The 1:1 cocrystals of the proton-transfer compound dilituric acid-phenyl­biguanide monohydrate

A proton-transfer compound, 1-phenyl­biguanidium 5-nitro-2,6-dioxo-1,2,3,6-tetra­hydro­pyrimidin-4-olate monohydrate, C₈H₁₂N₅⁺·C₄H₂N₃O₅^-·H₂O, has been synthesized by a reaction between dilituric acid (5-nitro-2,4,6-trihydroxy­pyrimi­dine, Dilit) and phenyl­biguanide (N-phenyl­imido­carbonimidic diamide, Big). This compound cocrystallized as a 1:1 adduct, and the asymmetric unit consists of two dilituric amino-oxo planar tautomeric anions (Dilit^-), two monoprotonated phenyl­biguanidium cations (BigH⁺) and two water mol­ecules of crystallization (Z' = 2). Protonation occurs at the N atom attached to the phenyl ring of Big as a result of the proton-transfer process from the acidic hydr­oxy group of Dilit. In the crystal structure, the hydrated 1:1 adduct is stabilized by 25 two- and three-center hydrogen bonds.

S1. Comment

Since Jean-Marie Lehn's famous description of supramolecular chemistry, the chemistry of molecular assemblies and the intermolecular bond, noncovalent binding interactions (i.e. hydrogen bonding, ionic interactions and π–π stacking) have attracted increasing attention in crystal engineering. In particular, it has been shown that hydrogen bonding plays a crucial role in the de novo design of self-assembled or self-associated compounds that may go by the more general title of 'supramolecule' (Desiraju, 1996). This is especially true for biological structures, and we previously demonstrated that crystalline adducts of DNA/RNA pyrimidine bases can mimic, if coupled with amino-derivatives of aromatic N-heterocycles via multiple hydrogen bonds, the base-pairing of nucleic acids. (Brunetti et al., 2000, 2002; Portalone et al., 1999, 2002; Portalone & Colapietro, 2004a, 2007).

There is a very closed relationship between hydrogen bonding and proton transfer: whenever the hydrogen-bonding associations result in complete proton transfer, an ionic compound is produced, and the non-covalent interactions between hydrogen-bonding groups are reinforced (Swift et al., 1998). As the relevance of proton transfer in DNA/RNA systems was demonstrated many years ago (Steenken, 1989), we thought it would be interesting to analyze uracil acidic derivatives coupled with aromatic N-heterocycles to obtain proton-transfer supramolecular structures. In this paper, the title compound, BigH^+.Dilit^-, (I), has been synthesized by a reaction between dilituric acid (5-nitro-2,4,6-trihydroxypyrimidine, Dilit), a quite strong acid (pK_a = 0.77 in dimethyl sulfoxide) structurally related to 5-nitrouracil (5-nitro-2,4-dihydroxypyrimidine), and phenylbiguanide (N-phenylimidocarbonimidic diamide, Big). Big, which has been chosen as the biguanide residue, mimics the aromatic N-heterocyclic fragment of 2-aminoadenine, as a Lewis base is readily protonated at the N atom attached to the benzene ring (Portalone & Colapietro, 2004b).

The asymmetric unit of the title compound, (I), comprises two subunits, each of them consisting of a planar aminooxo tautomeric anion (Dilit^-), a monoprotonated phenylbiguanidium cation (BigH⁺) and a water molecule (Fig. 1). Protonation occurs as a result of the proton-transfer process from the hydroxyl group of Dilit to the N atom attached to the phenyl ring of Big. The corresponding bond lengths and angles of the two independent 1:1 adducts are equal within the experimental error (Table 1). In planar Dilit^- anions the release of a proton from O3 and O31 causes a redistribution of π-electron density so that the geometry of the anions approaches mirror symmetry through a mirror plane along the line joining C2 and C5, and C21 and C51. In BigH⁺ cations, the two biguanidinium groups are not planar. In each cation, the two halves of the biguanide residue are slightly pyrimidal and make dihedral angles of 49.2 (1) and 53.2 (1)°. Nevertheless, the equivalence of the C—N bond lengths (Table 1) suggests some degree of delocalization of π-electron density through these fragments. Concerning the conformation of the two biguanidinium moieties, the groups are slightly rotated with respect to the phenyl rings by the angles τ1 [21.1 (4)°] and τ2 [9.7 (4)°; the angle τ is defined as τ = |ω1 + ω2 ± π|/2, the torsion angles ω1 and ω2 being, respectively, C8—C7—N5—C13 and C12—C7—N5—C13 for τ1, and C81—C71—N51—C131 and C121—C71—N51—C131 for τ2], at variance with that observed for the corresponding angle, 52.4 (5)° for phenylbiguanide hydrochloride (Portalone & Colapietro, 2004b) and 29.2 (2)° for 1-(p-chlorophenyl)biguanide hydrochloride (Brown & Sengier, 1984). This change in conformation is presumably a consequence of the different hydrogen-bonding configuration caused by the nature of the counter-ions, i.e. Dilit^- versus Cl^-.

