Hydrogen-bonding patterns in 5-fluoro­cytosine–melamine co-crystal (4/1)

Mohana, M.; Muthiah, P.T.; Sanjeewa, L.D.; McMillen, C.D.

doi:10.1107/S205698901600476X

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 72| Part 4| April 2016| Pages 552-555

https://doi.org/10.1107/S205698901600476X

Open

access

Hydrogen-bonding patterns in 5-fluorocytosine–melamine co-crystal (4/1)

Marimuthu Mohana,^a Packianathan Thomas Muthiah,^a ^* Liurukara D. Sanjeewa ^b and Colin D. McMillen ^b

^aSchool of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India, and ^bDepartment of Chemistry, Clemson University, H. L. Hunter Laboratories, Clemson, SC 29634, USA
^*Correspondence e-mail: tommtrichy@yahoo.co.in

Edited by P. C. Healy, Griffith University, Australia (Received 1 March 2016; accepted 21 March 2016; online 31 March 2016)

The asymmetric unit of the title compound, 4C₄H₄FN₃O·C₃H₆N₆, comprises of two independent 5-fluorocytosine (5FC) molecules (A and B) and one half-molecule of melamine (M). The other half of the melamine molecule is generated by a twofold axis. 5FC molecules A and B are linked through two different homosynthons [R₂²(8) ring motif]; one is formed via a pair of N—H⋯O hydrogen bonds and the second via a pair of N—H⋯N hydrogen bonds. In addition to this pairing, the O atoms of 5FC molecules A and B interact with the N2 amino group on both sides of the melamine molecule, forming a DDAA array of quadruple hydrogen bonds and generating a supramolecular pattern. The 5FC (molecules A and B) and two melamine molecules interact via N—H⋯O, N—H⋯N and N—H⋯O, N—H⋯N, C—H⋯F hydrogen bonds forming R₆⁶(24) and R₄⁴(15) ring motifs. The crystal structure is further strengthened by C—H⋯F, C—F⋯π and π–π stacking interactions.

Keywords: crystal structure; 5-fluorocytosine; melamine; homosynthons; hydrogen bonding.

CCDC reference: 1469709

1. Chemical context

Pyrimidine derivatives are used in the treatment of antiviral, antifungal, antitumor and cardiovascular diseases. 5-Fluorocytosine (5FC), a synthetic antimycotic compound, first synthesized in 1957 and widely used as an antitumor agent as a cytosine derivative (Tassel & Madoff, 1968 ; Benson & Nahata, 1988 ; Bennet, 1977 ; Polak & Scholer, 1980 ). It is active against fungal infection and was released in the year 1968 (Vermes et al., 2000 ). It becomes active by deamination of 5FC into 5-fluorouracil by the enzyme cytosine deaminase (CD) and inhibits RNA and DNA synthesis (Larsen et al., 2003 ; Mullen et al., 1994 ; Morschhäuser, 2003 ). Melamine is a triazine derivative. It shows antitumor activity as well as biological activities such as antiangiogenesis and antimicrobial effects. Triazine derivatives are useful synthons in supramolecular chemistry. In particular, aminotriazines have been used for the formation of supramolecular architectures using hydrogen bonds (Russell et al., 1998 ; MacDonald & Whitesides, 1994 ; Whitesides et al., 1991 ). The organic and inorganic salts develop well-defined non-covalent molecular recognition via multiple hydrogen bonds by self assembly of components which contain a complementary array of hydrogen-bonding sites (Desiraju, 1989 ). The present work is focused on the supramolecular hydrogen-bonding patterns exhibited by the co-crystal of 5-fluorocytosine with melamine.

2. Structural commentary

The asymmetric unit comprises two independent 5-fluorocytosine (5FC) molecules (A and B) and half a molecule of melamine (M). The twofold axis of melamine coincides with the crystallographic twofold axis. An ORTEP view of the crystal structure is shown in Fig. 1. The values for the C—F bond distance in the two molecules [1.3491 (18) in 5FC A and 1.3492 (18) Å in 5FC B and the corresponding internal angles at the carbon-carrying fluorine atom [C2A—N3A—C4A = 119.96 (13) in 5FC A and C2B—N3B—C4B = 119.92 (13)° in 5FC B] agree with those reported in the literature (Louis et al., 1982 ).

Figure 1
The asymmetric unit of the title compound, showing 30% probability displacement ellipsoids. Dashed lines indicate hydrogen bonds. Atoms with the suffix a are generated by the symmetry operation 1 − x, y, {\script{1\over 2}} − z.

