2'-De­oxy-5-propynyluridine: a nucleoside with two conformations in the asymmetric unit

The title compound, 1-(2-de­oxy-[beta]-D-erythro-pentofuranos­yl)-5-(prop-1-yn­yl)pyrimidin-2,4(1H,3H)-dione, C₁₂H₁₄N₂O₅, shows two conformations in the crystalline state: conformer 1 adopts a C2'-endo (close to ²E; S-type) sugar pucker and an anti nucleobase orientation [[chi] = -134.04 (19)°], while conformer 2 shows an S sugar pucker (twisted C2'-endo-C3'-exo), which is accompanied by a different anti base orientation [[chi] = -162.79 (17)°]. Both mol­ecules show a +sc (gauche, gauche) conformation at the exocyclic C4'-C5' bond and a coplanar orientation of the propynyl group with respect to the pyrimidine ring. The extended structure is a three-dimensional hydrogen-bond network involving inter­molecular N-H...O and O-H...O hydrogen bonds. Only O atoms function as H-atom acceptor sites.

S1. Comment

5-Propynylated pyrimidine nucleosides have been shown to increase duplex stability (Barnes & Turner, 2001; Froehler et al., 1992; He & Seela, 2002) and can strengthen triplex formation (Gilbert & Feigon, 1999). This makes them useful for the development of polymer therapeutics by antisense or antigene technology with the aim of gene silencing (Manoharan, 2004; Praseuth et al., 1999; Crooke, 2004). The structural changes caused by the incorporation of 2'-deoxy-5-propynyluridine (I) instead of dT in duplex DNA increase base stacking and enhance the hydrophobic interactions between the side chains (He & Seela, 2002). The electron-withdrawing propynyl group at position 5 of pyrimidine nucleosides enforces hydrogen bonding, which is reflected by a decrease of the pK_a value from 9.3 (2'-deoxyuridine; Fox & Shugar, 1952) to 8.7 for 2'-deoxy-5-propynyluridine. As the 5-subsituent of a pyrimidine nucleoside lies in the major groove of the DNA-duplex (Ahmadian et al., 1998), it is tolerated by DNA polymerases when corresponding triphosphates are used (Roychowdhury et al., 2004).

This background prompted us to perform a single-crystal X-ray analysis of the title compound, (I). Compound (I) was synthesized from 5-iodo-2'-deoxyuridine, (IIb), and propyne gas employing the palladium-catalyzed Sonogashira cross-coupling reaction (Hobbs, 1989; Froehler et al., 1992). Slow crystallization of 5-propynyl-2'-deoxyuridine from methanol gave colourless crystals which were submitted to single-crystal X-ray analysis. The crystal structures of the closely related 2'-deoxyuridine, (IIa) (Rahman & Wilson, 1972), 2'-deoxy-5-ethynyluridine, (IIc) (Barr et al., 1978), 5-propynyl-arabinouridine, (III) (Cygler et al., 1984), and 2'-deoxy-5-propynylcytidine, (IV) (Seela et al., 2007) have been reported before and are now compared with the crystal structure of (I).

In the asymmetric unit of (I), two conformational states exist, which differ mainly in their conformation around the N-glycosylic bond and the exocyclic C4'—C5' bond as demonstrated by Fig. 1. They are defined as conformers 1 and 2, denoted (I-1) and (I-2), respectively. Similar observations were made on the related crystals of (IIa) and (IV). The three-dimensional structures of the molecules of 2'-deoxy-5-propynyluridine, conformer 1 (I-1) and conformer 2 (I-2), are shown in Fig. 2 and selected geometric parameters are listed in Table 1.

For pyrimidine nucleosides, the orientation of the nucleobase relative to the sugar moiety (syn/anti) is defined by the torsion angle χ (O4'—C1'—N1—C2) (IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983). Commonly, an anti conformation at the N-glycosylic bond is observed for pyrimidine nucleosides and only in rare cases has a syn conformation been reported (Saenger, 1984). Both molecules of (I) adopt an anti conformation with respect to the sugar ring. The glycosoylic bond torsion angles are χ = -134.04 (19)° for (I-1) and χ = -162.79 (17)° for (I-2). For the molecules of the parent unsubstituted 2'-deoxyuridine (IIa), the closely related (IIc) and (III), anti conformations of the glycosylic bonds with very similar χ values were reported, which are within the range of the values found for the molecules of (I) [χ = -153.65 and -156.54° for (IIa); χ = - 157.36° for (IIc); χ = -153.65° for (III)].

