supporting information · i) binding data from nmr titration experiments a) nmr titration data for...

Supporting Information

© Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2005

Novel Enantioselective Receptors for N-Protected Glutamate and Aspartate

Andrea Ragusa,[a] Sara Rossi,[a] Joseph M. Hayes,[b] Matthias Stein[b] and Jeremy D. Kilburn,*[a]

[a] A. Ragusa, S. Rossi, Prof. J. D. Kilburn, School of Chemistry, University of Southampton, Southampton, SO17 1BJ,

U.K.; Fax: (+44)-2380-596805; E-mail: [email protected]

[b] Dr. J. M. Hayes, Dr. M. Stein, Anterio Consult & Res GmbH, Augustaanlage 26, D-68165 Mannheim, Germany

i) Binding data from NMR titration experiments

a) NMR titration data for N-Boc-L-Glu with macrocycle 1 in CD3CN

b) NMR titration data for N-Boc-D-Glu with macrocycle 1 in CD3CN

c) NMR titration data for N-Boc-L-Glu with macrocycle 1 in d6-DMSO

d) NMR titration data for Acetate with macrocycle 1 in CD3CN

e) NMR titration data for N-Ac-L-Glu with macrocycle 1 in CD3CN

f) NMR titration data for N-Ac-D-Glu with macrocycle 1 in CD3CN

g) NMR titration data for N-Ac-L-Glu with macrocycle 1 in d6-DMSO

h) NMR titration data for N-Ac-D-Glu with macrocycle 1 in d6-DMSO

i) NMR titration data for N-Boc-L-Asp with macrocycle 1 in CD3CN

j) NMR titration data for N-Boc-L-Asp with macrocycle 1 in d6-DMSO

at 363 K

k) NMR titration data for DiBz-L-tartrate with macrocycle 1 in d6-

DMSO

l) NMR titration data for DiBz-D-tartrate with macrocycle 1 in d6-

DMSO

ii) Binding data from isothermal calorimetry experiments

a) ITC data for N-Boc-L-Glu with macrocycle 1 in CH3CN

b) ITC data for N-Boc-D-Glu with macrocycle 1 in CH3CN

c) ITC data for N-Boc-L-Glu with macrocycle 1 in DMSO

d) ITC data for Acetate with macrocycle 1 in CH3CN

e) ITC data for N-Ac-L-Glu with macrocycle 1 in CH3CN

f) ITC data for N-Ac-D-Glu with macrocycle 1 in DMSO

g) ITC data for N-Boc-L-Glu with macrocycle 2 in CH3CN

h) ITC data for N-Boc-D-Glu with macrocycle 2 in CH3CN

i) ITC data for N-Boc-L-Glu with macrocycle 2 in DMSO

j) ITC data for N-Boc-L-Asp with macrocycle 2 in CH3CN

k) ITC data for N-Boc-D-Asp with macrocycle 2 in CH3CN

l) ITC data for N-Boc-L-Glu with macrocycle 3 in DMSO

m) ITC data for N-Boc-D-Glu with macrocycle 3 in DMSO

i) Binding data from NMR titration experiments

The binding constants were calculated by fitting the titration

data, using NMRTit HG software, kindly provided by Prof C. A.

Hunter, University of Sheffield (A. P. Bisson, C. A. Hunter, J. C.

Morales, K. Young, Chem. Eur. J. 1998, 4, 845). Data was recorded

using standard NMR titration protocols, recording the shift for

various 1H signals on addition of aliquots of guest. An association

constant was determined using the data from each separate 1H

signal, and averaged to give a final association constant. The

rather large discrepancies between association constants obtained

from the data for different 1H signals in CD3CN, in the same

titration experiment, is not surprising in view of the fact that

the data gives binding constants at the upper limit of

detectability using NMR titrations (104 - 105 M-1) (L. Fielding,

Tetrahedron 2000, 56, 6151; C. S. Wilcox, Frontiers in

Supramolecular Organic Chemistry and Photochemistry (Eds.: H.-J.

Schneider, H. Dürr), VCH, Weinheim, 1991, pp. 123-143; G. Weber,

S. R. Anderson, Biochemistry, 1965, 4, 1942.) In these cases it

can be concluded that Ka > 104 M-1, but more precise values cannot

be reliably obtained from the NMR titration data.

a) NMR titration data for N-Boc-L-Glu with macrocycle 1 in CD3CN

Starting volume of host solution: 600µL

Concentration of host solution: 1.5 mM

Concentration of guest solution: 13.6 mM

Association constant: Ka1:1 = 1.5×105 M-1 ie Ka

1:1 > 104 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm CH proton / ppm 0 9.1229 8.2484 5.3583 20 9.3901 8.5985 5.5302 40 9.6823 9.0186 5.7108 60 9.9558 9.4214 5.8587 80 10.1239 9.6020 5.9303 100 10.1728 9.6647 5.9454 120 10.1791 9.6810 5.9478 140 10.1816 9.6798 5.9492 170 10.1829 9.6861 5.9492 200 10.1854 9.6798 5.9492

Titration curves for N-Boc-L-Glu with macrocycle 1 in CD3CN

Boc-L-glu in MeCN (amide protons)

9.12

9.32

9.52

9.72

9.92

10.12

10.32

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03

[guest]

ppm

Boc-L-glu in MeCN (thiourea protons)

8.2

8.4

8.6

8.8

9

9.2

9.4

9.6

9.8

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03

[guest]

ppm

Boc-L-glu in MeCN (CH protons)

5.35

5.45

5.55

5.65

5.75

5.85

5.95

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03

[guest]

ppm

b) NMR titration data for N-Boc-D-Glu with macrocycle 1 in CD3CN




Association constant (guest:host): Ka2:1 = 1.4×105 M-1 ie Ka

2:1 > 104 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm CH proton / ppm 0 9.1153 8.2473 5.3521 20 9.2470 8.4154 5.4512 40 9.3424 8.5809 5.6117 60 9.5117 8.7980 5.6882 80 9.6397 8.9773 5.7535 100 9.7589 9.1216 5.8099 120 9.8768 9.2772 5.8501 140 9.9545 9.3788 5.8802 170 10.0336 9.4779 5.8839 200 10.0662 9.5155 5.8839

Titration curves for N-Boc-D-Glu with macrocycle 1 in CD3CN

Boc-D-glu in MeCN (amide protons)

9.1

9.3

9.5

9.7

9.9

10.1

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03

[guest]

ppm

Boc-D-glu in MeCN (thiourea protons)

8.2

8.4

8.6

8.8

9

9.2

9.4

9.6

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03

[guest]

ppm

Boc-D-glu in MeCN (CH protons)

5.4

5.5

5.6

5.7

5.8

5.9

6.0

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03

[guest]

ppm

c) NMR titration data for N-Boc-L-Glu with macrocycle 1 in d6-DMSO




Association constant: Ka1:1 = 3.7×103 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.471 8.395 20 9.496 8.447 40 9.555 8.548 60 9.603 8.653 80 9.656 8.754 100 9.713 8.856 140 9.803 9.093 180 9.886 9.251 220 9.946 9.359 260 9.989 9.444 300 10.011 9.483 360 10.033 9.510 420 10.048 9.537 480 10.050 9.556 540 10.058 9.556 600 10.068 9.564

Titration curves for N-Boc-L-Glu with macrocycle 1 in d6-DMSO

L-Boc Glu in DMSO (amide protons)

9.45

9.55

9.65

9.75

9.85

9.95

10.05

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03 4.0E-03 4.5E-03 5.0E-03

[guest]

ppm

L-Boc Glu in DMSO (thiourea protons)

8.3

8.5

8.7

8.9

9.1

9.3

9.5

9.7

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03 4.0E-03 4.5E-03 5.0E-03

[guest]

ppm

d) NMR titration data for Acetate with macrocycle 1 in CD3CN





2:1 > 104 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.0731 8.2417 10 9.1560 8.3567 20 9.2678 8.5170 30 9.3460 8.6789 40 9.4359 8.8267 50 9.4994 8.9167 60 9.5454 8.9933 70 9.5619 9.0269 80 9.5798 9.0598 90 9.6017 9.0833 100 9.6205 9.1075 110 9.6386 9.1239 120 9.6479 9.1364 130 9.6644 9.1552 140 9.6777 9.1724 150 9.6941 9.1842 160 9.7066 9.1982 170 9.7121 9.2076 180 9.7270 9.2240 190 9.7356 9.2350 200 9.7489 9.2514 220 9.7731 9.2694

Titration curves for Acetate with macrocycle 1 in CD3CN

Acetate in MeCN (amide protons)

9.0

9.1

9.2

9.3

9.4

9.5

9.6

9.7

9.8

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03 6.0E-03 7.0E-03

[guest]

ppm

Acetate in MeCN (thiourea protons)

8.2

8.4

8.6

8.8

9.0

9.2

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03 6.0E-03 7.0E-03

[guest]

ppm

e) NMR titration data for N-Ac-L-Glu with macrocycle 1 in CD3CN





1:1 > 104 M-1

Ka2:1 = 5.1×103 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.0953 8.2141 5 9.1380 8.2731 10 9.1832 8.3309 15 9.2460 8.4049 20 9.2811 8.4765 25 9.3301 8.5543 30 9.3903 8.6334 35 9.4481 8.7187 40 9.5146 8.7941 45 9.5611 8.8732 50 9.6176 8.9359 60 9.6900 9.0500 70 9.7556 9.1129 80 9.7808 9.1481 100 9.8448 9.2321 120 9.8962 9.2899 150 9.9678 9.3539 200 10.0180 9.4104 250 10.0419 9.4280 300 10.0569 9.4418

