7-Deaza-2′-deoxy­guanosine

In the title compound, 2-amino-7-(2-deoxy-β-D-erythro-pentofuran­osyl)-3,7-dihydro­pyrrolo[2,3-d]pyrimidin-4-one, C₁₁H₁₄N₄O₄, the N-glycosylic bond torsion angle, χ, is anti [−106.5 (3)°]. The 2′-deoxy­ribofuran­osyl moiety adopts the ³T₄ (N-type) conformation, with P = 39.1° and τ_m = 40.3°. The conformation around the exocyclic C—C bond is ap (trans), with a torsion angle, γ, of −173.8 (3)°. The nucleoside forms a hydrogen-bonded network, leading to a close-packed multiple-layer structure with a head-to-head arrangement of the bases. The nucleobase interplanar O=C—C...NH₂ distance is 3.441 (1) Å.

S1. Comment

7-Deaza-2'-deoxyguanosine, (I), is one of the most applicable modified nucleosides being used in chemistry, molecular biology and nanotechnology (purine numbering is used throughout the manuscript). The synthesis of (I) was reported by Winkeler & Seela (1983). The first oligonucleotide incorporating (I) was reported three years later (Seela & Driller, 1986). Compound (I) is known for applications in the form of its 5'-triphosphate in the Sanger DNA sequencing (Barr et al., 1986; Mizusawa, et al., 1986). 7-Alkynylamino derivatives of the corresponding 2',3'-dideoxy nucleoside triphosphate carrying fluorescent reporter groups are used as chain terminators in automatized DNA/RNA sequencing machines (Prober et al., 1987; Cocuzza, 1988; Hobbs, 1989). As nucleoside (I) cannot form dG-tetrads (Seela & Mersmann, 1993), band compression is reduced during gel electrophoresis. Moreover, the replacement of 2'-deoxyguanosine by (I) increases the sensitivity of MALDI-TOF mass spectra performed on DNA fragments (Schneider & Chait, 1995). In addition, the fluorescence of ethidium bromide is strongly quenched by (I) (Li et al., 2004), and 7-deaza-2',3'-dideoxyguanosine triphosphate proved to be an effective inhibitor of HIV reverse transcriptase (Seela et al., 1990). The incorporation of the 7-substituted derivatives of (I) into oligonucleotides results in the increase of DNA duplex stability (Seela et al., 1995; Ramzaeva & Seela, 1996; Seela & Shaikh, 2004), as well as of DNA–RNA duplexes (Buhr et al., 1996). Oligonucleotide triplexes are also stabilized when (I) is part of the 7-deazaguanine–guanine–cytosine triplet motif (Milligan et al., 1993). Thus, (I) and 7-substituted derivatives are applied in antisense technology (Lamm et al., 1991; Uhlmann et al., 2000) as well as in DNA/RNA diagnostics (Bailly & Waring, 1998). Consequently, it was of interest to perform a single-crystal X-ray analysis and report the structure.