The glycosylic bond N11—C11' = 1.473 (3) Å of (I-1) is shorter than the bond length observed for (I-2) [N21—C21' = 1.486 (2) Å]. These values are similar to the bond lengths found for the related molecules of (IIa) (1.45 and 1.50 Å), (IIc) [1.478 (3) Å] and (III) (1.485 Å) as well as for (IV) [1.475 (2) and 1.490 (2) Å].

The 2'-deoxyribofuranosyl moieties of (I-1) and (I-2) show an S-type sugar conformation, which is consistent with the preferred conformation of 2'-deoxyribonucleosides. Molecule (I-1) exhibits a pseudorotational phase angle P = 170.1 (2)° with the maximum amplitude τ_m = 42.7 (1)° which corresponds to a C2'-endo puckering (close to ²E) and molecule (I-2) shows a twisted C2'-endo-C3'-exo (²T₃) sugar conformation with P = 172.9 (2)° and τ_m = 36.2 (1)° (Rao et al., 1981). The S-type sugar conformation of (I-1) and (I-2) observed in the crystalline state is consistent with the predominant S (71%) conformation of molecule (I) found in solution. This value is very close to the value observed for (IIa) (70% S), indicating that the propynyl group introduced at position 5 of the pyrimidine moiety has almost no effect on the sugar conformation of (I). The sugar conformation of compound (I) in solution was determined from the vicinal ³J(H,H) coupling constants of the ¹H NMR spectra measured in a DMSO/D₂O mixture, applying the program PSEUROT 6.3 (Van Wijk et al., 1999). An S conformation with a 2'-endo sugar pucker was also observed in the crystalline state for (IIa) and (IIc).

The conformation about the exocyclic C4'—C5' bond is defined by the torsion angle γ (O5'—C5'—C4'—C3'). For both molecules of (I), γ adopts a +synclinal (+sc, gauche, gauche) conformation with γ = 62.6 (3)° for (I-1) and γ = 50.1 (3)° for (I-2). In the crystal structures of (IIa) and (III), the torsion angel γ is within the same range (40–71°; +sc, gauche, gauche), whereas a -antiperiplanar (-ap, gauche, trans) conformation has been reported for the exocyclic group of (IIc).

The heterocyclic ring systems of (I-1) and (I-2) are nearly planar. The r.m.s. deviation of the ring atoms from their calculated least-square planes are 0.0154 and 0.0164 Å, respectively with a maximum deviation of -0.0227 (14) Å for C14 (I-1) and -0.0269 (13) Å for N21 (I-2). In both molecules, the exocyclic groups lie on both sides of the pyrimidine ring system.

The propynyl group of (I-1) and (I-2) is almost linear with bond angles C15A—C15B—C15C = 177.3 (2)° for (I-1) and C25A—C25B—C25C = 178.5 (2)° for (I-2). In both molecules, the propynyl group is in a coplanar orientation with respect to the pyrimidine ring. The angles of inclination are close to 0° [0.4 (7)° for (I-1) and 0.8 (5)° for (I-2)]. Other nucleosides exhibit propynyl groups that are slightly inclined with respect to the nucleobase moiety. For the propynyl group of (III) and (IV-1), the angles of inclination are 3.7 and 3.5°, respectively (Cygler et al., 1984; Seela et al., 2007), whereas for molecule (IV-2) the propynyl group is inclined by 4.4° (Seela et al., 2007).

In the crystal structure of nucleoside (I), molecules (I-1) and (I-2) are linked into an infinite network by several intermolecular hydrogen bonds (Table 2 and Fig. 3). Molecules of one conformation are linked to those of the other conformation resulting in an alternating arrangement of the conformers. Both molecules form identical hydrogen-bonding patterns (N13—H13···O22ⁱ, O13'—H13B···O24ⁱⁱ, O15'—H15···O13'ⁱⁱⁱ, N23—H23···O12^iv, O23'—H23B···O14^v, O25'—H25···O23'^vi; see Table 2 for symmetry codes and geometry); only O atoms act as acceptors in hydrogen bonding. Most probably as a result of `hydrophobic interactions', the lipophilic propynyl group of molecules (I-1) and (I-2) is arranged in proximal positions with opposite chain orientation.

