A non-planar peptide bond in L-seryl-L-valine

The C^[alpha]-C'-N-C^[alpha] ([omega]) torsion angle of the peptide bond in the crystal structure of the title compound, C₈H₁₆N₂O₄, is 157.37 (15)°. This is the second-largest deviation from planarity observed for a small linear peptide.

S1. Comment

The structure of L-Ser-L-Val, (I), has been investigated as part of a systematic survey of dipeptides with one hydrophobic residue and one small polar residue. Special attention was focused on the hydrogen-bonding preferences and the aggregation patterns of the hydrophobic groups (Netland et al., 2004, and references therein). \sch

The molecular structure of (I) is shown in Fig. 1. Bond lengths and angles are normal, but the unusual nonplanarity of the peptide bond is quite evident. The associated torsion angle C1—C3—N2—C4 (ω) is 157.37 (15)°, a deviation from 180° that is superceded among small chiral peptides only by the 156.6° ω angle in N-(t-butoxycarbonyl)-L-Pro-L-Leu benzyl ester (Sugino et al., 1978).

Fig. 2(a) shows the molecular packing arrangement of (I). The crystal is divided into hydrophobic and hydrophilic layers in very much the same manner as for L-Ser-Leu, (II) (Fig. 2 b; Słowikowska & Lipkowski, 2001), despite a substantial shift for the β angle, which is 98.623 (6)° for (I) but just 84.189° for (II), after transformation of the originally reported unit cell to match the packing observed for (I). The length of the c axis increases from 15.588 (10) for (I) to 18.1263 (9) Å for (II), as the thickness of the hydrophobic layer increases to accommodate the bulkier Leu side chain. Changes for the other two other axes, however, are very modest [for (I), a = 5.383 (4) and b = 6.315 (4) Å, and for (II), a = 5.3288 (3) and b = 6.3696 (6) Å]. The peptide bond twist recurs for (II), which has ω = 157.99 (12)°.

The origin of the low ω values for (I) and (II) is indicated by the detailed view of the hydrogen-bonding interactions of (I) shown in Fig. 3. The C-terminal carboxylate group is clearly rotated away from the planar configuration in order to form good hydrogen bonds with four nearby donors, three amino groups and one Ser hydroxyl group (see also Table 2). The latter is twisted into an unusual eclipsed conformation, with a value of 131 (3)° for the C1—C2—O1—H5 torsion angle (Table 1).

The crystal packing arrangement of L-Ser-L-Ala (Görbitz, 2000), with a three-dimensional hydrogen-bonding pattern, is different from those of (I) and (II). The specific types of intermolecular interactions are nevertheless quite similar. The only modification concerns the amide H atom, which is donated to the C-terminal carboxylate group in (I) (Table 2) and (II), while the peptide carbonyl group is the acceptor in L-Ser-Ala. The only dipeptide in the Cambridge Structural Database (CSD, Version 5.25, November 2003; Allen, 2002) with an N-terminal Ser residue, other than L-Ser-Leu and L-Ser-Ala, is L-Ser-Gly (Jones et al., 1978). The crystal structure of L-Ser-Gly contains three –NH₃⁺···⁻OOC– interactions, while the hydroxyl H atom is donated to the peptide carbonyl group. The peptide bonds of L-Ser-L-Ala and L-Ser-Gly are both close to planar.

S2. Experimental

The title compound was obtained from Bachem. Crystals of (I) were prepared by slow diffusion of ethanol into an aqueous solution of the peptide at ambient temperature.

S3. Refinement

The absolute structure, which was known for the purchased material, could not be confirmed by the crystallographic experiment, due to the absence of significant anomalous dispersion effects. 976 Friedel pairs were thus merged in the final refinement cycles. Heavy atoms were refined anisotropically. Positional parameters were refined for H atoms involved in hydrogen bonds. Other H atoms were positioned geometrically 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 1.2U_eq of the carrier atom, or 1.5U_eq for amino and methyl groups.

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 (I). Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary size.
	Fig. 2. The molecular packing and unit cell of (a) L-Ser-L-Val, (I), and (b) L-Ser-L-Leu, (II), in the orginally reported unit cell (Słowikowska & Lipkowski, 2001). Both views are along the b axes.
	Fig. 3. A stereo drawing, showing the hydrogen bonds for the carboxylate group of an individual peptide molecule, depicted as capped sticks. The Val side chain and H atoms not involved in hydrogen bonds have been omitted for clarity. The pale grey line drawing indicates the position of the carboxylate group with a forced planar peptide bond. The dark grey line drawing shows a neighbouring peptide molecule along the a axis, as well as fragments of several others acting as hydrogen-bond donors or acceptors.

