5-Ethynyl-2′-de­oxy­cytidine: a DNA building block with a `clickable' side chain

The title compound [systematic name: 4-amino-1-(2-de­oxy-β-D-erythro-pentofuranos­yl)-5-ethynylpyrimidin-2(1H)-one], C₁₁H₁₃N₃O₄, shows two conformations in the crystalline state. The N-glycosylic bonds of both conformers adopt similar conformations, with χ = −149.2 (1)° for conformer (I-1) and −151.4 (1)° for conformer (I-2), both in the anti range. The sugar residue of (I-1) shows a C2′-endo envelope conformation (²E, S-type), with P = 164.7 (1)° and τ_m = 36.9 (1)°, while (I-2) shows a major C3′-exo sugar pucker (C3′-exo-C2′-endo, ₃T², S-type), with P = 189.2 (1)° and τ_m = 33.3 (1)°. Both conformers participate in the formation of a layered three-dimensional crystal structure with a chain-like arrangement of the conformers. The ethynyl groups do not participate in hydrogen bonding, but are arranged in proximal positions.

S1. Comment

The title compound, 5-ethynyl-2'-deoxycytidine, (I), was first synthesized by Walker and co-workers in 1978 (Barr, Jones et al., 1978). Compound (I) is an inhibitor of herpes simplex virus (HSV) and shows enhanced selectively [selectivity?] compared to the closely related 5-ethynyl-2'-deoxyuridine, (IV) (De Clercq et al., 1978). Molecular orbital studies were performed on both compounds (Saran, 1988).

The ethynyl group of nucleoside (I) is linked to the 5-position of the pyrimidine moiety, while the related 3'-ethynylcytidine carries this group at the sugar moiety. The latter develops potent cytotoxicity in vitro and in vivo against various human tumour cell lines (Hattori et al., 1996).

The terminal triple bond of compound (I) represents a target for the Huisgen–Meldal–Sharpless cycloaddition (`click' reaction; Kolb et al., 2001; Kolb & Sharpless, 2003; Meldal & Tornøe, 2008) and has been functionalized with benzyl azide affording a hydrogel (Seela & Xiong, 2012). Furthermore, this compound can be used in the Glaser coupling for the construction of novel nanostructures (Minakawa et al., 2003). A phenyl click derivative of 5-ethynyl-2'-deoxycytidine was introduced chemically into oligonucleotides, and improved duplex formation was observed with a complementary RNA oligomer using consecutive incorporations (Andersen et al., 2011). Nucleoside (I) was also incorporated enzymatically in the form of its triphosphate by DNA polymerases (Guan et al., 2011; Macíčková-Cahová et al., 2011). Labelling experiments demonstrated that compound (I) can be used as a specific reporter of DNA replication or cell proliferation (Guan et al., 2011; Qu et al., 2011).

From this background, we became interested in performing a single-crystal X-ray analysis of 5-ethynyl-2'-deoxycytidine, (I), and the results are reported herein.

The crystal structure of (I) was compared to the two conformers of 5-propynyl-2'-deoxycytidine, (II) (Seela et al., 2007), 5-methyl-2'-deoxycytidine, (IIIb) (Sato, 1988; Seela et al., 2000), and 5-ethynyl-2'-deoxyuridine, (IV) (Barr, Hamor et al., 1978). In the asymmetric unit of (I), two molecules were found, which are denoted (I-1) and (I-2). The three-dimensional structures of the two conformers, viz. (I-1) and (I-2), are shown in Fig. 1, and selected geometric parameters are summarized in Table 1. For the related crystal structure of (II) (Seela et al., 2007), two conformers were also formed in the unit cell. Both (I) and (II) crystallize in the same space group (triclinic, P1; Seela et al., 2007), while the space group of (IIIb) is orthorhombic (P2₁2₁2₁; Sato, 1988) and that of (IV) is monoclinic (P2₁; Barr, Hamor et al., 1978).

Fig. 2 shows an overlay of conformers (I-1) and (I-2), indicating that the pyrimidine moieties are almost superimposable, while the major differences between both conformers occur in the sugar moiety.

