Stavudine

The crystal structure of the title compound (systematic name: 2',3'-didehydro-2',3'-deoxy­thymidine), C₁₀H₁₂N₂O₄, consists of two mol­ecules in the asymmetric unit bound together by hydrogen bonds. The conformational geometry differentiates this form of stavudine from its two previously published polymorphs. In addition, a different hydrogen-bonding scheme is observed compared with the previous two structures. This polymorph is the thermodynamically most stable form of the anti­viral drug, as evidenced by differential scanning calorimetry (DSC) and IR data.

S1. Comment

Stavudine was one of numerous nucleosides first prepared nearly 40 years ago (Horwitz et al., 1966). Stavudine (Zerit) has since proven itself as a potent antiviral drug used for the treatment of HIV/AIDS (Canadian Pharmacists' Association, 2000). A plethora of nucleoside derivatives have been examined (Van Roey et al., 1993) in an attempt to find the most biologically active complex. Stavudine showed exceptional promise and thus various solvates of stavudine (Skonezny et al., 1995; Radatus & Murthy, 2003; Viterbo et al., 2000) have been examined. In addition, the physico-chemical properties and thermodynamics of the hydrate and two polymorphs of the pure compound have been studied extensively (Gandhi et al., 2000). Gandhi defined the two pure forms as Form I (the more stable polymorph) and Form II (a metastable polymorph), with the hydrate defined as Form III. Polymorph I of stavudine is the thermodynamically most stable form and is the marketed form.

Two crystallographic studies have already been carried out on stavudine. They have yielded a triclinic crystal (Gurskaya et al., 1991) and a monoclinc crystal (Harte et al., 1991). Neither of these publications identified the polymorphic form of their single-crystal in the course of their X-ray diffraction study. In an attempt to correlate the polymorph to the crystal structure, we used the techniques developed by Gandhi et al. to produce Form I, Form II, and Form III. DSC and solid -state FT–IR were used to confirm the polymorphic form before carrying out the X-ray diffraction experiment. Unfortunately, only Form I afforded X-ray quality single crystals. To our surprise, Form I corresponded to an as yet unpublished orthorhombic form of stavudine. This paper presents the crystal structure of stavudine, (I), along with a comparison with the two previously published polymorphs, hereafter referred to as stavudine (H) and stavudine (G).

The chemical formula of stavudine and the preferred numbering scheme are shown in the scheme. This discussion will compare the geometry of the three polymorphs and their hydrogen-bonding schemes. The structure of stavudine and its biological activity are typically described via three characteristic torsion angles, χ (C2—N1—C1'—O4'), ν (N1—C1'—O4'—C4') and γ (C3'—C4'—C5'—O5'). These torsion angles and some selected bond lengths are compared and contrasted for the three crystal structures. Similarly, the different hydrogen-bonding schemes are examined for the three polymorphs.

The present polymorph (Fig. 1) of stavudine consists of two crystallographically independent molecules, A and B. The two molecules are paired into dimers via intermolecular hydrogen bonds (N3B—H···O4A and N3A—H···O2B). Molecule B is disordered at the hydroxyl site and was modelled as a 0.72:0.28 mixture of CH₂OH atoms. The displacement parameters of the two methylene moieties and the two hydroxyl groups of the disorder were restrained to be identical. In addition, the bond lengths of the disordered region (C4'—C5' and C5'—O5') were restrained to be identical to the bond lengths in the well ordered molecule (A).

Table 1 contains the data for the present polymorph of stavudine (I), along with data from Harte's determination, stavudine (H), and Gurskaya's determination, stavudine (G). The unit-cell data are represented, as well as selected conformational features used to describe the thymine–furanose geometry of stavudine. The most notable comparison of the three unit cells is that a simple doubling of the a axis can transform the monoclinic cell very nearly into the orthorhombic cell. However, despite the unit-cell similarities, the polymorphs are quite different, as discussion of the geometry will show.

The majority of the geometry discussion hinges on rotation about the N1—C1' bond, so it is reproduced in Table 1 along with the three torsion angles defined earlier. Stavudine (H) and (G) both have two molecules in the asymmetric unit, similar to what we observe in stavudine (I). Thus, there are six molecules to compare in our examination of the geometry. Stavudine (H) and stavudine (G) both show a short and a long N1—C1' bond. Stavudine (I), in contrast, possesses two much more similar but shorter N1—C1' bonds. The χ torsion angles show the largest extremes, whereas both ν and γ vary little between the six configurations. In fact, there are four configurations, as molecule B of stavudine (I) is very similar to molecule A of stavudine (H). Similarly, molecule B of stavudine (H) is very similar to molecule A of stavudine (G). Finally, molecule A of stavudine (I) and molecule B of stavudine (G) both have different configurations again, as emphasized by the χ torsion angle.

