New pseudopolymorphs of 5-fluoro­cytosine

In order to better understand the inter­action between the pharmaceutically active compound 5-fluoro­cytosine [4-amino-5-fluoro­pyrimidin-2(1H)-one] and its receptor, hydrogen-bonded complexes with structurally similar bonding patterns have been investigated. During the cocrystallization screening, three new pseudopolymorphs of 5-fluoro­cytosine were ob­tained, namely 5-fluoro­cytosine dimethyl sulfoxide solvate, C₄H₄FN₃O·C₂H₆OS, (I), 5-fluoro­cytosine dimethyl­acetamide hemisolvate, C₄H₄FN₃O·0.5C₄H₉NO, (II), and 5-fluoro­cytosine hemihydrate, C₄H₄FN₃O·0.5H₂O, (III). Similar hydrogen-bond patterns are observed in all three crystal structures. The 5-fluoro­cytosine mol­ecules form ribbons with repeated R₂²(8) dimer inter­actions. These dimers are stabilized by N-H...N and N-H...O hydrogen bonds. The solvent mol­ecules adopt similar positions with respect to 5-fluoro­cytosine. Depending on the hydrogen bonds formed by the solvent, the 5-fluoro­cytosine ribbons form layers or tubes. A database study was carried out to compare the hydrogen-bond pattern of compounds (I)-(III) with those of other (pseudo)polymorphs of 5-fluoro­cytosine.

S1. Comment

5-Fluorocytosine is commonly used as a systemic antifungal drug. It becomes active by deamination within the fungal cells to 5-fluorouracil, and inhibits RNA and DNA synthesis (Morschhäuser, 2003). Furthermore, there is a novel application as a prodrug against liver tumours (Pierrefite-Carle et al., 1999). The interaction between 5-fluorocytosine and its receptor, as well as the base pairing, can be imitated by hydrogen-bonded complexes (Davis et al., 2003). In order to investigate these interactions, we co-crystallized 5-fluorocytosine together with model compounds containing complementary functional groups. During the co-crystallization screening three new pseudopolymorphs of 5-fluorocytosine were obtained: 5-fluorocytosine dimethyl sulfoxide solvate, (I), 5-fluorocytosine dimethylacetamide hemisolvate, (II), and 5-fluorocytosine hemihydrate, (III). Since 5-fluorocytosine is a rigid molecule, no significant geometric changes are to be expected and the molecules in (I)–(III) show the usual geometry.

Compound (I) crystallizes in the monoclinic space group P2₁/c, with one 5-fluorocytosine and one dimethyl sulfoxide (DMSO) molecule in the asymmetric unit (Fig. 1). The planar 5-fluorocytosine (r.m.s. deviation 0.016 Å for all non-H atoms) is coplanar with the S and one C atom of the solvent molecule. The other methyl C and the O atom deviate from this plane by 0.753 (4) and 0.890 (3) Å, respectively. Both molecules are connected by an N—H···O hydrogen bond. The 5-fluorocytosine molecules form ribbons parallel to the (302) plane, which are characterized by repeated R₂²(8) (Bernstein et al., 1995) dimer interactions with the N—H···N and N—H···O hydrogen bonds (Fig. 2).

Compound (II) crystallizes in the triclinic space group P1, with two essentially planar 5-fluorocytosine molecules (r.m.s. deviation 0.091 Å for all non-H atoms in both molecules) and one disordered dimethylacetamide (DMAC) molecule in the asymmetric unit (Fig. 3). Although the solvent molecule is disordered over two sites, all atoms of these two sites lie in a common plane (r.m.s. deviation 0.004 Å for all non-H atoms in both orientations). The 5-fluorocytosine molecules form planar ribbons and show exactly the same hydrogen-bond pattern as in (I). The O atom of the DMAC molecule adopts a position similar to that of the O atom of the DMSO molecule in (I). The planes through the non H-atoms of the solvent molecule and those of the 5-fluorocytosine ribbons enclose a dihedral angle of 68.0 (1)° (Fig. 4). The packing of (II) shows tubes of 5-fluorocytosine ribbons stabilized by N—H···O hydrogen bonds between 5-fluorocytosine and dimethylacetamide molecules (Fig. 5).

Compound (III) crystallizes in the non-centrosymmetric space group Cc, with four 5-fluorocytosine and two water molecules in the asymmetric unit (Fig. 6). There are two planar 5-fluorocytosine dimers, each stabilized by a R₂²(8) hydrogen-bond pattern. The r.m.s. deviations for all non-H atoms of the dimers are 0.066 and 0.105 Å, respectively. The water molecules are displaced by 2.337 (4) and 2.378 (4) Å from the planes of the dimers. As in (I) and (II), the 5-fluorocytosine molecules form hydrogen-bonded ribbons (Fig. 7). Each dimer is directly connected only to its symmetry equivalents, but not to the other symmetry-independent dimer. Neighbouring layers of the two symmetry-independent dimers are held together by water-mediated OW—H···O and N—H···OW hydrogen bonds (Fig. 8).

In order to compare the hydrogen-bonding patterns of compounds (I)-(III) with other (pseudo)polymorphs of 5-fluorocytosine, a study of the Cambridge Structural Database (CSD, Version?; Allen, 2002) was undertaken. Since (I)–(III) contain neutral 5-fluorocytosine, we restricted the search to neutral molecules and found nine entries: two polymorphs of solvent-free 5-fluorocytosine (forms I and II according to Hulme & Tocher, 2006; CSD refcodes MEBQEQ01 and MEBQEQ), two monohydrates [forms I(h) and II(h); refcodes BIRMEU and BIRMEU03], a hemipentahydrate (refcode MEBQUG), a methanol solvate (refcode MEBQOA) and a 2,2,2-trifluoroethanol solvate (refcode MEBQIU). The other two entries (refcodes BIRMEU01 and BIRMEU02) were redeterminations of the I(h) form (Louis et al., 1982; Portalone & Colapietro, 2006). [Please provide references for all refcodes]

The hydrogen-bond pattern in the anhydrous forms I and II is similar to that in (I)–(III). They form ribbons with repeated R₂²(8) dimer interactions stabilized by N—H···N and N—H···O hydrogen bonds. Form I crystallizes in the tetragonal space group P4₁2₁2 with one independent molecule; its crystal packing shows a zigzag arrangement of planar 5-fluorocytosine ribbons, which enclose a dihedral angle of 64.9°. Form II crystallizes in the monoclinic space group P2₁/n with one independent molecule. In contrast with (I)–(III), the 5-fluorocytosine ribbons in form II are rippled and are connected with adjacent ribbons into layers by R₂⁴(8) N—H···O interactions.

The 5-fluorocytosine molecules in form I(h) and in the hemipentahydrate structure show an identical hydrogen-bond pattern to that in (I)–(III). Form I(h) crystallizes in the monoclinic space group P2₁/c, with two 5-fluorocytosine and two water molecules in the asymmetric unit. The planar 5-fluorocytosine ribbons are stabilized by the water molecules, forming a tube. The water molecules themselves form cyclic tetramers and connect the tubes into a three-dimensional hydrogen-bonded network. The 5-fluorocytosine hemipentahydrate crystallizes in the monoclinic space group P2₁/c, with two 5-fluorocytosine and five water molecules in the asymmetric unit. The water molecules form a hydrogen-bonded sheet parallel to the bc plane. The 5-fluorocytosine ribbons are stacked nearly perpendicular to the water sheet and are stabilized in columns by water-mediated hydrogen bonds. The asymmetric unit of triclinic II(h) consists of one 5-fluorocytosine and one water molecule. In this case, a different hydrogen-bonding pattern of the 5-fluorocytosine molecules is observed. The 5-fluorocytosine molecules are held together by two kinds of dimer interactions. Although these dimers show the same R₂²(8) graph set, the hydrogen-bond pattern consists of either two centrosymmetric N—H···O or two centrosymmetric N—H···N interactions. The planar 5-fluorocytosine ribbons are further connected by two symmetry-equivalent water molecules.