3. Supramolecular features

Two different homosynthons are assembled via a pair of N—H⋯O and N—H⋯N hydrogen bonds (Table 1) to render a robust R₂²(8) ring motif. The first type of homosynthon is formed by the interaction of the protonated N1 and O atoms of 5FC molecules A and B through N—H⋯O hydrogen bonds. Another type of homosynthon is formed via the N4-amino and N3-pyrimidine ring nitrogen atoms of the 5FC A and B molecules through a pair of N—H⋯N hydrogen bonds (da Silva et al., 2013 ; Tutughamiarso et al., 2012 ). The melamine molecule and 5FC (molecules A and B) are involved in the generation of a quadruple hydrogen-bonded DDAA array having a fused-ring sequence of R₃³(10), R₂²(8) and R₃³(10). The R₃³(10) motif is formed on both sides via N—H⋯O and N—H⋯N hydrogen bonds. These quadruple arrays are further linked by three large ring motifs: R₆⁶(24), R₄³(16) and R₄³(14). The R₆⁶(24) ring motifs are formed by the interaction of two 5FC A molecules, two 5FC B molecules and two melamine molecules through several N—H⋯O and N—H⋯N hydrogen bonds, generating a hexameric supermolecule. The R₄³(16) ring motif links the one 5FC A molecule, two 5FC B molecules and one melamine molecule through N—H⋯O, N—H⋯N and C—H⋯F hydrogen bonds, generating a tetrameric supermolecule. Similarly, the R₄³(14) ring motifs are formed by the interaction of two 5FC A molecules, one 5FC B molecule and one melamine molecule through N—H⋯O, N—H⋯N and C—H⋯F hydrogen bonds, generating another tetrameric supermolecule. The association of these R₂²(8), DDAA array and R₆⁶(24), R₄³(16) and R₄³(14) motifs leads to the formation of supramolecular patterns (Fig. 2). The crystal structure is also stabilized by weak C—H⋯F hydrogen bonds and π–π stacking interactions between 5FC A and B molecules with an interplanar distance of 3.475 (6) Å, centroid-to-centroid distance of 3.6875 (11) Å, and slip angle of 19.52°. The crystal structure is further strengthened by a C—F⋯π interaction [3.4541 (14) Å] between 5-fluorocytosinium molecule A and the melamine molecule (Fig. 3).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4A—H4A1⋯F5A	0.86 (2)	2.47 (2)	2.7560 (18)	100.0 (18)
N4A—H4A1⋯N1	0.86 (2)	2.23 (2)	3.0664 (18)	164 (2)
N1A—H1A⋯O2Bⁱⁱ	0.88	1.90	2.773 (2)	173
N1B—H1B⋯O2Aⁱⁱⁱ	0.88	1.88	2.7545 (19)	175
N4A—H4A2⋯N3B	0.91 (2)	2.10 (2)	2.992 (2)	169 (2)
N2—H2A⋯O2B	0.89 (2)	2.10 (2)	2.9689 (19)	167.6 (18)
N2—H2B⋯O2A^iv	0.84 (2)	2.15 (2)	2.8949 (19)	149 (2)
N4B—H4B1⋯N3A	0.88 (2)	2.20 (2)	3.060 (2)	169 (2)
N4B—H4B2⋯F5B	0.86 (2)	2.42 (2)	2.7459 (19)	103 (2)
N4B—H4B2⋯N3^iv	0.86 (2)	2.53 (2)	3.360 (2)	162 (2)
N4—H4A⋯O2B^v	0.89 (2)	2.09 (2)	2.9600 (15)	165 (2)
C6B—H6B⋯F5A^vi	0.95	2.43	3.2444 (19)	143
Symmetry codes: (ii) $[x-{\script{1\over 2}}, y-{\script{1\over 2}}, z]$ ; (iii) $[x+{\script{1\over 2}}, y+{\script{1\over 2}}, z]$ ; (iv) $[-x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z]$ ; (v) $[-x+1, y-1, -z+{\script{1\over 2}}]$ ; (vi) $[x, -y+1, z-{\script{1\over 2}}]$ .

Figure 2
A view of the supramolecular pattern involving two synthons formed by N—H⋯O hydrogen bonds. 5FC A molecules are shown in green, 5FC B molecules in blue and melamine in red. Blue dashed lines indicate hydrogen bonds. Symmetry codes are given in Table 1

Figure 3
A view of C—F⋯π and aromatic π–π stacking interactions (dashed lines) between 5FC molecules A and B and melamine.

In this co-crystal, 5FC molecules A and B form two types of homosynthons (two types of base pairing) while the melamine molecule interacts with them via N—H⋯O and N—H⋯N hydrogen bonds, generating the supramolecular architecture.