Titration curves for N-Ac-L-Glu with macrocycle 1 in CD3CN

Ac-L-Glu in MeCN (amide protons)

9.0

9.2

9.4

9.6

9.8

10.0

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03

[guest]

ppm

Ac-L-Glu in MeCN (thiourea protons)

8.2

8.4

8.6

8.8

9.0

9.2

9.4

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03

[guest]

ppm

f) NMR titration data for N-Ac-D-Glu with macrocycle 1 in CD3CN




Association constant (guest:host): Ka1:1 = 4.5×103 M-1

Ka2:1 = 1.67×105 M-1 ie Ka

2:1 > 104 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.0916 8.2204 5 9.1142 8.2467 10 9.1518 8.3120 15 9.1995 8.3861 20 9.3025 8.5191 25 9.4079 8.6384 30 9.4845 8.7777 35 9.5937 8.8895 40 9.6828 9.0250 45 9.7494 9.0891 50 9.8322 9.1945 60 9.9490 9.3037 70 10.0055 9.3401 80 10.0318 9.3665 100 10.0469 9.3853 120 10.0544 9.3866 150 10.0645 9.3866 200 10.0594 9.3878 250 10.0632 9.3979 350 10.0607 9.3941

Titration curves for N-Ac-D-Glu with macrocycle 1 in CD3CN

Ac-D-Glu in MeCN (amide protons)

9.0

9.2

9.4

9.6

9.8

10.0

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03

[guest]

ppm

Ac-D-Glu in MeCN (thiourea protons)

8.2

8.4

8.6

8.8

9.0

9.2

9.4

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03

[guest]

ppm

g) NMR titration data for N-Ac-L-Glu with macrocycle 1 in d6-DMSO





1:1 > 104 M-1

Ka2:1 = 1.0×103 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.4256 8.3435 5 9.4419 8.3812 10 9.4708 8.4352 15 9.5085 8.5117 20 9.5499 8.5871 25 9.6064 8.6737 30 9.6553 8.7666 35 9.6900 8.8500 40 9.7432 8.9473 45 9.7809 9.0189 50 9.8198 9.0980 60 9.8762 9.1782 70 9.9139 9.2549 80 9.9441 9.3202 100 9.9891 9.3978 120 9.9968 9.4256 150 10.0156 9.4746 200 10.0345 9.5047 300 10.0520 9.5286

Titration curves for N-Ac-L-Glu with macrocycle 1 in d6-DMSO

Ac-L-Glu in DMSO (amide protons)

9.4

9.5

9.6

9.7

9.8

9.9

10.0

10.1

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03 4.0E-03 4.5E-03

[guest]

ppm

Ac-L-Glu in DMSO (thiourea protons)

8.3

8.5

8.7

8.9

9.1

9.3

9.5

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03 4.0E-03 4.5E-03

[guest]

ppm

h) NMR titration data for N-Ac-D-Glu with macrocycle 1 in d6-DMSO





Ka2:1 = 1.68×104 M-1 ie Ka

2:1 > 104 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.4269 8.3410 5 9.4369 8.3699 10 9.4620 8.4251 15 9.4809 8.4678 20 9.5160 8.5256 25 9.5400 8.6100 30 9.5913 8.6975 35 9.6240 8.7540 40 9.6541 8.8331 45 9.6892 8.8896 50 9.7219 8.9674 60 9.7730 9.0578 70 9.8035 9.1444 80 9.8361 9.1846 100 9.8725 9.2813 120 9.9026 9.3302 150 9.9227 9.3842 200 9.9378 9.4068 350 9.9554 9.4557

Titration curves for N-Ac-D-Glu with macrocycle 1 in d6-DMSO

Ac-D-Glu in DMSO (amide protons)

9.4

9.5

9.6

9.7

9.8

9.9

10.0

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03 4.0E-03 4.5E-03

[guest]

ppm

Ac-D-Glu in DMSO (thiourea protons)

8.3

8.5

8.7

8.9

9.1

9.3

9.5

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03 3.5E-03 4.0E-03 4.5E-03

[guest]

ppm

i) NMR titration data for N-Boc-L-Asp with macrocycle 1 in CD3CN





1:1 > 104 M-1

Ka2:1 < 100 M-1

Volume added / µL Aromatic protons / ppm CH proton / ppm 0 7.625 5.325 10 7.638 5.369 20 7.645 5.423 30 7.667 5.479 40 7.678 5.516 50 7.690 5.625 60 7.702 5.817 70 7.710 5.850 80 7.710 5.862 90 7.709 5.872 100 7.708 5.877 110 7.708 5.914 120 7.708 5.901 130 7.707 5.927 140 7.706 5.895 150 7.706 5.887

Titration curves for N-Ac-L-Asp with macrocycle 1 in CD3CN

Boc-L-Asp in MeCN (aromatic protons)

7.62

7.63

7.64

7.65

7.66

7.67

7.68

7.69

7.70

7.71

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03

[guest]

ppm

Boc-L-Asp in MeCN (CH protons)

5.32

5.37

5.42

5.47

5.52

5.57

5.62

5.67

5.72

5.77

5.82

5.87

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03

[guest]

ppm

j) NMR titration data for N-Boc-L-Asp with macrocycle 1 in d6-DMSO at 363 K





Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.2826 8.1808 20 9.3595 8.3035 40 9.4307 8.5045 60 9.506 8.5931 80 9.5223 8.6850 100 9.5475 8.7365 120 9.5826 8.7658 140 9.5972 8.8163

Titration curves for N-Ac-L-Asp with macrocycle 1 in d6-DMSO at 363 K

Boc-L-Asp in DMSO (amide protons)

9.28

9.33

9.38

9.43

9.48

9.53

9.58

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03

[guest]

ppm

Boc-L-Asp in DMSO (thiourea protons)

8.18

8.23

8.28

8.33

8.38

8.43

8.48

8.53

8.58

8.63

8.68

8.73

8.78

0.0E+00 1.0E-03 2.0E-03 3.0E-03 4.0E-03 5.0E-03

[guest]

ppm

k) NMR titration data for DiBz-L-tartrate with macrocycle 1 in d6-DMSO




Association constant (guest:host): Ka2:1 = 211 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.4428 8.3590 20 9.4478 8.3766 40 9.4554 8.4292 60 9.4591 8.4793 80 9.4641 8.5221 100 9.4641 8.5446 120 9.4654 8.5760 140 9.4704 8.5998 170 9.4654 8.6248 200 9.4679 8.6325

Titration curves for DiBz-L-tartrate with macrocycle 1 in d6-DMSO

DiBz-L-tartrate in DMSO (amide protons)

9.44

9.45

9.46

9.47

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03

[guest]

ppm

DiBz-L-tartrate in DMSO (thiourea protons)

8.35

8.40

8.45

8.50

8.55

8.60

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03

[guest]

ppm

l) NMR titration data for DiBz-D-tartrate with macrocycle 1 in d6-DMSO




Association constant (guest:host): Ka2:1 = 103 M-1

Volume added / µL Amide proton / ppm Thiourea proton / ppm 0 9.4428 8.3590 20 9.4491 8.3777 40 9.4529 8.4118 60 9.4591 8.4982 80 9.4641 8.5396 100 9.4654 8.5797 120 9.4679 8.6061 140 9.4717 8.6324 170 9.4704 8.6788 200 9.4729 8.6751

Titration curves for DiBz-D-tartrate with macrocycle 1 in d6-DMSO

DiBz-L-tartrate in DMSO (amide protons)

9.44

9.45

9.46

9.47

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03

[guest]

ppm

DiBz-L-tartrate in DMSO (thiourea protons)

8.35

8.40

8.45

8.50

8.55

8.60

8.65

0.0E+00 5.0E-04 1.0E-03 1.5E-03 2.0E-03 2.5E-03 3.0E-03

[guest]

ppm

ii) Binding data from ITC titration experiments

All binding experiments were performed on an isothermal titration

calorimeter from Microcal Inc. (Northampton, MA). In a typical

experiment a 1 - 2 mM receptor solution is added to the

calorimetric cell. A 48 - 78 mM solution of TBA acetate is

introduced in 50 injections of 5 µL, for a total of 250µL of added

guest. Such high concentrations of guests are important to

generate sharp curves, necessary for acceptable curve fitting. The

solution is continuously stirred to ensure rapid mixing and kept

at 25°C, through the combination of an external cooling bath and an

internal heater. Dilution effects are determined by performing a

blank experiment by adding the same guest solution into the pure

solvent and subtracting this from the raw titration to produce the

final binding curve. Association parameters are found by applying

either one-site or two-sites models, using the Origin software

provided. These methods rely on standard nonlinear least-squares

regression (Levenberg-Marquard method) to fit the curves, taking

into account the change in volume that occurs during the

calorimetric titration (W. H. Press, S. A. Teukolsky, W. T.