In the crystal structure, the hydrogen-bonding scheme is rather complex, and involves all available hydrogen donor/acceptor sites but O41, which remains partially unsaturated, and O7_water, which participates unexpectedly as hydrogen donor in only one intermolecular interaction. In total, the supramolecular structure of (I) is characterized by 25 two- and three-center hydrogen bonds, namely 22 N—H···O and three O_water—H···O bonds (Table 2). In one of the four three-center N—H···O interactions, where atom N81 acts as hydrogen-bond donor via H81A, there is some uncertainty as to whether this is a hydrogen bond or not. However, as is very frequently found for bifurcated hydrogen bonds, the sum of the inter-bond angles at the H atom is close to 360° and the H···O distance can be greater than the van der Waals separation (Jeffrey & Saenger, 1991; Desiraju & Steiner, 1999; Steiner, 2002).

Compound (I) crystallizes with Z' = 2. In the crystal structure, each independent molecular adduct is linked by multiple hydrogen bonds to form a three-dimensional framework. For descriptive purposes, it is convenient to select a 'superadduct' (Gregson et al., 2000) consisting of one asymmetric unit and then analyse firstly the hydrogen bonding within this aggregate and secondly the hydrogen-bonding patterns between neighbouring individual superadducts.

As previously mentioned, in the superadduct, one Big molecule forms a cation as a result of the incorporation of an H atom from one Dilit molecule (Fig. 1). Thus, the Dilit^- anion acts as an acceptor of bifurcated hydrogen bonds of descriptor R¹₂(6) and R²₁(6) (Etter, 1990; Bernstein et al., 1995; Motherwell et al., 1999) through the hydroxy O atom and one O atom of the nitro group. The BigH⁺ cation then links a solvent molecule through a bifurcated R¹₂(6) hydrogen bond. The two subunits are interconnected via N—H···O triple intermolecular hydrogen bonds, forming two adjoining hydrogen-bonded rings with graph-set motifs R²₂(8) and R²₃(8).

In addition to the 13 hydrogen bonds within the asymmetric unit, there are a further five distinct interactions which link, by translation along the b axis, neighbouring superadducts into sheets parallel to the ab plane (Fig. 2). N—H···O triple intermolecular hydrogen bonds, forming two adjoining hydrogen-bonded rings of R²₂(8) and R²₃(8) motif, connects two Dilit^- anions. The formation of this two-dimensional array is then reinforced by two water molecules, which act as bridges between Dilit^- anions and BigH⁺ cations to form two R⁴₄(18) hydrogen-bond rings. Overall, adjacent superadducts form a two-dimensional substructure built from a combination of 18 N—H···O and O_water—H···O interactions, and hydrogen bonds delineate patterns in which rings are the most prominent features.

The (010)-nets thus formed are themselves linked into a three-dimensional network by means of a further series of seven hydrogen bonds, all but one (O6_water—H614···O1^vi) of N—H···O type, generated by translation from the superadduct at (x, y, z) to the adjacent sheets in the [001] direction (Fig. 3).

Related literature

For related literature, see: Bernstein et al. (1995); Brown & Sengier (1984); Brunetti et al. (2000, 2002); Desiraju (1996); Desiraju & Steiner (1999); Etter (1990); Gregson et al. (2000); Jeffrey & Saenger (1991); Motherwell et al. (1999); Portalone & Colapietro (2004a, 2004b, 2007); Portalone et al. (1999, 2002); Steenken (1989); Steiner (2002); Swift et al. (1998).

S2. Experimental

BigH^+.Dilit^- was obtained as a white powder from an equimolar mixture of dilituric acid and phenylbiguanide (Sigma Aldrich, 99% purity, 1 mmol each compound) in an ethanol solution (20 ml). The 1:1 molecular adduct was recrystallized from water by slow evaporation of the solvent.

S3. Refinement

All H atoms were found in a difference map. Positional parameters of all H atoms but those from the benzene rings and N81 were refined. The latter H atoms were positioned with idealized geometry and refined isotropically using a riding model (C—H = 0.98 Å, N—H = 0.91 Å). The U_iso values of the H atoms were kept equal to 1.2U_eq(C,N) and 1.5U_eq(O) [please check treatment for water H atoms].

Computing details

Data collection: XCS (Colapietro et al., 1992); cell refinement: XCS; data reduction: XCS; program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. A view, down c, of the independent components of (I), showing the atom-labelling scheme and hydrogen bonding (dashed lines) within the selected asymmetric unit. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A part of the crystal structure of (I), viewed down c, showing the formation of a (010) two-dimensional network of hydrogen-bonded BigH^+.Dilit^- and water molecules. Displacements ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. Hydrogen bonding is indicated by dashed lines.
	Fig. 3. The packing of (I), viewed down c. All atoms are shown as small spheres of arbitrary radii. Hydrogen bonding is indicated by dashed lines.

