Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270104021523/sx1147sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270104021523/sx1147Isup2.hkl |
CCDC reference: 254955
The title compound was obtained from Bachem. Crystals were prepared by slow diffusion of ethanol into an aqueous solution of the peptide at ambient temperature.
Positional parameters were refined for H atoms involved in hydrogen bonds; other H atoms were positioned geometrically (C—H = 0.8381–1.0032 Å) and refined with constraints to keep all C—H distances and C—C—H angles on one C atom the same. Uiso(H) values were set at 1.2Ueq of the carrier atom, or 1.5Ueq for amine and methyl groups. In the absence of significant anomalous scattering effects, 1012 Friedel pairs were merged. The absolute configuration of the purchased material was known.
Data collection: SMART (Bruker, 1998); cell refinement: SAINT-Plus (Bruker, 2001); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Bruker, 2000); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.
C12H16N2O4 | Dx = 1.339 Mg m−3 |
Mr = 252.27 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 3760 reflections |
a = 5.3382 (13) Å | θ = 2.2–26.7° |
b = 6.3827 (16) Å | µ = 0.10 mm−1 |
c = 36.741 (9) Å | T = 105 K |
V = 1251.8 (5) Å3 | Needle, colourless |
Z = 4 | 0.75 × 0.15 × 0.10 mm |
F(000) = 536 |
Siemens SMART CCD diffractometer | 1592 independent reflections |
Radiation source: fine-focus sealed tube | 1428 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.054 |
Detector resolution: 8.3 pixels mm-1 | θmax = 26.7°, θmin = 2.2° |
Sets of exposures each taken over 0.3° ω rotation scans | h = −6→6 |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | k = −7→7 |
Tmin = 0.894, Tmax = 0.990 | l = −45→46 |
6723 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.038 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.098 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0645P)2 + 0.0136P] where P = (Fo2 + 2Fc2)/3 |
1592 reflections | (Δ/σ)max = 0.002 |
190 parameters | Δρmax = 0.28 e Å−3 |
0 restraints | Δρmin = −0.23 e Å−3 |
C12H16N2O4 | V = 1251.8 (5) Å3 |
Mr = 252.27 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 5.3382 (13) Å | µ = 0.10 mm−1 |
b = 6.3827 (16) Å | T = 105 K |
c = 36.741 (9) Å | 0.75 × 0.15 × 0.10 mm |
Siemens SMART CCD diffractometer | 1592 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 1428 reflections with I > 2σ(I) |
Tmin = 0.894, Tmax = 0.990 | Rint = 0.054 |
6723 measured reflections |
R[F2 > 2σ(F2)] = 0.038 | 0 restraints |
wR(F2) = 0.098 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | Δρmax = 0.28 e Å−3 |