L-Seryl-L-valine

Crystal data

C8H16N2O4	F(000) = 220
Mr = 204.23	Dx = 1.295 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 5.383 (4) Å	Cell parameters from 3525 reflections
b = 6.315 (4) Å	θ = 2.5–27.1°
c = 15.588 (10) Å	µ = 0.10 mm^−1
β = 98.623 (6)°	T = 105 K
V = 523.9 (6) Å^3	Plate, colourless
Z = 2	0.35 × 0.20 × 0.08 mm

Data collection

Siemens SMART CCD area-detector diffractometer	1248 independent reflections
Radiation source: fine-focus sealed tube	1201 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.034
Detector resolution: 8.3 pixels mm^-1	θmax = 27.1°, θmin = 2.6°
sets of exposures each taken over 0.3° ω rotation scans	h = −6→6
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −8→8
Tmin = 0.894, Tmax = 0.964	l = −19→19
4217 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)] = 0.029	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.075	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	w = 1/[σ^2(Fo^2) + (0.0402P)^2 + 0.0968P] where P = (Fo^2 + 2Fc^2)/3
1248 reflections	(Δ/σ)max < 0.001
152 parameters	Δρmax = 0.18 e Å^−3
1 restraint	Δρmin = −0.24 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	0.0814 (2)	0.6295 (2)	0.49601 (8)	0.0181 (3)
H5	0.123 (4)	0.652 (5)	0.4567 (15)	0.022*
O2	0.7198 (2)	0.7151 (2)	0.69758 (8)	0.0199 (3)
O3	0.7039 (2)	0.1936 (2)	0.64316 (7)	0.0179 (3)
O4	1.0779 (2)	0.1882 (2)	0.72748 (8)	0.0186 (3)
N1	0.2844 (3)	0.9077 (2)	0.62462 (10)	0.0151 (3)
H1	0.438 (5)	0.963 (4)	0.6260 (13)	0.023*
H2	0.194 (4)	0.932 (4)	0.5715 (15)	0.023*
H3	0.216 (4)	0.979 (5)	0.6629 (15)	0.023*
N2	0.5074 (3)	0.4504 (3)	0.75378 (9)	0.0149 (3)
H4	0.364 (4)	0.380 (4)	0.7524 (13)	0.018*
C1	0.2828 (3)	0.6777 (3)	0.64365 (11)	0.0147 (3)
H11	0.134 (4)	0.647 (4)	0.6699 (13)	0.018*
C2	0.2808 (3)	0.5553 (3)	0.55846 (11)	0.0179 (4)
H21	0.441	0.575	0.5370	0.022*
H22	0.259	0.404	0.5686	0.022*
C3	0.5241 (3)	0.6173 (3)	0.70306 (11)	0.0145 (3)
C4	0.7324 (3)	0.3306 (3)	0.78849 (11)	0.0145 (3)
H41	0.853	0.427	0.8185	0.017*
C5	0.6625 (3)	0.1665 (3)	0.85427 (11)	0.0191 (4)
H51	0.524	0.079	0.8248	0.023*
C6	0.5686 (4)	0.2815 (4)	0.92991 (13)	0.0283 (5)
H61	0.703	0.377	0.9587	0.042*
H62	0.525	0.176	0.9725	0.042*
H63	0.417	0.366	0.9076	0.042*
C7	0.8811 (4)	0.0201 (4)	0.88852 (13)	0.0287 (5)
H71	0.829	−0.076	0.9320	0.043*
H72	1.025	0.105	0.9153	0.043*
H73	0.930	−0.063	0.8403	0.043*
C8	0.8456 (3)	0.2289 (3)	0.71320 (11)	0.0151 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0150 (6)	0.0224 (7)	0.0165 (6)	0.0007 (5)	0.0013 (5)	0.0005 (5)
O2	0.0107 (6)	0.0198 (7)	0.0295 (6)	−0.0019 (5)	0.0037 (5)	0.0024 (6)
O3	0.0138 (5)	0.0203 (7)	0.0198 (6)	−0.0016 (5)	0.0030 (4)	−0.0016 (5)
O4	0.0104 (5)	0.0191 (6)	0.0266 (6)	0.0009 (5)	0.0044 (4)	−0.0028 (5)
N1	0.0101 (7)	0.0155 (8)	0.0197 (7)	0.0010 (6)	0.0026 (5)	−0.0005 (6)
N2	0.0082 (6)	0.0153 (7)	0.0212 (7)	0.0010 (6)	0.0025 (5)	0.0009 (6)
C1	0.0102 (7)	0.0151 (8)	0.0191 (7)	0.0001 (7)	0.0036 (6)	−0.0002 (7)
C2	0.0156 (8)	0.0170 (9)	0.0206 (8)	0.0034 (7)	0.0003 (6)	−0.0022 (7)
C3	0.0105 (7)	0.0163 (8)	0.0172 (7)	0.0011 (6)	0.0037 (6)	−0.0032 (6)
C4	0.0100 (7)	0.0154 (8)	0.0181 (8)	0.0009 (7)	0.0018 (6)	−0.0002 (7)
C5	0.0154 (8)	0.0216 (10)	0.0205 (8)	−0.0002 (8)	0.0032 (6)	0.0034 (8)
C6	0.0288 (10)	0.0359 (13)	0.0218 (9)	0.0020 (9)	0.0093 (7)	0.0027 (8)
C7	0.0252 (10)	0.0311 (11)	0.0296 (10)	0.0056 (9)	0.0042 (7)	0.0128 (9)
C8	0.0138 (8)	0.0108 (8)	0.0217 (8)	−0.0009 (6)	0.0059 (6)	0.0019 (7)