Table 2 contains the hydrogen-bonding data for the three polymorphs, stavudine (I), (H) and (G). All three polymorphs form dimers of the two independent molecules, utilizing hydrogen bonding between the amide and carbonyl groups of the thymidine base. Stavudine (H) and stavudine (G) both have a symmetric interaction between atoms N3 and O2. Stavudine (I), however, forms an asymmetric dimer between N3A—H···O2B and N3B—H···O4A. This is closer to what is expected, since it is typically atom O4 of the thymidine which is involved in the Watson–Crick interaction. These N—H···O bonds are all in the ranges 2.820 (4)–2.934 (3) Å and 168 (3)–174 (3)°.

Stavudine (G) continues its hydrogen bonding to form continuous layers with bonding between adjacent hydroxyl groups. Stavudine (H) has a different hydrogen-bonding pattern in that one of the hydroxyl H atoms bonds to an adjacent hydroxyl O atom, and that second hydroxyl O atom has its H atom in close contact with an adjacent furanyl O atom This is counter to what Harte reports, since he claims two hydroxy–furanyl interactions, but his second D···A distance is too long [3.862 (5) Å] to be considered a hydrogen-bonding interaction. The present structure also shows this `mixed' hydrogen-bonding interaction. The well resolved molecule A very clearly shows the hydroxyl H atom bonding to a neighbouring hydroxyl O atom of molecule B. Molecule B, due to its disordered CH₂OH moiety, shows two hydrogen-bonding schemes. The major interaction (72%) sees the hydroxyl H atom bonding to a neighbouring hydroxyl O atom of molecule A. The minor component (28%) forms a hydrogen bond towards the furanyl O atom of an adjacent molecule B. This hydrogen bonding observed in the minor component is undoubtedly a constricted geometry, as evidenced by the very different value of γ (31°) from the remaining values (50.5–61.5°) in Table 1.

The two potential donor atoms and the four potential acceptor atoms allow for a varied number of hydrogen-bonding schemes in this versatile molecule. Stavudine, in its three polymorphs, has shown three unique crystal structures to date. All three exist in the solid state as dimers formed by intermolecular hydrogen bonding between two crystallographically independent molecules. The extended hydrogen-bonding structure differs in all three incarnations of stavudine. Stavudine (G) shows a pure hydroxyl–hydroxyl extended network. Stavudine (H) shows a hydroxyl–furanyl and a hydroxyl–hydroxyl interaction. Finally, stavudine (I) shows a hydroxyl–hydroxyl interaction, and the disordered portion of the second molecule reveals both a hydroxyl–furanyl and a hydroxyl–hydroxyl hydrogen-bonding scheme.

Single crystals of the marketed form of stavudine, Form I, have been unequivocally characterized by IR and DSC in our laboratories. Furthermore, the single-crystal X-ray structure of polymorph I is presented here, 14 years after two other polymorphs were published. The geometry of the three polymorphs has been discussed herein, as has the hydrogen-bonding scheme. We will continue our attempts to grow single crystals of Form II to verify which, if either, of the two published structures corresponds to it.

S2. Experimental

Stavudine at 99.5% purity was provided by Apotex PharmaChem Inc. Solvents were purchased from Sigma–Aldrich. Stavudine was dissolved in propan-2-ol at 323 K and the solution filtered to remove any insoluble particles. The clean filtrate was cooled down to 298 K with a linear cooling profile (0.1 K min⁻¹) while agitating the solution to recrystallize the stavudine. The DSC and FT–IR analyses confirmed that pure Form I of stavudine was produced. To produce Form II, the purified Form I of stavudine was dissolved in propan-2-ol at 321 K and cooled down to 298 K in 10 min (approximately linearly) without stirring. The final product was identified as pure Form 2 using DSC and FT–IR. Various solvents were tested using a slow evaporative crystallization technique. Approximately 3 ml of saturated solutions of stavudine (I) were prepared in various solvents (deionized water, methanol, methyl ethyl ketone, propan-2-ol and acetonitrile). For each solvent, five vials of equal concentration were prepared. The vials were placed in a nitrogen-filled oven at room temperature under slight vacuum for about one month. The only solvent that produced X-ray quality single crystals was water. Interestingly, the single-crystal turned out to be polymorph I and not the hydrate.