Earlier efforts were made to grow a single-crystal of (I). Recently, we were able to crystallize (I) as colorless needles from an aqueous solution of (I) at room temperature. The three-dimensional structure of (I) {systematic numbering: 2-amino-7-(2-deoxy-β-D-erythro-pentofuranosyl) −3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one} is shown in Fig. 1, and selected bond lengths and angles are summarized in Table 1. The orientation of the nucleobase relative to the sugar moiety (syn/anti) is defined in analogy to the purine nucleosides by the torsion angle χ (O4'—C1'—N9—C4) (IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983). In the crystalline state of (I), the glycosylic bond torsion angle is in the anti range [χ = −106.5 (3)°], which is similar to that of the recently reported 7-deaza-2'-deoxy-7-propynylguanosine, (II) (Seela et al., 2004), in which the propynyl group is slightly tilted [C4—C5—C7—C71 = 177.2 (5)°], and the 8-methyl derivative of 7-deaza-2'-deoxyguanosine (Seela et al., 1997), as well as that of queuosine 5'-monophosphate (Yokoyama et al., 1979). The sugar ring is puckered, as shown by the C3'—C4'—O4'—C1' [34.5 (3)°] and C4'—O4'—C1'—C2' [−14.4 (3)°] torsion angles. The pseudorotation phase angle, P, of 39.1°, with an amplitude, τ_m, of 40.3°, indicates an N-type sugar conformation (3'-endo-4'-exo, ³T₄), which is an unusual sugar puckering compared with the canonical nucleosides (Rao et al., 1981). The torsion angle γ [O5'—C5'—C4'—C3' = −173.8 (3)°] describing the orientation of the 5'-hydroxy group relative to the sugar ring shows that the C4'—C5' bond is in an -ap (trans) orientation (Saenger, 1984). The N-type sugar pucker of (I) found in the solid state is in contrast to the conformation found in solution (70% S). In this case, the conformational analysis was carried out on the basis of ¹H NMR vicinal [¹H, ¹H] coupling constants using the PSEUROT6.3 program (Van Wijk et al., 1999). The base moiety of (I) is nearly planar, the r.m.s. deviation of the ring atoms from their calculated least-squares planes being 0.0323 Å [N1 0.030 (2) Å, C2 − 0.027 (2) Å, N3 − 0.009 (2) Å, C4 − 0.014 (3) Å, C5 − 0.049 (3) Å, C6 0.042 (2) Å, C7 − 0.033 (3) Å, C8 0.019 (3) Å and N9 0.043 (2) Å]. The O6 substituent of (I) lies 0.144 (4) Å above and the N atom of the 2-amine group lies −0.103 (4) Å below this plane. The structure of (I) is stabilized by several intermolecular hydrogen bonds leading to a three-dimensional multiple-layer network (Fig. 2 and Table 2). In the close-packed network of nucleoside (I), the head-to-head stacking patterns are strikingly similar to the head-to-head stacking of nucleobases observed for 7-deaza-2'-deoxy-7-propynylguanosine, (II) (Seela et al., 2004). The nucleobases are not skewed, and the closest distance of the stacked bases for (I) is 3.441 (1) Å (C5 and N2), while the closest base distance for (II) is 3.728 (1) Å (C5 and N2) (Fig. 3). This corresponds to a plane separation that is similar to the average base pair stacking distance in B-DNA (3.5 Å). Within each monolayer, the molecules of (I) are interconnected with one another by five strong hydrogen bonds, as listed in Table 2, viz. three N—H···O and two O—H···O interactions. As there are two lone electron pairs on atom O6, it can form bifurcated hydrogen-bonds with the H1/N1 and H5'/O5' groups. In addition, another hydrogen-bond interaction, between atom O6 and the H2A/N2 group, is observed. C—H···Oⁱ (H···O = 2.52 Å) and C—H···π(C═C)ⁱ (H···C = 2.77 Å) interactions complete the hydrogen bonding [symmetry code: (i) −1/2 + x, 1/2 − y, −z].

S2. Experimental

Compound (I) was synthesized from 7-(2-deoxy-β-D-erythro-pentofuranosyl)-4-methoxy-7H-pyrrolo[2,3-d] pyrimidin-2-amine as described by Winkeler & Seela (1983). It was crystallized slowly from a dilute solution of (I) in double distilled water at room temperature within a period of one week as colorless needles. M.p. 535–538 K. For the diffraction experiment, a single-crystal was fixed at the top of a Lindemann capillary with epoxy resin.

S3. Refinement

In the absence of suitable anomalous scattering, Friedel equivalents could not be used to determine the absolute structure. Refinement of the Flack (1983) parameter led to inconclusive values (Flack & Bernardinelli, 2000) for this parameter −1(2). Therefore, Friedel pairs were merged before the final refinements. The known configuration of the parent molecule was used to define the enantiomer used in the refined model. In order to maximize the data/parameter ratio, H atoms bonded to C were placed in geometrically idealized positions (C—H = 0.93–0.98 Å) and constrained to ride on their parent atoms, with U_iso(H) values of 1.2U_eq(C). The hydroxy H atoms were initially placed in the difference map positions, then geometrically idealized and constrained to ride on their parent O atoms, although the chemically equivalent O—H bond lengths were allowed to refine while being constrained to be equal.

Computing details

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

Figures

	Fig. 1. A perspective view of (I). Displacement ellipsoids for non-H atoms are drawn at the 50% probability level, and H atoms are shown as spheres of arbitrarily size.
	Fig. 2. Details of the three-dimentional multilayered network showing the hydrogen bonds (dashed lines) within the monolayers and the stacking of nucleobases.
	Fig. 3. (a) Head-to-head nucleobase stacking in nucleoside (I). (b) Head-to-head nucleobase stacking in nucleoside II.

