The α-D anomer of 5-aza-7-deaza-2′-deoxyguanosine

In the monohydrate of 2-amino-8-(2-deoxy-α-D-erythro-pento­furan­osyl)-8H-imidazo­[1,2-a]­[1,3,5]­triazin-4-one, C₁₀H₁₃N₅O₄·H₂O, denoted (I) or αZ_d, the conformation of the N-gly­cosyl­ic bond is in the high-anti range [χ = 87.5 (3)°]. The 2′-deoxy­ribo­furan­ose moiety adopts a C2′-endo,C3′-exo(^2′T_3′) sugar puckering (S-type sugar) and the conformation at the C4′—C5′ bond is −sc (trans).

S1. Comment

5-Aza-7-deazapurines [imidazo[1,2-a][1,3,5]-triazines, (I)] can be formally constructed by transposition of the purine N-7 atom to the bridgehead 5-position (Seela & Rosemeyer, 2002). 5-Aza-7-deaza-2'-deoxyguanosine [(II), purine numbering is used throughout discussion] (Rosemeyer & Seela, 1987) is a structural analogue of both 2'-deoxyguanosine and 7-deaza-2'-deoxyguanosine. Therefore, it is isosteric to 2'-deoxyguanosine but shows an altered Watson–Crick recognition site.

Within oligodeoxynucleotides, the β-D-configured 5-aza-7-deaza-2'-deoxyguanosine [βZ_d, (II)] forms strong tridentate `purine–purine' base pairs with 2'-deoxyguanosine (neutral conditions), with parallel (ps) chain orientations (Seela & Melenewski, 1999). However, antiparallel tridentate base pairs are formed between βZ_d and 2'-deoxycytidine (dC) under acidic (pH 5) conditions (Seela & Melenewski, 1999). Duplexes with parallel strands can be formed when all the sugar moieties in one oligonucleotide strand are in an α-D-configuration (Imbach et al., 1989). These oligonucleotides show nuclease resistance.

Nucleoside (I) was synthesized according to Rosemeyer & Seela (1987) and crystallizes from water as the monohydrate (Fig. 1 and Table 1). The orientation of the nucleobase relative to the sugar (syn/anti) is defined by the torsion angle χ¹(O4'—C1'—N9—C4) (IUPAC-IUB Joint Commission on Biochemical Nomenclature, 1983). The preferred conformation at the N-glycosylic bond in natural 2'-deoxynucleosides is usually in the anti range (-150° ≤ χ¹ ≤ -140°). For an α-D nucleoside, the `perfect' anti range is 140° ≤ χ¹ ≤ 150°. In the case of compound (I), χ¹ is 87.5 (3)°. This indicates that the title compound adopts a high-anti conformation, with the C1'—C2' and N9—C8 bonds nearly eclipsed [torsion angle C1'—C2'—N9—C8 = 30.3 (4)°].

This conformation is quite unusual. It is displayed by 8-azapurine-2'-deoxy-β-D-ribofuranosides and 8-aza-7-deazapurine-2'-deoxy-β-D-ribofuranosides, where it is attributed to Coulombic repulsion between non-bonding electron pairs at O4' and N8 (Seela et al., 1999, 1999a, 1999b). The β-D-ribonucleoside of 5-aza-7-deazaguanine shows an anti conformation. The reason for the difference between the β-D-ribonucleoside and the α-D-2'-deoxyribonucleoside is still unknown.

The C2'-endo (N) and C3'-endo (S) puckerings are the most frequently observed sugar-ring conformations of nucleosides. Among these, 2'-deoxy-α-D-ribonucleosides often show C2'-endo sugar puckering with either a half-chair or envelope conformation (Seela et al., 1999a; Hamor et al., 1977; Revankar et al., 1990; Leumann et al., 1995; Marfurt et al., 1996). The puckering of the deoxyribose ring of (I) is C2'-endo,C3'-exo (^2'T_3'), with P = 177.43° and τ_m = 30.5° (Rao et al., 1981). The γ(O5'—C5'—C4'—C3') torsion angle is -71.6 (3)°, which corresponds to -sc, a conformation often found in nucleosides with ^2'T_3' sugar puckering. The conformational parameters of (I) in the crystal are generally identical to those in solution (Seela et al., 2001).