S3. Refinement

H atoms were positioned geometrically and constrained as riding atoms, with C—H = 0.93 Å and U_iso(H) = 1.2U_eq(C), and N—H = 0.86 Å and U_iso(H) = 1.2U_eq(N) for aromatic H atoms, C—H = 0.96 Å and U_iso(H) = 1.5U_eq(C) for methyl H atoms, C—H = 0.97 Å and U_iso(H) = 1.2U_eq(C) for methylene H atoms, C—H = 0.98 Å and U_iso(H) = 1.2U_eq(C) for methyne H atoms, and O—H = 0.82 Å and U_iso(H) = 1.5U_eq(C) for hydroxyl H atoms. Restrained bond lengths were C4'B—C5'B = 1.476, C4'B—C5'C = 1.476, C5'B—O5'B = 1.402 and C5'C—O5'C = 1.402 Å. The absolute structure could not be determined reliably and the Friedel pairs were merged for the final refinement. The crystals were weakly diffracting and thus a large crystal was used to ensure data out to 50° in 2θ.

Computing details

Data collection: COLLECT (Nonius, 2001); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL/PC (Sheldrick, 2001); software used to prepare material for publication: SHELXTL/PC.

Figures

Fig. 1. The structure of stavudine (I), showing 30% probability displacement ellipsoids and the atom-labelling scheme.

2',3'-Didehydro-2',3'-deoxythymidine

Crystal data

C10H12N2O4	F(000) = 944
Mr = 224.22	Dx = 1.411 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 20837 reflections
a = 5.4230 (2) Å	θ = 1.7–25.0°
b = 16.2077 (9) Å	µ = 0.11 mm^−1
c = 24.0104 (13) Å	T = 296 K
V = 2110.38 (18) Å^3	Needle, colourless
Z = 8	0.80 × 0.25 × 0.17 mm

Data collection

Nonius KappaCCD area-detector diffractometer	3680 independent reflections
Radiation source: fine-focus sealed tube	2526 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.130
ϕ scans, and ω scans with κ offsets	θmax = 25.0°, θmin = 2.7°
Absorption correction: multi-scan (SORTAV; Blessing 1995)	h = −6→6
Tmin = 0.917, Tmax = 0.981	k = −15→19
13427 measured reflections	l = −28→28

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.059	H-atom parameters constrained
wR(F^2) = 0.168	w = 1/[σ^2(Fo^2) + (0.0965P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
3680 reflections	Δρmax = 0.22 e Å^−3
296 parameters	Δρmin = −0.21 e Å^−3
4 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: 0.028 (4)

Special details

Experimental. FT—IR data: Form I distinguished by peak at 865 cm⁻¹; Form II distinguished by peak at 975 cm⁻¹. DSC data: Form I exhibited melting onset at 441 K; Form II exhibited melting onset at 438 K.

