N-(6-Amino-3,4-di­hydro-3-methyl-5-nitro­so-4-oxopyrimidin-2-yl)-(S)-glutamic acid: a three-dimensional framework structure built from O-H...O, N-H...O and O-H...N hydrogen bonds

The title compound, C₁₀H₁₃N₅O₆, exhibits a highly polarized molecular-electronic structure and the conformation is influenced by two intramolecular N-H...O hydrogen bonds. The mol­ecules are linked into a single framework by hydrogen bonds of types O-H...O [O-H = 1.22, H...O = 1.38, O...O = 2.558 (6) Å and O-H...O = 160°], N-H...O [H...O = 2.26, N...O = 2.866 (6) Å and N-H...O = 126°] and O-H...N [O-H = 1.26, H...N = 1.56, O...N = 2.811 (6) Å and O-H...N = 170°]. The substructure generated by the O-H...O and N-H...O hydrogen bonds takes the form of a double helix.

S1. Comment

The neutral N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl) derivatives of the amino acids glycine, valine, serine, threonine and methionine, (I)–(V), all exhibit highly polarized molecular-electronic structures, and their supramolecular structures are characterized by the formation of extremely short O—H···O hydrogen bonds (Low et al., 2000). In each compound, the carboxyl group provides the donor and the O atom of the nitroso group provides the acceptor in the short hydrogen bond, where the O···O distance is generally less than 2.50 Å. By contrast, in the analogue (VI) derived from glycylglycine (Low et al., 2002), there are no O—H····O hydrogen bonds at all, but instead the nitroso group acts as acceptor of both N—H···O and O—H···N intermolecular hydrogen bonds, in which the donors are the peptide N—H and carboxyl group respectively.

Continuing our structural investigation of compounds of this type, we have now extended this study to encompass a derivative (VII) (Fig. 1) of the dicarboxylic amino acid (S)-glutamic acid [(S)-(+)-2-aminopentane-1,5-dioic acid, C₅H₉NO₄], and we report here on its polarized molecular-electronic structure and its three-dimensional supramolecular structure.

The intramolecular distances associated with the heterocyclic ring and its immediate substituents (Table 1) show the general pattern of behaviour now expected for amino-nitrosopyrimidines of this type, but the polarization appears from the individual bond distances to be less extreme than that observed in the derivatives of the monocarboxylic amino acids (I)–(V). The distances in (VII) are, however, very similar to those in the glycylglycine derivative (VI). Overall the intramolecular distances indicate that the polarized form, (VIIa), is an important contributor to the molecular-electronic structure.

Within the molecule of (VII) there are two intramolecular N—H···O hydrogen bonds (Table 2). In addition to the usual intramolecular hydrogen bond, which has the nitroso O atom as acceptor, there is a second such bond between N2 and O23, which probably influences the overall molecular conformation. In the absence of this hydrogen bond, a chain-extended conformation might have been expected for the glutamic fragment.

The formation of the three-dimensional supramolecular structure depends on just three intermolecular hydrogen bonds, one each of types O—H···O, N—H···O and O—H···N (Table 2), and the supramolecular structure is most readily analysed by considering the effect of each of these hydrogen bonds in turn. Note the absence from (VII) of both of the hydrogen-bond motifs, viz. R²₂(8) dimer-forming rings and C(4) chains, that are so characteristic of simple carboxylic acids.

Carboxyl atom O24 in the molecule at (x, y, z) acts as hydrogen-bond donor to nitrosyl atom O5 in the molecule at (1 − x, 1 − y, −1 + z), while O24 at (1 − x, 1 − y, −1 + z) in turn acts as donor to O5 at (x, y, −2 + z), so producing a helical C(13) chain running parallel to the [001] direction (Fig. 2). The repeat period of this helix means that there are in fact two such chains, which form a double helix and are related to one another by the twofold rotation axis along (1/2, 1/2, z) (Fig. 3). The paired helices are linked by the intermolecular N—H···O hydrogen bond. Amino atom N4 in the molecule at (x, y, z) acts as hydrogen-bond donor, via H4A, to carboxyl atom O23 in the molecule at (x, y, 1 + z). Since the molecules at (x, y, z) and (x, y, 1 + z) lie in different C(13) helices, this interaction serves to link together the two chains of the double helix. Two double helices of this type run through each unit cell, along the axes at (0, 0, z) and (1/2, 1/2, z), and the helices are all linked into a single continuum by the action of the O—H···N hydrogen bond.

