From a binary salt to salt co-crystals of antibacterial agent lomefloxacin with improved solubility and bioavailability

The cocrystallization of lomefloxacin (Lf) with barbituric acid (HBA) and/or isophthalic acid (H₂ip) leads to novel binary and ternary salts via hydrogen-bonding recognition. X-ray single-crystal diffraction analyses show that zwitterionic lomefloxacin can adjust itself to fulfill a different supramolecular array in either binary salts or ternary salt co-crystals, formulated as [HLf]·[Hip]·H₂O (1), [HLf]·[BA]·[HBA]·H₂O (2) and [HLf]·[BA]·[H₂ip]·CH₃OH·H₂O (3). These pharmaceutical agents present uniform charge-assisted hydrogen-bonding networks between HLf cations and acidic coformers with the lattice capturing water molecules. Structural comparison of (2) and (3) indicated that a delicate balance of geometries and hydrogen-bonding partners is required for stacking to favor the formation of ternary salt co-crystals. Cocrystallization was able to overcome the water insolubility of lomefloxacin. Both the salt co-crystals display enhanced solubility and better pharmaceutical applicability.

Computing details

For all compounds, data collection: Bruker APEX2 (Bruker, 2009); cell refinement: Bruker SAINT (Bruker, 2009); data reduction: Bruker SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: Bruker SHELXTL; software used to prepare material for publication: Bruker SHELXTL.

Figures

(1)

Crystal data

C17H20F2N3O3·C8H5O4·H2O	Z = 2
Mr = 535.50	F(000) = 560
Triclinic, P1	Dx = 1.437 Mg m^−3
a = 8.6341 (15) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.5326 (18) Å	Cell parameters from 1443 reflections
c = 14.302 (2) Å	θ = 2.4–23.7°
α = 89.016 (4)°	µ = 0.12 mm^−1
β = 73.535 (4)°	T = 296 K
γ = 82.924 (4)°	Block, colorless
V = 1237.6 (4) Å^3	0.26 × 0.23 × 0.20 mm

Data collection

Bruker APEX-II CCD diffractometer	4305 independent reflections
Radiation source: fine-focus sealed tube	2537 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.029
φ and ω scans	θmax = 25.0°, θmin = 1.5°
Absorption correction: multi-scan SADABS	h = −10→10
Tmin = 0.970, Tmax = 0.977	k = −12→10
6932 measured reflections	l = −17→14

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)] = 0.076	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.314	H-atom parameters constrained
S = 1.07	w = 1/[σ^2(Fo^2) + (0.2P)^2 + 0.001P] where P = (Fo^2 + 2Fc^2)/3
4305 reflections	(Δ/σ)max = 0.004
347 parameters	Δρmax = 0.76 e Å^−3
0 restraints	Δρmin = −0.49 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
C1	0.2531 (10)	1.0517 (5)	0.2235 (5)	0.085 (2)
H1	0.3684	1.0618	0.1960	0.102*
C2	0.2467 (8)	0.9396 (5)	0.2799 (4)	0.0759 (18)
H2A	0.1340	0.9329	0.3148	0.091*
H2B	0.3048	0.9480	0.3280	0.091*
C3	0.2517 (10)	0.8056 (5)	0.1433 (4)	0.088 (2)
H3A	0.3162	0.7330	0.1043	0.106*
H3B	0.1408	0.7855	0.1678	0.106*
C4	0.2531 (10)	0.9127 (5)	0.0836 (4)	0.089 (2)
H4A	0.1905	0.9002	0.0386	0.107*
H4B	0.3643	0.9186	0.0453	0.107*
C5	0.1706 (8)	1.1768 (5)	0.2756 (4)	0.0779 (17)
H5A	0.2291	1.1997	0.3195	0.117*
H5B	0.0608	1.1669	0.3118	0.117*
H5C	0.1698	1.2428	0.2286	0.117*
C6	0.3841 (5)	0.7195 (4)	0.2663 (3)	0.0423 (10)
C7	0.5200 (6)	0.7317 (4)	0.2962 (3)	0.0458 (11)
C8	0.5990 (5)	0.6330 (4)	0.3405 (3)	0.0393 (10)
C9	0.5320 (5)	0.5168 (4)	0.3521 (3)	0.0397 (10)
C10	0.3958 (5)	0.5027 (4)	0.3217 (3)	0.0466 (11)
H10	0.3537	0.4248	0.3288	0.056*
C11	0.3243 (5)	0.6027 (4)	0.2819 (3)	0.0462 (11)
C12	0.6052 (5)	0.4072 (4)	0.3952 (3)	0.0436 (10)
C13	0.7455 (5)	0.4284 (4)	0.4230 (3)	0.0446 (11)
C14	0.8008 (5)	0.5431 (4)	0.4114 (3)	0.0464 (11)
H14	0.8910	0.5527	0.4328	0.056*
C15	0.8312 (6)	0.3237 (5)	0.4694 (3)	0.0551 (12)
C16	0.8136 (6)	0.7646 (5)	0.3641 (4)	0.0566 (12)
H16A	0.8189	0.8031	0.3013	0.068*
H16B	0.9240	0.7435	0.3681	0.068*
C17	0.7202 (8)	0.8605 (5)	0.4450 (5)	0.0754 (16)
H17A	0.6156	0.8898	0.4361	0.113*
H17B	0.7802	0.9320	0.4428	0.113*
H17C	0.7060	0.8201	0.5070	0.113*
C18	0.2885 (5)	0.5878 (4)	0.8824 (3)	0.0441 (10)
