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Page 1: The Inner Space of Molecules - Nobel Prize
Page 2: The Inner Space of Molecules - Nobel Prize

The Inner Space of Molecules

Page 3: The Inner Space of Molecules - Nobel Prize

L. Marshall, K. ParrisL. Marshall, K. ParrisD. Nemeth, B. Askew 1985D. Nemeth, B. Askew 1985

Molecular Chelating AgentsMolecular Chelating Agents

Page 4: The Inner Space of Molecules - Nobel Prize

D. NemethD. NemethB. AskewB. Askew

19851985

Pyrazine and QuinoxalinePyrazine and Quinoxaline

Page 5: The Inner Space of Molecules - Nobel Prize

K. S. Jeong, 1990K. S. Jeong, 1990

Barbiturates and DiketopiperazinesBarbiturates and Diketopiperazines

Page 6: The Inner Space of Molecules - Nobel Prize

Receptor for 3Receptor for 3‘‘, 5, 5‘‘ Cyclic AMP Cyclic AMP

Dr. G. DeslongchampsDr. G. DeslongchampsDr. A. GalanDr. A. GalanProf. J. de Mendoza, (UAM) 1993Prof. J. de Mendoza, (UAM) 1993

Receptor for 3Receptor for 3‘‘,5,5‘‘ Cyclic AMP Cyclic AMP

Page 7: The Inner Space of Molecules - Nobel Prize

Reversible Encapsulation PhenomenaReversible Encapsulation Phenomena

Anticipated:Size and Shape RecognitionReaction ChambersAsymmetric Recognition

Page 8: The Inner Space of Molecules - Nobel Prize

Reversible Encapsulation PhenomenaReversible Encapsulation Phenomena

Unanticipated : Single Molecule Solvation Isotope Effects

Binary CodingHelical Alkanes

Chiral SpacesChemical AmplificationSuper Capsules

Page 9: The Inner Space of Molecules - Nobel Prize

““Tennis BallTennis Ball““

Dimeric Assembly

Page 10: The Inner Space of Molecules - Nobel Prize

““Tennis BallTennis Ball““

Synthesis

Dr. Rene WylerProf. J. de Mendoza (UAM)

Page 11: The Inner Space of Molecules - Nobel Prize

““Tennis BallTennis Ball““

NMR Spectrum of Encapsulated Guests

Guest Guest

Niel R. Branda Dr. Rene Wyler, 1994

Page 12: The Inner Space of Molecules - Nobel Prize

““Tennis BallTennis Ball““Methane and Ethane Guests

Dr. Lubo Sebo Prof. Mike Pique (TSRI)

7x107x10-26-26 L L

Capsule x10Capsule x108 8 = tennis ball x10 = tennis ball x108 8 = earth = earth

Page 13: The Inner Space of Molecules - Nobel Prize

““SoftballSoftball““

Dr. Robert MeissnerProf. J. de Mendoza (UAM)