Carboxyl atom O22 in the molecule at (x, y, z) lies in the double helix along (1/2, 1/2, z) and acts as hydrogen-bond donor to nitroso atom N5, which is in the molecule at (0.5 + x, 1.5 − y, 2 − z) and lies in the double helix along (1, 1, z). Nitroso atom N5 at (x, y, z) similarly accepts a hydrogen bond from O222, which is in the molecule at (−0.5 + x, 1.5 − y, 2 − z) and lies in the double helix along (0, 1, z). Propagation of this hydrogen bond by the twofold axis links the (1/2, 1/2, z) helix to those along (0, 0, z) and (1, 0, z); hence each double helix is linked to the four adjacent helices (Fig. 4), so generating a single three-dimensional framework.

In the O—H···O hydrogen bond in (VII), the O···O distance is greater than those in (I)–(V), and this fact may be readily associated with the lesser polarization of the molecular electronic structure in (VII). On the other hand (VII) exhibits an O—H···N(nitroso) hydrogen bond, previously observed in this series only in (VI). The presence of additional hydrogen-bonding functionality in the side-chain R of compounds of this type may yet provide further unexpected patterns in the supramolecular aggregation

S2. Experimental

The title compound was prepared by adding 6-amino-3,4-dihydro-3-methyl-2-methoxy-5-nitroso-4-oxopyrimidine (2.66 mmol) to a solution of the potassium salt of (S)-glutamic acid (2.66 mmol) in methanol 40 cm³ of (40 cm³). The mixture was stirred at 293 K for 2 d. After removal of the solvent, the residue was dissolved in distilled water and the pH was adjusted to 2.15 by dropwise addition of hydrochloric acid. Slow evaporation of this solution provided crystals suitable for single-crystal X-ray diffraction. Analysis; found: C 40.6, H 5.1, N 24.1%; C₁₀H₁₃N₅O₆ requires: C 40.1, H 4.4, N 23.4%.

S3. Refinement

Crystals of (VII) are orthorhombic and the space group P2₁2₁2 was uniquely assigned from the systematic absences. H atoms bonded to C and N atoms were treated as riding, with C—H distances of 0.98 Å (CH₃), 0.99 Å (CH₂) or 1.00 Å (CH) and N—H distances of 0.88 Å. H atoms bonded to O atoms were located from difference maps and allowed to ride at the distances deduced from the maps. The resulting O22—H22 and O24—H24 distances are 1.26 and 1.22 Å, respectively. In the absence of any significant anomalous scattering, the Flack (1983) parameter was indeterminate (Flack & Bernardinelli, 2000). Hence the Friedel equivalents were merged, and the absolute structure was set by reference to the known configuration of the (S)-glutamic acid employed in the synthesis.

Computing details

Data collection: KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997) and PRPKAPPA (Ferguson, 1999).

Figures

	Fig. 1. The molecular structure of (VII), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Part of the crystal structure of (VII), showing the formation of a C(13) chain along [001]. For the sake of clarity, H atoms bonded to C atoms have been omitted. Atoms marked with an asterisk (*), hash (#) or dollar sign ($) are at the symmetry postions (1 − x, 1 − y, −1 + z), (1 − x, 1 − y, 1 + z) or (x, y, −2 + z), respectively.
	Fig. 3. A stereoview of part of the crystal structure of (VII), showing the formation of a double helix around the (1/2, 1/2, z) axis. For the sake of clarity, H atoms bonded to C atoms have been omitted.
	Fig. 4. A stereoview of part of the crystal structure of (VII), showing the linking of the double helix into a three-dimensional framework. For the sake of clarity, H atoms bonded to C atoms have been omitted.

