Racemic dipeptide glycyl-DL-leucine at 120 K

The structure of glycyl-DL-leucine, C₈H₁₆N₂O₃, has been determined at 120 K by single-crystal X-ray diffraction. In addition to three N-H...O-type hydrogen bonds of the positively charged RNH₃⁺ group of the zwitterionic mol­ecule, an intermolecular N-H...O contact exists between the peptide bond and the carboxyl­ate group. Four hydrogen-bond cycles were identified, giving a complex pattern.

S1. Comment

Study of small peptides has gained interest in the investigation of the geometry of the peptide bond. Structures of over 120 dipeptides can be found in the Cambridge Structural Database (Allen & Kennard, 1993) today. In most cases the naturally occurring l-form, less often the racemic dl-form and simple derivatives of dipeptides, were investigated. In the course of our ongoing research of comparative charge-density studies of different oligopeptides, we have examined several dipeptides. The structure of the racemic dipeptide glycyl-dl-leucine, (I), was not known until now, but the structure of the resolved l-form was investigated by Pattabhi et al. (1974). \sch

Crystals of the title compound were obtained by vapor diffusion of methanol into a saturated aqueous solution of glycyl-dl-leucine. An ORTEP (Burnett & Johnson, 1996) representation of the molecular structure and the atomic numbering scheme is shown in Fig. 1.

Although the two C—O bonds of the carboxylate group are chemically equivalent, they are of different lengths [1.2468 (10) and 1.2773 (10) Å] (Table 1). The oxygen atom of the shorter bond is an acceptor of two N—H···O hydrogen bonds and of two weak C—H···O bonds, while the oxygen of the longer C—O bond has stronger intractions, namely three N—H···O hydrogen bonds (Table 2). When fitting the l-enantiomer of the dl-structure to the resolved glycyl-l-leucine, one finds the positions of the short and long C—O bonds [1.240 (5) and 1.263 (5) Å] exchanged. This is not surprising, because the hydrogen-bonding scheme of the dl-structure is very different from that of the resolved structure. In the latter, both O atoms of the carboxylate group are acceptors of two N—H···O bonds, and the O-atom of the longer C—O bond forms the stronger hydrogen bonds.

A comparison between the torsion angles of the title compound and the corresponding angles of the l-enantiomer (see Table 3) shows, that the conformations are basically the same. The placement of the terminal N1 atom differs the most in the two crystals. The differences in the torsion angles are 18.2° for N1–C1–C2–N2 and 17.3° for N1–C1–C2–O1. Two of the three torsion angles describing the backbone conformation are only slightly different from each other; the third one, C2–N2–C3–C4, is −170.49 (7)° in the dl-form and 172.5° in the l-form. However, as already mentioned in the case of the the l-enantiomer, the angle ω of the peptide bond (ω¹: C1–C2–N2–C3) shows a slight deviation [167.07 (7)°] from planarity. The calculated molecular isometricity index comparing the l-conformer of the racemic crystal and the l-enantiomer from the resolved crystal is 94.4% (Kálmán et al., 1993).

Hydrophobic and hydrophilic layers alternate in the crystal of glycyl-dl-leucine as shown in a SCHAKAL representation (Fig. 2). The zwitterionic functional groups are at x = 1/4 and 3/4, while the aliphatic hydrophobic regions are at x = 1/2 and 1. These layers are parallel to the bc crystallographic plane and their thickness is a/4. Within each hydrophilic layer the molecules are connected by a complex system of hydrogen bonds. Hydrogen bonds are listed in Table 2.

The three hydrogen atoms of the N1 amino group take part in four intermolecular interactions to three neighbouring molecules [N1–H1A···O3ⁱ (3/2 − x, 3/2 − y, 2 − z), N1–H1B···O3ⁱⁱ (3/2 − x, 1/2 + y, 3/2 − z), N1–H1C···O2ⁱⁱⁱ (x, 1 + y, z), N1–H1C···O3ⁱⁱⁱ (x, 1 + y, z)]. O2 is an acceptor of hydrogen bonds from two neighbouring molecules [O2···H2—N2^v (x, 1 − y, −1/2 + z), O2···H1D—C1^v (x, 1 − y, −1/2 + z) and O2···H1C—N1^vi (x, −1 + y, z)] while O3 from three different neighbours O3···H1A–N1ⁱ (3/2 − x, 3/2 − y, 2 − z), [O3···H1C—N1^vi (x, −1 + y, z) and O3···H1B—N1^vii (3/2 − x, −1/2 + y, 3/2 − z)]. The N2 atom in the peptide bond participates in an intermolecular interaction with the carboxyl oxygen O2 [N2—H2···O2^iv (x, 1 − y, 1/2 + z)]. There are two intramolecular hydrogen bonds stabilizing the molecular conformation. These are O1···H1B–N1 and O2···H7–C7.

