A novel Janus-type AT nucleoside with benzoyl protecting groups forming a pleated-sheet structure

The title compound, 5-amino-8-(2,3,5-tri-O-benzoyl-[beta]-D-ribofuranosyl)pyrimido[4,5-d]pyrimidine-2,4(3H,8H)-dione methanol monosolvate, C₃₂H₂₅N₅O₉·CH₄O, which crystallized slowly from methanol, exhibits an anti conformation with a glycosyl-bond torsion angle of [chi] = -141.28 (17)°. The furan­ose moiety adopts an N-type sugar puckering (³T₄). The corresponding pseudo­rotation phase angle and maximum amplitude are P = 24.5 (2)° and [tau]_m = 38.3 (2)°, respectively. In the solid state, one methanol mol­ecule acts as a bridge joining adjacent nucleoside mol­ecules head-to-head, leading to a pleated-ribbon supra­molecular structure, with the base moieties located in the centre of the ribbon and the sugar residues protruding to the outside of the layers, as in a DNA helix. The pleated-ribbon supra­molecular structure is tethered together into a two-dimensional infinite pleated-sheet structure through aromatic stacking between the nucleobase planes and the benzene rings of the benzoyl protecting groups on the 5'-OH group of furanose.

S1. Comment

Recently, a novel Janus-type GC (J-GC) nucleoside, (II) (from the two-faced Roman god Janus), has been synthesized in our laboratory which showed antiviral potential (Yang et al., 2011). The base moiety of J-GC has one face with a Watson–Crick donor–donor–acceptor (DDA) hydrogen-bond array of guanine and the other face with an acceptor–acceptor–donor (AAD) hydrogen-bond array of cytosine. In principle, J-GC could pair with cytidine or guanosine via rotation of the glycosyl bond. At the same time, this J-GC nucleoside can also associate through self-supplementary hydrogen-bond formation. This property has been employed to construct nano-architectures such as trimers (Sessler et al., 2003), rosettes (Marsh et al., 1996; Fenniri et al., 2001) and regular noncovalent polymer arrays (Asadi et al., 2007' Marsh et al., 1994). In order to make full use of these properties to generate different supramolecular structures in the field of nucleosides and oligonucleotides, we wish to expand these Janus nucleosides from a tridentate GC series to a bidentate AT series. Very few structures with the Janus-type AT base moiety have been reported (Tominaga et al., 1991; Asadi et al., 2007). Consequently, we synthesized the Janus-type AT nucleoside (J-AT),; the full synthetic route will be reported elsewhere. The base moiety of J-AT has one face with a Watson–Crick acceptor–donor (AD) hydrogen-bond array of adenine and the other face with a donor–acceptor (DA) hydrogen-bond array of thymine. Interestingly, we have found for the first time that the solid-state structure of the benzolyted J-AT nucleoside, (I), can form a pleated sheet suprastructure, findings which we report in this paper. The expecting hydrogen-bonds patterns of compound (I) and (II) are shown in the scheme (the arrows of A represent the hydrogen bond acceptors; the arrows of D represent the hydrogen bond donors).

The single-crystal of compound (I) was obtained by dissolving it in hot methanol and cooling slowly to room temperature in an incubator, giving colourless needle crystals suitable for single-crystal X-ray diffraction. The structure of compound (I) is shown in Fig. 1, selected geometric parameters are listed in Table 1 and the hydrogen-bond geometry is listed in Table 2.

The pyrimido[4,5-d]pyrimidine ring is almost planar. For the thymine pyrimidine ring, the deviations of the ring atoms from the least-squares plane (N1/C2/N3/C4/C10/C9) range from -0.009 (2) (C2) to 0.016 (1) Å (N1), with an r.m.s. deviation of 0.010 Å. The exocyclic atoms N11, O12, O13 and the C1' substituent group deviate from this plane with distances of -0.135 (4), 0.067 (3), -0.043 (3) and -0.189 (4) Å. For the adenine pyrimidine ring, the deviations of the ring atoms from the least-squares plane (C10/C9/N8/C7/N6/C5) range from -0.017 (1) (C5) to 0.012 (1) (C10) Å, with an r.m.s. deviation of 0.011 Å. The deviations of exocyclic atoms N11, O12 and O13 from this ring are -0.135 (4), 0.055 (4) and -0.129 (4) Å, respectively. The dihedral angle between the two rings is 1.62 (11)°. Therefore, the parameters of each ring of the pyrimido[4,5-d]pyrimidine are quite close to those of canonical adenine (Lai & Marsh, 1972) and thymine (Ozeki et al., 1969). The orientation of the nucleobase relative to the sugar ring (anti/syn conformation) in a normal N9-glycosylated purine nucleoside system is defined by the torsion angle χ (O4'—C1'—N9— C4) (IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983).When the pyrimidine ring of the purine is located outside of the sugar plane, the conformation is defined as anti; on the other hand, when the pyrimidine ring of purine is located inside of the sugar plane, the conformation is defined as syn. In the case of compound (I), the anti/syn conformation is also defined by the torsion angle χ (O4'—C1'—N8— C9) correspondingly which is -141.28 (17)°, with the thymine ring located outside the sugar ring. Therefore, compound (I) adopts an anti conformation. Another conformational parameter of interest is the puckering of the ribofuranose moiety which is defined by the pseudorotation phase angle and the maximum puckering amplitude (Altona & Sundaralingam, 1972). The values of these two parameters are P = 25.5 (2)°, τ_m = 38.3 (2)°, respectively. The corresponding sugar puckering mode is an asymmetrical twist of ³T ₄ in the North (3'-endo) region, which is in the normal range of the pyrimidine or purine ribonucleoside system. The orientation of the exocyclic 5'-hydroxyl group relative to the ribofuranose ring is characterized by the torsion angle γ (O5'—C5'—C4'—C3'), which is 57.3 (3)° for compound (I) corresponding to the +sc (gauche) conformation.

