shown is the second complex in the trimeric

asymmetric unit. right: View along the 100 axis of the helical polymer

16

The structural similarity or 1-3 was a desired feature since it enabled us to compare the

effects of different aromatic amino acid side chains on the deposition of helical

coordination polymers on HOPG by scanning tunneling microscopy (STM). It turned

out that the phenylalanine and napthylalanine derivatives 1 and 3 do not form

sufficiently stable patterns. Only the tyrosine derivative 2 gave satisfactory results. The

phenolic tyrosyl OH groups seem to be necessary for a sufficient grip on the substrate

surface. Samples of 2 on HOPG were conveniently prepared by allowing 10-9 M

aqueous solutions of pH 5 to 6 to evaporate under air. Figure 3 shows that the polymer

adopts two different structures depending on the local environment. A double-helical

plait is formed on undisturbed flat surface areas (Figure 3 a and b). The distance

between two crossing points is approximately 6 nm. Each of the two intertwined strands

has a diameter of roughly 13.8 Å indicating that it consists of a single helical

coordination polymer. Interestingly, the double-helical superstructure has a left-handed

chirality which is opposite to the right-handed molecular helicity. Double-helices are

most probably formed because a flat surface does not provide any means of stabilization

for the polymer and intermolecular interactions are dominant. However, the

macromolecules show a preference for steps which may be regarded as one-dimensional

distortions. Figure 3c shows that the polymer 2 nicely decorates a step and even follows

a sharp kink. The structure has changed drastically, presumably as a consequence of

stronger interactions with the distorted surface. Linearly stretched polymer strands are

formed. Single strands are not resolved in Figure 3c but the width of ca. 11 nm indicates

that roughly eight helices are packed together, most likely in the same antiparallel

fashion as it is observed in the crystal structure.

17

a)

b)

c)

Figure 3. STM topographies (HOPG) showing a) the formation of double-helical

superstructures on two different undisturbed surface areas (left: 108 x 108 nm2; right:

42 x 42 nm2); b) a 10 x 10 nm2 detail of a double-helix (left: 2D, right: 3D); c) the

aggregation of linear polymer strands at steps on the surface (left: 2D, right: 3D; 100 x

100 nm2)

18

In a few cases we were able to map single linear polymer strands with high

magnification (Fig. 4a). Again, the width of the structure conforms to the diameter of a

single molecular strand. Fig. 4b depicts a CITS image recorded simultaneously. CITS

(current imaging tunneling spectroscopy) records tunneling current-voltage

characteristics at every point of the topography map. The tip to sample distance is

defined by the topography parameters. CITS reveals a 3-dimensional data set of current

and bias voltage vs. position. Usually cross sections at some selected bias points are

plotted as current images. The current contrast changes significantly when at certain

bias values new molecular energy levels come into play thus enhancing the information

obtained from topography alone. Fig. 4b is a current image taken at a tunneling bias of

-135 mV. One clearly recognizes a periodicity along the strand which conforms to the

length of a single molecule (14.85 Å, see line in Fig. 4b).

a) b)

Figure 4. Topography and CITS image of a linear polymer strand recorded

simultaneously. The set point was: bias voltage = 72.9 mV and tunneling current = 0.2

nA. (a) Topography (5 x 5 nm2) (b) Current image (5 x 5 nm2) at -135 mV

As a control, we have prepared and investigated samples of the amino acid ligand alone

under similar conditions as the polymer solution. The structures formed are completely

different from those of the coordination polymer. Linear arrangements of single, or

multiple strands of molecules were observed. Helical topologies were not detected. For

these low concentrations the surface is rather empty. Effects resulting from the self

organization of dense molecular layers are certainly not to be expected.11

19

Scheme 2 summarizes our findings. On undisturbed surface areas two right-handed

homochiral helical coordination polymers self-assemble to form a left-handed double-

helical superstructure. In contrast, steps on the surface induce the formation of linearly

stretched helical single strands which aggregate to two dimensional ribbons. The latter

structure resembles a 2D slice through the 3D crystal structure of 2 indicating that

crystal growth starts at surface irregularities. These results shed first light on some

elementary steps during the pattern formation of metal-organic polymers on solid

substrate surfaces.

2D, step:Antiparallel aggregation

of linear strands

2D, undisturbed:Strands coil to double-helical

superstructure

3D:Antiparallel linear strands

SSSS

=

HelicalPolymer

LinearStrand=

Scheme 2. Structure formation processes in the coordination polymer 2. Linear strands

are built from helical chains. On undisturbed 2D surfaces these strands coil to form a

double-helical superstructure. Steps in the surface result in an antiparallel aggregation of

linear strands. Layers of such sheets build a 3D crystal

20

2.3. Experimental Section

[Zn(Dpg-Nal-OBn)(H2O)](CF3SO3)2 and [Zn(Dpg-Tyr-OCH3)(H2O)](CF3SO3)2

Solid Zn(CF3SO3)2 was added in one portion to a stirred solution of the respective

ligand in CH3CN. Stirring was continued overnight followed by removal of all solvent

under vacuum. Addition of CH2Cl2 resulted in the formation of a cloudy solution which

was left in a refrigerator at -20°C overnight in order to complete the precipitation of

unchanged Zn(CF3SO3)2. Filtration and removal of all solvent under vacuum yielded the

product as a white solid.

[Zn(Dpg-Tyr-OCH3)(H2O)](CF3SO3)2:1.56 g (4.30 mmol) Zn(CF3SO3)2, 1.87 g (4.30

mmol) Dpg-Nal-OBn, 100 ml CH3CN, 50 ml CH2Cl2. Yield: 2.80 g, 3.43 mmol, 79.80

% C,H,N,S-Analysis (%) calcd. for C26H28F6N4O11S2Zn (816.03 g/mol): C 38.27, H

3.46, N 6.87, S 7.86; found: C 39.26, H 3.59, N 6.66, S 7.63; FAB-MS (nitrobenzyl

alcohol): m/z = 649 [M+ − CF3SO3 − H2O]; 1H-NMR (300 MHz, CD3OD): δ (ppm) =

2.58 (dd, 1H, βCH2), 2.95 (dd, 1H, βCH2), 3.58 (s, 3H, OCH3), 3.61 (d, 1H, C(O)-CH2),

3.73 (d, 1H, C(O)-CH2), 4.39-4.54 (m, 5H, pyCH2, αCH), 6.50 (m, 2H, H2,6PhOH), 6.69

(m, H3,5PhOH), 7.66 (m, 4H, H3,5py), 8.13 (m, 2H, H4py), 8.54 (m, 1H, H5py), 8.60 (m,

1H, H6py). 13C NMR (75MHz, CD3OD): δ (ppm) = 35.20 (βC), 50.98 (OCH3), 57.85

(C(O)-CH2), 60.72 (αC), 60.80 (py-CH2), 114.25 (C2,6PhOH), 124.24, 124.39 (C3py),

124.68, 124.76 (C5py), 128.94, 128.97 (C3,5PhOH), 140.44, 140.45 (C4py), 146.57,

146,70 (C6py), 152.88, 153.09 (C2py), 155.41 (C4PhOH), 169.83 (C(O)amide), 171.77

(C(O)ester). IR (KBr) / cm-1 = 1746 νCOOCH3, 1635 νCONHR, 1286 νCF3SO3, 1244 νCF3SO3.

[Zn(Dpg-Nal-OBn)(H2O)](CF3SO3)2: 1.33 g (3.67 mmol) Zn(CF3SO3)2, 2.00 g (3.67

mmol) Dpg-Nal-OBn, 100 ml CH3CN, 100 ml CH2Cl2. Yield: 3.00 g, 3.24 mmol, 88.26

%. C,H,N,S-Analysis (%) calcd. for C36H34F6N4O10S2Zn (926.19 g/mol): C 46.68, H


alcohol): m/z = 757 [M+-CF3SO3-H2O]; 1H-NMR (300 MHz, CDCl3): δ (ppm) = 2.95

(m, 1H, βCH2), 3.24-3.37 (m, 6H, βCH2, C(O)CH2, n H2O), 3.53 (d, 1H, pyCH2), 3.75-

3.96 (m, 2H, pyCH2), 4.21 (d, 1H, pyCH2), 4.96-5.07 (m, 3H, αCH, OCH2Bn),

21

6.80-7.84 (m, 18H, 5 x HBn, 7 x Hnaphtyl, H3,4,5py), 8.50 (d, 1H, H6py), 8.70 (d, 1H,

H6py), 9.05 (d, 1H, 3JH,H = 8.62Hz, NH). 13C NMR (75MHz, CDCl3): 13C NMR

(75MHz, CDCl3): δ = 37.07 (βC), 54.17 (αC), 54.96 (C(O)CH2), 56.47 (pyCH2), 66.63

(OCH2Bn), 117.05, 121.27, 123.71 (C3,6,7naphtyl), 124.07, 124.94 (C3,5py), 127.24-

130.99 (C2,4,6,5benzyl), 131.96 (C10naphtyl), 132.25 (C9naphtyl), 133.80 (C2naphtyl), 140.35,

140.53 (C4py), 147.57, 147.86 (C6py), 152.39, 152.85 (C2py), 168.40 (C(O)amide),172.20

(C(O)ester). IR (KBr) / cm-1: 1748 νCOOBn, 1634νCONHR I, 1288 νCF3SO3, 1240 νCF3SO3.

[{Zn(Dpg-Tyr-O)}n](CF3SO3)n (2): [Zn(Dpg-Tyr-OCH3)(H2O)](CF3SO3)2 (1.00 g,

1.23 mmol) was dissolved in 30 ml H2O. The pH was adjusted to 9.00 with 1M NaOH.

Consumption of base was monitored using a pH meter and 1M NaOH was used to keep

the pH approximately constant at 9. The mixture was stirred at room temperature until

the pH remained constant (ca. 2d). Lowering the pH to 4 with 0.2 M HCl was followed

by the immediate precipitation of the product 2 . 3H2O which was collected on a

sintered glass filter funnel and dried under vacuum (0.50 g, 0.77 mmol, 62.35%).

C,H,N,S-Analysis (%) calcd. for (C24H23F3N4O7SZn)3 . 3H2O (1953.9 g/mol): C 44.22,

H 3.87, N 8.59, S 4.92; found: C 44.15, H 3.75, N 8.54, S 4.96; FAB-MS (nitrobenzyl

alcohol): m/z = 483 [M+– CF3SO3]; 1H-NMR (300 MHz, CD3OD): δ = 3.03 (dd, 1H, βCH2), 3.24 (dd, 1H, βCH2), 3.75 (s, 2H, C(O)CH2), 3.95-4.39 (m, 4H, pyCH2), 4.78 (m,

1H, αCH), 6.63 (m, 2H, H2,6PhOH), 7.11 (m, 2H, H3,5PhOH), 7.41-7.56 (m, 4H, H3,5py),

8.05 (m, 2H, H4py), 8.22 (s, br, 1H, 1 H6py), 8.81 (d, 1H, 3JH,H = 4.94Hz, H6py). 13C

NMR (75MHz, CD3OD): δ = 40.18 (βC), 59.92 C(O)CH2), 61.14 (αC), 61.67 (pyCH2),

118.14 (C2,6PhOH), 127.44-128.07 (C3,5py), 133.45 (C3,5PhOH), 144.11, 144.23 (C4py),

151.73, 152.39 (C6py), 157.42, 157.83 (C2py), 159.16 (C4PhOH), 175.98 (C(O)amide),

179.78 (C(O)carboxylate). IR (KBr) / cm-1: 1617νCOO-, 1257νCF3SO3.

[{Zn(Dpg-Nal-O)Zn}n](CF3SO3)n (3): [(Dpg-Nal-OBn)(H2O)Zn](CF3SO3)2 (1.68 g,

1.81 mmol) was dissolved in 150 ml absolute CH3OH. Palladium/charcoal was added as

a catalyst. Hydrogen was passed over the stirred solution for 6 h at 70°C. The mixture

was filtered through celite and the solvent removed by rotary evaporation. The product

3 . 4H2O was obtained as a white powder after washing the residual with diethyl ether

22

and drying under vacuum (1.15 g, 1.68 mmol, 92.62%). C,H,N,S-Analysis (%) calcd.

for (C28H25F3N4O6SZn)3 . 4 H2O (2003.91 g/mol): C 48.60, H 4.03, N 8.10, S 4.63;

found: C 48.67, H 3.96, N 8.14, S 4.48; FAB-MS (nitrobenzyl alcohol): m/z = 667 [M+],

517 [M+−CF3SO3]; 1H-NMR (300 MHz, CD3CN): δ = 3.00 (dd, 1H, βCH2), 3.36-3.68

(m, 4H, βCH2, C(O)CH2, pyCH2), 3.95-4.23 (m, 3H, pyCH2), 4.92 (m, 1H, αCH), 7.27-

7.69 (m, 11H, Hnaphtyl, H3,5py), 7.96 (m, 1H, H4py), 8.05 (m, 1H, H4py), 8.22 (d, 1H, 3JH,H = 8.60Hz, NH), 8.38 (d, 1H, H6py), 8.60 (d, 1H, H6py). 13C NMR (75MHz,

CD3CN): δ = 37.25 (βC), 54.49 (αC), 56.12 C(O)CH2), 57.61, 57.70 (pyCH2), 124.62,

124.75 (C3naphtyl), 125.11, 125.17 (C6naphtyl), 125.67 (C7naphtyl), 125.93 (C3py), 126.90

(C5py), 127.15, 127,24, 127.33, 127,81 (C1,4,8,10naphtyl), 131.74 (C9naphtyl), 132.72

(C2naphtyl), 133.52, 141.50 (C4py), 147.42, 147.56 (C6py), 153.26, 153.96 (C2py), 169.61

(C(O)amide), 173.10 (C(O)carboxylate). IR (KBr) / cm-1: 1632 νCOO-, 1245 νCF3SO3.

X-ray structure analyses. Colorless needles of [{Zn(Dpg-Tyr-O)n}](CF3SO3)n.8.5

CH3OH.H2O (2) were obtained after slow diffusion of diethylether into a CH3OH

solution of the product over a period of several weeks at room temperature. Colorless

crystals of [{Zn(Dpg-Nal-O)n](CF3SO3)n.2.5CH3OH (3) were obtained after slow

diffusion of diethyl ether into a methanol solution of the product over a period of

several weeks at room temperature. Suitable single crystals were embedded in

protective perfluoropolyether oil and data were collected at 100 K on a Bruker-Nonius

KappaCCD diffractometer using MoKα radiation (λ = 0.71073 Å, graphite

monochromator). Images were taken using φ - and ω-rotations with a rotation angle of

1.0° for 2 and 1.4° for 3 and an irradiation time of 100 s per frame for 2 and 210 s per

frame for 3, respectively.Lorentz, polarization, and semiempirical absorption

corrections (SADABS on the basis of multiple scans) were applied. The structures were

solved by direct methods and refined using full-matrix least-squares procedures on F2

(SHELXTL NT 6.12). All non-hydrogen atoms were refined anisotropically (with the

exception of some disordered CH3OH molecules in 3 that were refined isotropically).

All hydrogen atoms were geometrically positioned with isotropic displacement

parameters being 1.2 or 1.5 times U(eq) of the corresponding C, N or O atom.

Compound 2 crystallizes with 8.5 molecules CH3OH and one H2O per formula unit.

Some of the CH3OH molecules in 2 are disordered and have been refined using

23

similarity restraints. Compound 3 crystallizes with 2.5 molecules CH3OH per formula

unit. These solvate molecules and two of the CF3SO3 anions of 3 are subjected to

disorder and were refined using a number of restraints. Selected crystallographic data

for 2: C80.5H108F9N12O30.5S3Zn3; orthorhombic P212121 (no. 19), a = 14.834(2), b =

22.470(4), c = 29.320(4) Å; Z = 4; V = 9773(3) Å3; ρcalcd = 1.492 g cm-3, µ = 0.895 mm-

1, Tmin = 0.743, Tmax = 1.000, 51406 measured reflections (7.1° ≤ 2θ ≤ 51.4°), 16501

unique reflections, 9940 observed reflections [I > 2σ(I)], 1312 parameters, wR2 =

0.1727 (all data), R1 = 0.0764 [I > 2σ(I)]. Selected crystallographic data for 3:

C86.5H85F9N12O20.5S3Zn3; monoclinic P21 (no.4), a = 15.065(2), b = 13.053(2), c =

24.108(2) Å, β = 93.30(1)°, Z = 2; V = 4732.8(9) Å3; ρcalcd = 1.462 g cm-3, µ = 0.912

mm-1, Tmin = 0.804, Tmax = 1.000, 105250 measured reflections (6.4° ≤ 2θ ≤ 54.0°),

20414 unique reflections, 14676 observed reflections [I > 2σ(I)], 1305 parameters, wR2

= 0.1627 (all data), R1 = 0.0598 [I > 2σ(I)]. CCDC 243711 (2) and CCDC 243712 (3)

contain the supplementary crystallographic data for this paper. These data can be

obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the

Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK,

fax: (+44)1223-336-033; or [email protected]).

STM measurements. The STM imaging was carried out under ambient conditions

using a home built, low drift microscope equipped with RHK1000 control electronics or

with a commercial Nanoscope III system. A drop of 10-9 M aqueous solution was placed

onto a freshly cleaved HOPG surface. Sections without molecules clearly showed

monoatomic resolution of the graphite structure. Typically, tunneling currents between

10 and 200 pA were employed. The bias voltage was ± 72.9 mV. The scan frequency

was varied between 2 to 5 Hz. Resolution was 256x256 points for topography, and

128x128 in the CITS measurements. In most cases, Pt/10% Ir tips were used.

24

Synthesis of the coordination homochiral helical coordination polymer

[{Zn(Dpg-Trp-O)}n](CF3SO3)n and cyclic tetramer [{Zn(Dpg-Gly-

O)}4](CF3SO3)4

The synthesis followed general method listed above. These data has not been published

because the single crystals of [{Zn(Dpg-Trp-O)}n](CF3SO3)n were not x-ray suitable,

and of cyclic tetramer [{Zn(Dpg-Gly-O)}4](CF3SO3)4 x-ray data were poor of quality

(Figure 5).