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	Occ. (<1)
N1A	−0.6200 (6)	0.36928 (17)	0.29258 (12)	0.0532 (8)
C2A	−0.4515 (7)	0.3575 (2)	0.33461 (15)	0.0530 (9)
O2A	−0.4039 (5)	0.29044 (15)	0.35461 (11)	0.0662 (7)
N3A	−0.3376 (6)	0.42789 (17)	0.35210 (12)	0.0522 (7)
H3A	−0.2325	0.4223	0.3786	0.063*
C4A	−0.3706 (7)	0.5069 (2)	0.33235 (15)	0.0520 (9)
O4A	−0.2406 (5)	0.56377 (16)	0.34961 (11)	0.0647 (7)
C5A	−0.5652 (8)	0.5158 (2)	0.29172 (16)	0.0566 (10)
C6A	−0.6716 (7)	0.4475 (2)	0.27260 (16)	0.0558 (10)
H6A	−0.7872	0.4526	0.2442	0.067*
C7A	−0.6298 (11)	0.6007 (2)	0.2723 (2)	0.0811 (15)
H7A	−0.5553	0.6106	0.2366	0.122*
H7B	−0.5701	0.6405	0.2986	0.122*
H7C	−0.8057	0.6056	0.2691	0.122*
C1'A	−0.7036 (7)	0.2967 (2)	0.26116 (16)	0.0551 (9)
H1'A	−0.6671	0.2463	0.2822	0.066*
C2'A	−0.9688 (8)	0.2981 (3)	0.2452 (2)	0.0801 (14)
H2'A	−1.0994	0.3031	0.2701	0.096*
C3'A	−0.9917 (7)	0.2912 (3)	0.1913 (2)	0.0766 (14)
H3'A	−1.1414	0.2897	0.1724	0.092*
C4'A	−0.7458 (7)	0.2860 (2)	0.16413 (16)	0.0603 (10)
H4'A	−0.7259	0.2306	0.1485	0.072*
O4'A	−0.5791 (4)	0.29513 (14)	0.20949 (10)	0.0532 (6)
C5'A	−0.6957 (11)	0.3470 (3)	0.12003 (18)	0.0833 (13)
H5'A	−0.5237	0.3434	0.1092	0.100*
H5'B	−0.7952	0.3340	0.0876	0.100*
O5'A	−0.7477 (8)	0.42790 (19)	0.13734 (13)	0.1011 (11)
H5'C	−0.6441	0.4595	0.1245	0.152*
N1B	0.3792 (5)	0.45715 (16)	0.48170 (13)	0.0527 (8)
C2B	0.1982 (7)	0.4697 (2)	0.44285 (15)	0.0534 (9)
O2B	0.0619 (6)	0.41418 (17)	0.42689 (12)	0.0689 (8)
N3B	0.1797 (5)	0.54766 (17)	0.42282 (12)	0.0504 (7)
H3B	0.0618	0.5567	0.3997	0.060*
C4B	0.3290 (7)	0.6144 (2)	0.43541 (15)	0.0509 (9)
O4B	0.2911 (5)	0.68122 (15)	0.41417 (11)	0.0645 (7)
C5B	0.5252 (6)	0.5960 (2)	0.47463 (14)	0.0484 (9)
C6B	0.5384 (7)	0.5205 (2)	0.49562 (15)	0.0507 (9)
H6B	0.6625	0.5094	0.5213	0.061*
C7B	0.7035 (8)	0.6634 (2)	0.48899 (17)	0.0648 (10)
H7D	0.6230	0.7036	0.5121	0.097*
H7E	0.7602	0.6894	0.4554	0.097*
H7F	0.8415	0.6405	0.5087	0.097*
C1'B	0.3963 (7)	0.3778 (2)	0.50985 (17)	0.0595 (10)
H1'B	0.2721	0.3399	0.4949	0.071*
C2'B	0.6414 (8)	0.3395 (2)	0.50712 (18)	0.0621 (10)
H2'B	0.7243	0.3266	0.4743	0.075*
C3'B	0.7275 (8)	0.3257 (2)	0.55752 (18)	0.0655 (11)
H3'B	0.8794	0.3014	0.5648	0.079*
C4'B	0.5552 (9)	0.3535 (3)	0.60114 (18)	0.0736 (12)
H4'B	0.4902	0.3047	0.6203	0.088*
O4'B	0.3556 (5)	0.39006 (19)	0.56786 (14)	0.0786 (9)
C5'B	0.641 (3)	0.4142 (6)	0.6445 (3)	0.096 (3)	0.72
H5'D	0.5092	0.4230	0.6710	0.116*	0.72
H5'E	0.7796	0.3904	0.6644	0.116*	0.72
O5'B	0.7130 (10)	0.4906 (3)	0.62253 (19)	0.0882 (13)	0.72
H5'F	0.6079	0.5253	0.6299	0.132*	0.72
C5'C	0.709 (7)	0.416 (2)	0.6309 (8)	0.096 (3)	0.28
H5'G	0.5929	0.4529	0.6488	0.116*	0.28
H5'H	0.7900	0.3859	0.6608	0.116*	0.28
O5'C	0.892 (3)	0.4669 (7)	0.6072 (5)	0.0882 (13)	0.28
H5'I	1.0108	0.4386	0.5980	0.132*	0.28