In the case of conformer (I-1), triple-bonded atoms C5A and C5B together with heterocyclic atom C5 form an almost linear entity with C15B—C15A—C15 = 179.1 (1)°. For the propynyl groups of conformers (II-1) and (II-2), comparable angles were observed [179.3 (3) and 178.7 (3)°, respectively; Seela et al., 2007]. However, for molecule (I-2), this entity is slightly bended with C25B—C25A—C25 = 175.8 (1)°. The length of the C5A—C5B triple bond is within the same range for both conformers [1.198 (2) Å for (I-1) and 1.193 (2) Å for (I-2)].

In the crystalline state of (I), both types of molecules, (I-1) and (I-2), adopt anti conformations for the glycosylic bond; a conformation that is mainly found in pyrimidine nucleosides (Saenger, 1984). Both conformers show similar torsion angles around the glycosylic bond, χ (O4'—C1'—N1—C2) = -149.2 (1)° for conformer (I-1) and χ = -151.4 (1)° for conformer (I-2). Both conformers of (II) adopt similar anti conformations with χ = -135.0 (2) and -156.4 (2)° for (II-1) and (II-2), respectively (Seela et al., 2007). The glycosylic torsion angle in (IIIb) was also found to be anti with χ = -131.7° (Sato, 1988; Seela et al., 2000). The length of the glycosylic N1—C1' bond is 1.477 (1) Å for (I-1) and 1.487 (1) Å for (I-2), which is almost identical to the bond length observed for the two conformers of (II) [1.475 (2) Å for (II-1) and 1.490 (2) Å for (II-2); Seela et al., 2007].

The sugar residue of (I-1) shows a C2'-endo envelope conformation (²E, S-type), with P = 164.7 (1)° and τ_m = 36.9 (1)°, while (I-2) shows a major C3'-exo conformation (C3'-exo-C2'-endo, ₃T², S-type), with P = 189.2 (1)° and τ_m = 33.3 (1)°. The sugar moieties of (II-1), (II-2) and (IV) also show an S-type conformation and exhibit twisted C2'-endo sugar puckers (Seela et al., 2007; Barr, Hamor et al., 1978). The sugar ring of (IIIb) is also puckered in a typical C2'-endo envelope form (²E, S-type), with P = 161.5° and τ_m= 37.9° (Sato, 1988; Seela et al., 2000).

The γ torsion angle (O5'—C5'—C4'—C3') characterizes the orientation of the exocyclic 5'-hydroxy group relative to the 2'-deoxyribose ring. Molecules (I-1) and (I-2) display similar conformations about the C4'—C5' bond. Both (I-1) and (I-2) show a synclinar (+sc; gauche, gauche) conformation. The torsion angle γ is 55.5 (1)° for (I-1) and 51.7 (1)° for (I-2). In the case of (II), molecule (II-1) shows a similar torsion angle with γ = 57.8 (3)° (+sc; gauche, gauche), while molecule (II-2) adopts an antiperiplanar conformation [+ap; gauche,trans, γ = 166.1 (2)°; Seela et al., 2007].

In the crystal structure of nucleoside (I), molecules (I-1) and (I-2) are linked into layers by several intermolecular hydrogen bonds (Table 2 and Fig. 3) involving all H atoms linked to heteroatoms. Hydrogen bonds between neighbouring bases and sugar units (N14—H14A···N23ⁱ, O13'—H13O···O22, N24—H24A···N13ⁱⁱⁱ, O23'—H23O···O12 and O25'—H25O···O15'^iv; for symmetry codes and geometry see Table 2) connect the different conformers. One further hydrogen bond was found linking molecules of identical conformation (O15'—H15O···O12ⁱⁱ). Atom O12 of conformer (I-1) functions as an acceptor for a bifurcated hydrogen bond with O15'—H15O of (I-1) and O23'—H23O of (I-2) acting as hydrogen donors.

The layers are built up by alternating chains of conformer (I-1) and (I-2), and each of these chains contains only one type of conformer. Interestingly, the ethynyl group of one conformer is located in a proximal position to the ethynyl group of the other conformer of the neighbouring chain (Fig. 3). However, the ethynyl groups of both conformers do not participate in hydrogen bonding. The individual layers are connected by an intermolecular hydrogen bond (O25'—H25O···O15'^iv).