1592 reflections | Δρmin = −0.23 e Å−3 |
190 parameters |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Data were collected by measuring five sets of exposures with the detector set at 2θ = 29°, crystal-to-detector distance 5.00 cm. Refinement of F2 against ALL reflections. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.0763 (3) | 0.5056 (2) | 0.24905 (4) | 0.0190 (3) | |
H5 | 0.170 (5) | 0.533 (4) | 0.2302 (7) | 0.029* | |
O2 | 0.6408 (3) | 0.6014 (2) | 0.33254 (4) | 0.0201 (3) | |
O3 | 0.6547 (3) | 0.0811 (2) | 0.30975 (4) | 0.0204 (3) | |
O4 | 0.9972 (3) | 0.0694 (2) | 0.34486 (4) | 0.0184 (3) | |
N1 | 0.2372 (3) | 0.7865 (3) | 0.30197 (5) | 0.0158 (4) | |
H1 | 0.399 (5) | 0.828 (4) | 0.3016 (7) | 0.024* | |
H2 | 0.159 (5) | 0.808 (4) | 0.2827 (7) | 0.024* | |
H3 | 0.131 (4) | 0.877 (4) | 0.3187 (6) | 0.024* | |
N2 | 0.4110 (3) | 0.3350 (3) | 0.35679 (5) | 0.0161 (4) | |
H4 | 0.269 (5) | 0.267 (4) | 0.3559 (6) | 0.019* | |
C1 | 0.2235 (4) | 0.5586 (3) | 0.31063 (5) | 0.0151 (4) | |
H11 | 0.068 (5) | 0.529 (4) | 0.3212 (6) | 0.018* | |
C2 | 0.2534 (4) | 0.4336 (3) | 0.27505 (5) | 0.0186 (4) | |
H21 | 0.420 | 0.451 | 0.2657 | 0.022* | |
H22 | 0.227 | 0.287 | 0.2797 | 0.022* | |
C3 | 0.4448 (4) | 0.5022 (3) | 0.33503 (5) | 0.0143 (4) | |
C4 | 0.6302 (4) | 0.2236 (3) | 0.37044 (5) | 0.0163 (4) | |
H41 | 0.745 | 0.327 | 0.3825 | 0.020* | |
C5 | 0.5471 (4) | 0.0592 (3) | 0.39892 (6) | 0.0220 (5) | |
H51 | 0.419 | 0.122 | 0.4148 | 0.026* | |
H52 | 0.470 | −0.060 | 0.3862 | 0.026* | |
C6 | 0.7605 (4) | −0.0210 (3) | 0.42224 (5) | 0.0213 (5) | |
C7 | 0.8623 (5) | −0.2192 (4) | 0.41690 (7) | 0.0315 (6) | |
H71 | 0.793 | −0.312 | 0.3973 | 0.038* | |
C8 | 1.0574 (5) | −0.2893 (5) | 0.43838 (9) | 0.0483 (8) | |
H81 | 1.124 | −0.421 | 0.4344 | 0.058* | |
C9 | 1.1536 (6) | −0.1652 (6) | 0.46566 (8) | 0.0531 (10) | |
H91 | 1.270 | −0.209 | 0.4789 | 0.064* | |
C10 | 1.0563 (6) | 0.0314 (6) | 0.47099 (7) | 0.0494 (9) | |
H101 | 1.125 | 0.120 | 0.4897 | 0.059* | |
C11 | 0.8601 (5) | 0.1041 (4) | 0.44959 (6) | 0.0345 (6) | |
H111 | 0.796 | 0.236 | 0.4536 | 0.055 (10)* | |
C12 | 0.7725 (4) | 0.1166 (3) | 0.33893 (5) | 0.0152 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0226 (8) | 0.0219 (7) | 0.0126 (7) | −0.0003 (6) | −0.0039 (6) | 0.0000 (6) |
O2 | 0.0181 (7) | 0.0222 (8) | 0.0200 (7) | −0.0013 (6) | −0.0035 (6) | 0.0031 (6) |
O3 | 0.0234 (7) | 0.0219 (7) | 0.0159 (7) | 0.0007 (7) | −0.0041 (6) | −0.0031 (6) |
O4 | 0.0188 (7) | 0.0186 (8) | 0.0178 (7) | 0.0014 (6) | −0.0012 (6) | −0.0011 (6) |