4. Database survey

The crystal structure of 5-fluorocytosine monohydrate (Louis et al., 1982; Portalone & Colapietro, 2006 ; Portalone, 2011 ), polymorphs (Hulme & Tocher, 2006 ; Tutughamiarso et al., 2009 ), salts (Perumalla et al., 2013a ,b ) and co-crystals (Tutughamiarso et al., 2012; Da Silva et al., 2013) have been reported in the literature. From our laboratory, 5-fluorocytosinium salicylate (Prabakaran et al., 2001 ) and 5-fluorocytosinium 3-hydroxypicolinate (Karthikeyan et al., 2014 ) have been reported. Various salts, co-crystals and metal complexes of melamine have also been reported (Janczak & Perpétuo, 2001a ,b , 2002 , 2004 ; Perpétuo et al., 2005 ; Zerkowski & Whitesides, 1994 ; Wang et al., 2007 ).

5. Synthesis and crystallization

Hot aqueous solutions of 5-fluorocytosine (32 mg) and melamine (31 mg) were mixed in a 1:1 molar ratio. The resulting solution was warmed to 353 K using a water bath for half an hour and kept at room temperature for crystallization. After one week, colourless crystals were obtained.

6. Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2. The hydrogen atoms of amino (N2, N4, N4A, N4B) groups were located in a difference Fourier map and refined freely. The other hydrogen atoms were positioned geometrically (C—H = 0.95, N—H = 0.88 Å) and were refined using a riding model with U_iso(H) = 1.2U_eq(parent atom).

Table 2
Experimental details

Crystal data
Chemical formula	4C₄H₄FN₃O·C₃H₆N₆
M_r	642.55
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	200
a, b, c (Å)	18.343 (4), 7.9591 (16), 19.680 (4)
β (°)	114.65 (3)
V (Å³)	2611.3 (11)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.14
Crystal size (mm)	0.20 × 0.20 × 0.20

Data collection
Diffractometer	Rigaku AFC–8S
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2008 )
T_min, T_max	0.972, 0.972
No. of measured, independent and observed [I > 2σ(I)] reflections	10071, 2564, 2362
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.045, 0.123, 1.07
No. of reflections	2564
No. of parameters	233
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.44, −0.34
Computer programs: CrystalClear (Rigaku/MSC, 2008), SHELXS97 and SHELXL97 (Sheldrick, 2008 ), PLATON (Spek, 2009 ), Mercury (Macrae et al., 2008 ), POV-RAY (Cason, 2004 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 1469709

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S205698901600476X/hg5470sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S205698901600476X/hg5470Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S205698901600476X/hg5470Isup3.cml

checkCIF report

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2008); cell refinement: CrystalClear (Rigaku/MSC, 2008); data reduction: CrystalClear (Rigaku/MSC, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009), Mercury (Macrae et al., 2008) and POV-RAY (Cason, 2004); software used to prepare material for publication: PLATON (Spek, 2009) and publCIF (Westrip, 2010).

4-Amino-5-fluoro-1,2-dihydropyrimidin-2-one–1,3,5-triazine-2,4,6-triamine (4/1) top

Crystal data top

4(C₄H₄FN₃O)·C₃H₆N₆	F(000) = 1320
M_r = 642.55	D_x = 1.634 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 2564 reflections
a = 18.343 (4) Å	θ = 2.4–26.0°
b = 7.9591 (16) Å	µ = 0.14 mm⁻¹
c = 19.680 (4) Å	T = 200 K
β = 114.65 (3)°	Prism, colorless
V = 2611.3 (11) Å³	0.20 × 0.20 × 0.20 mm
Z = 4

Data collection top

Rigaku AFC–8S diffractometer	2564 independent reflections
Radiation source: fine focus sealed tube	2362 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.019
Detector resolution: 14.6199 pixels mm^-1	θ_max = 26.0°, θ_min = 2.4°
ω scans	h = −22→18
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2008)	k = −9→9
T_min = 0.972, T_max = 0.972	l = −24→24
10071 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.123	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.0741P)² + 1.8751P] where P = (F_o² + 2F_c²)/3
2564 reflections	(Δ/σ)_max < 0.001
233 parameters	Δρ_max = 0.44 e Å⁻³
0 restraints	Δρ_min = −0.34 e Å⁻³

Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > 2sigma(F²) is used only for calculating -R-factor-obs 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 (Å²) top