Related literature

For related literature, see: Andersen et al. (2008, 2011); Barr, Hamor & Walker (1978); Barr, Jones, Serafinowski & Walker (1978); De Clercq, Balzarini, Descamps, Huang, Torrence, Bergstrom, Jones, Serafinowski, Verhelst & Walker (1978); Dodd et al. (2010); Flack (1983); Guan et al. (2011); Hattori et al. (1996); Hooft et al. (2008); Kolb & Sharpless (2003); Kolb et al. (2001); Macíčková-Cahová, Pohl & Hocek (2011); Meldal & Tornøe (2008); Minakawa et al. (2003); Qu et al. (2011); Saenger (1984); Saran (1988); Sato (1988); Seela & Xiong (2012); Seela et al. (2000, 2007); Spek (2009).

S2. Experimental

Compound (I) was synthesized from (IIIa) according to literature procedures (Andersen et al., 2008, 2011; Dodd et al., 2010). Slow crystallization from a dichloromethane–methanol mixture afforded (I) as colourless crystals (decomposition at 464 K). For the diffraction experiment, a single crystal was mounted on a MiTeGen Micro-Mountsfibre in a thin smear of oil.

S3. Refinement

The known configuration of the parent molecule was used to define the enantiomer employed in the refined model. 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 for this parameter [-0.3 (3)]. Further confirmation of the configuration was sought by the Hooft analysis. The absolute structure parameter y (Hooft et al., 2008) was calculated using PLATON (Spek, 2009). The resulting Hooft analysis parameters were P2(true) = P3(true) = 1.000, P3(false) = 0.2E-27 [0.2 × 10^-27?], P3(rac-twin) = 0.1E-08 [0.1 × 10^-8?] and y = -0.20 (10) calculated for 3602 Bijvoet pairs (97% coverage), indicating that the known absolute configuration used for analysis is correct. All H atoms were found in a difference Fourier synthesis. In order to maximize the data/parameter ratio, H atoms were placed in geometrically idealized positions, with C—H = 0.95–1.00 Å and N—H 0.88 Å (AFIX 93), and constrained to ride on their parent atoms with U_iso(H) = 1.2U_eq(C) = U_eq(N). The hydroxy groups were refined as groups allowed to rotate but not tip (AFIX 147), with O—H = 0.84 Å and U_iso(H) = 1.5U_eq(O).

Computing details

Data collection: APEX2 (Bruker, 2008); cell refinement: APEX2 (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 1999) and PLATON (Spek, 2009); software used to prepare material for publication: Please supply.

Figures

	Fig. 1. Perspective views of conformer (I-1) (left) and conformer (I-2) (right) connected by two hydrogen bonds and showing the atom-numbering schemes. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. An overlay of molecules (I-1) and (I-2).
	Fig. 3. A detailed view of the two-dimensional hydrogen-bonded (dashed lines) network of (I). The projection is parallel to the ab plane. For the sake of clarity, H atoms not involved in the intermolecular hydrogen-bonding motifs have been omitted.

4-Amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-5- ethynylpyrimidin-2(1H)-one

Crystal data

C11H13N3O4	Z = 2
Mr = 251.24	F(000) = 264
Triclinic, P1	Dx = 1.436 Mg m^−3
Hall symbol: P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.8754 (6) Å	Cell parameters from 9541 reflections
b = 8.1504 (6) Å	θ = 2.8–32.1°
c = 10.0893 (7) Å	µ = 0.11 mm^−1
α = 108.637 (3)°	T = 130 K
β = 96.327 (3)°	Block, colourless
γ = 104.562 (3)°	0.3 × 0.2 × 0.2 mm
V = 580.98 (7) Å^3

Data collection

Bruker APEXII CCD diffractometer	3715 independent reflections
Radiation source: fine-focus sealed tube	3671 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.022
ϕ and ω scans	θmax = 31.0°, θmin = 3.2°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −11→11
Tmin = 0.710, Tmax = 0.746	k = −11→11
37435 measured reflections	l = −14→14

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)] = 0.029	H-atom parameters constrained
wR(F^2) = 0.080	w = 1/[σ^2(Fo^2) + (0.0629P)^2 + 0.0405P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max < 0.001
3715 reflections	Δρmax = 0.37 e Å^−3
329 parameters	Δρmin = −0.29 e Å^−3
3 restraints	Absolute structure: established by known chemical absolute configuration
Primary atom site location: structure-invariant direct methods