C19	0.3060 (5)	0.4676 (4)	0.9210 (3)	0.0440 (10)
H19	0.3926	0.4438	0.9468	0.053*
C20	0.1960 (5)	0.3821 (4)	0.9218 (3)	0.0427 (10)
C21	0.0678 (5)	0.4207 (4)	0.8818 (3)	0.0481 (11)
H21	−0.0068	0.3644	0.8809	0.058*
C22	0.0509 (6)	0.5406 (5)	0.8439 (3)	0.0535 (12)
H22	−0.0365	0.5657	0.8190	0.064*
C23	0.1630 (5)	0.6244 (4)	0.8424 (3)	0.0488 (11)
H23	0.1536	0.7045	0.8148	0.059*
C24	0.4080 (6)	0.6791 (5)	0.8829 (3)	0.0484 (11)
C25	0.2063 (6)	0.2535 (4)	0.9668 (3)	0.0499 (11)
F1	0.5805 (3)	0.8441 (2)	0.2784 (2)	0.0652 (9)
F2	0.1888 (3)	0.5886 (3)	0.2559 (2)	0.0651 (8)
N1	0.1857 (6)	1.0363 (4)	0.1382 (3)	0.0593 (11)
H1A	0.0767	1.0401	0.1602	0.071*
H1B	0.2092	1.1015	0.0972	0.071*
N2	0.3141 (5)	0.8240 (3)	0.2244 (3)	0.0516 (10)
N3	0.7355 (4)	0.6460 (3)	0.3710 (2)	0.0428 (9)
O1	0.5472 (4)	0.3035 (3)	0.4034 (3)	0.0670 (10)
O2	0.7686 (5)	0.2138 (3)	0.4786 (3)	0.0731 (11)
H2	0.6954	0.2186	0.4521	0.110*
O3	0.9482 (5)	0.3363 (3)	0.4957 (3)	0.0785 (12)
O4	0.3962 (5)	0.7902 (3)	0.8579 (3)	0.0696 (11)
O5	0.5308 (5)	0.6259 (3)	0.9143 (3)	0.0700 (11)
H5	0.5848	0.6814	0.9225	0.105*
O6	0.2986 (4)	0.2319 (3)	1.0225 (3)	0.0603 (10)
O7	0.1247 (5)	0.1739 (3)	0.9498 (3)	0.0703 (11)
O8	0.8534 (5)	0.0225 (4)	0.1788 (3)	0.0818 (12)
H8A	0.8624	−0.0474	0.1522	0.123*
H8B	0.7749	0.0763	0.1819	0.123*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.146 (6)	0.053 (3)	0.081 (4)	−0.002 (3)	−0.075 (4)	0.000 (3)
C2	0.109 (5)	0.064 (3)	0.063 (3)	0.025 (3)	−0.053 (3)	−0.014 (3)
C3	0.144 (6)	0.068 (4)	0.070 (4)	0.026 (4)	−0.074 (4)	−0.015 (3)
C4	0.157 (6)	0.059 (3)	0.069 (4)	0.012 (4)	−0.071 (4)	−0.005 (3)
C5	0.114 (5)	0.054 (3)	0.073 (4)	−0.002 (3)	−0.041 (4)	−0.003 (3)
C6	0.038 (2)	0.052 (3)	0.038 (2)	0.0007 (19)	−0.0150 (18)	0.0021 (19)
C7	0.058 (3)	0.042 (2)	0.045 (2)	−0.009 (2)	−0.027 (2)	0.0046 (19)
C8	0.037 (2)	0.048 (2)	0.037 (2)	−0.0031 (18)	−0.0169 (18)	−0.0002 (18)
C9	0.038 (2)	0.047 (2)	0.035 (2)	−0.0042 (18)	−0.0117 (18)	0.0020 (18)
C10	0.049 (3)	0.046 (2)	0.050 (3)	−0.006 (2)	−0.022 (2)	−0.005 (2)
C11	0.042 (2)	0.055 (3)	0.049 (2)	−0.008 (2)	−0.024 (2)	0.001 (2)
C12	0.044 (2)	0.047 (2)	0.040 (2)	−0.0081 (19)	−0.0125 (19)	0.0033 (19)
C13	0.047 (3)	0.051 (2)	0.041 (2)	0.003 (2)	−0.024 (2)	−0.0021 (19)
C14	0.042 (2)	0.058 (3)	0.042 (2)	0.001 (2)	−0.019 (2)	0.001 (2)
C15	0.066 (3)	0.050 (3)	0.051 (3)	0.008 (2)	−0.026 (2)	−0.004 (2)
C16	0.049 (3)	0.065 (3)	0.069 (3)	−0.018 (2)	−0.033 (2)	0.011 (2)
C17	0.093 (4)	0.060 (3)	0.085 (4)	−0.022 (3)	−0.040 (3)	−0.001 (3)
C18	0.052 (3)	0.048 (2)	0.037 (2)	−0.012 (2)	−0.018 (2)	0.0000 (19)
C19	0.048 (3)	0.050 (3)	0.040 (2)	−0.0101 (19)	−0.020 (2)	−0.0025 (19)
C20	0.047 (2)	0.047 (2)	0.040 (2)	−0.0142 (19)	−0.020 (2)	−0.0023 (19)
C21	0.042 (2)	0.055 (3)	0.053 (3)	−0.016 (2)	−0.020 (2)	−0.005 (2)
C22	0.054 (3)	0.059 (3)	0.057 (3)	−0.010 (2)	−0.030 (2)	0.002 (2)
C23	0.048 (3)	0.055 (3)	0.047 (3)	−0.011 (2)	−0.017 (2)	0.001 (2)
C24	0.051 (3)	0.060 (3)	0.039 (2)	−0.019 (2)	−0.017 (2)	0.003 (2)
C25	0.051 (3)	0.053 (3)	0.055 (3)	−0.016 (2)	−0.026 (2)	−0.005 (2)
F1	0.0735 (19)	0.0535 (16)	0.088 (2)	−0.0240 (14)	−0.0491 (17)	0.0256 (14)
F2	0.0545 (17)	0.0723 (18)	0.086 (2)	−0.0094 (14)	−0.0477 (16)	0.0015 (15)
N1	0.083 (3)	0.049 (2)	0.056 (2)	−0.003 (2)	−0.039 (2)	0.0055 (18)
N2	0.062 (2)	0.052 (2)	0.051 (2)	0.0016 (18)	−0.036 (2)	−0.0004 (17)
N3	0.043 (2)	0.052 (2)	0.0407 (19)	−0.0103 (16)	−0.0218 (16)	0.0055 (16)
O1	0.077 (2)	0.0466 (19)	0.094 (3)	−0.0150 (17)	−0.048 (2)	0.0140 (18)
O2	0.087 (3)	0.054 (2)	0.088 (3)	−0.0020 (19)	−0.045 (2)	0.0152 (18)
O3	0.091 (3)	0.067 (2)	0.099 (3)	0.013 (2)	−0.071 (3)	−0.002 (2)
O4	0.079 (3)	0.053 (2)	0.091 (3)	−0.0252 (17)	−0.040 (2)	0.0129 (19)
O5	0.087 (3)	0.059 (2)	0.093 (3)	−0.0381 (19)	−0.062 (2)	0.0233 (19)
O6	0.071 (2)	0.0496 (18)	0.077 (2)	−0.0234 (16)	−0.0430 (19)	0.0142 (16)
O7	0.084 (3)	0.0527 (19)	0.096 (3)	−0.0316 (18)	−0.050 (2)	0.0071 (18)
O8	0.091 (3)	0.071 (2)	0.099 (3)	−0.027 (2)	−0.046 (2)	−0.001 (2)