N1 | 0.0177 (9) | 0.0166 (8) | 0.0131 (8) | 0.0028 (7) | −0.0047 (7) | −0.0005 (7) |
N2 | 0.0159 (8) | 0.0171 (9) | 0.0154 (9) | 0.0011 (7) | −0.0001 (7) | 0.0005 (6) |
C1 | 0.0169 (9) | 0.0154 (10) | 0.0132 (9) | 0.0000 (8) | −0.0014 (8) | −0.0004 (7) |
C2 | 0.0235 (10) | 0.0180 (10) | 0.0142 (9) | 0.0032 (9) | −0.0033 (8) | −0.0003 (8) |
C3 | 0.0171 (9) | 0.0164 (9) | 0.0096 (9) | 0.0020 (8) | 0.0011 (7) | −0.0025 (8) |
C4 | 0.0182 (10) | 0.0174 (10) | 0.0134 (9) | −0.0002 (9) | −0.0015 (8) | 0.0015 (7) |
C5 | 0.0233 (10) | 0.0259 (11) | 0.0168 (10) | 0.0007 (10) | 0.0021 (8) | 0.0090 (9) |
C6 | 0.0229 (10) | 0.0273 (11) | 0.0137 (9) | −0.0028 (9) | 0.0008 (8) | 0.0076 (8) |
C7 | 0.0371 (13) | 0.0268 (12) | 0.0307 (12) | 0.0018 (11) | −0.0026 (11) | 0.0095 (10) |
C8 | 0.0373 (15) | 0.0483 (17) | 0.059 (2) | 0.0102 (15) | 0.0007 (15) | 0.0318 (15) |
C9 | 0.0289 (13) | 0.092 (3) | 0.0386 (16) | −0.0057 (16) | −0.0098 (13) | 0.0450 (17) |
C10 | 0.0449 (17) | 0.085 (3) | 0.0179 (12) | −0.0200 (19) | −0.0090 (12) | 0.0063 (14) |
C11 | 0.0439 (15) | 0.0439 (15) | 0.0156 (11) | −0.0069 (13) | −0.0004 (11) | −0.0037 (10) |
C12 | 0.0196 (9) | 0.0122 (9) | 0.0139 (9) | −0.0030 (8) | −0.0001 (8) | 0.0028 (7) |
O1—C2 | 1.420 (2) | C4—C12 | 1.544 (3) |
O1—H5 | 0.87 (3) | C4—C5 | 1.547 (3) |
O2—C3 | 1.226 (2) | C4—H41 | 1.0010 |
O3—C12 | 1.264 (2) | C5—C6 | 1.515 (3) |
O4—C12 | 1.255 (3) | C5—H51 | 0.9822 |
N1—C1 | 1.490 (3) | C5—H52 | 0.9822 |
N1—H1 | 0.90 (3) | C6—C11 | 1.389 (3) |
N1—H2 | 0.83 (3) | C6—C7 | 1.391 (3) |
N1—H3 | 1.02 (2) | C7—C8 | 1.381 (4) |
N2—C3 | 1.345 (3) | C7—H71 | 1.0032 |
N2—C4 | 1.458 (3) | C8—C9 | 1.377 (5) |
N2—H4 | 0.87 (3) | C8—H81 | 0.9238 |
C1—C3 | 1.526 (3) | C9—C10 | 1.372 (5) |
C1—C2 | 1.540 (3) | C9—H91 | 0.8381 |
C1—H11 | 0.94 (2) | C10—C11 | 1.390 (4) |
C2—H21 | 0.9603 | C10—H101 | 0.9613 |
C2—H22 | 0.9603 | C11—H111 | 0.9195 |
C2—O1—H5 | 102.7 (17) | C12—C4—H41 | 108.8 |
C1—N1—H1 | 109.7 (17) | C5—C4—H41 | 108.8 |
C1—N1—H2 | 108.7 (18) | C6—C5—C4 | 113.32 (18) |
H1—N1—H2 | 114 (2) | C6—C5—H51 | 108.9 |
C1—N1—H3 | 113.5 (14) | C4—C5—H51 | 108.9 |
H1—N1—H3 | 112 (2) | C6—C5—H52 | 108.9 |
H2—N1—H3 | 98 (2) | C4—C5—H52 | 108.9 |
C3—N2—C4 | 118.92 (17) | H51—C5—H52 | 107.7 |
C3—N2—H4 | 119.3 (16) | C11—C6—C7 | 118.4 (2) |
C4—N2—H4 | 117.7 (16) | C11—C6—C5 | 120.2 (2) |
N1—C1—C3 | 108.55 (16) | C7—C6—C5 | 121.4 (2) |
N1—C1—C2 | 108.63 (15) | C8—C7—C6 | 120.6 (3) |
C3—C1—C2 | 107.23 (15) | C8—C7—H71 | 119.7 |
N1—C1—H11 | 109.1 (15) | C6—C7—H71 | 119.7 |
C3—C1—H11 | 113.3 (14) | C9—C8—C7 | 120.7 (3) |
C2—C1—H11 | 109.9 (15) | C9—C8—H81 | 119.7 |
O1—C2—C1 | 109.55 (16) | C7—C8—H81 | 119.7 |