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
N11	0.20809 (12)	0.43953 (13)	0.20122 (10)	0.01442 (17)
C12	0.03746 (14)	0.36738 (15)	0.22218 (12)	0.01459 (19)
O12	−0.00494 (12)	0.44509 (13)	0.33721 (9)	0.01904 (17)
N13	−0.07812 (13)	0.21897 (14)	0.11876 (11)	0.01527 (17)
C14	−0.03033 (14)	0.13994 (15)	−0.00347 (12)	0.01487 (19)
N14	−0.15101 (14)	−0.00409 (15)	−0.10213 (12)	0.0203 (2)
H14A	−0.2584	−0.0448	−0.0862	0.024*
H14B	−0.1237	−0.0591	−0.1836	0.024*
C15	0.14773 (15)	0.20714 (15)	−0.02631 (12)	0.01476 (19)
C15A	0.20166 (17)	0.11933 (17)	−0.15420 (13)	0.0180 (2)
C15B	0.2448 (2)	0.04364 (19)	−0.26186 (16)	0.0256 (2)
H15C	0.2791	−0.0164	−0.3472	0.031*
C16	0.26164 (15)	0.35732 (16)	0.08056 (12)	0.01514 (19)
H16	0.3805	0.4053	0.0705	0.018*
C11'	0.33639 (15)	0.59665 (15)	0.31882 (12)	0.01489 (19)
H11'	0.2702	0.6709	0.3789	0.018*
C12'	0.45714 (15)	0.53873 (15)	0.41158 (12)	0.01529 (19)
H12B	0.4852	0.4289	0.3544	0.018*
H12A	0.4022	0.5154	0.4900	0.018*
C13'	0.62359 (16)	0.70526 (16)	0.46870 (12)	0.0175 (2)
H13'	0.7336	0.6722	0.4937	0.021*
O13'	0.60188 (16)	0.84633 (14)	0.58620 (11)	0.0293 (2)
H13O	0.5465	0.8007	0.6388	0.044*
C14'	0.63144 (15)	0.77133 (15)	0.34308 (12)	0.01531 (18)
H14'	0.6692	0.9072	0.3808	0.018*
C15'	0.75398 (17)	0.70724 (18)	0.24649 (14)	0.0206 (2)
H15A	0.7443	0.7508	0.1658	0.025*
H15B	0.8796	0.7609	0.3008	0.025*
O15'	0.71121 (13)	0.51379 (14)	0.19138 (10)	0.02194 (18)
H15O	0.7763	0.4815	0.2435	0.033*
O14'	0.45024 (11)	0.70271 (12)	0.25845 (9)	0.01637 (15)
N21	0.18064 (13)	0.69955 (13)	0.85458 (10)	0.01416 (17)
C22	0.36007 (14)	0.74465 (16)	0.84257 (12)	0.0153 (2)
O22	0.39671 (13)	0.66786 (14)	0.72627 (10)	0.02227 (19)
N23	0.48657 (13)	0.86851 (14)	0.95527 (11)	0.01648 (18)
C24	0.44075 (14)	0.94509 (15)	1.07889 (11)	0.01389 (19)
N24	0.56902 (14)	1.07296 (15)	1.18449 (11)	0.01856 (19)
H24A	0.6796	1.1046	1.1717	0.022*
H24B	0.5434	1.1261	1.2672	0.022*
C25	0.25911 (15)	0.89344 (15)	1.09751 (11)	0.01397 (19)
C25A	0.21500 (16)	0.97711 (17)	1.23093 (13)	0.0185 (2)
C25B	0.1884 (2)	1.0554 (2)	1.34477 (16)	0.0318 (3)
H25C	0.1672	1.1178	1.4355	0.038*
C26	0.13338 (15)	0.77132 (15)	0.98071 (12)	0.01407 (19)
H26	0.0112	0.7361	0.9877	0.017*
C21'	0.04531 (14)	0.58385 (15)	0.72081 (11)	0.01455 (18)
H6	0.0878	0.6123	0.6386	0.017*
C22'	0.00606 (17)	0.38068 (16)	0.68952 (13)	0.0192 (2)
H22A	0.0768	0.3281	0.6216	0.023*
H22B	0.0332	0.3566	0.7784	0.023*
C23'	−0.19400 (17)	0.30364 (16)	0.62382 (12)	0.0188 (2)
H23	−0.2479	0.1942	0.6474	0.023*
O23'	−0.23315 (15)	0.25925 (15)	0.47273 (10)	0.0281 (2)
H23O	−0.1568	0.3328	0.4505	0.042*
C24'	−0.26492 (15)	0.45919 (16)	0.70095 (12)	0.0171 (2)
H24	−0.3661	0.4609	0.6327	0.021*
C25'	−0.32987 (16)	0.4499 (2)	0.83440 (14)	0.0223 (2)
H25B	−0.3572	0.5633	0.8842	0.027*
H25A	−0.4410	0.3468	0.8085	0.027*