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1A	0.0709 (19)	0.0384 (16)	0.0503 (17)	−0.0004 (15)	−0.0067 (15)	−0.0012 (13)
C2A	0.065 (2)	0.046 (2)	0.048 (2)	0.001 (2)	0.0051 (18)	−0.0023 (17)
O2A	0.0849 (18)	0.0450 (15)	0.0688 (17)	0.0043 (14)	−0.0046 (15)	0.0130 (12)
N3A	0.0628 (18)	0.0451 (16)	0.0488 (17)	0.0024 (15)	−0.0059 (14)	0.0004 (13)
C4A	0.065 (2)	0.043 (2)	0.048 (2)	0.0037 (19)	−0.0013 (19)	−0.0003 (16)
O4A	0.0761 (17)	0.0477 (14)	0.0703 (18)	−0.0033 (14)	−0.0169 (15)	−0.0033 (12)
C5A	0.074 (3)	0.040 (2)	0.056 (2)	0.0062 (18)	−0.010 (2)	−0.0033 (17)
C6A	0.070 (2)	0.046 (2)	0.051 (2)	0.002 (2)	−0.0116 (18)	0.0000 (16)
C7A	0.117 (4)	0.046 (2)	0.080 (3)	0.004 (2)	−0.035 (3)	0.008 (2)
C1'A	0.070 (2)	0.0369 (19)	0.058 (2)	−0.0069 (18)	0.012 (2)	−0.0050 (15)
C2'A	0.056 (2)	0.076 (3)	0.108 (4)	−0.009 (2)	0.022 (2)	−0.021 (3)
C3'A	0.048 (2)	0.079 (3)	0.102 (4)	−0.007 (2)	−0.006 (2)	−0.030 (3)
C4'A	0.058 (2)	0.058 (2)	0.065 (2)	0.010 (2)	−0.012 (2)	−0.0188 (19)
O4'A	0.0494 (12)	0.0565 (15)	0.0538 (15)	0.0008 (11)	0.0014 (11)	−0.0072 (12)
C5'A	0.114 (4)	0.074 (3)	0.062 (3)	0.020 (3)	−0.010 (3)	−0.001 (2)
O5'A	0.158 (3)	0.0615 (18)	0.084 (2)	0.022 (2)	0.004 (3)	0.0032 (15)
N1B	0.0548 (16)	0.0380 (16)	0.0651 (19)	−0.0050 (14)	−0.0134 (15)	0.0113 (13)
C2B	0.056 (2)	0.045 (2)	0.059 (2)	−0.0025 (19)	−0.0033 (19)	0.0013 (17)
O2B	0.0744 (17)	0.0509 (15)	0.0813 (19)	−0.0086 (15)	−0.0242 (15)	0.0084 (13)
N3B	0.0551 (17)	0.0431 (16)	0.0529 (17)	0.0000 (15)	−0.0078 (14)	0.0060 (13)
C4B	0.060 (2)	0.045 (2)	0.048 (2)	−0.0034 (18)	0.0014 (17)	−0.0029 (16)
O4B	0.0779 (17)	0.0425 (14)	0.0732 (18)	0.0042 (13)	−0.0082 (15)	0.0103 (12)
C5B	0.053 (2)	0.0423 (19)	0.050 (2)	−0.0002 (16)	−0.0005 (16)	−0.0023 (15)
C6B	0.0497 (19)	0.047 (2)	0.056 (2)	−0.0070 (17)	−0.0073 (18)	0.0052 (16)
C7B	0.073 (2)	0.050 (2)	0.072 (3)	−0.008 (2)	−0.011 (2)	0.0006 (18)
C1'B	0.066 (2)	0.046 (2)	0.067 (3)	−0.0096 (18)	−0.012 (2)	0.0179 (18)
C2'B	0.074 (3)	0.043 (2)	0.070 (3)	0.0053 (19)	0.003 (2)	0.0041 (18)
C3'B	0.063 (2)	0.050 (2)	0.083 (3)	0.007 (2)	−0.006 (2)	0.010 (2)
C4'B	0.087 (3)	0.059 (2)	0.075 (3)	0.009 (2)	−0.010 (3)	0.024 (2)
O4'B	0.0636 (17)	0.085 (2)	0.087 (2)	0.0207 (15)	0.0090 (15)	0.0345 (16)
C5'B	0.158 (9)	0.094 (4)	0.037 (4)	−0.002 (5)	0.007 (4)	0.012 (4)
O5'B	0.110 (4)	0.068 (3)	0.087 (3)	0.016 (3)	−0.012 (3)	−0.006 (2)
C5'C	0.158 (9)	0.094 (4)	0.037 (4)	−0.002 (5)	0.007 (4)	0.012 (4)
O5'C	0.110 (4)	0.068 (3)	0.087 (3)	0.016 (3)	−0.012 (3)	−0.006 (2)