Geometric parameters (Å, º)

C1—C2	1.417 (8)	C14—N3	1.356 (5)
C1—N1	1.512 (6)	C14—H14	0.9300
C1—C5	1.516 (8)	C15—O3	1.197 (6)
C1—H1	0.9800	C15—O2	1.325 (6)
C2—N2	1.431 (6)	C16—N3	1.480 (6)
C2—H2A	0.9700	C16—C17	1.523 (7)
C2—H2B	0.9700	C16—H16A	0.9700
C3—C4	1.402 (8)	C16—H16B	0.9700
C3—N2	1.436 (6)	C17—H17A	0.9600
C3—H3A	0.9700	C17—H17B	0.9600
C3—H3B	0.9700	C17—H17C	0.9600
C4—N1	1.494 (7)	C18—C23	1.374 (6)
C4—H4A	0.9700	C18—C19	1.381 (6)
C4—H4B	0.9700	C18—C24	1.497 (6)
C5—H5A	0.9600	C19—C20	1.384 (6)
C5—H5B	0.9600	C19—H19	0.9300
C5—H5C	0.9600	C20—C21	1.398 (6)
C6—C7	1.378 (6)	C20—C25	1.493 (6)
C6—C11	1.382 (6)	C21—C22	1.374 (6)
C6—N2	1.398 (5)	C21—H21	0.9300
C7—F1	1.344 (5)	C22—C23	1.384 (6)
C7—C8	1.413 (6)	C22—H22	0.9300
C8—N3	1.389 (5)	C23—H23	0.9300
C8—C9	1.405 (6)	C24—O4	1.219 (5)
C9—C10	1.389 (6)	C24—O5	1.324 (5)
C9—C12	1.459 (6)	C25—O7	1.227 (5)
C10—C11	1.354 (6)	C25—O6	1.277 (5)
C10—H10	0.9300	N1—H1A	0.9000
C11—F2	1.349 (5)	N1—H1B	0.9000
C12—O1	1.246 (5)	O2—H2	0.8200
C12—C13	1.421 (6)	O5—H5	0.8200
C13—C14	1.344 (6)	O8—H8A	0.8201
C13—C15	1.502 (6)	O8—H8B	0.8201
C2—C1—N1	110.9 (5)	N3—C14—H14	117.5
C2—C1—C5	117.5 (6)	O3—C15—O2	121.6 (4)
N1—C1—C5	107.7 (4)	O3—C15—C13	123.4 (5)
C2—C1—H1	106.7	O2—C15—C13	115.0 (4)
N1—C1—H1	106.7	N3—C16—C17	111.6 (4)
C5—C1—H1	106.7	N3—C16—H16A	109.3
C1—C2—N2	114.3 (5)	C17—C16—H16A	109.3
C1—C2—H2A	108.7	N3—C16—H16B	109.3
N2—C2—H2A	108.7	C17—C16—H16B	109.3
C1—C2—H2B	108.7	H16A—C16—H16B	108.0
N2—C2—H2B	108.7	C16—C17—H17A	109.5
H2A—C2—H2B	107.6	C16—C17—H17B	109.5
C4—C3—N2	113.3 (5)	H17A—C17—H17B	109.5
C4—C3—H3A	108.9	C16—C17—H17C	109.5
N2—C3—H3A	108.9	H17A—C17—H17C	109.5
C4—C3—H3B	108.9	H17B—C17—H17C	109.5
N2—C3—H3B	108.9	C23—C18—C19	120.7 (4)
H3A—C3—H3B	107.7	C23—C18—C24	119.4 (4)
C3—C4—N1	114.1 (5)	C19—C18—C24	119.9 (4)
C3—C4—H4A	108.7	C18—C19—C20	120.7 (4)
N1—C4—H4A	108.7	C18—C19—H19	119.6
C3—C4—H4B	108.7	C20—C19—H19	119.6
N1—C4—H4B	108.7	C19—C20—C21	118.2 (4)
H4A—C4—H4B	107.6	C19—C20—C25	122.4 (4)
C1—C5—H5A	109.5	C21—C20—C25	119.4 (4)
C1—C5—H5B	109.5	C22—C21—C20	120.8 (4)
H5A—C5—H5B	109.5	C22—C21—H21	119.6
C1—C5—H5C	109.5	C20—C21—H21	119.6
H5A—C5—H5C	109.5	C21—C22—C23	120.4 (4)
H5B—C5—H5C	109.5	C21—C22—H22	119.8
C7—C6—C11	116.5 (4)	C23—C22—H22	119.8
C7—C6—N2	119.2 (4)	C18—C23—C22	119.2 (4)
C11—C6—N2	124.3 (4)	C18—C23—H23	120.4
F1—C7—C6	116.4 (4)	C22—C23—H23	120.4
F1—C7—C8	119.7 (4)	O4—C24—O5	122.7 (4)
C6—C7—C8	123.9 (4)	O4—C24—C18	124.9 (4)
N3—C8—C9	120.4 (4)	O5—C24—C18	112.4 (4)
N3—C8—C7	123.7 (4)	O7—C25—O6	122.8 (4)
C9—C8—C7	115.9 (4)	O7—C25—C20	118.9 (4)
C10—C9—C8	120.9 (4)	O6—C25—C20	118.2 (4)
C10—C9—C12	118.3 (4)	C4—N1—C1	112.5 (4)
C8—C9—C12	120.8 (4)	C4—N1—H1A	109.1
C11—C10—C9	119.8 (4)	C1—N1—H1A	109.1
C11—C10—H10	120.1	C4—N1—H1B	109.1
C9—C10—H10	120.1	C1—N1—H1B	109.1
F2—C11—C10	119.0 (4)	H1A—N1—H1B	107.8
F2—C11—C6	118.1 (4)	C6—N2—C2	120.4 (4)
C10—C11—C6	123.0 (4)	C6—N2—C3	120.5 (4)
O1—C12—C13	124.5 (4)	C2—N2—C3	114.9 (4)
O1—C12—C9	120.5 (4)	C14—N3—C8	117.8 (4)
C13—C12—C9	115.0 (4)	C14—N3—C16	117.4 (3)
C14—C13—C12	120.9 (4)	C8—N3—C16	124.8 (3)
C14—C13—C15	118.8 (4)	C15—O2—H2	109.5
C12—C13—C15	120.3 (4)	C24—O5—H5	109.5
C13—C14—N3	125.1 (4)	H8A—O8—H8B	121.3
C13—C14—H14	117.5
N1—C1—C2—N2	50.2 (8)	C23—C18—C19—C20	−1.1 (6)
C5—C1—C2—N2	174.7 (5)	C24—C18—C19—C20	179.5 (4)
N2—C3—C4—N1	−47.3 (9)	C18—C19—C20—C21	0.4 (6)
C11—C6—C7—F1	178.2 (4)	C18—C19—C20—C25	−177.2 (4)
N2—C6—C7—F1	−2.8 (6)	C19—C20—C21—C22	−0.7 (7)
C11—C6—C7—C8	0.1 (7)	C25—C20—C21—C22	177.0 (4)
N2—C6—C7—C8	179.1 (4)	C20—C21—C22—C23	1.6 (7)
F1—C7—C8—N3	2.4 (6)	C19—C18—C23—C22	1.9 (7)
C6—C7—C8—N3	−179.6 (4)	C24—C18—C23—C22	−178.7 (4)
F1—C7—C8—C9	−177.1 (4)	C21—C22—C23—C18	−2.2 (7)
C6—C7—C8—C9	1.0 (6)	C23—C18—C24—O4	6.8 (7)
N3—C8—C9—C10	−179.9 (4)	C19—C18—C24—O4	−173.8 (4)
C7—C8—C9—C10	−0.5 (6)	C23—C18—C24—O5	−173.4 (4)
N3—C8—C9—C12	−0.7 (6)	C19—C18—C24—O5	6.0 (6)
C7—C8—C9—C12	178.7 (4)	C19—C20—C25—O7	−166.9 (4)
C8—C9—C10—C11	−1.1 (6)	C21—C20—C25—O7	15.5 (7)
C12—C9—C10—C11	179.7 (4)	C19—C20—C25—O6	14.0 (7)
C9—C10—C11—F2	−177.8 (4)	C21—C20—C25—O6	−163.7 (4)
C9—C10—C11—C6	2.3 (7)	C3—C4—N1—C1	47.2 (8)
C7—C6—C11—F2	178.3 (4)	C2—C1—N1—C4	−47.6 (8)
N2—C6—C11—F2	−0.6 (6)	C5—C1—N1—C4	−177.4 (5)
C7—C6—C11—C10	−1.8 (7)	C7—C6—N2—C2	−63.2 (6)
N2—C6—C11—C10	179.3 (4)	C11—C6—N2—C2	115.7 (6)
C10—C9—C12—O1	0.7 (6)	C7—C6—N2—C3	140.8 (5)
C8—C9—C12—O1	−178.5 (4)	C11—C6—N2—C3	−40.3 (7)
C10—C9—C12—C13	179.1 (4)	C1—C2—N2—C6	150.8 (5)
C8—C9—C12—C13	−0.1 (6)	C1—C2—N2—C3	−52.0 (8)
O1—C12—C13—C14	179.7 (4)	C4—C3—N2—C6	−153.3 (5)
C9—C12—C13—C14	1.4 (6)	C4—C3—N2—C2	49.5 (8)
O1—C12—C13—C15	−2.4 (7)	C13—C14—N3—C8	1.1 (6)
C9—C12—C13—C15	179.3 (4)	C13—C14—N3—C16	−179.8 (4)
C12—C13—C14—N3	−2.0 (7)	C9—C8—N3—C14	0.3 (6)
C15—C13—C14—N3	−179.9 (4)	C7—C8—N3—C14	−179.1 (4)
C14—C13—C15—O3	−0.9 (7)	C9—C8—N3—C16	−178.7 (4)
C12—C13—C15—O3	−178.8 (5)	C7—C8—N3—C16	1.9 (6)
C14—C13—C15—O2	179.7 (4)	C17—C16—N3—C14	−100.5 (5)
C12—C13—C15—O2	1.8 (6)	C17—C16—N3—C8	78.5 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O8^i	0.90	1.90	2.783 (7)	166
N1—H1B···O6^ii	0.90	1.83	2.720 (6)	167
N1—H1B···O7^ii	0.90	2.50	3.181 (6)	133
O2—H2···O1	0.82	1.77	2.528 (6)	153
O5—H5···O6^iii	0.82	1.78	2.564 (5)	159
O8—H8A···O7^iv	0.82	1.96	2.745 (6)	159
O8—H8B···O4^v	0.82	2.10	2.893 (6)	162
C2—H2B···F1	0.97	2.41	2.928 (7)	113
C3—H3B···F2	0.97	2.46	2.792 (6)	101
C14—H14···O3	0.93	2.48	2.813 (6)	101
C14—H14···O3^vi	0.93	2.36	3.232 (6)	155
C16—H16A···F1	0.97	2.17	2.684 (6)	112
C16—H16B···O3^vi	0.97	2.58	3.333 (7)	135
C17—H17A···F1	0.96	2.42	2.976 (8)	116
C19—H19···O5	0.93	2.35	2.691 (6)	101
C19—H19···O5^iii	0.93	2.34	3.157 (6)	146

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

(2)