Related literature

For related literature, see: Ahmadian et al. (1998); Barnes & Turner (2001); Barr et al. (1978); Crooke (2004); Cygler et al. (1984); Fox & Shugar (1952); Froehler et al. (1992); Gilbert & Feigon (1999); He & Seela (2002); Hobbs (1989); Manoharan (2004); Praseuth et al. (1999); Rahman & Wilson (1972); Rao et al. (1981); Roychowdhury et al. (2004); Saenger (1984); Seela et al. (2007); Van Wijk, Haasnoot, de Leeuw, Huckriede, Westra Hoekzema & Altona (1999).

S2. Experimental

Compound (I) was synthesized from 2'-deoxy-5-iodouridine (IIb) and propyne gas according to literature procedures (Hobbs, 1989; Froehler et al., 1992) and was slowly crystallized from methanol as colourless crystals (474 K). For the diffraction experiment, a single crystal was mounted on a MiTeGen MicroMounts fibre in a thin smear of oil.

S3. Refinement

In the absence of suitable anomalous scattering, Friedel equivalents could not be used to determine the absolute structure. Refinement of the Flack (1983) parameter led to inconclusive values for this parameter [0.3 (6)]. Therefore, Friedel equivalents (2617) were merged before the final refinement. The known configuration of the parent molecule was used to define the enantiomer employed in the refined model. All H atoms were found in a difference Fourier synthesis. In order to maximize the data/parameter ratio, the H atoms bonded to C atoms were placed in geometrically idealized positions, with C—H distances from 0.95 to 1.00 Å and U_iso(H) = xU_eq(C), where x = 1.5 for the methyl groups and 1.2 for the other H atoms. All H atoms bonded to O and N atoms were located in a difference Fourier map and allowed to refine freely. The refined O—H distances are in the range 0.79 (3)–0.94 (4) Å and the N—H distances are 0.90 (3) and 0.91 (3) Å.

Computing details

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXTL (Release 5.1; Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Release 5.1; Sheldrick, 2008); molecular graphics: SHELXTL (Release 5.1; Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Release 5.1; Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. Overlay of molecules (I-1) and (I-2) [(I-1): red balls and (I-2): black balls].
	Fig. 2. Perspective views of (a) molecule (I-1) and (b) molecule (I-2), with the atom-numbering schemes. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary size.
	Fig. 3. The crystal packing of (I), showing the intermolecular hydrogen-bonding network (projection parallel to the a axis).

1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-(prop-1-ynyl)-pyrimidin- 2,4(1H,3H)-dione

Crystal data

C12H14N2O5	F(000) = 560
Mr = 266.25	Dx = 1.465 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 8767 reflections
a = 5.6201 (4) Å	θ = 2.1–27.2°
b = 11.3645 (9) Å	µ = 0.12 mm^−1
c = 19.0281 (16) Å	T = 130 K
β = 96.659 (4)°	Splitter, colourless
V = 1207.12 (16) Å^3	0.32 × 0.23 × 0.15 mm
Z = 4

Data collection

Bruker APEXII CCD diffractometer	3046 independent reflections
Radiation source: fine-focus sealed tube	2749 reflections with I > I > 2σ(I)
Graphite monochromator	Rint = 0.032
ϕ and ω scans	θmax = 28.0°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −6→7
Tmin = 0.866, Tmax = 0.932	k = −15→15
22751 measured reflections	l = −24→21

