Monohydrous dihydrogen phosphate salts of norfloxacin and ciprofloxacin

Norfloxacin and ciprofloxacin crystallize with phosphoric acid in aqueous solution to give the salts 4-(3-carb­oxy-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinol­yl)piperazinium dihydrogen­phosphate monohydrate, C₁₆H₁₉FN₃O₃⁺·H₂PO₄^-·H₂O, and 4-(3-carb­oxy-1-cyclo­propyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolyl)­piperazinium dihydrogenphosphate monohydrate, C₁₇H₁₉FN₃O₃⁺·H₂PO₄^-·H₂O, respectively. In the crystal structures, the phosphate anions and the piperazine rings of norfloxacin or ciprofloxacin form a 12-membered supra­molecular synthon, viz. R₄⁴(12). The synthons R₄⁴(12) and R₂²(8) formed between adjacent phosphate anions result in the three-dimensional structures.

S1. Comment

The design and synthesis of multicomponent crystals of active pharmaceutical ingredients (APIs) has attracted considerable attention in recent years (Almarsson & Zaworotko, 2004; Childs et al., 2007). Many types of supramolecular synthons have been exploited for generating multicomponent crystals by the use of suitable guest molecules with complementary functional groups to APIs (Trask et al., 2005; Wenger & Bernstein, 2006). Although an organic acid is preferable to a basic drug molecule, an inorganic acid, such as phosphoric acid, displays its uniqueness in the formation of multicomponent crystals [pelase clarify; what is meant by `displays its uniqueness'] (Chen et al., 2007). We treated norfloxacin and ciprofloxacin with phosphoric acid in aqueous solution and prepared the title compounds, (I) and (II), respectively, in which phosporic acid participates in different supramolecular synthons.

The crystal structure of (I) contains one norfloxacin, one phosphoric acid and one water molecule in the asymmetric unit. Difference Fourier maps show that phosphoric acid transfers one H atom to the piperazinyl ring N atom of norfloxacin, thus forming the dihydrogen phosphate salt of norfloxacin. The carboxylic acid group of norfloxacin is involved in intramolecular hydrogen bonding with the quinolone O atom (O2—H2···O3; Table 1). The piperazinyl ring N atom of norfloxacin is hydrogen-bonded to two symmetry-dependent phosphate anions (N1⁺—H1A···O4^iv and N1⁺—H1B··· O5; symmetry code as in Table 1), and this results in a neutral tetramer based on a 12-membered supramolecular synthon, R₄⁴(12) (Fig.1). The solvent water molecule interacts with the phosphate anion through two types of hydrogen bonds (O8—H8A ···O5 and O7—H7···O8ⁱⁱⁱ; Table 1) to give rise to another 12-membered supramolecular synthon, R₄⁴(12). Two adjacent phosphate anions also form a homosynthon, R₂²(8), through hydrogen bonding (O6—H6···O4ⁱⁱ; Table 1). Along the (110) direction, the two synthons result in a one-dimensional hydrogen-bonded chain containing phosphate anions and solvent water moleucles (Fig. 2). the water molecule is also hydrogen bonded to the carboxylic acid group of norfloxacin (O8—H8B···O2ⁱ; Table 1). As a result, phosphoric acid and water molecules link norfloxacin into a three-dimensional structure through three types of supramolecular synthon (Fig. 3).

The structure of (II) is very similar to that of (I). It contains one ciprofloxacin, one phosphoric acid and one water molecule in the asymmetric unit (Fig. 4). In the crystal structure, phosphoric acid again transfers one H atom to the piperazinyl ring N atom of ciprofloxacin, forming a similar 12-membered supramolecular synthon, R₄⁴(12). A similar one-dimensional chain along the (110) direction, including phosphate anions and water molecules, is formed. Three similar supramolecular synthons result in the three-dimensional structure (Fig. 5). The hydrogen-bond geometry in (II) is given in Table 2.

Several dicarboxylate salts of norfloxacin have been reported recently (Basavoju, et al., 2006). For example, in the structure of the succinate salt of norfloxacin, the carboxylate group of succinic acid and the piperazinyl rings of norfloxacin form a supramolecular R₄⁴(12) synthon. In the structure of the hydrated lactate salt of ciprofloxacin (Prasanna & Guru Row, 2001), centrosymmetrically related lactate and water molecules form a two-dimensional hydrogen-bonded sheet which links ciprofloxacin into a three-dimensional network. Compared with these organic salt formers, phosphoric acid displays more flexible hydrogen-bonding patterns through participating in three kinds of supramolecular synthons in (I) and (II).

In conclusion, norfloxacin and ciprofloxacin crystallize with phosphoric acid in aqueous solution to give rise to their dihydrogen phosphate monohydrate salts. In the structures, the phosphate anion and water molecule link norfloxacin or ciprofloxacin into three-dimensional structures through three types of supramolecular synthons. The structures show that phosphoric acid could be a good candidate for forming multicomponent crystals of APIs, as it can provide various hydrogen-bonding interactions.