[{Zn(Dpg-Trp-O)}n](CF3SO3)n: 1.00g (1.19 mmol) of [Zn(Dpg-Trp-

OCH3)(H2O)Zn]OTf)2, 30 ml H2O. Yield: (0.60 g, 0.89 mmol, 74.70%). C,H,N,S-

analysis calcd. (%) for (C26H24F3N5O6SZn)3⋅3H2O (M = 2024.88 g/mol): C 46.27, H


alcohol): m/z = 674 [M+], 542 [M+ − CF3SO3], 506 [M+ − CF3SO3 − H2O]. 1H NMR

(300MHz, D2O/DCl; pH = 4.00): δ = 2.91 (m, 1H, βCH2), 3.40 (m, 4H, βCH2,

C(O)CH2), pyCH2), 4.03 (d,d, 2H, pyCH2), 4.22 (d, 1H, pyCH2), 4.69 (αCH), 7.05 (m,

4H, H4,5,6,7Indolyl), 7.46 (m, 5H, H3,5py, H1Indolyl), 7.99 (m, 2H, H4py), 8.39 – 8.59 (2xd,

2H, 3JH,H = 4.89Hz, H6py). 13C NMR (75MHz, D2O/DCl): δ = 28.28 (βC), 56.93 (αC),

57.27 (C(O)CH2), 59.00 (pyCH2), 110.39 (C1Indolyl), 112.00 (C4Indolyl), 118.53 (C5Indolyl),

119.37 (C7Indolyl), 122.01 (C6Indolyl), 124.45 (C2Indolyl), 124.81 (C5py), 124.97, 125.39

(C3py), 127.06 (C8Indolyl), 136.03 (C9Indolyl), 144.45, 141.52 (C4py), 147.83, 148.03

(C6py), 153.66, 154.05 (C2py), 172.26 (C(O)amide), (C(O)carboxylate). IR (KBr) / cm-1:

1622νCOO-, 1258νCF3SO3.

25

[{Zn(Dpg-Gly-O)}4](CF3SO3)4: 1.66g (2.40mmol) of [Zn(Dpg-Gly-

OCH3Me)(H2O)](OTf)2, 50ml of H2O. (1.00 g, 1.83 mmol, 76.34%). C,H,N,S-Analysis

(%) calcd. for (C17H17F3N4O6SZn)4 . 2 NaCF3SO3 (2455.28 g/mol): C 34.24, H 2.79, N

9.13, S 7.84; found: C 33.86, H 2.91, N 8.89, S 7.39; FAB-MS (nitrobenzyl alcohol):

m/z = 377 [M+−CF3SO3]; 1H NMR (300MHz, D2O/DCl; pH = 4.00): δ = 3.74 (s, br, 2H,

C(O)CH2), 3.82 (s, br, 2H, αCH2), 4.42 (m, 4H, pyCH2), 7.58 (m, 4H, H3,5py), 8.06 (m,

2H, H4py), 8.66 (d, 2H, 3JH,H = 5.12 Hz, H6py). 13C NMR (75MHz, D2O/DCl): δ =

46.60 (αC), 59.67 (C(O)CH2), 61.55 (pyCH2), 127.47 (C5py), 127.93 (C3py), 144.13

(C4py), 150.65 (C6py), 156.61 (C2py), 175.92 (C(O)amide), 178.18 (C(O) carboxylate). IR

(KBr) / cm-1: 1613νCOO-, 1265νCF3SO3.

Figure 5. Structural asignment for [{Zn(Dpg-Gly-O)}4](CF3SO3)4

26


1. C. Janiak, Dalton Trans. 2003, 2781.

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H. Zhang, R.-Q. Sun, Inorg. Chem. 2002, 41, 1391; b) C. Seward, W.-L. Jia, R.-

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27

Chapter 3

3. Aromatic Interactions in Unusual Backbone N-Coordinated

Zinc Peptide Complexes: A Crystallographic and

Spectroscopic Study

This work was published in Inorganic Chemistry.

S. Novokmet, F. W. Heinemann, A. Zahl, R. Alsfasser, Inorg. Chem., 2005, 13, 4796-

4805

3.1. Introduction

Weak non-covalent aromatic interactions are ubiquitous in biological systems as well as

in synthetic supramolecular compounds.1 In their classical papers Burley and Petsko

have shown that aromatic amino acid side chains help stabilizing protein structures by a

calculated free enthalpy change of ca. -4.2 to -8.4 kJ/mol.2 Much higher stacking

energies of more than -40 kJ/mol have been measured between porphyrin rings.3 The

large variation between different π-systems, and the difficulty to assess the importance

of electrostatic contributions and hydrophobic effects shows that a classification based

on experimental data is desirable.4 However, a single aromatic interaction is difficult to

study, in particular when amino acids are concerned. The energy is usually small and in

most cases obscured by other effects. One possible method to obtain quantitative data is

to compare chemically related species which allow the isolation of a single contribution

in a thermodynamic cycle.5

28

This applies not only to organic compounds but also to metal complexes with aromatic

substituents.6 Such compounds are interesting, for example, because of their relevance

for the structures and functions of metalloproteins7 or their potential for the chiral

discrimination between L and D amino acids.8 However, most probably due to their

kinetic lability only a few papers have dealt with a quantitative determination of

aromatic interactions in metal amino acid complexes. Yamauchi and co-workers have

used the formation constants of ternary amino acid complexes to calculate free enthalpy

changes of -3.6 to -7.9 kJ/mol in copper(II),9 and -2.1 to -9.7 kJ/mol in palladium(II)10

species. The methodology followed earlier papers by Sigel et al., who have reported

∆∆log K values as measures for aromatic interactions in ternary copper(II) complexes

and zinc(II) complexes but stated that calculated differences between stability constants

are rather inaccurate.11 Fabbrizzi et al., have used a fluorescent anthracene substituted

zinc complex as a sensor for phenylalanine and tryptophan.12 Titration experiments

were performed to obtain anthracene–phenyl and anthracene–indolyl interaction

energies of –8 and –7 kJ/mol, respectively. To the best of our knowledge, there is no

report on quantitative data for structurally characterized coordination complexes.

Here, we present the first examples as a part of our work on zinc(II) complexes with

bioinorganic hybrid ligands containing a dipicolylamine unit in a dipeptide

framework.13 Intramolecular aromatic interactions between a pyridine ligand and an

aromatic amino acid side chain are shown to promote the deprotonation and

coordination of a peptide nitrogen atom. This is unprecedented for zinc peptide

complexes and was confirmed by X-ray crystallography. Acidification and protonation

triggers carbonyl oxygen coordination which is accompanied by a structural re-

organization with complete loss of π stacking in aqueous solution. NMR–pH-titration

experiments afforded pKa values, which were used to calculate the free enthalpy

changes brought about by aromatic interactions involving different amino acid side

chains.

29

3.2. Results and discussion

Synthesis of N-Coordinated Zinc Peptide Complexes. Scheme 1 shows the

compounds investigated.

O Zn

NN

OH2

N

HN

(S)

O

O

2+

O Zn

NN

OH2

N

HN

(S)

R

O

O

2+H3C

NaOH (pH 9)1. H2/Pd/CH3OH2. NaOH (pH 9)

1: R = H: [(Dpg-Gly-OMe)(H2O)Zn]2+

2: R = C6H5: [(Dpg-Phe-OMe)(H2O)Zn]2+

3: R = C6H4OH: [(Dpg-Tyr-OMe)(H2O)Zn]2+

4: R = indolyl: [(Dpg-Trp-OMe)(H2O)Zn]2+

5: [(Dpg-Nal-OBz)(H2O)Zn]2+

N Zn

NN

O

N(S)

O

RH

6: [(Dpg-Gly)-HZn] 7: [(Dpg-Phe)-HZn] 8: [(Dpg-Tyr)-HZn] 9: [(Dpg-Trp)-HZn]

10: [(Dpg-Nal)-HZn]

O

Scheme 1. Synthesis of the N-coordinated zinc peptide complexes 6-10

Starting materials were zinc complexes of dipeptide ester ligands containing the

chelating amino acid dipicolylglycine (Dpg). Their synthesis followed our earlier report

on the glycine ethyl ester complex [(Dpg-Gly-OEt)(H2O)Zn]2+ (1') and the

phenylalanine methyl ester complex [(Dpg-Phe-OMe)(H2O)Zn]2+ (2).13 To compare

effects of different aromatic side chains the tyrosine methyl ester (3), tryptophan methyl

ester (4), and 2-naphtylalanine benzyl ester (5) derivatives were prepared.

30

To apply the complexes in peptide coupling reactions, we removed the methyl ester

functions in 1-4 under basic conditions at pH 9. Surprisingly, this resulted not only in

the coordination of the free carboxylate function but also in the deprotonation and

coordination of the amide nitrogen atom. The electrically neutral distorted trigonal-

bipyramidal complexes 6-9 were formed (see Scheme 2). For [(Dpg-Phe)-HZn] (7)

[(Dpg-Tyr)-HZn] (8) and [(Dpg-Trp)-HZn] (9) single crystals were grown and the

structures confirmed by X-ray diffraction. The benzyl ester function in 5 was removed

by catalytic hydrogenation in methanol. The complex [(Dpg-Nal)-HZn] (10) formed

after dissolving the product in aqueous NaOH at pH 9. It was also characterized by X-

ray structure analysis.

N Zn

NN

O

N(S)

O

RH

+ H+

- H+O Zn

NN

N

HN(S)

R H

O

O

L

6a: [(Dpg-Gly)(L)Zn] 7a: [(Dpg-Phe)(L)Zn] 8a: [(Dpg-Tyr)(L)Zn] 9a: [(Dpg-Trp)(L)Zn]

10a: [(Dpg-Nal)(L)Zn]

L = H2O or Carboxylate6: [(Dpg-Gly)-HZn] 7: [(Dpg-Phe)-HZn] 8: [(Dpg-Tyr)-HZn] 9: [(Dpg-Trp)-HZn]

10: [(Dpg-Nal)-HZn]

+

O

Scheme 2. pH-Dependent equilibrium between N-coordinated and O-coordinated

complexes

Protonation of the amide function in 6-10 with hydrochloric acid triggers a

rearrangement of the dipeptide ligand which now binds via its carbonyl oxygen atom

(6a-10a). This reaction is interesting because coordination of the free carboxylate

function in 7a-10a resulted in the precipitation of a new class of homochiral, right-

handed helical coordination polymers.14 We have studied their aggregation on graphite

substrates by STM in order to characterize effects of amino acid side chains and the

local surface environment on structure formation processes.15 The glycine 6a derivative

does not polymerize but forms the cyclic tetramer [{(Dpg-Gly-O)Zn}]4(CF3SO3)4.16 The

pH-dependent switching of the amide group coordination mode is fully reversible in all

31

cases and can be conveniently monitored by 1H-NMR spectroscopy. Following a

description of the crystal structures of 8-10 we will discuss how this property was used

for a quantitative evaluation of aromatic interaction energies.

It should be noted that the nitrogen coordinated complexes 6-10 are most conveniently

synthesized by treating the solid polymers with aqueous NaOH at pH 9 (see

Experimental Section). The latter are easy to purify from all organic materials which is

important for the quality of the NMR studies described below. However, fast atom

bombardment (FAB) mass spectrometry and IR spectroscopy showed that the so

obtained materials always contained variable amounts of Na(CF3SO3), which could not

be removed. Because this did not influence the relevant properties of the compounds, all

experiments including crystallization were performed with these samples. The

tryptophan derivative 9, which was the most difficult to purify, was also synthesized

using an alternative route starting from ZnCl2. The method is described in the

Experimental Section. Although the samples yielded better elemental analysis data, they

always contained 2 equivs of methanol that could not be removed by extended drying

under a vacuum and affected the interpretation of NMR spectra in the aliphatic region.

Structures. Before we discuss the key feature, the anionic nitrogen coordination of the

peptide backbone, it is useful to look at some general properties. Crystallographic

details are summarized in Table 1 and a comparison of selected structural parameters is

given in Table 2. Ortep plots of the complexes 8-10 are shown in Figure 1.

The coordination mode of the tridentate dipicolylamine moiety is typical for zinc

complexes of this ligand fragment.17 However, the compounds 7, 8 and 10 do not

crystallize as mononuclear complexes. Figure 2 shows that they form distinctly different

coordination polymers. In the phenylalanine and tyrosine derivatives 7 and 8 infinite

chains are built by bridging of the two carboxylate oxygen donors. The zinc(II) center is

therefore 6-coordinate which causes larger N2-Zn-N3 angles of 128.9° in 7 and 144.8°

in 8 compared with 114.0° in 9 and 103.7° in 10. A slight elongation of all zinc to

ligand distances is also observed. The naphtylalanine derivative 10 co-crystallizes with

1 equivalent of sodium triflate. The amide oxygen atom O1, as well as both carboxylate

oxygen donors O2 and O3 bind to Na+. A triflato ligand completes the distorted

tetrahedral coordination sphere which contains four different oxygen donor ligands.

32

8

O1

N4

N1

N2N3

ZnO2

O3

N5

9

O1

N4

ZnN1

N3N2

O2

O3

10

ZnN3

N2

N1

N4

O1

O2

O3

O4

7

Zn

N3

N2

N1

N4

O1

O2

O3

Figure 1. ORTEP representations (30 % ellipsoids) of the complexes 7-10

(hydrogen atoms omitted for clarity)

Interestingly, only the (R)-isomer is observed. The result is a band-type structure with a

sodium triflate central part connecting two rows of 10. The bridging function of sodium

ions in coordination polymers is not unknown,18 although we are not aware of any other

example with a chiral coordination sphere around Na+.

Unprecedented in structurally characterized zinc peptide complexes is the coordination

of a deprotonated dipeptide nitrogen atom to zinc(II). Only a few related examples for

zinc complexes with anionic carboxamide nitrogen ligands have been reported. The

closest is a bleomycine model by Goto et al., which resembles an Xaa-His complex.19

Kimura et al., have applied the macrocyclic effect in a pyridine substitute cyclam amide

derivative to support the amide nitrogen coordination.20 Interestingly, the Zn-Namide

distances in both compounds are ca. 2.10 Å.

33

This is significantly longer than in our dipeptide complexes which have zinc nitrogen

contacts of 1.94-2.04 Å. A comparable value of 1.97 Å has been reported by the Kimura

group for a complex containing a relatively acidic nitrophenylamide moiety tethered to

a cyclen ligand.21

{ . Na(CF SO )}10 3 3 ∞

Na

SO11

O2

O1 O3’Zn

{ }8 ∞

ZnO3’’

O2’’O2

O3 O3’O2’Zn’

Triflate

Figure 2. (top) Structure of {8}∞ illustrates how bridging of the carboxylate function

between two zinc ions in 7 and 8 results in formation of coordination polymers.

(bottom) A polymer containing (R)-configurated distorted tetrahedral sodium atoms is

formed when Na(CF3SO3) is coordinated by the amide and the two carboxylate oxygen

atoms of 10.

Peptide backbone coordination involving one or more deprotonated amide nitrogen

donors has recently attracted much attention due to its role in the copper(II) binding

sites of prion and Alzheimer proteins.22

34

It also appears in the N-terminal nickel(II) and copper(II) binding ATCUN motif of

proteins such as serum albumin.23 That zinc(II) ions usually do not promote the

deprotonation of peptide backbone nitrogen atoms is a long-accepted concept in

metallopeptide chemistry.24 The only exceptions are dipeptides of the type Xaa-His,

were Xaa is a variable amino acid.25 Interestingly, histidine may be replaced by

bis(pyridine-2-yl)methylamine.26 However, the heterocyclic amine donor must be at the

C-terminus because of the more favorable chelate ring.24 No deprotonation is observed

when the oder of the peptide sequence changes. Thus, our compounds are unique not

only because they are the first crystalline zinc(II) peptide complexes with an anionic

backbone nitrogen donor but also because the heterocyclic amine ligand is not at the C

terminus but instead at the N terminus. Their unexpected stability is, in part, certainly

due to the coordinarting carboxylate function and the concurent formation of five-

membered chelate ring. However, a more interesting stabilizing factor is the observed

stacking of the aromatic amino acid side chain with one of the pyridine ligands. The

average distances between the aromatic planes are 3.7 Å in 7, 3.4 Å in 8 and 9, and 3.2

Å in 10. To test the relevance noncovalent interactions, we determined the pKa values

for the amide deprotonation in 6–10. The glycine derivative 6 does not contain a side

chain functional group but has a potentially coordinating terminal carboxylate function.

It therefore provides a standard which that enables us to single out the contribution of

aromatic interactions to the stabilization of 7–10.

1H-NMR spectra in D2O and the Determination of pKa values. A convenient way to

perform pH-titration experiments with our complexes is by NMR-spectroscopy in D2O.

In an earlier report on the formation of a helical coordination polymer from 7a we have

shown that the spectra at high and low pH* are distinctly different (pH* = pH-meter

reading in D2O solution without correction).14 They are assignable to the amide N- and

O-coordinated species, respectively. Figure 3 shows the spectra of the glycine

derivatives 6/6a (Figure 3a) and the phenylalanine derivatives 7/7b (Figure 3b).

35

(ppm)0.01.02.03.04.05.06.07.08.0

pH* 11

pH* 5

C

βCH2 + A

C + B

βCH2

2.53.03.54.0(ppm)

6.07.08.0

4Ph

3.5Ph2,6Ph

2,4,6Ph3.5Ph

6py

6,6‘py 4,4‘py

6‘py +4,4‘py

A

B

A = C(O)-CH2

B = py-CH2

C = αCH2

C

C A + B

pH* 9

pH* 4

a)

b)

B A

AB

B

Figure 3. 1H-NMR-Spectra in D2O/NaOD and D2O/DCl of

(a) the glycine derivatives 6 at pH* 11 and 6a at pH* 5 and

(b) the phenylalanine derivatives 7 at pH* 9 and 7a at pH* 4

Similar patterns were observed for the tyrosine, tryptophan, and napthylalanine species

8-10 and 8a-10a. Most informative are the high field shifts of the C(O)-CH2 group in all

complexes, as well as of the aromatic side chain and the pyridine 6'CH resonances in 7-

10 at high pH. The former indicate that all complexes including the nonaromatic glycine

derivative 6 have similar structures. The latter are characteristic for π stacking and

confirm that the crystallographically determined conformation of the amino acid side

chains is retained in solution. In contrast, no indication for stacking was observed in the

spectra of the amide O-coordinated species 7a–10a formed under acidic conditions.

36

The aromatic proton resonances appear in the typical range of the free ligand signals

without any significant shift. This is interesting because we have had earlier observed a

significant high-field shift of the methyl ester 2 in CDCl3.13 The differences cannot be

explained based on the basis of the available data, but it is safe to conclude that

aromatic interactions are not relevant in D2O solutions of 7a–10a and that the pKa

values for amide deprotonation reflect the stabilization of the N-coordinated form by

aromatic interactions. Because the transition from amide O to N coordination occurs in

the slow exchange regime, the integral of either an aromatic proton resonance, or the

C(O)–CH2 group signal was plotted against pH* (Figure 4). Following the so-called

“cancel-out approach” for the determination of pKa values, we did not consider

deuterium effects.27 Application of a correction function developed by Krezel and Bal

showed no significant differences.28 Problems were sometimes encountered because of

the precipitation of coordination polymers at pH values below 7. It was, therefore,

generally better to follow the signals of the N-coordinated species.