2-amino-7-(2-deoxy-β-D-erythro-pentofuranosyl-3,7- dihydropyrrolo[2,3-d]pyrimidin-4-one

Crystal data

C11H14N4O4	F(000) = 560
Mr = 266.26	Dx = 1.491 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 51 reflections
a = 5.4146 (12) Å	θ = 2.0–15.2°
b = 10.969 (2) Å	µ = 0.12 mm^−1
c = 19.968 (4) Å	T = 293 K
V = 1185.9 (4) Å^3	Needle, colourless
Z = 4	0.53 × 0.33 × 0.26 mm

Data collection

Bruker P4 diffractometer	Rint = 0.043
Radiation source: fine-focus sealed tube	θmax = 28.0°, θmin = 2.0°
Graphite monochromator	h = −7→1
2θ/ω scans	k = −14→1
2301 measured reflections	l = −26→1
1679 independent reflections	3 standard reflections every 97 reflections
1204 reflections with I > 2σ(I)	intensity decay: none

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)] = 0.051	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.120	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0542P)^2 + 0.1063P] where P = (Fo^2 + 2Fc^2)/3
1679 reflections	(Δ/σ)max = 0.001
179 parameters	Δρmax = 0.20 e Å^−3
4 restraints	Δρmin = −0.21 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. 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	1.1373 (6)	0.6234 (2)	0.04283 (12)	0.0317 (7)
H1	1.2094	0.6896	0.0307	0.038*
C2	1.2246 (6)	0.5670 (3)	0.09958 (15)	0.0281 (8)
N2	1.4235 (6)	0.6178 (3)	0.12847 (13)	0.0382 (7)
H2B	1.4853	0.5860	0.1641	0.046*
H2A	1.4890	0.6820	0.1113	0.046*
N3	1.1213 (5)	0.4687 (2)	0.12496 (12)	0.0286 (6)
C4	0.9345 (6)	0.4267 (3)	0.08720 (14)	0.0249 (7)
C5	0.8428 (7)	0.4720 (3)	0.02674 (14)	0.0271 (7)
C6	0.9439 (7)	0.5827 (3)	0.00372 (14)	0.0278 (7)
O6	0.8766 (5)	0.6456 (2)	−0.04594 (10)	0.0359 (6)
C7	0.6421 (7)	0.3956 (3)	0.00656 (15)	0.0349 (8)
H7	0.5469	0.4038	−0.0320	0.042*
C8	0.6174 (8)	0.3089 (3)	0.05448 (16)	0.0364 (8)
H8	0.5008	0.2467	0.0541	0.044*
N9	0.7932 (6)	0.3272 (3)	0.10441 (12)	0.0309 (7)
C1'	0.8162 (7)	0.2591 (3)	0.16642 (16)	0.0324 (8)
H1'	0.9198	0.3050	0.1978	0.039*
C2'	0.5708 (8)	0.2294 (3)	0.19985 (17)	0.0358 (8)
H2'1	0.4366	0.2741	0.1790	0.043*
H2'2	0.5754	0.2491	0.2472	0.043*