Related literature

For related literature, see: Almarsson & Zaworotko (2004); Basavoju et al. (2006); Chen et al. (2007); Childs et al. (2007); Prasanna & Guru Row (2001); Trask et al. (2005); Wenger & Bernstein (2006).

S2. Experimental

For the preparation of (I), a mixture of norfloxacin (0.032 g, 0.1 mmol) and phosphoric acid (0.020 g, 0.2 mmol) in water (10 ml) was heated until dissolved. The solution was kept in a fume hood and colorless crystals were obtained after several days. Differential scanning calorimetry showed two endothermic peaks at 405 and 543 K, respectively. Compound (II) was prepared as (I) except that ciprofloxacin was used instead of norfloxacin. Differential scanning calorimetry showed two endothermic peaks at 406 and 529 K, respectively.

S3. Refinement

For both structures, H atoms bonded to N and O(water) atoms were located in difference maps and were refined as riding with N,O—H distances of 0.84–0.88 Å [U_iso(H) = 1.2U_eq(parent atom) please check; this statement does not agree with values given in CIF]. All other H atoms were positioned geometrically (C—H = 0.95–1.00 Å and O—H = 0.84 Å) and refined as riding with U_iso(H) = 1.2U_eq(C,O) or 1.5U_eq(C). The maximum residual electron density in (II) is larger than normally expected. The nearest atom to this maximum is atom P1 and its distance from the maximum is 0.951 Å.

Computing details

For both compounds, data collection: COLLECT (Nonius, 1999); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures

	Fig. 1. The structure of (I), with 30% probablity displacement ellipsoids. Dashed lines indicate hydrogen bonds. H atoms on C atoms have been omitted for clarity. Atoms labeled with the suffic A are at the symmetry position (1 - x, -y, 2 - z).
	Fig. 2. The one-dimensional chain of phosphate anions and water molecules along the [110] direction. Dashed lines indicate hydrogen bonds.
	Fig. 3. The three-dimensional structure of (I), viewed along the [110] direction. Dashed lines indicate hydrogen bonds.
	Fig. 4. The structure of (II), with 30% probability displacement ellipsoids. Dashed lines indicate hydrogen bonds. H atoms on C atoms have been omitted for clarity.
	Fig. 5. The three-dimensional structure of (II), viewed along the [110] direction. Dashed lines indicate hydrogen bonds.

(I) 4-(3-carboxy-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolyl)piperazinium dihydrogen phosphate monohydrate

Crystal data

C16H19FN3O3^+·H2PO4^−·H2O	Z = 2
Mr = 435.34	F(000) = 456
Triclinic, P1	Dx = 1.546 Mg m^−3
Hall symbol: -P1	Mo Kα radiation, λ = 0.71073 Å
a = 7.1918 (14) Å	Cell parameters from 58178 reflections
b = 8.9400 (18) Å	θ = 2.6–30.0°
c = 15.792 (3) Å	µ = 0.21 mm^−1
α = 103.81 (3)°	T = 100 K
β = 94.01 (3)°	Plate, colorless
γ = 106.51 (3)°	0.25 × 0.20 × 0.08 mm
V = 934.9 (4) Å^3

Data collection

Nonius KappaCCD diffractometer	4398 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.030
Graphite monochromator	θmax = 30.0°, θmin = 2.7°
ϕ and ω scans	h = −9→10
10002 measured reflections	k = −12→12
5425 independent reflections	l = −22→22