Vetterling, B. P. Flannery, Numerical recipes in C, 2nd ed.,

Cambridge University Press, Cambridge, 1988).

a) Data for N-Boc-L-Glu and macrocycle 1 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-189.249 -153.764 -48.8784 -38.8221 -39.0044 -37.446

-28.8245 -27.3975 -19.1454 -3.40689 23.05663 68.71635 123.3233 155.6574 182.2862 185.8849 195.1904 195.5603 198.4545 200.9079 197.6934 201.0834 199.4598 199.4112 199.9179 197.5559 204.3711 197.0166 198.3899 199.3671 408.6134 397.7125 397.2287 392.9763 387.8707 383.2565 380.2648 378.5055 373.7875 371.6359 368.181 362.3546 358.7509 355.7086 353.4957 345.1381 341.4609 337.9775 336.817 330.3869 328.342 325.628 324.4354 319.7499

2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5

0 0.10922 0.21825 0.3271 0.43576 0.54423 0.65251 0.76061 0.86852 0.97624 1.08378 1.19113 1.29829 1.40527 1.51206 1.61866 1.72507 1.8313 1.93734 2.04319 2.14886 2.25434 2.35963 2.46474 2.56966 2.67439 2.77893 2.88329 2.98746 3.09144 3.19524 3.40227 3.60856 3.81409 4.01888 4.22292 4.42621 4.62876 4.83055 5.0316 5.2319 5.43145 5.63025 5.82831 6.02562 6.22218 6.41799 6.61305 6.80737 7.00094 7.19376 7.38583 7.57715 7.76773

1.29 1.2878 1.28559 1.2834 1.2812 1.27901 1.27683 1.27464 1.27247 1.27029 1.26812 1.26595 1.26379 1.26163 1.25947 1.25732 1.25517 1.25302 1.25088 1.24874 1.24661 1.24448 1.24235 1.24022 1.2381 1.23599 1.23387 1.23176 1.22966 1.22755 1.22545 1.22126 1.21709 1.21293 1.20878 1.20465 1.20053 1.19642 1.19233 1.18825 1.18419 1.18013 1.17609 1.17207 1.16806 1.16406 1.16007 1.1561 1.15213 1.14819 1.14425 1.14033 1.13642 1.13252

0.08481 0.16977 0.25487 0.34011 0.42551 0.51104 0.59672 0.68255 0.76852 0.85464 0.9409 1.0273 1.11385 1.20055 1.28739 1.37438 1.46151 1.54878 1.6362 1.72377 1.81148 1.89933 1.98733 2.07548 2.16377 2.2522 2.34078 2.42951 2.51838 2.6074 2.78586 2.96491 3.14453 3.32473 3.50552 3.68688 3.86883 4.05135 4.23446 4.41814 4.6024 4.78725 4.97267 5.15867 5.34526 5.53242 5.72016 5.90848 6.09739 6.28687 6.47693 6.66757 6.85879 7.0506

-1162.51 -1234.32

-- -- -- --

-621.702 -625.842 -603.787 -494.202 -355.264 -60.2823 262.9994 484.5682 634.4697 671.4336 714.1357 707.7618 736.8489 746.3467 728.3377 744.327 736.6176 732.5924 736.027 722.5011 764.1504 722.6998 734.2305 737.2481 747.1079 724.165 727.0855 717.4262 698.1583 689.2948 684.52 683.213 671.6182 668.813 657.3806 644.8344 637.9774 632.1624 626.5861 606.4587 595.0101 590.042 588.205 573.8739 570.6078 566.5464 561.2056 553.1474

317.4505 313.8304 308.8789 306.1113 304.1368 302.4893 297.8454 295.0179 292.5818 291.6189 287.6484

5 5 5 5 5 5 5 5 5 5 5

7.95756 8.14664 8.33497 8.52255 8.70939 8.89548 9.08082 9.26541 9.44925 9.63235 9.8147

1.12864 1.12476 1.1209 1.11706 1.11322 1.1094 1.10559 1.10179

1.098 1.09422 1.09046

7.24298 7.43594 7.62948 7.8236 8.0183 8.21358 8.40944 8.60588 8.8029 9.0005 9.19868

548.6419 541.9815 530.8968 525.0446 521.322 518.0835 505.7222 500.6646 495.67

494.4923 486.2193

N-Boc-L-Glu and macrocycle 1 in CH3CN

Data fitted using two binding site model:

Ka1:1 = 27270 ± 4820 M-1

∆H = -4.49 ± 0.18 kJmol-1,

∆S = 70.48 Jmol-1K-1)

(Ka2:1 = 25 ± 4 M-1)

0 2 4 6 8 10

-1.0

-0.5

0.0

0.5

1.0

LGluMeCNC_NDH LGluMeCNC_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

b) Data for N-Boc-D-Glu and macrocycle 1 in CH3CN (data corrected by subtracting the background dilution data for an injection of

the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-163.719 -196.252 -188.462 -183.107 -186.473 -185.276 -178.878 -186.245 -173.145 -171.419 -162.417 -131.26

-94.9491 -61.1531 -42.0515 -28.0974 -20.2937 -13.1429 -8.54055 -4.22314 -0.45496 1.15022 2.37363 4.78172 7.65869 8.14733 9.06747 9.9707

12.13907 13.29957 29.02517 31.09795 34.02882 36.58593 38.94935 40.09813 40.88099 42.01826 43.33526 43.74343 45.50059 45.81537 46.65492 47.17971 47.51448 47.64501 48.34218 49.1942 49.67137 48.73941 49.47997 49.06059 49.83424 50.39214

2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5

0 0.10905 0.21791 0.32659 0.43507 0.54338 0.65149 0.75942 0.86716 0.97472 1.08208 1.18927 1.29626 1.40307 1.50969 1.61612 1.72237 1.82843 1.93431

2.04 2.1455 2.25081 2.35594 2.46088 2.56563 2.6702 2.77458 2.87878 2.98278 3.08661 3.19024 3.39695 3.60291 3.80812 4.01259 4.21631 4.41928 4.62151 4.82299 5.02372 5.22371 5.42295 5.62144 5.81919 6.01619 6.21244 6.40795 6.60271 6.79672 6.98998 7.1825 7.37427 7.5653 7.75557

0.94 0.93839 0.93679 0.93519 0.93359 0.93199 0.9304 0.92881 0.92722 0.92564 0.92406 0.92248 0.9209 0.91933 0.91775 0.91618 0.91462 0.91306 0.91149 0.90994 0.90838 0.90683 0.90528 0.90373 0.90218 0.90064 0.8991 0.89756 0.89603 0.8945 0.89297 0.88991 0.88687 0.88384 0.88082 0.87781 0.8748 0.87181 0.86883 0.86586 0.8629 0.85994

0.857 0.85407 0.85114 0.84823 0.84532 0.84243 0.83954 0.83666 0.8338 0.83094 0.82809 0.82525

0.11621 0.23261 0.34922 0.46602 0.58302 0.70023 0.81763 0.93522 1.05302 1.17102 1.28921 1.4076 1.52619 1.64498 1.76397 1.88316 2.00254 2.12213 2.24191 2.36189 2.48207 2.60245 2.72303 2.84381 2.96478 3.08595 3.20733 3.3289 3.45067 3.57263 3.81717 4.06249 4.30861 4.55553 4.80324 5.05174 5.30104 5.55113 5.80202 6.0537 6.30618 6.55945 6.81352 7.06838 7.32403 7.58048 7.83772 8.09576 8.35459 8.61422 8.87464 9.13586 9.39787 9.66068

-- -- --

-1953 -1994.29 -2042.53 -1990.68 -2074.57 -1970.88 -1964.27 -1927.97 -1713.25 -1516.77 -1283.92 -1183.63 -1085.22 -1019.05 -999.216 -951.25

-936.936 -903.327 -890.811 -876.484 -849.993 -844.294 -823.989 -826.177 -814.06 -791.97

-799.035 -787.032 -755.91

-735.573 -718.604 -700.216 -688.415 -675.368 -662.838 -649.707 -641.149 -623.003 -611.197 -607.127 -594.563 -583.136 -577.195 -561.819 -550.084 -539.863 -535.845 -522.743 -517.462 -509.725 -500.277

50.46469 50.54157 50.91086 51.19185 50.30102 50.31416 50.05067 49.99682 50.63248 50.94008 50.28977

5 5 5 5 5 5 5 5 5 5 5

7.9451 8.13389 8.32193 8.50922 8.69576 8.88156 9.06661 9.25091 9.43447 9.61727 9.79934

0.82242 0.8196 0.81678 0.81398 0.81118 0.8084 0.80562 0.80285 0.80009 0.79734 0.7946

9.92427 10.18867 10.45386 10.71984 10.98662 11.25419 11.52256 11.79172 12.06167 12.33242 12.60397

-493.883 -482.286 -473.826 -465.492 -459.291 -453.488 -447.322 -446.568

-432.4 -425.134 -423.894

N-Boc-D-Glu and macrocycle 1 in CH3CN


Ka2:1 = 49150 ± 675 M-1

∆H = -6.73 ± 0.067 kJmol-1,

∆S = 67.58 Jmol-1K-1

(Ka1:1 = 38 ± 2 M-1)