Crystal data

C17H19F2N3O3·C4H4N2O3·C4H3N2O3·H2O	Z = 2
Mr = 624.54	F(000) = 650
Triclinic, P1	Dx = 1.524 Mg m^−3
a = 9.551 (4) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.701 (4) Å	Cell parameters from 891 reflections
c = 15.450 (7) Å	θ = 2.3–21.9°
α = 83.870 (11)°	µ = 0.13 mm^−1
β = 73.816 (11)°	T = 296 K
γ = 83.271 (11)°	Block, colorless
V = 1361.2 (10) Å^3	0.17 × 0.13 × 0.10 mm

Data collection

Bruker APEX-II CCD diffractometer	4758 independent reflections
Radiation source: fine-focus sealed tube	2302 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.043
φ and ω scans	θmax = 25.0°, θmin = 1.4°
Absorption correction: multi-scan SADABS	h = −11→11
Tmin = 0.979, Tmax = 0.987	k = −9→11
7618 measured reflections	l = −18→18

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)] = 0.082	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.310	H-atom parameters constrained
S = 0.93	w = 1/[σ^2(Fo^2) + (0.1943P)^2] where P = (Fo^2 + 2Fc^2)/3
4758 reflections	(Δ/σ)max < 0.001
409 parameters	Δρmax = 0.49 e Å^−3
0 restraints	Δρmin = −0.47 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)
O9	0.2725 (5)	0.8205 (4)	0.1072 (3)	0.0461 (11)
O4	−0.0748 (7)	0.2163 (5)	0.6444 (4)	0.0842 (18)
O7	0.2273 (5)	0.4594 (4)	−0.0632 (3)	0.0494 (11)
O8	−0.0252 (5)	0.8823 (4)	−0.0806 (3)	0.0491 (11)
O5	0.2164 (5)	0.1320 (5)	0.8487 (3)	0.0668 (14)
C1	0.2456 (8)	0.1785 (7)	0.1966 (5)	0.062 (2)
H1	0.1581	0.2074	0.1755	0.075*
C2	0.3237 (7)	0.3000 (6)	0.2031 (4)	0.0516 (17)
H2A	0.3553	0.3493	0.1440	0.062*
H2B	0.2579	0.3637	0.2436	0.062*
C3	0.5537 (7)	0.1568 (6)	0.1796 (4)	0.0443 (15)
H3A	0.6362	0.1275	0.2044	0.053*
H3B	0.5903	0.2039	0.1203	0.053*
C4	0.4809 (7)	0.0301 (6)	0.1709 (5)	0.0518 (17)
H4	0.5498	−0.0305	0.1285	0.062*
C5	0.4286 (14)	−0.0527 (11)	0.2665 (8)	0.080 (3)	0.70
H5A	0.3972	0.0118	0.3126	0.120*	0.70
H5B	0.5083	−0.1155	0.2776	0.120*	0.70
H5C	0.3487	−0.1046	0.2672	0.120*	0.70
C5'	0.211 (3)	0.086 (3)	0.2845 (15)	0.099 (12)	0.30
H5'1	0.1857	0.1435	0.3347	0.149*	0.30
H5'2	0.2956	0.0236	0.2873	0.149*	0.30
H5'3	0.1307	0.0341	0.2870	0.149*	0.30
C6	0.5069 (5)	0.3443 (5)	0.2801 (4)	0.0319 (13)
C7	0.4891 (7)	0.4899 (6)	0.2658 (4)	0.0421 (14)
C8	0.5403 (7)	0.5767 (6)	0.3124 (4)	0.0403 (14)
H8	0.5249	0.6727	0.3017	0.048*
C9	0.6147 (6)	0.5212 (5)	0.3752 (3)	0.0329 (13)
C10	0.6377 (6)	0.3758 (5)	0.3932 (4)	0.0343 (13)
C11	0.5836 (7)	0.2942 (6)	0.3445 (4)	0.0407 (14)
C12	0.6677 (6)	0.6183 (6)	0.4250 (4)	0.0351 (13)
C13	0.7445 (6)	0.5572 (6)	0.4881 (4)	0.0398 (14)
C14	0.7639 (7)	0.4129 (6)	0.5021 (4)	0.0457 (15)
H14	0.8132	0.3752	0.5445	0.055*
C15	0.7982 (7)	0.6428 (7)	0.5418 (4)	0.0474 (16)
C16	0.7508 (10)	0.1722 (7)	0.4820 (6)	0.078 (2)
H16A	0.7672	0.1593	0.5416	0.093*
H16B	0.6698	0.1202	0.4825	0.093*
C17	0.8838 (11)	0.1218 (10)	0.4139 (8)	0.115 (4)
H17A	0.8793	0.1609	0.3549	0.172*
H17B	0.8902	0.0221	0.4157	0.172*
H17C	0.9686	0.1497	0.4269	0.172*
N5	0.1143 (5)	0.3474 (5)	0.8199 (3)	0.0402 (12)
H5	0.1508	0.3797	0.8577	0.048*
C19	0.1393 (7)	0.2050 (6)	0.8089 (4)	0.0441 (15)
C20	0.0336 (6)	0.4403 (6)	0.7732 (4)	0.0392 (14)
C21	−0.0187 (7)	0.2509 (6)	0.6968 (4)	0.0460 (16)
N6	0.1063 (5)	0.6729 (4)	−0.0700 (3)	0.0391 (12)
H6	0.0737	0.6449	−0.1110	0.047*
C23	0.2000 (6)	0.5791 (5)	−0.0333 (4)	0.0342 (13)
C24	0.0621 (6)	0.8052 (5)	−0.0465 (4)	0.0318 (12)
C25	0.2246 (6)	0.7651 (5)	0.0539 (3)	0.0273 (12)
F1	0.4248 (5)	0.5489 (4)	0.2035 (3)	0.0713 (13)
F2	0.5955 (4)	0.1539 (3)	0.3610 (2)	0.0592 (11)
N1	0.3504 (5)	0.0782 (5)	0.1367 (3)	0.0434 (13)
H1C	0.3041	0.0040	0.1336	0.052*
H1D	0.3801	0.1196	0.0806	0.052*
N2	0.4520 (5)	0.2515 (5)	0.2374 (3)	0.0360 (11)
N3	0.7154 (5)	0.3252 (5)	0.4578 (3)	0.0423 (12)
N4	−0.0218 (6)	0.3884 (5)	0.7140 (3)	0.0478 (13)