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)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.146	H-atom parameters constrained
S = 1.10	w = 1/[σ^2(Fo^2) + (0.0744P)^2 + 0.5378P] where P = (Fo^2 + 2Fc^2)/3
5425 reflections	(Δ/σ)max = 0.001
263 parameters	Δρmax = 0.65 e Å^−3
0 restraints	Δρmin = −0.94 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
P1	0.26619 (6)	0.19362 (5)	1.03625 (3)	0.01445 (12)
F1	0.63740 (17)	0.05683 (12)	0.58606 (7)	0.0201 (2)
O1	0.8875 (2)	0.86360 (17)	0.37912 (10)	0.0248 (3)
O2	0.8116 (2)	0.60851 (17)	0.29690 (9)	0.0244 (3)
H2	0.7775	0.5156	0.3050	0.029*
O3	0.7211 (2)	0.37859 (16)	0.36427 (9)	0.0228 (3)
O4	0.23844 (18)	0.01377 (15)	1.00534 (9)	0.0180 (3)
O5	0.33740 (19)	0.28479 (16)	0.96982 (9)	0.0191 (3)
O6	0.07364 (19)	0.22224 (16)	1.06646 (9)	0.0207 (3)
H6	−0.0146	0.1903	1.0226	0.025*
O7	0.4173 (2)	0.26902 (16)	1.12405 (9)	0.0207 (3)
H7	0.5276	0.2613	1.1136	0.025*
O8	0.27395 (19)	0.49945 (16)	0.88775 (9)	0.0201 (3)
H8A	0.2826	0.4314	0.9150	0.022*
H8B	0.2268	0.4373	0.8373	0.022*
N1	0.6274 (2)	0.17217 (19)	0.90820 (10)	0.0170 (3)
H1A	0.6621	0.1193	0.9426	0.022*
H1B	0.5380	0.2171	0.9269	0.022*
N2	0.6833 (2)	0.26701 (17)	0.74962 (10)	0.0152 (3)
N3	0.7932 (2)	0.70539 (17)	0.60544 (10)	0.0150 (3)
C1	0.8381 (3)	0.7199 (2)	0.37381 (12)	0.0186 (3)
C2	0.8012 (2)	0.6508 (2)	0.45008 (12)	0.0154 (3)
C3	0.7468 (3)	0.4804 (2)	0.43895 (12)	0.0159 (3)
C4	0.7246 (2)	0.4285 (2)	0.51906 (11)	0.0147 (3)
C5	0.6831 (2)	0.2631 (2)	0.51488 (12)	0.0158 (3)
H5	0.6667	0.1852	0.4599	0.019*
C6	0.6666 (2)	0.2159 (2)	0.59061 (12)	0.0156 (3)
C7	0.6881 (2)	0.3247 (2)	0.67461 (11)	0.0142 (3)
C8	0.7269 (2)	0.4880 (2)	0.67830 (12)	0.0150 (3)
H8	0.7394	0.5646	0.7333	0.018*
C9	0.7480 (2)	0.5408 (2)	0.60124 (11)	0.0141 (3)
C10	0.8209 (2)	0.7549 (2)	0.53215 (12)	0.0164 (3)
H10	0.8560	0.8678	0.5373	0.020*
C11	0.8203 (3)	0.8283 (2)	0.69051 (12)	0.0187 (3)
H11A	0.7191	0.7870	0.7259	0.022*
H11B	0.8023	0.9280	0.6793	0.022*
C12	1.0220 (3)	0.8693 (2)	0.74262 (13)	0.0232 (4)
H12A	1.1227	0.9084	0.7074	0.035*
H12B	1.0375	0.7722	0.7568	0.035*
H12C	1.0362	0.9539	0.7973	0.035*
C13	0.7605 (3)	0.3864 (2)	0.83513 (12)	0.0167 (3)
H13A	0.6623	0.4407	0.8542	0.020*
H13B	0.8807	0.4698	0.8302	0.020*
C14	0.8071 (3)	0.3015 (2)	0.90225 (12)	0.0184 (3)
H14A	0.9109	0.2527	0.8848	0.022*