A very interesting phenomenon is that the intermolecular connection of compound (I) is not mediated through self-complementary Watson–Crick base pairs as proposed in J-GC base pairs (Fenniri et al., 2001; Marsh et al., 1996; Yang et al., 2011) (scheme). The crystal cell of compound (I) consists of four nucleoside molecules and four methanol molecules (Fig. 2). There are seven hydrogen bonds on one nucleoside molecule which ware displayed in Fig.3. Six of them are intermolecular hydrogen bonds: O10—H10···O13, N3—H3···N6, N11—H11A···O7', N11—H11B···O10, N6···H3—N3 and O7'···H11A—N11. The remaining one is an intramolecular hydrogen bond formed between the N11—H11A and O12. Four intermolecular hydrogen bonds act as the repeated units connecting adjacent nucleosides head to head in an anti-parallel way to form a wavy ribbon in one layer (Fig. 4). The hydrogen bond N3—H3···N6 is not shown owing to the large distance between the H3 and N6 atoms. Three of them are highlighted in the red rectangle in Fig. 4: the first one is formed between the H atom of the exocyclic amino group of one nucleoside molecule and the O atom of the benzoyl group of the former nucleoside molecule; the second hydrogen bond is formed between the H atom of the exocyclic amino group of the nucleoside molecule and the O atom of the methanol molecule; the third one is formed between the H atom of the same methanol molecule and the exocyclic oxygen of the next nucleoside molecule. This wavy ribbon forms a three-dimensional pleated sheet structure when viewed along the [001] orientation as shown in Fig. 5. This arrangement is quite different from the flattened structure reported for 5,7-diamino-1-heptylpyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione and 5,7-diamino-1-butyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione (Asadi et al., 2007). In this pleated sheet structure, the base moieties are located inside and the sugar residues located outside (see Fig. 4) as in a DNA helix. Finally, the layers are tethered together in a parallel fashion [ok as edited?] and stretched in all directions to form an infinite three-dimensional wall through short contacts. Whether the special pleated sheet structure exists in [at the?] RNA (or DNA) level will be explored in future studies.

Related literature

For related literature, see: Altona & Sundaralingam (1972); Asadi et al. (2007); Fenniri et al. (2001); IUPAC–IUB Joint Commission on Biochemical Nomenclature (1983); Lai & Marsh (1972); Marsh et al. (1994, 1996); Ozeki et al. (1969); Sessler et al. (2003); Tominaga et al. (1991); Yang et al. (2011).

S2. Experimental

Compound (I) was dissolved in methanol at 323 K, and slowly cooled in steps of 0.5 K h^-1 to ambient temperature in an incubator, giving colourless needle crystals suitable for single-crystal X-ray diffraction. The crystal of compound (I) was protected in the mother liquor in a tiny glass tube and the epoxy resin was used to minimize the loss of the solvent.

S3. Refinement

In the absence of suitable anomalous scattering, Friedel equivalents cannot be used to determine the absolute structure.The Flack parameter leads to an inconclusive value [the Flack parameter is 0.3 (9)]. The known configuration of the D-ribofuranose derivatives was used to define the enantiomer employed in the refined model. All H atoms were placed in geometrically idealized positions and treated as riding. For the OH and CH₃ groups, the O—H distance is 0.82 Å, and the C—H distance is 0.96 Å, with U_iso(H) = 1.5U_eq(O, C). For the remaining groups, the C—H distance is 0.93–0.98 Å and the N—H distance is 0.857–0.874 Å, with U_iso(H) = 1.2U_eq (C, N).