O25'	−0.19509 (14)	0.42658 (14)	0.92620 (10)	0.02288 (19)
H25O	−0.2299	0.4247	1.0016	0.034*
O24'	−0.11762 (11)	0.62413 (11)	0.73418 (9)	0.01591 (15)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N11	0.0112 (4)	0.0147 (4)	0.0136 (4)	0.0017 (3)	0.0022 (3)	0.0019 (3)
C12	0.0117 (4)	0.0172 (5)	0.0140 (5)	0.0034 (4)	0.0019 (4)	0.0054 (4)
O12	0.0155 (4)	0.0227 (4)	0.0141 (4)	0.0026 (3)	0.0044 (3)	0.0024 (3)
N13	0.0114 (4)	0.0166 (4)	0.0145 (4)	0.0026 (3)	0.0016 (3)	0.0030 (3)
C14	0.0130 (4)	0.0148 (5)	0.0150 (5)	0.0037 (4)	0.0009 (4)	0.0042 (4)
N14	0.0139 (4)	0.0190 (5)	0.0188 (4)	0.0017 (3)	0.0015 (3)	−0.0019 (4)
C15	0.0133 (4)	0.0151 (5)	0.0145 (5)	0.0043 (4)	0.0026 (4)	0.0036 (4)
C15A	0.0183 (5)	0.0161 (5)	0.0181 (5)	0.0039 (4)	0.0041 (4)	0.0051 (4)
C15B	0.0332 (7)	0.0215 (6)	0.0219 (6)	0.0087 (5)	0.0114 (5)	0.0055 (5)
C16	0.0130 (4)	0.0157 (4)	0.0154 (5)	0.0037 (4)	0.0037 (4)	0.0040 (4)
C11'	0.0130 (4)	0.0130 (4)	0.0145 (4)	0.0007 (3)	0.0027 (3)	0.0021 (4)
C12'	0.0168 (5)	0.0143 (4)	0.0109 (4)	−0.0004 (4)	0.0014 (3)	0.0040 (3)
C13'	0.0176 (5)	0.0174 (5)	0.0115 (4)	−0.0016 (4)	0.0003 (4)	0.0038 (4)
O13'	0.0408 (6)	0.0191 (4)	0.0139 (4)	−0.0055 (4)	0.0074 (4)	−0.0018 (3)
C14'	0.0139 (4)	0.0146 (4)	0.0141 (4)	−0.0003 (3)	0.0017 (3)	0.0047 (4)
C15'	0.0166 (5)	0.0248 (6)	0.0200 (5)	0.0029 (4)	0.0067 (4)	0.0091 (4)
O15'	0.0222 (4)	0.0273 (4)	0.0205 (4)	0.0127 (3)	0.0077 (3)	0.0090 (3)
O14'	0.0135 (3)	0.0164 (4)	0.0184 (4)	0.0016 (3)	0.0007 (3)	0.0084 (3)
N21	0.0124 (4)	0.0164 (4)	0.0094 (4)	0.0011 (3)	0.0009 (3)	0.0020 (3)
C22	0.0126 (4)	0.0183 (5)	0.0124 (5)	0.0031 (4)	0.0022 (4)	0.0035 (4)
O22	0.0188 (4)	0.0284 (5)	0.0134 (4)	0.0039 (3)	0.0057 (3)	0.0013 (3)
N23	0.0123 (4)	0.0193 (4)	0.0130 (4)	0.0012 (3)	0.0015 (3)	0.0028 (3)
C24	0.0121 (4)	0.0145 (5)	0.0124 (4)	0.0017 (4)	0.0005 (4)	0.0038 (4)
N24	0.0144 (4)	0.0201 (5)	0.0132 (4)	−0.0013 (4)	0.0004 (3)	0.0015 (4)
C25	0.0136 (4)	0.0147 (4)	0.0110 (4)	0.0018 (4)	0.0022 (3)	0.0032 (4)
C25A	0.0168 (5)	0.0184 (5)	0.0149 (5)	0.0011 (4)	0.0033 (4)	0.0024 (4)
C25B	0.0374 (8)	0.0277 (7)	0.0210 (6)	0.0041 (6)	0.0124 (6)	−0.0009 (5)
C26	0.0133 (4)	0.0152 (4)	0.0109 (4)	0.0022 (4)	0.0023 (3)	0.0028 (4)
C21'	0.0138 (4)	0.0159 (4)	0.0098 (4)	0.0018 (3)	0.0004 (3)	0.0018 (3)
C22'	0.0220 (5)	0.0151 (5)	0.0159 (5)	0.0057 (4)	0.0018 (4)	0.0004 (4)
C23'	0.0246 (5)	0.0145 (4)	0.0103 (4)	−0.0017 (4)	0.0010 (4)	0.0021 (4)
O23'	0.0318 (5)	0.0267 (5)	0.0096 (4)	−0.0098 (4)	0.0001 (3)	0.0011 (3)
C24'	0.0134 (4)	0.0188 (5)	0.0144 (4)	−0.0007 (4)	−0.0011 (3)	0.0053 (4)
C25'	0.0157 (5)	0.0300 (6)	0.0186 (5)	0.0021 (4)	0.0045 (4)	0.0088 (5)
O25'	0.0290 (5)	0.0278 (5)	0.0151 (4)	0.0098 (4)	0.0067 (3)	0.0104 (3)
O24'	0.0132 (3)	0.0140 (3)	0.0172 (4)	0.0024 (3)	−0.0007 (3)	0.0041 (3)

