Probing helix propensity of monomers within a helical oligomer

Dolain et al. 10.1073/pnas.0506262102.

Supporting Information

Files in this Data Supplement:

Supporting Figure 7
Supporting Figure 8
Supporting Figure 9
Supporting Figure 10
Supporting Figure 11
Supporting Figure 12
Supporting Figure 13
Supporting Table 1
Supporting Materials and Methods

Supporting Figure 7

Fig. 7. Part of the 400-MHz ¹H NMR spectra showing the signals of amide (10.3-11.8 ppm) and aromatic (5.4-8.6 ppm) protons. (a) 1 in CDCl₃ at 20°C shortly after dissolving crystals grown from CHCl₃. (b) 1 in CDCl₃ at 20°C at equilibrium. (c) 1 in toluene-d₈ at 20°C shortly after dissolving crystals grown from CHCl₃. (d) 1 in toluene-d₈ at 20°C at equilibrium. The asterisks mark signals of residual hydrogenated solvent. The open and filled circles mark signals of the phenyl ring for P-M and P-P/M-M isomers, respectively.

Supporting Figure 8

Fig. 8. ROESY spectrum (mixing time t = 300 ms) of 1 in toluene-d₈ at 25°C. Red arrows mark NOEs between the central amide protons and protons of the phenyl ring. Protons of the major P-P/M-M isomer are labeled in red, and protons of the minor P-M isomer are in blue.

Supporting Figure 9

Fig. 9. Molecular dynamics simulation of the P-M conformer of 1 in chloroform at 300 K over 1 ns. The initial folded conformation is a local conformational energy minimum found upon minimization using the MM3 force field on MACROMODEL. Snapshots are taken at different time intervals. In each case, five structures stored every 2 ps are superimposed. The meta-xylylene unit is represented in red.

Supporting Figure 10

Fig. 10. Molecular dynamics simulation of the P-P conformer of 1 in chloroform at 300 K over 1 ns. The initial folded conformation is a local conformational energy minimum found upon minimization using the MM3 force field on MACROMODEL. Snapshots are taken at different time intervals. In each case, five structures stored every 2 ps are superimposed. The meta-xylylene unit is represented in red.

Supporting Figure 11

Fig. 11. Molecular dynamics simulation of the P-P conformer of 1 in chloroform at 400 K over 1 ns. The initial folded conformation is a local conformational energy minimum found upon minimization using the MM3 force field on MACROMODEL. Snapshots are taken at different time intervals. In each case, five structures stored every 2 ps are superimposed. The meta-xylylene unit is represented in red.

Supporting Figure 12

Fig. 12. Molecular dynamics simulation of the P-P conformer of 1 in chloroform at 500 K over 1 ns. The initial folded conformation is a local conformational energy minimum found upon minimization using the MM3 force field on MACROMODEL. Snapshots are taken at different time intervals. In each case, five structures stored every 2 ps are superimposed. The meta-xylylene unit is represented in red.

Supporting Figure 13

Fig. 13. Molecular dynamics simulation of the P-P conformer of 1 in chloroform at 600 K over 1 ns. The initial folded conformation is a local conformational energy minimum found upon minimization using the MM3 force field on MACROMODEL. Snapshots are taken at different time intervals. In each case, five structures stored every 2 ps are superimposed. The meta-xylylene unit is represented in red.

Table 1. Crystallographic parameters for the structures determined

	1(Cl)₂	2	3
Solvent/precipitant	C₆H₅Cl/hexane	CHCl₃/hexane	CHCl₃/hexane
Formula	C₂₃₂H₂₃₀Cl₂N₃₄O₃₆-5(C₆H₅Cl)-8(H₂O)	C₁₂₀H₁₂₀N₁₈O₂₀-(C₆H₅Cl)-(CHCl₃)	C₁₁₂H₁₁₀N₁₆O_21-(C₆H₁₄)-3(CHCl₃)
Dimensions, mm	0.20 x 0.15 x 0.10	0.20 x 0.10 x 0.10	0.15 x 0.10 x 0.10
Aspect	Yellow	Yellow	Yellow
Crystal system	Triclinic	Monoclinic	Monoclinic
Space group	P-1	P21/c	P21/n
Z	2	4	4
Unit cell parameters
a, Å	20.6050(13)	25.118(3)	18.805(10)
b, Å	26.0197(17)	18.677(2)	19.963(11)
c, Å	26.9496(18)	26.833(3)	32.084(17)
α, °	85.310(5)	90	90
β, °	74.073(4)	110.373(4)	96.421(11)
γ, °	76.365(4)	90	90
Temperature, K	153(2)	100(2)	193(2)
Volume, Å³	13500(15)	11801(2)	11969(11)
FW, g·mol^-1	4525.40	2366.26	2431.38
ρ, g·cm^-3	1.113	1.332	1.349
λ, Ε	1.54178	0.71073	0.71073
θ measured	6.55 ≤ θ ≤ 72.11	2.96 ≤ θ ≤ 19.00	2.92 ≤ θ ≤ 26.37
Radiation	Cu-K_α	Mo-K_α	Mo-K_α
Reflections measured	44691	96057	67548
Reflections unique	44691	9426	24180
GOF	1.073	1.111	1.145
R₁ (I > 2σ(I))	0.1691	0.1875	0.1423
wR₂	0.4252	0.5673	0.3270
CCDC no.	279127	279126	279125