Computing details

Data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell refinement: CrysAlis PRO (Oxford Diffraction, 2010); data reduction: CrysAlis PRO (Oxford Diffraction, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures

	Fig. 1. A perspective view of compound (I), showing the atom-labelling scheme and the intramolecular hydrogen bond (dashed line). Displacement ellipsoids are drawn at the 30% probability level. H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. An arrangement of the nucleoside and methanol molecules in the crystal cell of compound (I), viewed along [100]. The hydrogen bonds have been omitted for clarity.
	Fig. 3. A detailed view of the hydrogen bonds on one nucleoside molecule. Hydrogen bonds are indicated by dashed lines; the bifurcated hydrogen bonds are shown in green and the hydrogen bonds with large distances are shown in yellow. The remaining hydrogen bonds are shown in black. H atoms in compound (I) and some groups which are not involved in hydrogen bonds have been omitted for clarity. Atoms are coded as follows: red, oxygen; blue, nitrogen; grey, carbon; white, hydrogen.
	Fig. 4. A packing diagram of compound (I) viewed along [100]. Hydrogen bonds are indicated by dashed lines. The hydrogen-bond motif in the red rectangle frame is the repeated unit. H atoms have been omitted for clarity.
	Fig. 5. A four-layered packing diagram of compound (I), viewed along [001]. H atoms and short contacts have been omitted for clarity.

5-amino-8-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrimido[4,5- d]pyrimidine-2,4(3H,8H)-dione methanol monosolvate

Crystal data

C32H25N5O9·CH4O	F(000) = 1368
Mr = 655.61	Dx = 1.372 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.7107 Å
Hall symbol: P 2ac 2ab	Cell parameters from 4443 reflections
a = 8.2526 (3) Å	θ = 3.0–28.6°
b = 11.9486 (4) Å	µ = 0.10 mm^−1
c = 32.1865 (10) Å	T = 293 K
V = 3173.82 (18) Å^3	Block, colourless
Z = 4	0.42 × 0.36 × 0.20 mm

Data collection

Xcalibur, Eos diffractometer	6101 independent reflections
Radiation source: fine-focus sealed tube	4128 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.019
Detector resolution: 16.0874 pixels mm^-1	θmax = 26.4°, θmin = 3.0°
ω scans	h = −5→10
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm	k = −12→14
Tmin = 0.443, Tmax = 1.0	l = −40→37
9151 measured reflections

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)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.093	w = 1/[σ^2(Fo^2) + (0.0545P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.91	(Δ/σ)max = 0.001
6101 reflections	Δρmax = 0.20 e Å^−3
441 parameters	Δρmin = −0.17 e Å^−3
4 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.3 (9)