Geometric parameters (Å, º)

N11—C16	1.3575 (14)	N21—C26	1.3558 (14)
N11—C12	1.3932 (14)	N21—C22	1.3970 (14)
N11—C11'	1.4773 (14)	N21—C21'	1.4869 (14)
C12—O12	1.2576 (13)	C22—O22	1.2442 (13)
C12—N13	1.3456 (14)	C22—N23	1.3474 (15)
N13—C14	1.3395 (14)	N23—C24	1.3380 (14)
C14—N14	1.3250 (14)	C24—N24	1.3287 (14)
C14—C15	1.4440 (15)	C24—C25	1.4373 (15)
N14—H14A	0.8800	N24—H24A	0.8800
N14—H14B	0.8800	N24—H24B	0.8800
C15—C16	1.3626 (15)	C25—C26	1.3629 (15)
C15—C15A	1.4286 (16)	C25—C25A	1.4259 (16)
C15A—C15B	1.1978 (18)	C25A—C25B	1.1925 (18)
C15B—H15C	0.9500	C25B—H25C	0.9500
C16—H16	0.9500	C26—H26	0.9500
C11'—O14'	1.4104 (14)	C21'—O24'	1.4121 (14)
C11'—C12'	1.5215 (16)	C21'—C22'	1.5245 (17)
C11'—H11'	1.0000	C21'—H6	1.0000
C12'—C13'	1.5269 (15)	C22'—C23'	1.5239 (18)
C12'—H12B	0.9900	C22'—H22A	0.9900
C12'—H12A	0.9900	C22'—H22B	0.9900
C13'—O13'	1.4244 (15)	C23'—O23'	1.4275 (15)
C13'—C14'	1.5287 (16)	C23'—C24'	1.5318 (18)
C13'—H13'	1.0000	C23'—H23	1.0000
O13'—H13O	0.8400	O23'—H23O	0.8400
C14'—O14'	1.4502 (13)	C24'—O24'	1.4517 (14)
C14'—C15'	1.5131 (17)	C24'—C25'	1.5092 (17)
C14'—H14'	1.0000	C24'—H24	1.0000
C15'—O15'	1.4282 (17)	C25'—O25'	1.4206 (16)
C15'—H15A	0.9900	C25'—H25B	0.9900
C15'—H15B	0.9900	C25'—H25A	0.9900
O15'—H15O	0.8400	O25'—H25O	0.8400
C16—N11—C12	120.77 (10)	C26—N21—C22	120.75 (10)
C16—N11—C11'	120.22 (9)	C26—N21—C21'	122.20 (9)
C12—N11—C11'	118.73 (9)	C22—N21—C21'	116.83 (9)
O12—C12—N13	121.80 (10)	O22—C22—N23	122.32 (10)
O12—C12—N11	118.69 (10)	O22—C22—N21	117.99 (10)
N13—C12—N11	119.50 (10)	N23—C22—N21	119.68 (10)
C14—N13—C12	120.63 (10)	C24—N23—C22	120.06 (10)
N14—C14—N13	117.80 (10)	N24—C24—N23	117.70 (10)
N14—C14—C15	120.95 (10)	N24—C24—C25	120.67 (10)
N13—C14—C15	121.24 (10)	N23—C24—C25	121.63 (10)
C14—N14—H14A	120.0	C24—N24—H24A	120.0
C14—N14—H14B	120.0	C24—N24—H24B	120.0
H14A—N14—H14B	120.0	H24A—N24—H24B	120.0
C16—C15—C15A	121.85 (10)	C26—C25—C25A	122.76 (10)
C16—C15—C14	116.64 (10)	C26—C25—C24	116.93 (10)
C15A—C15—C14	121.51 (10)	C25A—C25—C24	120.20 (10)
