7-Fluoro­tubercidin: a halogenated derivative of a naturally occurring nucleoside anti­metabolite

The title compound [systematic name: 4-amino-5-fluoro-7-(β-D-ribofuranos­yl)-7H-pyrrolo[2,3-d]pyrimidine], C₁₁H₁₃FN₄O₄, exhibits an anti glycosylic bond conformation, with a χ torsion angle of −124.7 (3)°. The furan­ose moiety shows a twisted C2′-endo sugar pucker (S-type), with P = 169.8 (3)° and τ_m = 38.7 (2)°. The orientation of the exocyclic C4′—C5′ bond is +sc (gauche, gauche), with a γ torsion angle of 59.3 (3)°. The nucleobases are stacked head-to-head. The extended crystal structure is a three-dimensional hydrogen-bond network involving O—H...O, O—H...N and N—H...O hydrogen bonds. The crystal structure of the title nucleoside demonstrates that the C—C bonds nearest the F atom of the pyrrole system are significantly shortened by the electronegative halogen atom.

S1. Comment

The naturally occurring nucleoside antibiotic tubercidin is a close structural analogue of adenosine and shows significant biological activities (Suhadolnik, 1970, and references therein). 50 years ago, tubercidin was isolated from Streptomyces tubercidicus (Anzai et al., 1957), while its crystal structure was reported by Stroud and Abola & Sundaralingam in 1973 (Stroud, 1973; Abola & Sundaralingam, 1973). A series of 7-substituted tubercidin derivatives (purine numbering is used throughout this discussion) exhibit antiviral activity against various RNA and DNA viruses, including herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) (Bergstrom et al., 1984; De Clercq et al., 1986). Moreover, 2'-C-methyltubercidin, as well as its 7-fluoro derivative, are potent and selective inhibitors of hepatitis C virus (HCV) RNA replication (Olsen et al., 2004; Eldrup et al., 2004).

The introduction of an F atom as a substituent of the sugar residue or of the heterocyclic ring moiety of nucleosides has a positive effect on the biological activity. A number of fluorine-substituted analogues of nucleic acid components were established as antiviral, anticancer and antifungal agents (Pankiewicz, 2000). Recently, Wang et al. (2004) reported the synthesis and characteristics of 7-fluorotubercidin, (I), which exhibits reduced cytotoxicity compared to its parent derivative tubercidin.

Due to the favorable biological activity of 7-fluorotubercidin, (I), we became interested in performing a single-crystal X-ray analysis of (I) and comparing the solid-state structure with closely related nucleosides. The parent tubercidin, (IIa) (Stroud, 1973; Abola & Sundaralingam, 1973), 2'-deoxytubercidin, (IIb) (Zabel et al., 1987), 7-fluoro-2'-deoxytubercidin, (IIc) (Seela et al., 2005), 2'-deoxy-2-fluorotubercidin, (III) (Seela et al., 2007), as well as the difluorinated tubercidin analogue (IV) (Seela et al., 2006), were selected for comparison.

Compound (I) was synthesized according to the `one-pot' Vorbrüggen glycosylation protocol recently reported by Wang et al. (2004) and was crystallized from methanol as colorless needles. The three-dimensional structure of (I) is shown in Fig. 1 and selected geometric parameters are listed in Table 1.

From the crystal structure of (I), the orientation of the nucleobase relative to the sugar moiety was determined to be in the anti range, with χ (O4'—C1'–N9—C4) = -124.7 (3)° according to IUPAC–IUB (Joint Commission on Biochemical Nomenclature, 1983). The glycosylic bond conformation of the parent unsubstituted compound, (IIa), as well as that of the difluorinated nucleoside (IV) adopt, χ values within the same anti range, with χ values of -112.8 (4)° for (IIa) (Abola & Sundaralingam, 1973) and -117.8 (2)° for (IV) (Seela et al., 2006). For comparison, the conformation of the 2'-deoxyribonucleoside analogues (IIb), (IIc) and (III) fall into the range between anti and high-anti [χ values of -104.4 (2)° for (IIb) (Zabel et al., 1987), -101.1 (3)° for (IIc) (Seela et al., 2005) and -110.2 (3)° for (III) (Seela et al., 2007)]. The glycosylic bond length (N9—C1') in (I) is 1.444 (3)Å, which is identical to that in (IIc) [1.444 (4)Å; Seela et al., 2005].