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
O1'	−0.1064 (2)	0.9166 (2)	0.57869 (5)	0.0981 (7)
O2'	0.16180 (18)	0.92186 (14)	0.57869 (4)	0.0602 (4)
O3'	0.30283 (19)	1.11731 (12)	0.59472 (4)	0.0536 (4)
O4'	0.41924 (18)	0.86301 (12)	0.64316 (4)	0.0509 (4)
O5'	0.59502 (18)	1.03297 (12)	0.68253 (4)	0.0574 (4)
O6'	0.7952 (4)	0.9171 (3)	0.69536 (6)	0.1580 (14)
O7'	0.0843 (3)	1.19406 (17)	0.62259 (5)	0.0988 (7)
O10	0.7211 (3)	1.35557 (18)	0.62921 (7)	0.1071 (7)
H10	0.7564	1.4195	0.6272	0.161*
O12	−0.1258 (2)	0.60344 (14)	0.77627 (4)	0.0688 (5)
O13	−0.1604 (2)	0.56157 (16)	0.63710 (5)	0.0849 (6)
N1	0.0126 (2)	0.69619 (14)	0.65928 (5)	0.0478 (4)
N3	−0.1379 (2)	0.58429 (16)	0.70634 (5)	0.0551 (5)
H3	−0.2080	0.5317	0.7094	0.066*
N6	0.2396 (2)	0.85321 (14)	0.75736 (5)	0.0477 (4)
N8	0.1959 (2)	0.82240 (13)	0.68565 (4)	0.0425 (4)
N11	0.1053 (2)	0.74897 (16)	0.80589 (5)	0.0535 (5)
C1	0.0181 (3)	0.91044 (19)	0.56044 (6)	0.0534 (5)
C1'	0.2495 (3)	0.84454 (18)	0.64265 (5)	0.0482 (5)
H1'	0.2267	0.7784	0.6256	0.058*
C2	−0.0961 (3)	0.6135 (2)	0.66577 (6)	0.0557 (6)
C2'	0.1714 (3)	0.94616 (18)	0.62242 (5)	0.0472 (5)
H2'	0.0675	0.9676	0.6349	0.057*
C3	0.0371 (3)	0.88356 (18)	0.51572 (6)	0.0517 (5)
C3'	0.3025 (2)	1.03413 (17)	0.62692 (5)	0.0444 (5)
H3'	0.2981	1.0692	0.6544	0.053*
C4	−0.0764 (2)	0.63233 (18)	0.74197 (6)	0.0480 (5)
C4'	0.4559 (2)	0.96579 (18)	0.62195 (6)	0.0477 (5)
H4'	0.4707	0.9493	0.5924	0.057*
C6	0.1716 (3)	0.9130 (2)	0.49378 (7)	0.0738 (8)
H6	0.2543	0.9526	0.5068	0.089*
C5'	0.6121 (3)	1.0112 (2)	0.63873 (7)	0.0624 (6)
H5'B	0.6985	0.9574	0.6342	0.075*
H5'A	0.6402	1.0798	0.6243	0.075*
C8	0.1863 (4)	0.8843 (3)	0.45209 (7)	0.0890 (9)
H8	0.2783	0.9052	0.4373	0.107*
C7	0.2670 (3)	0.87387 (17)	0.71838 (6)	0.0479 (5)
H7	0.3427	0.9292	0.7124	0.057*
C11	0.0678 (4)	0.8266 (3)	0.43322 (8)	0.0859 (9)
H11	0.0783	0.8069	0.4054	0.103*
C9	0.0778 (2)	0.74186 (15)	0.69249 (6)	0.0387 (5)
C10	0.0425 (2)	0.71700 (16)	0.73433 (6)	0.0399 (4)
C12	−0.0664 (4)	0.7970 (3)	0.45441 (10)	0.1094 (12)
H12	−0.1478	0.7566	0.4412	0.131*
C13	−0.0833 (4)	0.8267 (3)	0.49569 (8)	0.0894 (9)
H13	−0.1774	0.8078	0.5099	0.107*
C14	0.1853 (3)	1.19359 (19)	0.59607 (6)	0.0553 (6)
C15	0.1917 (3)	1.27433 (18)	0.56114 (6)	0.0526 (5)
C16	0.0966 (3)	1.3687 (2)	0.56331 (8)	0.0733 (7)
H16	0.0312	1.3814	0.5864	0.088*
C17	0.0994 (4)	1.4443 (3)	0.53078 (10)	0.0908 (9)
H17	0.0370	1.5090	0.5323	0.109*
C18	0.1920 (4)	1.4253 (3)	0.49675 (9)	0.0922 (9)
H18	0.1910	1.4762	0.4749	0.111*
C19	0.2850 (4)	1.3335 (3)	0.49442 (8)	0.0868 (9)
H19	0.3484	1.3212	0.4710	0.104*
C20	0.2875 (3)	1.2568 (2)	0.52666 (7)	0.0687 (7)
H20	0.3534	1.1938	0.5251	0.082*
C21	0.6937 (3)	0.9786 (2)	0.70792 (8)	0.0707 (7)
C22	0.6645 (3)	1.0037 (2)	0.75222 (7)	0.0590 (6)
C23	0.5612 (3)	1.0867 (2)	0.76491 (8)	0.0653 (6)
H23	0.5041	1.1289	0.7455	0.078*
C24	0.5428 (3)	1.1070 (3)	0.80733 (10)	0.0811 (9)
H24	0.4734	1.1632	0.8164	0.097*
C25	0.6271 (4)	1.0439 (3)	0.83574 (10)	0.0969 (10)
H25	0.6149	1.0576	0.8640	0.116*
C26	0.7278 (4)	0.9620 (3)	0.82271 (10)	0.1052 (11)
H26	0.7844	0.9196	0.8421	0.126*
C27	0.7475 (4)	0.9407 (3)	0.78108 (8)	0.0878 (9)
H27	0.8166	0.8838	0.7724	0.105*
C28	0.6092 (6)	1.3387 (3)	0.60040 (14)	0.1419 (16)
H28A	0.6491	1.2862	0.5803	0.213*
H28B	0.5845	1.4083	0.5869	0.213*
H28C	0.5130	1.3094	0.6131	0.213*
C5	0.1272 (2)	0.77177 (16)	0.76612 (6)	0.0414 (5)
H11B	0.160 (2)	0.7844 (15)	0.8251 (5)	0.050*
H11A	0.034 (2)	0.7008 (15)	0.8132 (6)	0.050*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1'	0.0547 (10)	0.190 (2)	0.0499 (10)	0.0053 (13)	0.0024 (9)	−0.0181 (12)