In the methanol solvate and the 2,2,2-trifluoroethanol solvate, the 5-fluorocytosine molecules show again the same hydrogen-bonded ribbons as in (I)–(III). The 5-fluorocytosine methanol solvate crystallizes in the monoclinic space group P2₁/n, with two 5-fluorocytosine and one methanol molecule in the asymmetric unit. Similar to (III), the 5-fluorocytosine molecules are directly connected only to their symmetry equivalents. The methanol molecule holds three different 5-fluorocytosine ribbons together. The 1:1 5-fluorocytosine 2,2,2-trifluoroethanol solvate crystallizes in the monoclinic space group P2₁/c. The packing shows some similarity to (II). The tubes of 5-fluorocytosine ribbons are stabilized by hydrogen bonds to solvent molecules which participate in N—H···O and O—H···O interactions.

Almost all structures discussed show the same hydrogen-bond pattern between the 5-fluorocytosine molecules. Apparently, the latter molecules prefer the formation of R₂²(8) dimers, which are further hydrogen-bonded into ribbons. The dimers are usually stabilized by an N—H···O and an N—H···N interaction. Only in the case of monohydrate form II(h) is a different pattern observed: the 5-fluorocytosine molecules form centrosymmetric dimers, which are stabilized either by two N—H···O or by two N—H···N hydrogen bonds. The crystal packing shows layers or tubes depending on the hydrogen bonds formed with adjacent 5-fluorocytosine ribbons or solvent molecules.

S2. Experimental

Single crystals of (I)–(III) were obtained by co-crystallization of commercially available 5-fluorocytosine with various compounds. The crystallization method used was solvent evaporation at 323 K for (I) and (II), and at room temperature for (III). Compound (I) was obtained by crystallization of 5-fluorocytosine with carbamylurea from dimethyl sulfoxide. 5-Fluorocytosine and N,N'-(pyridine-2,6-diyl)diacetamide dissolved in dimethylacetamide yielded (II). Crystals of (III) were obtained by crystallization of 5-fluorocytosine and 2-aminopyridine in dimethylacetamide. [Please give mole ratios or quantities of reagents]

S3. Refinement

In (I) and (II), all H atoms were initially located by difference Fourier synthesis. Subsequently, H atoms bonded to C atoms were refined using a riding model, with methyl C—H = 0.98 Å and aromatic C—H = 0.95 Å, and with U_iso(H) = 1.5U_eq(C_methyl) or 1.2U_eq(C). H atoms bonded to N atoms were refined isotropically. In (III), all H atoms of the 5-fluorocytosine molecules were refined using a riding model, with aromatic C—H = 0.95 Å, and amide and terminal N—H = 0.88 Å, with U_iso(H) = 1.2U_eq(C,N). For the water molecules, the following restraints were applied: O—H = 0.88 (2) and H···H = 1.44 (4) Å.

In (II), all solvent atoms except O are disordered over two positions, with a site occupation factor of 0.66 (2) for the major occupied orientation. However, the positions of the methyl C atoms coincide.

In spite of the E-value distribution, which suggests a centrosymmetric space group (mean value of E² - 1 = 0.958), the structure solution of (III) in the centrosymmetric space group C2/c failed. 2113 Friedel pairs were merged prior to refinement, due to the absence of anomalous scatterers. The absolute structure was arbitrarily assigned.

Computing details

For all compounds, data collection: X-AREA (Stoe & Cie, 2001); cell refinement: X-AREA (Stoe & Cie, 2001); data reduction: X-AREA (Stoe & Cie, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Version 2.2; Macrae et al., 2008) and XP (Sheldrick, 2008); software used to prepare material for publication: publCIF (Westrip, 2009).

Figures

	Fig. 1. A perspective view of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. The dashed line indicates the N—H···O hydrogen bond.
	Fig. 2. A partial packing diagram for (I), viewed along [001]. Hydrogen bonds are shown as dashed lines.
	Fig. 3. A perspective view of (II), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. Dashed lines indicate hydrogen bonds. The dimethylacetamide molecule is disordered and the minor occupied sites are not shown.
	Fig. 4. The hydrogen-bond pattern of (II), viewed along [001]. Hydrogen bonds are shown as dashed lines. The minor occupied sites of the dimethylacetamide molecules have been omitted.
	Fig. 5. A packing diagram for (II), showing the tubular arrangement of the molecules. Hydrogen bonds are shown as dashed lines. The minor occupied sites of the dimethylacetamide molecules have been omitted.
	Fig. 6. Perspective views of (a) the first dimer (including the solvent water) and (b) the second dimer (including the solvent water) in the asymmetric unit of (III), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. Dashed lines indicate hydrogen bonds.
	Fig. 7. The hydrogen-bond pattern of (III), viewed along [001]. Hydrogen bonds are shown as dashed lines.
	Fig. 8. A packing diagram for (III). Hydrogen bonds are shown as dashed lines.

(I) 4-amino-5-fluoropyrimidin-2(1H)-one dimethyl sulfoxide solvate

Crystal data

C4H4FN3O·C2H6OS	F(000) = 432
Mr = 207.23	Dx = 1.471 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 6720 reflections
a = 12.4467 (12) Å	θ = 4.0–26.6°
b = 9.1849 (8) Å	µ = 0.33 mm^−1
c = 8.5635 (8) Å	T = 173 K
β = 107.065 (8)°	Plate, colourless
V = 935.89 (15) Å^3	0.31 × 0.14 × 0.05 mm
Z = 4

Data collection

Stoe IPDS II two-circle diffractometer	1904 independent reflections
Radiation source: fine-focus sealed tube	1509 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.049
ω scans	θmax = 26.4°, θmin = 4.1°
Absorption correction: multi-scan [MULABS (Spek, 2009; Blessing, 1995)]	h = −15→15
Tmin = 0.903, Tmax = 0.984	k = −11→9
8061 measured reflections	l = −10→10

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) = 0.100	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0576P)^2 + 0.0842P] where P = (Fo^2 + 2Fc^2)/3
1904 reflections	(Δ/σ)max < 0.001
132 parameters	Δρmax = 0.26 e Å^−3
0 restraints	Δρmin = −0.27 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
N1	0.54297 (14)	0.11389 (16)	0.33369 (18)	0.0300 (4)
H1	0.514 (2)	0.035 (3)	0.278 (3)	0.041 (6)*
C2	0.49989 (16)	0.24607 (18)	0.2677 (2)	0.0278 (4)
O21	0.41905 (12)	0.25078 (14)	0.14085 (16)	0.0357 (3)
N3	0.54901 (13)	0.37009 (16)	0.34453 (17)	0.0274 (3)
C4	0.63599 (15)	0.36507 (19)	0.48044 (19)	0.0253 (4)
N41	0.68134 (15)	0.48979 (18)	0.54895 (19)	0.0322 (4)
H411	0.739 (2)	0.489 (3)	0.626 (3)	0.038 (6)*
H412	0.652 (2)	0.574 (3)	0.497 (3)	0.043 (6)*
C5	0.67761 (15)	0.22642 (19)	0.5482 (2)	0.0280 (4)
F51	0.76422 (10)	0.22291 (12)	0.68946 (13)	0.0388 (3)
C6	0.63106 (16)	0.1036 (2)	0.4720 (2)	0.0305 (4)
H6	0.6593	0.0111	0.5142	0.037*
S1M	0.89390 (5)	0.67960 (6)	0.90065 (6)	0.04211 (18)
O1M	0.90100 (14)	0.57959 (18)	0.76343 (18)	0.0499 (4)
C1M	1.0318 (2)	0.7510 (3)	0.9899 (3)	0.0589 (7)
H1M1	1.0832	0.6714	1.0384	0.088*
H1M2	1.0301	0.8217	1.0749	0.088*
H1M3	1.0578	0.7991	0.9055	0.088*
C2M	0.8305 (2)	0.8437 (3)	0.8087 (3)	0.0583 (6)
H2M1	0.8726	0.8822	0.7373	0.087*
H2M2	0.8311	0.9152	0.8939	0.087*
H2M3	0.7527	0.8243	0.7440	0.087*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0353 (9)	0.0167 (7)	0.0314 (7)	−0.0004 (6)	−0.0007 (6)	−0.0012 (6)
C2	0.0305 (9)	0.0202 (8)	0.0290 (8)	0.0006 (7)	0.0030 (7)	0.0001 (6)
O21	0.0360 (8)	0.0226 (6)	0.0370 (7)	−0.0002 (6)	−0.0072 (6)	0.0004 (5)
N3	0.0299 (8)	0.0182 (7)	0.0299 (7)	−0.0003 (6)	0.0021 (6)	−0.0001 (5)
C4	0.0266 (9)	0.0243 (8)	0.0246 (8)	−0.0007 (7)	0.0068 (6)	−0.0005 (6)
N41	0.0342 (9)	0.0242 (8)	0.0306 (8)	−0.0031 (6)	−0.0023 (7)	−0.0023 (6)
C5	0.0283 (9)	0.0269 (9)	0.0247 (8)	0.0022 (7)	0.0014 (7)	0.0026 (6)
F51	0.0383 (6)	0.0355 (6)	0.0309 (6)	−0.0001 (5)	−0.0078 (5)	0.0030 (4)
C6	0.0330 (10)	0.0229 (8)	0.0312 (9)	0.0042 (7)	0.0024 (7)	0.0042 (7)
S1M	0.0453 (3)	0.0455 (3)	0.0326 (3)	−0.0113 (3)	0.0070 (2)	−0.0037 (2)
O1M	0.0485 (9)	0.0477 (9)	0.0443 (8)	−0.0061 (7)	−0.0007 (7)	−0.0155 (7)
C1M	0.0482 (14)	0.0643 (16)	0.0507 (14)	−0.0107 (12)	−0.0064 (11)	−0.0185 (12)
C2M	0.0550 (15)	0.0635 (16)	0.0573 (14)	0.0118 (13)	0.0178 (12)	−0.0020 (12)