Geometric parameters (Å, º)

N1A—C2A	1.375 (5)	C2B—O2B	1.225 (4)
N1A—C6A	1.384 (5)	C2B—N3B	1.356 (4)
N1A—C1'A	1.470 (5)	N3B—C4B	1.384 (4)
C2A—O2A	1.216 (4)	N3B—H3B	0.8600
C2A—N3A	1.363 (5)	C4B—O4B	1.215 (4)
N3A—C4A	1.377 (5)	C4B—C5B	1.452 (5)
N3A—H3A	0.8600	C5B—C6B	1.326 (5)
C4A—O4A	1.232 (4)	C5B—C7B	1.500 (5)
C4A—C5A	1.444 (5)	C6B—H6B	0.9300
C5A—C6A	1.330 (5)	C7B—H7D	0.9600
C5A—C7A	1.495 (5)	C7B—H7E	0.9600
C6A—H6A	0.9300	C7B—H7F	0.9600
C7A—H7A	0.9600	C1'B—O4'B	1.424 (5)
C7A—H7B	0.9600	C1'B—C2'B	1.469 (6)
C7A—H7C	0.9600	C1'B—H1'B	0.9800
C1'A—O4'A	1.413 (4)	C2'B—C3'B	1.316 (6)
C1'A—C2'A	1.488 (6)	C2'B—H2'B	0.9300
C1'A—H1'A	0.9800	C3'B—C4'B	1.474 (6)
C2'A—C3'A	1.307 (7)	C3'B—H3'B	0.9300
C2'A—H2'A	0.9300	C4'B—O4'B	1.471 (5)
C3'A—C4'A	1.486 (6)	C4'B—C5'C	1.492 (10)
C3'A—H3'A	0.9300	C4'B—C5'B	1.506 (7)
C4'A—O4'A	1.423 (4)	C4'B—H4'B	0.9800
C4'A—C5'A	1.474 (6)	C5'B—O5'B	1.401 (8)
C4'A—H4'A	0.9800	C5'B—H5'D	0.9700
C5'A—O5'A	1.404 (5)	C5'B—H5'E	0.9700
C5'A—H5'A	0.9700	O5'B—H5'F	0.8200
C5'A—H5'B	0.9700	C5'C—O5'C	1.414 (10)
O5'A—H5'C	0.8200	C5'C—H5'G	0.9700
N1B—C2B	1.369 (5)	C5'C—H5'H	0.9700
N1B—C6B	1.382 (4)	O5'C—H5'I	0.8200
N1B—C1'B	1.455 (4)
C2A—N1A—C6A	121.0 (3)	C2B—N3B—C4B	127.4 (3)
C2A—N1A—C1'A	118.1 (3)	C2B—N3B—H3B	116.3
C6A—N1A—C1'A	119.6 (3)	C4B—N3B—H3B	116.3
O2A—C2A—N3A	122.0 (3)	O4B—C4B—N3B	120.4 (3)
O2A—C2A—N1A	123.7 (3)	O4B—C4B—C5B	125.4 (3)
N3A—C2A—N1A	114.3 (3)	N3B—C4B—C5B	114.2 (3)
C2A—N3A—C4A	127.8 (3)	C6B—C5B—C4B	118.4 (3)
C2A—N3A—H3A	116.1	C6B—C5B—C7B	123.4 (3)
C4A—N3A—H3A	116.1	C4B—C5B—C7B	118.2 (3)
O4A—C4A—N3A	120.4 (3)	C5B—C6B—N1B	124.1 (3)
O4A—C4A—C5A	124.8 (3)	C5B—C6B—H6B	118.0
N3A—C4A—C5A	114.9 (3)	N1B—C6B—H6B	118.0
C6A—C5A—C4A	117.8 (3)	C5B—C7B—H7D	109.5
C6A—C5A—C7A	123.8 (4)	C5B—C7B—H7E	109.5
C4A—C5A—C7A	118.3 (3)	H7D—C7B—H7E	109.5
C5A—C6A—N1A	123.7 (3)	C5B—C7B—H7F	109.5
C5A—C6A—H6A	118.1	H7D—C7B—H7F	109.5
N1A—C6A—H6A	118.1	H7E—C7B—H7F	109.5