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)] = 0.033	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.088	w = 1/[σ^2(Fo^2) + (0.0569P)^2 + 0.1534P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
3046 reflections	Δρmax = 0.22 e Å^−3
363 parameters	Δρmin = −0.23 e Å^−3
1 restraint	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	0.7378 (3)	0.86579 (17)	0.85035 (9)	0.0210 (4)
C12	0.8339 (4)	0.95301 (19)	0.81214 (11)	0.0203 (4)
O12	1.0174 (3)	1.00561 (15)	0.83437 (8)	0.0269 (4)
N13	0.7095 (3)	0.97674 (17)	0.74761 (10)	0.0203 (4)
H13	0.784 (4)	1.029 (2)	0.7210 (14)	0.024*
C14	0.5018 (4)	0.92284 (19)	0.71755 (11)	0.0202 (4)
O14	0.4145 (3)	0.95057 (15)	0.65774 (8)	0.0259 (3)
C15	0.4035 (4)	0.83586 (19)	0.76243 (11)	0.0204 (4)
C15A	0.1882 (4)	0.7760 (2)	0.73550 (11)	0.0221 (4)
C15B	0.0130 (4)	0.7267 (2)	0.70879 (12)	0.0237 (5)
C15C	−0.1945 (4)	0.6626 (2)	0.67431 (14)	0.0309 (5)
H15A	−0.1423	0.6082	0.6392	0.046*
H15B	−0.3101	0.7186	0.6507	0.046*
H15C	−0.2701	0.6182	0.7099	0.046*
C16	0.5264 (4)	0.8107 (2)	0.82633 (11)	0.0213 (4)
H16	0.4642	0.7530	0.8554	0.026*
C11'	0.8771 (4)	0.8255 (2)	0.91631 (11)	0.0202 (4)
H11	1.0464	0.8533	0.9177	0.024*
C12'	0.7777 (4)	0.86196 (19)	0.98385 (11)	0.0223 (4)
H12A	0.8318	0.9417	0.9994	0.027*
H12B	0.6005	0.8587	0.9787	0.027*
C13'	0.8887 (4)	0.7678 (2)	1.03343 (11)	0.0226 (4)
H13A	0.8053	0.7599	1.0769	0.027*
O13'	1.1371 (3)	0.79645 (17)	1.04968 (9)	0.0339 (4)
H13B	1.185 (6)	0.772 (3)	1.0920 (18)	0.051*
O14'	0.8719 (3)	0.70062 (13)	0.91573 (8)	0.0231 (3)
C14'	0.8609 (4)	0.65840 (19)	0.98698 (11)	0.0209 (4)
H14A	1.0021	0.6061	1.0002	0.025*
C15'	0.6351 (4)	0.5863 (2)	0.98959 (14)	0.0288 (5)
H15D	0.6442	0.5152	0.9599	0.035*
H15E	0.6272	0.5600	1.0389	0.035*
O15'	0.4227 (3)	0.64869 (17)	0.96585 (11)	0.0392 (4)
H15	0.380 (6)	0.694 (4)	1.0033 (19)	0.059*
N21	0.2689 (3)	0.25813 (16)	0.64819 (9)	0.0181 (3)
C22	0.1537 (3)	0.18063 (19)	0.68903 (10)	0.0192 (4)
O22	−0.0312 (3)	0.13036 (14)	0.66568 (8)	0.0237 (3)
N23	0.2617 (3)	0.16513 (17)	0.75642 (9)	0.0201 (4)
H23	0.183 (5)	0.120 (2)	0.7850 (14)	0.024*
C24	0.4672 (4)	0.21946 (19)	0.78774 (11)	0.0190 (4)
O24	0.5462 (3)	0.19467 (15)	0.84885 (8)	0.0266 (3)
C25	0.5714 (3)	0.30420 (19)	0.74306 (11)	0.0191 (4)
C25A	0.7817 (4)	0.3677 (2)	0.77105 (11)	0.0216 (4)
C25B	0.9560 (4)	0.4205 (2)	0.79559 (12)	0.0234 (4)
C25C	1.1650 (4)	0.4875 (2)	0.82612 (13)	0.0282 (5)
H25A	1.2495	0.5192	0.7880	0.042*
H25B	1.2728	0.4357	0.8562	0.042*
H25C	1.1129	0.5524	0.8546	0.042*
C26	0.4661 (3)	0.31987 (19)	0.67593 (11)	0.0189 (4)
H26	0.5325	0.3763	0.6469	0.023*
C21'	0.1675 (3)	0.2691 (2)	0.57282 (10)	0.0186 (4)
H21	0.1275	0.1892	0.5528	0.022*
C22'	−0.0533 (3)	0.3478 (2)	0.56150 (11)	0.0214 (4)
H22A	−0.2023	0.3020	0.5632	0.026*
H22B	−0.0462	0.4115	0.5972	0.026*
C23'	−0.0366 (4)	0.3963 (2)	0.48803 (11)	0.0215 (4)
H23A	−0.1206	0.4737	0.4809	0.026*
O23'	−0.1352 (3)	0.31115 (16)	0.43779 (9)	0.0298 (4)
H23B	−0.197 (6)	0.341 (3)	0.4027 (18)	0.045*
O24'	0.3430 (2)	0.32191 (14)	0.53589 (8)	0.0214 (3)
C24'	0.2340 (4)	0.40943 (19)	0.48614 (11)	0.0203 (4)
H24A	0.2727	0.3891	0.4376	0.024*
