2′-De­oxy-5-propynyl­cytidine: a nucleoside forming two solid-state conformations

The title compound, 4-amino-1-(2-deoxy-β-D-erythropentofuranosyl)-5-(prop-1-ynyl)pyrimidin-2(1H)-one, C₁₂H₁₅N₃O₄, shows two conformations in the crystalline state which differ mainly in the glycosylic bond torsion angle and the sugar pucker. Both mol­ecules exhibit an anti glycosylic bond conformation, with torsion angles χ = −135.0 (2) and −156.4 (2)° for mol­ecules 1 and 2, respectively. The sugar moieties show a twisted C2′-endo sugar pucker (S-type), with P = 173.3 and 192.5° for mol­ecules 1 and 2, respectively. The crystal structure is characterized by a three-dimensional network that is stabilized by several inter­molecular hydrogen bonds between the two conformers.

S1. Comment

Advances in synthetic nucleic acid chemistry have led to a broad variety of structurally modified DNA constituents, including modifications on the nucleobase or the sugar moiety (Seela & Zulauf, 1998; Wang et al., 2000). Their introduction into DNA oligonucleotides has provided modified nucleic acids with superior properties compared with their parent counterparts, e.g. increased duplex stability or mismatch recognition (Barnes & Turner, 2001; Froehler et al., 1992; He & Seela, 2002). For pyrimidine nucleosides, the 5-position of the nucleobases is an appropriate place to introduce functional groups such as halogens or propynyl groups, as this site lies in the major groove of the DNA duplex (Ahmadian et al., 1998). Modifications at this position are also well tolerated by RNA and DNA polymerases, which do not interact with the nucleobases in the major groove (Roychowdhury et al., 2004). 5-Propynylated pyrimidine nucleosides have been shown to increase duplex and triplex stability significantly, which makes them useful tools for application in antisense technology or in primer probe interactions, as well as for the construction of novel DNA constructs (Froehler et al., 1992; He & Seela, 2002; Seela & Budow, 2006; Seela, Budow & Leonard, 2006). The introduction of the propynyl group at the 5-position of cytosine lowers the pK_a value of the heterocycle from 4.5 to 3.3 (Robles et al., 2002). Thus, the protonation of N3 requires more strongly acidic conditions than the unsubstituted species. The shift of the pK_a value has a significant influence on the formation of the tetrameric i-motif structure, which is well known to be formed by cytosine-rich oligonucleotides under weakly acidic conditions (pH 5; Guéron & Leroy, 2000). The self-assembly of oligonucleotides in which consecutive 2'-deoxycytidine stretches are replaced by 2'-deoxy-5-propynylcytidine residues into the i-motif structure is simply achieved under significantly stronger acidic conditions (pH 3.5). 2'-Deoxy-5-propynylcytidine, (I), has also been used for the construction of a novel colorimetric assay, which is based on DNA gold nanoparticle conjugates responding selectively to pH changes in a narrow pH range between 4 and 3 (Seela & Budow, 2006; Seela, Budow & Leonard, 2006). Consequently, we became interested in performing a single-crystal X-ray analysis of compound (I), which is reported here.

This is the first X-ray structure of a propynylated 2'-deoxypyrimidine nucleoside. The X-ray structures of some purine-like propynyl nucleosides and ribonucleosides, such as 7-deaza-2'-deoxy-7-propynyladenosine, (IIIa) (Seela, Shaikh et al., 2006), 8-aza-7-deaza-7-propynyladenosine, (IIIb) (Lin et al., 2005) and 7-deaza-2'-deoxy-7-propynylguanosine, (IV) (Seela, Shaikh & Eickmeier, 2004), have been reported recently.

Compound (I) was synthesized from 2'-deoxy-5-iodocytidine, (IIa), and propyne gas using the palladium-catalyzed Sonogashira cross-coupling reaction (Hobbs, 1989; Froehler et al., 1992; Seela, Budow & Leonard, 2006). Slow crystallization of 2'-deoxy-5-propynylcytidine from a mixture of dichloromethane and methanol (85:15) gave colourless crystals. The crystals consist of two forms of molecules which differ in their conformation. They are here denoted (I-1) and (I-2). Similar results have been found for crystals of 2'-deoxy-5-propynyluridine (Seela, Budow & Eickmeier, 2006) and 4-nitro-2H-indazole-N²-ribonucleoside (Seela, Peng et al., 2004). The three-dimensional structures of the two molecules of 2'-deoxy-5-propynylcytidine, type 1, (I-1), and type 2, (I-2), are shown in Fig. 1, and selected geometric parameters are listed in Table 1. The glycosylic torsion angle in pyrimidine nucleosides is generally found to be anti and only in rare cases has the syn conformation been reported (Saenger, 1984). 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).