In the crystal lattice, four loops are formed with the participation of hydrogen bonds (Fig. 3). The largest one is a homodromic cycle of four molecules, the hydrogen-bond network graph-set notation is R₄⁴(26) (Grell et al., 1999). Two cycles include three molecules, R₃²(12) and R₃³(11), respectively. One loop consists of two molecules, R₂²(16), being built up from a D– and an l-form connected through an inversion center (molecules 0 and i on Figure 2).

S2. Refinement

All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were found in difference Fourier maps. Five types of hydrogen atoms were refined with a free variable of the displacement parameters.

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SMART; data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996), PLATON (Spek, 1990), SCHAKAL (Keller, 1997).

Figures

	Fig. 1. The molecular structure and numbering scheme of (I). Displacement ellipsoids are plotted at 50% probability (ORTEPIII; Burnett & Johnson, 1996 and PLATON; Spek, 1990). The directions of intra- and intermolecular hydrogen bonds are presented by dashed lines.
	Fig. 2. Packing of the unit cell of (I) drawn with SCHAKAL97 (Keller, 1997). Hydrophilic parts of the cell are drawn in black, while hydrophobic regions are gray.
	Fig. 3. Diagram showing the cycles formed by N–H···O type strong hydrogen bonding. Symmetry operations, chirality and the sequence number from Table 2 are inscribed into the rectangles representing the molecules [symmetry code: (viii) 3/2 − x, 3/2 − y, 1 − z].

dl-2-(2-amino-acetylamino)-4-metyhl-pentanoic acid

Crystal data

C8H16N2O3	F(000) = 816
Mr = 188.23	Dx = 1.242 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 29.038 (6) Å	Cell parameters from 9661 reflections
b = 7.233 (1) Å	θ = 1.4–30.8°
c = 9.629 (2) Å	µ = 0.10 mm^−1
β = 95.45 (3)°	T = 120 K
V = 2013.3 (7) Å^3	Column, colourless
Z = 8	0.82 × 0.32 × 0.30 mm

Data collection

Bruker AXS SMART CCD diffractometer	3108 independent reflections
Radiation source: fine-focus sealed tube	2782 reflections with I > 2 σ (I)
Graphite monochromator	Rint = 0.024
ω and ϕ scans	θmax = 30.8°, θmin = 1.4°
Absorption correction: empirical (using intensity measurements) SADABS (Blessing, 1995; Sheldrick, 1996)	h = −40→41
Tmin = 0.926, Tmax = 0.972	k = −10→10
13963 measured reflections	l = −13→13

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.115	w = 1/[σ^2(Fo^2) + (0.0697P)^2 + 0.7749P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max = 0.001
3108 reflections	Δρmax = 0.47 e Å^−3
172 parameters	Δρmin = −0.26 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0043 (8)

Special details

Experimental. A Bruker AXS low temperature device was used. The crystal - detector distance was 4 cm and each frame covered 0.4° in ω or ϕ. A 0.8 mm collimator was used due to the comparably large crystal size. The reciprocal space was explored by a combination of four different runs with 2θ = 30°, adding a ϕ-scan to the standard settings giving a coverage of 100% up to d = 0.75 Å. No intensity decay was observed.