Jongmin KangDr. Y. Tokunaga

3x103x10-25-25 L L

Page 14: The Inner Space of Molecules - Nobel Prize

Guest Exchange

SoftballSoftball

Dr. Javier SantamariaDr. Tomás MartínDr. Göran HilmerssonDr. Stephen Craig

k1

k-1

A supramolecular substitution reaction:para cyclophane is a much better guest

Page 15: The Inner Space of Molecules - Nobel Prize

Opening the SoftballOpening the Softball

4 Hydrogen Bonds 6 Hydrogen Bonds

Opposite Flaps Adjacent Flaps

Page 16: The Inner Space of Molecules - Nobel Prize

Guest Exchange in the SoftballGuest Exchange in the Softball

16 HB

Page 17: The Inner Space of Molecules - Nobel Prize

Guest Exchange in the SoftballGuest Exchange in the Softball

16 HB 10 HB

Page 18: The Inner Space of Molecules - Nobel Prize

Guest Exchange in the SoftballGuest Exchange in the Softball

16 HB 10 HB 6 HB

Page 19: The Inner Space of Molecules - Nobel Prize

Guest Exchange in the SoftballGuest Exchange in the Softball

16 HB 10 HB 6 HB 6 HB

Page 20: The Inner Space of Molecules - Nobel Prize

Guest Exchange in the SoftballGuest Exchange in the Softball

16 HB 10 HB 6 HB 6 HB 10 HB

Page 21: The Inner Space of Molecules - Nobel Prize

Guest Exchange in the SoftballGuest Exchange in the Softball

16 HB 10 HB 6 HB 6 HB 10 HB 16 HB

Page 22: The Inner Space of Molecules - Nobel Prize

Guest Exchange in the SoftballGuest Exchange in the Softball

16 HB 10 HB 6 HB 6 HB 10 HB 16 HB

Page 23: The Inner Space of Molecules - Nobel Prize

SoftballSoftball

Accelerated Diels-Alder Reaction

S =

Jongmin KangDr. Javier SantamariaDr. Tomas MartinDr. Göran Hilmersson

4.2 M each!3.5 x 10-25 Liters 4 x 10-3 M each

slow

k1 = 0.44 d-1

D10

Page 24: The Inner Space of Molecules - Nobel Prize

SoftballSoftball

Accelerated Diels-Alder Reaction

Prof. Mike Pique (TSRI)

Page 25: The Inner Space of Molecules - Nobel Prize

Resorcin[4]arene SynthesisResorcin[4]arene Synthesis

Dr. S. Högberg, KTH 1980

side view

top view

H+

Page 26: The Inner Space of Molecules - Nobel Prize

Dr. C. SchalleyB. O'Leary

G

Ar = p-C6H4-n-C7H15D. J. Cram

R = n-C11H23

PyBOP, NEt3CH2Cl2, 48%

Molecular SieveMolecular Sieve

Dr. A. LuetzenDr. A. Renslo

8 x108 x10-25-25 L L

Holes permit rapid exchange of solventsHoles permit rapid exchange of solvents

Page 27: The Inner Space of Molecules - Nobel Prize

Ions Inside Molecules Inside MoleculesIons Inside Molecules Inside Molecules

Dr. A. LuetzenDr. A. RensloDr. C. SchalleyB. O'Leary

J.-M. LehnM = K+, Sr2+, Ba2+

Page 28: The Inner Space of Molecules - Nobel Prize

Cylindrical CapsuleCylindrical Capsule

Dr. Thomas HeinzProf. Dmitry Rudkevich

R = C11H23

1 nm

1.8

nm

Page 29: The Inner Space of Molecules - Nobel Prize

Cavity of the Cylindrical CapsuleCavity of the Cylindrical Capsule

GRASPGRASP

4.2 x 10-25 L

Page 30: The Inner Space of Molecules - Nobel Prize

Single guests and combinations fill the space

PackingCoefficient

= 0.48

PackingCoefficient

= 0.57

PackingCoefficient

= 0.66

Cylindrical CapsuleCylindrical Capsule

Prof. Dmitry Rudkevich Dr. Sandro Mecozzi

Page 31: The Inner Space of Molecules - Nobel Prize

Single Solute - Solvent InteractionsSingle Solute - Solvent Interactions

Dr. A. ScarsoDr. A. ScarsoDr. A. ShivanyukDr. A. Shivanyuk

86%86%14%14%

CH3

H2C CH3 CH3

H2CCH3

Page 32: The Inner Space of Molecules - Nobel Prize

Single Solute - Solvent InteractionsSingle Solute - Solvent Interactions

Dr. A. ScarsoDr. A. ScarsoDr. A. ShivanyukDr. A. Shivanyuk

40%40%60%60%

CH3

HN CH3CH3

HN CH3

Revealed by a panel of 15 solventsRevealed by a panel of 15 solvents

Page 33: The Inner Space of Molecules - Nobel Prize

Dr. A. ScarsoDr. D. Rechavi-RobinsonTheory:Prof. K. N. Houk (U.C.L.A.)