In the crystalline state of (I), both types of molecules, (I-1) and (I-2), adopt anti conformations for the glycosylic bond. For (I-1), the torsion angle of the glycosylic bond is χ = −135.0 (2)°, which is very similar to the torsion angle in 2'-deoxy-5-methylcytidine, (IIb) (χ = −131.7°; Sato, 1988; Seela et al., 2000). In comparison, the glycosylic bond torsion angle of (I-2) is χ = −156.4 (2)°.

The lengths of the N1—C1' glycosylic bonds of (I-1) and (I-2) are very similar [1.475 (2) Å for (I-1) and 1.490 (2) Å for (I-2)], while the N21—C1' bond of (IIb) is slightly shorter [1.461 (3) Å; Sato, 1988].

The 2'-deoxyribofuranosyl moieties of (I-1) and (I-2) show an S-type conformation and exhibit a twisted C2'-endo sugar puckering. This is consistent with the preferred conformation of 2'-deoxyribonucleotides (Saenger, 1984). Molecule (I-1) shows a pseudorotational phase angle P = 173.3°, with the maximum amplitude τ_m = 37.5° referring to a major C2'-endo sugar puckering (C2'-endo–C3'-exo, ²T₃) (Rao et al., 1981), and molecule (I-2) exhibits a minor 2'-endo sugar puckering (C3'-exo–C2'-endo, ₃T²), with P = 192.5° and τ_m = 34.2°. Compound (IIb) also exhibits a similar sugar conformation (C2'-endo, ²E, with P = 161.5° and τ_m = 37.9°; Sato, 1988; Seela et al., 2000).

Both (I-1) and (I-2) display different conformations about the C4'—C5' bond, which is defined by the torsion angle γ (O5'—C5'—C4'—C3'). For molecule (I-1), the torsion angle γ = 57.8 (3)°, representing a synclinal (+gauche) conformation, whereas in (I-2) the C4'—C5' bond adopts an antiperiplanar (trans) conformation, with γ = 166.1 (2)°. The same antiperiplanar conformation of the exocyclic group has been reported for 2'-deoxy-5-methylcytidine, (IIb) [γ = 178.7 (2)°; Sato, 1988].

The heterocyclic ring systems of (I-1) and (I-2) are nearly planar; the r.m.s. deviations of the ring atoms (N1/C2/N3/C4/C5/C6) from their calculated least-squares planes are 0.0074 and 0.0143 Å, respectively. In both molecules, the exocyclic groups lie on both sides of the pyrimidine ring system.

The propynyl groups of (I-1) and (I-2) form an almost linear and rigid residue [C151—C152—C153 = 179.3 (3)° for (I-1) and C251—C252—C253 = 178.7 (3)° for (I-2)]. In both molecules, the propynyl groups are inclined with respect to the pyrimidine ring plane. The angles of inclination have been calculated as the deviation of the propynyl group (atoms C151 and C251) from the normal to the pyrimidine plane (atoms C15 and C25). For molecule (I-1), the angle is 3.5°, which is within the range observed in 1-(β-D-arabinofuranosyl)-5-propynyluracil (3.7°; Cygler et al., 1984). The angle of inclination of (I-2) is larger (4.4°) and similar to the angles found for 7-deaza-2'-deoxy-7-propynylguanosine, (IV) (4.6°; Seela, Shaikh & Eickmeier, 2004), and 8-aza-7-deaza-7-propynyladenosine, (IIIb) (4.0°; Lin et al., 2005). Only in the case of 7-deaza-2'-deoxy-7-propynyladenosine, (IIIa), is the propynyl group in a nearly coplanar orientation with respect to the nucleobase moiety (1.6°; Seela, Shaikh et al., 2006). The triple-bond length of (I-1) is 1.190 (3) Å and that for (I-2) is 1.183 (3) Å, which are both in the range of non-conjugated triple bonds (Cygler et al., 1984).