C25'	0.3314 (4)	0.5304 (2)	0.50523 (13)	0.0284 (5)
H25D	0.5086	0.5284	0.5104	0.034*
H25E	0.2767	0.5864	0.4668	0.034*
O25'	0.2520 (4)	0.56944 (17)	0.56967 (11)	0.0393 (5)
H25	0.242 (7)	0.639 (4)	0.566 (2)	0.059*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N11	0.0194 (8)	0.0267 (9)	0.0160 (8)	−0.0019 (7)	−0.0027 (7)	0.0051 (8)
C12	0.0192 (9)	0.0235 (11)	0.0178 (10)	−0.0016 (8)	0.0006 (8)	0.0006 (9)
O12	0.0246 (8)	0.0323 (9)	0.0222 (8)	−0.0081 (7)	−0.0044 (6)	0.0056 (7)
N13	0.0222 (8)	0.0237 (9)	0.0143 (9)	−0.0023 (7)	−0.0011 (7)	0.0039 (7)
C14	0.0194 (9)	0.0229 (10)	0.0178 (10)	0.0013 (8)	−0.0006 (8)	−0.0033 (8)
O14	0.0293 (8)	0.0293 (8)	0.0171 (8)	−0.0024 (7)	−0.0051 (6)	0.0016 (7)
C15	0.0179 (9)	0.0238 (10)	0.0188 (10)	0.0001 (8)	−0.0008 (8)	−0.0004 (8)
C15A	0.0226 (10)	0.0243 (11)	0.0189 (10)	0.0010 (9)	0.0004 (8)	0.0024 (9)
C15B	0.0231 (10)	0.0263 (11)	0.0211 (10)	−0.0002 (9)	−0.0008 (8)	0.0007 (9)
C15C	0.0234 (10)	0.0294 (12)	0.0390 (14)	−0.0046 (10)	−0.0009 (9)	−0.0049 (11)
C16	0.0180 (9)	0.0251 (10)	0.0205 (10)	−0.0026 (9)	0.0006 (8)	0.0018 (9)
C11'	0.0163 (9)	0.0250 (11)	0.0181 (10)	−0.0022 (8)	−0.0028 (8)	0.0052 (8)
C12'	0.0298 (11)	0.0159 (9)	0.0204 (10)	−0.0003 (8)	−0.0004 (8)	−0.0018 (8)
C13'	0.0243 (10)	0.0254 (10)	0.0175 (9)	−0.0048 (9)	−0.0007 (8)	0.0021 (9)
O13'	0.0318 (9)	0.0468 (11)	0.0200 (8)	−0.0163 (8)	−0.0108 (7)	0.0096 (8)
O14'	0.0271 (8)	0.0222 (8)	0.0197 (7)	0.0054 (6)	0.0020 (6)	−0.0016 (6)
C14'	0.0199 (9)	0.0203 (10)	0.0219 (10)	0.0016 (8)	−0.0001 (8)	0.0019 (8)
C15'	0.0282 (11)	0.0225 (11)	0.0357 (13)	−0.0070 (9)	0.0034 (9)	−0.0007 (10)
O15'	0.0220 (8)	0.0405 (10)	0.0554 (12)	−0.0037 (8)	0.0055 (8)	−0.0057 (10)
N21	0.0172 (8)	0.0215 (8)	0.0148 (8)	−0.0002 (7)	−0.0015 (6)	0.0006 (7)
C22	0.0198 (9)	0.0214 (10)	0.0161 (10)	0.0013 (8)	0.0009 (8)	0.0021 (9)
O22	0.0204 (7)	0.0293 (8)	0.0202 (8)	−0.0069 (6)	−0.0033 (6)	0.0044 (6)
N23	0.0192 (8)	0.0236 (9)	0.0166 (9)	−0.0030 (7)	−0.0011 (6)	0.0027 (7)
C24	0.0183 (9)	0.0204 (10)	0.0177 (10)	0.0015 (8)	−0.0005 (8)	−0.0022 (8)
O24	0.0289 (8)	0.0321 (9)	0.0170 (7)	−0.0046 (7)	−0.0051 (6)	0.0022 (7)
C25	0.0176 (9)	0.0210 (10)	0.0187 (10)	0.0001 (8)	0.0015 (7)	−0.0031 (8)
C25A	0.0231 (10)	0.0246 (11)	0.0169 (10)	0.0003 (9)	0.0012 (8)	−0.0005 (8)
C25B	0.0251 (10)	0.0238 (11)	0.0209 (11)	−0.0016 (9)	0.0013 (8)	−0.0011 (9)
C25C	0.0248 (11)	0.0260 (11)	0.0325 (13)	−0.0064 (9)	−0.0027 (9)	−0.0039 (10)
C26	0.0174 (9)	0.0207 (10)	0.0187 (10)	−0.0011 (8)	0.0022 (8)	−0.0009 (9)
C21'	0.0180 (9)	0.0248 (10)	0.0128 (9)	0.0013 (8)	0.0004 (7)	−0.0002 (8)
C22'	0.0156 (9)	0.0296 (11)	0.0188 (10)	0.0008 (8)	0.0006 (7)	0.0014 (9)
C23'	0.0208 (10)	0.0236 (10)	0.0191 (10)	0.0003 (8)	−0.0018 (8)	0.0014 (8)
O23'	0.0364 (9)	0.0322 (9)	0.0175 (8)	−0.0042 (7)	−0.0104 (7)	0.0037 (7)
O24'	0.0176 (7)	0.0290 (8)	0.0180 (7)	0.0036 (6)	0.0036 (5)	0.0049 (6)
C24'	0.0224 (10)	0.0225 (10)	0.0162 (10)	0.0023 (8)	0.0028 (8)	0.0022 (8)
C25'	0.0256 (11)	0.0272 (11)	0.0323 (13)	−0.0021 (9)	0.0037 (9)	0.0039 (10)
O25'	0.0541 (12)	0.0268 (9)	0.0380 (10)	−0.0042 (9)	0.0098 (8)	−0.0075 (8)