The base moiety of (I) is nearly planar. The average deviation of the ring atoms from the least-squares plane is ±0.014 Å. The ring substituents were not used for calculation of the plane. They deviate as follows: amino N2 - 0.061 Å and carboxy O6 0.004 Å. In the crystalline state, the structure of the monohydrate of (I) is stabilized by several hydrogen bonds (listed in Table 2), leading to the formation of double layers. Within each monolayer, the molecules of (I) are interconneted with each other and the water molecules by four strong hydrogen bonds: N2—H22···O6, N1—H11···O1, O1···H3'—O3' and O1···O5'—H5'. Because of steric hindrance, however, the second H atom of the NH₂-group can only from a weak hydrogen bond, N2—H21···O5', which is characterized by a narrow angle at the H atom and a long donor–acceptor distance. Between two of these monolayers there exists only one hydrogen bond, O1—H12···N3; this is also weak and connects the water molecule with the nucleoside in the neigbouring layer and vice versa.

S2. Refinement

In the absence of suitable anomalous scatterers, the measured Friedel data (h¯kl, h¯k¯l, ¯hkl, ¯hk¯l) could not be used to determine the absolute structure. However, comparison with the known configuration of the parent molecule indicates that the proposed configuration is correct. Friedel-opposite reflections were merged. All H atoms were found in a difference Fourier synthesis and were included in the structure model in the usual fashion; H atoms on C atoms geometrically positioned and riding (C—H = 0.93–0.98 Å), and H atoms on O and N atoms refined freely with restraints.

Computing details

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: SHELXTL (Sheldrick, 1997a); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997b); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997b); molecular graphics: DIAMOND (Brandenburg, 1999) and SHELXTL; software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. Perspective view of the α-D anomer of 5-aza-7-deaza-2'-deoxyguanosine monohydrate. Displacement ellipsoids of non-H atoms are drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radii. One H atom of the water molecule is eclipsed.
	Fig. 2. Detail of the hydrogen bonding within one monolayer in the crystal structure of (I).

2-amino-8-(2-deoxy-α-D-erythro-pentofuranosyl) -8H-imidazo[1,2-a][1,3,5]triazin-4-one monohydrate

Crystal data

C10H13N5O4·H2O	Dx = 1.528 Mg m^−3
Mr = 285.27	Melting point: no K
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 8.5397 (14) Å	Cell parameters from 38 reflections
b = 7.1025 (14) Å	θ = 4.9–17.2°
c = 10.7187 (16) Å	µ = 0.12 mm^−1
β = 107.460 (13)°	T = 293 K
V = 620.17 (18) Å^3	Prism, colourless
Z = 2	0.5 × 0.4 × 0.2 mm
F(000) = 300

Data collection

Siemens P4 diffractometer	1123 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.049
Graphite monochromator	θmax = 25.0°, θmin = 2.0°
2θ/ω scans	h = −10→10
Absorption correction: empirical (using intensity measurements) ψ scans (SHELXTL; Sheldrick, 1997a)	k = −8→8
Tmin = 0.296, Tmax = 0.359	l = −12→12
2526 measured reflections	3 standard reflections every 97 reflections
1194 independent reflections	intensity decay: none

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.030	w = 1/[σ^2(Fo^2) + (0.0256P)^2 + 0.0846P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.076	(Δ/σ)max < 0.001
S = 1.09	Δρmax = 0.13 e Å^−3
1194 reflections	Δρmin = −0.19 e Å^−3
204 parameters	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
60 restraints	Extinction coefficient: 0.041 (4)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.9 (17)