C15B—C15A—C15	179.09 (14)	C25B—C25A—C25	175.83 (14)
C15A—C15B—H15C	180.0	C25A—C25B—H25C	180.0
N11—C16—C15	121.12 (10)	N21—C26—C25	120.77 (10)
N11—C16—H16	119.4	N21—C26—H26	119.6
C15—C16—H16	119.4	C25—C26—H26	119.6
O14'—C11'—N11	108.30 (9)	O24'—C21'—N21	108.52 (9)
O14'—C11'—C12'	106.37 (9)	O24'—C21'—C22'	107.12 (9)
N11—C11'—C12'	112.16 (9)	N21—C21'—C22'	113.60 (9)
O14'—C11'—H11'	110.0	O24'—C21'—H6	109.2
N11—C11'—H11'	110.0	N21—C21'—H6	109.2
C12'—C11'—H11'	110.0	C22'—C21'—H6	109.2
C11'—C12'—C13'	101.47 (9)	C23'—C22'—C21'	103.44 (9)
C11'—C12'—H12B	111.5	C23'—C22'—H22A	111.1
C13'—C12'—H12B	111.5	C21'—C22'—H22A	111.1
C11'—C12'—H12A	111.5	C23'—C22'—H22B	111.1
C13'—C12'—H12A	111.5	C21'—C22'—H22B	111.1
H12B—C12'—H12A	109.3	H22A—C22'—H22B	109.0
O13'—C13'—C12'	111.94 (10)	O23'—C23'—C22'	113.34 (10)
O13'—C13'—C14'	107.61 (10)	O23'—C23'—C24'	111.04 (11)
C12'—C13'—C14'	102.69 (9)	C22'—C23'—C24'	102.40 (9)
O13'—C13'—H13'	111.4	O23'—C23'—H23	109.9
C12'—C13'—H13'	111.4	C22'—C23'—H23	109.9
C14'—C13'—H13'	111.4	C24'—C23'—H23	109.9
C13'—O13'—H13O	109.5	C23'—O23'—H23O	109.5
O14'—C14'—C15'	108.15 (10)	O24'—C24'—C25'	110.64 (10)
O14'—C14'—C13'	106.28 (9)	O24'—C24'—C23'	105.31 (9)
C15'—C14'—C13'	115.30 (10)	C25'—C24'—C23'	115.36 (11)
O14'—C14'—H14'	109.0	O24'—C24'—H24	108.4
C15'—C14'—H14'	109.0	C25'—C24'—H24	108.4
C13'—C14'—H14'	109.0	C23'—C24'—H24	108.4
O15'—C15'—C14'	112.24 (10)	O25'—C25'—C24'	109.43 (10)
O15'—C15'—H15A	109.2	O25'—C25'—H25B	109.8
C14'—C15'—H15A	109.2	C24'—C25'—H25B	109.8
O15'—C15'—H15B	109.2	O25'—C25'—H25A	109.8
C14'—C15'—H15B	109.2	C24'—C25'—H25A	109.8
H15A—C15'—H15B	107.9	H25B—C25'—H25A	108.2
C15'—O15'—H15O	109.5	C25'—O25'—H25O	109.5
C11'—O14'—C14'	109.75 (8)	C21'—O24'—C24'	110.77 (9)
C16—N11—C12—O12	178.09 (10)	C26—N21—C22—O22	176.49 (11)
C11'—N11—C12—O12	4.16 (15)	C21'—N21—C22—O22	−8.78 (16)
C16—N11—C12—N13	−2.92 (16)	C26—N21—C22—N23	−3.72 (16)
C11'—N11—C12—N13	−176.85 (10)	C21'—N21—C22—N23	171.01 (10)
O12—C12—N13—C14	179.23 (10)	O22—C22—N23—C24	−178.87 (11)
N11—C12—N13—C14	0.27 (16)	N21—C22—N23—C24	1.34 (16)