C3'	0.5405 (6)	0.0927 (3)	0.18920 (15)	0.0301 (8)
H3'1	0.4631	0.0767	0.1457	0.036*
O3'	0.4021 (5)	0.0366 (2)	0.24127 (11)	0.0382 (6)
H3'	0.291 (5)	−0.005 (3)	0.2247 (3)	0.057*
C4'	0.8063 (6)	0.0509 (3)	0.18855 (15)	0.0270 (7)
H4'	0.8695	0.0487	0.2345	0.032*
O4'	0.9327 (5)	0.1438 (2)	0.15171 (11)	0.0361 (6)
C5'	0.8525 (7)	−0.0713 (3)	0.15510 (17)	0.0370 (9)
H5'1	0.7435	−0.1320	0.1745	0.044*
H5'2	0.8142	−0.0650	0.1078	0.044*
O5'	1.1028 (5)	−0.1100 (2)	0.16292 (11)	0.0404 (6)
H5'	1.167 (2)	−0.113 (4)	0.1258 (3)	0.061*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0438 (18)	0.0216 (13)	0.0298 (12)	−0.0039 (14)	−0.0001 (14)	0.0048 (11)
C2	0.036 (2)	0.0231 (16)	0.0250 (14)	0.0016 (16)	0.0015 (15)	−0.0003 (13)
N2	0.0476 (18)	0.0321 (15)	0.0348 (13)	−0.0105 (16)	−0.0075 (15)	0.0078 (13)
N3	0.0302 (15)	0.0258 (13)	0.0298 (12)	−0.0025 (14)	0.0004 (13)	0.0026 (12)
C4	0.0296 (17)	0.0201 (14)	0.0249 (13)	0.0046 (15)	0.0032 (14)	0.0010 (12)
C5	0.0321 (19)	0.0224 (15)	0.0268 (13)	0.0004 (16)	0.0015 (15)	0.0006 (13)
C6	0.0341 (18)	0.0250 (16)	0.0242 (13)	0.0069 (16)	0.0034 (15)	−0.0018 (13)
O6	0.0501 (16)	0.0264 (11)	0.0314 (10)	0.0046 (14)	−0.0070 (12)	0.0078 (10)
C7	0.040 (2)	0.0330 (17)	0.0315 (15)	0.0030 (19)	−0.0080 (17)	0.0015 (14)
C8	0.037 (2)	0.0318 (18)	0.0400 (17)	−0.0088 (19)	−0.0059 (18)	0.0024 (16)
N9	0.0367 (17)	0.0265 (15)	0.0293 (12)	−0.0060 (14)	−0.0045 (13)	0.0041 (12)
C1'	0.040 (2)	0.0252 (16)	0.0323 (16)	−0.0006 (17)	−0.0006 (17)	0.0062 (14)
C2'	0.043 (2)	0.0279 (16)	0.0367 (16)	0.0007 (18)	0.0029 (19)	0.0041 (15)
C3'	0.0349 (19)	0.0305 (17)	0.0249 (14)	−0.0055 (17)	−0.0006 (15)	0.0047 (14)
O3'	0.0378 (14)	0.0425 (15)	0.0342 (11)	−0.0143 (14)	0.0031 (12)	0.0032 (11)
C4'	0.0320 (19)	0.0227 (16)	0.0262 (14)	−0.0056 (15)	−0.0001 (14)	0.0036 (13)
O4'	0.0374 (13)	0.0279 (12)	0.0429 (12)	−0.0004 (12)	0.0094 (13)	0.0087 (11)
C5'	0.042 (2)	0.0305 (17)	0.0385 (17)	−0.0036 (19)	−0.0014 (19)	−0.0016 (16)
O5'	0.0443 (15)	0.0360 (13)	0.0408 (12)	0.0071 (14)	0.0005 (13)	−0.0029 (12)