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. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.81131 (2)	0.78160 (9)	0.75669 (6)	0.01954 (15)
O2	0.83434 (2)	0.29341 (9)	0.73969 (6)	0.02348 (16)
O3	0.78940 (2)	0.40562 (8)	0.89423 (6)	0.01934 (15)
N1	0.75988 (2)	1.03912 (10)	0.87725 (7)	0.01717 (15)
H1A	0.7345 (5)	1.042 (2)	0.9217 (16)	0.033 (2)*
H1B	0.7537 (5)	0.985 (2)	0.7965 (16)	0.033 (2)*
H1C	0.7670 (5)	1.152 (2)	0.8596 (14)	0.033 (2)*
N2	0.85126 (2)	0.69033 (10)	0.95998 (7)	0.01762 (15)
H2	0.8522 (4)	0.6970 (18)	1.0480 (14)	0.023 (3)*
C1	0.79826 (3)	0.94821 (12)	0.96517 (9)	0.02118 (18)
H1D	0.7862 (5)	0.893 (2)	1.0459 (15)	0.0331 (18)*
H1E	0.8208 (5)	1.038 (2)	0.9994 (15)	0.0331 (18)*
C2	0.82104 (3)	0.79867 (10)	0.88302 (8)	0.01597 (16)
C3	0.86819 (3)	0.51863 (11)	0.90167 (8)	0.01707 (16)
H3	0.8885 (5)	0.546 (2)	0.8296 (14)	0.028 (2)*
C4	0.89521 (3)	0.40951 (13)	1.02003 (9)	0.02230 (18)
H4A	0.9189 (5)	0.495 (2)	1.0641 (15)	0.0331 (18)*
H4B	0.8728 (5)	0.379 (2)	1.0903 (15)	0.0331 (18)*
C5	0.82755 (3)	0.39834 (11)	0.83844 (8)	0.01661 (16)
C6	0.95832 (5)	0.2663 (2)	0.88833 (16)	0.0465 (3)
H6A	0.9823 (7)	0.335 (3)	0.941 (2)	0.062 (2)*
H6B	0.9492 (7)	0.342 (3)	0.805 (2)	0.062 (2)*
H6C	0.9734 (7)	0.152 (3)	0.863 (2)	0.062 (2)*
C7	0.91846 (4)	0.22970 (15)	0.97724 (11)	0.0293 (2)
H7	0.8945 (5)	0.158 (2)	0.9193 (14)	0.028 (2)*
C8	0.93426 (6)	0.1156 (2)	1.10710 (16)	0.0504 (4)
H8A	0.9062 (7)	0.085 (3)	1.164 (2)	0.062 (2)*
H8B	0.9575 (7)	0.192 (3)	1.152 (2)	0.062 (2)*
H8C	0.9496 (7)	−0.004 (3)	1.079 (2)	0.062 (2)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0244 (3)	0.0189 (3)	0.0152 (3)	0.0012 (2)	0.0010 (2)	−0.00066 (19)
O2	0.0318 (4)	0.0214 (3)	0.0176 (3)	−0.0009 (2)	0.0040 (2)	−0.0043 (2)
O3	0.0198 (3)	0.0186 (3)	0.0199 (3)	−0.0005 (2)	0.0033 (2)	0.0007 (2)
N1	0.0203 (3)	0.0136 (3)	0.0174 (3)	0.0013 (2)	0.0011 (2)	0.0002 (2)
N2	0.0208 (3)	0.0169 (3)	0.0149 (3)	0.0022 (2)	−0.0002 (2)	−0.0018 (2)
C1	0.0276 (4)	0.0191 (4)	0.0164 (3)	0.0073 (3)	−0.0005 (3)	−0.0010 (3)
C2	0.0178 (3)	0.0134 (3)	0.0169 (3)	−0.0012 (2)	0.0024 (3)	0.0004 (2)
C3	0.0174 (3)	0.0180 (3)	0.0160 (3)	0.0019 (3)	0.0023 (3)	−0.0014 (3)
C4	0.0222 (4)	0.0252 (4)	0.0189 (4)	0.0070 (3)	−0.0012 (3)	−0.0007 (3)
C5	0.0204 (4)	0.0146 (3)	0.0145 (3)	0.0010 (3)	0.0000 (3)	0.0017 (2)
C6	0.0356 (6)	0.0548 (8)	0.0509 (7)	0.0189 (6)	0.0140 (5)	−0.0048 (6)
C7	0.0275 (5)	0.0294 (5)	0.0301 (5)	0.0132 (4)	−0.0018 (3)	−0.0021 (4)
C8	0.0550 (8)	0.0469 (7)	0.0477 (7)	0.0283 (6)	−0.0037 (6)	0.0102 (6)

Geometric parameters (Å, º)