1-phenylbiguanidium 5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate monohydrate

Crystal data

C8H12N^5+·C4H2N3O5^−·H2O	Z = 4
Mr = 368.33	F(000) = 768
Triclinic, P1	Dx = 1.563 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.710689 Å
a = 11.387 (2) Å	Cell parameters from 95 reflections
b = 12.135 (3) Å	θ = 10–20°
c = 13.804 (3) Å	µ = 0.13 mm^−1
α = 97.48 (3)°	T = 298 K
β = 106.37 (3)°	Tablet, colourless
γ = 116.39 (4)°	0.20 × 0.20 × 0.10 mm
V = 1565.3 (10) Å^3

Data collection

Huber CS four-circle diffractometer	Rint = 0.032
Radiation source: X-ray tube	θmax = 26.0°, θmin = 2.1°
Graphite monochromator	h = 0→13
ω scans	k = −14→14
6392 measured reflections	l = −17→17
6002 independent reflections	3 standard reflections every 97 reflections
5586 reflections with I > 2σ(I)	intensity decay: 3%

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)] = 0.064	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.191	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.136P)^2 + 0.5189P] where P = (Fo^2 + 2Fc^2)/3
6002 reflections	(Δ/σ)max < 0.001
529 parameters	Δρmax = 0.31 e Å^−3
0 restraints	Δρmin = −0.31 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
O1	1.18953 (17)	0.69889 (16)	0.42246 (16)	0.0555 (5)
O2	0.79039 (17)	0.30877 (14)	0.29188 (14)	0.0473 (4)
O3	0.78012 (16)	0.69715 (14)	0.27764 (13)	0.0435 (4)
O4	0.55338 (17)	0.29896 (14)	0.19354 (14)	0.0488 (4)
O5	0.55813 (19)	0.46928 (18)	0.15946 (18)	0.0649 (6)
N1	0.98064 (18)	0.69260 (17)	0.35069 (14)	0.0386 (4)
N3	0.98463 (19)	0.50534 (17)	0.36151 (15)	0.0409 (4)
N4	0.61940 (18)	0.41711 (16)	0.20522 (14)	0.0381 (4)
C2	1.0587 (2)	0.63662 (19)	0.38038 (17)	0.0399 (5)
C4	0.8397 (2)	0.42679 (18)	0.30602 (16)	0.0363 (4)
C5	0.7637 (2)	0.49055 (18)	0.26890 (15)	0.0345 (4)
C6	0.8341 (2)	0.63028 (19)	0.29612 (15)	0.0341 (4)
H1	1.027 (3)	0.781 (3)	0.368 (2)	0.046*
H3	1.025 (3)	0.466 (3)	0.388 (2)	0.049*
O11	0.72780 (19)	0.98749 (17)	0.25228 (18)	0.0714 (6)
O21	1.11466 (16)	0.96282 (14)	0.42248 (13)	0.0449 (4)
O31	1.11980 (16)	1.36359 (13)	0.45811 (12)	0.0425 (4)
O41	1.32533 (17)	1.17208 (16)	0.57376 (14)	0.0514 (4)
O51	1.35341 (17)	1.35278 (14)	0.54834 (15)	0.0531 (4)
N11	0.92758 (19)	1.17249 (17)	0.36030 (15)	0.0420 (4)
N31	0.92461 (19)	0.97923 (17)	0.34010 (15)	0.0421 (4)
N41	1.27818 (18)	1.23434 (16)	0.52942 (14)	0.0377 (4)
C21	0.8525 (2)	1.0425 (2)	0.31422 (19)	0.0454 (5)
C41	1.0646 (2)	1.03439 (18)	0.40932 (16)	0.0351 (4)
C51	1.1368 (2)	1.17169 (18)	0.45673 (15)	0.0343 (4)
C61	1.0692 (2)	1.24560 (18)	0.42800 (15)	0.0345 (4)
H11	0.885 (3)	1.212 (3)	0.339 (2)	0.050*
H31	0.885 (3)	0.890 (3)	0.317 (2)	0.051*
N5	0.3395 (2)	0.50835 (18)	0.04211 (16)	0.0438 (4)
N6	0.5300 (2)	0.7077 (2)	0.13517 (18)	0.0516 (5)
N7	0.3327 (2)	0.68254 (17)	−0.00397 (15)	0.0442 (4)
N8	0.3986 (2)	0.8748 (2)	0.11813 (18)	0.0542 (5)
N9	0.3436 (2)	0.8557 (2)	−0.05896 (18)	0.0516 (5)
C7	0.2025 (2)	0.4081 (2)	−0.02590 (17)	0.0406 (5)
C8	0.1865 (3)	0.2855 (2)	−0.0504 (2)	0.0558 (6)