Geometric parameters (Å, º)

N1—C6	1.361 (2)	C5—F51	1.3640 (19)
N1—C2	1.380 (2)	C6—H6	0.9500
N1—H1	0.88 (3)	S1M—O1M	1.5143 (16)
C2—O21	1.246 (2)	S1M—C2M	1.775 (3)
C2—N3	1.367 (2)	S1M—C1M	1.786 (2)
N3—C4	1.338 (2)	C1M—H1M1	0.9800
C4—N41	1.334 (2)	C1M—H1M2	0.9800
C4—C5	1.432 (2)	C1M—H1M3	0.9800
N41—H411	0.82 (3)	C2M—H2M1	0.9800
N41—H412	0.91 (3)	C2M—H2M2	0.9800
C5—C6	1.346 (3)	C2M—H2M3	0.9800
C6—N1—C2	122.32 (15)	C5—C6—H6	120.5
C6—N1—H1	120.9 (16)	N1—C6—H6	120.5
C2—N1—H1	116.6 (16)	O1M—S1M—C2M	106.88 (11)
O21—C2—N3	121.56 (16)	O1M—S1M—C1M	106.70 (12)
O21—C2—N1	120.33 (16)	C2M—S1M—C1M	97.16 (14)
N3—C2—N1	118.10 (15)	S1M—C1M—H1M1	109.5
C4—N3—C2	121.58 (15)	S1M—C1M—H1M2	109.5
N41—C4—N3	118.87 (16)	H1M1—C1M—H1M2	109.5
N41—C4—C5	121.95 (16)	S1M—C1M—H1M3	109.5
N3—C4—C5	119.18 (15)	H1M1—C1M—H1M3	109.5
C4—N41—H411	120.1 (17)	H1M2—C1M—H1M3	109.5
C4—N41—H412	117.2 (15)	S1M—C2M—H2M1	109.5
H411—N41—H412	122 (2)	S1M—C2M—H2M2	109.5
C6—C5—F51	121.73 (16)	H2M1—C2M—H2M2	109.5
C6—C5—C4	119.71 (16)	S1M—C2M—H2M3	109.5
F51—C5—C4	118.57 (15)	H2M1—C2M—H2M3	109.5
C5—C6—N1	119.09 (16)	H2M2—C2M—H2M3	109.5
C6—N1—C2—O21	−179.93 (19)	N3—C4—C5—C6	2.0 (3)
C6—N1—C2—N3	0.6 (3)	N41—C4—C5—F51	1.8 (3)
O21—C2—N3—C4	−179.82 (18)	N3—C4—C5—F51	−178.12 (17)
N1—C2—N3—C4	−0.4 (3)	F51—C5—C6—N1	178.36 (17)
C2—N3—C4—N41	179.20 (17)	C4—C5—C6—N1	−1.7 (3)
C2—N3—C4—C5	−0.9 (3)	C2—N1—C6—C5	0.5 (3)
N41—C4—C5—C6	−178.12 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N41—H411···O1M	0.82 (3)	2.18 (3)	2.929 (2)	152 (2)
N41—H412···O21^i	0.91 (3)	2.05 (3)	2.959 (2)	174 (2)
N1—H1···N3^ii	0.88 (3)	1.88 (3)	2.762 (2)	179 (2)

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

(II) 5-fluorocytosine dimethylacetamide hemisolvate

Crystal data

C4H4FN3O·0.5C4H9NO	Z = 4
Mr = 172.67	F(000) = 360
Triclinic, P1	Dx = 1.473 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.7247 (12) Å	Cell parameters from 3061 reflections
b = 8.2840 (13) Å	θ = 3.6–25.6°
c = 13.238 (2) Å	µ = 0.13 mm^−1
α = 90.204 (13)°	T = 173 K
β = 104.336 (12)°	Block, colourless
γ = 107.774 (12)°	0.40 × 0.25 × 0.10 mm
V = 778.7 (2) Å^3

Data collection

Stoe IPDS II two-circle diffractometer	1647 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.169
Graphite monochromator	θmax = 25.6°, θmin = 3.6°
ω scans	h = −9→9
8171 measured reflections	k = −10→10
2911 independent reflections	l = −16→16