The most frequently observed sugar ring conformations of nucleosides are C2'-endo (`south') and C3'-endo (`north') (Arnott & Hukins, 1972). The sugar moiety of nucleoside (I) shows an S conformation with an unsymmetrical twist of C2'-endo–C3'-exo (²T₃), a pseudorotation phase angle, P (Rao et al., 1981), of 169.8 (3)° with the maximum amplitude of pucker, τ_m, of 38.7 (2)°. This is very similar to compound (IIc) which also has a ²T₃ sugar conformation (P = 164.7 (3)°; Seela et al., 2005). In the case of the parent unsubstituted compound, (IIa), and closely related (IIb), the sugar ring conformation is C2'-endo–C1'-exo (²T₁; S conformation), with P = 149.3° and P = 186.6 (2)° (Abola & Sundaralingam, 1973; Zabel et al., 1987). In contrast, an N conformation was observed for difluorinated compound (IV) (C4'-exo, between ³T₄ and E₄, with P = 45.3°; Seela et al., 2006) and nucleoside (III) (C3'-endo–C4'-exo, with P = 40.3°; Seela et al., 2007). From the examples mentioned above, it can be seen that the sugar conformation obtained for nucleosides in the solid state do not reflect the sugar conformations found in DNA or RNA. The S conformation of the sugar moiety of ribonucleoside (I) is in contrast to the N sugar conformation of RNA.

The sugar conformation of nucleoside (I) was also determined in solution and compared to the conformation of the parent tubercidin (IIa). In solution, both compounds show a predominantly S conformation [85% S for (I) and 88% S for (IIa)], which is consistent with their sugar conformation in solid state. The conformation analysis was performed on the basis of the vicinal ³J(H,H) coupling constants of ¹H NMR spectra measured in D₂O, applying the program PSEUROT6.3 (Van Wijk et al., 1999).

The conformation about the exocyclic C4'—C5' bond, which is defined by the torsion angle γ (O5'—C5'—C4'—C3'), is 59.3 (3)° for (I), representing a +sc (gauche, gauche) conformation, whereas in the parent (IIa) and in compound (IIb), the C4'—C5' bond shows an ap (gauche, trans) conformation [(IIa): γ = -178.3 (4)°; (IIb): γ = -179.6 (2)°] (Abola & Sundaralingam, 1973; Zabel et al., 1987).

The 7-deazapurine ring system is nearly planar. The r.m.s. deviation of the ring atoms from their calculated least-squares planes is 0.0103Å, with a maximum deviation of 0.0159 (2)Å for atom C6. The F7 substituent of (I) lies -0.0142 (8)Å below and atom N6 of the amino group lies 0.0379 (3)Å above this plane. The C5—C7 [1.409 (4)Å] and C7—C8 [1.349 (4)Å] bond lengths in (I) are shorter than those in the parent (IIa) [C5—C7 = 1.433 (4)Å and C7—C8 = 1.359 (5)Å; Abola & Sundaralingam, 1973]. This might be caused by the strong electron-withdrawing effect of the 7-fluoro substituent.

In the close-packed network of (I), both the nucleobases and sugar residues are stacked. The bases are arranged head-to-head. The structure is stabilized by several hydrogen bonds, leading to a three-dimensional layered network (Fig. 2 and Table 2). In the solid-state structure of nucleoside (I), the distance of each atom between neighboring sheets is 3.264Å, which is less than the average base-pair stacking distance in B-DNA (3.5Å). Hydrogen bonds are mainly formed between adjacent nucleobases and sugar moieties. N6—H6A···O2' and O3'—H3'···N1 hydrogen bonds are formed within each sheet, while N6—H6B···O5', O2'—H2'···N3 and O5'—H5'A···O4' hydrogen bonds connect neighboring sheets. Contrary to nucleoside (IIc), the 7-fluoro substituent does not take part in hydrogen-bond formation (Seela et al., 2005).