H8	0.2686	0.2741	−0.0247	0.067*
C9	0.0530 (4)	0.1799 (3)	−0.1115 (3)	0.0694 (9)
H9	0.0415	0.0938	−0.1287	0.083*
C10	−0.0627 (3)	0.1942 (3)	−0.1480 (2)	0.0683 (9)
H10	−0.1564	0.1190	−0.1910	0.082*
C11	−0.0467 (3)	0.3146 (3)	−0.1240 (2)	0.0622 (7)
H11A	−0.1299	0.3244	−0.1498	0.075*
C12	0.0855 (2)	0.4231 (2)	−0.0638 (2)	0.0498 (6)
H12	0.0959	0.5088	−0.0484	0.060*
C13	0.4002 (2)	0.6374 (2)	0.05911 (17)	0.0403 (5)
C14	0.3610 (2)	0.8042 (2)	0.02028 (17)	0.0418 (5)
H5	0.391 (3)	0.483 (3)	0.076 (2)	0.053*
H61	0.574 (3)	0.803 (3)	0.149 (2)	0.062*
H62	0.568 (4)	0.671 (3)	0.170 (3)	0.062*
H811	0.400 (3)	0.836 (3)	0.172 (3)	0.065*
H812	0.400 (4)	0.944 (3)	0.121 (3)	0.065*
H911	0.310 (3)	0.810 (3)	−0.125 (3)	0.062*
H912	0.336 (3)	0.927 (3)	−0.054 (2)	0.062*
O7	0.3181 (3)	1.0752 (3)	0.0459 (3)	0.1111 (13)
H711	0.384 (7)	1.145 (6)	0.074 (5)	0.142*
H712	0.266 (7)	1.094 (6)	0.047 (5)	0.142*
N51	1.5692 (2)	1.61335 (18)	0.65324 (15)	0.0421 (4)
N61	1.3751 (2)	1.61569 (19)	0.54975 (16)	0.0455 (5)
N71	1.59544 (19)	1.80863 (17)	0.63508 (16)	0.0423 (4)
N81	1.4436 (2)	1.88339 (19)	0.65789 (18)	0.0507 (5)
H81A	1.4206	1.9462	0.6570	0.061*
H81B	1.3950	1.8147	0.6789	0.061*
N91	1.6186 (2)	1.99329 (19)	0.59798 (18)	0.0483 (5)
C71	1.7076 (2)	1.6528 (2)	0.72202 (17)	0.0394 (5)
C81	1.8137 (3)	1.7786 (2)	0.7774 (2)	0.0586 (7)
H81	1.7968	1.8503	0.7717	0.070*
C91	1.9461 (3)	1.8005 (3)	0.8418 (3)	0.0751 (9)
H91	2.0226	1.8893	0.8806	0.090*
C101	1.9725 (3)	1.7032 (4)	0.8523 (3)	0.0697 (9)
H101	2.0664	1.7217	0.8980	0.084*
C111	1.8662 (4)	1.5789 (4)	0.7982 (3)	0.0683 (8)
H111	1.8833	1.5075	0.8058	0.082*
C121	1.7363 (3)	1.5544 (3)	0.7337 (2)	0.0570 (6)
H121	1.6615	1.4650	0.6947	0.068*
C131	1.5123 (2)	1.68276 (19)	0.61418 (16)	0.0369 (4)
C141	1.5486 (2)	1.89194 (19)	0.62851 (16)	0.0389 (5)
H51	1.519 (3)	1.538 (3)	0.634 (2)	0.050*
H611	1.336 (3)	1.659 (3)	0.521 (2)	0.054*
H612	1.330 (3)	1.531 (3)	0.541 (2)	0.054*
H913	1.605 (3)	2.056 (3)	0.606 (2)	0.058*
H914	1.692 (3)	1.997 (3)	0.585 (2)	0.058*
O6	1.5985 (2)	2.2172 (2)	0.68223 (17)	0.0602 (5)
H613	1.522 (5)	2.227 (4)	0.654 (3)	0.095*
H614	1.658 (5)	2.267 (4)	0.652 (3)	0.095*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0313 (8)	0.0326 (8)	0.0744 (12)	0.0076 (6)	0.0023 (7)	0.0037 (7)
O2	0.0364 (8)	0.0236 (7)	0.0646 (10)	0.0106 (6)	0.0078 (7)	0.0038 (6)
O3	0.0373 (8)	0.0278 (7)	0.0507 (9)	0.0130 (6)	0.0080 (6)	0.0003 (6)
O4	0.0355 (8)	0.0267 (7)	0.0593 (10)	0.0050 (6)	0.0080 (7)	0.0007 (6)
O5	0.0377 (9)	0.0407 (10)	0.0859 (14)	0.0141 (7)	−0.0040 (9)	0.0107 (9)
N1	0.0313 (8)	0.0223 (8)	0.0451 (9)	0.0065 (6)	0.0077 (7)	0.0006 (6)
N3	0.0325 (9)	0.0239 (8)	0.0519 (10)	0.0114 (7)	0.0054 (7)	0.0024 (7)
N4	0.0303 (8)	0.0263 (8)	0.0414 (9)	0.0081 (6)	0.0066 (7)	0.0005 (6)
C2	0.0306 (10)	0.0274 (10)	0.0443 (11)	0.0075 (8)	0.0071 (8)	0.0014 (8)
C4	0.0302 (9)	0.0257 (9)	0.0391 (10)	0.0086 (7)	0.0078 (7)	0.0008 (7)
C5	0.0279 (9)	0.0243 (9)	0.0374 (9)	0.0081 (7)	0.0064 (7)	0.0003 (7)