C5A—C7A—H7A	109.5	O4'B—C1'B—N1B	108.8 (3)
C5A—C7A—H7B	109.5	O4'B—C1'B—C2'B	104.0 (3)
H7A—C7A—H7B	109.5	N1B—C1'B—C2'B	114.3 (3)
C5A—C7A—H7C	109.5	O4'B—C1'B—H1'B	109.9
H7A—C7A—H7C	109.5	N1B—C1'B—H1'B	109.9
H7B—C7A—H7C	109.5	C2'B—C1'B—H1'B	109.9
O4'A—C1'A—N1A	108.5 (3)	C3'B—C2'B—C1'B	110.6 (4)
O4'A—C1'A—C2'A	103.7 (3)	C3'B—C2'B—H2'B	124.7
N1A—C1'A—C2'A	114.7 (3)	C1'B—C2'B—H2'B	124.7
O4'A—C1'A—H1'A	109.9	C2'B—C3'B—C4'B	112.2 (4)
N1A—C1'A—H1'A	109.9	C2'B—C3'B—H3'B	123.9
C2'A—C1'A—H1'A	109.9	C4'B—C3'B—H3'B	123.9
C3'A—C2'A—C1'A	110.2 (4)	O4'B—C4'B—C3'B	101.7 (3)
C3'A—C2'A—H2'A	124.9	O4'B—C4'B—C5'C	113 (2)
C1'A—C2'A—H2'A	124.9	C3'B—C4'B—C5'C	101.1 (13)
C2'A—C3'A—C4'A	110.7 (4)	O4'B—C4'B—C5'B	109.9 (7)
C2'A—C3'A—H3'A	124.6	C3'B—C4'B—C5'B	119.6 (6)
C4'A—C3'A—H3'A	124.6	C5'C—C4'B—C5'B	18.8 (12)
O4'A—C4'A—C5'A	111.3 (4)	O4'B—C4'B—H4'B	108.4
O4'A—C4'A—C3'A	103.2 (3)	C3'B—C4'B—H4'B	108.4
C5'A—C4'A—C3'A	116.3 (4)	C5'C—C4'B—H4'B	121.5
O4'A—C4'A—H4'A	108.6	C5'B—C4'B—H4'B	108.4
C5'A—C4'A—H4'A	108.6	C1'B—O4'B—C4'B	111.2 (3)
C3'A—C4'A—H4'A	108.6	O5'B—C5'B—C4'B	113.9 (6)
C1'A—O4'A—C4'A	111.7 (3)	O5'B—C5'B—H5'D	108.8
O5'A—C5'A—C4'A	112.1 (4)	C4'B—C5'B—H5'D	108.8
O5'A—C5'A—H5'A	109.2	O5'B—C5'B—H5'E	108.8
C4'A—C5'A—H5'A	109.2	C4'B—C5'B—H5'E	108.8
O5'A—C5'A—H5'B	109.2	H5'D—C5'B—H5'E	107.7
C4'A—C5'A—H5'B	109.2	C5'B—O5'B—H5'F	109.5
H5'A—C5'A—H5'B	107.9	O5'C—C5'C—C4'B	126.6 (14)
C5'A—O5'A—H5'C	109.5	O5'C—C5'C—H5'G	105.7
C2B—N1B—C6B	120.2 (3)	C4'B—C5'C—H5'G	105.7
C2B—N1B—C1'B	119.5 (3)	O5'C—C5'C—H5'H	105.7
C6B—N1B—C1'B	120.3 (3)	C4'B—C5'C—H5'H	105.7
O2B—C2B—N3B	121.9 (3)	H5'G—C5'C—H5'H	106.1
O2B—C2B—N1B	122.5 (3)	C5'C—O5'C—H5'I	109.5
N3B—C2B—N1B	115.6 (3)
C6A—N1A—C2A—O2A	178.1 (4)	C1'B—N1B—C2B—N3B	173.5 (3)
C1'A—N1A—C2A—O2A	−15.0 (5)	O2B—C2B—N3B—C4B	−176.7 (4)
C6A—N1A—C2A—N3A	−2.6 (5)	N1B—C2B—N3B—C4B	3.0 (5)
C1'A—N1A—C2A—N3A	164.3 (3)	C2B—N3B—C4B—O4B	179.9 (4)
O2A—C2A—N3A—C4A	178.6 (3)	C2B—N3B—C4B—C5B	0.0 (5)