O1—C2	1.2286 (10)	C3—C5	1.5442 (12)
O2—C5	1.2468 (10)	C3—H3	0.973 (14)
O3—C5	1.2773 (10)	C4—C7	1.5395 (13)
N1—C1	1.4872 (11)	C4—H4A	0.990 (15)
N1—H1A	0.888 (15)	C4—H4B	1.007 (14)
N1—H1B	0.875 (16)	C6—C7	1.5266 (18)
N1—H1C	0.864 (17)	C6—H6A	0.96 (2)
N2—C2	1.3452 (11)	C6—H6B	0.99 (2)
N2—C3	1.4670 (11)	C6—H6C	0.98 (2)
N2—H2	0.847 (14)	C7—C8	1.5317 (17)
C1—C2	1.5274 (12)	C7—H7	0.995 (14)
C1—H1D	0.970 (14)	C8—H8A	1.05 (2)
C1—H1E	0.961 (15)	C8—H8B	0.94 (2)
C3—C4	1.5387 (12)	C8—H8C	1.02 (2)
C1—N1—H1A	110.4 (10)	C7—C4—H4A	109.8 (9)
C1—N1—H1B	112.7 (10)	C3—C4—H4B	107.2 (8)
H1A—N1—H1B	109.3 (14)	C7—C4—H4B	108.6 (9)
C1—N1—H1C	110.6 (9)	H4A—C4—H4B	108.5 (12)
H1A—N1—H1C	107.1 (13)	O2—C5—O3	123.52 (8)
H1B—N1—H1C	106.6 (13)	O2—C5—C3	118.25 (7)
C2—N2—C3	120.48 (7)	O3—C5—C3	118.15 (7)
C2—N2—H2	118.4 (9)	C7—C6—H6A	109.9 (12)
C3—N2—H2	116.8 (9)	C7—C6—H6B	113.2 (11)
N1—C1—C2	110.88 (7)	H6A—C6—H6B	105.8 (18)
N1—C1—H1D	109.4 (9)	C7—C6—H6C	112.0 (12)
C2—C1—H1D	109.2 (9)	H6A—C6—H6C	104.7 (17)
N1—C1—H1E	110.2 (9)	H6B—C6—H6C	110.7 (17)
C2—C1—H1E	110.1 (9)	C6—C7—C8	111.53 (10)
H1D—C1—H1E	107.0 (12)	C6—C7—C4	112.25 (10)
O1—C2—N2	124.30 (8)	C8—C7—C4	109.98 (9)
O1—C2—C1	120.91 (7)	C6—C7—H7	107.7 (8)
N2—C2—C1	114.79 (7)	C8—C7—H7	108.5 (8)
N2—C3—C4	108.47 (7)	C4—C7—H7	106.7 (8)
N2—C3—C5	110.88 (7)	C7—C8—H8A	110.6 (11)
C4—C3—C5	108.65 (7)	C7—C8—H8B	101.5 (13)
N2—C3—H3	110.4 (8)	H8A—C8—H8B	116.3 (17)
C4—C3—H3	109.3 (8)	C7—C8—H8C	110.1 (11)
C5—C3—H3	109.1 (8)	H8A—C8—H8C	110.0 (16)
C3—C4—C7	116.16 (7)	H8B—C8—H8C	108.0 (16)
C3—C4—H4A	106.4 (9)
N1—C1—C2—N2	−170.25 (7)	N2—C3—C5—O3	−31.8 (1)
N1—C1—C2—O1	9.0 (1)	N2—C3—C5—O2	151.25 (7)
C1—C2—N2—C3	167.07 (7)	N2—C3—C4—C7	−176.25 (8)
C2—N2—C3—C4	−170.49 (7)	C3—C4—C7—C6	68.0 (1)
C2—N2—C3—C5	−51.3 (1)	C3—C4—C7—C8	−167.2 (1)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O3^i	0.89 (2)	2.00 (2)	2.765 (1)	143.7 (1)
N1—H1B···O1	0.87 (2)	2.29 (2)	2.716 (1)	110.2 (1)
N1—H1B···O3^ii	0.87 (2)	2.20 (2)	3.017 (1)	155.9 (1)
N1—H1C···O2^iii	0.86 (1)	2.58 (1)	3.218 (1)	132.1 (1)
N1—H1C···O3^iii	0.86 (1)	1.96 (1)	2.786 (1)	158.7 (1)
N2—H2···O2^iv	0.85 (1)	1.97 (1)	2.786 (1)	162.9 (1)
C1—H1D···O2^iv	0.97 (1)	2.60 (1)	3.258 (1)	125.4 (1)
C7—H7···O2	1.00 (1)	2.54 (1)	3.217 (1)	125.5 (1)

Symmetry codes: (i) −x+3/2, −y+3/2, −z+2; (ii) −x+3/2, y+1/2, −z+3/2; (iii) x, y+1, z; (iv) x, −y+1, z+1/2.