In the crystal structure of nucleoside (I), molecules (I-1) and (I-2) are linked into sheets by several intermolecular hydrogen bonds (Table 2 and Fig. 2). These sheets are stabilized by two types of hydrogen bonds. Molecules of different conformation are linked through hydrogen bonds between neighbouring base and sugar units (O13'—H13'···O22ⁱⁱⁱ and N14—H14A···N23ⁱ, and O23'—H23'···O12^vii and N24—H24A···N13^v; symmetry codes are given in Table 2). Two further hydrogen bonds between the sugar moieties and the nucleobases are found connecting molecules of identical conformation (N14—H14B···O13'ⁱⁱ and O15'—H15'···N13^iv for (I-1), and N24—H24B···O23'^vi and O25'—H25'···N23^viii for (I-2); symmetry codes are given in Table 2). The sheets are built up by alternating chains consisting of conformers (I-1) and (I-2). Each of these chains contains only one type of conformer, as demonstrated in Fig. 2.

S2. Experimental

Compound (I) was synthesized from (IIa) following literature procedures (Hobbs, 1989; Froehler et al., 1992; Seela, Budow & Leonard, 2006) and was slowly crystallized from a mixture of dichoromethane and methanol (85:15) as colourless crystals [481 K (decomposition)]. For the X-ray diffraction experiment, a single-crystal was fixed at the top of a Lindemann capillary using epoxy resin.

S3. Refinement

In the absence of suitable anomalous scattering, Friedel equivalents could not be used to determine the absolute structure. Refinement of the Flack parameter (Flack, 1983) led to an inconclusive value (Flack & Bernardinelli, 2000) [−0.2 (8)]. Therefore, Friedel equivalents (428) 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, H atoms were placed in geometrically idealized positions, with C—H = 0.93–0.98 Å and N—H 0.86 Å, and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C) or 1.2U_eq(N). The OH groups were refined as rigid groups allowed to rotate but not tip, with O—H = 0.82 Å and U_iso(H) = 1.5U_eq(O).

Computing details

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: SHELXTL (Sheldrick, 1997); program(s) used to solve structure: SHELXTL; program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and DIAMOND (Brandenburg, 1999); software used to prepare material for publication: SHELXTL and PLATON (Spek, 2003).

Figures

	Fig. 1. Perspective views of (a) molecule (I-1) and (b) molecule (I-2). Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary radii.
	Fig. 2. A ball-and-stick model of molecules (I-1) and (I-2) within one sheet of the crystal structure of (I), viewed perpendicular to the sheet of molecules. Intermolecular hydrogen bonds are represented by dashed lines. [Figure seems to have been cropped. Please provide complete image]

4-amino-1-(2-deoxy-β-D-erythropentofuranosyl)-5-(prop-1- ynyl)pyrimidine-2(1H)-one

Crystal data

C12H15N3O4	Z = 2
Mr = 265.27	F(000) = 280
Triclinic, P1	Dx = 1.395 Mg m^−3
Hall symbol: P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.3908 (7) Å	Cell parameters from 38 reflections
b = 9.0698 (8) Å	θ = 5.1–12.5°
c = 9.7303 (10) Å	µ = 0.11 mm^−1
α = 64.734 (5)°	T = 293 K
β = 71.721 (10)°	Block, colourless
γ = 88.198 (11)°	0.3 × 0.2 × 0.2 mm
V = 631.33 (10) Å^3

Data collection

Bruker P4 diffractometer	Rint = 0.018
Radiation source: fine-focus sealed tube	θmax = 30.0°, θmin = 2.5°
Graphite monochromator	h = −1→11
ω/2θ scans	k = −11→11
4107 measured reflections	l = −13→13
3456 independent reflections	3 standard reflections every 97 reflections
3173 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.112	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0675P)^2 + 0.0502P] where P = (Fo^2 + 2Fc^2)/3
3456 reflections	(Δ/σ)max < 0.001
350 parameters	Δρmax = 0.28 e Å^−3
3 restraints	Δρmin = −0.19 e Å^−3