H14B	0.8564	0.3811	0.9606	0.022*
C15	0.4997 (3)	0.1452 (2)	0.75467 (12)	0.0178 (3)
H15A	0.4472	0.0674	0.6959	0.021*
H15B	0.4008	0.1993	0.7728	0.021*
C16	0.5384 (3)	0.0558 (2)	0.82058 (12)	0.0183 (3)
H16A	0.4138	−0.0219	0.8261	0.022*
H16B	0.6282	−0.0062	0.7996	0.022*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
P1	0.0158 (2)	0.0127 (2)	0.0153 (2)	0.00331 (16)	0.00235 (15)	0.00589 (16)
F1	0.0294 (6)	0.0098 (5)	0.0207 (5)	0.0040 (4)	0.0020 (4)	0.0060 (4)
O1	0.0320 (7)	0.0198 (7)	0.0225 (7)	0.0025 (6)	0.0022 (6)	0.0128 (6)
O2	0.0345 (8)	0.0216 (7)	0.0165 (6)	0.0046 (6)	0.0044 (5)	0.0089 (5)
O3	0.0339 (7)	0.0180 (6)	0.0152 (6)	0.0063 (6)	0.0047 (5)	0.0041 (5)
O4	0.0180 (6)	0.0127 (6)	0.0237 (7)	0.0046 (5)	0.0014 (5)	0.0064 (5)
O5	0.0219 (6)	0.0199 (6)	0.0198 (6)	0.0072 (5)	0.0049 (5)	0.0118 (5)
O6	0.0193 (6)	0.0170 (6)	0.0242 (7)	0.0046 (5)	0.0055 (5)	0.0034 (5)
O7	0.0199 (6)	0.0221 (7)	0.0182 (6)	0.0014 (5)	−0.0009 (5)	0.0091 (5)
O8	0.0219 (6)	0.0172 (6)	0.0196 (6)	0.0027 (5)	−0.0010 (5)	0.0074 (5)
N1	0.0193 (7)	0.0173 (7)	0.0173 (7)	0.0062 (6)	0.0045 (6)	0.0092 (6)
N2	0.0174 (7)	0.0121 (6)	0.0147 (7)	0.0008 (5)	0.0014 (5)	0.0060 (5)
N3	0.0181 (7)	0.0115 (6)	0.0155 (7)	0.0036 (5)	0.0029 (5)	0.0053 (5)
C1	0.0181 (8)	0.0212 (8)	0.0169 (8)	0.0033 (7)	0.0025 (6)	0.0092 (7)
C2	0.0154 (7)	0.0158 (8)	0.0161 (8)	0.0035 (6)	0.0020 (6)	0.0083 (6)
C3	0.0166 (7)	0.0161 (8)	0.0154 (8)	0.0042 (6)	0.0031 (6)	0.0056 (6)
C4	0.0151 (7)	0.0141 (7)	0.0158 (8)	0.0040 (6)	0.0033 (6)	0.0062 (6)
C5	0.0176 (8)	0.0129 (7)	0.0153 (8)	0.0028 (6)	0.0016 (6)	0.0032 (6)
C6	0.0166 (8)	0.0098 (7)	0.0195 (8)	0.0023 (6)	0.0012 (6)	0.0050 (6)
C7	0.0149 (7)	0.0135 (7)	0.0154 (8)	0.0039 (6)	0.0022 (6)	0.0066 (6)
C8	0.0172 (8)	0.0122 (7)	0.0156 (8)	0.0029 (6)	0.0036 (6)	0.0056 (6)
C9	0.0143 (7)	0.0113 (7)	0.0172 (8)	0.0029 (6)	0.0021 (6)	0.0059 (6)
C10	0.0156 (7)	0.0156 (8)	0.0199 (8)	0.0039 (6)	0.0039 (6)	0.0089 (7)
C11	0.0285 (9)	0.0114 (7)	0.0165 (8)	0.0059 (7)	0.0056 (7)	0.0041 (6)
C12	0.0302 (10)	0.0175 (8)	0.0172 (9)	0.0008 (7)	0.0006 (7)	0.0049 (7)
C13	0.0204 (8)	0.0126 (7)	0.0161 (8)	0.0025 (6)	0.0015 (6)	0.0056 (6)
C14	0.0181 (8)	0.0179 (8)	0.0184 (8)	0.0022 (6)	0.0013 (6)	0.0080 (7)
C15	0.0180 (8)	0.0145 (8)	0.0196 (8)	0.0004 (6)	0.0016 (6)	0.0079 (6)
C16	0.0234 (8)	0.0138 (8)	0.0183 (8)	0.0035 (6)	0.0035 (7)	0.0080 (6)