Supporting Materials and Methods

Synthetic Procedure for the Preparation of 1 and 2. The tetrameric or octameric acid precursor (1) was dissolved in dry dimethylformamide. Diisopropylamine was added, followed by 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate. The mixture was stirred at room temperature for 20 min. Then, meta-xylylenediamine was added, and the mixture was stirred for 4 h. The solvents were evaporated in vacuo, and the residue was purified by silica gel chromatography.

Oligomer 1. Oligomer 1 was prepared from the octamer acid (1) (20 mg, 11 mmol) and meta-xylylene diamine (0.6 ml, 5 mmol). Yield: 12 mg of a yellow solid (65%). Mp: > 250°C. IR (ATR) n (cm^-1): 3318, 2959, 2918, 2873, 2849, 1686, 1592, 1571, 1560, 1540 1535, 1508, 1502, 1492, 1484, 1467, 1460 1453, 1419, 1383, 1357, 1330, 1262, 1211, 1115, 1054. 400 MHz ¹H NMR d ppm (CDCl₃, 25°C): P-P (M-M) and P-M species: 11.30 (1H, s), 11.19 (1H, s), 11.14 (1H, s), 11.10 (1H, s), 10.98 (3H, m), 10.96 (1H, s), 10.95 (1H, s), 10.88 (1H, s), 10.84 (1H, s), 10.83 (1H, s), 10.78 (1H, s), 10.76 (1H, s), 8.33 (1H, d, J = 4.6Hz), 8.31(1H, d, J = 4.6 Hz), 8.25-7.10 (34H, m), 7.09 (1H, s), 7.07 (1H, s), 7.06 (1H, s), 6.97 (1H, t, J = 8.2 Hz), 6.92 (1H, t, J = 8.2 Hz), 6.56 (1H, s), 6.53 (1H, s), 6.52 (2H, m), 6.50 (1H, s), 6.45 (1H, s), 6.35 (2H, m), 6.31 (1H, s), 6.26 (1H, s), 6.15 (1H, s), 6.12 (1H, s), 5.93 (1H, d, J = 7.2 Hz), 5.92 (1H, s), 5.88 (1H, s), 5.87 (1H, d, J = 7.2 Hz), 5.74 (2H, t, J = 7.5 Hz), 4.25-3.45 (32H, m), 2.71 (2H, t, J = 13.2 Hz), 2.57-2.13 (16H, m), 1.45-0.82 (96H, m). MS: TOF-MS m/z: 4071.32 [M+H]⁺ (Calc. for C₂₃₂H₂₃₂N₃₄O₃₆: 4069.74).