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	0.2528 (2)	0.8420 (2)	0.5264 (2)	0.0312 (4)
C12	0.3927 (3)	0.8667 (3)	0.5657 (2)	0.0343 (4)
O12	0.3998 (3)	0.7764 (3)	0.7011 (2)	0.0524 (5)
N13	0.5185 (2)	0.9888 (2)	0.4528 (2)	0.0364 (4)
C14	0.5073 (2)	1.0835 (2)	0.3077 (2)	0.0298 (4)
N14	0.6358 (2)	1.1976 (3)	0.2009 (2)	0.0397 (4)
H14A	0.7226	1.2087	0.2263	0.048*
H14B	0.6323	1.2604	0.1065	0.048*
C15	0.3630 (3)	1.0625 (2)	0.2646 (2)	0.0292 (4)
C151	0.3583 (3)	1.1594 (3)	0.1057 (3)	0.0345 (4)
C152	0.3673 (4)	1.2376 (3)	−0.0312 (3)	0.0457 (6)
C153	0.3766 (7)	1.3322 (5)	−0.1990 (4)	0.0767 (11)
H15A	0.2645	1.3479	−0.2041	0.115*
H15B	0.4300	1.2738	−0.2600	0.115*
H15C	0.4412	1.4371	−0.2431	0.115*
C16	0.2383 (3)	0.9403 (3)	0.3802 (2)	0.0312 (4)
H16A	0.1416	0.9238	0.3588	0.037*
C11'	0.1217 (2)	0.7021 (2)	0.6418 (2)	0.0295 (4)
H11A	0.1661	0.6232	0.7229	0.035*
C12'	−0.0426 (3)	0.7491 (3)	0.7249 (2)	0.0322 (4)
H12A	−0.0654	0.8556	0.6550	0.039*
H12B	−0.0415	0.7506	0.8237	0.039*
C13'	−0.1712 (2)	0.6118 (3)	0.7592 (2)	0.0319 (4)
H13C	−0.2834	0.6487	0.7674	0.038*
O13'	−0.1782 (3)	0.4660 (2)	0.8981 (2)	0.0510 (5)
H13'	−0.1080	0.4787	0.9359	0.077*
C14'	−0.1002 (3)	0.5807 (3)	0.6105 (2)	0.0326 (4)
H14C	−0.1210	0.4627	0.6440	0.039*
C15'	−0.1712 (4)	0.6716 (4)	0.4757 (3)	0.0501 (6)
H15D	−0.1164	0.6445	0.3870	0.060*
H15E	−0.2909	0.6348	0.5138	0.060*
O15'	−0.1485 (3)	0.8445 (3)	0.4185 (3)	0.0587 (6)
H15'	−0.2370	0.8750	0.4577	0.088*
O14'	0.08167 (19)	0.6265 (2)	0.5534 (2)	0.0353 (3)
N21	0.1558 (2)	0.4391 (2)	0.2363 (2)	0.0343 (4)
C22	0.0112 (3)	0.4245 (4)	0.2001 (3)	0.0480 (7)
O22	0.0105 (3)	0.5114 (4)	0.0625 (3)	0.0827 (10)
N23	−0.1239 (3)	0.3179 (3)	0.3171 (2)	0.0498 (6)
C24	−0.1198 (3)	0.2342 (3)	0.4670 (3)	0.0361 (5)
N24	−0.2572 (3)	0.1340 (3)	0.5776 (3)	0.0483 (6)
H24A	−0.3440	0.1251	0.5514	0.058*
H24B	−0.2593	0.0782	0.6753	0.058*
C25	0.0246 (3)	0.2523 (3)	0.5095 (2)	0.0311 (4)
C251	0.0180 (3)	0.1685 (3)	0.6742 (3)	0.0356 (4)
C252	−0.0079 (4)	0.1007 (3)	0.8148 (3)	0.0446 (5)
C253	−0.0432 (6)	0.0189 (6)	0.9898 (4)	0.0780 (12)
H25A	−0.1456	0.0511	1.0424	0.117*
H25B	0.0488	0.0501	1.0145	0.117*
H256	−0.0558	−0.0980	1.0269	0.117*
C26	0.1604 (3)	0.3557 (3)	0.3883 (2)	0.0318 (4)
H26A	0.2578	0.3695	0.4099	0.038*
C21'	0.3014 (2)	0.5564 (3)	0.1025 (2)	0.0324 (4)
H2'A	0.3081	0.5523	0.0018	0.039*
C22'	0.2894 (3)	0.7317 (3)	0.0809 (3)	0.0384 (5)
H22A	0.2190	0.7345	0.1800	0.046*
H22B	0.2436	0.7940	−0.0043	0.046*
C23'	0.4728 (3)	0.7987 (3)	0.0360 (2)	0.0346 (4)
H23C	0.4768	0.8816	0.0747	0.042*
O23'	0.5618 (2)	0.8647 (2)	−0.1320 (2)	0.0451 (4)
H23'	0.5047	0.8417	−0.1763	0.068*
C24'	0.5432 (3)	0.6453 (3)	0.1306 (2)	0.0331 (4)
H24C	0.6635	0.6517	0.0726	0.040*
C25'	0.5205 (4)	0.6241 (4)	0.2999 (3)	0.0459 (6)
H25D	0.5989	0.7056	0.2928	0.055*
H25E	0.4068	0.6443	0.3472	0.055*
O25'	0.5475 (3)	0.4664 (3)	0.4024 (2)	0.0569 (5)
H25'	0.6425	0.4473	0.3619	0.085*