H4A	−0.0649	0.4486	0.6826	0.057*
C18	0.0681 (7)	0.1500 (6)	0.7481 (4)	0.0448 (15)
H18A	0.0030	0.0830	0.7839	0.054*
H18B	0.1437	0.0992	0.7041	0.054*
C22	0.2589 (6)	0.6284 (5)	0.0294 (4)	0.0377 (14)
H22	0.3223	0.5689	0.0553	0.045*
N7	0.1245 (5)	0.8469 (4)	0.0135 (3)	0.0345 (11)
H7	0.1008	0.9310	0.0285	0.041*
O1	0.6445 (5)	0.7489 (4)	0.4097 (3)	0.0576 (13)
O2	0.8701 (5)	0.5937 (4)	0.5940 (3)	0.0571 (13)
O3	0.7718 (6)	0.7778 (4)	0.5281 (3)	0.0644 (14)
H3	0.7278	0.7947	0.4891	0.097*
O6	0.0200 (5)	0.5649 (4)	0.7828 (3)	0.0569 (13)
O10	0.5776 (5)	0.7658 (5)	0.0262 (3)	0.0605 (13)
H10A	0.4897	0.7721	0.0517	0.091*
H10B	0.6362	0.7161	0.0485	0.091*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O9	0.064 (3)	0.026 (2)	0.056 (3)	0.0021 (19)	−0.027 (2)	−0.0138 (18)
O4	0.137 (5)	0.063 (3)	0.081 (4)	0.009 (3)	−0.074 (4)	−0.033 (3)
O7	0.062 (3)	0.032 (2)	0.071 (3)	0.0096 (19)	−0.044 (2)	−0.021 (2)
O8	0.063 (3)	0.033 (2)	0.065 (3)	0.013 (2)	−0.043 (2)	−0.0166 (19)
O5	0.065 (3)	0.057 (3)	0.102 (4)	0.017 (2)	−0.065 (3)	−0.020 (3)
C1	0.053 (4)	0.064 (5)	0.077 (5)	0.009 (3)	−0.025 (4)	−0.037 (4)
C2	0.059 (4)	0.048 (4)	0.066 (4)	0.012 (3)	−0.044 (3)	−0.032 (3)
C3	0.052 (4)	0.040 (3)	0.044 (4)	−0.003 (3)	−0.014 (3)	−0.016 (3)
C4	0.058 (4)	0.030 (3)	0.081 (5)	0.012 (3)	−0.044 (4)	−0.018 (3)
C5	0.102 (9)	0.043 (6)	0.099 (9)	−0.014 (6)	−0.037 (7)	0.012 (6)
C5'	0.10 (2)	0.18 (3)	0.034 (13)	−0.10 (2)	0.014 (13)	−0.041 (16)
C6	0.025 (3)	0.033 (3)	0.046 (3)	−0.003 (2)	−0.018 (3)	−0.012 (2)
C7	0.049 (4)	0.040 (3)	0.043 (3)	−0.006 (3)	−0.024 (3)	0.002 (3)
C8	0.051 (4)	0.035 (3)	0.043 (3)	−0.003 (3)	−0.028 (3)	−0.003 (2)
C9	0.044 (3)	0.027 (3)	0.032 (3)	−0.005 (2)	−0.017 (3)	−0.004 (2)
C10	0.037 (3)	0.033 (3)	0.040 (3)	−0.004 (2)	−0.018 (3)	−0.009 (2)
C11	0.059 (4)	0.031 (3)	0.042 (3)	−0.002 (3)	−0.030 (3)	−0.005 (2)
C12	0.036 (3)	0.037 (3)	0.039 (3)	−0.003 (3)	−0.020 (3)	−0.007 (2)
C13	0.045 (4)	0.034 (3)	0.041 (3)	−0.004 (3)	−0.011 (3)	−0.007 (2)
C14	0.063 (4)	0.038 (3)	0.046 (4)	0.005 (3)	−0.033 (3)	−0.011 (3)
C15	0.044 (4)	0.046 (4)	0.053 (4)	−0.005 (3)	−0.009 (3)	−0.017 (3)
C16	0.115 (7)	0.045 (4)	0.094 (6)	0.006 (4)	−0.066 (6)	−0.012 (4)
C17	0.096 (7)	0.067 (6)	0.204 (12)	0.026 (5)	−0.079 (8)	−0.044 (7)
N5	0.046 (3)	0.035 (3)	0.046 (3)	0.001 (2)	−0.022 (2)	−0.012 (2)
C19	0.048 (4)	0.036 (3)	0.046 (4)	0.000 (3)	−0.010 (3)	−0.007 (3)
C20	0.043 (4)	0.041 (4)	0.042 (3)	−0.003 (3)	−0.023 (3)	−0.011 (3)
C21	0.045 (4)	0.048 (4)	0.049 (4)	−0.003 (3)	−0.013 (3)	−0.022 (3)
N6	0.046 (3)	0.027 (3)	0.058 (3)	0.003 (2)	−0.033 (3)	−0.018 (2)
C23	0.033 (3)	0.030 (3)	0.043 (3)	−0.003 (2)	−0.018 (3)	0.001 (2)
C24	0.038 (3)	0.024 (3)	0.043 (3)	0.001 (2)	−0.027 (3)	−0.007 (2)
C25	0.029 (3)	0.031 (3)	0.031 (3)	−0.005 (2)	−0.021 (2)	−0.006 (2)
F1	0.125 (4)	0.041 (2)	0.073 (3)	−0.002 (2)	−0.073 (3)	0.0033 (18)
F2	0.097 (3)	0.033 (2)	0.070 (2)	−0.0033 (19)	−0.061 (2)	−0.0057 (16)
N1	0.062 (3)	0.035 (3)	0.046 (3)	−0.011 (2)	−0.033 (3)	−0.005 (2)
N2	0.036 (3)	0.041 (3)	0.037 (3)	0.002 (2)	−0.019 (2)	−0.016 (2)
N3	0.057 (3)	0.032 (3)	0.054 (3)	0.002 (2)	−0.042 (3)	−0.011 (2)
N4	0.064 (4)	0.035 (3)	0.050 (3)	0.009 (2)	−0.026 (3)	−0.015 (2)
C18	0.059 (4)	0.039 (3)	0.042 (3)	0.002 (3)	−0.022 (3)	−0.011 (3)
C22	0.051 (4)	0.024 (3)	0.044 (3)	−0.004 (2)	−0.023 (3)	−0.001 (2)
N7	0.038 (3)	0.027 (2)	0.046 (3)	0.003 (2)	−0.023 (2)	−0.0131 (19)
O1	0.087 (4)	0.030 (3)	0.070 (3)	−0.009 (2)	−0.043 (3)	−0.004 (2)
O2	0.073 (3)	0.054 (3)	0.067 (3)	−0.006 (2)	−0.052 (3)	−0.016 (2)
O3	0.093 (4)	0.039 (3)	0.076 (3)	−0.015 (2)	−0.041 (3)	−0.011 (2)
O6	0.081 (3)	0.036 (2)	0.066 (3)	0.005 (2)	−0.039 (3)	−0.015 (2)
O10	0.048 (3)	0.061 (3)	0.072 (3)	0.006 (2)	−0.024 (2)	0.006 (2)