C12—N13—C14—N14	−178.96 (11)	C22—N23—C24—N24	−176.72 (11)
C12—N13—C14—C15	2.13 (16)	C22—N23—C24—C25	2.55 (17)
N14—C14—C15—C16	179.20 (12)	N24—C24—C25—C26	175.16 (11)
N13—C14—C15—C16	−1.92 (16)	N23—C24—C25—C26	−4.10 (16)
N14—C14—C15—C15A	−1.28 (17)	N24—C24—C25—C25A	−1.07 (17)
N13—C14—C15—C15A	177.60 (11)	N23—C24—C25—C25A	179.68 (11)
C12—N11—C16—C15	3.11 (17)	C22—N21—C26—C25	2.06 (16)
C11'—N11—C16—C15	176.94 (10)	C21'—N21—C26—C25	−172.38 (11)
C15A—C15—C16—N11	179.77 (11)	C25A—C25—C26—N21	177.82 (11)
C14—C15—C16—N11	−0.71 (16)	C24—C25—C26—N21	1.70 (16)
C16—N11—C11'—O14'	36.87 (13)	C26—N21—C21'—O24'	23.26 (14)
C12—N11—C11'—O14'	−149.17 (10)	C22—N21—C21'—O24'	−151.39 (10)
C16—N11—C11'—C12'	−80.21 (13)	C26—N21—C21'—C22'	−95.76 (12)
C12—N11—C11'—C12'	93.75 (11)	C22—N21—C21'—C22'	89.59 (12)
O14'—C11'—C12'—C13'	34.78 (11)	O24'—C21'—C22'—C23'	24.02 (12)
N11—C11'—C12'—C13'	153.00 (9)	N21—C21'—C22'—C23'	143.84 (9)
C11'—C12'—C13'—O13'	80.54 (11)	C21'—C22'—C23'—O23'	87.43 (12)
C11'—C12'—C13'—C14'	−34.61 (11)	C21'—C22'—C23'—C24'	−32.25 (11)
O13'—C13'—C14'—O14'	−94.60 (11)	O23'—C23'—C24'—O24'	−91.50 (11)
C12'—C13'—C14'—O14'	23.65 (11)	C22'—C23'—C24'—O24'	29.77 (11)
O13'—C13'—C14'—C15'	145.59 (11)	O23'—C23'—C24'—C25'	146.21 (10)
C12'—C13'—C14'—C15'	−96.16 (12)	C22'—C23'—C24'—C25'	−92.52 (11)
O14'—C14'—C15'—O15'	−63.25 (12)	O24'—C24'—C25'—O25'	−67.73 (13)
C13'—C14'—C15'—O15'	55.52 (14)	C23'—C24'—C25'—O25'	51.66 (14)
N11—C11'—O14'—C14'	−141.55 (9)	N21—C21'—O24'—C24'	−128.27 (9)
C12'—C11'—O14'—C14'	−20.80 (11)	C22'—C21'—O24'—C24'	−5.25 (12)
C15'—C14'—O14'—C11'	122.28 (10)	C25'—C24'—O24'—C21'	109.57 (11)
C13'—C14'—O14'—C11'	−2.08 (11)	C23'—C24'—O24'—C21'	−15.72 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N14—H14A···N23^i	0.88	2.09	2.9696 (14)	178
O13′—H13O···O22	0.84	1.88	2.7127 (14)	170
O15′—H15O···O12^ii	0.84	2.01	2.8119 (13)	160
N24—H24A···N13^iii	0.88	2.11	2.9708 (14)	166
O23′—H23O···O12	0.84	2.00	2.8090 (13)	162
O25′—H25O···O15′^iv	0.84	1.97	2.7733 (13)	160

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