Related literature

For related literature, see: Abola & Sundaralingam (1973); Anzai et al. (1957); Arnott & Hukins (1972); Bergstrom et al. (1984); De Clercq, Bernaerts, Bergstrom, Robins, Montgomery & Holy (1986); Eldrup et al. (2004); Olsen et al. (2004); Pankiewicz (2000); Rao et al. (1981); Seela et al. (2005, 2006, 2007); Stroud (1973); Suhadolnik (1970); Van Wijk, Haasnoot, de Leeuw, Huckriede, Westra Hoekzema & Altona (1999); Wang et al. (2004); Zabel et al. (1987).

S2. Experimental

Compound (I) was synthesized according to the `one-pot' Vorbrüggen glycosylation protocol recently reported by Wang et al. (2004) and was crystallized from methanol as colorless needles (m.p. 494–495 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. Therefore, Friedel equivalents were merged before the final refinements. The known configuration of the parent molecule was used to define the enantiomer of the final model. All H atoms were initially found in a difference Fourier synthesis. In order to maximize the data/parameter ratio, the H atoms were placed in geometrically idealized positions (C—H = 0.93–0.98Å, O—H = 0.82Å and N—H = 0.86Å) and constrained to ride on their parent atoms [U_iso(H)= 1.2U_eq(C) = U_eq(N) and 1.5U_eq(O).

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 nucleoside (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary size.
	Fig. 2. The crystal packing of (I), showing the intermolecular hydrogen-bonding network. The projection is parallel to the a axis.

4-amino-5-fluoro-7-(β-D-ribofuranosyl)-7H- pyrrolo[2,3-d]pyrimidine

Crystal data

C11H13FN4O4	F(000) = 592
Mr = 284.25	Dx = 1.549 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 52 reflections
a = 4.9394 (13) Å	θ = 2.4–22.4°
b = 14.6718 (19) Å	µ = 0.13 mm^−1
c = 16.8181 (16) Å	T = 293 K
V = 1218.8 (4) Å^3	Needle, colourless
Z = 4	0.5 × 0.3 × 0.2 mm

Data collection

Bruker P4 diffractometer	Rint = 0.025
Radiation source: fine-focus sealed tube	θmax = 27.0°, θmin = 1.8°
Graphite monochromator	h = −6→1
2θ/ω scans	k = −18→1
2181 measured reflections	l = −1→21
1580 independent reflections	3 standard reflections every 97 reflections
1438 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.039	w = 1/[σ^2(Fo^2) + (0.0475P)^2 + 0.4749P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.107	(Δ/σ)max < 0.001
S = 1.10	Δρmax = 0.22 e Å^−3
1580 reflections	Δρmin = −0.20 e Å^−3
185 parameters	Extinction correction: SHELXTL (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.014 (3)
Primary atom site location: structure-invariant direct methods	Absolute structure: establisched by known chemical absolute configuration
Secondary atom site location: difference Fourier map