Geometric parameters (Å, º)

P1—O5	1.5077 (14)	C3—C4	1.452 (2)
P1—O4	1.5142 (14)	C4—C9	1.404 (2)
P1—O6	1.5641 (14)	C4—C5	1.407 (2)
P1—O7	1.5762 (16)	C5—C6	1.362 (2)
F1—C6	1.3607 (19)	C5—H5	0.9500
O1—C1	1.212 (2)	C6—C7	1.414 (2)
O2—C1	1.336 (2)	C7—C8	1.392 (2)
O2—H2	0.8400	C8—C9	1.409 (2)
O3—C3	1.271 (2)	C8—H8	0.9500
O6—H6	0.8400	C10—H10	0.9500
O7—H7	0.8400	C11—C12	1.518 (3)
O8—H8A	0.8377	C11—H11A	0.9900
O8—H8B	0.8384	C11—H11B	0.9900
N1—C16	1.489 (2)	C12—H12A	0.9800
N1—C14	1.495 (2)	C12—H12B	0.9800
N1—H1A	0.8659	C12—H12C	0.9800
N1—H1B	0.8828	C13—C14	1.514 (2)
N2—C7	1.399 (2)	C13—H13A	0.9900
N2—C13	1.463 (2)	C13—H13B	0.9900
N2—C15	1.474 (2)	C14—H14A	0.9900
N3—C10	1.343 (2)	C14—H14B	0.9900
N3—C9	1.398 (2)	C15—C16	1.511 (2)
N3—C11	1.479 (2)	C15—H15A	0.9900
C1—C2	1.487 (2)	C15—H15B	0.9900
C2—C10	1.375 (3)	C16—H16A	0.9900
C2—C3	1.424 (2)	C16—H16B	0.9900
O5—P1—O4	113.91 (8)	C7—C8—H8	119.7
O5—P1—O6	111.52 (8)	C9—C8—H8	119.7
O4—P1—O6	110.10 (8)	N3—C9—C4	119.04 (15)
O5—P1—O7	108.89 (8)	N3—C9—C8	120.61 (16)
O4—P1—O7	108.97 (8)	C4—C9—C8	120.35 (15)
O6—P1—O7	102.84 (8)	N3—C10—C2	123.42 (16)
C1—O2—H2	109.5	N3—C10—H10	118.3
P1—O6—H6	109.5	C2—C10—H10	118.3
P1—O7—H7	109.5	N3—C11—C12	111.90 (16)
H8A—O8—H8B	99.8	N3—C11—H11A	109.2
C16—N1—C14	111.85 (14)	C12—C11—H11A	109.2
C16—N1—H1A	108.3	N3—C11—H11B	109.2
C14—N1—H1A	107.6	C12—C11—H11B	109.2
C16—N1—H1B	106.6	H11A—C11—H11B	107.9
C14—N1—H1B	109.2	C11—C12—H12A	109.5
H1A—N1—H1B	113.4	C11—C12—H12B	109.5
C7—N2—C13	117.46 (14)	H12A—C12—H12B	109.5
C7—N2—C15	116.64 (14)	C11—C12—H12C	109.5
C13—N2—C15	110.71 (14)	H12A—C12—H12C	109.5
C10—N3—C9	120.08 (15)	H12B—C12—H12C	109.5
C10—N3—C11	118.82 (15)	N2—C13—C14	109.17 (14)
C9—N3—C11	121.04 (14)	N2—C13—H13A	109.8
O1—C1—O2	121.88 (17)	C14—C13—H13A	109.8
O1—C1—C2	124.22 (18)	N2—C13—H13B	109.8
O2—C1—C2	113.90 (16)	C14—C13—H13B	109.8
C10—C2—C3	120.35 (16)	H13A—C13—H13B	108.3
C10—C2—C1	118.62 (16)	N1—C14—C13	110.14 (15)
C3—C2—C1	121.03 (16)	N1—C14—H14A	109.6
O3—C3—C2	122.92 (16)	C13—C14—H14A	109.6
O3—C3—C4	121.27 (16)	N1—C14—H14B	109.6
C2—C3—C4	115.80 (16)	C13—C14—H14B	109.6
C9—C4—C5	119.16 (15)	H14A—C14—H14B	108.1
C9—C4—C3	121.21 (15)	N2—C15—C16	109.76 (15)
C5—C4—C3	119.61 (16)	N2—C15—H15A	109.7
C6—C5—C4	119.17 (16)	C16—C15—H15A	109.7
C6—C5—H5	120.4	N2—C15—H15B	109.7
C4—C5—H5	120.4	C16—C15—H15B	109.7
F1—C6—C5	118.39 (16)	H15A—C15—H15B	108.2
F1—C6—C7	117.99 (15)	N1—C16—C15	110.35 (14)
C5—C6—C7	123.54 (16)	N1—C16—H16A	109.6
C8—C7—N2	123.20 (16)	C15—C16—H16A	109.6
C8—C7—C6	117.09 (15)	N1—C16—H16B	109.6
N2—C7—C6	119.56 (15)	C15—C16—H16B	109.6
C7—C8—C9	120.67 (16)	H16A—C16—H16B	108.1

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3	0.84	1.69	2.482 (2)	156
O8—H8A···O5	0.84	1.85	2.6783 (19)	172
O8—H8B···O2^i	0.84	2.04	2.807 (2)	151
O6—H6···O4^ii	0.84	1.99	2.566 (2)	125
O7—H7···O8^iii	0.84	2.21	2.623 (2)	110
N1—H1B···O5	0.88	1.83	2.706 (2)	172
N1—H1A···O4^iv	0.87	1.86	2.714 (2)	167

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

(II) 4-(3-carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolyl)piperazinium dihydrogen phosphate monohydrate

Crystal data

C17H19FN3O3^+·H2PO4^−·H2O	Z = 2
Mr = 447.35	F(000) = 468
Triclinic, P1	Dx = 1.553 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.2582 (15) Å	Cell parameters from 26945 reflections
b = 8.9979 (18) Å	θ = 2.6–30.0°
c = 15.712 (3) Å	µ = 0.21 mm^−1
α = 100.93 (3)°	T = 100 K
β = 96.00 (3)°	Plate, colorless
γ = 105.74 (3)°	0.26 × 0.22 × 0.05 mm
V = 956.4 (4) Å^3

Data collection

Nonius KappaCCD diffractometer	4311 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.041
Graphite monochromator	θmax = 30.1°, θmin = 2.7°
ϕ and ω scans	h = −9→10
9764 measured reflections	k = −12→12
5568 independent reflections	l = −22→22