2 3 4 5 6 7 8 9 10 11

0,0

0,2

0,4

0,6

0,8

1,0

Inte

gral

Inte

nsiti

es

pH*

Figure 4. 1H-NMR-titration curves for the complexes 6 ( ), 7 ( ), 8 ( ), 9 ( ), and

10 ( )

37

Figure 4 clearly indicates that our assumption concerning π-stacking interactions were

correct. The pKa values which were determined by fitting the curves to a two state

equilibrium are significantly smaller for those complexes having aromatic side chains.

π-stacking energies are given by the difference

∆∆G = ∆G(7-10) – ∆G(6) (1)

They were calculated using the relationship

∆G = 2.303RTpKa (2)

The results are summarized in Table 3. They show that aromatic interactions contribute

ca. -7 to -11 kJ/mol to the stabilization of the N-coordinated peptide complexes, a range

which is comparable to data reported for π-cation interactions.29 This seems reasonable

because a metal coordinated pyridine ligand is similar to an alkylpyridinium ion.

Table 3. Thermodynamic Parameters at 298 K for the Amide Deprotonation Reactions

Reaction pKa ∆G, kJ/mol ∆∆G, kJ/mol

6a → 6 (Gly) 8.54 ± 0.02 48.7 ± 0.1

7a → 7 (Phe) 7.17 ± 0.01 40.9 ± 0.1 -7.8 ± 0.2

8a → 8 (Tyr) 6.85 ± 0.02 39.1 ± 0.1 -9.7 ± 0.2

9a → 9 (Trp) 6.85 ± 0.01 39.1 ± 0.1 -9.7 ± 0.2

10a → 10 (Nal) 6.64 ± 0.09 37.9 ± 0.5 -10.8 ± 0.6

It is interesting that the data on ternary metal amino acid complexes published by

Yamauchi et al.9,10 and Sigel et al.11 showed a broader range and, in most cases, smaller

energies of ca. -2.1 to -10 kJ/mol. The authors have assigned them to normal π-π-

stacking. As a result of the larger electrostatic energies involved, π-cation attractions are

38

expected to be significantly stronger than pure π-π stacking1c,30 and π-π-interactions in

peptides were experimentally determined to be on the order of ca. -2 to -5 kJ/mol free

enthalpy change.31 However, several authors have observed π-cation interactions which

are as small as ca. -2 to -3 kJ/mol.32 Furthermore, Fabbrizzi and co-workers have

determined stacking energies of -7 to -8 kJ/mol for interactions between anthracene

rings and aromatic amino acid side chains in fluorescent zinc complexes.12 This is

comparable to our findings, but unlike the pyridine ligands in 7-10, the anthracene rings

are not directly bound to the metal center, and hence are not cationic. Thus, it is not easy

to reach a conclusion concerning the nature of aromatic interactions in metal complexes.

We hope that the picture may become clearer with a growing number of data on

structurally characterized complexes were important parameters such as the interplane

distances between the stacked rings are reasonably well-defined. This study is intended

to underline the importance and provide a starting point.

In addition, our findings have implications for the modification of peptides with

synthetic metal binding sites. Such compounds are of considerable interest because of

their applicability, for example, in biomedicine or catalysis.33 It may be of particular

importance for molecular recognition events in medical applications that noncovalent

interactions involving a synthetic ligand can significantly change the secondary

structure of a small peptide. Our complexes show that a pyridine ligand suffices to

introduce structural motifs that are not known in comparable histidine peptides. Thus,

synthetic modifications may help to overcome the lack of secondary structure in small

peptides without engineered geometric restrictions and the design of rigid ligands.34

This could provide a new strategy in the development of enantioselective catalysts

which require a sterically well-defined chiral environment.

3.3. Conclusions

We have shown that aromatic interactions can result in the unusual folding of small

metallo-peptides. 1H-NMR experiments permitted a quantitative determination of

stabilizing free enthalpy changes and confirmed the conformational integrity of the

peptides in aqueous solution. Although it is not yet possible to distinguish between π-

cation and π-π-stacking interactions it is evident that moderate modifications such as the

39

exchange of a histidyl-imidazole donor for a pyridine ligand may have considerable

consequences for the secondary structure of a synthetic metal complex–peptide

conjugate.

3.4. Experimental Section

3.4.1. General Methods. Spectra were recorded with the following instruments:

For 1H-NMR a Bruker Avance DPX 300. All chemical shifts are referenced to TSP

(trimethylsilylpropionic acid) as internal standard, with high frequency shifts recorded

as positive. For elemental analysis a Carlo Erba Elemental Analyzer Modell 1106. For

FD- and FAB-MS a Varian MAT 212.

Absolute solvents were purchased from Fluka and stored under nitrogen. Solvents were

used without further purification. The water was bidistilled. All other reagents were of

commercially available reagent grade quality. Amino acid derivatives were purchased

from Bachem. All other chemicals were from Aldrich. Bis[(2-pyridyl)methyl]amine

(bpa) was prepared according to literature procedures35 or purchased from Aldrich. The

syntheses of the ligand Dpg-Phe-OMe13 and the coordination polymers 6a-10a14,15 were

published previously.

Chromatographic separations were achieved on flash columns under nitrogen pressure.

The stationary phase was silica (Merck Type 9385, 230-400 mesh, 60 Å) from Aldrich.

Technical grade dichloromethane was used after purification by rotary evaporation.

Methanol was of p.a. quality. The separation was optimized and followed by TLC

(silica).

40

3.4.2. Bromoacetylated Amino Acid Esters. BrAc-Gly-OMe. Gly-OMe x HCl (12.3

g, 98 mmol) was suspended in 200ml of THF. Triethylamine (27.8 ml, 200 mmol) was

added with stirring and the mixture was cooled to -78 °C in a dry ice bath.

Bromoacetylbromide (8.5 ml, 100 mmol) was dissolved in 100 ml of THF, and the

solution was added dropwise to the cold suspension over a period of 4 h. The mixture

was stirred without further cooling for another 2 h. Upon warming to room temperature

the color turned from yellow to dark-brown. Insoluble HNEt3Br was filtered off through

a layer of silica on a glass filter frit and the solvent was removed to dryness under

reduced pressure. The crude dark brown oil was dissolved in ethylacetate, filtered again

through a layer of silica and washed with an ethylacetate/n-hexane mixture. The brown

filtrate was evaporated under vacuum and the dry solid residue was purified by silica gel

column chromatography using ethyl acetate/n-hexane (2:1) as the eluent. A brown

fraction containing some amino acid ester starting material eluted first, followed by a

broad yellow fraction containing the product. The product fraction was concentrated

under vacuum and the product was solidified by addition of diethyl ether to the resulting

yellow oil. The white solid material was collected and repeatedly washed with diethyl

ether. Re-crystallization from ethyl acetate in a refrigerator (-20°C) over night afforded

the product as colorless block shaped crystals (1.80 g, 8.6 mmol, 8.60 %).

C5H8BrNO3 (210.03 g/mol): FAB-MS (nitrobenzyl alcohol) m/z: 210 [M+]. 1H-NMR

(300 MHz, CDCl3): δ = 3.79 (s, 3H, OCH3), 3.92 (s, 2H, BrCH2), 4.10 (d, 2H, αCH2),

6.96 (s, br, 1H, NH). 13C NMR (75MHz, CDCl3): δ = 28.56 (BrC), 41.79 (αC), 52.59

(OCH3), 165.68 (C(O)amide), 169.65 (C(O)ester). IR (KBr) / cm-1: 1750νCOOCH3,

1625νCONHR I, 1573 νCONHR II.

BrAc-Tyr-OMe. L-Tyr-OMe x HCl (5.00 g, 21.6 mmol) was suspended in 100ml of

THF. Triethylamine (6.01 ml, 43.2 mmol) was added with stirring and the mixture was

cooled to -40 °C in a dry ice/methanol/salt bath. Bromoacetylbromide (1.88 ml, 21.6

mmol) was dissolved in 50ml of THF, and the solution was added dropwise to the cold

suspension over a period of 3h. Stirring was continued for 2h without further cooling.

Insoluble HNEt3Br was filtered off and the solvent removed under reduced pressure.

The crude red brown oil was purified by silica gel column chromatography using

CH2Cl2/petrolether (40-60°C)/MeOH (11:5:1) as the eluent. The product was contained

in the second light-yellow fraction. The other layers were not collected. The product

41

fraction was concentrated by rotary evaporation and the resulting yellow oil dried under

vacuum (4.33 g, 13.7 mmol, 63.40 %).

C12H14O4NBr (316.15g/mol): FD-MS (CDCl3) m/z: 317 [M+]. 1H NMR (300MHz,

CDCl3): δ = 3.08 (m, 2H, βCH2), 3.75 (s, 3H, OCH3), 3.85 (dd, 2H, BrCH2), 4.83 (m,

1H, αCH), 5.18 (s, br, 1H; PhOH), 6.77 (d, 2H, H2,6PhOH), 6.83 (d, br, 1H, NH), 6.97 (d,

2H, H3,5PhOH). 13C NMR (75MHz, CDCl3): δ = 28.66 (BrC), 36.96 (βC), 52.55 (OCH3),

53.86 (αC), 115.62 (C2,6PhOH), 127.23 (C1PhOH), 130.48 (C3,5PhOH), 154.99 (C4PhOH),

165.21 (C(O)amide), 171.41 (C(O)ester). IR (KBr) / cm-1: 1739νCOOCH3, 1656νCONHR I,

1515νCONHR II.

BrAc-Trp-OMe. L-Trp-OMe x HCl (4.91 g, 19.3 mmol) was suspended in 150 ml of

THF. Triethylamine (5.73 ml, 38.6 mmol) was added with stirring and the mixture was

cooled to -78°C in a dry ice bath. Bromoacetylbromide (1.68 ml, 19.3 mmol) was

dissolved in 100 ml of THF, and the solution was added dropwise to the cold

suspension over a period of 2h. The mixture was stirred for another 2h without further

cooling. The resulting brown mixture was filtered through a glass filter frit with a layer

of silica in order to remove insoluble HNEt3Br, and the solvent removed under reduced

pressure until dryness. The crude brown solid was purified by silica gel column

chromatography using CH2Cl2/MeOH (11:1) as the eluent. A yellow fraction containing

some amino acid ester starting material eluted first. The product was contained in the

light yellow second fraction. The other layers were not collected. The solution

containing the desired product was concentrated by rotary evaporator. Re-crystallization

of the residual yellow solid from CH2Cl2 overnight in a refrigerator (-20°C) afforded the

product as colorless blocks which were collected on a sintered-glass filter and dried

under vacuum (4.17 g, 12.3 mmol, 63.73 %).

C14H15BrN2O3 (339.18g/mol): calcd. C 49.57, H 4.46, N 8.26; found C 49.72, H 4.99, N

8.33; FAB-MS (nitrobenzyl alcohol) m/z: 339 [M+]. 1H NMR (300 MHz, CDCl3): δ =

3.37 (m, 2H, βCH2), 3.70 (s, 3H, OCH3), 3.82 (s, 2H, BrCH2), 4.91 (m, 1H, αCH), 6.94

(d, br, 1H, NH), 7.03 (s, 1H, H6Indolyl), 7.14 (m, 2H, H2,5Indolyl), 7.38 (d, 1H, H4Indolyl),

7.55(d, 1H, H7Indolyl), 8.16 (s, br, 1H, NHIndolyl). 13C NMR (75MHz, CDCl3): δ 27.40

(BrC), 36.96 (βC), 52.51 (OCH3), 53.47 (αC), 111.28 (C1Indolyl), 118.51 (C5Indolyl),

119.75 (C7Indolyl), 122.33 (C6Indolyl), 122.84 (C2Indolyl), 127.41 (C8Indolyl), 136.10

42

(C9Indolyl), 165.24 (C(O)amide), 171.65 (C(O)ester). IR (KBr) / cm-1: 1732 νCOOCH3,

1657νCONHR I, 1543νCONHR II.

BrAc-2-Nal-OBz. L-2-Nal-OBz x HOTos (HOTos = p-tolylsulfonic acid) (10.12 g, 21.2

mmol) was dissolved in 150 ml of THF followed by addition of triethylamine (5.90 ml,

42.4 mmol) with stirring. The mixture was cooled to -60°C in a dry ice/acetone/salt

bath. Bromoacetylbromide (1.85 ml, 21.2 mmol) was dissolved in 100 ml of THF, and

the solution added dropwise to the cold solution over a period of 4h. Stirring was

continued for 2h without further cooling. Upon warming to room temperature the color

of the mixture turned form purple to dark blue. Insoluble HNEt3Br was filtered off

through a small layer of silica on a frit and the brown filtrate evaporated to dryness

under reduced pressure. The crude brown solid was purified by silica gel column

chromatography using CH2Cl2/MeOH (11:1) as the eluent. The product was contained

in the first yellow fraction. Other fractions were not collected. All solvent was removed

by rotary evaporation and the product was solidified by addition of diethylether to the

resulting yellow oil. Re-crystallization from ethyl acetate in a refrigerator at -20°C over

several days afforded the compound as white pellets which were collected on a sintered-

glass filter and dried under vacuum (7.89 g, 18.5 mmol, 87.35 %).

C22H20BrNO3 (426.30 g/mol): FAB-MS (nitrobenzyl alcohol); m/z: 426 [M+]. 1H NMR

(300 MHz, CDCl3): δ = 3.32 (m, 2H, βCH2), 3.83 (s, 2H, BrCH2), 4.96 (m, 1H, αCH),

5.18 (m, 2H, CH2Bz), 6.91 (d, br, 1H, NH), 7.15 (2xd, br, 1H, H3naphtyl), 7.25 (m, br,

5Hbenzyl), 7.47 (m, 3H, H1,6,7naphtyl), 7.70 (m, 2H, H4,8naphtyl), 7.79 (m, 1H, H5naphtyl). 13C NMR (75MHz, CDCl3): δ = 28.59 (BrC), 37.79 (βC), 53.72 (αC), 67.44 (CH2Bz),

125.82 (C2,6benzyl), 126.17 (C6,7naphtyl), 127.24 (C3naphtyl), 127.59 (C5naphtyl), 127.63

(C4naphtyl), 128.22 (C8naphtyl), 128.31 (C1naphtyl), 128.53 (C3benzyl), 128.57 (C5benzyl),

128.59 (C4benzyl), 132.49 (C2naphtyl), 132.74 (C10naphtyl), 133.34 (C9naphtyl), 134.83

(C1benzyl), 165.27 (C(O)amide), 170.69 (C(O)ester). IR (KBr) / cm-1: 1730νCOOBz,


43

3.4.3. Ligands. General Procedure. Equimolar amounts of bis(picolyl)amine (bpa), the

respective bromoacetylated amino acid ester, and diisopropylethylamine (DIPEA) were

dissolved in DMF or CH3CN. The solution was stirred for 20h at room temperature. All

solvents were removed by rotary evaporation. Ethyl acetate was added, resulting in the

precipitation of the ammonium halide salt which was filtered off and discarded. The

filtrate was concentrated to dryness yielding a brown oil which was purified on a silica

gel column using CH2Cl2/MeOH (11:1) as the eluent. A small yellow fraction

containing some amino acid starting material eluted first. The product followed in a

broad light yellow fraction. Other layers were not collected. The product fraction was

concentrated to dryness by rotary evaporation and the resulting brown oil dried under

vacuum.

Dpg-Gly-OMe: 1.00 g (4.8 mmol) BrAc-Gly-OMe, 0.95 g (4.8 mmol) bpa, 9 ml

DIPEA, 30 ml CH3CN, 30 ml AcOEt. Yield: 1.17 g (3.6 mmol, 74.77%). C24H26N4O4

(328.39g/mol): FD-MS (CDCl3) m/z: 329 [M+]. 1H NMR (300 MHz, CDCl3): δ = 3.31

(s, 2H, C(O)CH2), 3.65 (s, 3H, OCH3), 3.82 (s, 4H, pyCH2), 4.04 (d, 2H, αCH2), 7.10

(m, 2H, H4py), 7.28 (d, br, 2H, H3py), 7.55 (m, 2H, H5py), 8.49 (d, 2H, 3JH,H = 4.90Hz,

H6py). 13C NMR (75MHz, CDCl3): δ = 41.30 (αC), 52.48 (OCH3), 58.26 (C(O)CH2),

60.68 (pyCH2), 122.78 (C3py), 123.70 (C5py), 137.04 (C4py), 149,66 (C6py), 158.55

(C2py), 170.80 (C(O)amide), 172.24 (C(O)ester). IR (film on NaCl) / cm-1: 1749 νCOOCH3,


Dpg-Tyr-OMe: 2.56 g (8.1 mmol) BrAc-Tyr-OMe, 1.61 g (8.1 mmol) bpa, 1.41 ml

(8.1 mmol) DIPEA, 50ml DMF, 50 ml of AcOEt. Yield: 2.62 g, (6.0 mmol, 74.45 %).

C24H26N4O4 (434.49g/mol): FD-MS (CHCl3) m/z: 435 [M+]. 1H NMR (300MHz,

CDCl3): δ = 2.98-3.21 (m, 2H, βCH2), 3.70 (s, 2H, C(O)CH2), 3.74, 3.82 (2 x d, 4H,

pyCH2), 4.89 (m, 1H, αCH), 6.34 (d, 2H; H2,6PhOH), 6.94 (d, 2H, H3,5PhOH), 7.24 (m,

4H, H3,5py), 7.59 (m, 2H, H4py), 8.51 (d, 2H, H6py), 9.09 (d, 1H, NH). 13C NMR

(75MHz, CDCl3): δ = 36.98 (βC), 52.24 (OCH3), 53.33 (αC), 57.64 (C(O)CH2), 60.08

(pyCH2), 115.52 (C2,6PhOH), 122.52 (C3py), 123.22 (C5py), 127.57 (C1PhOH), 130.23

(C3,5PhOH), 136.84 (C4py), 149.04 (C6py), 155.64 (C4PhOH), 158.12 (C2py), 171.56

(C(O)amide), 172.32 (C(O)ester). IR (KBr) / cm-1: 1744 νCOOCH3, 1656 νCONHR I,

1515νCONHR II.

44

Dpg-Trp-OMe: 3.37 g (9.9 mmol) BrAc-Trp-OMe, 1.97 g (9.9 mmol) bpa, 1.73 ml

(9.9 mmol) DIPEA, 50 ml DMF, 50 ml AcOEt. Yield: 3.01 g (6.6 mmol, 66.41%).