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	0.2075 (6)	0.23532 (15)	0.25078 (14)	0.0352 (6)
C2	0.1758 (6)	0.14486 (18)	0.25525 (16)	0.0327 (6)
H2	0.0488	0.1202	0.2205	0.039*
N3	0.2996 (5)	0.08544 (14)	0.30212 (13)	0.0300 (5)
C4	0.4782 (6)	0.12533 (17)	0.35141 (14)	0.0260 (5)
C5	0.5333 (6)	0.21937 (16)	0.35384 (14)	0.0281 (5)
C6	0.3855 (6)	0.27452 (17)	0.30116 (15)	0.0302 (6)
N6	0.4134 (6)	0.36538 (15)	0.29766 (15)	0.0413 (7)
H6A	0.3196	0.3964	0.2642	0.050*
H6B	0.5251	0.3926	0.3289	0.050*
C7	0.7356 (6)	0.22930 (17)	0.41226 (16)	0.0310 (6)
F7	0.8474 (4)	0.31034 (11)	0.43370 (12)	0.0486 (5)
C8	0.7976 (6)	0.14735 (17)	0.44374 (17)	0.0326 (6)
H8	0.9254	0.1362	0.4832	0.039*
N9	0.6354 (5)	0.08245 (14)	0.40646 (13)	0.0285 (5)
C1'	0.6578 (6)	−0.01487 (16)	0.41729 (15)	0.0262 (5)
H1'	0.5292	−0.0455	0.3818	0.031*
C2'	0.9388 (5)	−0.05223 (16)	0.40231 (14)	0.0244 (5)
H2'1	1.0740	−0.0100	0.4238	0.029*
O2'	0.9889 (5)	−0.06665 (12)	0.32045 (10)	0.0335 (5)
H2'	1.0963	−0.0283	0.3043	0.050*
C3'	0.9395 (6)	−0.13988 (16)	0.45067 (15)	0.0288 (6)
H3'1	1.1237	−0.1587	0.4648	0.035*
O3'	0.7967 (5)	−0.21047 (12)	0.41137 (12)	0.0408 (5)
H3'	0.8474	−0.2137	0.3650	0.061*
C4'	0.7767 (6)	−0.11186 (17)	0.52391 (15)	0.0302 (6)
H4'	0.6652	−0.1638	0.5404	0.036*
O4'	0.5963 (4)	−0.03845 (13)	0.49768 (11)	0.0339 (5)
C5'	0.9376 (7)	−0.07980 (19)	0.59485 (16)	0.0366 (6)
H5'1	0.8127	−0.0651	0.6375	0.044*
H5'2	1.0511	−0.1296	0.6130	0.044*
O5'	1.1047 (5)	−0.00242 (14)	0.58021 (13)	0.0400 (5)
H5'	1.2411	−0.0184	0.5562	0.060*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0427 (14)	0.0299 (11)	0.0330 (11)	0.0007 (12)	−0.0081 (12)	0.0049 (9)
C2	0.0344 (15)	0.0313 (12)	0.0325 (12)	−0.0051 (13)	−0.0074 (13)	0.0026 (10)
N3	0.0314 (11)	0.0276 (10)	0.0309 (11)	−0.0047 (10)	−0.0031 (10)	0.0035 (9)
C4	0.0271 (12)	0.0243 (11)	0.0265 (11)	0.0006 (11)	0.0032 (11)	0.0024 (9)
C5	0.0324 (13)	0.0242 (11)	0.0276 (11)	−0.0010 (11)	0.0010 (12)	−0.0010 (9)
C6	0.0365 (14)	0.0246 (11)	0.0294 (12)	0.0007 (11)	0.0010 (13)	0.0012 (10)
N6	0.0555 (17)	0.0236 (10)	0.0448 (13)	0.0022 (12)	−0.0147 (14)	0.0048 (10)
C7	0.0321 (14)	0.0243 (11)	0.0366 (14)	0.0009 (11)	−0.0072 (13)	−0.0045 (10)
F7	0.0583 (12)	0.0267 (8)	0.0609 (11)	−0.0015 (9)	−0.0255 (10)	−0.0064 (7)
C8	0.0343 (14)	0.0274 (12)	0.0362 (13)	0.0054 (12)	−0.0099 (13)	−0.0037 (10)
N9	0.0294 (11)	0.0228 (10)	0.0332 (10)	0.0019 (9)	−0.0050 (11)	0.0016 (8)
C1'	0.0268 (12)	0.0219 (11)	0.0299 (12)	−0.0022 (10)	−0.0020 (12)	0.0035 (9)
C2'	0.0258 (12)	0.0206 (10)	0.0267 (11)	−0.0021 (10)	−0.0002 (11)	−0.0011 (9)
O2'	0.0413 (12)	0.0314 (9)	0.0279 (8)	−0.0099 (9)	0.0065 (9)	−0.0022 (7)
C3'	0.0342 (14)	0.0203 (10)	0.0318 (12)	−0.0010 (11)	−0.0035 (12)	−0.0009 (9)
O3'	0.0627 (14)	0.0247 (9)	0.0350 (10)	−0.0122 (10)	−0.0016 (11)	−0.0015 (8)
C4'	0.0375 (15)	0.0225 (11)	0.0307 (12)	−0.0002 (11)	0.0006 (12)	0.0061 (9)
O4'	0.0310 (10)	0.0355 (10)	0.0354 (10)	0.0057 (9)	0.0083 (10)	0.0091 (8)
C5'	0.0436 (16)	0.0338 (13)	0.0323 (12)	0.0018 (14)	−0.0026 (14)	−0.0006 (11)
O5'	0.0351 (11)	0.0389 (11)	0.0461 (11)	−0.0043 (10)	0.0027 (11)	−0.0128 (9)