0 2 4 6 8 10 12

-1.5

-1.0

-0.5

0.0

DGluMeCNB_NDH DGluMeCNB_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

c) Data for N-Boc-L-Glu and macrocycle 1 in DMSO (data corrected by subtracting the background dilution data for an injection of

the guest solution into the cell containing neat DMSO).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-619.179 -304.269 -222.763 -183.857 -85.3283 1.27622 53.82913 81.51115 96.5027 111.7939 124.4743 139.3054 152.0669 162.0422 172.2156 178.1855 184.0366 189.3605 194.1516 194.4186 195.8559 199.1482 200.2779 201.7373 200.8781 200.9426 202.1667 201.1533 199.376 199.1672 198.4799 196.0795 196.3583 194.5739 193.5206 193.2806 190.5462 190.9743 190.7106 189.3373 187.1899 185.095 183.6648 182.276 180.1428 179.9729 177.0212 176.2865 175.6264 173.5617

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5

0 0.21791 0.43507 0.65149 0.86716 1.08208 1.29626 1.50969 1.72237 1.93431 2.1455 2.35594 2.56563 2.77458 2.98278 3.19024 3.39695 3.60291 3.80812 4.01259 4.21631 4.41928 4.62151 4.82299 5.02372 5.22371 5.42295 5.62144 5.81919 6.01619 6.21244 6.40795 6.60271 6.79672 6.98998 7.1825 7.37427 7.5653 7.75557 7.9451 8.13389 8.32193 8.50922 8.69576 8.88156 9.06661 9.25091 9.43447 9.61727 9.79934

1.4 1.39522 1.39045 1.3857 1.38097 1.37625 1.37155 1.36687 1.3622 1.35754 1.35291 1.34828 1.34368 1.33909 1.33451 1.32995 1.3254 1.32087 1.31636 1.31186 1.30737 1.3029 1.29844

1.294 1.28958 1.28516 1.28077 1.27638 1.27201 1.26766 1.26332 1.25899 1.25468 1.25038 1.24609 1.24182 1.23757 1.23332 1.22909 1.22488 1.22067 1.21648 1.21231 1.20815

1.204 1.19986 1.19574 1.19163 1.18753 1.18345

0.15618 0.3129 0.47015 0.62794 0.78625 0.9451 1.10449 1.26441 1.42486 1.58584 1.74736 1.90941

2.072 2.23512 2.39877 2.56295 2.72767 2.89293 3.05871 3.22503 3.39188 3.55927 3.72719 3.89564 4.06463 4.23415 4.4042 4.57479 4.74591 4.91756 5.08975 5.26247 5.43573 5.60951 5.78383 5.95869 6.13408

6.31 6.48645 6.66344 6.84096 7.01902 7.19761 7.37673 7.55639 7.73657 7.9173 8.09855 8.28034 8.46266

-2204.11 -1685.22

-1561 -1469.19 -1171.09 -893.42

-714.804 -622.951 -561.644 -499.076 -447.928 -392.581 -342.44

-303.265 -258.999 -231.477 -200.229 -175.519 -149.353 -135.855 -122.111 -103.635 -91.2995 -78.2756 -71.4866 -62.8806 -52.1727 -48.3605 -44.8698 -38.0242 -28.0197 -33.5746 -22.1267 -26.6567 -10.2245 -7.21463 -14.1484 -5.07739 1.56024 3.18772 4.32944 1.88594 1.28534 4.43816 0.89774 3.44965 2.04426 2.53264 5.15434 4.17212

N-Boc-L-Glu and macrocycle 1 in DMSO


Ka1:1 = 2281 ± 258 M-1

∆H = -10.73 ± 0.32 kJmol-1,

∆S = 28.56 Jmol-1K-1

(Ka2:1 = 28 ± 1 M-1)

0 2 4 6 8 10

-2.0

-1.5

-1.0

-0.5

0.0

srLbocglu4_NDH srLbocglu4_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

d) Data for Acetate and macrocycle 1 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

27.48395 5 0 0.7 0.10771 -- 353.1491 5 0.07514 0.69761 0.21579 --

534.4007 5 0.15003 0.69523 0.32424 --

537.5806 5 0.22465 0.69285 0.43306 4840.67

414.798 5 0.29902 0.69049 0.54224 3793.619

232.6422 5 0.37313 0.68813 0.6518 2153.909

79.75142 5 0.44699 0.68578 0.76172 856.0021

-7.07607 5 0.52058 0.68343 0.872 46.55876

-54.8458 5 0.59392 0.6811 0.98266 -391.044

-80.1968 5 0.667 0.67877 1.09368 -689.01

-94.1475 5 0.73983 0.67645 1.20508 -790.584

-100.88 5 0.81239 0.67414 1.31684 -802.869

-105.2 5 0.8847 0.67184 1.42896 -876.027

-107.712 5 0.95675 0.66954 1.54146 -816.877

-115.521 5 1.02855 0.66725 1.65432 -924.35

-117.849 5 1.10008 0.66497 1.76755 -964.503

-118.827 5 1.17136 0.6627 1.88115 -997.75

-115.41 5 1.24238 0.66044 1.99512 -949.577

-117.851 5 1.31315 0.65818 2.10946 -948.094

-116.813 5 1.38365 0.65593 2.22416 -955.266

-114.247 5 1.4539 0.65369 2.33923 -924.585

-114.628 5 1.52389 0.65145 2.45467 -945.067

-112.597 5 1.59362 0.64922 2.57048 -932.944

-110.41 5 1.6631 0.647 2.68665 -914.888

-109.113 5 1.73232 0.64479 2.80319 -886.63

-110.926 5 1.80128 0.64258 2.9201 -920.155

-107.61 5 1.86998 0.64038 3.03738 -872.229

-105.783 5 1.93843 0.63819 3.15503 -833.541

-101.07 5 2.00662 0.63601 3.27304 -792.678

-100.063 5 2.07455 0.63383 3.39142 -813.583

-97.5315 5 2.14222 0.63166 3.51017 -766.788

-94.2183 5 2.20964 0.6295 3.62929 -744.404

-92.4658 5 2.27679 0.62734 3.74878 -696.03

-90.7906 5 2.3437 0.62519 3.86863 -701.474

-88.4277 5 2.41034 0.62305 3.98885 -646.497

-87.3031 5 2.47672 0.62091 4.10944 -678.056

-83.7412 5 2.54285 0.61878 4.2304 -669.866

-81.3188 5 2.60872 0.61666 4.35172 -660.036

-78.6804 5 2.67434 0.61455 4.47342 -611.159

-75.8436 5 2.73969 0.61244 4.59548 -586.745

-76.3901 5 2.80479 0.61034 4.71791 -599.614

-71.3492 5 2.86963 0.60824 4.8407 -549.858

-70.1711 5 2.93421 0.60615 4.96387 -522.438

-67.4958 5 2.99854 0.60407 5.0874 -509.733

-65.4191 5 3.06261 0.602 5.2113 -465.177

-63.6086 5 3.12642 0.59993 5.33557 -442.424

-60.634 5 3.18997 0.59787 5.4602 -443.242

-56.662 5 3.25326 0.59581 5.58521 -391.451

-56.8592 5 3.3163 0.59377 5.71058 -421.343

-56.7613 5 3.37908 0.59172 5.83632 -372.347

Acetate and macrocycle 1 in CH3CN


Ka1:1 = 222 ± 28 M-1

∆H = -2.73 ± 0.12 kJmol-1,

∆S = 35.21 Jmol-1K-1

Ka2:1 = 5100 ± 127 M-1

∆H = -5.81 ± 0.22 kJmol-1,

∆S = 50.33 Jmol-1K-1

0 1 2 3 4 5 6

0

2

4

6

S4166641_NDH S4166641_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

e) Data for N-Ac-L-Glu and macrocycle 1 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