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)] = 0.075	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.242	H-atom parameters constrained
S = 1.12	w = 1/[σ^2(Fo^2) + (0.1168P)^2 + 1.9184P] where P = (Fo^2 + 2Fc^2)/3
5568 reflections	(Δ/σ)max < 0.001
271 parameters	Δρmax = 1.22 e Å^−3
0 restraints	Δρmin = −0.84 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
P1	0.74080 (11)	0.34080 (9)	0.02097 (5)	0.0169 (2)
F1	0.9155 (3)	1.0576 (2)	0.59692 (12)	0.0257 (4)
O1	0.5798 (4)	0.0738 (3)	0.38840 (17)	0.0325 (6)
O2	0.5449 (4)	0.2442 (3)	0.30680 (16)	0.0319 (6)
H2	0.5695	0.3430	0.3143	0.038*
O3	0.6576 (4)	0.5387 (3)	0.37474 (15)	0.0274 (5)
O4	0.7689 (3)	0.4975 (3)	−0.00437 (14)	0.0194 (4)
O5	0.6253 (3)	0.1970 (3)	−0.04980 (15)	0.0223 (5)
O6	0.6379 (4)	0.3480 (3)	0.10412 (16)	0.0295 (6)
H6	0.6201	0.2618	0.1199	0.035*
O7	0.9441 (3)	0.3229 (3)	0.05363 (16)	0.0238 (5)
H7	1.0110	0.3268	0.0131	0.029*
O8	0.3778 (3)	0.0970 (3)	0.12570 (14)	0.0216 (4)
H8A	0.4042	0.1129	0.1819	0.027*
H8B	0.3645	−0.0005	0.1024	0.027*
N1	1.2762 (4)	1.2361 (3)	0.90427 (17)	0.0191 (5)
H1A	1.3878	1.2193	0.9117	0.027*
H1B	1.2855	1.3234	0.9414	0.027*
N2	1.0552 (4)	0.9981 (3)	0.75344 (16)	0.0172 (5)
N3	0.8167 (4)	0.4364 (3)	0.61033 (16)	0.0173 (5)
C1	0.5987 (5)	0.2085 (4)	0.3828 (2)	0.0260 (7)
C2	0.6847 (4)	0.3490 (4)	0.4574 (2)	0.0202 (6)
C3	0.7068 (4)	0.5066 (4)	0.44717 (19)	0.0204 (6)
C4	0.7915 (4)	0.6310 (3)	0.52628 (18)	0.0170 (5)
C5	0.8179 (4)	0.7906 (4)	0.52491 (19)	0.0194 (6)
H5	0.7769	0.8186	0.4723	0.023*
C6	0.9023 (4)	0.9056 (3)	0.59912 (19)	0.0191 (6)
C7	0.9731 (4)	0.8740 (3)	0.67940 (18)	0.0163 (5)
C8	0.9424 (4)	0.7157 (3)	0.68102 (18)	0.0161 (5)
H8	0.9849	0.6889	0.7337	0.019*
C9	0.8495 (4)	0.5939 (3)	0.60621 (18)	0.0163 (5)
C10	0.7384 (4)	0.3195 (4)	0.5376 (2)	0.0204 (6)
H10	0.7197	0.2127	0.5419	0.024*
C11	0.8632 (5)	0.3979 (4)	0.6945 (2)	0.0216 (6)
H11	1.0040	0.4191	0.7172	0.026*
C12	0.7370 (5)	0.4255 (4)	0.7617 (2)	0.0262 (7)
H12A	0.6276	0.4660	0.7453	0.031*
H12B	0.7996	0.4645	0.8241	0.031*
C13	0.7251 (5)	0.2590 (4)	0.7169 (2)	0.0255 (6)
H13A	0.7804	0.1959	0.7518	0.031*
H13B	0.6084	0.1974	0.6729	0.031*
C14	1.0918 (4)	0.9543 (3)	0.83737 (18)	0.0181 (5)
H14A	1.2099	0.9192	0.8403	0.022*
H14B	0.9810	0.8653	0.8423	0.022*
C15	1.1187 (4)	1.0959 (4)	0.91233 (19)	0.0198 (6)
H15A	0.9956	1.1235	0.9126	0.024*
H15B	1.1507	1.0678	0.9688	0.024*
C16	1.2206 (5)	1.1288 (3)	0.7446 (2)	0.0213 (6)
H16A	1.1972	1.1543	0.6866	0.026*