C6	0.0315 (9)	0.0258 (9)	0.0335 (9)	0.0100 (7)	0.0081 (7)	0.0005 (7)
O11	0.0383 (9)	0.0316 (9)	0.0928 (15)	0.0084 (7)	−0.0177 (9)	−0.0064 (9)
O21	0.0327 (7)	0.0232 (7)	0.0600 (9)	0.0084 (6)	0.0080 (6)	−0.0009 (6)
O31	0.0374 (8)	0.0210 (7)	0.0496 (8)	0.0085 (6)	0.0067 (6)	−0.0027 (6)
O41	0.0383 (8)	0.0388 (9)	0.0552 (10)	0.0145 (7)	0.0016 (7)	0.0032 (7)
O51	0.0346 (8)	0.0229 (7)	0.0673 (11)	0.0008 (6)	0.0037 (7)	−0.0038 (7)
N11	0.0305 (9)	0.0229 (8)	0.0503 (10)	0.0078 (6)	0.0008 (7)	−0.0014 (7)
N31	0.0312 (8)	0.0204 (8)	0.0502 (10)	0.0057 (6)	0.0014 (7)	−0.0045 (7)
N41	0.0298 (8)	0.0255 (8)	0.0401 (9)	0.0069 (6)	0.0074 (7)	−0.0029 (6)
C21	0.0329 (10)	0.0252 (10)	0.0517 (12)	0.0071 (8)	−0.0010 (9)	−0.0016 (8)
C41	0.0284 (9)	0.0210 (8)	0.0403 (10)	0.0053 (7)	0.0093 (7)	−0.0015 (7)
C51	0.0267 (9)	0.0226 (8)	0.0359 (9)	0.0057 (7)	0.0046 (7)	−0.0026 (7)
C61	0.0295 (9)	0.0242 (9)	0.0358 (9)	0.0074 (7)	0.0079 (7)	0.0002 (7)
N5	0.0318 (9)	0.0312 (9)	0.0495 (11)	0.0101 (7)	0.0032 (7)	0.0041 (7)
N6	0.0341 (10)	0.0355 (11)	0.0585 (12)	0.0111 (8)	−0.0004 (8)	−0.0011 (8)
N7	0.0404 (9)	0.0272 (9)	0.0430 (9)	0.0105 (7)	0.0027 (7)	−0.0014 (7)
N8	0.0549 (13)	0.0359 (11)	0.0521 (12)	0.0192 (9)	0.0084 (9)	−0.0051 (9)
N9	0.0505 (12)	0.0296 (10)	0.0529 (12)	0.0134 (9)	0.0060 (9)	0.0030 (8)
C7	0.0371 (10)	0.0300 (10)	0.0377 (10)	0.0078 (8)	0.0106 (8)	0.0012 (7)
C8	0.0553 (15)	0.0328 (11)	0.0687 (16)	0.0162 (10)	0.0251 (12)	0.0031 (10)
C9	0.0712 (19)	0.0298 (12)	0.0751 (19)	0.0058 (12)	0.0287 (16)	−0.0075 (11)
C10	0.0548 (16)	0.0451 (15)	0.0510 (14)	−0.0049 (12)	0.0067 (12)	−0.0038 (11)
C11	0.0381 (12)	0.0524 (15)	0.0572 (15)	0.0042 (11)	0.0007 (11)	0.0091 (12)
C12	0.0364 (11)	0.0354 (11)	0.0540 (13)	0.0094 (9)	0.0040 (9)	0.0048 (9)
C13	0.0340 (10)	0.0321 (10)	0.0389 (10)	0.0106 (8)	0.0081 (8)	−0.0014 (8)
C14	0.0268 (9)	0.0277 (10)	0.0470 (11)	0.0057 (7)	0.0017 (8)	−0.0026 (8)
O7	0.0658 (16)	0.0449 (13)	0.158 (3)	0.0227 (11)	−0.0113 (17)	−0.0243 (15)
N51	0.0352 (9)	0.0220 (8)	0.0482 (10)	0.0074 (7)	0.0047 (7)	−0.0011 (7)
N61	0.0349 (9)	0.0272 (9)	0.0486 (10)	0.0074 (7)	0.0012 (8)	−0.0020 (7)
N71	0.0321 (9)	0.0254 (8)	0.0543 (11)	0.0081 (7)	0.0107 (7)	0.0036 (7)
N81	0.0405 (10)	0.0314 (9)	0.0700 (13)	0.0140 (8)	0.0202 (9)	0.0019 (8)
N91	0.0426 (11)	0.0297 (9)	0.0660 (13)	0.0157 (8)	0.0185 (9)	0.0096 (8)
C71	0.0356 (10)	0.0324 (10)	0.0380 (10)	0.0117 (8)	0.0104 (8)	0.0026 (8)
C81	0.0442 (13)	0.0346 (12)	0.0646 (16)	0.0096 (10)	−0.0004 (11)	0.0044 (10)
C91	0.0420 (14)	0.0663 (19)	0.0680 (18)	0.0025 (13)	−0.0012 (12)	0.0167 (15)
C101	0.0459 (15)	0.099 (3)	0.0690 (18)	0.0370 (16)	0.0210 (13)	0.0393 (18)
C111	0.0679 (19)	0.086 (2)	0.0646 (17)	0.0529 (18)	0.0202 (15)	0.0210 (16)
C121	0.0630 (16)	0.0478 (14)	0.0541 (14)	0.0325 (13)	0.0110 (12)	0.0052 (11)
C131	0.0324 (9)	0.0270 (9)	0.0370 (9)	0.0084 (7)	0.0093 (7)	0.0006 (7)
C141	0.0296 (9)	0.0246 (9)	0.0411 (10)	0.0069 (7)	0.0023 (8)	−0.0036 (7)
O6	0.0510 (11)	0.0492 (11)	0.0694 (12)	0.0256 (9)	0.0122 (9)	0.0075 (9)