278.2733 5 0 1 0.17479 -- 505.0682 5 0.17419 0.99658 0.35017 --

415.5797 5 0.34779 0.99318 0.52616 --

126.969 5 0.52078 0.98979 0.70274 --

-62.9556 5 0.69318 0.98641 0.87991 547.8061

-105.289 5 0.86499 0.98304 1.05769 376.2888

-114.218 5 1.0362 0.97968 1.23606 319.3029

-116.969 5 1.20681 0.97633 1.41503 277.1702

-125.705 5 1.37682 0.973 1.59459 220.7007

-131.88 5 1.54623 0.96967 1.77475 183.1136

-133.597 5 1.71505 0.96636 1.95551 165.5847

-138.31 5 1.88327 0.96306 2.13687 132.3266

-137.51 5 2.0509 0.95977 2.31882 136.332

-142.527 5 2.21793 0.95649 2.50137 106.3029

-146.147 5 2.38436 0.95322 2.68452 93.79639

-148.146 5 2.55019 0.94996 2.86826 76.54938

-150.154 5 2.71543 0.94672 3.0526 62.64744

-151.878 5 2.88007 0.94348 3.23754 52.17631

-151.003 5 3.04411 0.94025 3.42307 54.4694

-148.424 5 3.20756 0.93704 3.6092 67.57537

-150.496 5 3.3704 0.93384 3.79593 60.86384

-151.141 5 3.53266 0.93064 3.98326 43.50492

-151.133 5 3.69431 0.92746 4.17118 41.20537

-151.176 5 3.85537 0.92429 4.3597 36.72307

-150.306 5 4.01583 0.92113 4.54882 35.76104

-150.652 5 4.17569 0.91797 4.73853 33.70992

-151.162 5 4.33496 0.91483 4.92884 22.9673

-149.708 5 4.49363 0.9117 5.11975 25.51959

-150.493 5 4.6517 0.90858 5.31125 22.06272

-148.197 5 4.80918 0.90547 5.50335 27.76487

-149.277 5 4.96606 0.90237 5.69605 10.22058

-149.934 5 5.12234 0.89928 5.88935 8.28937

-149.934 5 5.27802 0.8962 6.08324 9.80645

-149.448 5 5.43311 0.89313 6.27773 7.7555

-147.57 5 5.5876 0.89007 6.47282 10.73838

-145.108 5 5.7415 0.88702 6.6685 15.13758

-148.479 5 5.89479 0.88398 6.86478 -3.36891

-147.121 5 6.04749 0.88094 7.06166 2.00785

-143.684 5 6.1996 0.87792 7.25913 12.50763

-144.889 5 6.3511 0.87491 7.45721 11.03006

-144.921 5 6.50201 0.87191 7.65587 1.81596

-146.556 5 6.65232 0.86892 7.85514 -3.21853

-144.01 5 6.80204 0.86593 8.055 -2.27012

-141.361 5 6.95116 0.86296 8.25546 3.86182

-144.622 5 7.09968 0.86 8.45652 -14.0371

-141.213 5 7.2476 0.85704 8.65817 -0.95278

-143.384 5 7.39493 0.8541 8.86042 -6.07434

-140.788 5 7.54166 0.85116 9.06327 -5.25443

-139.69 5 7.68779 0.84824 9.26672 2.33798

-137.23 5 7.83333 0.84532 9.47076 6.82351

N-Ac-L-Glu and macrocycle 1 in CH3CN


Ka1:1 = 10210 ± 428 M-1

∆H = 2.37 ± 0.23 kJmol-1,

∆S = 76.75 Jmol-1K-1

Ka2:1 = 1201 ± 89 M-1

∆H = 2.04 ± 0.18 kJmol-1,

∆S = 64.73 Jmol-1K-1

0 2 4 6 8 10

0.0

0.1

0.2

0.3

0.4

0.5

0.6

S4166304ar_NDH S4166304ar_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

f) Data for N-Ac-D-Glu and macrocycle 1 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-221.759 5 0 0.75 0.11424 -- -194.953 5 0.08539 0.74744 0.22887 --

-114.827 5 0.17048 0.74489 0.34389 --

-63.746 5 0.25529 0.74234 0.45931 --

-33.403 5 0.3398 0.73981 0.57511 --

-18.1534 5 0.42401 0.73728 0.6913 --

-11.341 5 0.50794 0.73476 0.80788 1090.615

-18.7213 5 0.59157 0.73225 0.92485 1017.931

-32.5127 5 0.67491 0.72975 1.04222 903.7822

-52.1443 5 0.75796 0.72726 1.15997 727.2042

-71.839 5 0.84071 0.72477 1.27811 560.8852

-88.5154 5 0.92317 0.72229 1.39664 431.4605

-111.364 5 1.00534 0.71983 1.51557 237.9472

-126.367 5 1.08722 0.71737 1.63488 124.4941

-132.915 5 1.1688 0.71492 1.75459 52.96839

-134.707 5 1.25009 0.71247 1.87468 37.90549

-139.959 5 1.33109 0.71004 1.99516 -6.59837

-136.838 5 1.4118 0.70761 2.11604 13.16458

-139 5 1.49221 0.70519 2.2373 2.10895

-142.273 5 1.57233 0.70278 2.35896 -30.8697

-142.456 5 1.65216 0.70038 2.481 -22.5812

-143.224 5 1.73169 0.69798 2.60344 -40.4059

-140.522 5 1.81094 0.69559 2.72626 -10.9662

-141.54 5 1.88989 0.69322 2.84948 -26.3939

-143.953 5 1.96854 0.69084 2.97308 -40.4583

-146.427 5 2.04691 0.68848 3.09708 -67.9596

-140.416 5 2.12498 0.68612 3.22146 -12.957

-143.147 5 2.20276 0.68378 3.34624 -36.597

-143.409 5 2.28025 0.68144 3.47141 -34.5234

-145.673 5 2.35744 0.6791 3.59696 -45.0446

-149.585 5 2.43434 0.67678 3.72291 -76.9401

-144.709 5 2.51095 0.67446 3.84925 -46.7871

-146.672 5 2.58727 0.67215 3.97598 -56.3195

-147.891 5 2.66329 0.66985 4.10309 -65.2876

-146.631 5 2.73902 0.66755 4.2306 -55.8779

-145.113 5 2.81446 0.66526 4.3585 -49.0303

-147.3 5 2.8896 0.66298 4.48679 -75.9782

-143.058 5 2.96446 0.66071 4.61546 -22.6095

-147.337 5 3.03902 0.65844 4.74453 -74.1015

-143.766 5 3.11329 0.65618 4.87399 -37.0838

-140.751 5 3.18726 0.65393 5.00384 -14.4072

-143.133 5 3.26094 0.65169 5.13408 -39.5481

-142.913 5 3.33433 0.64945 5.26471 -27.1402

-141.842 5 3.40743 0.64722 5.39573 -24.9534

-146.204 5 3.48023 0.645 5.52714 -84.8392

-142.435 5 3.55275 0.64278 5.65894 -36.8902

-141.836 5 3.62496 0.64057 5.79113 -18.9316

-141.518 5 3.69689 0.63837 5.92371 -13.7272

-141.077 5 3.76852 0.63618 6.05668 -21.9565

-138.016 5 3.83987 0.63399 6.19004 4.48711

N-Ac-D-Glu and macrocycle 1 in CH3CN


Ka1:1 = 3112 ± 132 M-1

∆H = -5.92 ± 0.27 kJmol-1,

∆S = 46.30 Jmol-1K-1

Ka2:1 = 16013 ± 1228 M-1

∆H = 12.51 ± 0.48 kJmol-1,

∆S = 120.45 Jmol-1K-1

0 2 4 6

0.0

0.5

1.0

1.5

S4166322ar_NDH S4166322ar_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

g) Data for N-Ac-D-Glu and macrocycle 1 in DMSO (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat DMSO).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-79.8204 5 0 0.6 0.1885 -- -142.007 5 0.11271 0.59795 0.37764 --

-164.055 5 0.22504 0.59591 0.56742 --

-135.572 5 0.33698 0.59387 0.75785 -1064.75

-71.4047 5 0.44853 0.59184 0.94893 -712.889

-23.6634 5 0.5597 0.58982 1.14064 -439.618

7.8213 5 0.67048 0.58781 1.333 -264.35

29.66179 5 0.78087 0.5858 1.52601 -150.246

44.30953 5 0.89088 0.5838 1.71966 -72.0762

54.38499 5 1.0005 0.5818 1.91395 -19.4201

61.95552 5 1.10974 0.57982 2.10888 18.12689

67.80546 5 1.21859 0.57784 2.30446 45.65264

73.5768 5 1.32705 0.57586 2.50069 67.65807

75.91952 5 1.43513 0.57389 2.69755 73.6753

78.11185 5 1.54282 0.57193 2.89507 60.34269

82.10485 5 1.65012 0.56998 3.09322 61.64274

86.52682 5 1.75704 0.56803 3.29202 63.15863

87.50279 5 1.86357 0.56609 3.49146 50.68085

88.75868 5 1.96972 0.56415 3.69155 51.92872

89.2455 5 2.07548 0.56222 3.89228 54.91998

89.06273 5 2.18085 0.5603 4.09365 56.27225

87.27867 5 2.28584 0.55839 4.29567 51.52905

87.24718 5 2.39044 0.55648 4.49833 59.18711

86.24453 5 2.49465 0.55457 4.70164 61.48504

84.71813 5 2.59848 0.55268 4.90559 51.47595

84.98468 5 2.70192 0.55078 5.11018 65.3158

82.89713 5 2.80497 0.5489 5.31542 50.35923

81.33911 5 2.90764 0.54702 5.5213 42.58948

81.92646 5 3.00993 0.54515 5.72782 57.17032

80.22306 5 3.11182 0.54328 5.93499 50.75474

78.22755 5 3.21333 0.54142 6.1428 31.07314

77.95998 5 3.31446 0.53957 6.35126 33.79863

77.44351 5 3.41519 0.53772 6.56036 36.90357

76.14324 5 3.51554 0.53588 6.7701 27.65998

76.33149 5 3.61551 0.53404 6.98049 33.58349

76.864 5 3.71509 0.53221 7.19152 33.07593

76.34105 5 3.81428 0.53039 7.4032 33.76892

74.51271 5 3.91308 0.52857 7.61552 22.04331

76.31938 5 4.0115 0.52675 7.82848 28.49482

74.58309 5 4.10954 0.52495 8.04208 18.76371

74.89448 5 4.20718 0.52315 8.25634 20.52174

75.63293 5 4.30444 0.52135 8.47123 26.74503

75.51682 5 4.40132 0.51956 8.68677 28.88892

70.79126 5 4.49781 0.51778 8.90295 0.35948

71.23486 5 4.59391 0.516 9.11978 4.7571

71.61063 5 4.68962 0.51423 9.33724 3.82284

72.24823 5 4.78495 0.51246 9.55536 6.74236

71.0056 5 4.8799 0.5107 9.77412 1.59857

71.33121 5 4.97445 0.50894 9.99352 7.72336

70.65046 5 5.06862 0.50719 10.21356 2.94226

N-Ac-D-Glu and macrocycle 1 in DMSO


Ka1:1 = 503 ± 52 M-1

∆H = 3.48 ± 0.19 kJmol-1,

∆S = 62.41 Jmol-1K-1

Ka2:1 = 24993 ± 1309 M-1

∆H = -6.38 ± 0.37 kJmol-1,

∆S = 61.74 Jmol-1K-1

0 2 4 6 8 10

-1.2

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

0.2

S4166631_NDH S4166631_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

h) Data for N-Boc-L-Glu and macrocycle 2 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-395.261 5 0 1.31 0.16691 -4738.71 -18.0526 5 0.21791 1.30553 0.3344 -4110.07