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)] = 0.069	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.199	H atoms treated by a mixture of independent and constrained refinement
S = 0.94	w = 1/[σ^2(Fo^2) + (0.0992P)^2] where P = (Fo^2 + 2Fc^2)/3
2911 reflections	(Δ/σ)max < 0.001
260 parameters	Δρmax = 0.29 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	Occ. (<1)
N1	0.6755 (4)	0.4441 (4)	0.4706 (2)	0.0325 (7)
H1	0.617 (6)	0.370 (6)	0.505 (4)	0.056 (13)*
C2	0.8323 (4)	0.5758 (4)	0.5227 (3)	0.0289 (7)
N3	0.9256 (4)	0.6894 (4)	0.4629 (2)	0.0318 (7)
C4	0.8722 (4)	0.6688 (4)	0.3592 (3)	0.0302 (7)
C5	0.7115 (4)	0.5274 (5)	0.3070 (3)	0.0342 (8)
C6	0.6156 (5)	0.4204 (4)	0.3648 (3)	0.0367 (8)
H6	0.5066	0.3286	0.3317	0.044*
O21	0.8860 (3)	0.5886 (3)	0.61967 (19)	0.0373 (6)
N41	0.9677 (4)	0.7820 (4)	0.3044 (3)	0.0393 (8)
H41A	1.065 (6)	0.871 (6)	0.348 (4)	0.053 (12)*
H41B	0.944 (6)	0.752 (6)	0.236 (4)	0.057 (13)*
F51	0.6585 (3)	0.5103 (3)	0.20080 (17)	0.0507 (6)
N1'	0.2381 (4)	−0.0518 (4)	0.5760 (2)	0.0344 (7)
H1'	0.126 (7)	−0.152 (7)	0.530 (4)	0.067 (14)*
C2'	0.3343 (4)	0.0753 (4)	0.5237 (3)	0.0312 (8)
N3'	0.4837 (4)	0.2039 (4)	0.5831 (2)	0.0315 (7)
C4'	0.5436 (4)	0.2019 (4)	0.6861 (3)	0.0322 (8)
C5'	0.4465 (5)	0.0634 (5)	0.7372 (3)	0.0356 (8)
C6'	0.2937 (5)	−0.0575 (5)	0.6810 (3)	0.0379 (9)
H6'	0.2248	−0.1466	0.7144	0.046*
O21'	0.2856 (3)	0.0705 (3)	0.42708 (19)	0.0386 (6)
N41'	0.6917 (4)	0.3294 (4)	0.7417 (3)	0.0389 (8)
H41C	0.737 (6)	0.400 (6)	0.697 (4)	0.060 (13)*
H41D	0.745 (5)	0.320 (5)	0.807 (3)	0.036 (10)*
F51'	0.5092 (3)	0.0644 (3)	0.84358 (17)	0.0502 (6)
C1D	1.2784 (6)	0.2097 (7)	1.0031 (4)	0.0585 (12)
H1DA	1.3251	0.1847	1.0752	0.088*	0.657 (19)
H1DB	1.3700	0.3107	0.9870	0.088*	0.657 (19)
H1DC	1.2607	0.1125	0.9548	0.088*	0.657 (19)
H1DD	1.3785	0.1742	1.0489	0.088*	0.343 (19)
H1DE	1.3327	0.3232	0.9816	0.088*	0.343 (19)
H1DF	1.2174	0.1286	0.9410	0.088*	0.343 (19)
C2D	1.0927 (10)	0.2425 (7)	0.9911 (6)	0.036 (2)	0.657 (19)
O21D	0.9921 (4)	0.2783 (4)	0.9091 (2)	0.0559 (8)
N3D	1.0404 (11)	0.2394 (7)	1.0790 (6)	0.039 (2)	0.657 (19)
C4D	0.8578 (6)	0.2796 (6)	1.0730 (4)	0.0590 (12)
H4DA	0.8326	0.2739	1.1421	0.088*	0.657 (19)
H4DB	0.7533	0.1964	1.0227	0.088*	0.657 (19)
H4DC	0.8703	0.3941	1.0503	0.088*	0.657 (19)
H4DD	0.9062	0.2530	1.1445	0.088*	0.343 (19)
H4DE	0.7304	0.2012	1.0433	0.088*	0.343 (19)
H4DF	0.8541	0.3968	1.0742	0.088*	0.343 (19)
C5D	1.1362 (7)	0.1816 (7)	1.1763 (3)	0.0614 (13)
H5DA	1.0742	0.1903	1.2314	0.092*	0.657 (19)
H5DB	1.2684	0.2531	1.1984	0.092*	0.657 (19)
H5DC	1.1297	0.0630	1.1636	0.092*	0.657 (19)
H5DD	1.2482	0.1483	1.2068	0.092*	0.343 (19)
H5DE	1.0232	0.0896	1.1799	0.092*	0.343 (19)
H5DF	1.1430	0.2850	1.2154	0.092*	0.343 (19)
C2D'	0.9825 (19)	0.2610 (13)	1.0080 (11)	0.033 (4)	0.343 (19)
N3D'	1.128 (2)	0.2150 (15)	1.0640 (10)	0.041 (4)	0.343 (19)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0272 (13)	0.0271 (15)	0.0416 (17)	0.0046 (11)	0.0109 (12)	0.0108 (13)
C2	0.0236 (15)	0.0214 (16)	0.0420 (19)	0.0058 (12)	0.0107 (13)	0.0088 (14)
N3	0.0242 (13)	0.0301 (15)	0.0406 (17)	0.0047 (11)	0.0123 (11)	0.0081 (13)
C4	0.0266 (16)	0.0265 (17)	0.0388 (19)	0.0078 (13)	0.0118 (14)	0.0057 (15)
C5	0.0264 (16)	0.0357 (19)	0.0370 (19)	0.0053 (14)	0.0076 (14)	0.0005 (15)
C6	0.0262 (16)	0.0303 (18)	0.051 (2)	0.0064 (14)	0.0091 (15)	0.0034 (16)
O21	0.0382 (13)	0.0316 (13)	0.0393 (14)	0.0054 (10)	0.0124 (11)	0.0097 (11)
N41	0.0355 (16)	0.0408 (19)	0.0380 (18)	0.0038 (14)	0.0133 (14)	0.0101 (15)
F51	0.0453 (12)	0.0554 (15)	0.0419 (13)	0.0020 (10)	0.0117 (10)	0.0019 (11)
N1'	0.0325 (15)	0.0247 (15)	0.0420 (17)	−0.0003 (12)	0.0141 (13)	0.0060 (13)
C2'	0.0304 (16)	0.0239 (17)	0.043 (2)	0.0104 (13)	0.0146 (14)	0.0128 (14)
N3'	0.0237 (13)	0.0245 (14)	0.0432 (17)	0.0030 (11)	0.0087 (11)	0.0094 (12)
C4'	0.0236 (16)	0.0285 (17)	0.048 (2)	0.0095 (13)	0.0147 (14)	0.0123 (15)
C5'	0.0300 (17)	0.0358 (19)	0.043 (2)	0.0092 (15)	0.0138 (15)	0.0146 (16)
C6'	0.0360 (18)	0.034 (2)	0.047 (2)	0.0087 (15)	0.0203 (16)	0.0137 (16)
O21'	0.0371 (13)	0.0326 (13)	0.0413 (15)	0.0039 (10)	0.0104 (11)	0.0080 (11)
N41'	0.0259 (14)	0.0381 (18)	0.0445 (19)	0.0021 (12)	0.0049 (13)	0.0114 (15)
F51'	0.0438 (12)	0.0551 (14)	0.0406 (12)	0.0007 (10)	0.0097 (9)	0.0145 (11)
C1D	0.039 (2)	0.066 (3)	0.071 (3)	0.018 (2)	0.013 (2)	0.003 (2)
C2D	0.038 (4)	0.036 (3)	0.028 (4)	0.003 (2)	0.006 (3)	0.001 (2)
O21D	0.0513 (16)	0.070 (2)	0.0404 (16)	0.0116 (14)	0.0099 (13)	0.0199 (14)
N3D	0.042 (4)	0.045 (3)	0.027 (4)	0.009 (3)	0.009 (3)	0.006 (2)
C4D	0.062 (3)	0.054 (3)	0.072 (3)	0.016 (2)	0.041 (2)	0.010 (2)
C5D	0.074 (3)	0.069 (3)	0.033 (2)	0.017 (2)	0.006 (2)	0.013 (2)
C2D'	0.028 (7)	0.030 (6)	0.036 (8)	−0.001 (4)	0.011 (6)	−0.007 (5)
N3D'	0.040 (7)	0.049 (6)	0.034 (8)	0.012 (5)	0.011 (5)	−0.002 (5)

Geometric parameters (Å, º)