Geometric parameters (Å, º)

O9—C25	1.240 (6)	C13—C14	1.392 (8)
O4—C21	1.181 (7)	C13—C15	1.458 (8)
O7—C23	1.268 (6)	C14—N3	1.343 (7)
O8—C24	1.243 (6)	C14—H14	0.9300
O5—C19	1.208 (7)	C15—O2	1.224 (8)
C1—C2	1.493 (9)	C15—O3	1.310 (7)
C1—N1	1.500 (8)	C16—C17	1.476 (12)
C1—C5'	1.52 (3)	C16—N3	1.514 (8)
C1—H1	0.9800	C16—H16A	0.9700
C2—N2	1.475 (7)	C16—H16B	0.9700
C2—H2A	0.9700	C17—H17A	0.9600
C2—H2B	0.9700	C17—H17B	0.9600
C3—N2	1.438 (7)	C17—H17C	0.9600
C3—C4	1.516 (8)	N5—C20	1.391 (7)
C3—H3A	0.9700	N5—C19	1.395 (7)
C3—H3B	0.9700	N5—H5	0.8600
C4—N1	1.493 (7)	C19—C18	1.475 (9)
C4—C5	1.582 (13)	C20—O6	1.222 (7)
C4—H4	0.9800	C20—N4	1.341 (7)
C5—H5A	0.9600	C21—N4	1.384 (7)
C5—H5B	0.9600	C21—C18	1.511 (9)
C5—H5C	0.9600	N6—C24	1.358 (6)
C5'—H5'1	0.9600	N6—C23	1.390 (7)
C5'—H5'2	0.9600	N6—H6	0.8600
C5'—H5'3	0.9600	C23—C22	1.396 (7)
C6—N2	1.396 (6)	C24—N7	1.351 (6)
C6—C7	1.404 (8)	C25—C22	1.395 (7)
C6—C11	1.408 (8)	C25—N7	1.408 (7)
C7—F1	1.326 (7)	N1—H1C	0.9000
C7—C8	1.375 (8)	N1—H1D	0.9000
C8—C9	1.386 (7)	N4—H4A	0.8600
C8—H8	0.9300	C18—H18A	0.9700
C9—C10	1.412 (7)	C18—H18B	0.9700
C9—C12	1.490 (7)	C22—H22	0.9300
C10—C11	1.378 (7)	N7—H7	0.8600
C10—N3	1.419 (7)	O3—H3	0.8200
C11—F2	1.356 (6)	O10—H10A	0.8201
C12—O1	1.269 (7)	O10—H10B	0.8201
C12—C13	1.419 (8)
C2—C1—N1	109.0 (6)	C17—C16—H16A	110.0
C2—C1—C5'	111.9 (10)	N3—C16—H16A	110.0
N1—C1—C5'	99.4 (13)	C17—C16—H16B	110.0
C2—C1—H1	111.9	N3—C16—H16B	110.0
N1—C1—H1	111.9	H16A—C16—H16B	108.4
C5'—C1—H1	111.9	C16—C17—H17A	109.5
N2—C2—C1	109.9 (5)	C16—C17—H17B	109.5
N2—C2—H2A	109.7	H17A—C17—H17B	109.5
C1—C2—H2A	109.7	C16—C17—H17C	109.5
N2—C2—H2B	109.7	H17A—C17—H17C	109.5
C1—C2—H2B	109.7	H17B—C17—H17C	109.5
H2A—C2—H2B	108.2	C20—N5—C19	123.7 (5)
N2—C3—C4	110.8 (5)	C20—N5—H5	118.1
N2—C3—H3A	109.5	C19—N5—H5	118.1
C4—C3—H3A	109.5	O5—C19—N5	119.8 (6)
N2—C3—H3B	109.5	O5—C19—C18	122.8 (6)
C4—C3—H3B	109.5	N5—C19—C18	117.4 (5)
H3A—C3—H3B	108.1	O6—C20—N4	121.6 (6)
N1—C4—C3	108.5 (5)	O6—C20—N5	120.9 (5)
N1—C4—C5	108.8 (6)	N4—C20—N5	117.4 (5)
C3—C4—C5	110.1 (6)	O4—C21—N4	122.9 (6)
N1—C4—H4	109.8	O4—C21—C18	123.2 (6)
C3—C4—H4	109.8	N4—C21—C18	113.9 (5)
C5—C4—H4	109.8	C24—N6—C23	125.4 (5)
C4—C5—H5A	109.5	C24—N6—H6	117.3
C4—C5—H5B	109.5	C23—N6—H6	117.3
C4—C5—H5C	109.5	O7—C23—N6	116.2 (5)
C1—C5'—H5'1	109.5	O7—C23—C22	127.0 (5)
C1—C5'—H5'2	109.5	N6—C23—C22	116.7 (5)
H5'1—C5'—H5'2	109.5	O8—C24—N7	123.3 (5)
C1—C5'—H5'3	109.5	O8—C24—N6	122.0 (5)
H5'1—C5'—H5'3	109.5	N7—C24—N6	114.7 (5)
H5'2—C5'—H5'3	109.5	O9—C25—C22	126.8 (5)
N2—C6—C7	124.8 (5)	O9—C25—N7	117.5 (4)
N2—C6—C11	120.3 (5)	C22—C25—N7	115.6 (4)
C7—C6—C11	114.8 (5)	C4—N1—C1	111.9 (5)
F1—C7—C8	117.2 (5)	C4—N1—H1C	109.2
F1—C7—C6	120.3 (5)	C1—N1—H1C	109.2
C8—C7—C6	122.5 (5)	C4—N1—H1D	109.2
C7—C8—C9	120.0 (5)	C1—N1—H1D	109.2
C7—C8—H8	120.0	H1C—N1—H1D	107.9
C9—C8—H8	120.0	C6—N2—C3	118.7 (4)
C8—C9—C10	120.9 (5)	C6—N2—C2	118.7 (4)
C8—C9—C12	118.7 (5)	C3—N2—C2	112.0 (4)
C10—C9—C12	120.4 (5)	C14—N3—C10	121.1 (5)
C11—C10—C9	116.4 (5)	C14—N3—C16	115.0 (5)
C11—C10—N3	125.3 (5)	C10—N3—C16	123.9 (5)
C9—C10—N3	118.3 (4)	C20—N4—C21	128.5 (5)
F2—C11—C10	119.7 (5)	C20—N4—H4A	115.8
F2—C11—C6	114.8 (4)	C21—N4—H4A	115.8
C10—C11—C6	125.4 (5)	C19—C18—C21	118.8 (5)
O1—C12—C13	123.0 (5)	C19—C18—H18A	107.6
O1—C12—C9	120.2 (5)	C21—C18—H18A	107.6
C13—C12—C9	116.8 (5)	C19—C18—H18B	107.6
C14—C13—C12	119.7 (5)	C21—C18—H18B	107.6
C14—C13—C15	119.0 (6)	H18A—C18—H18B	107.0
C12—C13—C15	121.2 (5)	C25—C22—C23	121.4 (5)
N3—C14—C13	123.6 (5)	C25—C22—H22	119.3
N3—C14—H14	118.2	C23—C22—H22	119.3
C13—C14—H14	118.2	C24—N7—C25	126.0 (4)
O2—C15—O3	120.8 (6)	C24—N7—H7	117.0
O2—C15—C13	122.8 (6)	C25—N7—H7	117.0
O3—C15—C13	116.3 (6)	C15—O3—H3	109.5
C17—C16—N3	108.4 (7)	H10A—O10—H10B	121.4
N1—C1—C2—N2	−57.1 (7)	C19—N5—C20—N4	−0.4 (8)
C5'—C1—C2—N2	51.8 (15)	C24—N6—C23—O7	179.2 (5)
N2—C3—C4—N1	56.6 (7)	C24—N6—C23—C22	−3.6 (8)
N2—C3—C4—C5	−62.4 (8)	C23—N6—C24—O8	−178.0 (5)
N2—C6—C7—F1	−4.8 (9)	C23—N6—C24—N7	4.4 (8)
C11—C6—C7—F1	176.7 (5)	C3—C4—N1—C1	−56.5 (7)
N2—C6—C7—C8	177.3 (5)	C5—C4—N1—C1	63.2 (7)
C11—C6—C7—C8	−1.2 (8)	C2—C1—N1—C4	57.8 (7)
F1—C7—C8—C9	−176.9 (5)	C5'—C1—N1—C4	−59.5 (11)
C6—C7—C8—C9	1.1 (9)	C7—C6—N2—C3	117.2 (6)
C7—C8—C9—C10	−0.7 (8)	C11—C6—N2—C3	−64.5 (7)
C7—C8—C9—C12	−179.6 (5)	C7—C6—N2—C2	−24.7 (8)
C8—C9—C10—C11	0.6 (8)	C11—C6—N2—C2	153.7 (5)
C12—C9—C10—C11	179.4 (5)	C4—C3—N2—C6	156.6 (5)
C8—C9—C10—N3	179.6 (5)	C4—C3—N2—C2	−59.2 (7)
C12—C9—C10—N3	−1.5 (8)	C1—C2—N2—C6	−156.2 (5)
C9—C10—C11—F2	−176.9 (5)	C1—C2—N2—C3	59.6 (7)
N3—C10—C11—F2	4.1 (9)	C13—C14—N3—C10	−0.8 (9)
C9—C10—C11—C6	−0.8 (9)	C13—C14—N3—C16	178.8 (6)
N3—C10—C11—C6	−179.8 (5)	C11—C10—N3—C14	−180.0 (6)
N2—C6—C11—F2	−1.1 (8)	C9—C10—N3—C14	1.1 (8)
C7—C6—C11—F2	177.4 (5)	C11—C10—N3—C16	0.5 (9)
N2—C6—C11—C10	−177.4 (5)	C9—C10—N3—C16	−178.5 (6)
C7—C6—C11—C10	1.1 (9)	C17—C16—N3—C14	−97.0 (7)
C8—C9—C12—O1	0.1 (8)	C17—C16—N3—C10	82.6 (9)
C10—C9—C12—O1	−178.8 (5)	O6—C20—N4—C21	−178.3 (6)
C8—C9—C12—C13	−179.5 (5)	N5—C20—N4—C21	5.1 (9)
C10—C9—C12—C13	1.7 (8)	O4—C21—N4—C20	177.9 (7)
O1—C12—C13—C14	179.1 (6)	C18—C21—N4—C20	−4.5 (9)
C9—C12—C13—C14	−1.4 (8)	O5—C19—C18—C21	−176.3 (6)
O1—C12—C13—C15	1.8 (9)	N5—C19—C18—C21	4.0 (8)
C9—C12—C13—C15	−178.6 (5)	O4—C21—C18—C19	177.2 (6)
C12—C13—C14—N3	1.0 (9)	N4—C21—C18—C19	−0.3 (8)
C15—C13—C14—N3	178.3 (6)	O9—C25—C22—C23	−178.5 (5)
C14—C13—C15—O2	5.9 (9)	N7—C25—C22—C23	1.8 (8)
C12—C13—C15—O2	−176.8 (6)	O7—C23—C22—C25	177.1 (5)
C14—C13—C15—O3	−177.5 (5)	N6—C23—C22—C25	0.3 (8)
C12—C13—C15—O3	−0.2 (8)	O8—C24—N7—C25	−179.5 (5)
C20—N5—C19—O5	176.5 (6)	N6—C24—N7—C25	−1.9 (8)
C20—N5—C19—C18	−3.8 (8)	O9—C25—N7—C24	179.3 (5)
C19—N5—C20—O6	−177.1 (5)	C22—C25—N7—C24	−1.0 (8)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1C···O9^i	0.90	1.94	2.807 (6)	160
N1—H1D···O10^ii	0.90	1.86	2.750 (7)	170
O3—H3···O1	0.82	1.75	2.516 (7)	154
N4—H4A···O2^iii	0.86	2.02	2.875 (7)	170
N5—H5···O7^iv	0.86	1.86	2.718 (7)	177
N6—H6···O6^v	0.86	2.10	2.951 (7)	173
N7—H7···O8^vi	0.86	2.03	2.885 (6)	172
O10—H10A···O9	0.82	2.03	2.844 (7)	171
O10—H10B···O7^ii	0.82	2.05	2.819 (7)	155
C1—H1···O8^vii	0.98	2.47	3.257 (9)	137
C2—H2B···O2^viii	0.97	2.52	3.365 (8)	146
C3—H3A···F2	0.97	2.38	2.936 (7)	116
C4—H4···O5^ix	0.98	2.43	3.078 (8)	123
C14—H14···O4^x	0.93	2.43	3.339 (9)	164
C16—H16B···F2	0.97	2.17	2.721 (10)	115