O24'	0.45129 (19)	0.5095 (2)	0.1374 (2)	0.0354 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N11	0.0262 (7)	0.0335 (9)	0.0260 (8)	−0.0064 (6)	−0.0095 (6)	−0.0046 (6)
C12	0.0287 (9)	0.0403 (11)	0.0273 (9)	−0.0065 (8)	−0.0112 (7)	−0.0070 (8)
O12	0.0499 (10)	0.0585 (11)	0.0313 (8)	−0.0201 (9)	−0.0220 (7)	0.0037 (8)
N13	0.0301 (8)	0.0392 (10)	0.0303 (8)	−0.0092 (7)	−0.0123 (7)	−0.0041 (7)
C14	0.0261 (8)	0.0295 (9)	0.0281 (9)	−0.0017 (7)	−0.0068 (7)	−0.0088 (7)
N14	0.0332 (9)	0.0386 (10)	0.0325 (9)	−0.0108 (8)	−0.0100 (7)	−0.0018 (7)
C15	0.0311 (9)	0.0285 (9)	0.0268 (9)	−0.0014 (7)	−0.0122 (7)	−0.0088 (7)
C151	0.0388 (10)	0.0317 (10)	0.0304 (9)	−0.0031 (8)	−0.0140 (8)	−0.0091 (8)
C152	0.0599 (16)	0.0397 (12)	0.0335 (11)	−0.0005 (11)	−0.0203 (11)	−0.0088 (9)
C153	0.115 (3)	0.070 (2)	0.0351 (13)	0.006 (2)	−0.0346 (18)	−0.0068 (14)
C16	0.0285 (9)	0.0329 (10)	0.0273 (9)	−0.0029 (7)	−0.0115 (7)	−0.0069 (7)
C11'	0.0249 (8)	0.0294 (9)	0.0275 (8)	−0.0049 (7)	−0.0082 (7)	−0.0062 (7)
C12'	0.0318 (9)	0.0336 (10)	0.0285 (8)	−0.0030 (7)	−0.0063 (7)	−0.0135 (7)
C13'	0.0266 (8)	0.0361 (10)	0.0275 (8)	−0.0040 (7)	−0.0062 (7)	−0.0106 (7)
O13'	0.0595 (11)	0.0440 (10)	0.0313 (8)	−0.0198 (9)	−0.0136 (8)	0.0006 (7)
C14'	0.0268 (8)	0.0367 (10)	0.0317 (9)	−0.0067 (7)	−0.0069 (7)	−0.0141 (8)
C15'	0.0434 (13)	0.0691 (18)	0.0369 (11)	−0.0098 (12)	−0.0174 (10)	−0.0184 (11)
O15'	0.0389 (9)	0.0623 (12)	0.0545 (11)	0.0008 (8)	−0.0214 (8)	−0.0029 (9)
O14'	0.0273 (7)	0.0387 (8)	0.0400 (8)	−0.0009 (6)	−0.0053 (6)	−0.0212 (6)
N21	0.0286 (8)	0.0382 (9)	0.0260 (8)	−0.0092 (7)	−0.0095 (6)	−0.0037 (7)
C22	0.0393 (12)	0.0552 (15)	0.0329 (11)	−0.0180 (11)	−0.0194 (9)	0.0024 (10)
O22	0.0638 (13)	0.102 (2)	0.0397 (10)	−0.0442 (14)	−0.0331 (10)	0.0221 (11)
N23	0.0388 (10)	0.0541 (13)	0.0349 (10)	−0.0195 (9)	−0.0176 (9)	0.0053 (9)
C24	0.0323 (10)	0.0349 (11)	0.0312 (10)	−0.0053 (8)	−0.0124 (8)	−0.0038 (8)
N24	0.0379 (10)	0.0490 (12)	0.0349 (10)	−0.0136 (9)	−0.0114 (8)	0.0030 (9)
C25	0.0325 (10)	0.0296 (9)	0.0265 (8)	−0.0021 (8)	−0.0107 (7)	−0.0070 (7)
C251	0.0389 (10)	0.0339 (11)	0.0298 (9)	−0.0015 (8)	−0.0115 (8)	−0.0098 (8)
C252	0.0485 (13)	0.0479 (14)	0.0324 (10)	0.0049 (11)	−0.0144 (9)	−0.0123 (10)
C253	0.085 (3)	0.102 (3)	0.0334 (13)	0.030 (2)	−0.0217 (15)	−0.0174 (16)
C26	0.0318 (9)	0.0338 (10)	0.0270 (9)	−0.0032 (7)	−0.0116 (7)	−0.0089 (7)
C21'	0.0269 (8)	0.0371 (10)	0.0247 (8)	−0.0054 (7)	−0.0059 (7)	−0.0072 (7)
C22'	0.0295 (9)	0.0395 (11)	0.0351 (10)	0.0025 (8)	−0.0086 (8)	−0.0078 (8)
C23'	0.0359 (10)	0.0313 (10)	0.0293 (9)	−0.0033 (8)	−0.0068 (7)	−0.0092 (7)
O23'	0.0421 (9)	0.0479 (10)	0.0281 (7)	−0.0163 (7)	−0.0043 (6)	−0.0050 (7)
C24'	0.0272 (8)	0.0388 (10)	0.0292 (9)	−0.0025 (7)	−0.0074 (7)	−0.0121 (8)
C25'	0.0513 (14)	0.0522 (14)	0.0364 (11)	0.0002 (11)	−0.0196 (10)	−0.0175 (10)
O25'	0.0585 (12)	0.0636 (13)	0.0374 (9)	0.0079 (10)	−0.0205 (9)	−0.0090 (9)
O24'	0.0283 (7)	0.0344 (7)	0.0415 (8)	0.0014 (6)	−0.0116 (6)	−0.0147 (6)