N1—C6	1.356 (5)	C1D—N3D'	1.584 (17)
N1—C2	1.381 (4)	C1D—H1DA	0.9800
N1—H1	0.85 (5)	C1D—H1DB	0.9800
C2—O21	1.240 (4)	C1D—H1DC	0.9800
C2—N3	1.381 (4)	C1D—H1DD	0.9800
N3—C4	1.326 (4)	C1D—H1DE	0.9800
C4—N41	1.340 (4)	C1D—H1DF	0.9800
C4—C5	1.439 (5)	C2D—O21D	1.262 (8)
C5—C6	1.344 (5)	C2D—N3D	1.322 (14)
C5—F51	1.357 (4)	O21D—C2D'	1.335 (14)
C6—H6	0.9500	N3D—C5D	1.478 (8)
N41—H41A	0.94 (5)	N3D—C4D	1.529 (10)
N41—H41B	0.90 (5)	C4D—C2D'	1.481 (15)
N1'—C6'	1.355 (5)	C4D—H4DA	0.9800
N1'—C2'	1.388 (4)	C4D—H4DB	0.9800
N1'—H1'	1.06 (5)	C4D—H4DC	0.9800
C2'—O21'	1.237 (4)	C4D—H4DD	0.9800
C2'—N3'	1.371 (5)	C4D—H4DE	0.9800
N3'—C4'	1.329 (5)	C4D—H4DF	0.9800
C4'—N41'	1.344 (5)	C5D—N3D'	1.501 (14)
C4'—C5'	1.438 (4)	C5D—H5DA	0.9800
C5'—C6'	1.337 (5)	C5D—H5DB	0.9800
C5'—F51'	1.370 (4)	C5D—H5DC	0.9800
C6'—H6'	0.9500	C5D—H5DD	0.9800
N41'—H41C	0.89 (5)	C5D—H5DE	0.9800
N41'—H41D	0.88 (4)	C5D—H5DF	0.9800
C1D—C2D	1.511 (9)	C2D'—N3D'	1.34 (3)
C6—N1—C2	122.6 (3)	O21D—C2D—N3D	119.1 (9)
C6—N1—H1	117 (3)	O21D—C2D—C1D	127.0 (6)
C2—N1—H1	120 (3)	N3D—C2D—C1D	113.8 (7)
O21—C2—N1	120.4 (3)	C2D—N3D—C4D	116.3 (7)
O21—C2—N3	122.2 (3)	C5D—N3D—C4D	119.9 (6)
N1—C2—N3	117.5 (3)	C2D'—C4D—H4DA	147.3
C4—N3—C2	121.4 (3)	N3D—C4D—H4DA	109.5
N3—C4—N41	119.2 (3)	C2D'—C4D—H4DB	88.0
N3—C4—C5	119.8 (3)	N3D—C4D—H4DB	109.5
N41—C4—C5	120.9 (3)	H4DA—C4D—H4DB	109.5
C6—C5—F51	122.3 (3)	C2D'—C4D—H4DC	89.0
C6—C5—C4	119.0 (3)	N3D—C4D—H4DC	109.5
F51—C5—C4	118.7 (3)	H4DA—C4D—H4DC	109.5
C5—C6—N1	119.5 (3)	H4DB—C4D—H4DC	109.5
C5—C6—H6	120.2	C2D'—C4D—H4DD	109.5
N1—C6—H6	120.2	N3D—C4D—H4DD	71.6
C4—N41—H41A	112 (3)	H4DB—C4D—H4DD	121.6
C4—N41—H41B	116 (3)	H4DC—C4D—H4DD	125.4
H41A—N41—H41B	130 (4)	C2D'—C4D—H4DE	109.5
C6'—N1'—C2'	122.5 (3)	N3D—C4D—H4DE	125.4
C6'—N1'—H1'	120 (3)	H4DA—C4D—H4DE	89.1
C2'—N1'—H1'	117 (3)	H4DC—C4D—H4DE	111.5
O21'—C2'—N3'	122.2 (3)	H4DD—C4D—H4DE	109.5
O21'—C2'—N1'	120.5 (3)	C2D'—C4D—H4DF	109.5
N3'—C2'—N1'	117.4 (3)	N3D—C4D—H4DF	121.7
C4'—N3'—C2'	121.8 (3)	H4DA—C4D—H4DF	87.9
N3'—C4'—N41'	120.1 (3)	H4DB—C4D—H4DF	116.1
N3'—C4'—C5'	119.2 (3)	H4DD—C4D—H4DF	109.5
N41'—C4'—C5'	120.6 (3)	H4DE—C4D—H4DF	109.5
C6'—C5'—F51'	122.0 (3)	N3D—C5D—H5DA	109.5
C6'—C5'—C4'	119.6 (3)	N3D'—C5D—H5DA	141.6
F51'—C5'—C4'	118.4 (3)	N3D—C5D—H5DB	109.5
C5'—C6'—N1'	119.4 (3)	N3D'—C5D—H5DB	91.2
C5'—C6'—H6'	120.3	H5DA—C5D—H5DB	109.5
N1'—C6'—H6'	120.3	N3D—C5D—H5DC	109.5
C4'—N41'—H41C	108 (3)	N3D'—C5D—H5DC	92.4
C4'—N41'—H41D	120 (3)	H5DA—C5D—H5DC	109.5
H41C—N41'—H41D	129 (4)	H5DB—C5D—H5DC	109.5
C2D—C1D—H1DA	109.5	N3D—C5D—H5DD	141.5
N3D'—C1D—H1DA	72.5	N3D'—C5D—H5DD	109.5
C2D—C1D—H1DB	109.5	H5DA—C5D—H5DD	108.6
N3D'—C1D—H1DB	124.4	H5DB—C5D—H5DD	51.2
H1DA—C1D—H1DB	109.5	H5DC—C5D—H5DD	61.6
C2D—C1D—H1DC	109.5	N3D—C5D—H5DE	93.9
N3D'—C1D—H1DC	122.3	N3D'—C5D—H5DE	109.5
H1DA—C1D—H1DC	109.5	H5DA—C5D—H5DE	60.6
H1DB—C1D—H1DC	109.5	H5DB—C5D—H5DE	156.7
C2D—C1D—H1DD	146.4	H5DC—C5D—H5DE	60.4
N3D'—C1D—H1DD	109.5	H5DD—C5D—H5DE	109.5
H1DB—C1D—H1DD	91.8	N3D—C5D—H5DF	89.8
H1DC—C1D—H1DD	86.1	N3D'—C5D—H5DF	109.5
C2D—C1D—H1DE	90.3	H5DA—C5D—H5DF	52.2
N3D'—C1D—H1DE	109.5	H5DB—C5D—H5DF	71.8
H1DA—C1D—H1DE	119.3	H5DC—C5D—H5DF	158.1
H1DC—C1D—H1DE	116.7	H5DD—C5D—H5DF	109.5
H1DD—C1D—H1DE	109.5	H5DE—C5D—H5DF	109.5
C2D—C1D—H1DF	87.7	O21D—C2D'—N3D'	110.8 (14)
N3D'—C1D—H1DF	109.5	O21D—C2D'—C4D	137.8 (12)
H1DA—C1D—H1DF	127.5	N3D'—C2D'—C4D	111.4 (13)
H1DB—C1D—H1DF	110.4	C2D'—N3D'—C5D	118.6 (16)
H1DD—C1D—H1DF	109.5	C2D'—N3D'—C1D	114.5 (12)
H1DE—C1D—H1DF	109.5	C5D—N3D'—C1D	126.8 (12)
C6—N1—C2—O21	−177.2 (3)	C2'—N1'—C6'—C5'	0.2 (5)
C6—N1—C2—N3	2.2 (5)	N3D'—C1D—C2D—O21D	−178.1 (10)
O21—C2—N3—C4	176.4 (3)	N3D'—C1D—C2D—N3D	5.1 (8)
N1—C2—N3—C4	−3.0 (5)	N3D—C2D—O21D—C2D'	−1.3 (7)
C2—N3—C4—N41	−179.7 (3)	C1D—C2D—O21D—C2D'	−177.9 (10)
C2—N3—C4—C5	1.3 (5)	O21D—C2D—N3D—C5D	173.3 (5)
N3—C4—C5—C6	1.4 (5)	C1D—C2D—N3D—C5D	−9.7 (8)
N41—C4—C5—C6	−177.6 (3)	O21D—C2D—N3D—C4D	0.3 (7)
N3—C4—C5—F51	179.3 (3)	C1D—C2D—N3D—C4D	177.3 (5)
N41—C4—C5—F51	0.3 (5)	C2D—N3D—C4D—C2D'	1.0 (7)
F51—C5—C6—N1	180.0 (3)	C5D—N3D—C4D—C2D'	−172.2 (9)
C4—C5—C6—N1	−2.2 (5)	C2D—N3D—C5D—N3D'	1.3 (8)
C2—N1—C6—C5	0.4 (5)	C4D—N3D—C5D—N3D'	174.0 (12)
C6'—N1'—C2'—O21'	175.7 (3)	C2D—O21D—C2D'—N3D'	−2.1 (6)
C6'—N1'—C2'—N3'	−4.2 (5)	C2D—O21D—C2D'—C4D	177.4 (15)
O21'—C2'—N3'—C4'	−175.1 (3)	N3D—C4D—C2D'—O21D	−177.0 (16)
N1'—C2'—N3'—C4'	4.8 (5)	N3D—C4D—C2D'—N3D'	2.4 (7)
C2'—N3'—C4'—N41'	179.3 (3)	O21D—C2D'—N3D'—C5D	−177.3 (8)
C2'—N3'—C4'—C5'	−1.6 (5)	C4D—C2D'—N3D'—C5D	3.1 (12)
N3'—C4'—C5'—C6'	−2.5 (5)	O21D—C2D'—N3D'—C1D	5.2 (11)
N41'—C4'—C5'—C6'	176.6 (3)	C4D—C2D'—N3D'—C1D	−174.4 (7)
N3'—C4'—C5'—F51'	−179.4 (3)	N3D—C5D—N3D'—C2D'	−5.3 (6)
N41'—C4'—C5'—F51'	−0.3 (5)	N3D—C5D—N3D'—C1D	171.9 (16)
F51'—C5'—C6'—N1'	179.8 (3)	C2D—C1D—N3D'—C2D'	−2.1 (6)
C4'—C5'—C6'—N1'	3.1 (5)	C2D—C1D—N3D'—C5D	−179.4 (14)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N3′	0.85 (5)	1.92 (5)	2.772 (4)	179 (5)
N41—H41A···O21′^i	0.94 (5)	2.03 (5)	2.965 (4)	174 (4)
N41—H41B···O21D^ii	0.90 (5)	2.13 (5)	2.976 (5)	157 (4)
N1′—H1′···N3^iii	1.06 (5)	1.72 (5)	2.774 (4)	173 (4)
N41′—H41C···O21	0.89 (5)	2.08 (5)	2.955 (4)	168 (4)
N41′—H41D···O21D	0.88 (4)	2.17 (4)	2.922 (4)	143 (3)