Equilibrium Isotope Effects

43% 57%

Page 34: The Inner Space of Molecules - Nobel Prize

Coencapsulation of three solvent

Cylindrical CapsuleCylindrical Capsule

Dr. Alex Shivanyuk Prof. P. BallesterDr. Masamichi Yamanaka

CHCl3 ClCH2 CH2Cl (CH3)2CHCl

Page 35: The Inner Space of Molecules - Nobel Prize

Dr. A. Shivanyuk

Isomeric Constellations

Dr. M. Yamanaka

A binary coding scheme

chloroform

isopropyl chloride

Page 36: The Inner Space of Molecules - Nobel Prize

+ C10

+ C12

+ C14

+ C15

Complexes of the Capsule with Linear Hydrocarbons

1H NMR, 600 MHz

Dr. Alessandro ScarsoDr. Laurent Trembleau

Page 37: The Inner Space of Molecules - Nobel Prize

Straight Chain HydrocarbonsCoil to fit into the Capsule

Dr. Alessandro ScarsoDr. Laurent Trembleau

Gauche conformation: 0.55 kcal/mol

Page 38: The Inner Space of Molecules - Nobel Prize

2D-NOESY, 600 MHz, mixing time: 300ms

Capsule-Tetradecane Complex

Dr. AlessandroScarso

Dr. LaurentTrembleau

Page 39: The Inner Space of Molecules - Nobel Prize

Chiral Spaces

Page 40: The Inner Space of Molecules - Nobel Prize

Achiral SpacesAchiral Spaces

Dr. Alessandro ScarsoDr. Alexander Shivanyuk

Page 41: The Inner Space of Molecules - Nobel Prize

Chiral SpacesChiral Spaces

Dr. Alessandro ScarsoDr. Alexander Shivanyuk

G G

Chiral objects in achiral spaces

Page 42: The Inner Space of Molecules - Nobel Prize

Asymmetric CoencapsulationAsymmetric Coencapsulation

Dr. Alessandro ScarsoDr. Alexander Shivanyuk

An ensemble of environmentsAn ensemble of environments

CO2H

OHH CO2HHO

H HO2C

HOHG G G

Page 43: The Inner Space of Molecules - Nobel Prize

Asymmetric CoencapsulationAsymmetric Coencapsulation

Dr. Alessandro ScarsoDr. Alexander Shivanyuk

Fixed orientations enhance recognitionFixed orientations enhance recognition

CO2H

OHH G HO2C

HOH G HO2C

HOH

G

Page 44: The Inner Space of Molecules - Nobel Prize

Asymmetric CoencapsulationAsymmetric Coencapsulation

Magnetic and steric effects coexistMagnetic and steric effects coexist

Dr. Alessandro ScarsoDr. Alexander Shivanyuk

CO2HHOH

CH3

H3C

HOH

CH2O

H

CH3

CH3Cl

H

Page 45: The Inner Space of Molecules - Nobel Prize

Asymmetric ExteriorsAsymmetric Exteriors

Dr. Alessandro ScarsoDr. Alexander Shivanyuk

G

GGG

GG G G G

GGGGG

G ? ?

Separation of Steric and Magnetic Effects

Page 46: The Inner Space of Molecules - Nobel Prize

Asymmetric ExteriorsAsymmetric Exteriors

Dr. Toru Amaya

Separation of Steric and Magnetic Effects

Page 47: The Inner Space of Molecules - Nobel Prize

Chemical Amplification:A Chain Reaction

Page 48: The Inner Space of Molecules - Nobel Prize

Length SelectionLength Selection

Dr. Steffi KörnerDr. Fabio TucciDr. Thomas HeinzProf. Dmitry Rudkevich

N

H2C

CH3

O H

CH3

Fits

Doesn‘t fit

N

H2C

H2C

O H

CH3

CH3

Rigid guests have no choice

Page 49: The Inner Space of Molecules - Nobel Prize

Dr. J. ChenDr. S LinDr. S. Körner

Prof. S. CraigProf. D. Rudkevich

Long and short anilides formed at theLong and short anilides formed at thesame rate in solutionsame rate in solution

AcidR = Me, Et

AnilineCarbodiimide

(DCC)

R

OHO

NH2

CH3

CN

NNHO

R

CH3

NHO

NH

Anilide Urea(DCU)

Page 50: The Inner Space of Molecules - Nobel Prize

Dr. J. Chen, Dr. S. LinDr. S. Körner

Prof. S. CraigProf. D. Rudkevich

Chemical Amplification with Encapsulated ReagentsChemical Amplification with Encapsulated Reagents

Carbodiimide(DCC)

Anilide Urea(DCU)

AcidR = Me, Et

Aniline

CN

NNHO

R

CH3

NH2

CH3

R

OHO

NHO

NH

Page 51: The Inner Space of Molecules - Nobel Prize

Dr. J. Chen, Dr. S. LinDr. S. Körner

Prof. S. CraigProf. D. Rudkevich

Sigmoidal product generation of theSigmoidal product generation of theshorter anilideshorter anilide

Page 52: The Inner Space of Molecules - Nobel Prize

Dr. J. Chen, Dr. S. LinDr. S. Körner

Prof. S. CraigProf. D. Rudkevich

1.2

1.4

1.6

1.8

2

2.2

0 2000 4000 6000 8000 1 104 1.2 104 1.4 104 1.6 104

[DCC

] enca

p (mM

)

time (sec)

R = Me, squaresR = Et, triangles

CN

N

NH2

CH3

R

OHONHO

R

CH3

Product Recognition and AutocatalysisProduct Recognition and Autocatalysisof the shorter, but not longer anilideof the shorter, but not longer anilide