H16B	1.3404	1.0962	0.7483	0.026*
C17	1.2458 (5)	1.2738 (4)	0.8169 (2)	0.0223 (6)
H17A	1.3587	1.3606	0.8117	0.027*
H17B	1.1290	1.3101	0.8109	0.027*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
P1	0.0156 (4)	0.0118 (3)	0.0205 (4)	0.0009 (3)	0.0030 (3)	0.0014 (2)
F1	0.0367 (11)	0.0143 (9)	0.0256 (9)	0.0071 (8)	0.0009 (8)	0.0067 (7)
O1	0.0322 (13)	0.0219 (12)	0.0333 (13)	0.0034 (10)	0.0025 (10)	−0.0091 (10)
O2	0.0330 (13)	0.0296 (13)	0.0234 (11)	0.0042 (11)	−0.0018 (9)	−0.0060 (9)
O3	0.0306 (12)	0.0288 (12)	0.0185 (10)	0.0063 (10)	−0.0022 (9)	0.0024 (9)
O4	0.0177 (10)	0.0137 (9)	0.0261 (10)	0.0032 (8)	0.0043 (8)	0.0044 (8)
O5	0.0182 (10)	0.0146 (10)	0.0283 (11)	0.0016 (8)	−0.0004 (8)	−0.0022 (8)
O6	0.0374 (14)	0.0154 (11)	0.0321 (12)	0.0003 (10)	0.0191 (10)	0.0006 (9)
O7	0.0182 (10)	0.0221 (11)	0.0305 (11)	0.0030 (9)	−0.0004 (8)	0.0115 (9)
O8	0.0253 (11)	0.0153 (10)	0.0227 (10)	0.0046 (8)	0.0046 (8)	0.0026 (8)
N1	0.0174 (11)	0.0154 (11)	0.0208 (11)	0.0033 (9)	0.0003 (9)	−0.0012 (9)
N2	0.0204 (12)	0.0116 (10)	0.0168 (11)	0.0008 (9)	0.0021 (9)	0.0029 (8)
N3	0.0166 (11)	0.0118 (11)	0.0205 (11)	0.0022 (9)	0.0001 (9)	0.0012 (8)
C1	0.0176 (14)	0.0266 (16)	0.0261 (15)	0.0038 (12)	0.0018 (11)	−0.0072 (12)
C2	0.0149 (13)	0.0183 (13)	0.0225 (13)	0.0021 (10)	0.0018 (10)	−0.0024 (10)
C3	0.0163 (13)	0.0231 (15)	0.0177 (13)	0.0033 (11)	0.0013 (10)	−0.0011 (10)
C4	0.0149 (12)	0.0170 (13)	0.0171 (12)	0.0038 (10)	0.0015 (9)	0.0010 (10)
C5	0.0201 (14)	0.0210 (14)	0.0171 (12)	0.0060 (11)	0.0017 (10)	0.0051 (10)
C6	0.0218 (14)	0.0135 (12)	0.0211 (13)	0.0041 (11)	0.0022 (10)	0.0047 (10)
C7	0.0154 (12)	0.0129 (12)	0.0179 (12)	0.0008 (10)	0.0029 (9)	0.0023 (9)
C8	0.0151 (12)	0.0123 (12)	0.0184 (12)	0.0014 (10)	0.0004 (9)	0.0027 (9)
C9	0.0125 (12)	0.0142 (12)	0.0199 (13)	0.0021 (10)	0.0018 (9)	0.0020 (10)
C10	0.0171 (13)	0.0148 (13)	0.0259 (14)	0.0037 (10)	0.0029 (10)	−0.0013 (10)
C11	0.0231 (14)	0.0135 (13)	0.0250 (14)	0.0031 (11)	−0.0034 (11)	0.0042 (10)
C12	0.0367 (18)	0.0166 (14)	0.0219 (14)	0.0026 (13)	0.0040 (12)	0.0045 (11)
C13	0.0293 (16)	0.0144 (13)	0.0285 (15)	−0.0007 (12)	0.0030 (12)	0.0058 (11)
C14	0.0211 (13)	0.0157 (13)	0.0162 (12)	0.0047 (11)	0.0017 (10)	0.0024 (10)
C15	0.0211 (14)	0.0155 (13)	0.0196 (13)	0.0027 (11)	0.0021 (10)	0.0011 (10)
C16	0.0250 (15)	0.0122 (12)	0.0215 (13)	−0.0024 (11)	0.0053 (11)	0.0024 (10)
C17	0.0283 (15)	0.0143 (13)	0.0209 (13)	0.0020 (11)	0.0032 (11)	0.0025 (10)