Geometric parameters (Å, º)

N11—C16	1.374 (3)	N21—C26	1.365 (3)
N11—C12	1.376 (3)	N21—C22	1.384 (3)
N11—C11'	1.473 (3)	N21—C21'	1.486 (2)
C12—O12	1.224 (3)	C22—O22	1.224 (3)
C12—N13	1.367 (3)	C22—N23	1.365 (3)
N13—C14	1.382 (3)	N23—C24	1.382 (3)
N13—H13	0.91 (3)	N23—H23	0.90 (3)
C14—O14	1.227 (3)	C24—O24	1.228 (3)
C14—C15	1.456 (3)	C24—C25	1.452 (3)
C15—C16	1.358 (3)	C25—C26	1.356 (3)
C15—C15A	1.431 (3)	C25—C25A	1.433 (3)
C15A—C15B	1.194 (3)	C25A—C25B	1.197 (3)
C15B—C15C	1.464 (3)	C25B—C25C	1.462 (3)
C15C—H15A	0.9800	C25C—H25A	0.9800
C15C—H15B	0.9800	C25C—H25B	0.9800
C15C—H15C	0.9800	C25C—H25C	0.9800
C16—H16	0.9500	C26—H26	0.9500
C11'—O14'	1.420 (3)	C21'—O24'	1.410 (2)
C11'—C12'	1.517 (3)	C21'—C22'	1.524 (3)
C11'—H11	1.0000	C21'—H21	1.0000
C12'—C13'	1.513 (3)	C22'—C23'	1.516 (3)
C12'—H12A	0.9900	C22'—H22A	0.9900
C12'—H12B	0.9900	C22'—H22B	0.9900
C13'—O13'	1.432 (3)	C23'—O23'	1.427 (3)
C13'—C14'	1.523 (3)	C23'—C24'	1.533 (3)
C13'—H13A	1.0000	C23'—H23A	1.0000
O13'—H13B	0.86 (3)	O23'—H23B	0.79 (3)
O14'—C14'	1.446 (3)	O24'—C24'	1.458 (2)
C14'—C15'	1.516 (3)	C24'—C25'	1.509 (3)
C14'—H14A	1.0000	C24'—H24A	1.0000
C15'—O15'	1.417 (3)	C25'—O25'	1.423 (3)
C15'—H15D	0.9900	C25'—H25D	0.9900
C15'—H15E	0.9900	C25'—H25E	0.9900
O15'—H15	0.94 (4)	O25'—H25	0.80 (4)
C16—N11—C12	121.99 (18)	C26—N21—C22	121.44 (17)
C16—N11—C11'	119.71 (17)	C26—N21—C21'	122.23 (17)
C12—N11—C11'	118.14 (17)	C22—N21—C21'	116.33 (16)
O12—C12—N13	122.43 (19)	O22—C22—N23	123.19 (18)
O12—C12—N11	122.38 (19)	O22—C22—N21	121.74 (18)
N13—C12—N11	115.19 (18)	N23—C22—N21	115.07 (18)
C12—N13—C14	127.11 (18)	C22—N23—C24	127.27 (18)
C12—N13—H13	114.0 (17)	C22—N23—H23	116.4 (17)
C14—N13—H13	118.6 (16)	C24—N23—H23	116.0 (17)
O14—C14—N13	119.83 (19)	O24—C24—N23	119.85 (19)
O14—C14—C15	125.47 (19)	O24—C24—C25	125.49 (19)
N13—C14—C15	114.69 (18)	N23—C24—C25	114.66 (17)
C16—C15—C15A	122.8 (2)	C26—C25—C25A	122.3 (2)
C16—C15—C14	118.70 (19)	C26—C25—C24	118.50 (19)
C15A—C15—C14	118.39 (18)	C25A—C25—C24	119.16 (18)
C15B—C15A—C15	175.8 (2)	C25B—C25A—C25	178.8 (2)
C15A—C15B—C15C	177.3 (2)	C25A—C25B—C25C	178.5 (2)