217.1694 5 0.43507 1.30107 0.50245 -3976.36

218.5506 5 0.65149 1.29662 0.67108 -3679.89

345.9632 5 0.86716 1.29219 0.84027 -3213.71

401.026 5 1.08208 1.28778 1.01004 -2998.11

413.8809 5 1.29626 1.28338 1.18037 -2918.83

424.3791 5 1.50969 1.279 1.35127 -2814.75

429.1041 5 1.72237 1.27463 1.52275 -2749.86

437.1479 5 1.93431 1.27027 1.69479 -2646.95

439.5955 5 2.1455 1.26593 1.86741 -2588.65

446.2682 5 2.35594 1.26161 2.04059 -2516.02

441.9686 5 2.56563 1.2573 2.21435 -2488.01

420.4742 5 2.77458 1.253 2.38867 -2485.92

455.0899 5 2.98278 1.24872 2.56357 -2321.26

479.042 5 3.19024 1.24445 2.73903 --

444.6691 5 3.39695 1.2402 2.91507 --

442.6216 5 3.60291 1.23596 3.09168 -2195.86

438.0617 5 3.80812 1.23173 3.26885 -2278.91

433.8685 5 4.01259 1.22752 3.4466 --

429.6047 5 4.21631 1.22333 3.62491 -2105.85

433.8393 5 4.41928 1.21914 3.8038 -2046.33

426.4315 5 4.62151 1.21497 3.98326 -2021.4

423.8645 5 4.82299 1.21082 4.16328 -1984.1

416.5014 5 5.02372 1.20667 4.34388 -1966

415.6812 5 5.22371 1.20255 4.52504 -1927.89

412.9732 5 5.42295 1.19843 4.70678 -1894.87

404.246 5 5.62144 1.19433 4.88909 -1875.51

402.3044 5 5.81919 1.19024 5.07196 -1849.63

400.1466 5 6.01619 1.18617 5.25541 -1824.11

394.5112 5 6.21244 1.1821 5.43943 -1801.69

392.9762 5 6.40795 1.17806 5.62402 -1753.18

386.5491 5 6.60271 1.17402 5.80917 -1738.29

383.1872 5 6.79672 1.17 5.9949 -1720.64

381.7875 5 6.98998 1.16599 6.1812 -1677.53

375.9513 5 7.1825 1.16199 6.36806 -1657.43

374.7868 5 7.37427 1.15801 6.5555 -1630.41

372.7234 5 7.5653 1.15404 6.74351 -1603.5

366.7657 5 7.75557 1.15008 6.93209 -1588.96

363.1843 5 7.9451 1.14613 7.12124 -1566.56

362.5511 5 8.13389 1.1422 7.31095 -1538.1

360.4525 5 8.32193 1.13828 7.50124 -1522.61

355.0395 5 8.50922 1.13437 7.6921 -1492.78

353.0595 5 8.69576 1.13048 7.88353 -1467.15

346.3298 5 8.88156 1.1266 8.07553 -1463.05

347.2566 5 9.06661 1.12273 8.26809 -1423.82

335.6471 5 9.25091 1.11887 8.46123 -1433.31

340.3261 5 9.43447 1.11502 8.65494 -1388.2

328.4469 5 9.61727 1.11119 8.84922 -1396.16

333.6669 5 9.79934 1.10737 9.04407 -1344.24

N-Boc-L-Glu and macrocycle 2 in CH3CN


Ka1:1 = 1804 ± 1082 M-1

∆H = -21.84 ± 2.74 kJmol-1,

∆S = -11.25 Jmol-1K-1

(Ka2:1 = 11 ± 5 M-1)

0 2 4 6 8 10

-5

-4

-3

-2

-1

SRmacroLgl_NDH SRmacroLgl_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

i) Data for N-Boc-D-Glu and macrocycle 2 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-95.1721 5 0 1.25 0.17849 -- -178.098 5 0.22235 1.24573 0.35759 -2644.15

105.351 5 0.44394 1.24148 0.5373 -1762.82

193.9395 5 0.66477 1.23724 0.71762 -1497.53

233.9105 5 0.88483 1.23301 0.89855 -1350.73

257.3857 5 1.10413 1.2288 1.08009 -1268.58

284.3982 5 1.32267 1.2246 1.26223 -1161.79

299.4787 5 1.54045 1.22042 1.44499 -1093.66

305.9875 5 1.75747 1.21625 1.62836 -1037.23

297.7314 5 1.97372 1.21209 1.81233 -1038.24

307.8205 5 2.18921 1.20795 1.99692 -969.666

317.3467 5 2.40394 1.20382 2.18212 -915.321

320.6082 5 2.61791 1.19971 2.36792 -870.234

309.3379 5 2.83112 1.19561 2.55434 -881.594

317.4429 5 3.04356 1.19153 2.74136 -836.684

317.6478 5 3.25524 1.18745 2.929 -804.291

317.6342 5 3.46616 1.1834 3.11724 -775.894

318.3204 5 3.67632 1.17935 3.3061 -742.89

310.0876 5 3.88572 1.17532 3.49556 -743.057

312.2355 5 4.09435 1.1713 3.68563 -714.017

308.4497 5 4.30222 1.1673 3.87632 -686.694

310.6111 5 4.50933 1.1633 4.06761 -666.212

305.2017 5 4.71568 1.15932 4.25951 -640.607

293.0352 5 4.92127 1.15536 4.45202 -677.271

298.8794 5 5.12609 1.15141 4.64514 -616.282

299.5859 5 5.33015 1.14747 4.83888 -608.516

295.8911 5 5.53345 1.14354 5.03322 -594.949

299.2872 5 5.73599 1.13963 5.22817 -564.103

293.7691 5 5.93776 1.13573 5.42373 -557.338

289.7578 5 6.13878 1.13184 5.6199 -549.435

287.7317 5 6.33903 1.12796 5.81668 -530.913

283.8299 5 6.53852 1.1241 6.01406 -516.642

288.7942 5 6.73724 1.12025 6.21206 -480.116

280.8526 5 6.93521 1.11641 6.41067 -490.786

284.7717 5 7.13241 1.11258 6.60989 -456.533

280.4919 5 7.32885 1.10877 6.80972 -448.627

281.7936 5 7.52453 1.10497 7.01015 -437.801

281.7778 5 7.71945 1.10118 7.2112 -414.914

274.9901 5 7.9136 1.0974 7.41286 -409.693

268.7288 5 8.107 1.09364 7.61512 -423.917

272.9118 5 8.29963 1.08989 7.818 -399.117

263.376 5 8.49149 1.08615 8.02148 -398.862

264.1807 5 8.6826 1.08242 8.22558 -387.223

267.5108 5 8.87295 1.0787 8.43028 -354.269

266.1047 5 9.06253 1.075 8.6356 -344.118

263.7852 5 9.25135 1.0713 8.84152 -337.559

258.847 5 9.43941 1.06762 9.04806 -341.548

257.3103 5 9.6267 1.06395 9.2552 -327.827

256.6965 5 9.81324 1.06029 9.46295 -319.989

252.5119 5 9.99901 1.05665 9.67131 -318.538

N-Boc-D-Glu and macrocycle 2 in CH3CN


Ka2:1 = 2071 ± 1136 M-1

∆H = -11.73 ± 3.41 kJmol-1,

∆S = 24.16 Jmol-1K-1

(Ka1:1 = 28 ± 17 M-1)

0 2 4 6 8 10

-2.5

-2.0

-1.5

-1.0

-0.5

SRmacroDgl_NDH SRmacroDgl_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

j) Data for N-Boc-L-Glu and macrocycle 2 in DMSO (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat DMSO).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