O1—C2—H21 | 109.8 | C10—C9—C8 | 119.2 (3) |
C1—C2—H21 | 109.8 | C10—C9—H91 | 120.4 |
O1—C2—H22 | 109.8 | C8—C9—H91 | 120.4 |
C1—C2—H22 | 109.8 | C9—C10—C11 | 120.7 (3) |
H21—C2—H22 | 108.2 | C9—C10—H101 | 119.7 |
O2—C3—N2 | 124.65 (18) | C11—C10—H101 | 119.7 |
O2—C3—C1 | 119.62 (17) | C6—C11—C10 | 120.4 (3) |
N2—C3—C1 | 115.63 (17) | C6—C11—H111 | 119.8 |
N2—C4—C12 | 110.65 (16) | C10—C11—H111 | 119.8 |
N2—C4—C5 | 109.46 (17) | O4—C12—O3 | 125.4 (2) |
C12—C4—C5 | 110.39 (17) | O4—C12—C4 | 116.48 (17) |
N2—C4—H41 | 108.8 | O3—C12—C4 | 118.08 (18) |
N1—C1—C3—N2 | 154.21 (16) | C3—N2—C4—C5 | 171.98 (17) |
C4—N2—C3—C1 | 157.51 (17) | C12—C4—C5—C6 | 74.3 (2) |
C3—N2—C4—C12 | −66.2 (2) | C11—C6—C7—C8 | 0.1 (3) |
N2—C4—C12—O3 | −21.2 (3) | C5—C6—C7—C8 | 179.8 (2) |
N1—C1—C2—O1 | −53.3 (2) | C6—C7—C8—C9 | 0.5 (4) |
C1—C2—O1—H5 | 127.4 (17) | C7—C8—C9—C10 | −1.1 (4) |
N2—C4—C5—C6 | −163.69 (17) | C8—C9—C10—C11 | 1.1 (4) |
C4—C5—C6—C7 | −105.0 (2) | C7—C6—C11—C10 | −0.1 (3) |
C4—C5—C6—C11 | 74.7 (3) | C5—C6—C11—C10 | −179.8 (2) |
C3—C1—C2—O1 | −170.44 (15) | C9—C10—C11—C6 | −0.5 (4) |
C4—N2—C3—O2 | −18.8 (3) | N2—C4—C12—O4 | 159.76 (17) |
N1—C1—C3—O2 | −29.3 (2) | C5—C4—C12—O4 | −78.9 (2) |
C2—C1—C3—O2 | 87.9 (2) | C5—C4—C12—O3 | 100.1 (2) |
C2—C1—C3—N2 | −88.6 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O3i | 0.90 (3) | 2.14 (3) | 2.930 (2) | 146 (2) |
N1—H2···O1ii | 0.84 (3) | 2.13 (3) | 2.876 (2) | 149 (2) |
N1—H3···O4iii | 1.01 (2) | 1.71 (3) | 2.718 (2) | 168 (2) |
N2—H4···O4iv | 0.87 (3) | 1.97 (3) | 2.819 (2) | 165 (2) |
O1—H5···O3v | 0.87 (3) | 1.77 (3) | 2.638 (2) | 176 (2) |
C1—H11···O2iv | 0.94 (2) | 2.36 (2) | 3.225 (3) | 153 (2) |
Symmetry codes: (i) x, y+1, z; (ii) −x, y+1/2, −z+1/2; (iii) x−1, y+1, z; (iv) x−1, y, z; (v) −x+1, y+1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C12H16N2O4 |
Mr | 252.27 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 105 |
a, b, c (Å) | 5.3382 (13), 6.3827 (16), 36.741 (9) |
V (Å3) | 1251.8 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.75 × 0.15 × 0.10 |
Data collection | |
Diffractometer | Siemens SMART CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.894, 0.990 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 6723, 1592, 1428 |
Rint | 0.054 |
(sin θ/λ)max (Å−1) | 0.633 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.038, 0.098, 1.07 |
No. of reflections | 1592 |
No. of parameters | 190 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.28, −0.23 |
Computer programs: SMART (Bruker, 1998), SAINT-Plus (Bruker, 2001), SAINT-Plus, SHELXTL (Bruker, 2000), SHELXTL.