	x	y	z	U_iso*/U_eq
N1	0.50000	0.1866 (2)	0.25000	0.0244 (5)
N2	0.48606 (8)	0.18336 (19)	0.12847 (8)	0.0326 (4)
N3	0.48592 (8)	−0.07579 (17)	0.18444 (7)	0.0342 (4)
N4	0.50000	−0.3280 (3)	0.25000	0.0501 (8)
C2	0.49100 (8)	0.09524 (18)	0.18883 (7)	0.0248 (4)
C4	0.50000	−0.1589 (3)	0.25000	0.0300 (6)
F5A	0.32327 (5)	0.12206 (14)	0.26116 (5)	0.0420 (3)
O2A	0.06416 (6)	0.34719 (15)	0.03132 (6)	0.0326 (3)
N1A	0.11896 (8)	0.17904 (17)	0.13300 (7)	0.0315 (4)
N3A	0.19980 (7)	0.34775 (15)	0.09362 (7)	0.0252 (3)
N4A	0.33640 (8)	0.35220 (17)	0.16222 (8)	0.0299 (4)
C2A	0.12590 (8)	0.29396 (19)	0.08380 (8)	0.0253 (4)
C4A	0.26467 (8)	0.29295 (18)	0.15183 (8)	0.0243 (4)
C5A	0.25656 (9)	0.17587 (19)	0.20310 (8)	0.0286 (4)
C6A	0.18349 (9)	0.1215 (2)	0.19258 (9)	0.0332 (5)
F5B	0.21480 (6)	0.72438 (14)	−0.15032 (5)	0.0419 (3)
O2B	0.46711 (6)	0.54980 (13)	0.09792 (6)	0.0280 (3)
N1B	0.41539 (7)	0.70320 (16)	−0.00875 (7)	0.0278 (3)
N3B	0.33298 (7)	0.53026 (15)	0.02705 (7)	0.0261 (3)
N4B	0.19773 (8)	0.51382 (18)	−0.04738 (8)	0.0328 (4)
C2B	0.40666 (8)	0.59203 (17)	0.04058 (8)	0.0240 (4)
C4B	0.26965 (9)	0.57389 (18)	−0.03540 (8)	0.0259 (4)
C5B	0.27992 (9)	0.68402 (19)	−0.08772 (8)	0.0285 (4)
C6B	0.35239 (9)	0.74902 (19)	−0.07308 (8)	0.0298 (4)
H2A	0.4807 (12)	0.294 (3)	0.1263 (11)	0.037 (5)*
H2B	0.4701 (12)	0.135 (3)	0.0868 (12)	0.042 (5)*
H4A	0.5134 (13)	−0.381 (3)	0.2935 (11)	0.048 (6)*
H4A1	0.3799 (13)	0.308 (3)	0.1947 (11)	0.040 (5)*
H1A	0.07100	0.14180	0.12550	0.0380*
H4A2	0.3380 (13)	0.418 (3)	0.1253 (13)	0.049 (6)*
H6A	0.17710	0.04390	0.22640	0.0400*
H1B	0.46300	0.74610	0.00150	0.0330*
H4B1	0.1965 (13)	0.453 (3)	−0.0107 (12)	0.047 (6)*
H4B2	0.1569 (13)	0.543 (3)	−0.0874 (13)	0.045 (6)*
H6B	0.35960	0.82540	−0.10690	0.0360*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0248 (8)	0.0253 (8)	0.0219 (8)	0.0000	0.0085 (7)	0.0000
N2	0.0389 (8)	0.0345 (8)	0.0244 (7)	−0.0006 (6)	0.0133 (6)	0.0007 (5)
N3	0.0418 (8)	0.0307 (7)	0.0290 (7)	−0.0010 (5)	0.0138 (6)	−0.0013 (5)
N4	0.098 (2)	0.0262 (10)	0.0346 (11)	0.0000	0.0362 (13)	0.0000
C2	0.0196 (6)	0.0293 (7)	0.0231 (7)	0.0011 (5)	0.0064 (5)	−0.0001 (5)
C4	0.0387 (11)	0.0260 (10)	0.0245 (10)	0.0000	0.0124 (9)	0.0000
F5A	0.0276 (5)	0.0583 (7)	0.0320 (5)	0.0010 (4)	0.0043 (4)	0.0153 (4)
O2A	0.0229 (5)	0.0448 (7)	0.0268 (5)	−0.0027 (4)	0.0070 (4)	0.0085 (5)
N1A	0.0245 (6)	0.0405 (7)	0.0289 (7)	−0.0059 (5)	0.0106 (5)	0.0071 (5)
N3A	0.0222 (6)	0.0289 (6)	0.0244 (6)	−0.0020 (5)	0.0096 (5)	0.0018 (5)
N4A	0.0216 (6)	0.0349 (7)	0.0318 (7)	−0.0005 (5)	0.0099 (6)	0.0054 (5)
C2A	0.0245 (7)	0.0299 (7)	0.0219 (7)	−0.0018 (5)	0.0101 (6)	−0.0004 (5)
C4A	0.0250 (7)	0.0249 (7)	0.0239 (7)	−0.0008 (5)	0.0112 (6)	−0.0031 (5)
C5A	0.0261 (7)	0.0334 (8)	0.0226 (7)	0.0005 (6)	0.0065 (6)	0.0033 (6)
C6A	0.0312 (8)	0.0387 (8)	0.0283 (8)	−0.0037 (6)	0.0111 (6)	0.0090 (6)
F5B	0.0300 (5)	0.0569 (6)	0.0302 (5)	−0.0019 (4)	0.0041 (4)	0.0115 (4)
O2B	0.0250 (5)	0.0298 (5)	0.0269 (5)	−0.0040 (4)	0.0085 (4)	0.0023 (4)
N1B	0.0246 (6)	0.0310 (6)	0.0282 (6)	−0.0051 (5)	0.0114 (5)	0.0032 (5)
N3B	0.0245 (6)	0.0270 (6)	0.0279 (6)	−0.0055 (5)	0.0119 (5)	−0.0003 (5)
N4B	0.0258 (7)	0.0408 (8)	0.0294 (7)	−0.0066 (5)	0.0092 (6)	0.0010 (6)
C2B	0.0267 (7)	0.0226 (6)	0.0241 (7)	−0.0030 (5)	0.0119 (6)	−0.0030 (5)
C4B	0.0274 (7)	0.0254 (7)	0.0259 (7)	−0.0032 (5)	0.0122 (6)	−0.0045 (5)
C5B	0.0267 (7)	0.0341 (8)	0.0217 (7)	0.0007 (6)	0.0072 (6)	0.0014 (6)
C6B	0.0320 (8)	0.0328 (8)	0.0257 (7)	−0.0021 (6)	0.0130 (6)	0.0040 (6)