C15B—C15C—H15A	109.5	C25B—C25C—H25A	109.5
C15B—C15C—H15B	109.5	C25B—C25C—H25B	109.5
H15A—C15C—H15B	109.5	H25A—C25C—H25B	109.5
C15B—C15C—H15C	109.5	C25B—C25C—H25C	109.5
H15A—C15C—H15C	109.5	H25A—C25C—H25C	109.5
H15B—C15C—H15C	109.5	H25B—C25C—H25C	109.5
C15—C16—N11	122.2 (2)	C25—C26—N21	122.88 (19)
C15—C16—H16	118.9	C25—C26—H26	118.6
N11—C16—H16	118.9	N21—C26—H26	118.6
O14'—C11'—N11	107.19 (17)	O24'—C21'—N21	107.74 (15)
O14'—C11'—C12'	105.68 (17)	O24'—C21'—C22'	106.56 (17)
N11—C11'—C12'	115.16 (17)	N21—C21'—C22'	113.62 (16)
O14'—C11'—H11	109.5	O24'—C21'—H21	109.6
N11—C11'—H11	109.5	N21—C21'—H21	109.6
C12'—C11'—H11	109.5	C22'—C21'—H21	109.6
C13'—C12'—C11'	99.75 (17)	C23'—C22'—C21'	101.96 (16)
C13'—C12'—H12A	111.8	C23'—C22'—H22A	111.4
C11'—C12'—H12A	111.8	C21'—C22'—H22A	111.4
C13'—C12'—H12B	111.8	C23'—C22'—H22B	111.4
C11'—C12'—H12B	111.8	C21'—C22'—H22B	111.4
H12A—C12'—H12B	109.5	H22A—C22'—H22B	109.2
O13'—C13'—C12'	107.14 (18)	O23'—C23'—C22'	108.09 (18)
O13'—C13'—C14'	110.06 (18)	O23'—C23'—C24'	111.08 (18)
C12'—C13'—C14'	102.04 (16)	C22'—C23'—C24'	102.99 (16)
O13'—C13'—H13A	112.3	O23'—C23'—H23A	111.4
C12'—C13'—H13A	112.3	C22'—C23'—H23A	111.4
C14'—C13'—H13A	112.3	C24'—C23'—H23A	111.4
C13'—O13'—H13B	108 (2)	C23'—O23'—H23B	112 (3)
C11'—O14'—C14'	109.12 (16)	C21'—O24'—C24'	110.38 (15)
O14'—C14'—C15'	109.69 (18)	O24'—C24'—C25'	110.62 (17)
O14'—C14'—C13'	105.11 (17)	O24'—C24'—C23'	105.17 (16)
C15'—C14'—C13'	116.88 (18)	C25'—C24'—C23'	114.59 (18)
O14'—C14'—H14A	108.3	O24'—C24'—H24A	108.8
C15'—C14'—H14A	108.3	C25'—C24'—H24A	108.8
C13'—C14'—H14A	108.3	C23'—C24'—H24A	108.8
O15'—C15'—C14'	113.38 (19)	O25'—C25'—C24'	110.49 (18)
O15'—C15'—H15D	108.9	O25'—C25'—H25D	109.6
C14'—C15'—H15D	108.9	C24'—C25'—H25D	109.6
O15'—C15'—H15E	108.9	O25'—C25'—H25E	109.6
C14'—C15'—H15E	108.9	C24'—C25'—H25E	109.6
H15D—C15'—H15E	107.7	H25D—C25'—H25E	108.1
C15'—O15'—H15	109 (2)	C25'—O25'—H25	105 (3)
C16—N11—C12—O12	177.2 (2)	C26—N21—C22—O22	175.6 (2)
C11'—N11—C12—O12	−7.4 (3)	C21'—N21—C22—O22	−5.0 (3)
C16—N11—C12—N13	−2.8 (3)	C26—N21—C22—N23	−4.4 (3)
C11'—N11—C12—N13	172.68 (18)	C21'—N21—C22—N23	174.96 (18)