(I)

Crystal data

C10H13N5O6	F(000) = 624
Mr = 299.25	Dx = 1.629 Mg m^−3
Orthorhombic, P21212	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2 2ab	Cell parameters from 1614 reflections
a = 19.4182 (10) Å	θ = 3.1–27.4°
b = 6.942 (1) Å	µ = 0.14 mm^−1
c = 9.0534 (10) Å	T = 120 K
V = 1220.4 (2) Å^3	Plate, orange
Z = 4	0.56 × 0.32 × 0.03 mm

Data collection

KappaCCD diffractometer	1614 independent reflections
Radiation source: rotating anode	881 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.140
ϕ scans, and ω scans with κ offsets	θmax = 27.4°, θmin = 3.1°
Absorption correction: multi-scan DENZO-SMN (Otwinowski & Minor, 1997)	h = −24→25
Tmin = 0.925, Tmax = 0.996	k = −8→8
13181 measured reflections	l = −11→11

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.153	H-atom parameters constrained
S = 0.99	w = 1/[σ^2(Fo^2) + (0.0816P)^2] where P = (Fo^2 + 2Fc^2)/3
1614 reflections	(Δ/σ)max = 0.002
191 parameters	Δρmax = 0.37 e Å^−3
0 restraints	Δρmin = −0.30 e Å^−3

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

	x	y	z	Uiso*/Ueq
N1	0.55498 (18)	0.7037 (6)	0.8253 (5)	0.0280 (10)
C1	0.5473 (3)	0.7370 (9)	0.6668 (6)	0.0427 (15)
C2	0.6141 (2)	0.6244 (7)	0.8813 (6)	0.0269 (12)
N2	0.66156 (19)	0.5679 (6)	0.7864 (5)	0.0308 (10)
C21	0.7249 (2)	0.4746 (7)	0.8319 (6)	0.0326 (13)
C22	0.7834 (3)	0.6147 (8)	0.8436 (6)	0.0349 (13)
O21	0.78412 (18)	0.7689 (5)	0.7842 (5)	0.0453 (10)
O22	0.83511 (18)	0.5439 (6)	0.9226 (5)	0.0477 (11)
C23	0.7481 (3)	0.3185 (9)	0.7166 (8)	0.0522 (17)
C24	0.6954 (3)	0.1743 (9)	0.6696 (7)	0.0492 (16)
C25	0.6524 (3)	0.2356 (9)	0.5431 (6)	0.0424 (14)
O23	0.6447 (2)	0.4069 (6)	0.5076 (4)	0.0516 (11)
O24	0.6216 (2)	0.0946 (6)	0.4777 (4)	0.0478 (10)
N3	0.6258 (2)	0.5957 (6)	1.0230 (5)	0.0299 (10)
C4	0.5793 (3)	0.6513 (8)	1.1198 (6)	0.0331 (13)
N4	0.5902 (2)	0.6147 (6)	1.2604 (5)	0.0430 (12)
C5	0.5152 (2)	0.7408 (7)	1.0743 (6)	0.0323 (13)
N5	0.4631 (2)	0.8010 (7)	1.1607 (6)	0.0417 (12)
O5	0.47226 (19)	0.7897 (6)	1.3003 (5)	0.0489 (11)