Geometric parameters (Å, º)

O1—C2	1.416 (2)	C2—H21	0.9798
O1—H5	0.70 (2)	C2—H22	0.9798
O2—C3	1.235 (2)	C4—C8	1.541 (2)
O3—C8	1.254 (2)	C4—C5	1.543 (2)
O4—C8	1.263 (2)	C4—H41	0.9595
N1—C1	1.483 (3)	C5—C7	1.528 (3)
N1—H1	0.90 (3)	C5—C6	1.534 (3)
N1—H2	0.91 (2)	C5—H51	0.9870
N1—H3	0.87 (3)	C6—H61	0.9939
N2—C3	1.329 (3)	C6—H62	0.9939
N2—C4	1.462 (2)	C6—H63	0.9939
N2—H4	0.89 (2)	C7—H71	0.9823
C1—C3	1.526 (2)	C7—H72	0.9823
C1—C2	1.535 (2)	C7—H73	0.9823
C1—H11	0.97 (2)
C2—O1—H5	111 (2)	N2—C4—C5	108.83 (14)
C1—N1—H1	114.3 (17)	C8—C4—C5	112.94 (15)
C1—N1—H2	109.3 (18)	N2—C4—H41	108.5
H1—N1—H2	109 (2)	C8—C4—H41	108.5
C1—N1—H3	110.6 (17)	C5—C4—H41	108.5
H1—N1—H3	106 (2)	C7—C5—C6	110.06 (16)
H2—N1—H3	108 (2)	C7—C5—C4	112.76 (15)
C3—N2—C4	120.33 (14)	C6—C5—C4	109.52 (17)
C3—N2—H4	121.2 (15)	C7—C5—H51	108.1
C4—N2—H4	114.8 (16)	C6—C5—H51	108.1
N1—C1—C3	109.65 (15)	C4—C5—H51	108.1
N1—C1—C2	108.65 (14)	C5—C6—H61	109.5
C3—C1—C2	107.10 (14)	C5—C6—H62	109.5
N1—C1—H11	107.9 (15)	H61—C6—H62	109.5
C3—C1—H11	112.1 (12)	C5—C6—H63	109.5
C2—C1—H11	111.4 (13)	H61—C6—H63	109.5
O1—C2—C1	109.54 (14)	H62—C6—H63	109.5
O1—C2—H21	109.8	C5—C7—H71	109.5
C1—C2—H21	109.8	C5—C7—H72	109.5
O1—C2—H22	109.8	H71—C7—H72	109.5
C1—C2—H22	109.8	C5—C7—H73	109.5
H21—C2—H22	108.2	H71—C7—H73	109.5
O2—C3—N2	124.90 (16)	H72—C7—H73	109.5
O2—C3—C1	119.35 (16)	O3—C8—O4	124.99 (16)
N2—C3—C1	115.61 (15)	O3—C8—C4	118.61 (15)
N2—C4—C8	109.52 (13)	O4—C8—C4	116.40 (15)
N1—C1—C3—N2	152.57 (14)	N1—C1—C3—O2	−31.6 (2)
C1—C3—N2—C4	157.37 (15)	C2—C1—C3—O2	86.1 (2)
C3—N2—C4—C8	−63.7 (2)	N1—C1—C3—N2	152.57 (14)
N2—C4—C8—O3	−24.7 (2)	C2—C1—C3—N2	−89.72 (18)
N1—C1—C2—O1	−52.65 (18)	C3—N2—C4—C5	172.45 (15)
C1—C2—O1—H5	131 (3)	C8—C4—C5—C7	53.2 (2)
N2—C4—C5—C6	−62.00 (18)	C8—C4—C5—C6	176.16 (15)
N2—C4—C5—C7	175.09 (16)	C5—C4—C8—O3	96.77 (19)
C3—C1—C2—O1	−171.01 (14)	N2—C4—C8—O4	155.07 (16)
C4—N2—C3—O2	−18.2 (3)	C5—C4—C8—O4	−83.48 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3^i	0.90 (3)	2.03 (3)	2.871 (2)	156 (2)
N1—H2···O1^ii	0.91 (2)	2.10 (2)	2.875 (2)	143 (2)
N1—H3···O4^iii	0.87 (3)	1.88 (3)	2.735 (2)	166 (2)
N2—H4···O4^iv	0.89 (2)	1.95 (2)	2.824 (2)	166 (2)
O1—H5···O3^v	0.70 (2)	1.95 (2)	2.637 (2)	170 (3)
C1—H11···O2^iv	0.97 (2)	2.37 (2)	3.273 (2)	153.9 (19)

Symmetry codes: (i) x, y+1, z; (ii) −x, y+1/2, −z+1; (iii) x−1, y+1, z; (iv) x−1, y, z; (v) −x+1, y+1/2, −z+1.