O1—C2 | 1.420 (2) | C4—C12 | 1.544 (3) |
O2—C3 | 1.226 (2) | C4—C5 | 1.547 (3) |
O3—C12 | 1.264 (2) | C5—C6 | 1.515 (3) |
O4—C12 | 1.255 (3) | C6—C11 | 1.389 (3) |
N1—C1 | 1.490 (3) | C6—C7 | 1.391 (3) |
N2—C3 | 1.345 (3) | C7—C8 | 1.381 (4) |
N2—C4 | 1.458 (3) | C8—C9 | 1.377 (5) |
C1—C3 | 1.526 (3) | C9—C10 | 1.372 (5) |
C1—C2 | 1.540 (3) | C10—C11 | 1.390 (4) |
N1—C1—C3—N2 | 154.21 (16) | C1—C2—O1—H5 | 127.4 (17) |
C4—N2—C3—C1 | 157.51 (17) | N2—C4—C5—C6 | −163.69 (17) |
C3—N2—C4—C12 | −66.2 (2) | C4—C5—C6—C7 | −105.0 (2) |
N2—C4—C12—O3 | −21.2 (3) | C4—C5—C6—C11 | 74.7 (3) |
N1—C1—C2—O1 | −53.3 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O3i | 0.90 (3) | 2.14 (3) | 2.930 (2) | 146 (2) |
N1—H2···O1ii | 0.84 (3) | 2.13 (3) | 2.876 (2) | 149 (2) |
N1—H3···O4iii | 1.01 (2) | 1.71 (3) | 2.718 (2) | 168 (2) |
N2—H4···O4iv | 0.87 (3) | 1.97 (3) | 2.819 (2) | 165 (2) |
O1—H5···O3v | 0.87 (3) | 1.77 (3) | 2.638 (2) | 176 (2) |
C1—H11···O2iv | 0.94 (2) | 2.36 (2) | 3.225 (3) | 153 (2) |
Symmetry codes: (i) x, y+1, z; (ii) −x, y+1/2, −z+1/2; (iii) x−1, y+1, z; (iv) x−1, y, z; (v) −x+1, y+1/2, −z+1/2. |
The structure of L-Ser-L-Phe, (I), has been investigated as part of a systematic survey of dipeptides with one hydrophobic and one small polar residue (Netland et al., 2004, and references therein). The molecular structure of (I) is shown in Fig. 1. Bond lengths and bond angles are normal, except in the Phe phenyl ring, where the bond lengths, in particular C8—C9 and C9—C10, are shortened significantly (Table 1) as a result of strong librational motion, reflected by the very elongated displacement ellipsoids in Fig. 1.
The peptide bond of (I) is unusually non-planar for a small linear peptide. The associated C1—C3—N2—C4 torsion angle (ω) is 157.51 (17)° (Table 1). Equivalent deviations from 180° occur also for L-Ser-L-Leu, (II) [157.99 (12)°; Słowikowska & Lipkowski, 2001], and L-Ser-L-Val, (III) [157.37 (15)°; Moen et al., 2004], which, despite the shift in space group from P21 for (II) and (III) to P212121 for (I), share the hydrogen-bonding network and general crystal packing arrangement of (I). The conversion to an orthorhombic system, which involves an increase in the length of the c axis from 18.1263 (9) Å for (II) and 15.588 (10) Å for (III) to 36.741 (9) Å for (I), is a prerequisite for the formation of the classical herringbone stacking pattern of aromatic groups seen in Fig. 2, with C9—H91···C9(1/2 + x, −1/2 − y, 1 − z) as the most prominent intermolecular C—H···π interaction (H···C = 3.00 Å). Retention of the monoclinic space group would have given a less favorable, almost coplanar, arrangement of the phenyl rings.
The origin of the low ω values for these structures results, as discussed for (III) (Moen et al., 2004), from the need to fix the side-chain Ser–OH group as well as the C-terminal carboxylate group in favourable positions for the formation of hydrogen bonds (Table 2). Notably, the hydroxy H atom points in the direction of its carboxylate acceptor thanks to a conformation [C1—C2—O1—H5 = 127.4 (17)°; Table 1] that causes an eclipse with one of the H atoms bonded to atom C2 (H21—C2—O1—H5 = 6.5°). The overall molecular geometry of (I) corresponds closely to that observed for (II) and (III). The Phe side chain is in a common trans orientation as defined by the N2—C4—C5—C6 torsion angle.
The hydrophobic layers in the structure of (I) are composed of the benzyl side chains of the Phe residues. Similarly, isobutyl and isopropyl side chains of Leu and Val residues can also form hydrophobic layers on their own, as in the structures of (II) and (III). In contrast, no examples, to the authors' knowledge, have been found of peptide structures with hydrophobic layers composed exclusively of Ala methyl groups, which are apparently too small to fill a layer without leaving large unfavorable voids. Hence, L-Ser-L-Ala, the third peptide in the Cambridge Structural Database (Version 5.25 of November 2003; Allen, 2002) in which an N-terminal Ser residue is coupled with a hydrophobic residue, forms a structure with a three-dimensional hydrogen-bonding pattern that is completely different from that of (I), (II) and (III).