Geometric parameters (Å, º)

N1—C2	1.375 (4)	C5'—O5'	1.429 (5)
N1—C6	1.380 (4)	N1—H1	0.8600
C2—N3	1.316 (4)	N2—H2B	0.8600
C2—N2	1.343 (4)	N2—H2A	0.8600
N3—C4	1.343 (4)	C7—H7	0.9300
C4—C5	1.397 (4)	C8—H8	0.9300
C5—C6	1.409 (4)	C1'—H1'	0.9800
C5—C7	1.431 (5)	C2'—C3'	1.524 (5)
C6—O6	1.261 (3)	C2'—H2'1	0.9700
C4—N9	1.376 (4)	C2'—H2'2	0.9700
N9—C8	1.393 (4)	C3'—C4'	1.510 (5)
C7—C8	1.355 (5)	C3'—H3'1	0.9800
N9—C1'	1.451 (4)	O3'—H3'	0.82 (3)
C1'—O4'	1.443 (4)	C4'—H4'	0.9800
C4'—O4'	1.431 (4)	C5'—H5'1	0.9700
C1'—C2'	1.522 (5)	C5'—H5'2	0.9700
C3'—O3'	1.422 (4)	O5'—H5'	0.819 (8)
C4'—C5'	1.518 (5)
N3—C4—N9	123.4 (3)	N9—C1'—C2'	114.2 (3)
N3—C4—C5	129.1 (3)	O4'—C1'—H1'	109.3
N9—C4—C5	107.5 (3)	N9—C1'—H1'	109.3
C4—C5—C6	116.8 (3)	C2'—C1'—H1'	109.3
C4—C5—C7	107.7 (3)	C1'—C2'—C3'	104.1 (3)
C6—C5—C7	135.1 (3)	C1'—C2'—H2'1	110.9
C4—N9—C8	108.3 (3)	C3'—C2'—H2'1	110.9
C4—N9—C1'	125.0 (3)	C1'—C2'—H2'2	110.9
C8—N9—C1'	126.5 (3)	C3'—C2'—H2'2	110.9
C5—C7—C8	106.7 (3)	H2'1—C2'—H2'2	109.0
C7—C8—N9	109.7 (3)	O3'—C3'—C4'	112.2 (3)
C1'—O4'—C4'	108.1 (2)	O3'—C3'—C2'	112.4 (3)
C2—N1—C6	125.6 (3)	C4'—C3'—C2'	101.4 (3)
C2—N1—H1	117.2	O3'—C3'—H3'1	110.2
C6—N1—H1	117.2	C4'—C3'—H3'1	110.2
N3—C2—N2	121.0 (3)	C2'—C3'—H3'1	110.2
N3—C2—N1	122.7 (3)	C3'—O3'—H3'	109.3 (10)
N2—C2—N1	116.3 (3)	O4'—C4'—C3'	104.1 (3)
C2—N2—H2B	120.0	O4'—C4'—C5'	108.9 (3)
C2—N2—H2A	120.0	C3'—C4'—C5'	115.4 (3)
H2B—N2—H2A	120.0	O4'—C4'—H4'	109.4
C2—N3—C4	112.6 (3)	C3'—C4'—H4'	109.4
O6—C6—N1	119.2 (3)	C5'—C4'—H4'	109.4
O6—C6—C5	128.0 (3)	O5'—C5'—C4'	111.7 (3)
N1—C6—C5	112.9 (3)	O5'—C5'—H5'1	109.3
C8—C7—H7	126.7	C4'—C5'—H5'1	109.3
C5—C7—H7	126.7	O5'—C5'—H5'2	109.3
C7—C8—H8	125.1	C4'—C5'—H5'2	109.3
N9—C8—H8	125.1	H5'1—C5'—H5'2	107.9
O4'—C1'—N9	108.3 (3)	C5'—O5'—H5'	108.4 (12)
O4'—C1'—C2'	106.5 (3)
C6—N1—C2—N3	−3.5 (5)	C5—C4—N9—C1'	−175.2 (3)
C6—N1—C2—N2	176.5 (3)	C7—C8—N9—C4	−0.8 (4)
N2—C2—N3—C4	−176.1 (3)	C7—C8—N9—C1'	175.4 (3)
N1—C2—N3—C4	3.9 (4)	C4—N9—C1'—O4'	−106.5 (3)
C2—N3—C4—N9	−177.9 (3)	C8—N9—C1'—O4'	77.9 (4)
C2—N3—C4—C5	0.7 (5)	C4—N9—C1'—C2'	135.1 (3)
N3—C4—C5—C6	−5.7 (5)	C8—N9—C1'—C2'	−40.5 (5)
N9—C4—C5—C6	173.1 (3)	O4'—C1'—C2'—C3'	−11.1 (3)
N3—C4—C5—C7	−179.8 (3)	N9—C1'—C2'—C3'	108.3 (3)
N9—C4—C5—C7	−0.9 (3)	C1'—C2'—C3'—O3'	150.5 (3)
C2—N1—C6—O6	177.5 (3)	C1'—C2'—C3'—C4'	30.6 (3)
C2—N1—C6—C5	−1.7 (4)	O3'—C3'—C4'—O4'	−160.0 (2)
C4—C5—C6—O6	−173.5 (3)	C2'—C3'—C4'—O4'	−39.9 (3)
C7—C5—C6—O6	−1.6 (6)	O3'—C3'—C4'—C5'	80.7 (4)
C4—C5—C6—N1	5.6 (4)	C2'—C3'—C4'—C5'	−159.2 (3)
C7—C5—C6—N1	177.5 (3)	C3'—C4'—O4'—C1'	34.5 (3)
C4—C5—C7—C8	0.5 (4)	C5'—C4'—O4'—C1'	158.1 (3)
C6—C5—C7—C8	−172.0 (4)	N9—C1'—O4'—C4'	−137.6 (3)
C5—C7—C8—N9	0.2 (4)	C2'—C1'—O4'—C4'	−14.4 (3)
N3—C4—N9—C8	180.0 (3)	O4'—C4'—C5'—O5'	69.6 (3)
C5—C4—N9—C8	1.1 (3)	C3'—C4'—C5'—O5'	−173.8 (3)
N3—C4—N9—C1'	3.7 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O6^i	0.86	2.04	2.847 (4)	155
N2—H2A···O6^i	0.86	2.38	3.085 (4)	140
N2—H2B···O3′^ii	0.86	2.06	2.907 (4)	169
O3′—H3′···O5′^iii	0.82 (3)	1.97 (2)	2.767 (3)	162 (2)
O5′—H5′···O6^iv	0.82 (1)	1.99 (1)	2.794 (3)	167 (3)

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