-108.462 5 0 1.2 0.18221 -514.989 -66.8496 5 0.21791 1.1959 0.36505 -617.304

-26.5499 5 0.43507 1.19182 0.54851 -507.419

3.31264 5 0.65149 1.18775 0.73259 -430.309

19.273 5 0.86716 1.18369 0.9173 -396.834

20.00068 5 1.08208 1.17965 1.10262 -411.167

21.08862 5 1.29626 1.17562 1.28857 -424.426

30.42911 5 1.50969 1.1716 1.47514 -393.692

48.33094 5 1.72237 1.1676 1.66233 -347.208

65.99387 5 1.93431 1.16361 1.85015 -299.62

78.27402 5 2.1455 1.15963 2.03859 -270.706

86.32697 5 2.35594 1.15567 2.22765 -242.885

94.31854 5 2.56563 1.15172 2.41733 -218.614

100.9725 5 2.77458 1.14779 2.60764 -197.917

107.7744 5 2.98278 1.14387 2.79856 -164.019

111.3553 5 3.19024 1.13996 2.99011 -154.228

114.1639 5 3.39695 1.13606 3.18229 -144.25

116.0986 5 3.60291 1.13218 3.37508 -133.559

119.223 5 3.80812 1.12831 3.5685 -117.498

116.3975 5 4.01259 1.12445 3.76254 -121.807

119.6677 5 4.21631 1.1206 3.9572 -104.092

121.3333 5 4.41928 1.11677 4.15248 -95.9757

118.7878 5 4.62151 1.11295 4.34839 -99.1466

117.6171 5 4.82299 1.10914 4.54492 -97.977

121.9495 5 5.02372 1.10535 4.74207 -76.9825

120.6552 5 5.22371 1.10157 4.93984 -78.9524

118.3217 5 5.42295 1.0978 5.13824 -80.4157

119.2518 5 5.62144 1.09404 5.33725 -72.5174

120.548 5 5.81919 1.0903 5.53689 -58.7343

119.318 5 6.01619 1.08656 5.73716 -57.958

119.2199 5 6.21244 1.08284 5.93804 -54.9158

117.1565 5 6.40795 1.07913 6.13955 -59.6967

114.9613 5 6.60271 1.07544 6.34168 -57.1836

117.1894 5 6.79672 1.07175 6.54443 -46.6266

115.7506 5 6.98998 1.06808 6.74781 -42.9217

114.6413 5 7.1825 1.06442 6.9518 -49.1772

114.0004 5 7.37427 1.06077 7.15642 -42.6776

113.5383 5 7.5653 1.05713 7.36166 -41.0047

111.8289 5 7.75557 1.05351 7.56753 -42.7212

112.1663 5 7.9451 1.04989 7.77402 -35.909

110.696 5 8.13389 1.04629 7.98112 -38.4326

108.7372 5 8.32193 1.0427 8.18886 -42.7354

108.4469 5 8.50922 1.03912 8.39721 -39.6221

107.687 5 8.69576 1.03555 8.60618 -34.0158

106.374 5 8.88156 1.032 8.81578 -31.3372

106.6299 5 9.06661 1.02845 9.026 -31.2879

107.4048 5 9.25091 1.02492 9.23685 -23.8

104.5279 5 9.43447 1.02139 9.44831 -28.9614

100.2885 5 9.61727 1.01788 9.6604 -36.6289

101.1653 5 9.79934 1.01438 9.87311 -33.2215



Ka1:1 = 427 ± 28 M-1

∆H = 7.84 ± 0.25 kJmol-1,

∆S = 24.07 Jmol-1K-1

(Ka2:1 = 21 ± 5 M-1)

0 2 4 6 8 10

-0.6

-0.5

-0.4

-0.3

-0.2

-0.1

0.0

SRLgluDMSO_NDH SRLgluDMSO_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

k) Data for N-Boc-L-Asp and macrocycle 2 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

113.4196 5 0 1.24 0.17634 -- -21.4013 5 0.21791 1.23576 0.35328 --

272.1399 5 0.43507 1.23154 0.53082 -2404.4

345.9685 5 0.65149 1.22734 0.70896 -2150.45

395.3356 5 0.86716 1.22315 0.88771 -1945.51

454.1679 5 1.08208 1.21897 1.06705 -1708.36

509.3942 5 1.29626 1.2148 1.247 -1480.67

563.2501 5 1.50969 1.21065 1.42756 -1244.94

588.7566 5 1.72237 1.20652 1.60871 -1125.81

607.0309 5 1.93431 1.2024 1.79047 -1016.9

617.8467 5 2.1455 1.19829 1.97283 -930.758

614.8726 5 2.35594 1.19419 2.15579 -891.685

614.8521 5 2.56563 1.19011 2.33935 -831.687

608.2634 5 2.77458 1.18605 2.52352 -823.315

602.1144 5 2.98278 1.18199 2.70829 -784.84

595.1951 5 3.19024 1.17795 2.89366 -766.977

589.2062 5 3.39695 1.17393 3.07963 -741.659

578.0951 5 3.60291 1.16992 3.26621 -736.005

569.1938 5 3.80812 1.16592 3.45338 -715.961

561.8611 5 4.01259 1.16193 3.64116 -688.488

555.2768 5 4.21631 1.15796 3.82955 -666.282

547.9678 5 4.41928 1.154 4.01853 -641.222

538.8672 5 4.62151 1.15005 4.20812 -632.995

535.2448 5 4.82299 1.14612 4.39831 -606.457

527.0428 5 5.02372 1.1422 4.5891 -604.919

519.5921 5 5.22371 1.13829 4.78049 -583.471

513.5225 5 5.42295 1.13439 4.97249 -571.177

506.6473 5 5.62144 1.13051 5.16508 -557.617

498.3341 5 5.81919 1.12664 5.35829 -543.514

491.9654 5 6.01619 1.12278 5.55209 -525.359

488.6812 5 6.21244 1.11894 5.74649 -497.417

480.4525 5 6.40795 1.11511 5.9415 -490.119

473.565 5 6.60271 1.11129 6.13711 -485.469

465.2013 5 6.79672 1.10748 6.33332 -484.55

462.7295 5 6.98998 1.10368 6.53014 -456.465

454.6407 5 7.1825 1.0999 6.72755 -449.007

450.4784 5 7.37427 1.09613 6.92557 -425.768

444.4835 5 7.5653 1.09237 7.12419 -423.489

439.1584 5 7.75557 1.08863 7.32342 -413.13

434.8225 5 7.9451 1.08489 7.52324 -393.938

429.1925 5 8.13389 1.08117 7.72367 -384.541

422.2736 5 8.32193 1.07746 7.9247 -379.857

417.3219 5 8.50922 1.07376 8.12633 -367.34

410.0866 5 8.69576 1.07007 8.32857 -360.917

405.0114 5 8.88156 1.0664 8.5314 -347.406

401.9393 5 9.06661 1.06273 8.73484 -331.246

394.5031 5 9.25091 1.05908 8.93888 -331.818

390.8598 5 9.43447 1.05544 9.14353 -325.969

384.9848 5 9.61727 1.05181 9.34877 -313.307

379.6274 5 9.79934 1.04819 9.55462 -314.613

N-Boc-L-Asp and macrocycle 2 in CH3CN


Ka1:1 = 3919 ± 1773 M-1

∆H = -14.73 ± 1.44 kJmol-1,

∆S = 19.42 Jmol-1K-1

(Ka2:1 = 24 ± 16 M-1)

0 2 4 6 8 10-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

SRmacroLas_NDH SRmacroLas_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

l) Data for N-Boc-D-Asp and macrocycle 2 in CH3CN (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat CH3CN).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

1727.611 5 0 1.24 0.17744 -- 1774.855 5 0.21928 1.23576 0.35549 --

1784.452 5 0.4378 1.23154 0.53414 -11.2114

1772.393 5 0.65558 1.22734 0.7134 4.38203

1749.548 5 0.8726 1.22315 0.89327 8.7899

1776.496 5 1.08887 1.21897 1.07374 168.3662

1781.112 5 1.30439 1.2148 1.25482 248.98

1804.072 5 1.51915 1.21065 1.43651 414.7873

1823.299 5 1.73317 1.20652 1.6188 543.8012

1835.088 5 1.94644 1.2024 1.80169 654.4388

1837.472 5 2.15895 1.19829 1.9852 710.7435

1832.122 5 2.37071 1.19419 2.1693 754.9333

1818.242 5 2.58172 1.19011 2.35402 755.1242

1810.272 5 2.79198 1.18605 2.53934 765.3966

1794.855 5 3.00149 1.18199 2.72527 787.7359

1781.873 5 3.21024 1.17795 2.9118 796.8801

1753.841 5 3.41824 1.17393 3.09894 796.999

1734.489 5 3.6255 1.16992 3.28668 794.3373

1714.629 5 3.832 1.16592 3.47504 806.7799

1699.205 5 4.03775 1.16193 3.66399 798.313

1681.575 5 4.24275 1.15796 3.85356 790.2168

1662.684 5 4.44699 1.154 4.04372 782.0844

1649.271 5 4.65049 1.15005 4.2345 773.7968

1634.683 5 4.85323 1.14612 4.42588 777.1863

1615.328 5 5.05522 1.1422 4.61787 759.87

1601.738 5 5.25646 1.13829 4.81046 750.5448

1580.689 5 5.45695 1.13439 5.00366 --

1567.068 5 5.65669 1.13051 5.19747 728.9108

1551.534 5 5.85567 1.12664 5.39188 725.5576

1539.26 5 6.05391 1.12278 5.5869 737.5146

1520.831 5 6.25139 1.11894 5.78252 715.9899

1500.055 5 6.44812 1.11511 5.97875 --

1491.178 5 6.6441 1.11129 6.17559 721.8724

1479.314 5 6.83933 1.10748 6.37303 714.6847

1462.409 5 7.03381 1.10368 6.57108 709.4065

1450.789 5 7.22753 1.0999 6.76973 710.4806

1443.856 5 7.42051 1.09613 6.96899 --

1427.553 5 7.61273 1.09237 7.16886 700.4468

1415.443 5 7.8042 1.08863 7.36933 706.1012

1401.768 5 7.99492 1.08489 7.57041 698.2735

1389.129 5 8.18488 1.08117 7.77209 694.0906

1372.148 5 8.3741 1.07746 7.97438 683.2207

1353.013 5 8.56257 1.07376 8.17728 648.6628

1341.485 5 8.75028 1.07007 8.38078 655.6341

1329.359 5 8.93724 1.0664 8.58489 648.6679

1323.152 5 9.12345 1.06273 8.78961 659.2498

1306.038 5 9.30891 1.05908 8.99493 --

1303.291 5 9.49362 1.05544 9.20085 661.5095

1289.66 5 9.67757 1.05181 9.40739 651.9963

1279.571 5 9.86077 1.04819 9.61453 643.9757

N-Boc-D-Asp and macrocycle 2 in CH3CN


Ka2:1 = 2125 ± 633 M-1

∆H = -8.44 ± 0.98 kJmol-1,

∆S = 10.55 Jmol-1K-1

(Ka1:1 = 8 ± 4 M-1)