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

(3)

Crystal data

C17H20F2N3O3·C8H6O4·C4H3N2O3·CH4O·H2O	Z = 2
Mr = 695.63	F(000) = 728
Triclinic, P1	Dx = 1.453 Mg m^−3
a = 10.032 (4) Å	Mo Kα radiation, λ = 0.71073 Å
b = 12.123 (5) Å	Cell parameters from 834 reflections
c = 14.336 (6) Å	θ = 2.3–20.7°
α = 86.396 (12)°	µ = 0.12 mm^−1
β = 71.375 (11)°	T = 296 K
γ = 74.221 (12)°	Block, colorless
V = 1589.5 (11) Å^3	0.25 × 0.20 × 0.16 mm

Data collection

Bruker APEX-II CCD diffractometer	5533 independent reflections
Radiation source: fine-focus sealed tube	2356 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.053
φ and ω scans	θmax = 25.0°, θmin = 1.5°
Absorption correction: multi-scan SADABS	h = −11→11
Tmin = 0.971, Tmax = 0.981	k = −14→13
8932 measured reflections	l = −14→17

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)] = 0.088	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.292	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ^2(Fo^2) + (0.1255P)^2 + 0.978P] where P = (Fo^2 + 2Fc^2)/3
5533 reflections	(Δ/σ)max = 0.001
447 parameters	Δρmax = 0.40 e Å^−3
18 restraints	Δρmin = −0.35 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
C1	0.0648 (8)	0.1484 (7)	0.6973 (5)	0.065 (2)
H1A	0.1693	0.1272	0.6860	0.078*
H1B	0.0259	0.2262	0.7243	0.078*
C2	0.0021 (8)	0.0746 (7)	0.7679 (5)	0.063 (2)
H2	0.0555	−0.0034	0.7420	0.076*
C3	−0.1744 (9)	0.0843 (8)	0.6777 (5)	0.073 (3)
H3A	−0.1312	0.0071	0.6495	0.088*
H3B	−0.2782	0.1029	0.6871	0.088*
C4	−0.1127 (8)	0.1621 (8)	0.6096 (5)	0.074 (3)
H4A	−0.1681	0.2403	0.6306	0.089*
H4B	−0.1177	0.1487	0.5450	0.089*
C5	0.0162 (8)	0.0787 (7)	0.8696 (4)	0.061 (2)
H5A	0.1140	0.0792	0.8638	0.092*
H5B	−0.0056	0.0125	0.9049	0.092*
H5C	−0.0510	0.1468	0.9045	0.092*
C6	0.1463 (7)	0.1525 (6)	0.5147 (4)	0.0411 (16)
C7	0.1183 (7)	0.2358 (5)	0.4476 (4)	0.0419 (16)
C8	0.2209 (7)	0.2398 (5)	0.3526 (4)	0.0359 (15)
C9	0.3570 (7)	0.1603 (5)	0.3332 (4)	0.0401 (15)
C10	0.3863 (7)	0.0773 (6)	0.4027 (5)	0.0460 (17)
H10	0.4762	0.0230	0.3883	0.055*
C11	0.2845 (9)	0.0775 (6)	0.4885 (5)	0.055 (2)
C12	0.4731 (7)	0.1565 (6)	0.2389 (5)	0.0415 (16)
C13	0.4312 (7)	0.2396 (6)	0.1709 (4)	0.0446 (16)
C14	0.2990 (7)	0.3151 (5)	0.1947 (4)	0.0409 (15)
H14	0.2790	0.3681	0.1479	0.049*
C15	0.5383 (10)	0.2421 (7)	0.0673 (5)	0.061 (2)
C16	0.0566 (7)	0.4157 (5)	0.2981 (5)	0.0461 (17)
H16A	−0.0269	0.3893	0.3372	0.055*
H16B	0.0430	0.4393	0.2351	0.055*
C17	0.0654 (8)	0.5163 (6)	0.3499 (5)	0.060 (2)
H17A	0.0839	0.4920	0.4107	0.090*
H17B	−0.0253	0.5748	0.3634	0.090*
H17C	0.1431	0.5463	0.3088	0.090*
C18	0.6637 (6)	0.3064 (5)	0.3644 (4)	0.0350 (14)
C19	0.6006 (7)	0.2837 (5)	0.4624 (4)	0.0427 (16)
H19	0.6529	0.2268	0.4936	0.051*
C20	0.4608 (6)	0.3451 (5)	0.5139 (4)	0.0362 (15)
C21	0.3839 (7)	0.4292 (6)	0.4661 (4)	0.0457 (16)
H21	0.2907	0.4716	0.5016	0.055*
C22	0.4384 (7)	0.4517 (6)	0.3712 (5)	0.0516 (18)
H22	0.3831	0.5069	0.3406	0.062*
C23	0.5847 (7)	0.3887 (6)	0.3174 (4)	0.0469 (17)
H23	0.6256	0.4033	0.2514	0.056*
C24	0.8106 (7)	0.2425 (5)	0.3165 (4)	0.0402 (15)
C25	0.3944 (8)	0.3194 (6)	0.6211 (5)	0.0496 (18)
C26	0.4171 (7)	0.1209 (5)	0.9144 (4)	0.0376 (15)
N4	0.3344 (5)	0.1041 (4)	1.0071 (3)	0.0385 (13)
H4	0.3733	0.0500	1.0396	0.046*
C28	0.1936 (6)	0.1666 (5)	1.0530 (4)	0.0317 (14)
C29	0.2059 (7)	0.2719 (6)	0.9031 (4)	0.0444 (16)
C30	0.2187 (9)	0.5482 (8)	−0.0095 (6)	0.083 (3)
H30A	0.1997	0.6200	−0.0416	0.124*
H30B	0.1803	0.4954	−0.0334	0.124*
H30C	0.3221	0.5173	−0.0233	0.124*
F1	−0.0098 (4)	0.3151 (3)	0.4739 (2)	0.0527 (10)
F2	0.3102 (5)	−0.0062 (4)	0.5539 (3)	0.0769 (14)
N1	0.0394 (6)	0.1466 (5)	0.6040 (3)	0.0480 (14)
N2	−0.1525 (6)	0.0863 (5)	0.7752 (3)	0.0467 (14)
H2A	−0.1822	0.0288	0.8110	0.056*
H2B	−0.2085	0.1527	0.8071	0.056*
N3	0.1929 (6)	0.3195 (4)	0.2820 (3)	0.0375 (12)
C27	0.1306 (6)	0.2538 (6)	1.0010 (4)	0.0415 (16)
H27	0.0377	0.3007	1.0311	0.050*
N6	0.3441 (6)	0.2047 (4)	0.8653 (3)	0.0431 (13)
H6	0.3905	0.2155	0.8051	0.052*
O1	0.5988 (6)	0.0897 (4)	0.2208 (3)	0.0665 (14)
O2	0.6615 (6)	0.1717 (5)	0.0520 (4)	0.0788 (17)
H2C	0.6687	0.1644	0.1076	0.118*