Geometric parameters (Å, º)

O1—C2	1.235 (3)	N9—H912	0.91 (3)
O2—C4	1.247 (3)	C7—C12	1.388 (4)
O3—C6	1.229 (3)	C7—C8	1.398 (3)
O4—N4	1.249 (2)	C8—C9	1.388 (4)
O5—N4	1.239 (3)	C8—H8	0.9800
N1—C2	1.350 (3)	C9—C10	1.369 (5)
N1—C6	1.395 (3)	C9—H9	0.9800
N1—H1	0.92 (3)	C10—C11	1.371 (5)
N3—C2	1.375 (3)	C10—H10	0.9800
N3—C4	1.385 (3)	C11—C12	1.393 (3)
N3—H3	0.84 (3)	C11—H11A	0.9800
N4—C5	1.395 (3)	C12—H12	0.9800
C4—C5	1.435 (3)	O7—H711	0.79 (7)
C5—C6	1.454 (3)	O7—H712	0.72 (6)
O11—C21	1.232 (3)	N51—C131	1.351 (3)
O21—C41	1.239 (3)	N51—C71	1.408 (3)
O31—C61	1.238 (2)	N51—H51	0.79 (3)
O41—N41	1.237 (3)	N61—C131	1.339 (3)
O51—N41	1.245 (2)	N61—H611	0.89 (3)
N11—C21	1.362 (3)	N61—H612	0.90 (3)
N11—C61	1.387 (3)	N71—C131	1.326 (3)
N11—H11	0.85 (3)	N71—C141	1.339 (3)
N31—C21	1.363 (3)	N81—C141	1.333 (3)
N31—C41	1.389 (3)	N81—H81A	0.9100
N31—H31	0.93 (3)	N81—H81B	0.9100
N41—C51	1.407 (3)	N91—C141	1.334 (3)
C41—C51	1.441 (3)	N91—H913	0.84 (3)
C51—C61	1.445 (3)	N91—H914	0.89 (3)
N5—C13	1.355 (3)	C71—C81	1.382 (3)
N5—C7	1.409 (3)	C71—C121	1.389 (4)
N5—H5	0.83 (3)	C81—C91	1.401 (4)
N6—C13	1.336 (3)	C81—H81	0.9800
N6—H61	1.00 (3)	C91—C101	1.356 (5)
N6—H62	0.86 (3)	C91—H91	0.9800
N7—C13	1.331 (3)	C101—C111	1.368 (5)
N7—C14	1.335 (3)	C101—H101	0.9800
N8—C14	1.338 (3)	C111—C121	1.366 (4)
N8—H811	0.94 (3)	C111—H111	0.9800
N8—H812	0.83 (3)	C121—H121	0.9800
N9—C14	1.339 (3)	O6—H613	0.92 (5)
N9—H911	0.87 (3)	O6—H614	0.92 (4)
C2—N1—C6	126.80 (18)	C9—C8—H8	120.3
C2—N1—H1	118.1 (17)	C7—C8—H8	120.3
C6—N1—H1	115.1 (17)	C10—C9—C8	121.0 (3)
C2—N3—C4	124.9 (2)	C10—C9—H9	119.5
C2—N3—H3	121 (2)	C8—C9—H9	119.5
C4—N3—H3	114 (2)	C9—C10—C11	119.5 (2)
O5—N4—O4	120.45 (18)	C9—C10—H10	120.2
O5—N4—C5	119.73 (18)	C11—C10—H10	120.2
O4—N4—C5	119.81 (19)	C10—C11—C12	121.3 (3)
O1—C2—N1	122.4 (2)	C10—C11—H11A	119.4
O1—C2—N3	121.2 (2)	C12—C11—H11A	119.4
N1—C2—N3	116.38 (19)	C7—C12—C11	119.1 (3)
O2—C4—N3	116.6 (2)	C7—C12—H12	120.5
O2—C4—C5	127.31 (19)	C11—C12—H12	120.5
N3—C4—C5	116.05 (18)	N7—C13—N6	125.8 (2)
N4—C5—C4	119.39 (17)	N7—C13—N5	118.86 (19)
N4—C5—C6	119.31 (19)	N6—C13—N5	115.2 (2)
C4—C5—C6	121.30 (18)	N7—C14—N8	123.7 (2)
O3—C6—N1	117.96 (18)	N7—C14—N9	117.8 (2)
O3—C6—C5	127.99 (19)	N8—C14—N9	118.3 (2)
N1—C6—C5	114.05 (19)	H711—O7—H712	95 (6)
C21—N11—C61	126.5 (2)	C131—N51—C71	130.64 (19)
C21—N11—H11	115 (2)	C131—N51—H51	116 (2)