C6	0.5021 (3)	0.7630 (7)	0.9185 (6)	0.0321 (13)
O6	0.44824 (17)	0.8281 (6)	0.8674 (5)	0.0412 (10)
H1A	0.5842	0.8218	0.6322	0.064*
H1B	0.5026	0.7977	0.6475	0.064*
H1C	0.5498	0.6137	0.6143	0.064*
H2	0.6545	0.5876	0.6915	0.037*
H21	0.7176	0.4116	0.9299	0.039*
H22	0.8949	0.6038	0.8944	0.057*
H23A	0.7648	0.3861	0.6273	0.063*
H23B	0.7877	0.2476	0.7589	0.063*
H24A	0.7191	0.0530	0.6430	0.059*
H24B	0.6648	0.1466	0.7545	0.059*
H24	0.5828	0.1351	0.3763	0.057*
H4A	0.6279	0.5544	1.2879	0.052*
H4B	0.5597	0.6505	1.3269	0.052*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.019 (2)	0.033 (2)	0.031 (3)	0.0022 (19)	−0.0013 (19)	0.0054 (19)
C1	0.035 (3)	0.055 (4)	0.039 (4)	0.011 (3)	−0.008 (3)	0.003 (3)
C2	0.020 (3)	0.030 (3)	0.031 (3)	−0.004 (2)	−0.001 (2)	−0.001 (2)
N2	0.025 (2)	0.037 (2)	0.030 (2)	0.008 (2)	−0.0031 (19)	0.001 (2)
C21	0.021 (2)	0.033 (3)	0.044 (3)	0.007 (2)	−0.002 (2)	0.003 (2)
C22	0.031 (3)	0.032 (3)	0.041 (3)	0.008 (3)	−0.002 (3)	−0.005 (3)
O21	0.038 (2)	0.039 (2)	0.059 (3)	0.0005 (18)	−0.0112 (18)	0.003 (2)
O22	0.031 (2)	0.050 (2)	0.062 (3)	−0.0009 (19)	−0.016 (2)	0.009 (2)
C23	0.040 (3)	0.041 (3)	0.075 (5)	0.015 (3)	−0.010 (3)	−0.009 (3)
C24	0.046 (3)	0.045 (3)	0.057 (4)	0.009 (3)	−0.007 (3)	−0.009 (3)
C25	0.042 (3)	0.052 (4)	0.033 (3)	0.014 (3)	−0.001 (3)	−0.001 (3)
O23	0.069 (3)	0.052 (3)	0.034 (2)	0.021 (2)	−0.009 (2)	−0.001 (2)
O24	0.057 (2)	0.048 (2)	0.039 (2)	0.004 (2)	−0.007 (2)	0.000 (2)
N3	0.025 (2)	0.033 (2)	0.032 (3)	0.0009 (19)	0.0004 (19)	−0.0004 (19)
C4	0.036 (3)	0.029 (3)	0.035 (4)	−0.011 (2)	−0.010 (3)	0.004 (2)
N4	0.042 (3)	0.048 (3)	0.039 (3)	−0.013 (2)	−0.003 (2)	0.008 (2)
C5	0.029 (3)	0.033 (3)	0.035 (3)	−0.005 (3)	0.005 (2)	−0.005 (3)
N5	0.047 (3)	0.034 (3)	0.045 (3)	−0.014 (2)	0.000 (3)	0.001 (2)
O5	0.054 (2)	0.052 (2)	0.041 (3)	−0.004 (2)	0.0038 (19)	−0.001 (2)
C6	0.027 (3)	0.027 (3)	0.043 (3)	−0.006 (2)	−0.005 (3)	0.000 (3)
O6	0.0216 (19)	0.046 (2)	0.056 (3)	0.0049 (18)	0.0004 (18)	0.007 (2)