O2'	0.0529 (9)	0.1033 (12)	0.0245 (7)	−0.0130 (9)	0.0018 (7)	−0.0056 (7)
O3'	0.0575 (9)	0.0618 (9)	0.0415 (8)	0.0022 (9)	0.0098 (7)	0.0117 (7)
O4'	0.0526 (9)	0.0574 (9)	0.0426 (8)	0.0039 (8)	0.0160 (7)	0.0041 (6)
O5'	0.0494 (8)	0.0704 (10)	0.0525 (9)	0.0050 (8)	−0.0048 (7)	−0.0061 (7)
O6'	0.168 (2)	0.237 (3)	0.0693 (14)	0.146 (3)	−0.0011 (15)	−0.0096 (15)
O7'	0.1211 (16)	0.1150 (15)	0.0604 (11)	0.0562 (14)	0.0485 (12)	0.0290 (10)
O10	0.130 (2)	0.0960 (16)	0.0952 (15)	−0.0033 (15)	−0.0450 (14)	0.0166 (12)
O12	0.0765 (11)	0.0941 (12)	0.0357 (9)	−0.0300 (9)	0.0116 (7)	0.0062 (7)
O13	0.0976 (13)	0.1168 (14)	0.0404 (9)	−0.0545 (12)	−0.0191 (9)	0.0028 (9)
N1	0.0548 (11)	0.0605 (10)	0.0281 (9)	−0.0089 (10)	−0.0031 (8)	0.0021 (7)
N3	0.0507 (10)	0.0760 (13)	0.0384 (10)	−0.0207 (10)	−0.0039 (8)	0.0075 (8)
N6	0.0581 (10)	0.0558 (10)	0.0294 (9)	−0.0081 (9)	0.0068 (8)	−0.0051 (7)
N8	0.0525 (10)	0.0470 (9)	0.0281 (8)	−0.0059 (9)	0.0089 (7)	−0.0022 (7)
N11	0.0605 (12)	0.0708 (13)	0.0291 (10)	−0.0150 (10)	0.0037 (9)	0.0011 (8)
C1	0.0525 (13)	0.0724 (14)	0.0354 (12)	−0.0049 (12)	−0.0023 (11)	0.0051 (10)
C1'	0.0604 (13)	0.0589 (13)	0.0251 (10)	−0.0102 (11)	0.0131 (10)	−0.0065 (9)
C2	0.0548 (13)	0.0764 (16)	0.0360 (12)	−0.0115 (13)	−0.0089 (10)	0.0061 (11)
C2'	0.0479 (11)	0.0712 (14)	0.0225 (10)	−0.0062 (11)	0.0069 (9)	−0.0019 (9)
C3	0.0615 (13)	0.0586 (13)	0.0350 (11)	−0.0021 (12)	−0.0054 (10)	0.0038 (9)
C3'	0.0524 (12)	0.0535 (12)	0.0273 (10)	0.0016 (11)	0.0049 (9)	0.0031 (8)
C4	0.0460 (11)	0.0621 (13)	0.0358 (12)	−0.0035 (11)	0.0005 (10)	0.0038 (10)
C4'	0.0494 (12)	0.0620 (14)	0.0317 (11)	−0.0031 (11)	0.0088 (9)	0.0063 (9)
C6	0.0789 (17)	0.110 (2)	0.0328 (12)	−0.0239 (17)	−0.0004 (12)	0.0013 (12)
C5'	0.0520 (13)	0.0878 (17)	0.0473 (14)	−0.0057 (14)	0.0080 (11)	0.0096 (12)
C8	0.102 (2)	0.130 (2)	0.0347 (13)	−0.020 (2)	0.0072 (14)	0.0055 (14)
C7	0.0572 (13)	0.0503 (12)	0.0360 (11)	−0.0104 (11)	0.0107 (10)	−0.0066 (9)
C11	0.124 (3)	0.101 (2)	0.0329 (14)	−0.008 (2)	−0.0099 (16)	−0.0077 (13)
C9	0.0410 (11)	0.0436 (11)	0.0314 (10)	0.0062 (10)	0.0017 (8)	0.0003 (8)
C10	0.0394 (10)	0.0517 (11)	0.0286 (10)	0.0000 (10)	0.0022 (8)	0.0016 (8)
C12	0.116 (3)	0.154 (3)	0.0585 (19)	−0.049 (3)	−0.0145 (19)	−0.0302 (19)
C13	0.089 (2)	0.124 (2)	0.0557 (17)	−0.037 (2)	−0.0013 (15)	−0.0134 (15)
C14	0.0626 (14)	0.0664 (14)	0.0369 (12)	0.0045 (14)	0.0046 (11)	0.0025 (10)
C15	0.0566 (13)	0.0593 (14)	0.0418 (12)	0.0017 (13)	−0.0050 (10)	0.0051 (9)
C16	0.0741 (17)	0.0850 (18)	0.0609 (16)	0.0140 (16)	0.0026 (13)	0.0083 (13)
C17	0.087 (2)	0.087 (2)	0.098 (2)	0.0224 (18)	−0.0055 (19)	0.0323 (17)
C18	0.0802 (19)	0.110 (2)	0.086 (2)	−0.002 (2)	−0.0038 (17)	0.0500 (18)
C19	0.088 (2)	0.110 (2)	0.0619 (17)	0.005 (2)	0.0180 (15)	0.0303 (15)
C20	0.0750 (17)	0.0809 (17)	0.0502 (14)	0.0094 (15)	0.0115 (13)	0.0152 (12)
C21	0.0602 (15)	0.0870 (18)	0.0650 (16)	0.0250 (16)	−0.0012 (13)	−0.0045 (13)
C22	0.0460 (12)	0.0753 (15)	0.0557 (14)	0.0013 (13)	−0.0022 (11)	−0.0097 (11)
C23	0.0452 (12)	0.0763 (16)	0.0744 (18)	−0.0063 (13)	−0.0034 (12)	−0.0185 (14)
C24	0.0580 (16)	0.102 (2)	0.084 (2)	−0.0157 (16)	0.0078 (15)	−0.0399 (17)
C25	0.090 (2)	0.137 (3)	0.064 (2)	−0.027 (2)	0.0082 (18)	−0.022 (2)
C26	0.103 (2)	0.145 (3)	0.067 (2)	0.003 (3)	−0.0120 (18)	0.0083 (19)
C27	0.0834 (19)	0.116 (2)	0.0638 (18)	0.0215 (18)	−0.0092 (16)	−0.0017 (15)
C28	0.150 (3)	0.089 (2)	0.187 (4)	−0.028 (3)	−0.069 (3)	−0.009 (3)
C5	0.0443 (11)	0.0504 (12)	0.0294 (10)	0.0019 (10)	0.0050 (9)	0.0006 (8)