Geometric parameters (Å, º)

N1—C2	1.339 (3)	C1'—C2'	1.513 (4)
N1—C6	1.350 (4)	C1'—H1'	0.9800
C2—N3	1.325 (3)	C2'—O2'	1.415 (3)
C2—H2	0.9300	C2'—C3'	1.522 (3)
N3—C4	1.345 (4)	C2'—H2'1	0.9800
C4—N9	1.362 (3)	O2'—H2'	0.8200
C4—C5	1.407 (3)	C3'—O3'	1.417 (3)
C5—C6	1.405 (4)	C3'—C4'	1.527 (4)
C5—C7	1.409 (4)	C3'—H3'1	0.9800
C6—N6	1.341 (3)	O3'—H3'	0.8200
N6—H6A	0.8600	C4'—O4'	1.466 (3)
N6—H6B	0.8600	C4'—C5'	1.509 (4)
C7—C8	1.349 (4)	C4'—H4'	0.9800
C7—F7	1.360 (3)	C5'—O5'	1.425 (4)
C8—N9	1.394 (4)	C5'—H5'1	0.9700
C8—H8	0.9300	C5'—H5'2	0.9700
N9—C1'	1.444 (3)	O5'—H5'	0.8200
C1'—O4'	1.428 (3)
C2—N1—C6	117.6 (2)	N9—C1'—H1'	109.1
N3—C2—N1	129.2 (3)	C2'—C1'—H1'	109.1
N3—C2—H2	115.4	O2'—C2'—C1'	112.1 (2)
N1—C2—H2	115.4	O2'—C2'—C3'	113.2 (2)
C2—N3—C4	112.5 (2)	C1'—C2'—C3'	102.7 (2)
N3—C4—N9	126.3 (2)	O2'—C2'—H2'1	109.6
N3—C4—C5	124.9 (2)	C1'—C2'—H2'1	109.6
N9—C4—C5	108.8 (2)	C3'—C2'—H2'1	109.6
C6—C5—C4	116.5 (2)	C2'—O2'—H2'	109.5
C6—C5—C7	138.5 (2)	O3'—C3'—C2'	111.6 (2)
C4—C5—C7	105.0 (2)	O3'—C3'—C4'	108.1 (2)
N6—C6—N1	117.6 (3)	C2'—C3'—C4'	101.7 (2)
N6—C6—C5	123.1 (3)	O3'—C3'—H3'1	111.7
N1—C6—C5	119.3 (2)	C2'—C3'—H3'1	111.7
C6—N6—H6A	120.0	C4'—C3'—H3'1	111.7
C6—N6—H6B	120.0	C3'—O3'—H3'	109.5
H6A—N6—H6B	120.0	O4'—C4'—C5'	109.2 (2)
C8—C7—F7	125.7 (2)	O4'—C4'—C3'	105.96 (19)
C8—C7—C5	110.0 (2)	C5'—C4'—C3'	116.4 (2)
F7—C7—C5	124.3 (2)	O4'—C4'—H4'	108.3
C7—C8—N9	107.6 (2)	C5'—C4'—H4'	108.3
C7—C8—H8	126.2	C3'—C4'—H4'	108.3
N9—C8—H8	126.2	C1'—O4'—C4'	109.5 (2)
C4—N9—C8	108.5 (2)	O5'—C5'—C4'	114.6 (2)
C4—N9—C1'	125.9 (2)	O5'—C5'—H5'1	108.6
C8—N9—C1'	125.1 (2)	C4'—C5'—H5'1	108.6