Geometric parameters (Å, º)

N11—C16	1.361 (2)	N21—C26	1.356 (3)
N11—C12	1.395 (2)	N21—C22	1.390 (3)
N11—C11'	1.475 (2)	N21—C21'	1.490 (2)
C12—O12	1.239 (3)	C22—O22	1.232 (3)
C12—N13	1.362 (3)	C22—N23	1.355 (3)
N13—C14	1.335 (3)	N23—C24	1.338 (3)
C14—N14	1.328 (3)	C24—N24	1.328 (3)
C14—C15	1.442 (3)	C24—C25	1.432 (3)
N14—H14A	0.8600	N24—H24A	0.8600
N14—H14B	0.8600	N24—H24B	0.8600
C15—C16	1.363 (3)	C25—C26	1.360 (3)
C15—C151	1.428 (3)	C25—C251	1.434 (3)
C151—C152	1.190 (3)	C251—C252	1.183 (3)
C152—C153	1.462 (4)	C252—C253	1.469 (4)
C153—H15A	0.9600	C253—H25A	0.9600
C153—H15B	0.9600	C253—H25B	0.9600
C153—H15C	0.9600	C253—H256	0.9600
C16—H16A	0.9300	C26—H26A	0.9300
C11'—O14'	1.422 (3)	C21'—O24'	1.410 (3)
C11'—C12'	1.515 (3)	C21'—C22'	1.517 (4)
C11'—H11A	0.9800	C21'—H2'A	0.9800
C12'—C13'	1.527 (3)	C22'—C23'	1.529 (3)
C12'—H12A	0.9700	C22'—H22A	0.9700
C12'—H12B	0.9700	C22'—H22B	0.9700
C13'—O13'	1.417 (3)	C23'—O23'	1.420 (3)
C13'—C14'	1.525 (3)	C23'—C24'	1.525 (3)
C13'—H13C	0.9800	C23'—H23C	0.9800
O13'—H13'	0.8200	O23'—H23'	0.8200
C14'—O14'	1.456 (2)	C24'—O24'	1.441 (3)
C14'—C15'	1.514 (3)	C24'—C25'	1.523 (3)
C14'—H14C	0.9800	C24'—H24C	0.9800
C15'—O15'	1.419 (4)	C25'—O25'	1.413 (4)
C15'—H15D	0.9700	C25'—H25D	0.9700
C15'—H15E	0.9700	C25'—H25E	0.9700
O15'—H15'	0.8200	O25'—H25'	0.8200
C16—N11—C12	121.18 (17)	C26—N21—C22	121.15 (18)
C16—N11—C11'	119.07 (16)	C26—N21—C21'	121.90 (16)
C12—N11—C11'	119.69 (16)	C22—N21—C21'	116.88 (16)
O12—C12—N13	121.98 (19)	O22—C22—N23	122.5 (2)
O12—C12—N11	119.26 (18)	O22—C22—N21	118.3 (2)
N13—C12—N11	118.76 (18)	N23—C22—N21	119.19 (19)
C14—N13—C12	120.48 (18)	C24—N23—C22	119.88 (19)
N14—C14—N13	117.86 (19)	N24—C24—N23	117.3 (2)
N14—C14—C15	120.15 (19)	N24—C24—C25	120.58 (19)
N13—C14—C15	121.98 (18)	N23—C24—C25	122.12 (19)
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—C151	122.77 (18)	C26—C25—C24	116.61 (18)
C16—C15—C14	116.31 (17)	C26—C25—C251	123.54 (19)
C151—C15—C14	120.82 (18)	C24—C25—C251	119.80 (18)
C152—C151—C15	174.7 (3)	C252—C251—C25	172.1 (3)
C151—C152—C153	179.3 (3)	C251—C252—C253	178.7 (3)
C152—C153—H15A	109.5	C252—C253—H25A	109.5