Geometric parameters (Å, º) top

F5A—C5A	1.3491 (18)	N4A—C4A	1.331 (2)
F5B—C5B	1.3492 (18)	N1A—H1A	0.8800
O2A—C2A	1.2462 (19)	N4A—H4A2	0.91 (2)
O2B—C2B	1.2539 (19)	N4A—H4A1	0.86 (2)
N1—C2	1.3563 (16)	N1B—C2B	1.3714 (19)
N1—C2ⁱ	1.3563 (16)	N1B—C6B	1.361 (2)
N2—C2	1.350 (2)	N3B—C4B	1.338 (2)
N3—C2	1.365 (2)	N3B—C2B	1.356 (2)
N3—C4	1.3751 (18)	N4B—C4B	1.329 (2)
N4—C4	1.346 (3)	N1B—H1B	0.8800
N2—H2A	0.89 (2)	N4B—H4B1	0.88 (2)
N2—H2B	0.84 (2)	N4B—H4B2	0.86 (2)
N4—H4A	0.89 (2)	C4A—C5A	1.426 (2)
N4—H4Aⁱ	0.89 (2)	C5A—C6A	1.340 (3)
N1A—C2A	1.376 (2)	C6A—H6A	0.9500
N1A—C6A	1.352 (2)	C4B—C5B	1.423 (2)
N3A—C4A	1.335 (2)	C5B—C6B	1.341 (2)
N3A—C2A	1.356 (2)	C6B—H6B	0.9500