Geometric parameters (Å, º)

O1'—C1	1.186 (3)	C6—C8	1.390 (3)
O2'—C1	1.331 (3)	C5'—H5'B	0.9700
O2'—C2'	1.439 (2)	C5'—H5'A	0.9700
O3'—C3'	1.436 (2)	C8—H8	0.9300
O3'—C14	1.332 (3)	C8—C11	1.342 (4)
O4'—C1'	1.418 (3)	C7—H7	0.9300
O4'—C4'	1.437 (2)	C11—H11	0.9300
O5'—C5'	1.441 (2)	C11—C12	1.348 (4)
O5'—C21	1.324 (3)	C9—C10	1.409 (2)
O6'—C21	1.186 (3)	C10—C5	1.401 (3)
O7'—C14	1.193 (3)	C12—H12	0.9300
O10—H10	0.8200	C12—C13	1.382 (4)
O10—C28	1.324 (4)	C13—H13	0.9300
O12—C4	1.226 (2)	C14—C15	1.482 (3)
O13—C2	1.232 (2)	C15—C16	1.375 (3)
N1—C2	1.351 (3)	C15—C20	1.379 (3)
N1—C9	1.315 (2)	C16—H16	0.9300
N3—H3	0.8600	C16—C17	1.384 (4)
N3—C2	1.395 (3)	C17—H17	0.9300
N3—C4	1.379 (3)	C17—C18	1.355 (4)
N6—C7	1.299 (2)	C18—H18	0.9300
N6—C5	1.373 (2)	C18—C19	1.341 (4)
N8—C1'	1.477 (2)	C19—H19	0.9300
N8—C7	1.354 (2)	C19—C20	1.384 (3)
N8—C9	1.387 (2)	C20—H20	0.9300
N11—C5	1.321 (2)	C21—C22	1.477 (3)
N11—H11B	0.874 (13)	C22—C23	1.370 (3)
N11—H11A	0.857 (13)	C22—C27	1.378 (3)
C1—C3	1.483 (3)	C23—H23	0.9300
C1'—H1'	0.9800	C23—C24	1.395 (4)
C1'—C2'	1.521 (3)	C24—H24	0.9300
C2'—H2'	0.9800	C24—C25	1.374 (4)
C2'—C3'	1.516 (3)	C25—H25	0.9300
C3—C6	1.362 (3)	C25—C26	1.350 (4)
C3—C13	1.366 (3)	C26—H26	0.9300
C3'—H3'	0.9800	C26—C27	1.374 (4)
C3'—C4'	1.515 (3)	C27—H27	0.9300
C4—C10	1.431 (3)	C28—H28A	0.9600
C4'—H4'	0.9800	C28—H28B	0.9600
C4'—C5'	1.500 (3)	C28—H28C	0.9600
C6—H6	0.9300
O1'—C1—O2'	123.2 (2)	C5'—C4'—H4'	108.4
O1'—C1—C3	125.9 (2)	H5'B—C5'—H5'A	108.2
O2'—C1—C3	110.87 (19)	C8—C6—H6	119.7
O2'—C2'—C1'	106.31 (16)	C8—C11—H11	119.8
O2'—C2'—H2'	113.8	C8—C11—C12	120.3 (3)
O2'—C2'—C3'	105.82 (14)	C7—N6—C5	116.79 (17)
O3'—C3'—C2'	114.34 (16)	C7—N8—C1'	121.17 (17)
O3'—C3'—H3'	110.9	C7—N8—C9	119.77 (15)
O3'—C3'—C4'	107.17 (15)	C11—C8—C6	120.0 (3)
O3'—C14—C15	113.23 (19)	C11—C8—H8	120.0
O4'—C1'—N8	108.26 (17)	C11—C12—H12	119.9
O4'—C1'—H1'	108.8	C11—C12—C13	120.1 (3)
O4'—C1'—C2'	107.43 (17)	C9—N1—C2	116.70 (16)
O4'—C4'—C3'	103.57 (15)	C9—N8—C1'	118.92 (15)
O4'—C4'—H4'	108.4	C9—C10—C4	117.05 (17)
O4'—C4'—C5'	108.58 (17)	C12—C11—H11	119.8
O5'—C5'—C4'	109.49 (16)	C12—C13—H13	119.7
O5'—C5'—H5'B	109.8	C13—C3—C1	119.3 (2)
O5'—C5'—H5'A	109.8	C13—C12—H12	119.9
O5'—C21—C22	113.3 (2)	C14—O3'—C3'	116.66 (16)
O6'—C21—O5'	121.9 (2)	C15—C16—H16	120.4
O6'—C21—C22	124.8 (2)	C15—C16—C17	119.2 (3)