C26H27N5O3 (457.52 g/mol): FD-MS (CDCl3) m/z: 458 [M+]. 1H NMR (300 MHz,

CD3CN): δ = 3.20 (dd, 2H, C(O)CH2), 3.37 (m, 2H, βCH2), 3.65 (s, 3H, OCH3), 3.72,

3.79 (2 x d, 4H, 2JH,H = 13.94Hz, pyCH2), 4.79 (m, 1H, αCH), 7.06 – 7.19 (m, 7H,

H3,4,5py, H5,6Indolyl), 7.43 (d, 1H, H2Indolyl), 7.61 (m, 3H, H4,7Indolyl, H4py), 8.50 - 8.52

(2 x d, 2H, 3JH,H = 4.53Hz, 2 x H6py), 8.81 (d, br, 1H, NHamide), 9.36 (s, br, NHIndolyl). 13C NMR (75MHz, CD3CN): δ = 28.00 (βC), 52.61(OCH3), 53.65 (αC), 58.45

(C(O)CH2), 60.65 (pyCH2), 110.70 (C3Indolyl), 112.35 (C7Indolyl), 119.21 (C2Indolyl),

119.94 (C6Indolyl, 122.52 (C4Indolyl), 123.18 (C5py), 123.87 (C3py), 124.56 (C5Indolyl),

129.38 (C9Indolyl), 137.35 (C8Indolyl), 137.39 (C4py), 149.91 (C6py), 159.36 (C2py), 171.82

(C(O)amide), 173.41 (C(O)ester). IR (KBr) / cm-1: 1741 νCOOCH3, 1654 νCONHR I,

1590νCONHR II.

Dpg-2-Nal-OBz: 2.01 g (4.7 mmol) BrAc-2-Nal-OBz, 0.94 g (4.7 mmol) bpa, 0.82 ml

(4.7 mmol) DIPEA, 100 ml CH3CN, 100 ml AcOEt. Yield: 2.05 g (3.8 mmol, 79.74 %).

C34H32N4O3 (544.64 g/mol): FD-MS (CDCl3) m/z: 544 [M+]. 1H NMR (300 MHz,

CDCl3): δ = 3.23 (s, 2H, C(O)CH2), 3.31 - 3.48, (m, 2H, βCH2), 3.67, 3.75 (2 x d, 4H,

pyCH2), 5.05 (m, 1H, αCH), 5.09-5.19 (m, 2H, CH2Bz), 7.01 – 7.05 (m, 4H, H3,7naphtyl

H3py), 7.19 – 7.29 (m, 8Hbenzyl, H5py, H6naphtyl), 7.41 (m, 2H, H4py), 7.57 – 7.66 (m, 3H,

H1,4,8naphtyl), 7.74 (d, br, 1H, H5naphtyl), 8.44 (d, 2H, H6py), 9.13 (d, 1H, NH). 13C NMR

(75MHz, CDCl3): δ = 37.75 (βC), 53.30 (αC), 57.62 (C(O)-CH2), 60.10 (pyCH2), 67.05

(CH2Bz)], 122.22 (C5py), 122.85 (C3py), 125.62 (C6naphtyl), 126.05 (C7naphtyl), 125.34

(C1naphtyl), 127.55 (C3naphtyl), 127.60 (C5naphtyl), 127.60 (C4naphtyl), 127.96 (C8naphtyl),

128.11 (C1naphtyl), 128.30 (C3,5bezyl), 128.50 (C4bezyl), 132.37 (C2naphtyl), 133.37

(C10naphtyl), 134.06 (C9naphtyl), 135.27 (C1bezyl), 136.39 (C4py), 148.99 (C6py), 158.13

(C2py), 171.37 (C(O)amide), 171.57 (C(O)ester). IR (KBr) / cm-1: 1741 νCOOBz, 1673

νCONHR I, 1591 νCONHR II.

45

3.4.4. [(Dpg-Xaa-OMe)(H2O)Zn](CF3SO3)2 (1, 3-5). General Procedure.

Solid Zn(CF3SO3)2 was added to a stirred solution of 1 equiv of the respective ligand in

CH3CN. Stirring was at room temperature continued overnight followed by removal of

all solvent under vacuum. CH2Cl2 was added to the residue and the resulting suspension

left in refrigerator (-20°C) overnight. Unchanged Zn(CF3SO3)2 precipitated and was

filtered off. The product obtained after stripping all solvent from the filtrate was dried

under vacuum and used without further purification.

[(Dpg-Gly-OMe)(H2O)Zn](CF3SO3)2 (1): 1.29 g (3.9 mmol) Dpg-Gly-OMe, 1.43 g

(3.9 mmol) Zn(CF3SO3)2, 50 ml CH3CN, 50 ml CH2Cl2. Yield: 2.4 g (3.5 mmol, 88.26

%). C19H22F6N4O10S2Zn (709.91 g/mol): FAB-MS (nitrobenzyl alcohol); m/z: 541 [(M-

CF3SO3)+]; 1H NMR (300 MHz, CD3CN): δ (ppm) = 3.60 (s, 3H, OCH3), 3.82 (s, 2H,

C(O)CH2), 3.95 (d, 2H, 2JH,H = 5.85Hz, αCH2), 4.32 (s, 4H, pyCH2), 7.58 (d, 2H, H5py),

7.65 (m, 2H, H3py), 8.09 (m, 2H, H4py), 8.24 (s, br, 1H, NH), 8.70 (d, 2H, H6py). 13C

NMR (75MHz, CD3CN): δ = 41.44 (αC), 51.69 (OCH3), 56.85 (C(O)CH2), 58.67

(pyCH2), 124.73 (C5py), 125.11 (C3py), 141.37 (C4py), 147.49 (C6py), 153.91 (C2py),

167.80 (C(O)amide), 173.94 (C(O)ester). C, H, N, S Elem Anal. Calcd for 1: C, 32.98; H,

2.91; N, 8.10; S, 9.27%. Found: C, 32.73; H, 2.69; N, 7.99; S, 9.20%. IR (KBr) / cm-1:

1743νCOOCH3, 1637νCONHR, 1276νCF3SO3, 1261νCF3SO3.

[(Dpg-Tyr-OMe)(H2O)Zn](CF3SO3)2 (3): 1.87 g (4.3 mmol) Dpg-Tyr-OMe, 1.56 g

(4.3 mmol) Zn(CF3SO3)2, 100 ml CH3CN, 50 ml CH2Cl2. Yield: 2.80 g (3.4 mmol,

79.80 %). C26H28F6N4O11S2Zn (816.03 g/mol): FAB-MS (nitrobenzyl alcohol); m/z:

649 [(M-CF3SO3-H2O)+]. 1H NMR (300 MHz, CD3OD): δ (ppm) = 2.58-2.95 (m, 2H, βCH2), 3.58 – 3.75 [m, 5H, OCH3 + C(O)CH2), 4.39 – 4.54 (5H, 2 x pyCH2, αCH), 6.51

(m, 2H, H2,6PhOH), 6.67 (m, H3,5PhOH), 7.66 (m, 4H, H3,5py), 8.12 (m, 2H, H4py), 8.53 –

8.60 (2 x d, 2H, 3JH,H = 5.31Hz, H6py). 13C NMR (75MHz, CD3OD): δ = 35.20 (βC),

50.98 (OCH3), 57.85 (C(O)CH2), 60.72 (αC), 60.80 (pyCH2), 114.25 (C2,6PhOH),

124.24, 124.39 (C3py), 124.68, 124.76 (C5py), 128.94, 128.97 (C3,5PhOH), 140.44,

140.45 (C4py), 146.57, 146,70 (C6py), 152.88, 153.09 (C2py), 155.41 (C4PhOH), 169.83

(C(O)amide), 171.77 (C(O)ester). C, H, N, S Elem Anal. Calcd for 3: C, 38.27; H, 3.46; N,

6.87; S, 7.63%. Found: C, 39.26; H, 3.59; N, 6.67; S, 7.63%. IR (KBr) / cm-1: 1746

νCOOCH3, 1635 νCONHR, 1286 νCF3SO3, 1244 νCF3SO3.

46

[(Dpg-Trp-OMe)(H2O)Zn](CF3SO3)2 (4): 2.05 g (4.5mmol) of Dpg-Trp-OMe, 1.63 g

(4.5 mmol) Zn(CF3SO3)2, 100 ml CH3CN, 100 ml of CH2Cl2. Yield: 3.33 g (88.34 %).

C28H29F6N5O10S2Zn (839.07g/mol): FAB-MS (nitrobenzyl alcohol); m/z: 670 [(M-

CF3SO3-H2O)+]. 1H NMR (300 MHz, CD3CN): δ (ppm) = 2.92 (H2O), 3.00 – 3.08 (2 x

d, 1H, βCH2), 3.25 – 3.30 (2 x d, 1H, βCH2), 3.49 - 3.55 (d, 1H, pyCH2), 3.56 (s, 2H,

C(O)CH2), 3.64 (s, 3H, OCH3), 4.01 – 4.19 (3 x d, 3H, pyCH2), 4.88 (m, 1H, αCH), 6.96

(m, 4H, H2,3,4,6Indolyl), 7.40 (m, 1H, H5Indolyl), 7.50 (m, 2H, H5py), 7.62 (m, 2H, H3py),

8.11 (m, 2H, H4py), 8.18 (d, br, 1H, NHamide), 8.51 – 8.61 ( 2 x d, 2H, H6py), 9.17 (s, br,

1H, NHIndolyl). 13C NMR (75MHz, CD3CN): δ = 27.14 (βC), 51.93 (OCH3), 54.27 (αC),

56.36 (C(O)CH2), 57.97 (pyCH2), 108.42 (C1Indolyl), 111.06 (C4Indolyl), 117.71 (C5Indolyl),

118.61 (C7Indolyl), 121.19 (C6Indolyl), 124.02 (C2Indolyl), 124.73, 124.81 (C5py), 125.06,

125.18 (C3py), 126.76 (C8Indolyl, 135.77 (C9Indolyl), 141.40 (C4py), 141.49 (C4py), 147.53

(C6py), 147.59 (C6py), 153.69 (C2py), 153.93 (C2py), 169.80 (C(O)amide), 172.93

(C(O)ester). C, H, N, S Elem Anal. Calcd for 4·2H2O: C, 38.39; H, 3.77; N, 7.99; S,

7.31%. Found: C, 37.68; H, 3.06; N, 8.56; S, 7.32%. IR (KBr) / cm-1: 1743 νCOOCH3,

1633 νCONHR, 1280 νCF3SO3, 1254 νCF3SO3.

[(Dpg-2-Nal-OBz)(H2O)Zn](CF3SO3)2 (5): 2.00 g (3.7 mmol) of Dpg-2-Nal-OBzl,

1.33 g (3.7 mmol) of Zn(CF3SO3)2, 100 ml CH3CN, 100 ml of CH2Cl2. Yield: 3.00g

(3.2 mmol, 88.26 %). C36H34F6N4O10S2Zn (926.19 g/mol): FAB-MS (nitrobenzyl

alcohol); m/z: 757 [(M-CF3SO3-H2O)+]. 1H NMR (300 MHz, CDCl3): δ (ppm) = 2.91 –

3.00 (m, 1H, βCH2), 3.29 – 3.37 (m, 5H, βCH2, C(O)CH2, H2O), 3.55 (d, 1H, pyCH2),

3.75 - 3.96 (m, 2H, pyCH2), 4.24 (d, 1H, pyCH2), 4.96 – 5.07 (m, 3H, αCH, OCH2Bz),

6.80 – 7.84 (m, br, 18H, H3,4,5py Hnaphtyl, Hbenzyl), 8.49-8.70 (2 x d, 2H, 3JH,H = 4.89Hz),

9.05 (d, 1H, NH 3JH,H = 8.62Hz). 13C NMR (75MHz, CDCl3): δ = 37.07 (βC), 54.17

(αC), 54.96 (C(O)CH2), 56.47 (pyCH2), 66.63 (OCH2Bz), 117.05, 121.27, 123.71

(C3,6,7naphtyl), 124.07, 124.94 (C3,5py), 127.24-130.99 (C2,4,6,5benzyl), 131.96

(C10naphtyl), 132.25 (C9naphtyl), 133.80 (C2naphtyl), 140.35, 140.53 (C4py), 147.57, 147.86

(C6py), 152.39, 152.85 (C2py), 168.40 (C(O)amide),172.20 (C(O)ester). C, H, N, S Elem

Anal. Calcd for 5: C, 46.68; H, 3.70; N, 6.05; S, 6.92%. Found: C, 46.82; H, 3.36; N,

6.27; S, 7.63%. IR (KBr) / cm-1: 1748 νCOOBz, 1634 νCONHR, 1288 νCF3SO3, 1240 νCF3SO3.

47

3.4.5. Synthesis of [(Dpg-Xaa)-HZn] (6-10). General Procedure. The tetrameric

complex {[(Dpg-Gly)Zn](CF3SO3)}4 (6a)16 and the polymers {[(Dpg-

Xaa)Zn]3(CF3SO3)3}∞ (Xaa = Phe: 7a, Tyr: 8a, Trp: 9a, Nal: 10a) were synthesized as

described previously14,15 and used as starting materials. The respective complex was

dissolved in H2O and the pH adjusted to 9.00 with 1 M NaOH. The mixture was stirred

overnight and the solvent removed by rotary evaporation. The residual solid material

was dried under vacuum and purified by reprecipitation from methanol or ethanol. Bulk

samples obtained by this method contained variable quantities of NaCF3SO3 and/or

water, as is evident from elemental analysis and mass spectrometry data. The reported

yields are based on the C, H, N, S elemental analysis data of a characteristic sample.

Crystals for X-ray structure analyses of [(Dpg-Phe)Zn]∞ (7), [(Dpg-Tyr)Zn]∞ (8), and

{[(Dpg-2-Nal)Zn]·Na(CF3SO3)}∞ (10) were grown by slow diffusion of diethyl ether

into methanol solutions. Single crystals of [(Dpg-Trp)Zn] (9) were obtained after

several weeks at room temperature from an aqueous NaOH solution at pH 8.00.

[(Dpg-Gly)-HZn] (6):

400 mg (0.24 mmol) {[(Dpg-Gly)Zn](CF3SO3)}4, 15 ml H2O. Yield: 220 mg (0.56

mmol, 76.16 %). C16H16N4O3Zn (M = 377.71 g/mol): FAB-MS (nitrobenzyl alcohol)

m/z: 399 [(M+Na)+], 377 [M+]. 1H NMR (300 MHz, D2O/NaOD; pH* = 9.00): δ (ppm)

= 3.44 (s, br, 2H, C(O)CH2), 3.82 (s, br, 2H, αCH2), 4.28 (s, br, 4H, pyCH2), 7.16 (m,

4H, H3,5py), 8.09 (m, 2H, H4py), 8.65 (d, 2H, H6py); 13C NMR (75MHz, D2O/NaOD;

pH* = 9.00): δ 49.56 (αC), 51.76 (C(O)CH2), 61.27 (pyCH2), 127.44 (C5py), 127.79

(C3py), 144.07 (C4py), 151.12 (C6py), 158.70 (C2py), 173.72 (C(O)amide), 184.50 (C(O)

carboxylate). C, H, N, S Elem Anal. Calcd for 6·NaCF3SO3·0.5H2O: C, 36.51; H, 3.04; N,

10.02; S, 5.72%. Found: C, 36.66; H, 3.70; N, 9.99; S, 4.89%. IR (KBr) / cm-1:

1624 νCOO-, 1275 νCF3SO3. 1H NMR (300MHz, D2O/DCl; pH* = 4.00): δ (ppm) = 3.74 (s, br, 2H, C(O)CH2), 3.82

(s, br, 2H, αCH2), 4.42 (m, 4H, pyCH2), 7.58 (m, 4H, H3,5py), 8.06 (m, 2H, H4py), 8.66

(d, 2H, H6py).

48

[(Dpg-Phe)-HZn] (7):

500 mg (0.26 mmol) {[(Dpg-Phe)Zn]3(CF3SO3)3}∞, 30 ml H2O. Yield: 304 mg (0.65

mmol, 83.33 %). C23H22N4O3Zn (M = 467.84 g/mol): FAB-MS (nitrobenzyl alcohol);


= 3.17 [m, 3H, βCH2, C(O)CH2), 3.57 (d, 1H, C(O)CH2), 3.77, 3.83 (2 x d, 2H, pyCH2),

4.35 (m, 3H, αCH, pyCH2), 6.44 (m, 1H, H4phenyl), 6.75 (m, 2H, H3,5phenyl), 6.90 (m,

2H, H2,6phenyl), 7.49 (m, 4H, H3,5py), 8.02 (m, 3H, H4,6py), 8.42 (d, 1H, H6py); 13C

NMR (75MHz, D2O/NaOD; pH* = 9.00): 39.93 (βC), 51.76 (αC), 60.48 (pyCH2), 62.05

(C(O)CH2), 127.12 - 127.90 (C3,5py), 129.44, 130.14, 131.65 (C2,3,4,5,6phenyl), 139.49

(C1phenyl), 143.90, 144.05 (C4py), 150.75, 151.10 (C6py), 158.05, 158.58 (C2py), 172.18

(C(O)amide), 188.55 (C(O)carboxylate). C, H, N Elem Anal. Calcd for 7·3H2O: C, 52.93; H,

5.41; N, 10.74%. Found: C, 53.16; H, 5.01; N, 10.81%. IR (KBr) / cm-1: 1612 νCOO-,

1276 νCF3SO3. 1H NMR (300MHz, D2O/DCl; pH* = 4.00): δ (ppm) = 2.69 (dd, 1H, βCH2), 3.11 (dd,

1H, βCH2), 3.61 (m, 2H, C(O)CH2), 3.97 (d, 1H, pyCH2), 4.35 (m, 4H, αCH, pyCH2),

7.03 (m, 4H, H2,3,5,6phenyl), 7.57 (m, 4H, H3,5phenyl), 8.06 (m, 2H, H4phenyl), 8.56 (d, 2H,

H6py), 8.61 (d, 2H, H6py).

[(Dpg-Tyr)-HZn] (8):

300 mg (0.15 mmol) {[(Dpg-Tyr)Zn]3(CF3SO3)3}∞, 15ml H2O. Yield: 190mg (0.38

mmol, 81.79 %). C23H22N4O4Zn (M = 483.84 g/mol): FAB-MS (nitrobenzyl alcohol);


= 2.93 (m, 3H, βCH2 + C(O)CH2), 3.38 (d, 1H, C(O)CH2), 3.69 (d, 2H, pyCH2), 4.14

(m, 3H, αCH, pyCH2), 6.06 (d, 2H, H2,6PhOH), 6.59 (d, 2H, H3,5PhOH), 7.36 (m, 4H,

H3,5py), 7.87 (m, 3H, H4,6-py), 8.27 (d, 1H, H6py); 13C NMR (75MHz, pH* = 9.00):

δ 36.51 (βC), 57.89 (αC), 58.01 (pyCH2), 59.56 (C(O)CH2), 114.53 (C2,6PhOH), 124.61,

125.23 (C3,5py), 130.48 (C3,5PhOH), 141.38, 141.52 (C4py), 148.27 (C6py), 154.22

(C4PhOH), 155.67, 156.11 (C2py), 169.59 (C(O)amide), 183.86 (C(O)carboxylate). C, H, N

Elem Anal. Calcd for 8·0.5H2O: C, 56.00; H, 4.66; N, 11.36%. Found: C, 56.07; H,

3.84; N, 11.27%. IR (KBr) / cm-1: 1612νCOO-, 1271νCF3SO3.