F5A···C2ⁱ	3.134 (2)	C4B···C4B^ix	3.340 (2)
F5A···C6Bⁱⁱ	3.2444 (19)	C5A···C5B^v	3.541 (2)
F5A···N4A	2.7560 (18)	C5B···C6A^v	3.432 (2)
F5B···N4B	2.7459 (19)	C5B···C5A^v	3.541 (2)
F5B···C6Aⁱⁱⁱ	3.148 (2)	C5B···C4B^ix	3.500 (2)
F5A···H4A1	2.47 (2)	C6A···F5Bⁱⁱ	3.148 (2)
F5A···H6Bⁱⁱ	2.4300	C6A···C5B^v	3.432 (2)
F5B···H4B2	2.42 (2)	C6B···N3A^ix	3.325 (2)
O2A···N1B^iv	2.7545 (19)	C6B···F5Aⁱⁱⁱ	3.2444 (19)
O2A···N2^v	2.8949 (19)	C6B···N4B^ix	3.442 (2)
O2B···N4^vi	2.9600 (15)	C2···H4A1	2.69 (2)
O2B···N2	2.9689 (19)	C2···H4A1ⁱ	3.03 (2)
O2B···N4^vii	2.9600 (15)	C2···H4B2^v	2.84 (2)
O2B···N1A^viii	2.773 (2)	C2A···H4B1	2.96 (2)
O2A···H1B^iv	1.8800	C2A···H6B^ix	3.0600
O2A···H2B^v	2.15 (2)	C2A···H1B^iv	2.7700
O2B···H4A^vii	2.09 (2)	C2B···H1A^viii	2.8000
O2B···H4A2	2.84 (3)	C2B···H4A^vii	2.98 (2)
O2B···H1A^viii	1.9000	C2B···H4A2	2.84 (2)
O2B···H2A	2.10 (2)	C2B···H2A	2.90 (2)
N1···N4A	3.0664 (18)	C4A···H6A^xii	2.9600
N1···N4Aⁱ	3.0664 (18)	H4A1···C2	2.69 (2)
N1A···O2B^iv	2.773 (2)	H4A1···N1	2.23 (2)
N1B···O2A^viii	2.7545 (19)	H4A1···N2	2.93 (2)
N2···O2B	2.9689 (19)	H4A1···N1	2.23 (2)
N2···O2A^v	2.8949 (19)	H4A1···F5A	2.47 (2)
N3A···N4B	3.060 (2)	H4A1···C2ⁱ	3.03 (2)
N3A···C6B^ix	3.325 (2)	H1A···C2B^iv	2.8000
N3B···N4A	2.992 (2)	H1A···H1B^iv	2.5600
N4···O2B^x	2.9600 (15)	H1A···O2B^iv	1.9000
N4···O2B^xi	2.9600 (15)	H1B···C2A^viii	2.7700
N4A···N1	3.0664 (18)	H1B···O2A^viii	1.8800
N4A···N1	3.0664 (18)	H1B···H1A^viii	2.5600
N4A···C2	3.356 (2)	H4A2···O2B	2.84 (3)
N4A···N3B	2.992 (2)	H4A2···N3B	2.10 (2)
N4A···F5A	2.7560 (18)	H4A2···C2B	2.84 (2)
N4B···C4A^v	3.442 (2)	H2A···C2B	2.90 (2)
N4B···N3A	3.060 (2)	H2A···O2B	2.10 (2)
N4B···F5B	2.7459 (19)	H2B···O2A^v	2.15 (2)
N4B···C6B^ix	3.442 (2)	H4B1···N3A	2.20 (2)
N1···H4A1	2.23 (2)	H4B1···C2A	2.96 (2)
N1···H4A1ⁱ	2.23 (2)	H4B2···F5B	2.42 (2)
N2···H4A1	2.93 (2)	H4B2···N3^v	2.53 (2)
N3···H4B2^v	2.53 (2)	H4B2···C2^v	2.84 (2)
N3A···H6B^ix	2.8700	H4A···O2B^x	2.09 (2)
N3A···H4B1	2.20 (2)	H4A···C2B^x	2.98 (2)
N3B···H4A2	2.10 (2)	H6A···N4A^xiii	2.7700
N4A···H6A^xii	2.7700	H6A···C4A^xiii	2.9600
C2···N4A	3.356 (2)	H6B···F5Aⁱⁱⁱ	2.4300
C2···F5Aⁱ	3.134 (2)	H6B···N3A^ix	2.8700
C4A···N4B^v	3.442 (2)	H6B···C2A^ix	3.0600
C4B···C5B^ix	3.500 (2)

C2—N1—C2ⁱ	115.16 (14)	N3—C4—N3ⁱ	122.49 (19)
C2—N3—C4	116.06 (14)	N3—C4—N4	118.75 (11)
C2—N2—H2B	119.3 (16)	O2A—C2A—N1A	119.37 (15)
H2A—N2—H2B	115 (2)	N1A—C2A—N3A	119.33 (14)
C2—N2—H2A	121.7 (13)	O2A—C2A—N3A	121.30 (14)
C4—N4—H4A	118.2 (15)	N3A—C4A—N4A	119.11 (14)
H4A—N4—H4Aⁱ	124 (2)	N3A—C4A—C5A	120.14 (15)
C4—N4—H4Aⁱ	118.2 (15)	N4A—C4A—C5A	120.73 (14)
C2A—N1A—C6A	122.07 (15)	F5A—C5A—C6A	121.59 (14)
C2A—N3A—C4A	119.96 (13)	F5A—C5A—C4A	118.77 (15)
C6A—N1A—H1A	119.00	C4A—C5A—C6A	119.64 (15)
C2A—N1A—H1A	119.00	N1A—C6A—C5A	118.83 (15)
C4A—N4A—H4A1	121.3 (16)	N1A—C6A—H6A	121.00
C4A—N4A—H4A2	116.3 (16)	C5A—C6A—H6A	121.00
H4A1—N4A—H4A2	120 (2)	O2B—C2B—N3B	120.96 (14)
C2B—N1B—C6B	121.81 (14)	N1B—C2B—N3B	119.73 (14)
C2B—N3B—C4B	119.92 (13)	O2B—C2B—N1B	119.31 (14)
C2B—N1B—H1B	119.00	N3B—C4B—C5B	119.89 (16)
C6B—N1B—H1B	119.00	N4B—C4B—C5B	120.96 (15)
C4B—N4B—H4B2	119.0 (17)	N3B—C4B—N4B	119.15 (14)
H4B1—N4B—H4B2	126 (2)	C4B—C5B—C6B	120.04 (14)
C4B—N4B—H4B1	114.6 (16)	F5B—C5B—C4B	118.25 (15)
N2—C2—N3	119.01 (13)	F5B—C5B—C6B	121.68 (14)
N1—C2—N2	116.19 (14)	N1B—C6B—C5B	118.54 (14)
N1—C2—N3	124.81 (13)	N1B—C6B—H6B	121.00
N3ⁱ—C4—N4	118.75 (11)	C5B—C6B—H6B	121.00