O7'—C14—O3'	122.4 (2)	C15—C20—C19	119.6 (3)
O7'—C14—C15	124.4 (2)	C15—C20—H20	120.2
O10—C28—H28A	109.5	C16—C15—C14	118.3 (2)
O10—C28—H28B	109.5	C16—C15—C20	119.5 (2)
O10—C28—H28C	109.5	C16—C17—H17	119.6
O12—C4—N3	120.61 (18)	C17—C16—H16	120.4
O12—C4—C10	125.56 (19)	C17—C18—H18	119.8
O13—C2—N1	122.58 (19)	C18—C17—C16	120.7 (3)
O13—C2—N3	117.9 (2)	C18—C17—H17	119.6
N1—C2—N3	119.49 (18)	C18—C19—H19	119.7
N1—C9—N8	116.50 (16)	C18—C19—C20	120.5 (3)
N1—C9—C10	127.21 (18)	C19—C18—C17	120.4 (3)
N3—C4—C10	113.82 (17)	C19—C18—H18	119.8
N6—C7—N8	126.13 (19)	C19—C20—H20	120.2
N6—C7—H7	116.9	C20—C15—C14	122.1 (2)
N6—C5—C10	121.19 (16)	C20—C19—H19	119.7
N8—C1'—H1'	108.8	C21—O5'—C5'	117.06 (18)
N8—C1'—C2'	114.64 (16)	C22—C23—H23	120.5
N8—C7—H7	116.9	C22—C23—C24	119.0 (3)
N8—C9—C10	116.29 (16)	C22—C27—H27	120.1
N11—C5—N6	115.93 (17)	C23—C22—C21	122.4 (2)
N11—C5—C10	122.88 (18)	C23—C22—C27	120.3 (2)
C1—O2'—C2'	120.07 (16)	C23—C24—H24	120.0
C1'—O4'—C4'	109.59 (16)	C24—C23—H23	120.5
C1'—C2'—H2'	113.8	C24—C25—H25	119.9
C2—N3—H3	117.2	C25—C24—C23	120.1 (3)
C2'—C1'—H1'	108.8	C25—C24—H24	120.0
C2'—C3'—H3'	110.9	C25—C26—H26	119.7
C3—C6—H6	119.7	C25—C26—C27	120.7 (3)
C3—C6—C8	120.5 (2)	C26—C25—C24	120.2 (3)
C3—C13—C12	120.5 (3)	C26—C25—H25	119.9
C3—C13—H13	119.7	C26—C27—C22	119.8 (3)
C3'—C2'—C1'	102.10 (16)	C26—C27—H27	120.1
C3'—C2'—H2'	113.8	C27—C22—C21	117.3 (2)
C3'—C4'—H4'	108.4	C27—C26—H26	119.7
C4—N3—H3	117.2	C28—O10—H10	109.5
C4—N3—C2	125.67 (18)	H28A—C28—H28B	109.5
C4'—C3'—C2'	102.28 (15)	H28A—C28—H28C	109.5
C4'—C3'—H3'	110.9	H28B—C28—H28C	109.5
C4'—C5'—H5'B	109.8	C5—N11—H11B	120.9 (12)
C4'—C5'—H5'A	109.8	C5—N11—H11A	119.8 (13)
C6—C3—C1	122.2 (2)	C5—C10—C4	123.16 (17)
C6—C3—C13	118.5 (2)	C5—C10—C9	119.75 (17)
C6—C8—H8	120.0	H11B—N11—H11A	119.2 (19)
C5'—C4'—C3'	119.05 (18)
O1'—C1—C3—C6	157.8 (3)	C3'—O3'—C14—O7'	0.3 (3)
O1'—C1—C3—C13	−22.7 (4)	C3'—O3'—C14—C15	−178.42 (18)
O2'—C1—C3—C6	−25.3 (3)	C3'—C4'—C5'—O5'	57.3 (3)
O2'—C1—C3—C13	154.2 (2)	C4—N3—C2—O13	179.1 (2)
O2'—C2'—C3'—O3'	39.3 (2)	C4—N3—C2—N1	−0.5 (3)
O2'—C2'—C3'—C4'	−76.19 (17)	C4—C10—C5—N6	−179.49 (17)
O3'—C3'—C4'—O4'	−158.71 (15)	C4—C10—C5—N11	0.7 (3)
O3'—C3'—C4'—C5'	80.7 (2)	C4'—O4'—C1'—N8	−128.43 (16)
O3'—C14—C15—C16	−168.0 (2)	C4'—O4'—C1'—C2'	−4.1 (2)
O3'—C14—C15—C20	13.0 (3)	C6—C3—C13—C12	1.8 (4)