C61—N11—H11	118 (2)	C71—N51—H51	113 (2)
C21—N31—C41	126.22 (18)	C131—N61—H611	118 (2)
C21—N31—H31	124.7 (18)	C131—N61—H612	116.1 (19)
C41—N31—H31	109.0 (17)	H611—N61—H612	126 (3)
O41—N41—O51	121.20 (18)	C131—N71—C141	124.20 (19)
O41—N41—C51	120.07 (17)	C141—N81—H81A	120.0
O51—N41—C51	118.72 (19)	C141—N81—H81B	120.0
O11—C21—N11	121.3 (2)	H81A—N81—H81B	120.0
O11—C21—N31	122.9 (2)	C141—N91—H913	120 (2)
N11—C21—N31	115.81 (19)	C141—N91—H914	115 (2)
O21—C41—N31	117.85 (17)	H913—N91—H914	124 (3)
O21—C41—C51	127.12 (18)	C81—C71—C121	118.8 (2)
N31—C41—C51	115.02 (19)	C81—C71—N51	125.7 (2)
N41—C51—C41	118.42 (19)	C121—C71—N51	115.5 (2)
N41—C51—C61	120.01 (17)	C71—C81—C91	118.1 (3)
C41—C51—C61	121.52 (17)	C71—C81—H81	121.0
O31—C61—N11	116.7 (2)	C91—C81—H81	121.0
O31—C61—C51	128.64 (18)	C101—C91—C81	122.4 (3)
N11—C61—C51	114.64 (17)	C101—C91—H91	118.8
C13—N5—C7	130.1 (2)	C81—C91—H91	118.8
C13—N5—H5	116 (2)	C91—C101—C111	119.1 (3)
C7—N5—H5	114 (2)	C91—C101—H101	120.5
C13—N6—H61	115.4 (18)	C111—C101—H101	120.5
C13—N6—H62	120 (2)	C121—C111—C101	120.0 (3)
H61—N6—H62	124 (3)	C121—C111—H111	120.0
C13—N7—C14	123.86 (18)	C101—C111—H111	120.0
C14—N8—H811	119 (2)	C111—C121—C71	121.7 (3)
C14—N8—H812	114 (2)	C111—C121—H121	119.2
H811—N8—H812	126 (3)	C71—C121—H121	119.2
C14—N9—H911	121 (2)	N71—C131—N61	124.4 (2)
C14—N9—H912	123.9 (19)	N71—C131—N51	119.2 (2)
H911—N9—H912	112 (3)	N61—C131—N51	116.15 (19)
C12—C7—C8	119.8 (2)	N81—C141—N91	119.1 (2)
C12—C7—N5	124.6 (2)	N81—C141—N71	123.5 (2)
C8—C7—N5	115.5 (2)	N91—C141—N71	117.2 (2)
C9—C8—C7	119.4 (3)	H613—O6—H614	100 (4)
C6—N1—C2—O1	175.1 (2)	N41—C51—C61—O31	1.1 (3)
C6—N1—C2—N3	−5.1 (3)	C41—C51—C61—O31	−176.3 (2)
C4—N3—C2—O1	−173.6 (2)	N41—C51—C61—N11	−176.61 (18)
C4—N3—C2—N1	6.5 (3)	C41—C51—C61—N11	6.0 (3)
C2—N3—C4—O2	176.8 (2)	C13—N5—C7—C12	−22.8 (4)
C2—N3—C4—C5	−1.7 (3)	C13—N5—C7—C8	160.6 (2)
O5—N4—C5—C4	−168.8 (2)	C12—C7—C8—C9	−0.8 (4)
O4—N4—C5—C4	10.2 (3)	N5—C7—C8—C9	176.0 (2)
O5—N4—C5—C6	11.1 (3)	C7—C8—C9—C10	0.1 (5)
O4—N4—C5—C6	−169.92 (19)	C8—C9—C10—C11	0.0 (5)
O2—C4—C5—N4	−3.4 (3)	C9—C10—C11—C12	0.5 (5)
N3—C4—C5—N4	174.91 (18)	C8—C7—C12—C11	1.3 (4)
O2—C4—C5—C6	176.8 (2)	N5—C7—C12—C11	−175.1 (2)
N3—C4—C5—C6	−4.9 (3)	C10—C11—C12—C7	−1.2 (4)
C2—N1—C6—O3	178.4 (2)	C14—N7—C13—N6	−23.4 (4)
C2—N1—C6—C5	−1.0 (3)	C14—N7—C13—N5	161.7 (2)