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

(III) 5-fluorocytosine hemihydrate

Crystal data

C4H4FN3O·0.5H2O	F(000) = 1136
Mr = 138.11	Dx = 1.609 Mg m^−3
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2yc	Cell parameters from 2945 reflections
a = 14.7039 (13) Å	θ = 3.4–25.8°
b = 12.4546 (10) Å	µ = 0.15 mm^−1
c = 13.7921 (14) Å	T = 173 K
β = 115.474 (7)°	Block, colourless
V = 2280.2 (4) Å^3	0.30 × 0.30 × 0.20 mm
Z = 16

Data collection

Stoe IPDS II two-circle diffractometer	1631 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.104
Graphite monochromator	θmax = 25.7°, θmin = 3.4°
ω scans	h = −17→17
14246 measured reflections	k = −15→15
2141 independent reflections	l = −16→16

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)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.078	H atoms treated by a mixture of independent and constrained refinement
S = 0.88	w = 1/[σ^2(Fo^2) + (0.0397P)^2] where P = (Fo^2 + 2Fc^2)/3
2141 reflections	(Δ/σ)max < 0.001
355 parameters	Δρmax = 0.19 e Å^−3
8 restraints	Δρmin = −0.32 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
N1A	0.7211 (3)	0.6651 (3)	0.5596 (3)	0.0215 (8)
H1A	0.7418	0.7315	0.5602	0.026*
C2A	0.6239 (3)	0.6470 (3)	0.5445 (3)	0.0204 (10)
N3A	0.5915 (3)	0.5442 (3)	0.5449 (3)	0.0204 (8)
C4A	0.6545 (3)	0.4629 (4)	0.5575 (3)	0.0193 (10)
C5A	0.7542 (3)	0.4821 (4)	0.5719 (4)	0.0232 (10)
C6A	0.7862 (3)	0.5826 (4)	0.5737 (3)	0.0245 (10)
H6A	0.8535	0.5963	0.5847	0.029*
O21A	0.5662 (2)	0.7255 (2)	0.5311 (3)	0.0263 (8)
N41A	0.6204 (3)	0.3632 (3)	0.5544 (3)	0.0262 (9)
H41A	0.5578	0.3524	0.5442	0.031*
H41B	0.6605	0.3081	0.5625	0.031*
F51A	0.8156 (2)	0.3962 (2)	0.5869 (2)	0.0375 (7)
N1B	0.3981 (3)	0.5036 (3)	0.5387 (3)	0.0202 (8)
H1B	0.4572	0.5148	0.5389	0.024*
C2B	0.3681 (3)	0.4000 (3)	0.5427 (3)	0.0179 (9)
N3B	0.2762 (3)	0.3810 (3)	0.5405 (3)	0.0185 (8)
C4B	0.2158 (3)	0.4628 (4)	0.5338 (3)	0.0199 (10)
C5B	0.2488 (3)	0.5692 (4)	0.5322 (3)	0.0216 (10)
C6B	0.3397 (3)	0.5890 (4)	0.5344 (3)	0.0210 (10)
H6B	0.3619	0.6604	0.5330	0.025*
O21B	0.4265 (2)	0.3249 (2)	0.5486 (3)	0.0258 (7)
N41B	0.1242 (3)	0.4449 (3)	0.5280 (3)	0.0249 (9)
H41C	0.1036	0.3787	0.5286	0.030*
H41D	0.0844	0.4993	0.5235	0.030*
F51B	0.1859 (2)	0.6524 (2)	0.5265 (2)	0.0332 (7)
N1C	0.6303 (3)	0.3450 (3)	0.7936 (3)	0.0227 (9)
H1C	0.6110	0.4105	0.7995	0.027*
C2C	0.7256 (3)	0.3297 (3)	0.8011 (3)	0.0190 (9)
N3C	0.7559 (3)	0.2280 (3)	0.7933 (3)	0.0195 (8)
C4C	0.6945 (3)	0.1450 (4)	0.7797 (3)	0.0188 (9)
C5C	0.5955 (3)	0.1631 (4)	0.7710 (4)	0.0254 (11)
C6C	0.5644 (3)	0.2621 (4)	0.7771 (3)	0.0231 (10)
H6C	0.4982	0.2749	0.7703	0.028*
O21C	0.7820 (2)	0.4093 (2)	0.8153 (2)	0.0271 (7)
N41C	0.7259 (3)	0.0468 (3)	0.7751 (3)	0.0252 (9)
H41E	0.7872	0.0363	0.7810	0.030*
H41F	0.6855	−0.0082	0.7661	0.030*
F51C	0.5349 (2)	0.0759 (2)	0.7559 (2)	0.0350 (7)
N1D	0.9455 (3)	0.1854 (3)	0.7892 (3)	0.0206 (8)
H1D	0.8864	0.1970	0.7890	0.025*
C2D	0.9780 (3)	0.0815 (3)	0.7928 (3)	0.0199 (10)
N3D	1.0713 (3)	0.0633 (3)	0.7972 (3)	0.0196 (8)
C4D	1.1291 (3)	0.1473 (4)	0.7975 (3)	0.0189 (9)
C5D	1.0911 (3)	0.2535 (4)	0.7884 (4)	0.0249 (11)
C6D	1.0015 (3)	0.2710 (4)	0.7860 (4)	0.0247 (10)
H6D	0.9767	0.3421	0.7820	0.030*
O21D	0.9219 (2)	0.0058 (3)	0.7924 (3)	0.0259 (7)