O12—C12—N13—C14	179.9 (2)	O22—C22—N23—C24	−178.7 (2)
N11—C12—N13—C14	−0.1 (3)	N21—C22—N23—C24	1.3 (3)
C12—N13—C14—O14	−177.3 (2)	C22—N23—C24—O24	−178.5 (2)
C12—N13—C14—C15	3.2 (3)	C22—N23—C24—C25	1.8 (3)
O14—C14—C15—C16	177.0 (2)	O24—C24—C25—C26	178.5 (2)
N13—C14—C15—C16	−3.5 (3)	N23—C24—C25—C26	−1.9 (3)
O14—C14—C15—C15A	0.4 (3)	O24—C24—C25—C25A	−1.2 (3)
N13—C14—C15—C15A	179.87 (19)	N23—C24—C25—C25A	178.46 (18)
C15A—C15—C16—N11	177.5 (2)	C25A—C25—C26—N21	178.56 (19)
C14—C15—C16—N11	1.1 (3)	C24—C25—C26—N21	−1.1 (3)
C12—N11—C16—C15	2.3 (3)	C22—N21—C26—C25	4.5 (3)
C11'—N11—C16—C15	−173.1 (2)	C21'—N21—C26—C25	−174.86 (19)
C16—N11—C11'—O14'	41.5 (2)	C26—N21—C21'—O24'	16.6 (3)
C12—N11—C11'—O14'	−134.04 (19)	C22—N21—C21'—O24'	−162.79 (17)
C16—N11—C11'—C12'	−75.7 (2)	C26—N21—C21'—C22'	−101.2 (2)
C12—N11—C11'—C12'	108.7 (2)	C22—N21—C21'—C22'	79.4 (2)
O14'—C11'—C12'—C13'	38.6 (2)	O24'—C21'—C22'—C23'	32.0 (2)
N11—C11'—C12'—C13'	156.69 (18)	N21—C21'—C22'—C23'	150.47 (17)
C11'—C12'—C13'—O13'	74.6 (2)	C21'—C22'—C23'—O23'	82.53 (19)
C11'—C12'—C13'—C14'	−41.07 (19)	C21'—C22'—C23'—C24'	−35.1 (2)
N11—C11'—O14'—C14'	−143.82 (16)	N21—C21'—O24'—C24'	−137.97 (17)
C12'—C11'—O14'—C14'	−20.5 (2)	C22'—C21'—O24'—C24'	−15.7 (2)
C11'—O14'—C14'—C15'	120.12 (19)	C21'—O24'—C24'—C25'	117.15 (18)
C11'—O14'—C14'—C13'	−6.3 (2)	C21'—O24'—C24'—C23'	−7.1 (2)
O13'—C13'—C14'—O14'	−83.08 (19)	O23'—C23'—C24'—O24'	−88.7 (2)
C12'—C13'—C14'—O14'	30.4 (2)	C22'—C23'—C24'—O24'	26.8 (2)
O13'—C13'—C14'—C15'	155.03 (19)	O23'—C23'—C24'—C25'	149.61 (19)
C12'—C13'—C14'—C15'	−91.5 (2)	C22'—C23'—C24'—C25'	−94.9 (2)
O14'—C14'—C15'—O15'	−56.9 (3)	O24'—C24'—C25'—O25'	−68.6 (2)
C13'—C14'—C15'—O15'	62.6 (3)	C23'—C24'—C25'—O25'	50.1 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N13—H13···O22^i	0.91 (3)	1.94 (3)	2.851 (2)	174 (2)
O13′—H13B···O24^ii	0.86 (3)	1.98 (4)	2.727 (2)	144 (3)
O15′—H15···O13′^iii	0.94 (4)	2.06 (4)	2.921 (3)	152 (3)
N23—H23···O12^iv	0.90 (3)	1.91 (3)	2.801 (2)	171 (2)
O23′—H23B···O14^v	0.79 (3)	2.01 (3)	2.760 (2)	158 (3)
O25′—H25···O23′^vi	0.80 (4)	2.04 (4)	2.824 (3)	166 (4)

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