O4'—C1'—N9	110.0 (2)	O5'—C5'—H5'2	108.6
O4'—C1'—C2'	105.4 (2)	C4'—C5'—H5'2	108.6
N9—C1'—C2'	114.0 (2)	H5'1—C5'—H5'2	107.6
O4'—C1'—H1'	109.1	C5'—O5'—H5'	109.5
C6—N1—C2—N3	−1.3 (5)	C7—C8—N9—C4	1.0 (3)
N1—C2—N3—C4	0.7 (5)	C7—C8—N9—C1'	173.4 (3)
C2—N3—C4—N9	179.8 (3)	C4—N9—C1'—O4'	−124.7 (3)
C2—N3—C4—C5	−0.5 (4)	C8—N9—C1'—O4'	64.2 (4)
N3—C4—C5—C6	1.0 (4)	C4—N9—C1'—C2'	117.2 (3)
N9—C4—C5—C6	−179.3 (2)	C8—N9—C1'—C2'	−54.0 (4)
N3—C4—C5—C7	−178.6 (3)	O4'—C1'—C2'—O2'	157.02 (19)
N9—C4—C5—C7	1.1 (3)	N9—C1'—C2'—O2'	−82.2 (3)
C2—N1—C6—N6	−178.8 (3)	O4'—C1'—C2'—C3'	35.3 (2)
C2—N1—C6—C5	1.7 (4)	N9—C1'—C2'—C3'	156.0 (2)
C4—C5—C6—N6	178.9 (3)	O2'—C2'—C3'—O3'	−43.4 (3)
C7—C5—C6—N6	−1.6 (6)	C1'—C2'—C3'—O3'	77.6 (3)
C4—C5—C6—N1	−1.6 (4)	O2'—C2'—C3'—C4'	−158.5 (2)
C7—C5—C6—N1	177.8 (3)	C1'—C2'—C3'—C4'	−37.4 (2)
C6—C5—C7—C8	−180.0 (3)	O3'—C3'—C4'—O4'	−90.5 (2)
C4—C5—C7—C8	−0.5 (3)	C2'—C3'—C4'—O4'	27.0 (3)
C6—C5—C7—F7	0.7 (6)	O3'—C3'—C4'—C5'	147.9 (2)
C4—C5—C7—F7	−179.8 (3)	C2'—C3'—C4'—C5'	−94.6 (3)
F7—C7—C8—N9	179.0 (3)	N9—C1'—O4'—C4'	−141.9 (2)
C5—C7—C8—N9	−0.3 (3)	C2'—C1'—O4'—C4'	−18.5 (3)
N3—C4—N9—C8	178.4 (3)	C5'—C4'—O4'—C1'	120.4 (2)
C5—C4—N9—C8	−1.3 (3)	C3'—C4'—O4'—C1'	−5.6 (3)
N3—C4—N9—C1'	6.0 (4)	O4'—C4'—C5'—O5'	−60.5 (3)
C5—C4—N9—C1'	−173.7 (3)	C3'—C4'—C5'—O5'	59.3 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6A···O2′^i	0.86	2.15	2.982 (3)	161
N6—H6B···O5′^ii	0.86	2.26	3.026 (3)	149
O2′—H2′···N3^iii	0.82	1.95	2.726 (3)	158
O3′—H3′···N1^iv	0.82	2.10	2.841 (3)	149
O5′—H5′···O4′^iii	0.82	2.03	2.846 (3)	172

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