49

1H NMR (300 MHz, D2O/DCl; pH* = 4.00): δ (ppm) = 2.58 (dd, 1H, βCH2), 3.07 (dd,

1H, βCH2), 3.60 (m, 2H, (C(O)CH2), 3.88 (d, 1H, pyCH2), 4.33 (m, 4H, αCH, pyCH2),

6.52 (m, 2H, H2,6PhOH), 6.89 (m, 2H, H3,5PhOH), 7.54 (m, 4H, H3,5py), 8.04 (m, 2H,

H4py), 8.56 (d, 1H, H6py), 8.63 (d, 1H, H6py).

[(Dpg-Trp)-HZn] (9):

230 mg (0.11 mmol) of {[(Dpg-Trp)Zn]3(CF3SO3)3}∞, 10 ml H2O. Yield: 150mg (0.30

mmol, 87.04%). C25H23N5O3Zn (M = 506.87g/mol): FAB-MS (nitrobenzyl alcohol);

m/z: 506 [M+]. 1H NMR (300 MHz, D2O/NaOD; pH* = 9.00): δ (ppm) = 3.08 (d, 1H,

C(O)CH2), 3.29 (d, 1H, py-CH2), 3.36 (d, 1H, βCH2), 3.48 (d, 1H, pyCH2), 3.51 (m, 1H, βCH2), 3.69 (d, 1H, pyCH2), 3.89 (d, 1H, C(O)CH2), 4.16 (m, 1H, pyCH2), 4.37 (m, 1H, αCH), 6.82 (d, 1H, H6Indolyl), 6.95 (m, 3H, H2,4,5Indolyl), 7.17 (d, 1H, H5py), 7.39 (m, 4H,

H3,5,6py), 7.92 (m, 3H, H4py, H7Indolyl), 8.41 (d, 1H, H6py); 13C NMR (75MHz,

D2O/NaOD; pH* = 9.00): δ 30.00 (βC), 60.77 (αC), 60.88 (pyCH2), 61.25 (C(O)CH2),

62.36 (pyCH2), 112.56 (C1Indolyl), 114.64 (C4Indolyl), 120.93 (C5Indolyl), 121.73 (C5Indolyl),

121.73 (C7Indolyl), 124.04 (C2Indolyl), 125.67 (C4Indolyl), 126.95, 127.22, 127.54, 127.67

(C3py, C5py), 131.03 (C8Indolyl), 137.72 (C9Indolyl), 143.62, 143.91 (C4py), 149.94, 150.68

(C6py), 158.16, 158.57 (C2py), 172.19 (C(O)amide), 187.08 (C(O)carboxylate).

IR (KBr) / cm-1: 1606ν COO-, 1277νCF3SO3. 1H NMR (300 MHz, D2O/DCl; pH* = 4.00): δ (ppm) = 2.91 (m, 1H, βCH2), 3.40 (m,

4H, βCH2, C(O)CH2, pyCH2), 4.03 (d, 2H, pyCH2), 4.22 (d, 1H, pyCH2), 4.69 (m, 1H, αCH), 7.05 (m, 4H, H4,5,6,7Indolyl), 7.46 (m, 5H, H3,5py, H1Indolyl), 7.99 (m, 2H, H4py),

8.39 (d, 1H, H6py), 8.59 (d, 1H, H6py). 13C NMR (75MHz, D2O/DCl; pH = 4.00): δ =

28.28 (βC), 56.93 (αC), 57.27 (C(O)CH2), 59.00 (pyCH2), 110.39 (C1Indolyl), 112.00

(C4Indolyl), 118.53 (C5Indolyl), 119.37 (C7Indolyl), 122.01 (C6Indolyl), 124.45 (C2Indolyl),

124.81 (C5py), 124.97, 125.39 (C3py), 127.06 (C8Indolyl), 136.03 (C9Indolyl), 144.45,

141.52 (C4py), 147.83, 148.03 (C6py), 153.66, 154.05 (C2py), 172.26 (C(O)amide).

IR (KBr) / cm-1: 1622νCOO-, 1258νCF3SO3.

50

Alternative Synthesis. Analytically pure samples of 9 were obtained by the following

method: Equimolar amounts of Dpg-Trp-OMe (1.06 g, 2.32 mmol) and sodium

hydroxide (0.10 g, 2.32 mmol) were dissolved in 50 mL of CH3OH. The solution was

stirred for 2h at room temperature, and the solvent was removed by rotary evaporation.

The dry residue was dissolved in 50 mL of water, and the pH was adjusted to pH 9.00

with 2M aOH. After stirring overnight, 1M Cl was added to adjust the pH to 5.00. All

water was removed by rotary evaporation. Methanol was added to the dry residue,

resulting in the precipitation of NaCl salt, which was filtered off through a 0.2 µ filter.

The filtrate was concentrated to dryness, yielding a light-yellow solid, which was

purified by recrystallization from methanol/diethyl ether. Yield: 0.64 g (1.38 mmol,

59.77%). C, H, N Elem Anal. Calcd for Dpg-Trp-OH·H2O, C25H27N5O4 (M = 461.51

g/mol): C, 65.06; H, 5.90; N, 15.17. Found: C, 65.35; H, 5.70; N, 14.63. FAB-MS

(nitrobenzyl alcohol): m/z = 444 [M+]; 1H NMR (300MHz, D2O): δ 2.94 - 3.29 (m, 8H, βCH2, C(O)CH2, pyCH2), 4.47 (m, 1H, αCH), 6.69 (m, 2H, H6,7Indolyl), 6.87 (m, 4H,

H4,5Indolyl + H5py), 7.18 (m, 3H, H3py + H1Indolyl), 7.58 (m, 2H, H4py), 8.09 (d, H6py). 13C

NMR (75MHz, D2O): δ 27.11 (βC), 49.33 (αC), 54.40 (C(O)CH2), 58.33 (pyCH2),

110.31 (C1Indolyl), 112.74 (C4Indolyl), 118.53 (C5Indolyl), 119.34 (C7Indolyl), 120.23

(C6Indolyl), 122.75 (C2Indolyl), 125.52 (C5py), 127.76 (C3py), 135.71 (C3py), 140.17

(C8Indolyl), 142.37 (C9Indolyl), 144.45 (C4py), 146.42 (C6py), 154.49 (C2py), 171.74

(CONHR), 177.85 (COOH). IR (KBr) / cm-1: 1727νCOOH, 1660νCOO-, 1596νCONHR.

Solid ZnCl2 (153 mg, 1.13 mmol) was added to a stirred solution of Dpg-Trp-OH (499

mg, 1.13 mmol) in 50 mL of H2O. The pH was adjusted with 2 M NaOH to 9.00.

Precipitating excess zinc salts were filtered off, and the clear solution was stirred

overnight. The pH was set to 8.00 using 1 M HCl, and water was removed by rotary

evaporation. The crude product was dried in a vacuum and redissolved in methanol.

Insoluble NaCl was filtered off, and diethyl ether was added to the clear filtrate until the

product started to precipitate. The resulting suspension was left overnight in a deep

freezer at –20 °C. The product [(Dpg-Trp)-HZn]·2CH3OH (487 mg, 0.96 mmol, 85.0%)

was collected on a sintered-glass filter funnel and dried under a vacuum. The methanol

content was confirmed by 1H NMR spectroscopy. Other spectroscopic data are in

agreement with those of the material obtained as described above. C, H, N Elem Anal.

51

Calcd for C27H31N5O5Zn: C, 56.80; H, 5.47; N, 12.27%. Found: C, 56.89; H, 5.66; N,

12.68%.

[(Dpg-2-Nal)-HZn . Na(CF3SO3)] (10. Na(CF3SO3)):

400 mg (0.19 mmol) {[(Dpg-2-Nal)Zn]3(CF3SO3)3}n, 15 ml H2O. Yield: 230 mg (0.34

mmol, 58.60 %). C27H24N4O3Zn . CF3NaO3S (M = 667.02 g/mol); FAB-MS

(nitrobenzyl alcohol); m/z: 539 [(M-CF3SO3)+], 517 [10+]. 1H NMR (300 MHz,

D2O/NaOD; pH* = 9.00): δ (ppm) = 3.07 (d, 1H, C(O)CH2), 3.33 (m, 2H, βCH2), 3.55

(m, 2H, pyCH2, C(O)CH), 4.09 (2H, pyCH2), 4.39 (m, 1H, αCH), 6.58 (d, 2H,

H6,7naphtyl), 7.03 (d, 1H, H3naphtyl), 7.25 (m, 6H, H4,5,8naphtyl, H3,5py), 7.44 (m, 4H,

H1naphtyl, H3,4,6py), 7.90 (m, 1H, H4py), 8.32 (d, 1H, H6py). 13C NMR (75MHz,

D2O/NaOD; pH* = 9.00): δ = 37.47 (βC), 57.74 (αC), 59.14 (py-CH2), 59.67

(C(O)CH2), 122.10 (C6,7naphtyl), 123.56 – 124.59 (C3,5py), 125.07 (C4naphtyl), 126.60

(C3py), 127.14 (C1naphtyl), 127.51 (C8py), 127.71 (C7naphtyl), 127.81 (C5naphtyl), 128.26

(C3naphtyl), 131.51 (C2naphtyl), 132.54 (C9naphtyl), 134.95 (C10naphtyl), 140.89, 141.40

(C4py), 146.72, 148.09 (C6py), 154.26, 155.88 (C2py), 169.67 (C(O)amide), 183.72

(C(O)carboxylate). C, H, N, S Elem Anal. Calcd for 10·3NaCF3SO3: C, 34.84; H, 2.34; N,

5.42; S, 9.30%. Found: C, 34.69; H, 2.64; N, 5.41; S, 8.83%. IR (KBr) / cm-1:

1612νCOO-, 1276νCF3SO3. 1H NMR (300 MHz, D2O/DCl; pH* = 4.00): δ (ppm) = 2.79 (dd, 1H, βCH2), 3.38 (dd,

1H, βCH2), 3.55 (m, 4H, C(O)-CH2, py-CH2), 4.34 (m, 3H, αCH, py-CH2), 7.06-7.75

(m, 11H, H-naphtyl, H3,5-py), 7.96 (m, 1H, H4-py), 8.05 (m, 2H, H4-py), 8.23 (d, 1H,

H6-py), 8.54 (d, 1H, H6-py).

3.4.6. X-ray crystallography. A summary of the crystallographic data and structure

refinement details is given for all compounds in Table 1. Intensity data (MoKα, λ =

0.71073 Å) were collected on a Bruker-Nonius Kappa CCD diffractometer. Semi-

empirical absorption corrections based on equivalent reflections were made using the

program SADABS.36 All structures were solved by direct methods and refined using

full matrix least squares procedures on F2 using the program package SHELXTL NT

6.12.37 Non-H-atoms were anisotropically refined. H-atoms were fixed in geometrically

calculated positions (riding mode) with an isotropic displacement parameter of 1.2 or

52

1.5 times that of the respective C-, O-, or N-atom. One of the methanol molecules in {7 .

2.5 CH3OH}∞ is disorder on a crystallographic two-fold rotation axis. It was refined

without H-atoms. Details have been deposited at the Cambridge Crystallographic Data

Centre as supplementary publications CCDC nos. 255842 ({7 . 2.5 CH3OH}∞), 255843

({8}∞), 255844 (9), and 255845 (10 . Na(CF3SO3}∞). Copies are available free of charge

from CCDC, 12 Union Road, Cambridge CB2 1 EZ (UK) [Fax: (+44)1223-336033; E-

mail: [email protected]].

53

Table 1. Crystallographic Data for {7 . 2.5 CH3OH}∞, 8∞, 9 . 2.75 H2O, and {10 .

NaCF3SO3}∞ Compound {7 . 2.5 CH3OH}∞ 8∞ 9 . 2.75 H2O {10 . NaCF3SO3}∞

Formula C25.5H32N4O5.5Zn C23H22N4O4Zn C25H28.5N5O5.75Zn C28H24F3N4NaO6SZn

Formula weight 547.92 483.82 556.40 689.93

Crystal size [mm3] 0.26 x 0.18 x 0.08 0.16 x 0.15 x 0.06 0.30 x 0.18 x 0.12 0.26 x 0.10 x 0.09

Temperature [K] 100(2) 100(2) 100(2) 100(2)

Crystal system Monoclinic monoclinic triclinic orthorhombic

Space group C2 P21 P1 P212121

a [Å] 22.035(2) 9.5772(6) 9.8276(6) 7.602(1)

b [Å] 8.9883(6) 9.4446(5) 10.7925(7) 16.215 (1)

c [Å] 13.1047(8) 10.7966(6) 13.3530(6) 23.130(2)

α [°] 90 90 103.483(5) 90

β [°] 100.373(5) 95.039(4) 108.767(4) 90

γ [°] 90 90 101.066(5) 90

Volume [Å 3] 2553.1(3) 972.8(1) 1248.0(2) 2851.2(3)

Z 4 2 2 4

Dcalcd [Mg/m3] 1.425 1.652 1.481 1.607

µ [mm-1] 1.007 1.305 1.034 1.020

θ-range [°] 3.35 – 28.70 3.48 – 27.51 3.47 – 26.02 3.65 – 28.70

Measured refls 28183 16929 25211 34429

Independent refls 6266 (Rint =

0.0358)

4471 (Rint =

0.0500)

9420 (Rint =

0.0382) 7296 (Rint = 0.0552)

Observed refls a 5724 3975 7904 5836

Parameters 335 290 653 397

Goodness-of-Fit on

F2 1.087 1.057 1.012 0.897

R1a 0.0309 0.0296 0.0470 0.0375

wR2 (all data) 0.0844 0.0614 0.1096 0.0756

abs. struct. params38 0.02(1) 0.02(1) 0.02(2) 0.02(1)

∆ρmax./min. [eÅ-3] 0.756/-0.654 0.299/-0.379 0.988/-0.501 0.531/-0.331 a[I>2σ(I)]

54

Table 2. Selected bond distances (Å) and angles (°) in the structures of {[(Dpg-Phe)-

HZn] . 2.5 CH3OH}∞ ({7 . 2.5 CH3OH}∞), [(Dpg-Tyr)-HZn]∞ (8∞), [(Dpg-Trp)-HZn] .

2.75 H2O (9 . 2.75 H2O), and {[(Dpg-Nal)-HZn] . Na(CF3SO3)}∞ ({10 . Na(CF3SO3)}∞) {7 . 2.5 CH3OH}∞ 8∞ 9 . 2.75 H2O {10 . NaCF3SO3}∞

N1-Zn 2.358(2) 2.331(2) 2.264(3) 2.274(2)

N2-Zn 2.113(2) 2.085(2) 2.054(4) 2.062(2)

N3-Zn 2.168(2) 2.159(2) 2.032(4) 2.051(2)

N4-Zn 2,064(2) 2.036(2) 1.942(4) 1.963(2)

O2-Zn 2.102(1) 2.137(2) 2.044(4) 2.030(2)

O3#1-Zn 2.139(2) 2.127(2) - -

N1-Zn-N2 75.7(1) 78.4(1) 79.4(2) 79.2(1)

N1-Zn-N3 72.2(1) 74.4(1) 81.0(2) 79.7(1)

N1-Zn-N4 74.4(1) 78.4(1) 80.4(2) 78.4(1)

N1-Zn-O2 150.2(1) 156.2(1) 162.2(2) 159.0(1)

N1-Zn-O3#1 131.8(1) 118.5(1) - -

N2-Zn-N3 128.9(1) 144.8(1) 114.0(1) 103.7(1)

N2-Zn-N4 107.2(1) 99.8(1) 115.1(2) 122.9(1)

N2-Zn-O2 102.9(1) 103.8(1) 103.1(1) 104.4(1)

N2-Zn-O3#1 89.27(1) 89.8(1) - -

N3-Zn-N4 101.2(1) 96.2(1) 122.5(2) 122.6(1)

N3-Zn-O2 124.4(1) 110.1(1) 113.1(2) 118.5(1)

N3-Zn-O3#1 83.7(1) 84.0(1) - -

N4-Zn-O2 77.8(1) 77.9(1) 82.7(2) 82.5(7)

N4-Zn-O3#1 152.8(1) 162.2(1) - -

O2-Zn-O3#1 77.4(1) 85.3(1) - -

Coordination sphere around the sodium ion in {10 . Na(CF3SO3)}∞

Na-O1#2 2.287(2) O1#2-Na-O3#3 120.5(1)

Na-O2 2.329(2) O1#2-Na-O11#4 93.9(1)

Na-O3#3 2.303(2) O2-Na-O3#3 141.2(1)

Na-O11#4 2.377(2) O2-Na-O11#4 114.6(1)

O1#2-Na-O2 82.6(1) O3#3-Na-O11#4 95.9(1) #1 7: –x+1/2, y+1/2, -z; 8: –x+1, y-1/2, -z+2; #2 x-1, y, z; #3 x-1/2, -y+1/2, -z; #4 –x-1/2, -y+1, z-1/2

55

3.4.7. Apendix

These data were not published in this publication, because the x-ray analyeses data were

obtained after the publication has been accepted.

