L-Seryl-L-phenyl­alanine

The peptide bond in the crystal structure of the title compound, C₈H₁₆N₂O₄, deviates substantially from planarity in the same manner as in other L-Ser-L-Xaa dipeptides, where Xaa is a hydro­phobic residue.

S1. Comment

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).

S2. Experimental

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.

S3. Refinement

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. U_iso(H) values were set at 1.2U_eq of the carrier atom, or 1.5U_eq 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.

Computing details

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.

Figures

	Fig. 1. : The molecular structure of L-Ser-L-Phe. Displacement ellipsoids are shown at the 50% probability level and H atoms are shown as spheres of arbitrary size.
	Fig. 2. : The molecular packing and unit cell of L-Ser-L-Phe, viewed along the b axis.

L-Seryl-L-phenylalanine

Crystal data

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) Å^3	Needle, colourless
Z = 4	0.75 × 0.15 × 0.10 mm
F(000) = 536

Data collection

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

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.098	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0645P)^2 + 0.0136P] where P = (Fo^2 + 2Fc^2)/3
1592 reflections	(Δ/σ)max = 0.002
190 parameters	Δρmax = 0.28 e Å^−3
0 restraints	Δρmin = −0.23 e Å^−3

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	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)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

Geometric parameters (Å, º)

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)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3^i	0.90 (3)	2.14 (3)	2.930 (2)	146 (2)
N1—H2···O1^ii	0.84 (3)	2.13 (3)	2.876 (2)	149 (2)
N1—H3···O4^iii	1.01 (2)	1.71 (3)	2.718 (2)	168 (2)
N2—H4···O4^iv	0.87 (3)	1.97 (3)	2.819 (2)	165 (2)
O1—H5···O3^v	0.87 (3)	1.77 (3)	2.638 (2)	176 (2)
C1—H11···O2^iv	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.