N41D	1.2219 (3)	0.1290 (3)	0.8066 (3)	0.0233 (9)
H41G	1.2445	0.0627	0.8122	0.028*
H41H	1.2605	0.1831	0.8069	0.028*
F51D	1.1519 (2)	0.3343 (2)	0.7862 (2)	0.0371 (7)
O1W	0.9690 (2)	0.3874 (3)	0.9907 (3)	0.0337 (8)
H1WA	0.970 (4)	0.324 (2)	1.018 (3)	0.040*
H1WB	0.918 (3)	0.390 (4)	0.924 (2)	0.040*
O2W	0.3804 (2)	0.7076 (3)	0.3471 (3)	0.0314 (8)
H2WA	0.433 (3)	0.712 (4)	0.412 (2)	0.038*
H2WB	0.387 (4)	0.648 (3)	0.317 (3)	0.038*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1A	0.0149 (18)	0.018 (2)	0.032 (2)	−0.0035 (15)	0.0105 (16)	0.0006 (17)
C2A	0.019 (2)	0.019 (2)	0.023 (2)	−0.0039 (19)	0.0092 (19)	−0.0016 (19)
N3A	0.0187 (19)	0.017 (2)	0.027 (2)	−0.0036 (16)	0.0114 (17)	−0.0038 (16)
C4A	0.022 (2)	0.020 (2)	0.019 (2)	−0.0003 (19)	0.011 (2)	0.0022 (18)
C5A	0.017 (2)	0.021 (3)	0.031 (3)	0.006 (2)	0.010 (2)	0.003 (2)
C6A	0.017 (2)	0.029 (3)	0.030 (3)	0.0021 (19)	0.012 (2)	0.005 (2)
O21A	0.0189 (17)	0.0152 (16)	0.046 (2)	0.0016 (13)	0.0151 (15)	−0.0007 (14)
N41A	0.028 (2)	0.0150 (19)	0.042 (2)	−0.0027 (17)	0.0205 (19)	−0.0016 (17)
F51A	0.0302 (15)	0.0250 (15)	0.062 (2)	0.0115 (12)	0.0248 (14)	0.0090 (14)
N1B	0.0164 (18)	0.017 (2)	0.028 (2)	−0.0034 (15)	0.0109 (16)	0.0037 (16)
C2B	0.016 (2)	0.015 (2)	0.021 (2)	−0.0020 (18)	0.0071 (18)	−0.0021 (17)
N3B	0.018 (2)	0.014 (2)	0.024 (2)	−0.0011 (17)	0.0101 (16)	0.0018 (16)
C4B	0.022 (2)	0.016 (3)	0.021 (2)	0.000 (2)	0.0085 (19)	0.0018 (18)
C5B	0.021 (2)	0.016 (3)	0.025 (3)	0.0033 (18)	0.008 (2)	0.0010 (18)
C6B	0.022 (2)	0.015 (2)	0.028 (3)	0.0031 (19)	0.013 (2)	0.0036 (19)
O21B	0.0222 (16)	0.0145 (16)	0.0389 (18)	0.0009 (13)	0.0114 (14)	0.0001 (14)
N41B	0.024 (2)	0.012 (2)	0.042 (2)	−0.0026 (17)	0.0165 (18)	−0.0054 (17)
F51B	0.0325 (15)	0.0156 (13)	0.058 (2)	0.0069 (11)	0.0255 (14)	0.0017 (12)
N1C	0.021 (2)	0.022 (2)	0.028 (2)	0.0054 (17)	0.0133 (16)	0.0026 (17)
C2C	0.017 (2)	0.018 (2)	0.023 (2)	0.0030 (18)	0.0100 (18)	0.0011 (19)
N3C	0.019 (2)	0.011 (2)	0.030 (2)	0.0007 (16)	0.0121 (17)	0.0015 (15)
C4C	0.019 (2)	0.019 (2)	0.019 (2)	0.0014 (18)	0.0083 (19)	−0.0002 (18)
C5C	0.025 (3)	0.027 (3)	0.028 (3)	−0.007 (2)	0.016 (2)	−0.002 (2)
C6C	0.018 (2)	0.027 (3)	0.024 (3)	−0.002 (2)	0.009 (2)	0.0001 (19)
O21C	0.0246 (17)	0.0159 (16)	0.041 (2)	−0.0015 (14)	0.0140 (15)	0.0004 (14)
N41C	0.0202 (19)	0.017 (2)	0.040 (2)	−0.0055 (17)	0.0147 (18)	−0.0025 (18)
F51C	0.0255 (14)	0.0275 (15)	0.0546 (18)	−0.0085 (12)	0.0198 (13)	0.0004 (13)
N1D	0.0188 (19)	0.0140 (19)	0.034 (2)	0.0009 (14)	0.0161 (16)	0.0032 (16)
C2D	0.021 (2)	0.020 (3)	0.017 (2)	0.0011 (19)	0.0067 (19)	0.0001 (18)
N3D	0.0191 (19)	0.0159 (19)	0.025 (2)	−0.0015 (16)	0.0110 (16)	−0.0009 (16)
C4D	0.022 (2)	0.019 (2)	0.017 (2)	0.0003 (18)	0.0098 (18)	0.0007 (17)
C5D	0.027 (3)	0.011 (2)	0.040 (3)	−0.004 (2)	0.018 (2)	0.0009 (19)
C6D	0.027 (2)	0.014 (2)	0.033 (3)	0.0029 (18)	0.012 (2)	−0.0010 (19)
O21D	0.0245 (17)	0.0183 (17)	0.0394 (18)	−0.0029 (14)	0.0179 (15)	0.0017 (13)
N41D	0.0158 (19)	0.018 (2)	0.038 (2)	−0.0022 (16)	0.0136 (17)	−0.0021 (17)
F51D	0.0313 (16)	0.0180 (15)	0.070 (2)	−0.0032 (12)	0.0290 (15)	0.0025 (14)
O1W	0.0221 (16)	0.0291 (19)	0.047 (2)	−0.0027 (14)	0.0117 (15)	0.0040 (16)
O2W	0.0240 (16)	0.0294 (19)	0.043 (2)	0.0009 (14)	0.0163 (15)	−0.0056 (15)

Geometric parameters (Å, º)