Table 3. Crystallographic Data for {[(Dpg-Gly)-HZn] ∞.(NaCF3SO3) ∞}

Compound

Formula C18H20F3N4NaO7SZn

Formula weight 581.80

Crystal size [mm3] 0.17 x 0.05 x 0.04 mm

Temperature [K] 100(2)

Crystal system Orthorhombic

Space group Pbca

a [Å] 17.870(2)

b [Å] 9.277(1)

c [Å] 28.265(5)

α [°] 90

β [°] 90

γ [°] 90

Volume [Å 3] 4686(1)

Z 8

Dcalcd [Mg/m3] 1.649

µ [mm-1] 1.227

θ-range [°] 3.29 – 27.00

Measured refls 5101

Independent refls 5101 (Rint = 0.0875)

Observed refls a 7904

Parameters 376

Goodness-of-Fit on F2 1.042

R1a 0.0514

wR2 (all data) 0.1184

abs. struct. params38

∆ρmax./min. [eÅ-3] 0.826 / -0.544 a[I>2σ(I)]

56

Table 4. Selected bond distances (Å) and angles (°) in the structures of {[(Dpg-Gly)-

HZn] . Na(CF3SO3)}∞

Zn-N1 2.322(3)

Zn-N2 2.153(3)

Zn-N3 2.157(3)

Zn-N4 2.054(3)

Zn-O2 2.163(2)

Zn-O3#1 2.056(3)

N1-Zn-N2 75.95(12)

N1-Zn-N3 76.57(11)

N1-Zn-N4 78.95(11)

N1-Zn-O2 156.16(10)

N1-Zn1-O3#1 122.35(10)

N2-Zn-N3 148.39(12)

N2-Zn-N4 93.63(12)

N2-Zn-O2 104.21(11)

N2-Zn-O3#1 90.53(12)

N3-Zn-N4 96.15(12)

N3-Zn-O2 107.24(11)

N3-Zn-O3#1 91.14(11)

N4-Zn-O2 77.25(11)

N4-Zn-O3#1 158.63(11)

O2-Zn-O3#1 81.41(9)

Coordination sphere around the sodium ion

Na-O1 2.263(3)

Na-O11#3 2.245(4)

Na-O13 2.280(4)

O1-Na-O11#4 110.64(13)

O1-Na-O13 123.36(14)

O11#4-Na-O13 100.65(13) #1 -x+1,y+1/2,-z+3/2; #2 -x+1,y-1/2,-z+3/2; #3 -x+1/2,y+1/2,z; #4 -x+1/2,y-1/2,z;

57


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Hoveyda, Angew. Chem., Int. Ed. Engl., 1997, 36, 1704; d) B. M. Cole, K. D.

Shimizu, C. A. Krueger, J. P. A. Harrity, M. L. Snapper, A. H. Hoveyda, Angew.

Chem., Int. Ed. Engl., 1996, 35, 1668.

34. G. Xing, V. J. DeRose, Current Op. Chem. Biol., 2001, 5, 196.

60

35. a) F. Hojland, H. Toftlund, S. Yde-Andersen, Acta Chem. Scand., 1983, A 37,

251; b) J. K. Romary, R. D. Zachariasen, J. D. Barger, H. Schiesser, J. Chem.

Soc., Dalton Trans. (C) 1968, 2884.

36. SADABS, Bruker-AXS, Inc., Madison, WI, U.S.A., 2002.

37. SHELXTL NT 6.12, Bruker-AXS, Inc., Madison, WI, U.S.A., 2002.

38. H. D. Flack, Acta Crystallogr., 1983, A39, 876.

61

Chapter 4

4.1. Synthesis of chiral quadridentate ligands derived from L-alanine

and L-leucine methyl ester

4.1.1. Bromoacetylated Amino Acid Esters. BrAc–Ala–OCH3: L-Ala-OCH3 x HCl

(5.00 g, 35.8 mmol) was suspended in 150 mL of chloroform. Triethylamine (9.97 mL,

71.6 mmol) was added with vigorously stirring at room temperature.

Bromoacetylbromide (3.12 mL, 35.8 mmol) was dissolved in 150 mL of chloroform,

and the solution was added dropwise to the suspension over a period of 2h. The

resulting red-orange mixture was evaporated using a rotary evaporator, and dry

substance was redissolved in 150 mL ethyl acetate. Insoluble Et3N+HBr– and Et3N+HCl–

were filtered of and the solvent removed under reduced pressure until dryness. The

crude red-brown oil was purified by silica gel column chromatography using EtOAc/n-

C6H14 (2:1) as the eluent. A yellow fraction containing some amino acid ester starting

material, elueted first. The product was elueted next as a broad yellow fraction. The

other layers which were separated from the product were not collected. The solution

containing the desired product was concentrated by rotary evaporator and the resulting

light–yellow oil dried under vacuum. Colorless crystals were obtained after keeping the

oil in a deep freezer (-30 °C) overnight. Yield: 5.33g, 23.80 mmol, 66.45%.

C6H10O3NBr (224.05 g/mol) FAB-MS (nitrobenzyl alcohol): m/z = 224[M+]. 1H NMR

(300MHz, CDCl3): δ = 1.46 (m, 3H, αCHCH3), 3.77 (s, 3H, OCH3), 3.89 (s, 1H,

BrCH2), 4.07 (s, 1H, BrCH2), 4.59 (q, 1H, αCH), 7.17 (br. s, 1H, NHamide). 13C NMR

(75MHz, CDCl3): δ = 18.10 (αCHCH3), 28.67 (BrCH2), 48.53 (OCH3), 52.63 (αC),

165.41 (C(O)amide), 172.81 (C(O)ester). IR (KBr) / cm-1: 1747COOMe, 1667CONHR I,

1594CONHR II.

BrAc–Leu–OCH3: L–Leu–OCH3 x HCl (5.30 g, 29.18 mmol) was dissolved in 150 mL

of chloroform. Triethylamine (8.12 mL, 58.35 mmol) was added with stirring and the

mixture was cooled to 0°C in an ice/salt bath. Bromacetylbromide (2.54 mL, 29.18

mmol) was dissolved in 100 mL of chloroform, and the solution was added dropwise to

the cold suspension over period of 2h. The mixture was stirred in addition for another

62

1h, without further cooling. The chloroform was removed using a rotary evaporator and

the dry substance was redissolved in ethyacetate, insoluble Et3N+HBr– and Et3N+HCl–

were filtered of and the solvent removed under reduced pressure. The crude colorless oil

was purified by silica gel column chromatography using AcOEt/n–C6H14 (2:1) as

eluent. A light yellow fraction containing some amino acid ester starting material,

elueted first. The product was elueted next as a broad light yellow fraction. The other

layers which were separated from the product were not collected. The solution

containing the desired product was concentrated by rotary evaporator and the resulting

light–yellow oil dried under vacuum. By standing in a deep–freezer (–30°C) it’s solidify

as a colourless solid. Yield for C9H16BrNO3 (266.13 g/mol): 6.40 g, 24.03 mmol,

82.35%. FAB–MS (nitrobenzyl alcohol): m/z = 269 [M++2H], 267 [M+]. 1H NMR

(300MHz, CDCl3): δ = 0.96 (2xd, 6H, CH(CH3)2) 1.67 (m, 3H, βCH2 + CH(CH3)2), 3.75

(s, 3H, OCH3), 3.90 (s, 2H, BrCH2), 4.63 (m, 1H, αCH), 6.92 (d, br, 1H, NHamide). 13C

NMR (75MHz, CDCl3): δ = 21.94, 22.79 (CH(CH3)2), 24.87 (CH(CH3)2), (28.76

(BrCH2), 41.35 (βC), 51.38 (OCH3), 52.45 (αC), 165.49 (C(O)amide), 172.84 (C(O)ester).

IR (KBr) / cm–1: 1745νCOOMe, 1659νCONHR I, 1542νCONHR II.

4.1.2. Ligands. Genral Procedure. Equimolar amounts of bis(picolyl)amine (bpa), the

respective bromoacetylated amino acid ester, and diisopropylethylamine (DIPEA) were

dissolved in CH3CN. The solution was stirred for 20h at room temperature. All solvents

were removed by rotary evaporation. Ethyl acetate was added, resulting in the

precipitation of the ammonium halide salt which was filtered off and discarded. The

filtrate was concentrated to dryness yielding a brown oil which was purified on a silica

gel column using CH2Cl2/MeOH (11:1) as the eluent. A small yellow fraction

containing some amino acid starting material eluted first. The product followed in a

broad light yellow fraction. Other layers were not collected. The product fraction was

concentrated to dryness by rotary evaporation and the resulting brown oil dried under

vacuum.

Dpg–Ala–OCH3: BrAc–Leu–OMe (2.00 g, 8.92 mmol), bpa (1.78 g, 8.92 mmol),

DIPEA (1.56 mL, 8.92 mol), 100 mL CH3CN, 100 mL AcOEt. Yield for C18H22N4O3

(342.39 g/mol): 2.24 g, 6.54 mmol, 73.35 %. FD-MS (CDCl3): m/z = 343 [M+]. 1H

NMR (300MHz, CDCl3): δ = 1.48 (d, 3H, αCHCH3), 3.36 (s, 2H, C(O)CH2),

63

3.70 (s, 3H, OCH3), 3.89 (2xd, 4H, pyCH2), 4.62 (m, 1H, αCH), 7.17 (m, 2H, H5py),

7.34 (d, 2H, H3py), 7.62 (m, 2H, H4py), 8.55 (m, 2H, H6py), 9.27 (d, 1H, 3JH,H = 8.42Hz;

NHamide); 13C NMR (75MHz, CDCl3): δ = 18.34 (αCHCH3), 48.16 (αC), 52.59 (OCH3),

58.27 (C(O)CH2), 60.65 (pyCH2), 122.75 (C5py), 123.54 (C3py), 136.92 (C4py), 149.61

(C6py), 158.75 (C2py), 171.65 (C(O)amide), 173.91 (C(O)ester). IR (KBr) / cm-1:

1742νCOOMe, 1667νCONHR I, 1594νCONHR II.

Dpg–Leu–OCH3: BrAc–Leu–OCH3 (1.65 g, 6.19 mmol), bpa (1.23 g 6.19 mmol),

DIPEA (1.08 mL, 6.19 mmol), 100 mL CH3CN, 100 mL AcOEt. Yield for C21H28N4O3

(384.47 g/mol): 2.14 g, 5.56 mmol, 89.92 %. FD–MS (CDCl3): m/z = 385 [M+]. 1H

NMR (300MHz, CDCl3): δ = 0.93 (2 x d, 6H, CH(CH3)2), 1.73 (m, 3H, αCH2 +

CH(CH3)2), 3.35 (s, 2H, C(O)CH2), 3.68 (s, 3H, OCH3), 3.94 (2xd, 4H, 2 x pyCH2),

4.62 (m, 1H, αCH), 7.16 (m, 2H, H5py), 7.34 (br. d, 2H, H3py), 7.62 (m, 2H, H4py), 8.55

(d, 2H, H6py), 9.21 (br. d, 1H, 3JH,H = 8.42Hz; NHamide) 13C NMR (75MHz, CDCl3): δ =

21.66, 23.02 (CH(CH3)2), 24.95 (CH(CH3)2), 40.89 (βC), 50.61 (αC), 52.06 (OCH3),

57.72 (C(O)CH2), 60.14 (pyCH2), 122.37 (C5py), 123.15 (C3py), 136.55 (C4py), 149.17

(C6py), 158.40 (C2py), 171.53 (C(O)amide), 173.57 (C(O)ester). IR (KBr) / cm–1:


4.2. Synthesis of chiral quadridentate ligands Dpg-Xaa – type

General Procedure. Equimolar amounts of Dpg-Xaa (Xaa = Leu, Phe, Tyr, Trp) and

sodium hydroxide were dissolved in CH3OH. The solution was stirred for 2h at room

temperature and the solvent were removed by rotary evaporation. Dry residue were

dissolved in water, the pH was adjusted to pH 9.00, using 2M NaOH and the mixture

stirred overnight. The pH was adjusted to pH 5.00, using 1M HCl solution, and the

water was removed using rotary evaporator until dryness. Methanol was added,

resulting in the precipitation of the sodium chloride salt which was filtered using micro

filter (0.2µ). The filtrate was concentrated to dryness yielding a yellow or colorless solid

(foam) which was purified using diethyl ether/MeOH mixture or on a silica gel column

using CH2Cl2/MeOH (11:5) as the eluent. The product followed in a broad light yellow

fraction. Other layers were not collected. The product fraction was concentrated to

64

dryness by rotary evaporation and the resulting light yellow oil dried under vacuum

resulting solid foam (yellow or colorless) (Scheme 1).

HN

NN

O

OH

O

N

HN

NN

O

OCH3

O

N 1. NaOH / MeOH, r.t., 12h

2. 2M HClRR

1: R = C6H5: Dpg-Phe-OH2: R = C6H4OH: Dpg-Tyr-OH3: R = indolyl: Dpg-Trp-OH4: R = iso-propyl: Dpg-Leu-OH

Scheme 1. General strategy for synthesis of ligands Dpg-Xaa - type

Dpg–Leu–OH: Dpg–Leu–OCH3 (0.87 g, 2.30 mmol) and (0.09 g, 2.30 mmol) NaOH

were dissolved in 50 mL CH3OH. The solution was stirred for 2h at room temperature

and the solvent were removed by rotary evaporation. Dry residue were dissolved in

water, the pH was adjusted to pH 10.00, using 2M NaOH and the mixture stirred

overnight. The pH was adjusted to pH 4.00, using 1M HCl solution, and the water was

removed using rotary evaporator until dryness. 50 mL CH2Cl2 was added, resulting in

the precipitation of the sodium chloride salt which was filtered using micro filter (0.2µ).

The filtrate was concentrated to dryness yielding a yellow or colorless solid (foam).

Yield: 0.70 g, 1.76 mmol, 76.50 %. Elemental analysis (%) calcd. for Dpg–Leu–OH x

1.5H2O, C20H26N4O3 x 1.5H2O (397.82 g/mol): C 60.44, H 7.35, N 14.10 found: C

60.61, H 6.82, N 14.04. FAB–MS (nitrobenzyl alcohol); m/z: 372 [M+ + 2H]. 1H NMR

(300MHz, D2O / TSP): δ = 0.82 (td, 6H, CH(CH3)2), 1.36 (m, 1H, CH(CH3)2), 1.54 (m,

2H, βCH2), 3.47 (s, 2H, C(O)CH2), 4.03 (s, 4H, 2 x py–CH2), 4.13 (m, 1H, αCH), 7.47

(m, 2H, H5py), 7.60 (d, 2H, H3py), 7.96 (td, 2H, H4py), 8.50 (d, 2H, H6py). 13C NMR

(75MHz, CDCl3): δ = 23.76, 25.23 (CH(CH3)2), 27.33 (CH(CH3)2), 43.74 (βC), 56.43

(αC), 56.43 (C(O)CH2), 60.84 (pyCH2), 62.43 (pyCH2), 126.89 (C5py), 127.95 (C3py),

143.24 (C4py), 149.30 (C6py), 158.42 (C2py), 175.10 (C(O)amide), 182.20 (C(O)OH). IR

(KBr) / cm–1: 17299νCOOH, 1668νCONHR I, 1595νCONHR II.

65

Dpg-Phe-OH: 1.77 g (4.24 mmol) Dpg-Phe-OCH3, 0.17 g (4.24 mmol) NaOH, 100ml

CH3OH, 100 ml H2O. x-ray suitable crystals were obtained by keeping the methanol

solution of compound with addition af diethylether at deep-freezer (-30 °C) (Figure 1,

and Table 1).

Figure 1. Molecular structure of Dpg-Phe-OH

Table 1. Crystallographic data and selected bond distances (Å) and angles (°) Dpg-Phe-OH x CH3OH Formula C24H28N4O4 N1-C13 1.462(2) Formula weight 436.50 N1-C1 1.464(2) Crystal size [mm3] 0.16 x 0.14 x 0.11 mm N1-C7 1.469(2) Temperature [K] 100(2) N2-C6 1.346(2) Crystal system Triclinic N2-C2 1.347(2) Space group P-1 N3-C8 1.344(2) a [Å] 9.4957(6) N3-C12 1.348(2) b [Å] 9.9083(5) N4-C14 1.331(2) c [Å] 12.8647(8) N4-C15 1.452(2) α [°] 105.800(5) N4-H4N 0.888(19) β [°] 90.576(5) O1-C14 1.2465(19) γ [°] 96.492(5) O3-C16 1.319(2) Volume [Å 3] 1156.1(2) C13-C14 1.519(2) Z 2 C14-N4-C15 121.10(14) Dcalcd [Mg/m3] 1.254 C14-N4-H4N 118.8(12) µ [mm-1] 0.087 C15-N4-H4N 118.4(12) θ-range [°] 3.05 – 27.10 O1-C14-N4 124.01(15) Measured refl. 22573 O1-C14-C13 119.41(15) Independent refl. 5096 (Rint=0.0704) N4-C14-C13 116.55(14) Observed refl. a 7904 N4-C15-C16 110.29(14) Parameters 373 Goodness-of-Fit on F2 1.026 R1

a 0.0476 wR2 (all data) 0.1030 ∆ρmax./min. [eÅ-3] 0.242 / -0.253 a[I>2σ(I)]

66

Yield: 1.62 g, 3.71 mmol, 87.53%. Elemental analysis (%) calcd. for Dpg-Phe-OH x

CH3OH, C24H28N4O4 (436.50 g/mol): C 66.04, H 6.47, N 12.84; found: C 65.92, H 5.87,

N 13.33; FAB-MS (nitrobenzyl alcohol): m/z = 405 [M+]; 1H NMR (300MHz, D2O /

TSP): δ = 2.94 (dd, 1H, βCH2), 3.20 (dd, 1H, βCH2), 3.32 (d, 2H, C(O)-CH2), 3.77 (s,

4H, 2 x pyCH2), 4.43 (m, 1H, αCH), 6.98 - 7.12 (m, 5H, H2,3,4,5,6phenyl), 7.47 (m, 4H,

H3py + H5py), 7.93 (td, 2H, H4py), 8.43 (br. d, 2H, H6py). 13C NMR (75MHz, D2O /

TSP): δ = 40.18 (βC), 58.29 (αC), 61.11 (C(O)-CH2), 61.87 (pyCH2), 127.03 (C5py),

128.02 (C3py), 129.58 (C4phenyl), 131.23 (C3,5phenyl), 131.98 (C2,6phenyl), 140.14

(C1phenyl) 143.74 (C4py), 148.78 (C6py), 158.02 (C2py), 174.68 (C(O)amide), 180.32

(C(O)OH). IR (KBr) / cm-1: 1729νCOOH, 1667νCONHR I, 1598νCONHR II.

Dpg-Tyr-OH: 1.40 g (3.22 mmol) Dpg-Tyr-OCH3, 0.13 g (3.22 mmol) NaOH, 100ml

CH3OH, 100 ml H2O. Yield: 1.07 g, 2.23 mmol, 69.39%. Elemental analysis (%) calcd.

for Dpg-Tyr-OH x NaCl, C23H24N4O4NaCl (478.90 g/mol): C 57.68, H 5.05, N 11.70;

found: C 57.10, H 5.19, N 11.30; FAB-MS (nitrobenzyl alcohol): m/z = 422 [M++2H]; 1H NMR (300MHz, D2O / TSP): δ = 2.91 (dd, 1H, βCH2), 3.09 (dd, 1H, βCH2), 3.25

(2xd, 2H, C(O)-CH2), 3.66 (s, 4H, pyCH2), 4.35 (m, 1H, αCH), 6.50 (d, 2H, H2,6PhOH),

6.88 (d, 2H, H3,5PhOH), 7.33 (m, 4H, H3,5), 7.80 (td, 2H, H4py), 8.38 (br. d, 2H, H6py).