Oligomer 2. Oligomer 2 was prepared from the tetramer acid (1) (73 mg, 72 mmol) and meta-xylylene diamine (4.4 ml, 34 mmol). Yield: 60 mg of a yellow solid (83%). Mp: > 250°C. IR (ATR) n (cm^-1): 2961, 2931, 2874, 1685, 1648, 1637, 1618, 1591, 1570, 1540, 1535, 1507, 1469, 1420, 1398, 1384, 1358, 1330, 1301, 1263, 1213, 1163, 1116, 1051. 400 MHz ¹H NMR d ppm (CDCl₃, 25°C): 11.95 (1H, large), 11.43 (1H, s), 11.35 (1H, large), 8.73 (1H, large), 8.43 (1H, d, J = 8.0 Hz), 8.15 (1H, large), 8.02 (1H, d, J = 7.4 Hz), 7.88 (1H, d, J = 8.2 Hz), 7.80 (1H, d, J = 7.8 Hz), 7.76 (1H, d, J = 8.2 Hz), 7.62 (1H, large), 7.52 (1H, t, J = 8.1 Hz), 7.44 (1H, t, J = 7.8 Hz), 7.36 (1H, s), 7.31 (1H, large), 7.25 (1H, t, J = 7.9 Hz), 7.17 (1H, d, J = 7.3 Hz), 7.15 (1H, t, J = 7.8 Hz), 6.68 (1H, s), 6.62 (1H, s), 6.43 (1H, large), 6.26 (1H, large), 5.94 (1H, t, J = 7.6 Hz), 4.35-3.63 (8H, m), 2.45-2.07 (4H, m), 1.25-0.93 (24H, m). 100 MHz ¹³C NMR d ppm (CDCl₃, 25°C): 159.8, 158.8, 158.7, 158.4, 158.3, 157.9, 157.1, 156.3, 149.4, 146.7, 144.8, 144.3, 141.1, 134.8, 134.7, 134.0, 133.9, 133.1, 130.4, 129.3, 128.9, 123.6, 123.4, 122.3, 122.0, 121.4, 119.9, 119.6, 118.1, 117.7, 117.5, 113.8, 112.8, 112.7, 112.4, 112.2, 111.6, 96.1, 94.5, 94.3, 93.6, 71.5, 71.2, 70.9, 70.8, 24.0, 23.9, 15.1, 15.0. MS: TOF-MS m/z: 2133.56 [M+H]⁺ (Calc. for C₁₂₀H₁₂₀N₁₈O₂₀: 2132.89), 2155.58 [M+Na]⁺ (Calc. for C₁₂₀H₁₂₀N₁₈NaO₂₀: 2155.88), 2171.49 [M+K]⁺ (Calc. for C₁₂₀H₁₂₀KN₁₈O₂₀: 2171.86).

Oligomer 3. The tetramer acid precursor (1) (50 mg, 49 mmol) was dissolved in dry CH₂Cl₂ (2 ml). Diisopropylamine (2 eq) was added, followed by PyCloP (21 mg, 49 mmol). The mixture was stirred at room temperature for 4 h. Solvents were evaporated in vacuo, and the residue was purified by silica gel chromatography. Yield: 32 mg of a yellow solid (75%). Mp: > 250°C. IR (ATR) n (cm^-1): 2961, 2931, 2874, 1792, 1682, 1642, 1625, 1591, 1570, 1540, 1535, 1508, 1469, 1420, 1399, 1384, 1356, 1343, 1331, 1264, 1215, 1163, 1117, 1077, 1062, 1050, 1040. 400 MHz ¹H NMR d ppm (CDCl₃, 25°C): 11.34 (1H, s), 11.20 (1H, s), 11.12 (1H,s), 8.32 (1H, d, J = 8.0 Hz), 8.19 (1H, d, J = 7.5 Hz), 7.80 (2H, m), 7.54 (1H, s), 7.47 (1H, d, J = 7.4 Hz), 7.40 (1H, d, J = 8.3 Hz), 7.30 (1H, d, J = 8.3 Hz), 7.21 (1H, d, J = 7.4 Hz), 7.17-7.08 (4H, m), 7.09 (1H, t, J = 8.0 Hz), 7.04 (1H, t, J = 8.0 Hz), 6.51 (1H, s), 6.35 (1H, s), 4.28 (1H, t, J = 7.4 Hz), 4.15 (1H, t, J = 6.9 Hz), 4.11 (1H, t, J = 6.9 Hz), 4.05 (1H, t, J = 8.0 Hz), 4.03 (1H, t, J = 8.3 Hz), 3.88 (1H, t, J = 7.4 Hz), 3.84 (1H, t, J = 7.4 Hz), 3.74 (1H, t, J = 7.4 Hz), 2.50-2.25 (4H, m), 1.41-1.14 (24H, m). 100 MHz ¹³C NMR d ppm (CDCl₃, 25°C): 158.3, 158.0, 157.9, 157.6, 156.7, 156.0, 153.2, 151.2, 149.0, 146.3, 144.4, 140.2, 139.8, 139.3, 133.5, 133.4, 133.3, 129.1, 129.0, 128.3, 122.0, 121.4, 121.8, 119.3, 117.6, 116.3, 116.0, 112.8, 112.1, 112.0, 111.8, 111.8, 96.4, 95.9, 95.8, 93.3, 71.3, 71.1, 70.7, 24.2, 24.1, 24.0, 15.5, 15.4, 15.3, 15.2. MS: TOF-MS m/z: 2015.35 [M+H]⁺ (Calc. for C₁₁₂H₁₁₀N₁₆O₂₁: 2014.8), 2037.35 [M+Na]⁺ (Calc. for C₁₁₂H₁₁₀N₁₆NaO₂₁: 2037.79), 2053.30 [M+K]⁺ (Calc. for C₁₁₂H₁₁₀N₁₆KO₂₁: 2153.77).