C152—C153—H15B	109.5	C252—C253—H25B	109.5
H15A—C153—H15B	109.5	H25A—C253—H25B	109.5
C152—C153—H15C	109.5	C252—C253—H256	109.5
H15A—C153—H15C	109.5	H25A—C253—H256	109.5
H15B—C153—H15C	109.5	H25B—C253—H256	109.5
N11—C16—C15	121.26 (18)	N21—C26—C25	120.94 (19)
N11—C16—H16A	119.4	N21—C26—H26A	119.5
C15—C16—H16A	119.4	C25—C26—H26A	119.5
O14'—C11'—N11	107.38 (16)	O24'—C21'—N21	108.73 (16)
O14'—C11'—C12'	106.35 (15)	O24'—C21'—C22'	107.27 (17)
N11—C11'—C12'	114.48 (18)	N21—C21'—C22'	112.94 (18)
O14'—C11'—H11A	109.5	O24'—C21'—H2'A	109.3
N11—C11'—H11A	109.5	N21—C21'—H2'A	109.3
C12'—C11'—H11A	109.5	C22'—C21'—H2'A	109.3
C11'—C12'—C13'	101.95 (17)	C21'—C22'—C23'	103.45 (18)
C11'—C12'—H12A	111.4	C21'—C22'—H22A	111.1
C13'—C12'—H12A	111.4	C23'—C22'—H22A	111.1
C11'—C12'—H12B	111.4	C21'—C22'—H22B	111.1
C13'—C12'—H12B	111.4	C23'—C22'—H22B	111.1
H12A—C12'—H12B	109.2	H22A—C22'—H22B	109.0
O13'—C13'—C14'	109.13 (19)	O23'—C23'—C24'	111.66 (19)
O13'—C13'—C12'	112.82 (17)	O23'—C23'—C22'	112.89 (18)
C14'—C13'—C12'	102.21 (15)	C24'—C23'—C22'	101.54 (17)
O13'—C13'—H13C	110.8	O23'—C23'—H23C	110.2
C14'—C13'—H13C	110.8	C24'—C23'—H23C	110.2
C12'—C13'—H13C	110.8	C22'—C23'—H23C	110.2
C13'—O13'—H13'	109.5	C23'—O23'—H23'	109.5
O14'—C14'—C15'	110.12 (18)	O24'—C24'—C25'	110.54 (18)
O14'—C14'—C13'	105.78 (15)	O24'—C24'—C23'	105.72 (16)
C15'—C14'—C13'	115.8 (2)	C25'—C24'—C23'	112.1 (2)
O14'—C14'—H14C	108.3	O24'—C24'—H24C	109.5
C15'—C14'—H14C	108.3	C25'—C24'—H24C	109.5
C13'—C14'—H14C	108.3	C23'—C24'—H24C	109.5
O15'—C15'—C14'	112.9 (2)	O25'—C25'—C24'	113.3 (2)
O15'—C15'—H15D	109.0	O25'—C25'—H25D	108.9
C14'—C15'—H15D	109.0	C24'—C25'—H25D	108.9
O15'—C15'—H15E	109.0	O25'—C25'—H25E	108.9
C14'—C15'—H15E	109.0	C24'—C25'—H25E	108.9
H15D—C15'—H15E	107.8	H25D—C25'—H25E	107.7
C15'—O15'—H15'	109.5	C25'—O25'—H25'	109.5
C11'—O14'—C14'	109.77 (15)	C21'—O24'—C24'	110.40 (17)
C16—N11—C12—O12	178.7 (2)	C26—N21—C22—O22	175.2 (3)
C11'—N11—C12—O12	−4.2 (3)	C21'—N21—C22—O22	−1.8 (4)
C16—N11—C12—N13	−2.0 (3)	C26—N21—C22—N23	−3.9 (4)
C11'—N11—C12—N13	175.1 (2)	C21'—N21—C22—N23	179.1 (3)
O12—C12—N13—C14	179.6 (3)	O22—C22—N23—C24	−175.8 (3)