13C NMR (75MHz, D2O / TSP): δ = 38.98 (βC), 58.13 (αC), 60.93 (C(O)CH2), 62.42

(pyCH2), 117.79 (C1PhOH), 126.46 (C5py), 127.33 (C3py), 131.56 (C2,6PhOH), 133.22

(C3,5PhOH), 142.27 (C4PhOH), 149.77 (C4py), 156.86 (C6py), 158.76 (C2py), 174.90

(C(O)amide), 180.23 (C(O)OH). IR (KBr) / cm-1: 1709νCOOH, 1655νCONHR I,

1597νCONHR II.

Dpg-Trp-OH: The synthesis has been described in Chapter 3.

67

4.3. Synthesis of Zn(II) complexes using chiral quadridentate ligands

Dpg-Ala-OMe and Dpg-Leu-OMe

[Zn(Dpg–Leu–OCH3)(H2O)](CF3SO3)2: Solid Zn(CF3SO3)2 (1.20 g, 3.28 mmol) of

was added to a stirred solution of Dpg–Leu–OCH3 (1.26 g 3.28 mmol) in 50 mL

CH3CN. Stirring was continued overnight at room temperature followed by removal of

all solvent under vacuum. 50 mL CH2Cl2 was added to the residue and the resulting

suspension left in refrigerator (–20°C) overnight. Unchanged Zn(CF3SO3)2 precipitated

and was filtered off. The product obtained after stripping all solvent from the filtrate

was dried under vacuum and used without further purification. Yield: 2.20 g, 2.87

mmol, 87.56%. Elemental analysis (%) calcd. for C23H30F6N4O10S2Zn (766.02 g/mol):

C 36.06, H 3.95, N 7.31, S 8.37; found C 35.92, H 3.78, N 7.26, S 8.78%; FAB–MS

(nitrobenzyl alcohol): m/z = 598 [M+–CF3SO3–H2O], 497 [M+–2CF3SO3–H2O]. 1H

NMR (300MHz, CDCl3): δ 0.83 (2 x d, 6H, CH(CH3)2), 1.38 – 1.57 (m, 3H, αCH2,

CH(CH3)2), 3.62 (s, 3H, OCH3), 4.04 (s, 2H, C(O)CH2), 4.36 (m, 4H, pyCH2), 4.51 (m,

1H, αCH), 4.83 (br. s, 2H, H2O), 7.62 (m, 4H, H3,5py), 8.04 (m, 2H, H4py), 8.75 (d, 1H, 3JH,H = 8.42Hz; NHamide), 8.89 (m, 2H, H6py). 13C NMR (75MHz, CDCl3): δ 21.38,

22.41 (CH(CH3)2), 24.60 (CH(CH3)2), 39.94 (βC), 52.56 (αC), 52.65 (OCH3), 56.41

(C(O)CH2), 58.14 (pyCH2), 125.35 (C5py), 125.70 (C3py), 141.65 (C4py), 148.85 (C6py),

154.30 (C2py), 171.23 (C(O)amide), 173.78 (C(O)ester). IR (KBr) / cm–1: 1745νCOOMe,

1633νCONHR I, 1575νCONHR II, 1280νCF3SO3, 1253νCF3SO3.

68

[Zn(Dpg-Ala-OCH3)(Cl)2]: Solid ZnCl2 (0.41 g, 3.00 mmol) was added to a stirred

solution of Dpg-Ala-OCH3 (0.97 g, 3.00 mmol) in 50 mL of CH3CN. Stirring was

continued overnight at room temperature followed by removal of all solvent under

vacuum. The product was dissolved in 50 mL nonporous water (pH = 4.25) and the pH

was adjusted to 7.00, using 2M NaOH solution. The water was removed using rotary

evaporator and the substance was dried under vacuum until dryness. The product was

dissolved in CH2Cl2 and filtered off using micro filter (0.2µ). The clear filtrate was

concentrated to dryness and solid material dried under reduced pressure. The dry

substance was dissolved in CH2Cl2 with addition of diethyl ether. Keeping the cloudy

solution in a deep-freezer (-30°C), afforded x-ray suitable crystals (Figure 2 and Table

2). Yield (bulk): 1.24 g, 2.59 mmol, 86.64%. Elemental analysis (%) calcd. for

C18H22Cl2N4O3Zn (M = 478.69 g/mol): C 45.16, H 4.63, N 11.70; found C 45.48, H

4.64, N 11.64; FAB-MS (nitrobenzyl alcohol): m/z = 441[M+ - Cl], 406[M+ - 2Cl]. 1H

NMR (300MHz, D2O): δ = 1.04 (d, 3H, αCHCH3), 3.45 (s, 3H, OCH3), 3.60 (s, 2H,

C(O)CH2), 4.10 (q, 1H, αCH ), 4.34 (2xd, 4H, pyCH2), 7.48 (m, 4H, H5py + H3py), 7.95

(m, 2H, H4py), 8.55 (m, 2H, H6py). 13C NMR (75MHz, D2O): δ = 14.78 (αCCH3), 48.16

(αC), 52.21 (OCH3), 57.29 (C(O)CH2), 60.08 (pyCH2), 123.88 (C5py), 124.30 (C3py),

140.15 (C4py), 146.58 (C6py), 152.41 (C2py), 171.71 (C(O)amide), 173.18 (C(O)ester). IR

(KBr) / cm-1: 1745νCOMe, 1667νCONHR I, 1609νCONHR II.

69

Figure 2. Molecular structure of [Zn(Dpg-Ala-OMe)Cl2]

Table 2. Crystallographic data and selected bond distances (Å) and angles (°)

[Zn(Dpg-Ala-OMe)Cl2].CH2Cl2 Formula C19H24Cl4N4O3Zn Zn-N3 2.079(2) Formula weight 563.59 Zn-N2 2.088(2) Crystal size [mm3] 0.18 x 0.14 x 0.08 mm Zn-Cl2 2.2914(7) Temperature [K] 100(2) Zn-Cl1 2.3097(7) Crystal system Triclinic Zn-N1 2.349(2) Space group P1 N3-Zn-N2 115.31(9) a [Å] 8.9131(4) N3-Zn-Cl2 117.94(6) b [Å] 10.6909(6) N2-Zn-Cl2 118.42(7) c [Å] 13.1787(6) N3-Zn-Cl1 97.40(6) α [°] 74.944(4) N2-Zn-Cl1 98.61(7) β [°] 89.258(4) Cl2-Zn-Cl1 102.96(3) γ [°] 81.957(4) N3-Zn-N1 75.51(8) Volume [Å 3] 1200.39(10) N2-Zn-N1 75.53(8) Z 2 Cl2-Zn-N1 89.82(6) Dcalcd [Mg/m3] 1.559 Cl1-Zn-N1 167.20(6) µ [mm-1] 1.496 θ-range [°] 3.37 – 27.88 Measured refls 38351 Independent refls 10522 (Rint = 0.0259) Observed refls a 7904 Parameters 565 Goodness-of-Fit on F2 1.034 R1

a 0.0250 wR2 (all data) 0.0580 abs. struct. params38 0.024(6) ∆ρmax./min. [eÅ-3] 0.786 / -0.376 a[I>2σ(I)]

70

4.4. Synthesis of Zn(II)peptide based coordination polymer and N-

anionic coordinated monomer derived from leucine

[{Zn(Dpg–Leu–O)(H2O)}n](OTf)n: [Zn(Dpg–Leu–OCH3)(H2O)](CF3SO3)2 (1.20 g,

1.56 mmol) was dissolved in 30 mL H2O. The pH was adjusted to 11.00 using 2M

NaOH. Consumption of base was monitored using a pH meter to keep the pH

approximately constant at 10. The mixture was stirred at room temperature until the pH

remained constant (ca. 2d). Lowering the pH using 1M HCl solution, was followed by

immediate precipitation of the product which was collected on a sintered glass filter

funnel and dried under vacuum. The x–ray suitable crystals, as colorless blocks, has

been obtained from the supernatant solution at pH 7.54 by slow evaporation of the

solvent (Figure 3 and Table 3). Yield: 0.84 g, 1.40 mmol, 89.43%. Elemental analysis

(%) calcd. for [{Zn(Dpg–Leu–O)(H2O)}](OTf) x 2H2O, C21H31F3N4O9SZn (637.93

g/mol): C 39.54, H 4.90, N 8.78, S 5.03; found: C 39.88, H 4.35, N 8.89, S 5.82; FAB–

MS (nitrobenzyl alcohol): m/z = 433 [M+–(CF3SO3+3H2O)]; 1H NMR (300 MHz,

CD3CN): δ 0.95 (br. d, 6H, CH(CH3)2), 1.76 (br. s, 3H, βCH2 + CH(CH3)2), 2.32 (s, 5H,

XH2O), 3.66 (br. d, 1H, C(O)CH2), 3.90 (br. d, 1H, C(O)CH2), 4.08 – 4.23 (m, 5H, 2 x

pyCH2 + αCH), 7.33 – 7.53 (m, 4H, H3,5py), 7.93 – 8.03 (m, 3H, H4py + NHamide), 8.64

(s, br, 2H, H6py). 13C NMR (75MHz, CD3CN): δ 23.91, 24.83 (CH(CH3)2), 27.28

(CH(CH3)2), 42.79 (βC), 57.51 (αC), 61.12 (br. m, C(O)CH2 + pyCH2), 126.85 (C5py),

127.35 (C3py), 143.29 (C4py), 150.94, 151.14 (C6py), 157.05 (C2py), 174.86 (C(O)amide),

178.35 (C(O)ester). IR (KBr) / cm–1: 1634νCOO-, 1611νCONHR, 1277νCF3SO3, 1255νCF3SO3. 1H–NMR (300 MHz, D2O / DCl): δ 0.62 (d, br, 3H, CH(CH3)2), 0.74 (br. d, 3H,

CH(CH3)2), 0.93 (br. m, 1H, CH(CH3)2), 1.37 (br. s, 2H, βCH2), 3.74 (br. s, 2H,

C(O)CH2), 4.03 (m, 2H, pyCH2), 4.50 (m, 3H, αCH + pyCH2), 7.60 (m, 4H, H5py +

H3py), 8.08 (m, 2H, H4py), 8.69 (br. s, 2H, H6py). 13C NMR (75MHz, D2O/DCl – TSP):

δ = 23.54, 25.13 (CH(CH3)2), 27.09 (CH(CH3)2), 43.31 (βC), 57.17 (αC), 61.05

(C(O)CH2), 63.25, 63.55 (pyCH2), 127.27 (C5py), 127.70 (C3py), 143.78 (C4py), 150.43

(C6py), 155.97, 156.39 (C2py), 174.67 (C(O)amide), 181.64 (C(O)ester).

71

Figure 3. x-ray structure of [{Zn(Dpg–Leu–O)(H2O)}n](OTf)n


[{Zn(Dpg–Leu–O)(H2O)}n](OTf)n . H2O Formula C21H31F3N4O9SZn Zn-O2#1 2.003(4) Formula weight 637.93 Zn-N2 2.105(5) Crystal size [mm3] 0.23 x 0.10 x 0.08 mm Zn-N3 2.141(5) Temperature [K] 100(2) Zn-O4 2.143(4) Crystal system Orthorhombic Zn-O1 2.159(4) Space group P212121 Zn-N1 2.211(5) a [Å] 11.049(1) O2#1-Zn-N2 102.49(18) b [Å] 14.340(2) O2#1-Zn-N3 101.27(18) c [Å] 17.472(2) N2-Zn-N3 156.2(2) α [°] 90 O2#1-Zn-O4 95.65(17) β [°] 90 N2-Zn-O4 92.0(2) γ [°] 90 N3-Zn-O4 86.6(2) Volume [Å 3] 2768.3(6) O2#1-Zn-O1 87.85(15) Z 4 N2-Zn-O1 93.89(17) Dcalcd [Mg/m3] 1.531 N3-Zn-O1 86.08(16) µ [mm-1] 1.037 O4-Zn-O1 172.36(19) θ-range [°] 3.58 – 25.67 O2#1-Zn-N1 167.70(16) Measured refl. 31025 N2-Zn-N1 77.9(2) Independent refl. 5243 (Rint = 0.0802) N3-Zn-N1 78.7(2) Observed refl. a 7904 O4-Zn-N1 96.62(18) Parameters 427 O1-Zn-N1 79.87(16) Goodness-of-Fit on F2 1.105 R1

a 0.0471 wR2 (all data) 0.1271 abs. struct. param.38 -0.01(2) ∆ρmax./min. [eÅ-3] 0.978 / -0.654 a[I>2σ(I)]; #1 x+1/2,-y+3/2,-z+1; #2 x-1/2,-y+3/2,-z+1;

72

[Zn(Dpg–Leu)–H]: Solid [{Zn(Dpg–Leu–O)(H2O)}n](OTf)n (1.62 g, 2.54 mmol) was

dissolved in 30 mL H2O and the pH adjusted to 12.00 using 2M NaOH solution. The

mixture was stirred overnight and the solvent removed by rotary evaporation. The

residual solid material was dried under vacuum and purified by from

methanol/diethylether mixture. Yield: 1.19 g, 1.96 mmol, 77.33%. Elemental analysis

(%) calcd. for [Zn(Dpg–Leu)–H] x Na(CF3SO3), C21H24F3N4NaO6SZn (605.88gmol–1):

C 41.63, H 3.99, N 9.25, S 5.29; found: C 41.79, H 4.44, N 9.96, S 5.33; FAB–MS

(nitrobenzyl alcohol): m/z = 456 [M++Na], 434 [M+]. 1H–NMR (300 MHz, D2O/NaOD

– TSP): δ = 0.57 (d, 3H, CH(CH3)2), 0.77 (d, 3H, CH(CH3)2), 1.16 (br. m, 1H,

CH(CH3)2), 1.66 (m, 1H, βCH2), 1.83 (m, 1H, βCH2), 3.18 (d, 1H, C(O)CH2), 3.39 (d,

1H, C(O)CH2), 3.91 – 4.28 (4 x d, 4H, pyCH2), 4.42 (m, 1H, αCH), 7.45 (d, 2H, H5py),

7.58 (m, 2H, H3py), 8.00 (m, 2H, H4py), 8.69 (br. s, 2H, H6py). 13C NMR (75MHz,

D2O/NaOD – TSP): δ = 24.04, 25.32 (CH(CH3)2), 27.43 (CH(CH3)2), 45.60 (βC), 58.72

(αC), 59.54 (C(O)CH2), 60.49, 61.13 (pyCH2), 127.00 (C5py), 127.34 (C3py), 143.15

(C4py), 151.32 (C6py), 158.02 (C2py), 174.09 (C(O)amide), 186.47 (C(O)acid).

IR (KBr) / cm–1: 1655νCOO-, 1601νCONHR, 1264νCF3SO3.

4.5. Synthesis of Cu(II)peptide based coordination polymer derived

from leucine

[{Cu(Dpg–Leu–O)(H2O)}n](OTf)n: Solid Cu(OTf)2 (1.27 g, 3.51 mmol) was added to

a stirred solution of Dpg–Leu–OH (1.30 g, 3.51 mmol) in 30mL of H2O. The pH was

adjusted to 7.54 using 2M NaOH, followed by immediate precipitation of deep–blue

solid material which was collected on a sintered glass filter funnel and dried under

vacuum. The x–ray suitable crystals, as blue blocks, has been obtained from the

supernatant solution by slow evaporation of the solvent (Figure 4 and Table 4). Yield:

1.34 g, 2.11 mmol, 60.02%. Elemental analysis (%) calcd. for [Cu(Dpg–Leu–

O)(H2O)](OTf) x 2H2O, C21H27CuF3N4O7S (636.10 g/mol): C 39.65, H 4.91, N 8.81, S

5.04; found C 39.71, H 4.38, N 9.04, S 5.09; FAB–MS (nitrobenzyl alcohol): m/z = 433

[M+- (OTf + 3H2O)]. IR (KBr) / cm–1: 1650νCOO-, 1613νCONHR, 1255νCF3SO3.

73

Figure 4. x-ray structure of [{Cu(Dpg–Leu–O)(H2O)}n](OTf)n


[{Cu(Dpg–Leu–O)(H2O)}n](OTf)n . H2O Formula C21H31.50CuF3N4O9.25S Cu-O2#1 1.935(3) Formula weight 640.60 Cu-N2 1.996(4) Crystal size [mm3] 0.18 x 0.14 x 0.12 mm Cu-N3 2.009(3) Temperature [K] 100(2) Cu-N1 2.071(3) Crystal system Orthorhombic Cu-O1 2.274(3) Space group P212121 Cu-O4 2.496(3) a [Å] 11.230(1) O2#1-Cu-N2 98.57(14) b [Å] 14.006(2) O2#1-Cu-N3 96.65(13) c [Å] 17.390(2) N2-Cu-N3 164.25(14) α [°] 90 O2#1-Cu-N1 171.46(13) β [°] 90 N2-Cu-N1 82.20(15) γ [°] 90 N3-Cu-N1 83.34(13) Volume [Å 3] 2735.2(6) O2#1-Cu-O1 90.24(11) Z 4 N2-Cu-O1 95.56(12) Dcalcd [Mg/m3] 1.556 N3-Cu-O1 88.35(12) µ [mm-1] 0.952 N1-Cu-O1 81.22(11) θ-range [°] 3.62 – 27.10 O2#1-Cu-O4 98.57(12) Measured refl. 37644 N2-Cu-O4 91.18(13) Independent refl. 6007 (Rint = 0.0325) N3-Cu-O4 82.59(13) Observed refl. a 7904 N1-Cu-O4 89.91(12) Parameters 434 O1-Cu-O4 168.01(11) Goodness-of-Fit on F2 1.099 R1

a 0.0471 wR2 (all data) 0.1271 abs. struct. param.38 0.053(16) ∆ρmax./min. [eÅ-3] 0.693 / -0.655 a[I>2σ(I)]; #1 x-1/2,-y+3/2,-z+1; #2 x+1/2,-y+3/2,-z+1

74

4.6. Synthesis of Ni(II)peptide based coordination dimer derived from

phenylalanine

[{Ni(Dpg–Phe–O)(CH3OH)}2]Cl2: Solid NiCl2 x 6H2O (0.31g, 1.30mmol) was added

to a stirred solution of Dpg–Phe–OH (0.53g, 1.30 mmol) in 50 mL of H2O. Colour

turned from green to light–blue (pH = 2.4). pH was adjusted to 5.2 using 2M NaOH

solution. The mixture stirred overnight. Water was removed used a rotary evaporator

and the blue solid material was dissolved in methanol and into the solution a diethyl

ether was diffused for period of four days. Clear light–blue filtrate was transferred into

another flask, and left in deep–freezer (–30°C) overnight which resulted with x–ray

suitable violet crystals (Figure 5 and table 5). Yield (bulk): (0.70 g, 0.58 mmol, 45.12%)

calcd. to [(Dpg-Phe-O)Ni(H2O)]2Cl2 x 9H2O, C46H68Cl2Ni2O17; (M = 1193.37gmol-1).