Page 53: The Inner Space of Molecules - Nobel Prize

carbodiimide

urea + anilide

+acid

+aniline

In Solution(reactive)

Encapsulated(unreactive)

Encapsulated(unreactive)

Dr. J. Chen, Dr. S. LinDr. S. Körner

Prof. S. CraigProf. D. Rudkevich

Amplification mechanism

NH

OR

H3CNH

O

NH

C NN C NN

Page 54: The Inner Space of Molecules - Nobel Prize

Dr. S. Lin

CanDisplace

DCC

1 Product2 Products3 Products

DCC + Reactants Products

CN

N

Simulation of the Chain ReactionSimulation of the Chain Reaction

Page 55: The Inner Space of Molecules - Nobel Prize

Super Capsules

Page 56: The Inner Space of Molecules - Nobel Prize

Tetrameric CapsuleTetrameric Capsule

Dr. Tomás MartínDr. Ulrike Obst

3x103x10-25-25 L L

Page 57: The Inner Space of Molecules - Nobel Prize

Tetrameric CapsuleTetrameric Capsule

Adamantanedione

Assembles when the space is properly filled

Page 58: The Inner Space of Molecules - Nobel Prize

Adamantanedione Guest

Dr. Darren JohnsonFraser Hof

Tetrameric Capsule X-RayTetrameric Capsule X-Ray

Page 59: The Inner Space of Molecules - Nobel Prize

Resorcin[4]arene OctolsResorcin[4]arene Octols

Aoyama, et al 1988, 1989, 1993

Atwood, MacGillivray 1997

CHCl3

1.3 x101.3 x10-24-24 L L

Page 60: The Inner Space of Molecules - Nobel Prize

Hexameric AssemblyHexameric Assembly

Dr. Alex Shivanyuk

CDCl3

R = n-Hexyl

Page 61: The Inner Space of Molecules - Nobel Prize

Resorcin[4]arene Octol AssemblyResorcin[4]arene Octol Assembly

wetwet benzene benzene

Liam PalmerLiam PalmerDr. Alex ShivanyukDr. Alex Shivanyuk

22 molecules vs. entropy22 molecules vs. entropy

Page 62: The Inner Space of Molecules - Nobel Prize

Hexameric AssemblyHexameric Assembly

Dr. Alex ShivanyukDr. Alex Shivanyuk

Page 63: The Inner Space of Molecules - Nobel Prize

Reversible Encapsulation PhenomenaReversible Encapsulation Phenomena

Unanticipated : Single Molecule Solvation Isotope Effects

Binary CodingHelical Alkanes

Chiral SpacesChemical AmplificationSuper Capsules

Page 64: The Inner Space of Molecules - Nobel Prize

More Encapsulation PhenomenaMore Encapsulation Phenomena

Polymeric Capsules Fluorocarbons

Regioselecive ReactionsHindered Inversions, RotationsAnion Encapsulation

Page 65: The Inner Space of Molecules - Nobel Prize

SupportSupport

Skaggs Institute

National Instituteof General MedicalSciences

Page 66: The Inner Space of Molecules - Nobel Prize

VideosVideos

Dr. Lubomir Sebo

Page 67: The Inner Space of Molecules - Nobel Prize

“ …‘guest’ and ‘host’ are words that intertwine… Converging,mixing, reciprocating. …Guests bring ideas from outside”.Don DeLillo

Mao II

Viking (Penguin) New York, 1991

Page 68: The Inner Space of Molecules - Nobel Prize
Page 69: The Inner Space of Molecules - Nobel Prize

?

?

Page 70: The Inner Space of Molecules - Nobel Prize

Dr. Colin NuckollsFraser Hof

Dr. Tomás Martín

Chiral Tetrameric CapsuleChiral Tetrameric Capsule

Page 71: The Inner Space of Molecules - Nobel Prize

3-Methylcyclohexane Guest

Chiral Tetrameric CapsuleChiral Tetrameric Capsule

Dr. Colin NuckollsFraser Hof

Dr. Tomás Martín

Page 72: The Inner Space of Molecules - Nobel Prize

Chiral SoftballChiral Softball

José M. RiveraDr. Stephen L. CraigDr. Tomás Martín

Page 73: The Inner Space of Molecules - Nobel Prize

Chiral SoftballChiral Softball

0 min

17 min

191 h

B+B'A+A'

B

A

BA

A+A'B+B'