Geometric parameters (Å, º)

P1—O4	1.504 (2)	C4—C5	1.401 (4)
P1—O5	1.511 (2)	C4—C9	1.411 (4)
P1—O6	1.571 (2)	C5—C6	1.362 (4)
P1—O7	1.571 (2)	C5—H5	0.9500
F1—C6	1.352 (3)	C6—C7	1.420 (4)
O1—C1	1.203 (5)	C7—C8	1.386 (4)
O2—C1	1.340 (5)	C8—C9	1.408 (4)
O2—H2	0.8400	C8—H8	0.9500
O3—C3	1.265 (4)	C10—H10	0.9500
O6—H6	0.8400	C11—C12	1.498 (5)
O7—H7	0.8400	C11—C13	1.500 (4)
O8—H8A	0.8588	C11—H11	1.0000
O8—H8B	0.8593	C12—C13	1.505 (5)
N1—C17	1.484 (4)	C12—H12A	0.9900
N1—C15	1.491 (4)	C12—H12B	0.9900
N1—H1A	0.8634	C13—H13A	0.9900
N1—H1B	0.8663	C13—H13B	0.9900
N2—C7	1.399 (4)	C14—C15	1.516 (4)
N2—C14	1.465 (4)	C14—H14A	0.9900
N2—C16	1.475 (4)	C14—H14B	0.9900
N3—C10	1.349 (4)	C15—H15A	0.9900
N3—C9	1.387 (4)	C15—H15B	0.9900
N3—C11	1.458 (4)	C16—C17	1.514 (4)
C1—C2	1.490 (4)	C16—H16A	0.9900
C2—C10	1.374 (4)	C16—H16B	0.9900
C2—C3	1.426 (5)	C17—H17A	0.9900
C3—C4	1.454 (4)	C17—H17B	0.9900
O4—P1—O5	115.33 (13)	N3—C9—C4	119.5 (3)
O4—P1—O6	107.28 (13)	C8—C9—C4	120.3 (3)
O5—P1—O6	109.59 (14)	N3—C10—C2	122.6 (3)
O4—P1—O7	109.39 (13)	N3—C10—H10	118.7
O5—P1—O7	109.91 (13)	C2—C10—H10	118.7
O6—P1—O7	104.78 (15)	N3—C11—C12	116.9 (3)
C1—O2—H2	109.5	N3—C11—C13	118.5 (3)
P1—O6—H6	109.5	C12—C11—C13	60.3 (2)
P1—O7—H7	109.5	N3—C11—H11	116.5
H8A—O8—H8B	109.3	C12—C11—H11	116.5
C17—N1—C15	111.7 (2)	C13—C11—H11	116.5
C17—N1—H1A	108.2	C11—C12—C13	60.0 (2)
C15—N1—H1A	110.7	C11—C12—H12A	117.8
C17—N1—H1B	104.3	C13—C12—H12A	117.8
C15—N1—H1B	114.6	C11—C12—H12B	117.8
H1A—N1—H1B	106.9	C13—C12—H12B	117.8
C7—N2—C14	116.9 (2)	H12A—C12—H12B	114.9
C7—N2—C16	117.3 (2)	C11—C13—C12	59.8 (2)
C14—N2—C16	110.4 (2)	C11—C13—H13A	117.8
C10—N3—C9	120.4 (3)	C12—C13—H13A	117.8
C10—N3—C11	120.2 (3)	C11—C13—H13B	117.8
C9—N3—C11	119.4 (2)	C12—C13—H13B	117.8
O1—C1—O2	121.9 (3)	H13A—C13—H13B	114.9
O1—C1—C2	124.0 (3)	N2—C14—C15	109.5 (2)
O2—C1—C2	114.1 (3)	N2—C14—H14A	109.8
C10—C2—C3	121.2 (3)	C15—C14—H14A	109.8
C10—C2—C1	116.8 (3)	N2—C14—H14B	109.8
C3—C2—C1	122.0 (3)	C15—C14—H14B	109.8
O3—C3—C2	123.2 (3)	H14A—C14—H14B	108.2
O3—C3—C4	121.4 (3)	N1—C15—C14	111.6 (2)
C2—C3—C4	115.5 (3)	N1—C15—H15A	109.3
C5—C4—C9	118.4 (3)	C14—C15—H15A	109.3
C5—C4—C3	120.8 (3)	N1—C15—H15B	109.3
C9—C4—C3	120.8 (3)	C14—C15—H15B	109.3
C6—C5—C4	119.9 (3)	H15A—C15—H15B	108.0
C6—C5—H5	120.1	N2—C16—C17	109.7 (2)
C4—C5—H5	120.1	N2—C16—H16A	109.7
F1—C6—C5	118.3 (3)	C17—C16—H16A	109.7
F1—C6—C7	118.2 (3)	N2—C16—H16B	109.7
C5—C6—C7	123.5 (3)	C17—C16—H16B	109.7
C8—C7—N2	123.2 (3)	H16A—C16—H16B	108.2
C8—C7—C6	116.4 (3)	N1—C17—C16	110.3 (3)
N2—C7—C6	120.2 (3)	N1—C17—H17A	109.6
C7—C8—C9	121.4 (3)	C16—C17—H17A	109.6
C7—C8—H8	119.3	N1—C17—H17B	109.6
C9—C8—H8	119.3	C16—C17—H17B	109.6
N3—C9—C8	120.1 (3)	H17A—C17—H17B	108.1

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3	0.84	1.74	2.529 (4)	155
O6—H6···O8	0.84	1.99	2.625 (3)	131
O7—H7···O4^i	0.84	1.96	2.556 (3)	128
O8—H8A···O2	0.86	2.08	2.881 (3)	154
O8—H8B···O5^ii	0.86	1.83	2.681 (3)	171
N1—H1A···O5^iii	0.86	1.84	2.695 (3)	169
N1—H1B···O4^iv	0.87	1.89	2.726 (3)	163

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