N4—C5—C6—O3	7.0 (3)	C7—N5—C13—N7	−9.2 (4)
C4—C5—C6—O3	−173.2 (2)	C7—N5—C13—N6	175.4 (2)
N4—C5—C6—N1	−173.68 (17)	C13—N7—C14—N8	−35.7 (4)
C4—C5—C6—N1	6.2 (3)	C13—N7—C14—N9	148.0 (2)
C61—N11—C21—O11	−177.6 (2)	C131—N51—C71—C81	9.6 (4)
C61—N11—C21—N31	1.7 (4)	C131—N51—C71—C121	−170.5 (2)
C41—N31—C21—O11	−179.7 (3)	C121—C71—C81—C91	0.8 (4)
C41—N31—C21—N11	1.1 (4)	N51—C71—C81—C91	−179.4 (3)
C21—N31—C41—O21	−178.7 (2)	C71—C81—C91—C101	−0.8 (5)
C21—N31—C41—C51	0.1 (3)	C81—C91—C101—C111	0.0 (5)
O41—N41—C51—C41	−20.2 (3)	C91—C101—C111—C121	0.8 (5)
O51—N41—C51—C41	160.34 (19)	C101—C111—C121—C71	−0.8 (5)
O41—N41—C51—C61	162.32 (19)	C81—C71—C121—C111	0.0 (4)
O51—N41—C51—C61	−17.1 (3)	N51—C71—C121—C111	−179.8 (3)
O21—C41—C51—N41	−2.6 (3)	C141—N71—C131—N61	25.4 (4)
N31—C41—C51—N41	178.77 (18)	C141—N71—C131—N51	−159.6 (2)
O21—C41—C51—C61	174.9 (2)	C71—N51—C131—N71	4.8 (4)
N31—C41—C51—C61	−3.8 (3)	C71—N51—C131—N61	−179.8 (2)
C21—N11—C61—O31	177.0 (2)	C131—N71—C141—N81	38.6 (3)
C21—N11—C61—C51	−5.0 (3)	C131—N71—C141—N91	−146.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O21	0.92 (3)	1.90 (3)	2.814 (3)	171 (2)
N3—H3···O31^i	0.84 (3)	2.14 (3)	2.983 (3)	177 (3)
N11—H11···O2^ii	0.85 (3)	1.97 (3)	2.818 (3)	178 (3)
N31—H31···O3	0.93 (3)	2.01 (3)	2.932 (3)	171 (2)
N5—H5···O5	0.83 (3)	2.02 (3)	2.832 (3)	164 (3)
N6—H61···O11	1.00 (3)	2.09 (3)	2.989 (3)	148 (3)
N6—H62···O3	0.86 (3)	2.30 (3)	3.038 (3)	144 (3)
N6—H62···O5	0.86 (3)	2.38 (3)	3.099 (3)	142 (3)
N8—H811···O6^iii	0.94 (3)	2.18 (3)	3.103 (4)	167 (3)
N8—H812···O7	0.83 (3)	2.38 (3)	3.137 (4)	152 (3)
N9—H911···O2^iv	0.87 (3)	2.21 (3)	3.083 (3)	175 (3)
N9—H912···O7	0.91 (3)	2.23 (3)	3.033 (4)	147 (3)
N51—H51···O51	0.79 (3)	2.07 (3)	2.834 (3)	163 (3)
N61—H611···O1^ii	0.89 (3)	2.12 (3)	2.973 (3)	161 (3)
N61—H612···O31	0.90 (3)	2.17 (3)	2.903 (3)	139 (3)
N61—H612···O51	0.90 (3)	2.30 (3)	3.086 (3)	146 (3)
N81—H81A···O6	0.91	2.90	3.549 (3)	129
N81—H81A···O11^iii	0.91	2.69	3.374 (3)	133
N81—H81B···O2^v	0.91	2.17	2.993 (3)	151
N81—H81B···O4^v	0.91	2.47	3.211 (3)	138
N91—H913···O6	0.84 (3)	2.14 (3)	2.945 (3)	160 (3)
N91—H914···O21^vi	0.89 (3)	2.07 (3)	2.945 (3)	169 (3)
O6—H613···O41^ii	0.92 (5)	1.94 (5)	2.804 (3)	156 (4)
O6—H614···O1^vi	0.92 (4)	2.18 (4)	3.019 (3)	151 (4)
O7—H711···O4^ii	0.79 (7)	2.03 (7)	2.778 (4)	158 (6)

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