(+)-pinanediol (-)-pinanediol adamantanol

José M. RiveraDr. Stephen L. CraigDr. Tomás Martín

Page 74: The Inner Space of Molecules - Nobel Prize

Prof. M. Yamanaka

Diastereomeric Constellations

Page 75: The Inner Space of Molecules - Nobel Prize

Functional Groups ConvergeFunctional Groups Convergeto Form an Active Siteto Form an Active Site

Page 76: The Inner Space of Molecules - Nobel Prize

Receptor for AdenineReceptor for Adenine

DDG = 0.3 kcal mol-1H2O/D2O, 10 °Cm = 50 mM

Y. KatoY. KatoM. Conn,M. Conn,19901990Ka = 62 M-1

Ka = 36 M-1

Page 77: The Inner Space of Molecules - Nobel Prize

Extending the Tennis BallExtending the Tennis Ball

Robert M. GrotzfeldDr. Carlos Valdés

Niel R. BrandaBrendan O‘leary

Page 78: The Inner Space of Molecules - Nobel Prize

Hindered Inversion and Rotation

Page 79: The Inner Space of Molecules - Nobel Prize

Jelly Doughnut or HamburgerJelly Doughnut or Hamburger

Encapsulated Benzene

Page 80: The Inner Space of Molecules - Nobel Prize

Jelly Doughnut or HamburgerJelly Doughnut or Hamburger

Encapsulated Cyclohexane

Page 81: The Inner Space of Molecules - Nobel Prize

Dr. A. ScarsoDr. H. Onagi

Page 82: The Inner Space of Molecules - Nobel Prize

Regioselectivity

Page 83: The Inner Space of Molecules - Nobel Prize

Cylindrical CapsuleCylindrical Capsule

103 yrs

R.T.

1 mM1 mM

Dr. Jian ChenDr. Stephen Craig

Page 84: The Inner Space of Molecules - Nobel Prize

Dr. Jian ChenDr. Stephen Craig

NOT

days

R.T.

Cylindrical CapsuleCylindrical Capsule

Page 85: The Inner Space of Molecules - Nobel Prize

Anion Encapsulation

Page 86: The Inner Space of Molecules - Nobel Prize

-2.86 ppm

Anion EncapsulationAnion Encapsulation

Prof. Osamu HayashidaDr. Alex Shivanyuk

CHCl3

CHCl3

CHCl3

X-

Cl-Br-

BF4-

PF6-

IO4-

X- =

Page 87: The Inner Space of Molecules - Nobel Prize

Guests

Cylindrical CapsuleCylindrical Capsule

Dr. Alex Shivanyuk Prof. O. Hayashida

Page 88: The Inner Space of Molecules - Nobel Prize

Prof. Osamu HayashidaDr. Alex Shivanyuk

A widely separated ion pair

PF6- Et4N+

Page 89: The Inner Space of Molecules - Nobel Prize

Anion and two different solventsAnion and two different solvents

Prof. Osamu HayashidaDr. Alex Shivanyuk

Page 90: The Inner Space of Molecules - Nobel Prize

Filling Space

Page 91: The Inner Space of Molecules - Nobel Prize

Hacky-SackHacky-Sack

METHANE (PC~0.50) is bound,but ETHANE (PC=>.85) is not

The Smallest Dimeric Capsule

Dr. Leticia Toledo Dr. Carlos Valdes

Page 92: The Inner Space of Molecules - Nobel Prize

NMR Shifts of Coencapsulated Gases

Cylindrical CapsuleCylindrical Capsule

-3.6 ppm -4.4 ppm

Dr. Alex ShivanyukDr. Alessandro Scarso

H3C CH3 CH4

Page 93: The Inner Space of Molecules - Nobel Prize

NMR Shifts of Coencapsulated Gases

Cylindrical CapsuleCylindrical Capsule

-3.0 ppm -2.9 ppm -4.1 ppm

Dr. Alex ShivanyukDr. Alessandro Scarso

H3CC

H3C

CH3

H H3C CH3 H2C CH2

H2C

Page 94: The Inner Space of Molecules - Nobel Prize

LiquidsLiquids

Packing Coefficient

benzenetoluene

n-hexanemethylene chloride

chloroformdiethyl ether

acetoneacetonitrile

methanolethanol

water

0.540.540.510.540.530.510.520.530.540.550.63

In a liquid, only slightly more than half of the availablespace is physically filled by molecules.