C2ⁱ—N1—C2—N2	−176.73 (13)	C4B—N3B—C2B—O2B	−178.38 (14)
C2ⁱ—N1—C2—N3	3.98 (19)	C2B—N3B—C4B—N4B	−179.21 (14)
C4—N3—C2—N1	−7.5 (2)	C2B—N3B—C4B—C5B	0.5 (2)
C4—N3—C2—N2	173.24 (13)	C4B—N3B—C2B—N1B	2.1 (2)
C2—N3—C4—N4	−176.55 (11)	N3A—C4A—C5A—F5A	179.63 (13)
C2—N3—C4—N3ⁱ	3.45 (18)	N3A—C4A—C5A—C6A	−0.1 (2)
C6A—N1A—C2A—O2A	−177.48 (15)	N4A—C4A—C5A—F5A	−2.1 (2)
C6A—N1A—C2A—N3A	2.2 (2)	N4A—C4A—C5A—C6A	178.19 (15)
C2A—N1A—C6A—C5A	−1.3 (2)	F5A—C5A—C6A—N1A	−179.48 (14)
C4A—N3A—C2A—O2A	177.67 (14)	C4A—C5A—C6A—N1A	0.3 (2)
C4A—N3A—C2A—N1A	−2.0 (2)	N3B—C4B—C5B—F5B	179.56 (14)
C2A—N3A—C4A—N4A	−177.35 (14)	N3B—C4B—C5B—C6B	−2.6 (2)
C2A—N3A—C4A—C5A	1.0 (2)	N4B—C4B—C5B—F5B	−0.8 (2)
C6B—N1B—C2B—N3B	−2.7 (2)	N4B—C4B—C5B—C6B	177.13 (15)
C2B—N1B—C6B—C5B	0.6 (2)	F5B—C5B—C6B—N1B	179.78 (14)
C6B—N1B—C2B—O2B	177.75 (14)	C4B—C5B—C6B—N1B	2.0 (2)

Symmetry codes: (i) −x+1, y, −z+1/2; (ii) x, −y+1, z+1/2; (iii) x, −y+1, z−1/2; (iv) x−1/2, y−1/2, z; (v) −x+1/2, −y+1/2, −z; (vi) x, y+1, z; (vii) −x+1, y+1, −z+1/2; (viii) x+1/2, y+1/2, z; (ix) −x+1/2, −y+3/2, −z; (x) −x+1, y−1, −z+1/2; (xi) x, y−1, z; (xii) −x+1/2, y+1/2, −z+1/2; (xiii) −x+1/2, y−1/2, −z+1/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N4A—H4A1···F5A	0.86 (2)	2.47 (2)	2.7560 (18)	100.0 (18)
N4A—H4A1···N1	0.86 (2)	2.23 (2)	3.0664 (18)	164 (2)
N1A—H1A···O2B^iv	0.88	1.90	2.773 (2)	173
N1B—H1B···O2A^viii	0.88	1.88	2.7545 (19)	175
N4A—H4A2···N3B	0.91 (2)	2.10 (2)	2.992 (2)	169 (2)
N2—H2A···O2B	0.89 (2)	2.10 (2)	2.9689 (19)	167.6 (18)
N2—H2B···O2A^v	0.84 (2)	2.15 (2)	2.8949 (19)	149 (2)
N4B—H4B1···N3A	0.88 (2)	2.20 (2)	3.060 (2)	169 (2)
N4B—H4B2···F5B	0.86 (2)	2.42 (2)	2.7459 (19)	103 (2)
N4B—H4B2···N3^v	0.86 (2)	2.53 (2)	3.360 (2)	162 (2)
N4—H4A···O2B^x	0.89 (2)	2.09 (2)	2.9600 (15)	165 (2)
C6B—H6B···F5Aⁱⁱⁱ	0.95	2.43	3.2444 (19)	143

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

Acknowledgements

MM thanks the UGC–BSR, India, for the award of an RFSMS. PTM thanks the UGC–BSR faculty fellowship for a one-time grant.