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. 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
N1	0.1546 (3)	0.1286 (4)	−0.0719 (2)	0.0425 (6)
C2	0.2080 (3)	0.3054 (4)	−0.0367 (2)	0.0344 (6)
N2	0.1206 (3)	0.4459 (3)	−0.1047 (2)	0.0444 (6)
H21	0.020 (3)	0.431 (6)	−0.166 (2)	0.056 (2)*
H22	0.153 (4)	0.566 (3)	−0.078 (3)	0.056 (2)*
N3	0.3440 (2)	0.3536 (3)	0.06279 (18)	0.0347 (5)
C4	0.4222 (3)	0.2059 (4)	0.1264 (2)	0.0325 (5)
N5	0.3758 (3)	0.0247 (4)	0.0987 (2)	0.0378 (5)
C6	0.2350 (4)	−0.0188 (4)	−0.0050 (3)	0.0449 (7)
O6	0.1970 (4)	−0.1842 (4)	−0.0267 (3)	0.0720 (8)
C7	0.4833 (3)	−0.0936 (5)	0.1890 (3)	0.0475 (7)
H7	0.4781	−0.2242	0.1924	0.056 (2)*
C8	0.5944 (4)	0.0170 (5)	0.2691 (3)	0.0443 (7)
H8	0.6815	−0.0234	0.3392	0.056 (2)*
N9	0.5586 (3)	0.2050 (4)	0.2305 (2)	0.0363 (5)
C1'	0.6423 (3)	0.3777 (4)	0.2885 (2)	0.0380 (6)
H1'	0.6271	0.4721	0.2192	0.056 (2)*
C2'	0.8259 (3)	0.3554 (5)	0.3562 (2)	0.0413 (6)
H2'1	0.8690	0.2465	0.3228	0.056 (2)*
H2'2	0.8855	0.4665	0.3437	0.056 (2)*
C3'	0.8386 (3)	0.3295 (5)	0.4995 (2)	0.0417 (6)
H3'1	0.9418	0.3820	0.5557	0.056 (2)*
O3'	0.8285 (3)	0.1340 (4)	0.52308 (19)	0.0593 (6)
H3'2	0.818 (3)	0.130 (6)	0.598 (2)	0.056 (2)*
C4'	0.6928 (3)	0.4404 (5)	0.5133 (2)	0.0383 (6)
H4'	0.6442	0.3742	0.5729	0.056 (2)*
O4'	0.57465 (19)	0.4487 (4)	0.38377 (17)	0.0487 (6)
C5'	0.7331 (3)	0.6406 (5)	0.5601 (2)	0.0442 (6)
H5'2	0.7961	0.7017	0.5098	0.056 (2)*
H5'3	0.6329	0.7118	0.5494	0.056 (2)*
O5'	0.8264 (3)	0.6324 (3)	0.69483 (19)	0.0497 (5)
H5'1	0.834 (4)	0.744 (3)	0.720 (3)	0.056 (2)*
O1	0.8449 (2)	0.0247 (4)	0.76920 (17)	0.0511 (6)
H11	0.930 (2)	0.048 (6)	0.824 (2)	0.056 (2)*
H12	0.777 (2)	0.034 (6)	0.807 (2)	0.056 (2)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0456 (12)	0.0329 (12)	0.0430 (11)	−0.0037 (11)	0.0040 (9)	−0.0101 (11)
C2	0.0389 (12)	0.0313 (14)	0.0315 (12)	−0.0056 (12)	0.0085 (10)	−0.0060 (11)
N2	0.0435 (11)	0.0362 (13)	0.0409 (11)	−0.0014 (12)	−0.0064 (9)	−0.0021 (11)
N3	0.0388 (10)	0.0282 (11)	0.0325 (9)	−0.0033 (9)	0.0040 (8)	−0.0011 (9)
C4	0.0351 (11)	0.0297 (13)	0.0322 (11)	−0.0028 (11)	0.0091 (9)	−0.0024 (11)
N5	0.0439 (11)	0.0289 (12)	0.0402 (10)	−0.0001 (10)	0.0118 (8)	−0.0021 (10)
C6	0.0508 (15)	0.0313 (15)	0.0520 (15)	−0.0050 (13)	0.0145 (12)	−0.0106 (13)
O6	0.0814 (16)	0.0278 (12)	0.0904 (18)	−0.0108 (12)	0.0010 (14)	−0.0160 (12)
C7	0.0563 (15)	0.0311 (15)	0.0557 (15)	0.0080 (14)	0.0174 (13)	0.0049 (13)
C8	0.0474 (14)	0.0379 (16)	0.0434 (14)	0.0090 (14)	0.0073 (11)	0.0082 (13)
N9	0.0385 (11)	0.0329 (12)	0.0345 (10)	0.0033 (11)	0.0065 (8)	0.0036 (9)
C1'	0.0357 (11)	0.0354 (15)	0.0390 (12)	−0.0015 (11)	0.0051 (9)	0.0024 (11)
C2'	0.0326 (11)	0.0525 (17)	0.0373 (11)	0.0014 (13)	0.0082 (9)	0.0018 (13)
C3'	0.0376 (11)	0.0460 (16)	0.0360 (12)	0.0083 (14)	0.0028 (9)	0.0005 (13)
O3'	0.0909 (16)	0.0474 (13)	0.0354 (10)	0.0232 (14)	0.0128 (9)	0.0070 (11)
C4'	0.0356 (11)	0.0410 (15)	0.0374 (11)	−0.0018 (13)	0.0093 (9)	−0.0025 (12)
O4'	0.0309 (8)	0.0581 (15)	0.0493 (10)	0.0079 (10)	0.0001 (7)	−0.0145 (11)
C5'	0.0389 (12)	0.0419 (15)	0.0459 (13)	0.0022 (13)	0.0039 (10)	−0.0027 (14)
O5'	0.0559 (11)	0.0421 (11)	0.0431 (10)	−0.0024 (11)	0.0026 (8)	−0.0084 (10)
O1	0.0489 (10)	0.0640 (15)	0.0369 (9)	−0.0104 (12)	0.0075 (7)	−0.0031 (11)