Dr. Sandro Mecozzi

Page 95: The Inner Space of Molecules - Nobel Prize

Length SelectionLength Selection

Dr. Steffi KörnerDr. Fabio TucciDr. Thomas HeinzProf. Dmitry Rudkevich

N

H2C

CH3

O H

CH3

Fits

Doesn‘t fit

N

H2C

H2C

O H

CH3

CH3

Page 96: The Inner Space of Molecules - Nobel Prize

Length SelectionLength Selection

Dr. Steffi KörnerDr. Fabio TucciDr. Thomas HeinzProf. Dmitry Rudkevich

Fits Doesn’t fit

Page 97: The Inner Space of Molecules - Nobel Prize

Complexes Within Complexes

Prof D. RudkevichDr. T. HeinzDr. A. ShivanyukDr. A. ScarsoLiam Palmer

Page 98: The Inner Space of Molecules - Nobel Prize

Choleic Acids

from Steroids by Fieser and Fieser, 1959, p. 58.

F, 1959, p. 58.

Page 99: The Inner Space of Molecules - Nobel Prize

Polymeric Capsules

Page 100: The Inner Space of Molecules - Nobel Prize

Calixarene CapsuleCalixarene Capsule

Ken Shimizu

Page 101: The Inner Space of Molecules - Nobel Prize

Fluorescence Resonance EnergyTransfer (FRET)

NO H

alk

ON

Y

OO

N

O

ON

H

YH

alk alkalk

N

OO O

NOH

alk alkO

NHX

N

O

NH

O

NH

O

D

A

NO HH

alkOO O

NH

alk alkO

HX

N N

ON

NX

NX

OH

HNX

OH

H

NH

O

D

NO HH

alkOO O

NH

alk alkO

HY

N N

ON

NY

NY

OH

HNY

OH

H

NH

O

A

hn

hn''

+ GUEST GUEST

hn hn'

hn' hn''

alk = C10H21X = SO2-p-C6H4-CH32D X = p-C6H4-CH3 2A Y = p-C6H4-CH3

1D

• Color change signalsassembly

• Sensitive at lowconcentrations (nM); observefree monomer

• Excellent time resolution• Study behavior at dilute

concentrations where theassembly process is “slow”

FRET offers:

Sulfonyl ureas (1D) and aryl ureas(2A) form exclusive heterodimericpairs in solution.

Page 102: The Inner Space of Molecules - Nobel Prize

Polycaps: Polymeric Capsules

• Control of chemical andstereochemical preferences

• Strong association (KA 106–108 M-1)• Rapid dissociation/equilibrium• Functional: Responsive to external

signals (guest, solvent, temperature)• Modular construction leads to

structural variety

guestmonomer

polycaps

Why polymers?

NH ONH R2

O OO OR1R1 R1CH2

N H

NO

R2H

NHN

O

R2H

N HON HR2

HO

O

NH2

H2NX

PyBOPNEt3DMF

NH

ON

H

R2

O

OO

O R1

R1

R1

NHN

OR2

H

NHN

OR2

H

NH

ON

HR2

ON

HNH

ONHR2

O

OO

OR1

R1

R1

NH N

OR2

H

NH NO

R2H

NH

ONHR2

ON

HX

Page 103: The Inner Space of Molecules - Nobel Prize

1H NMR: Still a Valuable Tool

CDCl3

DMF-d7

• Dilution/VT studies• Chain termination experiments• Guest encapsulation studies

Measurements include:

NH

ON

H

R2

O

OO

O R1

R1

R1

NHN

OR2

H

NHN

OR2

H

NH

ON

HR2

ON

HNH

ONHR2

O

OO

OR1

R1

R1

NH N

OR2

H

NH NO

R2H

NH

ONHR2

ON

H

R1 = C10H21R2 = tolyl

Page 104: The Inner Space of Molecules - Nobel Prize

Quasielastic Light Scattering (Benedek, MIT)

CHCl3

2.2 5.1

+

+

(2.2)x(5.1)y2.2•2.2

X2.2/X5.11/2 (mmol1/2)

Rh-2

X 5.1

1/2 10

2 (nm

-2m

mol

1/2 )

terminated oligomers(x = 0, 1, 2)dimer

• KA = 2.3 x 106 M-1 in chloroform• Between 0.25–2.5 mM, DP =

10–60 (MW = 31,000–186,000)

• Persistence length ~ 4 monomers (ca. 9nm)

• c* ~ 2.7 mM

Polycaps are good models through which to study "living" polymerizations

Page 105: The Inner Space of Molecules - Nobel Prize

Liquid-Crystalline Polycaps

0 5 10 15 20 25

2Q (°)5 10 15 20

~ 2.2 nm

1.6 nm

electrondiffraction

X-raydiffraction

Page 106: The Inner Space of Molecules - Nobel Prize

LC Phases and Well-Ordered Fibers

30 mm

80 mm

uniformlyaligned fibers

hightensile strength

nematic phase (CHCl3)