N1A—C6A	1.361 (6)	N1C—H1C	0.8800
N1A—C2A	1.371 (5)	C2C—O21C	1.252 (5)
N1A—H1A	0.8800	C2C—N3C	1.362 (5)
C2A—O21A	1.256 (5)	N3C—C4C	1.331 (5)
C2A—N3A	1.366 (5)	C4C—N41C	1.318 (6)
N3A—C4A	1.332 (5)	C4C—C5C	1.427 (6)
C4A—N41A	1.333 (6)	C5C—C6C	1.330 (7)
C4A—C5A	1.413 (6)	C5C—F51C	1.362 (5)
C5A—C6A	1.334 (7)	C6C—H6C	0.9500
C5A—F51A	1.357 (5)	N41C—H41E	0.8800
C6A—H6A	0.9500	N41C—H41F	0.8800
N41A—H41A	0.8800	N1D—C6D	1.360 (6)
N41A—H41B	0.8800	N1D—C2D	1.373 (6)
N1B—C6B	1.353 (6)	N1D—H1D	0.8800
N1B—C2B	1.372 (5)	C2D—O21D	1.251 (5)
N1B—H1B	0.8800	C2D—N3D	1.366 (6)
C2B—O21B	1.249 (5)	N3D—C4D	1.347 (6)
C2B—N3B	1.359 (5)	C4D—N41D	1.335 (5)
N3B—C4B	1.328 (6)	C4D—C5D	1.421 (6)
C4B—N41B	1.333 (5)	C5D—C6D	1.321 (6)
C4B—C5B	1.415 (6)	C5D—F51D	1.355 (5)
C5B—C6B	1.346 (6)	C6D—H6D	0.9500
C5B—F51B	1.369 (5)	N41D—H41G	0.8800
C6B—H6B	0.9500	N41D—H41H	0.8800
N41B—H41C	0.8800	O1W—H1WA	0.87 (2)
N41B—H41D	0.8800	O1W—H1WB	0.90 (2)
N1C—C6C	1.366 (6)	O2W—H2WA	0.90 (2)
N1C—C2C	1.373 (5)	O2W—H2WB	0.88 (2)
C6A—N1A—C2A	121.4 (4)	C6C—N1C—H1C	118.8
C6A—N1A—H1A	119.3	C2C—N1C—H1C	118.8
C2A—N1A—H1A	119.3	O21C—C2C—N3C	122.1 (4)
O21A—C2A—N3A	121.0 (4)	O21C—C2C—N1C	119.2 (4)
O21A—C2A—N1A	119.2 (4)	N3C—C2C—N1C	118.7 (4)
N3A—C2A—N1A	119.8 (4)	C4C—N3C—C2C	120.5 (4)
C4A—N3A—C2A	119.2 (4)	N41C—C4C—N3C	119.8 (4)
N3A—C4A—N41A	118.3 (4)	N41C—C4C—C5C	120.5 (4)
N3A—C4A—C5A	120.7 (4)	N3C—C4C—C5C	119.7 (4)
N41A—C4A—C5A	121.0 (4)	C6C—C5C—F51C	121.9 (4)
C6A—C5A—F51A	122.1 (4)	C6C—C5C—C4C	120.4 (4)
C6A—C5A—C4A	119.8 (4)	F51C—C5C—C4C	117.6 (4)
F51A—C5A—C4A	118.1 (4)	C5C—C6C—N1C	118.2 (4)
C5A—C6A—N1A	119.1 (4)	C5C—C6C—H6C	120.9
C5A—C6A—H6A	120.5	N1C—C6C—H6C	120.9
N1A—C6A—H6A	120.5	C4C—N41C—H41E	120.0
C4A—N41A—H41A	120.0	C4C—N41C—H41F	120.0
C4A—N41A—H41B	120.0	H41E—N41C—H41F	120.0
H41A—N41A—H41B	120.0	C6D—N1D—C2D	122.3 (4)
C6B—N1B—C2B	122.2 (4)	C6D—N1D—H1D	118.9
C6B—N1B—H1B	118.9	C2D—N1D—H1D	118.9
C2B—N1B—H1B	118.9	O21D—C2D—N3D	121.5 (4)
O21B—C2B—N3B	121.3 (4)	O21D—C2D—N1D	119.5 (4)
O21B—C2B—N1B	118.9 (4)	N3D—C2D—N1D	119.0 (4)
N3B—C2B—N1B	119.8 (4)	C4D—N3D—C2D	119.5 (4)
C4B—N3B—C2B	119.7 (4)	N41D—C4D—N3D	119.1 (4)
N3B—C4B—N41B	120.3 (4)	N41D—C4D—C5D	121.0 (4)
N3B—C4B—C5B	119.7 (4)	N3D—C4D—C5D	119.9 (4)
N41B—C4B—C5B	120.0 (4)	C6D—C5D—F51D	122.5 (4)
C6B—C5B—F51B	120.2 (4)	C6D—C5D—C4D	120.4 (4)
C6B—C5B—C4B	121.0 (4)	F51D—C5D—C4D	117.1 (4)
F51B—C5B—C4B	118.8 (4)	C5D—C6D—N1D	118.8 (4)
C5B—C6B—N1B	117.5 (4)	C5D—C6D—H6D	120.6
C5B—C6B—H6B	121.3	N1D—C6D—H6D	120.6
N1B—C6B—H6B	121.3	C4D—N41D—H41G	120.0
C4B—N41B—H41C	120.0	C4D—N41D—H41H	120.0
C4B—N41B—H41D	120.0	H41G—N41D—H41H	120.0
H41C—N41B—H41D	120.0	H1WA—O1W—H1WB	109 (4)
C6C—N1C—C2C	122.4 (4)	H2WA—O2W—H2WB	107 (3)
C6A—N1A—C2A—O21A	−179.5 (4)	C6C—N1C—C2C—O21C	179.4 (4)
C6A—N1A—C2A—N3A	0.8 (6)	C6C—N1C—C2C—N3C	−0.9 (6)
O21A—C2A—N3A—C4A	178.8 (4)	O21C—C2C—N3C—C4C	179.1 (4)
N1A—C2A—N3A—C4A	−1.6 (6)	N1C—C2C—N3C—C4C	−0.7 (6)
C2A—N3A—C4A—N41A	−178.0 (4)	C2C—N3C—C4C—N41C	−178.2 (4)
C2A—N3A—C4A—C5A	0.9 (6)	C2C—N3C—C4C—C5C	1.4 (6)
N3A—C4A—C5A—C6A	0.5 (7)	N41C—C4C—C5C—C6C	179.1 (4)
N41A—C4A—C5A—C6A	179.4 (4)	N3C—C4C—C5C—C6C	−0.5 (6)
N3A—C4A—C5A—F51A	178.4 (4)	N41C—C4C—C5C—F51C	−1.2 (6)
N41A—C4A—C5A—F51A	−2.7 (6)	N3C—C4C—C5C—F51C	179.2 (4)
F51A—C5A—C6A—N1A	−179.1 (4)	F51C—C5C—C6C—N1C	179.3 (4)
C4A—C5A—C6A—N1A	−1.2 (7)	C4C—C5C—C6C—N1C	−1.0 (7)
C2A—N1A—C6A—C5A	0.6 (6)	C2C—N1C—C6C—C5C	1.7 (6)
C6B—N1B—C2B—O21B	−178.7 (4)	C6D—N1D—C2D—O21D	−177.8 (4)
C6B—N1B—C2B—N3B	1.2 (6)	C6D—N1D—C2D—N3D	2.4 (6)
O21B—C2B—N3B—C4B	−179.7 (4)	O21D—C2D—N3D—C4D	−180.0 (4)
N1B—C2B—N3B—C4B	0.4 (6)	N1D—C2D—N3D—C4D	−0.2 (6)
C2B—N3B—C4B—N41B	177.8 (4)	C2D—N3D—C4D—N41D	177.1 (4)
C2B—N3B—C4B—C5B	−1.9 (6)	C2D—N3D—C4D—C5D	−2.9 (6)
N3B—C4B—C5B—C6B	1.9 (7)	N41D—C4D—C5D—C6D	−175.9 (4)
N41B—C4B—C5B—C6B	−177.8 (4)	N3D—C4D—C5D—C6D	4.0 (7)
N3B—C4B—C5B—F51B	−179.2 (4)	N41D—C4D—C5D—F51D	1.8 (6)
N41B—C4B—C5B—F51B	1.1 (6)	N3D—C4D—C5D—F51D	−178.2 (4)
F51B—C5B—C6B—N1B	−179.2 (4)	F51D—C5D—C6D—N1D	−179.5 (4)
C4B—C5B—C6B—N1B	−0.3 (6)	C4D—C5D—C6D—N1D	−1.9 (7)
C2B—N1B—C6B—C5B	−1.2 (6)	C2D—N1D—C6D—C5D	−1.3 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1A—H1A···N3B^i	0.88	1.98	2.853 (5)	172
N41A—H41A···O21B	0.88	1.99	2.858 (5)	170
N1B—H1B···N3A	0.88	1.97	2.854 (5)	177
N41B—H41C···O21A^ii	0.88	1.99	2.869 (5)	176
N41B—H41D···O1W^iii	0.88	2.10	2.972 (5)	170
N1C—H1C···N3D^iv	0.88	1.99	2.861 (5)	173
N41C—H41E···O21D	0.88	1.95	2.834 (5)	177
N1D—H1D···N3C	0.88	1.98	2.862 (5)	178
N41D—H41G···O21C^v	0.88	1.98	2.862 (5)	175
N41D—H41H···O2W^vi	0.88	2.10	2.961 (5)	164
O1W—H1WA···O21B^vii	0.87 (2)	2.06 (3)	2.906 (5)	163 (4)
O1W—H1WB···O21C	0.90 (2)	1.93 (3)	2.786 (5)	158 (5)
O2W—H2WA···O21A	0.90 (2)	1.95 (2)	2.826 (5)	166 (5)
O2W—H2WB···O21D^viii	0.88 (2)	2.05 (3)	2.898 (5)	163 (4)

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