N11—C12—N13—C14	0.4 (3)	N21—C22—N23—C24	3.3 (5)
C12—N13—C14—N14	−178.2 (2)	C22—N23—C24—N24	178.6 (3)
C12—N13—C14—C15	0.7 (3)	C22—N23—C24—C25	−0.4 (4)
N14—C14—C15—C16	178.7 (2)	N24—C24—C25—C26	179.1 (2)
N13—C14—C15—C16	−0.1 (3)	N23—C24—C25—C26	−1.9 (4)
N14—C14—C15—C151	2.2 (3)	N24—C24—C25—C251	−3.3 (4)
N13—C14—C15—C151	−176.6 (2)	N23—C24—C25—C251	175.6 (3)
C12—N11—C16—C15	2.6 (3)	C22—N21—C26—C25	1.5 (4)
C11'—N11—C16—C15	−174.5 (2)	C21'—N21—C26—C25	178.4 (2)
C151—C15—C16—N11	174.9 (2)	C24—C25—C26—N21	1.3 (3)
C14—C15—C16—N11	−1.5 (3)	C251—C25—C26—N21	−176.1 (2)
C16—N11—C11'—O14'	42.1 (3)	C26—N21—C21'—O24'	26.6 (3)
C12—N11—C11'—O14'	−135.0 (2)	C22—N21—C21'—O24'	−156.4 (2)
C16—N11—C11'—C12'	−75.7 (2)	C26—N21—C21'—C22'	−92.4 (3)
C12—N11—C11'—C12'	107.2 (2)	C22—N21—C21'—C22'	84.6 (3)
O14'—C11'—C12'—C13'	33.06 (19)	O24'—C21'—C22'—C23'	23.3 (2)
N11—C11'—C12'—C13'	151.46 (16)	N21—C21'—C22'—C23'	143.07 (17)
C11'—C12'—C13'—O13'	80.6 (2)	C21'—C22'—C23'—O23'	87.0 (2)
C11'—C12'—C13'—C14'	−36.4 (2)	C21'—C22'—C23'—C24'	−32.7 (2)
O13'—C13'—C14'—O14'	−91.8 (2)	O23'—C23'—C24'—O24'	−89.1 (2)
C12'—C13'—C14'—O14'	27.9 (2)	C22'—C23'—C24'—O24'	31.4 (2)
O13'—C13'—C14'—C15'	145.9 (2)	O23'—C23'—C24'—C25'	150.36 (19)
C12'—C13'—C14'—C15'	−94.4 (2)	C22'—C23'—C24'—C25'	−89.1 (2)
O14'—C14'—C15'—O15'	−62.1 (3)	O24'—C24'—C25'—O25'	48.4 (3)
C13'—C14'—C15'—O15'	57.8 (3)	C23'—C24'—C25'—O25'	166.1 (2)
N11—C11'—O14'—C14'	−139.09 (17)	N21—C21'—O24'—C24'	−125.84 (18)
C12'—C11'—O14'—C14'	−16.1 (2)	C22'—C21'—O24'—C24'	−3.4 (2)
C15'—C14'—O14'—C11'	118.1 (2)	C25'—C24'—O24'—C21'	103.4 (2)
C13'—C14'—O14'—C11'	−7.7 (2)	C23'—C24'—O24'—C21'	−18.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N14—H14A···N23^i	0.86	2.23	3.024 (3)	154
N14—H14B···O13′^ii	0.86	2.25	2.877 (3)	130
O13′—H13′···O22^iii	0.82	1.92	2.726 (3)	167
O15′—H15′···N13^iv	0.82	2.27	3.032 (3)	154
N24—H24A···N13^v	0.86	2.36	3.115 (3)	147
N24—H24B···O23′^vi	0.86	2.20	2.812 (3)	128
O23′—H23′···O12^vii	0.82	1.96	2.773 (3)	171
O25′—H25′···N23^viii	0.82	2.27	3.064 (4)	162

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