0 2 4 6 8 10

-0.2

0.0

0.2

0.4

0.6

0.8

SRDAspMeCN_NDH SRDAspMeCN_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

m) Data for N-Boc-L-Glu and macrocycle 3 in DMSO (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat DMSO).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

74.50041 2.5 0 0.96 0.11379 -- 97.52066 2.5 0.10905 0.95836 0.22777 --

-29.821 2.5 0.21791 0.95672 0.34194 -1249.02

-70.8563 2.5 0.32659 0.95509 0.45631 -1397.78

-65.0043 2.5 0.43507 0.95345 0.57088 -1244.89

-59.6385 2.5 0.54338 0.95182 0.68564 -1231.21

-53.3412 2.5 0.65149 0.9502 0.80059 -1118.21

-44.5306 2.5 0.75942 0.94857 0.91574 -1092.06

-33.7178 2.5 0.86716 0.94695 1.03108 -1005.43

-16.6089 2.5 0.97472 0.94533 1.14662 -875.893

0.39347 2.5 1.08208 0.94372 1.26235 -780.586

17.38409 2.5 1.18927 0.9421 1.37828 -636.947

26.74415 2.5 1.29626 0.94049 1.4944 -617.174

32.39921 2.5 1.40307 0.93889 1.61071 -533.351

41.73516 2.5 1.50969 0.93728 1.72722 -489.626

45.87701 2.5 1.61612 0.93568 1.84393 -445.421

52.99478 2.5 1.72237 0.93408 1.96082 -385.822

55.71731 2.5 1.82843 0.93248 2.07792 -370.74

57.81987 2.5 1.93431 0.93089 2.19521 -342.512

60.84859 2.5 2.04 0.9293 2.31269 -335.504

60.13929 2.5 2.1455 0.92771 2.43036 -319.769

65.0282 2.5 2.25081 0.92612 2.54823 -287.322

65.15118 2.5 2.35594 0.92454 2.6663 -272.984

65.50691 2.5 2.46088 0.92296 2.78456 -262.728

67.2987 2.5 2.56563 0.92138 2.90301 -261.128

65.78315 2.5 2.6702 0.9198 3.02166 -270.504

68.09184 2.5 2.77458 0.91823 3.14051 -254.368

66.02349 2.5 2.87878 0.91666 3.25954 -260.327

67.38673 2.5 2.98278 0.91509 3.37878 -228.833

68.78892 2.5 3.08661 0.91353 3.4982 -228.674

134.0012 5 3.19024 0.91196 3.73764 -227.93

130.8076 5 3.39695 0.90885 3.97786 -210.406

131.3317 5 3.60291 0.90574 4.21885 -192.208

129.2559 5 3.80812 0.90264 4.46062 -190.157

129.3438 5 4.01259 0.89956 4.70317 -177.236

128.4375 5 4.21631 0.89648 4.9465 -174.287

127.2875 5 4.41928 0.89342 5.1906 -165.535

127.3219 5 4.62151 0.89036 5.43548 -157.21

129.2325 5 4.82299 0.88732 5.68115 -139.966

131.1952 5 5.02372 0.88428 5.92758 -124.587

130.9191 5 5.22371 0.88125 6.1748 -112.607

130.8043 5 5.42295 0.87824 6.4228 -103.942

130.1433 5 5.62144 0.87523 6.67157 -98.0994

129.0193 5 5.81919 0.87224 6.92112 -92.5438

128.8926 5 6.01619 0.86925 7.17145 -86.7879

127.217 5 6.21244 0.86627 7.42255 -81.5758

126.6934 5 6.40795 0.86331 7.67444 -75.9408

124.353 5 6.60271 0.86035 7.9271 -76.611

123.5786 5 6.79672 0.8574 8.18054 -71.1053

122.6288 5 6.98998 0.85446 8.43476 -68.3219



Ka1:1 = 27450 ± 8173 M-1

∆H = -5.93 ± 0.16 kJmol-1,

∆S = 65.09 Jmol-1K-1

Ka2:1 = 393 ± 38 M-1

∆H = -8.64 ± 0.34 kJmol-1,

∆S = 20.69 Jmol-1K-1

0 2 4 6 8 10 12 14

-1.4

-1.2

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

GKBLGlu1_NDH GKBLGlu1_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

n) Data for N-Boc-D-Glu and macrocycle 3 in DMSO (data corrected by subtracting the background dilution data for an injection of the guest solution into the cell containing neat DMSO).

area

(µcal)

injection

(µL)

[guest] (mM)

(before inj.)

[host] (mM)

(before inj.)

[host] / [guest]

(after inj.)

cal / mol of

injected guest

62.91751 2.5 0 0.96 0.11379 -- 51.89695 2.5 0.10905 0.95836 0.22777 --

-81.1643 2.5 0.21791 0.95672 0.34194 -1700.32

-118.208 2.5 0.32659 0.95509 0.45631 -1717.81

-123.3 2.5 0.43507 0.95345 0.57088 -1673.49

-113.732 2.5 0.54338 0.95182 0.68564 -1549.1

-92.9804 2.5 0.65149 0.9502 0.80059 -1374.42

-77.6178 2.5 0.75942 0.94857 0.91574 -1274.09

-51.2993 2.5 0.86716 0.94695 1.03108 -1101.81

-26.3541 2.5 0.97472 0.94533 1.14662 -950.899

-3.06833 2.5 1.08208 0.94372 1.26235 -784.097

21.84286 2.5 1.18927 0.9421 1.37828 -608.811

46.14084 2.5 1.29626 0.94049 1.4944 -467.679

52.79022 2.5 1.40307 0.93889 1.61071 -409.025

60.69648 2.5 1.50969 0.93728 1.72722 -361.994

63.13243 2.5 1.61612 0.93568 1.84393 -342.981

70.30955 2.5 1.72237 0.93408 1.96082 -293.15

79.02114 2.5 1.82843 0.93248 2.07792 -243.001

77.30496 2.5 1.93431 0.93089 2.19521 -228.703

84.52519 2.5 2.04 0.9293 2.31269 -193.837

83.26833 2.5 2.1455 0.92771 2.43036 -196.865

89.45713 2.5 2.25081 0.92612 2.54823 -153.039

88.53462 2.5 2.35594 0.92454 2.6663 -157.001

85.01858 2.5 2.46088 0.92296 2.78456 -170.776

86.70741 2.5 2.56563 0.92138 2.90301 -188.376

89.02892 2.5 2.6702 0.9198 3.02166 -160.371

93.22999 2.5 2.77458 0.91823 3.14051 -125.588

88.2301 2.5 2.87878 0.91666 3.25954 -149.696

94.04049 2.5 2.98278 0.91509 3.37878 -104.3

93.30024 2.5 3.08661 0.91353 3.4982 -118.132

184.2897 5 3.19024 0.91196 3.73764 -121.358

178.8933 5 3.39695 0.90885 3.97786 -118.409

179.6489 5 3.60291 0.90574 4.21885 -94.2429

181.234 5 3.80812 0.90264 4.46062 -85.9075

178.9776 5 4.01259 0.89956 4.70317 -88.1921

176.2317 5 4.21631 0.89648 4.9465 -91.3095

175.3992 5 4.41928 0.89342 5.1906 -80.7888

175.6947 5 4.62151 0.89036 5.43548 -65.6817

173.7684 5 4.82299 0.88732 5.68115 -64.0699

174.2266 5 5.02372 0.88428 5.92758 -56.2853

170.9364 5 5.22371 0.88125 6.1748 -58.5747

168.7411 5 5.42295 0.87824 6.4228 -59.2024

169.737 5 5.62144 0.87523 6.67157 -51.0549

170.5513 5 5.81919 0.87224 6.92112 -42.6537

168.1541 5 6.01619 0.86925 7.17145 -43.7751

168.948 5 6.21244 0.86627 7.42255 -37.3792

167.0643 5 6.40795 0.86331 7.67444 -35.4893

164.4968 5 6.60271 0.86035 7.9271 -41.4772

164.3187 5 6.79672 0.8574 8.18054 -37.5788

162.3624 5 6.98998 0.85446 8.43476 -38.2072

N-Boc-D-Glu and macrocycle 3 in DMSO


Ka1:1 = 262 ± 46 M-1

∆H = -4.37 ± 0.27 kJmol-1,

∆S = 31.03 Jmol-1K-1

Ka2:1 = 19380 ± 2061 M-1

∆H = -7.97 ± 0.10 kJmol-1,

∆S = 55.34 Jmol-1K-1

0 2 4 6 8 10 12 14-2.0

-1.5

-1.0

-0.5

0.0

GKBDGlu2_NDH GKBDGlu2_Fit

Molar Ratio

kcal

/mol

e of

inje

ctan

t

supporting information · i) binding data from nmr titration experiments a) nmr titration data for...

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