100 mm 30 mm

organization upon shear

Page 107: The Inner Space of Molecules - Nobel Prize

Rate and Equilibrium Constants

Solvent kass (M-1 s-1) a kdiss (s

-1) a KA (M-1) a

1•1 CHCl3 –b –b –b

1•2 CHCl3 2.7b ¥ 103 2.3 ¥ 10-5 1.2 ¥ 108

2•2 CHCl3 1.5 ¥ 104 6.4 ¥ 10-3 2.4 ¥ 106

1•1 C6H6 < 50 5.4 ¥ 10-5 < 106

1•2 C6H6 3 ¥ 103 5 ¥ 10-6 6 ¥ 108

2•2 C6H6 1.3 ¥ 104 2.8 ¥ 10-4 4.6 ¥ 107

aUncertainties in kdiss are ±15%, and in kass and KA are ±40%.bCompound 1 does not appear to form a well-defined dimer in CHCl3 by NMR, and itsbehavior in this work is consistent with a species that is effectively monomeric at theseconcentrations.

0.2

0.25

0.3

0.35

0.4

0.45

0.5

0 1 104 2 104 3 104 4 104

Rel

ativ

e Fl

uore

scen

ce

Time (s)

-4

-3.5

-3

-2.5

-2

-1.5

-1

0 5 103 1 104 1.5 104 2 104

ln[in

tens

ity(fi

nal)

- int

ensi

ty(t)

]

Time (s)

Page 108: The Inner Space of Molecules - Nobel Prize

Analyte Detection

aryl urea donor +valine urea acceptor(p-xylene, 150 nM)

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

380 400 420 440 460 480

50,000 equiv.40,000 equiv.25,000 equiv.20,000 equiv.10,000 equiv.5,000 equiv.

Fluo

resc

ence

Wavelength (nm)

O

KA ~ 3 x 109 M-2

Page 109: The Inner Space of Molecules - Nobel Prize

Coiling

Page 110: The Inner Space of Molecules - Nobel Prize
Page 111: The Inner Space of Molecules - Nobel Prize

Cavity DimensionsCavity Dimensions

7.1 Å

16.5 Å

Page 112: The Inner Space of Molecules - Nobel Prize

Folded and Unfolded GuestsFolded and Unfolded Guests

15.2 Å

18.0 Å

Page 113: The Inner Space of Molecules - Nobel Prize

22

33

44

55

77

66

Guest Volume and Packing CoeficientGuest Volume and Packing Coeficient

181 Å3

199 Å3

215 Å3

231 Å3

262 Å3

246 Å3

43%

47%

51%

55%

62%

58%

Dr. LuboSebo

Prof.Osamu

Hayashida

Page 114: The Inner Space of Molecules - Nobel Prize

Longest Encapsulated EsterLongest Encapsulated Ester

GRASPGRASP424 Å3

66

Page 115: The Inner Space of Molecules - Nobel Prize

+ C10

+ C12

+ C14

+ C15

Complexes of the Capsule with Linear Hydrocarbons

1H NMR, 600 MHz

Dr. Alessandro ScarsoDr. Laurent Trembleau

Page 116: The Inner Space of Molecules - Nobel Prize

2D-NOESY, 600 MHz, mixing time: 300ms

Capsule-Tetradecane Complex

Dr. AlessandroScarso

Dr. LaurentTrembleau

Page 117: The Inner Space of Molecules - Nobel Prize

2D-NOESY, 600 MHz, mixing time: 300ms

Capsule-Decane Complex

Dr. AlessandroScarso

Dr. LaurentTrembleau

Page 118: The Inner Space of Molecules - Nobel Prize

Straight Chain HydrocarbonsCoil to fit into the Capsule

Dr. Alessandro ScarsoDr. Laurent Trembleau

Gauche: 0.55 kcal/mol

Page 119: The Inner Space of Molecules - Nobel Prize

Characteristics of the Hydrocarbons

Alkane Length(Å)

SurfaceArea (Å2)

Volume(Å3)

PC (%)