Geometric parameters (Å, º)

N1—C2	1.370 (6)	C22—O22	1.327 (6)
C2—N3	1.318 (6)	O22—H22	1.2601
N3—C4	1.317 (7)	C23—C24	1.494 (8)
C4—C5	1.450 (7)	C23—H23A	0.99
C5—C6	1.442 (7)	C23—H23B	0.99
C6—N1	1.391 (7)	C24—C25	1.479 (8)
N1—C1	1.461 (7)	C24—H24A	0.99
C1—H1A	0.98	C24—H24B	0.99
C1—H1B	0.98	C25—O23	1.241 (7)
C1—H1C	0.98	C25—O24	1.291 (7)
C2—N2	1.320 (6)	O24—H24	1.2193
N2—C21	1.449 (6)	C4—N4	1.315 (7)
N2—H2	0.88	N4—H4A	0.88
C21—C22	1.500 (7)	N4—H4B	0.88
C21—C23	1.571 (8)	C5—N5	1.345 (7)
C21—H21	1.00	N5—O5	1.279 (6)
C22—O21	1.198 (7)	C6—O6	1.230 (6)
C2—N1—C6	120.8 (4)	C24—C23—H23B	108.0
C2—N1—C1	120.8 (4)	C21—C23—H23B	108.0
C6—N1—C1	118.2 (4)	H23A—C23—H23B	107.3
N1—C1—H1A	109.5	C25—C24—C23	114.5 (6)
N1—C1—H1B	109.5	C25—C24—H24A	108.6
H1A—C1—H1B	109.5	C23—C24—H24A	108.6
N1—C1—H1C	109.5	C25—C24—H24B	108.6
H1A—C1—H1C	109.5	C23—C24—H24B	108.6
H1B—C1—H1C	109.5	H24A—C24—H24B	107.6
N3—C2—N2	117.9 (4)	O23—C25—O24	123.5 (5)
N3—C2—N1	124.5 (4)	O23—C25—C24	123.0 (6)
N2—C2—N1	117.6 (4)	O24—C25—C24	113.5 (5)
C2—N2—C21	122.7 (4)	C25—O24—H24	117.2
C2—N2—H2	118.7	C4—N3—C2	119.0 (4)
C21—N2—H2	118.7	N4—C4—N3	118.5 (5)
N2—C21—C22	112.0 (4)	N4—C4—C5	119.7 (5)
N2—C21—C23	111.3 (4)	N3—C4—C5	121.7 (5)
C22—C21—C23	106.0 (4)	C4—N4—H4A	120.0
N2—C21—H21	109.2	C4—N4—H4B	120.0
C22—C21—H21	109.2	H4A—N4—H4B	120.0
C23—C21—H21	109.2	N5—C5—C6	113.7 (5)
O21—C22—O22	124.4 (5)	N5—C5—C4	127.8 (5)
O21—C22—C21	123.8 (5)	C6—C5—C4	118.4 (5)
O22—C22—C21	111.8 (4)	O5—N5—C5	116.8 (5)
C22—O22—H22	117.7	O6—C6—N1	120.5 (5)
C24—C23—C21	117.0 (5)	O6—C6—C5	123.9 (5)
C24—C23—H23A	108.0	N1—C6—C5	115.6 (5)
C21—C23—H23A	108.0
C6—N1—C2—N3	0.7 (7)	N1—C2—N3—C4	−2.2 (7)
C1—N1—C2—N3	177.7 (5)	C2—N3—C4—N4	177.2 (5)
C6—N1—C2—N2	178.7 (4)	C2—N3—C4—C5	0.7 (7)
C1—N1—C2—N2	−4.3 (7)	N4—C4—C5—N5	2.4 (8)
N3—C2—N2—C21	0.8 (7)	N3—C4—C5—N5	178.8 (5)
N1—C2—N2—C21	−177.3 (4)	N4—C4—C5—C6	−174.4 (5)
C2—N2—C21—C23	145.0 (5)	N3—C4—C5—C6	2.0 (7)
N2—C21—C23—C24	−50.4 (7)	C6—C5—N5—O5	−178.3 (4)
C21—C23—C24—C25	87.6 (7)	C4—C5—N5—O5	4.8 (8)
C2—N2—C21—C22	−96.6 (5)	C2—N1—C6—O6	−177.5 (5)
N2—C21—C22—O21	−19.9 (7)	C1—N1—C6—O6	5.4 (7)
C23—C24—C25—O23	−21.4 (8)	C2—N1—C6—C5	2.0 (6)
C23—C21—C22—O21	101.7 (6)	C1—N1—C6—C5	−175.1 (5)
N2—C21—C22—O22	162.6 (4)	N5—C5—C6—O6	−1.0 (8)
C23—C21—C22—O22	−75.9 (6)	C4—C5—C6—O6	176.3 (5)
C22—C21—C23—C24	−172.4 (5)	N5—C5—C6—N1	179.6 (4)
C23—C24—C25—O24	161.5 (5)	C4—C5—C6—N1	−3.2 (7)
N2—C2—N3—C4	179.9 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O23	0.88	2.09	2.779 (6)	134
N4—H4B···O5	0.88	1.97	2.617 (6)	129
O24—H24···O5^i	1.22	1.38	2.558 (6)	160
N4—H4A···O23^ii	0.88	2.26	2.866 (6)	126
O22—H22···N5^iii	1.26	1.56	2.811 (6)	170

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