FAB-MS (nitrobenzyl alcohol): m/z = 462 [M+]. IR (KBr) / cm–1: 1633νCOO-,

1607νCONHR. UV – Vis (MeOH); λmax, nm (ε, dm3 mol-1 cm-1): 586(1175).

Figure 5. Molecular structure of [{Ni(Dpg–Phe–O)(CH3OH)}2]Cl2

75


[{Ni(Dpg–Phe–O)(CH3OH)}2]Cl2 Formula C53H74Cl2N8Ni2O13 Ni1-N2 2.044(3) Formula weight 1219.52 Ni1-O6 2.058(2) Crystal size [mm3] 0.28 x 0.19 x 0.12 mm Ni1-N3 2.063(3) Temperature [K] 100(2) Ni1-O1 2.073(2) Crystal system Monoclinic Ni1-N1 2.086(2) Space group P21/n N2-Ni1-O6 173.10(10) a [Å] 14.391(2) N2-Ni1-N3 90.97(10) b [Å] 17.002(3) O6-Ni1-N3 87.45(9) c [Å] 24.136(4) N2-Ni1-O1 91.34(9) α [°] 90 O6-Ni1-O1 88.27(8) β [°] 97.923(8) N3-Ni1-O1 163.11(10) γ [°] 90 N2-Ni1-N1 83.72(10) Volume [Å 3] 5849(2) O6-Ni1-N1 89.42(9) Z 4 N3-Ni1-N1 82.96(10) Dcalcd [Mg/m3] 1.385 O1-Ni1-N1 80.66(9) µ [mm-1] 0.802 θ-range [°] 3.32 – 27.10 Measured refl. 143652 Independent refl. 12884 (Rint = 0.0686) Observed refl. a 7904 Parameters 777 Goodness-of-Fit on F2 1.011 R1

a 0.0510 wR2 (all data) 0.1238 abs. struct. param.38 0.02(2) ∆ρmax./min. [eÅ-3] 0.862 / -0.939 a[I>2σ(I)];

76

4.7. Synthesis of Cd(II), Co(II) and Mn(II) complexes using chiral

quadridentate ligand Dpg-Phe-OMe

[(Dpg–Phe–OCH3)Cd(NO3)2]: Solid Cd(NO3)2 x 6H2O (0.33 g, 1.06 mmol) was added

to a stirred solution of Dpg–Phe–OCH3 (0.45 g, 1.06 mmol) in 50 mL of CH3OH..

Stirring was continued overnight at room temperature followed by removal of all

solvent under vacuum. x–ray suitable crytsals (as colorless blocks) were afforded by

slow diffuson of diethylether to the methanol solution of compound at room

temperature (Figure 6 and Table 6). Yield: 0.43 g, 0.65 mmol, 61.32%. Elemental

analysis (%) calcd. for C24H26CdN6O9 (M = 654.91 g/mol): C 44.01, H 4.00, N 12.83;

found C 44.14, H 4.03, N 12.97; FAB-MS (nitrobenzyl alcohol): m/z = 594 [M+ - NO3],

406 [M+ - 2NO3]. 1H NMR (400 MHz, DMSO–d6): δ 2.92 (d,d, 1H, βCH2), 3.13 (d,d,

1H, βCH2), 3.26–3.45 (m, 3H, pyCH2 + (CO)CH2), 3.62 (s, 3H, OCH3), 3.78–3.91 (m,

3H, pyCH2), 4.68 (m, 1H, αCH), 7.12 (m, H4Phenyl), 7.20 (s, 4H, H2,3,5,6Phenyl), 7.47 (d,

2H, H5py), 7.55 (s, br, H3py), 7.99 (s, br, 2H, H4py), 8.56, 8.62 (2 x d, 2H, 3JH,H = 4.3Hz,

H6py), 9.62 (d, 1H, 3JH,H = 7.6Hz, NH). 1H NMR (75 MHz, DMSO–d6): 54.52 (βC),

56.25 (αC), 57.26 (pyCH2), 58.58 (C(O)CH2), 126.50, 126.75 (C3,5py), 126.86, 128.83,

130.48, 131.29 (C2,3,4,5,6phenyl), 138.88 (C1phenyl), 141.90 (C4py), 151.88 (C6py), 156.10

(C2py), 172.70 (C(O)amide), 173.50 (C(O)ester). IR (KBr) / cm–1: 1750νCOOMe,

1642νCONHR I, 1605νCONHR II,1385νNO3.

77

Figure 6. Molecular structure of [(Dpg–Phe–OCH3)Cd(NO3)2]

Table 6. Crystallographic data and selected bond distances (Å) and angles (°) [(Dpg–Phe–OCH3)Cd(NO3)2] Formula C24H26CdN6O9 Cd-N1 2.420(2) Formula weight 654.91 Cd-N2 2.268(3) Crystal size [mm3] 0.35 x 0.18 x 0.16 mm Cd-N3 2.320(3) Temperature [K] 100(2) Cd-O1 2.4141(17) Crystal system Orthorhombic Cd-O4 2.435(2) Space group P212121 Cd-O5 2.3249(19) a [Å] 9.8960(7) Cd-O7 2.4159(19) b [Å] 15.6803(8) N2-Cd-N3 121.11(18) c [Å] 17.6200(5) N2-Cd-O5 142.88(10) α [°] 90 N3-Cd-O5 89.52(14) β [°] 90 N2-Cd-O1 106.72(12) γ [°] 90 N3-Cd-O1 103.79(14) Volume [Å 3] 2734.1(3) O5-Cd-O1 82.84(7) Z 4 N2-Cd-O7 80.15(11) Dcalcd [Mg/m3] 1.591 N3-Cd-O7 87.48(13) µ [mm-1] 0.861 O5-Cd-O7 80.96(7) θ-range [°] 3.32 – 27.88 O1-Cd-O7 160.17(6) Measured refl. 38449 N2-Cd-N1 72.03(10) Independent refl. 6496 (Rint = 0.0522) N3-Cd-N1 73.12(12) Observed refl. a 6496 O5-Cd-N1 142.41(7) Parameters 399 O1-Cd-N1 69.93(7) Goodness-of-Fit on F2 1.040 O7-Cd-N1 129.61(7) R1

a 0.0278 N2-Cd-O4 90.75(11) wR2 (all data) 0.0562 N3-Cd-O4 142.07(13) abs. struct. param.38 -0.003(16) O5-Cd-O4 54.00(7) ∆ρmax./min. [eÅ-3] 0.537 / -0.420 O1-Cd-O4 83.57(6) O7-Cd-O4 77.67(7) N1-Cd-O4 141.73(7) a[I>2σ(I)];

78

[(Dpg–Phe–OCH3)Co(NO3)2]: Solid Co(NO3)2 x 6H2O (0.21 g, 0.74 mmol) was

added to a stirred solution of Dpg–Phe–OCH3 (0.25 g, 0.74 mmol) in 30 mL of

CH3CN. Stirring was continued overnight at room temperature followed by removal of

all solvent under vacuum. The product were dissolved in CH2Cl2 and the resulting

suspension left in refrigerator (–20°C) overnight. Unchanged Co(NO3)2 x 6H2O

precipitated and was filtered off. x-ray sutable crystals (as violet needels) were obtained

by keeping the CH2Cl2 solutionof compound with addition of diethylether in deep-

freezer for period of several weeks (Figure 7 and Table7). Yield: 0.30 g, 0.49 mmol,

67.40%. Elemental analysis (%) calcd. for C24H26CoN6O9 (M = 601.43 g/mol): C 47.93,

H 4.36, N 13.97; found C 47.08, H 4.03, N 13.67; FAB-MS (nitrobenzyl alcohol):

m/z = 540 [M+ - NO3], 477 [M+ - 2NO3]. ). IR (KBr) / cm–1: 1749νCOOMe, 1618νCONHR,

1380νNO3.

Figure 7. Molecular structure of [(Dpg–Phe–OCH3)Co(NO3)2]

79

Table 7. Crystallographic data and selected bond distances (Å) and angles (°) [(Dpg–Phe–OCH3)Co(NO3)2] Formula C24H26CoN6O9 Co-N3 2.122(2) Formula weight 601.44 Co-N2 2.137(3) Crystal size [mm3] 0.18 x 0.16 x 0.12 mm Co-O5 2.204(2) Temperature [K] 100(2) Co-O1 2.2057(17) Crystal system Orthorhombic Co-N1 2.233(2) Space group P212121 Co-O4 2.236(2) a [Å] 9.598(1) Co-O7 2.2857(19) b [Å] 15.808(1) N3-Co-N2 123.29(9) c [Å] 17.457(1) N3-Co-O5 84.99(9) α [°] 90 N2-Co-O5 141.15(9) β [°] 90 N3-Co-O1 107.02(9) γ [°] 90 N2-Co-O1 110.16(9) Volume [Å 3] 2648.7(4) O5-Co-O1 81.43(8) Z 4 N3-Co-N1 75.95(10) Dcalcd [Mg/m3] 1.508 N2-Co-N1 74.91(9) µ [mm-1] 0.712 O5-Co-N1 142.69(9) θ-range [°] 2.83 – 27.50 O1-Co-N1 74.16(8) Measured refl. 33360 N3-Co-O4 140.88(9) Independent refl. 6050 (Rint = 0.0859) N2-Co-O4 86.60(9) Observed refl. a 7904 O5-Co-O4 57.84(9) Parameters 362 O1-Co-O4 81.03(7) Goodness-of-Fit on F2 1.070 N1-Co-O4 141.22(9) R1

a 0.0510 N3-Co-O7 83.13(10) wR2 (all data) 0.0817 N2-Co-O7 78.30(9) abs. struct. param.38 -0.005(13) O5-Co-O7 79.73(7) ∆ρmax./min. [eÅ-3] 0.332 / -0.399 O1-Co-O7 157.70(6) N1-Co-O7 128.07(7) O4-Co-O7 78.90(7) a[I>2σ(I)];

(µ–Cl)2–[{Mn(Dpg–Phe–OCH3)(Cl)}2]: Solid MnCl2 x 4H2O (0.63 g, 5.04 mmol) was

added to a stirred solution of Dpg–Phe–OCH3 (2.11 g, 5.04 mmol) in 50 mL of CH3OH.

Stirring was continued overnight at room temperature followed by removal of methanol

under vacuum. The dry residue was dissolved in nonporous water, and the solution were

filtered off using micro filter (2 µ). Water was removed using a rotary evaporator and

material dried under reduced pressure untill dryness. Further purification undergoes by

dissolving dry material in dichloromethane and precipitation by addition of diethyl

ether. x-ray suitable crystals (colorless needles) were obtained by keeping the CH2C2

solution of the compound, with addition of diethyl ether, in a deep freezer (–30 °C) over

period of several weeks (Figure 8 and Table 8). Yield: 1.34 g, 1.23 mmol, 24.40%.

Elemental analysis (%) calcd. for C48H52Cl4Mn2N8O6 (M = 1088.66 g/mol): C 52.96, H

4.81, N 10.29; found: C 52.49, H 5.49, N 10.17;

80

FAB–MS (nitrobenzyl alcohol): m/z = 509 [M+ – Cl], 473 [M+ – 2Cl]. IR (KBr) / cm–1:


Figure 8. Molecular structure of (µ–Cl)2–[{Mn(Dpg–Phe–OCH3)(Cl)}2]

Table 8. Crystallographic data and selected bond distances (Å) and angles (°) (µ–Cl)2–[{Mn(Dpg–Phe–OCH3)(Cl)}2] Formula C49H54Cl6Mn2N8O6 Mn1-N2 2.249(3) Formula weight 1173.58 Mn1-N3 2.264(3) Crystal size [mm3] 0.23 x 0.12 x 0.07 mm Mn1-N1 2.433(3) Temperature [K] 100(2) Mn1-Cl2 2.4720(10) Crystal system Triclinic Mn1-Cl3 2.5267(10) Space group P1 Mn1-Cl1 2.5687(10) a [Å] 9.339(1) N2-Mn1-N3 98.13(11) b [Å] 9.954(2) N2-Mn1-N1 73.86(10) c [Å] 15.686(2) N3-Mn1-N1 72.00(10) α [°] 76.237(7) N2-Mn1-Cl2 93.77(8) β [°] 73.166(6) N3-Mn1-Cl2 92.25(8) γ [°] 79.472(5) N1-Mn1-Cl2 157.87(7) Volume [Å 3] 1345.4(4) N2-Mn1-Cl3 162.45(9) Z 1 N3-Mn1-Cl3 88.99(8) Dcalcd [Mg/m3] 1.448 N1-Mn1-Cl3 93.37(7) µ [mm-1] 0.822 Cl2-Mn1-Cl3 102.00(3) θ-range [°] 3.65 – 27.10 N2-Mn1-Cl1 86.01(8) Measured refl. 39261 N3-Mn1-Cl1 165.30(8) Independent refl. 11154 (Rint = 0.0431) N1-Mn1-Cl1 95.88(7) Observed refl. a 7904 Cl2-Mn1-Cl1 101.59(3) Parameters 677 Cl3-Mn1-Cl1 83.34(3) Goodness-of-Fit on F2 1.026 R1

a 0.0367 wR2 (all data) 0.0828 abs. struct. param.38 0.011(14) ∆ρmax./min. [eÅ-3] 0.933 / -0.663 a[I>2σ(I)];

81

5. Summary

A series of dipeptide ligands of the type Dpg-Xaa were synthesized, where Dpg is

dipicolylglycine and Xaa is phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), 2-

naphthylalanine (Nal), alanine (Ala), leucine (Leu), or glycine (Gly), and the zinc

complexes thereof. These complexes turned out to be excellent material for synthesis of

helical coordination polymers (with a well-defined array) of aromatic substituents. STM

studies indicate an ordered deposition of helical polymers on graphite substrates. The

pH dependent conformational switching of a peptidic amide group from oxygen to

anionic nitrogen coordination was observed in a series of zinc(II) complexes. It was

shown that aromatic interactions promote the unusual coordination of an anionic peptide

backbone nitrogen atom to zinc. For the first time this binding mode was characterized

by X-ray structure analyses of the electrically neutral complexes [(Dpg-Phe)-HZn],

[(Dpg-Tyr)-HZn], [(Dpg-Trp)-HZn], and [(Dpg-Nal)-HZn]. The pKa-values for amide

nitrogen deprotonation were determined by 1H-NMR titrations ([(Dpg-Phe)Zn]: 7.17,

[(Dpg-Tyr)Zn]: 6.85, [(Dpg-Trp)Zn]: 6.85, [(Dpg-Nal)Zn]: 6.64, [(Dpg-Gly)Zn]: 8.54).

These are the first quantitative data obtained for crystallographically characterized metal

complexes. A comparison with the literature shows that it is difficult to distinguish

between π-cation attraction and π-π-stacking. However, it is evident that modification

of small peptides with synthetic pyridine ligands enhances their ability to stabilize

secondary structures by non-covalent interactions. This is an important consideration for

the design of biomimetic metallopeptides. Copper(II), manganese(II), cobalt(II),

cadmium(II) and nickel(II) complexes were synthesised with a series of amino acid

derived ligands, mentioned above, to see coordination geometry depending to a

different metal center.

82

6. Zusammenfassung

Verschiedene Dipeptid-Liganden des Typs Dpg-Xaa, sowie deren Zink-Komplexe

wurden synthetisiert (Dpg = Dipicolylglycin, Xaa = Phenylalanin (Phe), Tyrosin (Tyr),

Tryptophan (Trp), 2-Naphthylalanin (Nal), Alanin (Ala), Leucin (Leu), oder Glycin

(Gly)). Diese Komplexe erwiesen sich als exzellente Bausteine für die Synthese

helikaler Koordinationspolymere mit aromatischen Substituenten. STM

Untersuchungen ergaben eine geordnete Abscheidung der helikalen Polymere auf

Graphit Oberflächen. In Abhängigkeit des pH-Wertes konnte an Zink(II)-Komplexen

ein Übergang der O-Koordination peptidischer Amidgruppen zu N-Koordination

beobachtet werden. Es konnte gezeigt werden, dass aromatische Wechselwirkungen für

diese ungewöhnliche Koordination des N-Atoms der anionischen Peptidkette am Zink

verantwortlich sind. Dieser Bindungsmodus wurde zum ersten Mal mittels Röntgen-

Strukturanalyse der neutralen Komplexe [(Dpg-Phe)-HZn], [(Dpg-Tyr)-HZn], [(Dpg-

Trp)-HZn], und [(Dpg-Nal)-HZn] beschrieben. Die pKs-Werte der Deprotonierung der

Amid-N-Atome wurden mittels 1H-NMR Titrationen ermittelt: ([(Dpg-Phe)Zn]: 7.17,

[(Dpg-Tyr)Zn]: 6.85, [(Dpg-Trp)Zn]: 6.85, [(Dpg-Nal)Zn]: 6.64, [(Dpg-Gly)Zn]: 8.54).

Es handelt sich hierbei um die ersten quantitativen Daten kristallografisch

charakterisierter Metallkomplexe. Durch einen Vergleich mit der Literatur wird

deutlich, wie schwierig es ist, zwischen π-Kation Wechselwirkung and π-π-stacking zu

unterscheiden. Dennoch zeigt sich deutlich, dass durch synthetische Pyridinliganden

modifizierte kleine Peptide, Sekundärstrukturen durch nicht-kovalente

Wechselwirkungen besser zu stabilisieren vermögen – ein wichtiger Gesichtspunkt für

das Design biomimetischer Metallopeptide. Des Weiteren wurden Kupfer(II)-,

Mangan(II)-, Kobalt(II)-, Kadmium(II)- und Nickel(II)-Komplexe mit einer Reihe von

Aminosäuren abgeleiteter Liganden (siehe oben) synthetisiert, um ihre geometrische

Anordnung in Abhängigkeit des Metallzentrums zu untersuchen.

83

7. Curriculum Vitae Personal Data

Name: Slobodan Novokmet Date of birth: 30. 09. 1970 Place of birth: Zadar, Croatia Martial status: Married Citizenship: Serbia and Montenegro e-Mail: [email protected] [email protected]

Education Primary School: Kragujevac, Serbia and Montenegro, 1985. Grammar School: Kragujevac, Serbia and Montenegro, 1989. Diploma in Chemistry: Faculty of Science, University of Kragujevac, Serbia and Montenegro, 1997. Postgraduate studies (Master in Science): Faculty of Medicine, University of Kragujevac, Serbia and Montenegro, 2001. PhD-studies: University of Erlangen-Nürnberg, Institut of Inorganic Chemistry, Erlangen, Germany, 2005.

metal complexes of amino acids which form tridentate n ... · redox-active aromatic amino acids...

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