O4'—C1'—C2'—O2'	90.79 (18)	C6—C8—C11—C12	0.6 (5)
O4'—C1'—C2'—C3'	−19.90 (18)	C5'—O5'—C21—O6'	2.1 (4)
O4'—C4'—C5'—O5'	−60.7 (2)	C5'—O5'—C21—C22	−178.4 (2)
O5'—C21—C22—C23	−8.7 (3)	C8—C11—C12—C13	0.5 (6)
O5'—C21—C22—C27	172.1 (2)	C7—N6—C5—N11	177.5 (2)
O6'—C21—C22—C23	170.8 (3)	C7—N6—C5—C10	−2.3 (3)
O6'—C21—C22—C27	−8.5 (5)	C7—N8—C1'—O4'	34.4 (3)
O7'—C14—C15—C16	13.4 (4)	C7—N8—C1'—C2'	−85.5 (2)
O7'—C14—C15—C20	−165.6 (3)	C7—N8—C9—N1	179.30 (18)
O12—C4—C10—C9	−177.1 (2)	C7—N8—C9—C10	−1.5 (3)
O12—C4—C10—C5	5.2 (3)	C11—C12—C13—C3	−1.7 (5)
N1—C9—C10—C4	0.4 (3)	C9—N1—C2—O13	−177.1 (2)
N1—C9—C10—C5	178.17 (19)	C9—N1—C2—N3	2.5 (3)
N3—C4—C10—C9	1.5 (3)	C9—N8—C1'—O4'	−141.28 (17)
N3—C4—C10—C5	−176.13 (18)	C9—N8—C1'—C2'	98.8 (2)
N8—C1'—C2'—O2'	−148.86 (16)	C9—N8—C7—N6	2.3 (3)
N8—C1'—C2'—C3'	100.45 (19)	C9—C10—C5—N6	2.9 (3)
N8—C9—C10—C4	−178.65 (16)	C9—C10—C5—N11	−176.94 (19)
N8—C9—C10—C5	−0.9 (3)	C13—C3—C6—C8	−0.8 (4)
C1—O2'—C2'—C1'	114.5 (2)	C14—O3'—C3'—C2'	73.8 (2)
C1—O2'—C2'—C3'	−137.44 (19)	C14—O3'—C3'—C4'	−173.63 (17)
C1—C3—C6—C8	178.7 (3)	C14—C15—C16—C17	−179.2 (2)
C1—C3—C13—C12	−177.7 (3)	C14—C15—C20—C19	178.1 (2)
C1'—O4'—C4'—C3'	26.60 (19)	C15—C16—C17—C18	1.3 (5)
C1'—O4'—C4'—C5'	154.05 (16)	C16—C15—C20—C19	−0.9 (4)
C1'—N8—C7—N6	−173.4 (2)	C16—C17—C18—C19	−1.3 (5)
C1'—N8—C9—N1	−4.9 (3)	C17—C18—C19—C20	0.2 (5)
C1'—N8—C9—C10	174.23 (18)	C18—C19—C20—C15	0.9 (5)
C1'—C2'—C3'—O3'	150.34 (16)	C20—C15—C16—C17	−0.2 (4)
C1'—C2'—C3'—C4'	34.87 (17)	C21—O5'—C5'—C4'	120.2 (2)
C2—N1—C9—N8	176.56 (17)	C21—C22—C23—C24	−178.6 (2)
C2—N1—C9—C10	−2.5 (3)	C21—C22—C27—C26	178.5 (3)
C2—N3—C4—O12	177.2 (2)	C22—C23—C24—C25	−0.2 (4)
C2—N3—C4—C10	−1.5 (3)	C23—C22—C27—C26	−0.7 (4)
C2'—O2'—C1—O1'	−1.9 (3)	C23—C24—C25—C26	−0.1 (4)
C2'—O2'—C1—C3	−178.89 (17)	C24—C25—C26—C27	0.0 (5)
C2'—C3'—C4'—O4'	−38.13 (17)	C25—C26—C27—C22	0.4 (5)
C2'—C3'—C4'—C5'	−158.73 (17)	C27—C22—C23—C24	0.6 (4)
C3—C6—C8—C11	−0.4 (4)	C5—N6—C7—N8	−0.3 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O10—H10···O13^i	0.82	1.86	2.661 (3)	166
N3—H3···N6^ii	0.86	2.40	3.113 (2)	141
N11—H11B···O10^iii	0.87 (1)	1.96 (1)	2.835 (3)	176 (2)
N11—H11A···O7′^ii	0.86 (1)	2.29 (2)	2.860 (2)	124 (2)
N11—H11A···O12	0.86 (1)	2.12 (2)	2.751 (2)	130 (2)

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