N1A—C2A—N3A—C4A	−0.7 (5)	O4B—C4B—C5B—C6B	178.0 (4)
C2A—N3A—C4A—O4A	−174.6 (3)	N3B—C4B—C5B—C6B	−2.2 (5)
C2A—N3A—C4A—C5A	5.8 (5)	O4B—C4B—C5B—C7B	−2.5 (5)
O4A—C4A—C5A—C6A	172.8 (4)	N3B—C4B—C5B—C7B	177.4 (3)
N3A—C4A—C5A—C6A	−7.8 (5)	C4B—C5B—C6B—N1B	1.3 (6)
O4A—C4A—C5A—C7A	−5.4 (6)	C7B—C5B—C6B—N1B	−178.3 (3)
N3A—C4A—C5A—C7A	174.1 (4)	C2B—N1B—C6B—C5B	2.0 (6)
C4A—C5A—C6A—N1A	5.3 (6)	C1'B—N1B—C6B—C5B	−175.5 (4)
C7A—C5A—C6A—N1A	−176.7 (4)	C2B—N1B—C1'B—O4'B	−117.2 (4)
C2A—N1A—C6A—C5A	0.2 (6)	C6B—N1B—C1'B—O4'B	60.3 (4)
C1'A—N1A—C6A—C5A	−166.5 (4)	C2B—N1B—C1'B—C2'B	127.1 (4)
C2A—N1A—C1'A—O4'A	−102.1 (3)	C6B—N1B—C1'B—C2'B	−55.4 (5)
C6A—N1A—C1'A—O4'A	65.0 (4)	O4'B—C1'B—C2'B—C3'B	3.7 (4)
C2A—N1A—C1'A—C2'A	142.6 (4)	N1B—C1'B—C2'B—C3'B	122.2 (4)
C6A—N1A—C1'A—C2'A	−50.3 (5)	C1'B—C2'B—C3'B—C4'B	−0.6 (5)
O4'A—C1'A—C2'A—C3'A	4.7 (5)	C2'B—C3'B—C4'B—O4'B	−2.7 (5)
N1A—C1'A—C2'A—C3'A	122.8 (4)	C2'B—C3'B—C4'B—C5'C	−119.8 (18)
C1'A—C2'A—C3'A—C4'A	−1.2 (6)	C2'B—C3'B—C4'B—C5'B	−123.8 (7)
C2'A—C3'A—C4'A—O4'A	−2.9 (5)	N1B—C1'B—O4'B—C4'B	−127.6 (3)
C2'A—C3'A—C4'A—C5'A	−125.0 (4)	C2'B—C1'B—O4'B—C4'B	−5.5 (4)
N1A—C1'A—O4'A—C4'A	−129.0 (3)	C3'B—C4'B—O4'B—C1'B	5.1 (4)
C2'A—C1'A—O4'A—C4'A	−6.7 (4)	C5'C—C4'B—O4'B—C1'B	112.9 (10)
C5'A—C4'A—O4'A—C1'A	131.4 (3)	C5'B—C4'B—O4'B—C1'B	132.8 (5)
C3'A—C4'A—O4'A—C1'A	6.0 (4)	O4'B—C4'B—C5'B—O5'B	−55.0 (11)
O4'A—C4'A—C5'A—O5'A	−67.3 (5)	C3'B—C4'B—C5'B—O5'B	62.0 (13)
C3'A—C4'A—C5'A—O5'A	50.5 (6)	C5'C—C4'B—C5'B—O5'B	50 (7)
C6B—N1B—C2B—O2B	175.8 (4)	O4'B—C4'B—C5'C—O5'C	−76 (4)
C1'B—N1B—C2B—O2B	−6.7 (6)	C3'B—C4'B—C5'C—O5'C	32 (5)
C6B—N1B—C2B—N3B	−3.9 (5)	C5'B—C4'B—C5'C—O5'C	−159 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3A—H3A···O2B	0.86	1.98	2.823 (4)	168
N3B—H3B···O4A	0.86	2.04	2.890 (4)	172
O5′A—H5′C···O5′C^i	0.82	1.86	2.674 (13)	171
O5′B—H5′F···O5′A^ii	0.82	2.10	2.870 (6)	156
O5′C—H5′I···O4′B^iii	0.82	2.15	2.959 (14)	167

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