References

Bennet, J. E. (1977). Ann. Intern. Med. 86, 319–21. CAS PubMed Google Scholar
Benson, J. M. & Nahata, M. C. (1988). Clin. Pharm. 7, 424–438. CAS PubMed Web of Science Google Scholar
Cason, C. J. (2004). POV-RAY for Windows. Persistence of Vision, Raytracer Pvt Ltd, Victoria, Australia. URL: https://www.povray.org. Google Scholar
Desiraju, G. R. (1989). Crystal Engineering. The Design of Organic Solids. Amsterdam: Elsevier. Google Scholar
Hulme, A. T. & Tocher, D. A. (2006). Cryst. Growth Des. 6, 481–487. Web of Science CSD CrossRef CAS Google Scholar
Janczak, J. & Perpétuo, G. J. (2001a). Acta Cryst. C57, 1431–1433. CrossRef CAS IUCr Journals Google Scholar
Janczak, J. & Perpétuo, G. J. (2001b). Acta Cryst. C57, 1120–1122. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Janczak, J. & Perpétuo, G. J. (2002). Acta Cryst. C58, o339–o341. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Janczak, J. & Perpétuo, G. J. (2004). Acta Cryst. C60, o211–o214. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Karthikeyan, A., Thomas Muthiah, P. & Perdih, F. (2014). Acta Cryst. E70, 328–330. CSD CrossRef IUCr Journals Google Scholar
Larsen, R. A., Kauffman, C. A., Pappas, P. G., Sobel, J. D. & Dismukes, W. E. (2003). In Essentials of Clinical Mycology, 2nd ed., pp. 57–60. Oxford University Press. UK. Google Scholar
Louis, T., Low, J. N. & Tollin, P. (1982). Cryst. Struct. Commun. 11, 1059–1064. CAS Google Scholar
MacDonald, J. C. & Whitesides, G. M. (1994). Chem. Rev. 94, 2383–2420. CrossRef CAS Web of Science Google Scholar
Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Morschhäuser, J. (2003). Pharm. Unserer Zeit, 32, 124–128. PubMed Google Scholar
Mullen, C. A., Coale, M. M., Lowe, R. & Blaese, R. M. (1994). Cancer Res. 54, 1503–1506. CAS PubMed Google Scholar
Perpétuo, G. J., Ribeiro, M. A. & Janczak, J. (2005). Acta Cryst. E61, o1818–o1820. Web of Science CSD CrossRef IUCr Journals Google Scholar
Perumalla, S. R., Pedireddi, V. R. & Sun, C. C. (2013a). Cryst. Growth Des. 13, 429–432. CrossRef CAS Google Scholar
Perumalla, S. R., Pedireddi, V. R. & Sun, C. C. (2013b). Mol. Pharm. 10, 2462–2466. CrossRef CAS PubMed Google Scholar
Polak, A. & Scholer, H. J. (1980). Rev. Inst. Pasteur Lyon. 13, 233–244. CAS Google Scholar
Portalone, G. (2011). Chem. Cent. J. 5, 51. CrossRef PubMed Google Scholar
Portalone, G. & Colapietro, M. (2006). Acta Cryst. E62, o1049–o1051. Web of Science CSD CrossRef IUCr Journals Google Scholar
Prabakaran, P., Murugesan, S., Muthiah, P. T., Bocelli, G. & Righi, L. (2001). Acta Cryst. E57, o933–o936. Web of Science CSD CrossRef IUCr Journals Google Scholar
Rigaku/MSC (2008). CrystalClear. Rigaku Americas Corporation, The Woodlands, Texas, USA. Google Scholar
Russell, K. C., Lehn, J. M., Kyritsakas, N., DeCian, A. & Fischer, J. (1998). New J. Chem. 22, 123–128. CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Silva, C. C. P. da, de Oliveira, R., Tenorio, J. C., Honorato, S., Ayala, A. P. & Ellena, J. (2013). Cryst. Growth Des. 13, 4315–4322. Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tassel, D. & Madoff, A. (1968). J. Am. Med. Assoc. 206, 830–832. CrossRef CAS Google Scholar
Tutughamiarso, M., Bolte, M. & Egert, E. (2009). Acta Cryst. C65, o574–o578. Web of Science CSD CrossRef IUCr Journals Google Scholar
Tutughamiarso, M., Wagner, G. & Egert, E. (2012). Acta Cryst. B68, 431–443. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Vermes, A., Guchelaar, H. J. & Dankert, J. (2000). J. Antimicrob. Chemother. 46, 171–179. Web of Science CrossRef PubMed CAS Google Scholar
Wang, G., Wu, W. & Zhuang, L. (2007). Acta Cryst. E63, m2552–m2553. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Whitesides, G. M., Mathias, J. P. & Seto, C. T. (1991). Science, 254, 1312–1319. CrossRef PubMed CAS Web of Science Google Scholar
Zerkowski, J. A. & Whitesides, G. M. (1994). J. Am. Chem. Soc. 116, 4298–4304. CSD CrossRef CAS Web of Science Google Scholar