C10H22 extended 15.0 196 167 39

C12H26 extended 17.5 230 200 47

C12H26 coiled 13.6 207 206 48

C14H30 extended 20.0 264 235 -

C14H30 coiled 15.5 235 240 56

C14H28 coiled 16.0 239 239 56

C15H32 coiled 16.3 251 258 -

Calculated using Grasp after energy minimization of the structures

Page 120: The Inner Space of Molecules - Nobel Prize

Dr. Alessandro Scarso, Byron Purse Dr. Laurent Trembleau

Page 121: The Inner Space of Molecules - Nobel Prize

Tridecane

Tetraethyleneglycol

Perfluorooctane

Dr. Alessandro Scarso, Byron Purse Dr. Laurent Trembleau

Page 122: The Inner Space of Molecules - Nobel Prize

Reactive Intermediates

Page 123: The Inner Space of Molecules - Nobel Prize

Stabilization of Reactive SpeciesStabilization of Reactive Species

Raymond, 2000 Fujita, 2000

Page 124: The Inner Space of Molecules - Nobel Prize

Heimacetal StabilizationHeimacetal Stabilization

Dr. Masamichi Yamanaka

Page 125: The Inner Space of Molecules - Nobel Prize

Hexamer

Page 126: The Inner Space of Molecules - Nobel Prize

Volleyball Seams

Page 127: The Inner Space of Molecules - Nobel Prize

Resorcin[4]arene Octol AssemblyResorcin[4]arene Octol Assembly

wetwetbenzenebenzene

Liam PalmerLiam PalmerDr. Alex ShivanyukDr. Alex Shivanyuk

Page 128: The Inner Space of Molecules - Nobel Prize

150 M-1C 8450 M-1C 7

1,200 M-1C 6>104 M-1C 3-5

KGuest

Dr. A. Shivanyuk, Dr. M. Yamanaka

150 M-1C 8450 M-1C 7

1,200 M-1C 6>104 M-1C 3-5

KGuest

Page 129: The Inner Space of Molecules - Nobel Prize

R4N+ in Hexamer

C3

C4

C5

C6

C7

Dr. A. Shivanyuk, Dr. M. Yamanaka

Page 130: The Inner Space of Molecules - Nobel Prize

17.1C 716.7C 5

14.8C 413.1C 3

DG* kcal/molGuest

Dr. A. Shivanyuk, Dr. M. Yamanaka

Page 131: The Inner Space of Molecules - Nobel Prize
Page 132: The Inner Space of Molecules - Nobel Prize

NMR Shifts of Coencapsulated Gases

Cylindrical CapsuleCylindrical Capsule

-3.0 ppm -2.9 ppm -4.1 ppm

Dr. Alex ShivanyukDr. Alessandro Scarso

CD3

CD3

H3CC

H3C

CH3

H

CD3

CD3

H3C CH3

CD3

CD3

H2C CH2

H2C

Page 133: The Inner Space of Molecules - Nobel Prize

Resorcin[4]arene Octol AssemblyResorcin[4]arene Octol Assembly

wetwetbenzenebenzene

Dr. Alex ShivanyukDr. Alex Shivanyuk

Page 134: The Inner Space of Molecules - Nobel Prize

Dr. Alex Shivanyuk

Cylindrical CapsuleCylindrical Capsule

Social isomers

1

CH2CH3

CH3

H

CH2CH3

CH3

H

2

34

6‘

1‘

2‘

5‘

80% 20%

ClC

Cl

H

Cl

ClC

Cl

H

Cl

Page 135: The Inner Space of Molecules - Nobel Prize

Dr. Alex Shivanyuk

Cylindrical CapsuleCylindrical Capsule

Social isomers

80% 20%

1

2

3

4

6’

1’

2’5’

Dr. Alessandro Scarso

Page 136: The Inner Space of Molecules - Nobel Prize

AcknowledgementsAcknowledgements

Ken ShimizuBlake HamannRon CastellanoDr. Colin NuckollsProfessor Dmitry RudkevichProfessor Byeang Hyean KimDr. Stephen CraigFraser Hof

Professor Reza GhadiriProfessor David MillarDr. Malcolm WoodDr. Teresa Fassell

AnimationsDr. Lubomir Sebo

Collaborators• Professor Tim Swager (MIT)

Dr. Holger Eichhorn (MIT)• Dr. Frank Würthner (Ulm)

Dr. Uwe Beginn (Ulm)• Dr. Andrew Lovinger

(Bell Laboratories)• Prof. J. de Mendoza

(Madrid)

Funding• The Skaggs Research Foundation• NIH• NASA

Page 137: The Inner Space of Molecules - Nobel Prize

Polymeric Capsules

Page 138: The Inner Space of Molecules - Nobel Prize

Molecular Assembly and Encapsulation