Geometric parameters (Å, º)

N1—C6	1.337 (4)	C1'—C2'	1.525 (3)
N1—C2	1.350 (4)	C1'—H1'	0.9800
C2—N2	1.326 (4)	C2'—C3'	1.518 (3)
C2—N3	1.364 (3)	C2'—H2'1	0.9700
N2—H21	0.914 (18)	C2'—H2'2	0.9700
N2—H22	0.914 (18)	C3'—O3'	1.419 (4)
N3—C4	1.318 (4)	C3'—C4'	1.518 (4)
C4—N9	1.349 (3)	C3'—H3'1	0.9800
C4—N5	1.354 (4)	O3'—H3'2	0.83 (2)
N5—C7	1.397 (4)	C4'—O4'	1.452 (3)
N5—C6	1.406 (3)	C4'—C5'	1.513 (4)
C6—O6	1.222 (4)	C4'—H4'	0.9800
C7—C8	1.329 (5)	C5'—O5'	1.426 (3)
C7—H7	0.9300	C5'—H5'2	0.9700
C8—N9	1.404 (4)	C5'—H5'3	0.9700
C8—H8	0.9300	O5'—H5'1	0.83 (2)
N9—C1'	1.461 (4)	O1—H11	0.802 (14)
C1'—O4'	1.408 (3)	O1—H12	0.802 (14)
C6—N1—C2	120.2 (2)	N9—C1'—H1'	108.4
N2—C2—N1	117.3 (2)	C2'—C1'—H1'	108.4
N2—C2—N3	116.6 (3)	C3'—C2'—C1'	104.2 (2)
N1—C2—N3	126.1 (3)	C3'—C2'—H2'1	110.9
C2—N2—H21	124 (3)	C1'—C2'—H2'1	110.9
C2—N2—H22	118 (2)	C3'—C2'—H2'2	110.9
H21—N2—H22	117 (4)	C1'—C2'—H2'2	110.9
C4—N3—C2	112.7 (2)	H2'1—C2'—H2'2	108.9
N3—C4—N9	127.6 (3)	O3'—C3'—C2'	108.0 (3)
N3—C4—N5	125.0 (2)	O3'—C3'—C4'	113.3 (3)
N9—C4—N5	107.5 (2)	C2'—C3'—C4'	103.0 (2)
C4—N5—C7	109.4 (2)	O3'—C3'—H3'1	110.8
C4—N5—C6	120.5 (2)	C2'—C3'—H3'1	110.8
C7—N5—C6	130.1 (3)	C4'—C3'—H3'1	110.8
O6—C6—N1	125.9 (3)	C3'—O3'—H3'2	104 (3)
O6—C6—N5	118.5 (3)	O4'—C4'—C5'	107.6 (2)
N1—C6—N5	115.6 (2)	O4'—C4'—C3'	106.4 (2)
C8—C7—N5	106.6 (3)	C5'—C4'—C3'	114.1 (2)
C8—C7—H7	126.7	O4'—C4'—H4'	109.5
N5—C7—H7	126.7	C5'—C4'—H4'	109.5
C7—C8—N9	108.8 (2)	C3'—C4'—H4'	109.5
C7—C8—H8	125.6	C1'—O4'—C4'	111.12 (18)
N9—C8—H8	125.6	O5'—C5'—C4'	107.4 (2)
C4—N9—C8	107.8 (2)	O5'—C5'—H5'2	110.2
C4—N9—C1'	122.6 (2)	C4'—C5'—H5'2	110.2
C8—N9—C1'	129.6 (2)	O5'—C5'—H5'3	110.2
O4'—C1'—N9	110.8 (2)	C4'—C5'—H5'3	110.2
O4'—C1'—C2'	106.20 (19)	H5'2—C5'—H5'3	108.5
N9—C1'—C2'	114.6 (2)	C5'—O5'—H5'1	105 (2)
O4'—C1'—H1'	108.4	H11—O1—H12	104 (2)
C6—N1—C2—N2	−178.3 (3)	N5—C4—N9—C1'	−179.4 (2)
C6—N1—C2—N3	1.7 (4)	C7—C8—N9—C4	0.8 (3)
N2—C2—N3—C4	179.1 (2)	C7—C8—N9—C1'	178.7 (3)
N1—C2—N3—C4	−0.9 (4)	C4—N9—C1'—O4'	87.6 (3)
C2—N3—C4—N9	−178.8 (2)	C8—N9—C1'—O4'	−90.1 (3)
C2—N3—C4—N5	−0.1 (4)	C4—N9—C1'—C2'	−152.3 (2)
N3—C4—N5—C7	−177.6 (2)	C8—N9—C1'—C2'	30.0 (4)
N9—C4—N5—C7	1.3 (3)	O4'—C1'—C2'—C3'	25.9 (3)
N3—C4—N5—C6	0.3 (4)	N9—C1'—C2'—C3'	−96.8 (3)
N9—C4—N5—C6	179.2 (2)	C1'—C2'—C3'—O3'	90.1 (3)
C2—N1—C6—O6	178.9 (4)	C1'—C2'—C3'—C4'	−30.0 (3)
C2—N1—C6—N5	−1.3 (4)	O3'—C3'—C4'—O4'	−92.4 (3)
C4—N5—C6—O6	−179.8 (3)	C2'—C3'—C4'—O4'	24.0 (3)
C7—N5—C6—O6	−2.3 (5)	O3'—C3'—C4'—C5'	149.1 (2)
C4—N5—C6—N1	0.4 (4)	C2'—C3'—C4'—C5'	−94.5 (3)
C7—N5—C6—N1	177.9 (3)	N9—C1'—O4'—C4'	114.1 (2)
C4—N5—C7—C8	−0.8 (3)	C2'—C1'—O4'—C4'	−11.0 (3)
C6—N5—C7—C8	−178.5 (3)	C5'—C4'—O4'—C1'	114.3 (3)
N5—C7—C8—N9	0.0 (3)	C3'—C4'—O4'—C1'	−8.4 (3)
N3—C4—N9—C8	177.6 (3)	O4'—C4'—C5'—O5'	170.3 (2)
N5—C4—N9—C8	−1.3 (3)	C3'—C4'—C5'—O5'	−71.9 (3)
N3—C4—N9—C1'	−0.5 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H22···O6^i	0.91 (2)	1.86 (2)	2.775 (4)	175 (3)
O5′—H5′1···O1^i	0.83 (2)	2.06 (2)	2.889 (4)	176 (3)
N2—H21···O5′^ii	0.91 (2)	2.35 (3)	3.073 (3)	135 (4)
O1—H11···N1^iii	0.80 (1)	1.99 (2)	2.782 (3)	168 (3)
O1—H12···N3^iv	0.80 (1)	2.35 (3)	3.010 (3)	140 (4)
O3′—H3′2···O1	0.83 (2)	1.93 (3)	2.713 (3)	156 (4)

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