O3	0.5027 (6)	0.3077 (5)	0.0077 (4)	0.0758 (16)
O4	0.8688 (5)	0.2551 (4)	0.2184 (3)	0.0589 (13)
H4C	0.9431	0.2030	0.1965	0.088*
O5	0.8919 (5)	0.1779 (4)	0.3588 (3)	0.0538 (12)
O6	0.4688 (7)	0.2426 (5)	0.6585 (3)	0.0884 (19)
O7	0.2681 (6)	0.3843 (4)	0.6656 (3)	0.0657 (14)
H7	0.2346	0.3695	0.7237	0.099*
O8	0.1514 (5)	0.3449 (4)	0.8485 (3)	0.0539 (13)
O9	0.5428 (5)	0.0650 (4)	0.8776 (3)	0.0547 (13)
O10	0.1357 (5)	0.1394 (4)	1.1407 (3)	0.0462 (12)
O12	0.2977 (6)	0.6792 (5)	0.1713 (3)	0.093 (2)
H12A	0.3810	0.6727	0.1343	0.139*
H12B	0.2397	0.6538	0.1557	0.139*
O14	0.1516 (6)	0.5653 (5)	0.0924 (4)	0.0760 (16)
H14A	0.0632	0.5913	0.1042	0.114*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.058 (5)	0.102 (6)	0.046 (4)	−0.035 (5)	−0.022 (4)	0.015 (4)
C2	0.055 (5)	0.093 (6)	0.049 (4)	−0.033 (5)	−0.018 (4)	0.021 (4)
C3	0.075 (6)	0.126 (7)	0.049 (4)	−0.063 (6)	−0.034 (4)	0.027 (5)
C4	0.044 (5)	0.142 (8)	0.045 (4)	−0.041 (5)	−0.014 (4)	0.012 (5)
C5	0.071 (6)	0.075 (5)	0.040 (4)	−0.025 (5)	−0.017 (4)	0.004 (4)
C6	0.038 (4)	0.062 (4)	0.035 (3)	−0.030 (4)	−0.016 (3)	0.022 (3)
C7	0.042 (4)	0.043 (4)	0.038 (4)	−0.011 (3)	−0.007 (3)	−0.004 (3)
C8	0.035 (4)	0.038 (4)	0.035 (3)	−0.016 (3)	−0.005 (3)	0.003 (3)
C9	0.034 (4)	0.043 (4)	0.036 (3)	−0.007 (3)	−0.003 (3)	−0.005 (3)
C10	0.028 (4)	0.061 (5)	0.046 (4)	−0.010 (3)	−0.009 (3)	0.008 (3)
C11	0.066 (6)	0.060 (5)	0.059 (5)	−0.031 (4)	−0.037 (4)	0.020 (4)
C12	0.012 (3)	0.053 (4)	0.048 (4)	−0.006 (3)	0.006 (3)	−0.006 (3)
C13	0.037 (4)	0.051 (4)	0.036 (3)	−0.015 (3)	0.005 (3)	−0.002 (3)
C14	0.036 (4)	0.043 (4)	0.032 (3)	−0.012 (3)	0.007 (3)	0.003 (3)
C15	0.065 (6)	0.065 (5)	0.050 (5)	−0.024 (5)	−0.008 (4)	0.005 (4)
C16	0.045 (4)	0.046 (4)	0.046 (4)	−0.008 (3)	−0.018 (3)	0.009 (3)
C17	0.059 (5)	0.037 (4)	0.075 (5)	−0.005 (4)	−0.016 (4)	0.000 (4)
C18	0.019 (3)	0.048 (4)	0.028 (3)	−0.002 (3)	0.001 (3)	−0.005 (3)
C19	0.051 (5)	0.043 (4)	0.037 (3)	−0.012 (3)	−0.018 (3)	0.005 (3)
C20	0.008 (3)	0.053 (4)	0.031 (3)	−0.004 (3)	0.014 (3)	−0.007 (3)
C21	0.027 (4)	0.056 (4)	0.042 (4)	−0.001 (3)	−0.006 (3)	0.003 (3)
C22	0.036 (4)	0.069 (5)	0.043 (4)	−0.007 (4)	−0.010 (3)	0.007 (3)
C23	0.040 (4)	0.068 (5)	0.030 (3)	−0.015 (4)	−0.006 (3)	0.006 (3)
C24	0.045 (4)	0.042 (4)	0.029 (3)	−0.008 (3)	−0.007 (3)	−0.004 (3)
C25	0.042 (5)	0.060 (5)	0.032 (3)	0.000 (4)	−0.004 (3)	−0.002 (3)
C26	0.028 (4)	0.036 (4)	0.033 (3)	0.003 (3)	0.002 (3)	−0.004 (3)
N4	0.017 (3)	0.052 (3)	0.029 (3)	−0.001 (2)	0.009 (2)	0.007 (2)
C28	0.024 (4)	0.040 (4)	0.023 (3)	−0.007 (3)	0.004 (3)	−0.001 (3)
C29	0.045 (5)	0.048 (4)	0.039 (4)	−0.012 (4)	−0.014 (3)	0.006 (3)
C30	0.040 (5)	0.103 (7)	0.079 (6)	−0.002 (5)	0.006 (4)	−0.008 (5)
F1	0.042 (2)	0.055 (2)	0.045 (2)	−0.004 (2)	0.0023 (18)	−0.0021 (18)
F2	0.086 (4)	0.081 (3)	0.072 (3)	−0.029 (3)	−0.039 (3)	0.041 (2)
N1	0.041 (4)	0.070 (4)	0.034 (3)	−0.018 (3)	−0.011 (3)	0.007 (3)
N2	0.042 (4)	0.057 (4)	0.040 (3)	−0.023 (3)	−0.005 (3)	0.012 (3)
N3	0.041 (3)	0.040 (3)	0.029 (3)	−0.013 (3)	−0.006 (2)	0.002 (2)
C27	0.019 (3)	0.057 (4)	0.030 (3)	−0.003 (3)	0.013 (3)	0.001 (3)
N6	0.046 (4)	0.044 (3)	0.030 (3)	−0.006 (3)	−0.005 (3)	0.008 (2)
O1	0.063 (4)	0.063 (3)	0.063 (3)	−0.010 (3)	−0.011 (3)	0.005 (3)
O2	0.057 (4)	0.082 (4)	0.065 (3)	0.002 (3)	0.009 (3)	−0.004 (3)
O3	0.075 (4)	0.089 (4)	0.053 (3)	−0.030 (3)	−0.001 (3)	0.020 (3)
O4	0.057 (4)	0.073 (4)	0.034 (2)	−0.010 (3)	−0.004 (2)	0.002 (2)
O5	0.048 (3)	0.062 (3)	0.044 (3)	−0.006 (3)	−0.013 (2)	0.002 (2)
O6	0.087 (5)	0.108 (5)	0.043 (3)	0.002 (4)	−0.013 (3)	0.030 (3)
O7	0.057 (4)	0.085 (4)	0.039 (3)	−0.008 (3)	−0.006 (3)	0.019 (3)
O8	0.041 (3)	0.068 (3)	0.036 (2)	0.002 (2)	−0.005 (2)	0.014 (2)
O9	0.051 (3)	0.066 (3)	0.036 (2)	−0.011 (3)	−0.006 (2)	0.017 (2)
O10	0.049 (3)	0.055 (3)	0.026 (2)	−0.016 (2)	0.000 (2)	0.011 (2)
O12	0.068 (4)	0.119 (5)	0.056 (3)	−0.017 (4)	0.027 (3)	−0.022 (3)
O14	0.070 (4)	0.086 (4)	0.059 (3)	−0.003 (3)	−0.020 (3)	0.019 (3)

Geometric parameters (Å, º)

C1—C2	1.417 (9)	C17—H17B	0.9600
C1—N1	1.442 (8)	C17—H17C	0.9600
C1—H1A	0.9700	C18—C23	1.380 (9)
C1—H1B	0.9700	C18—C19	1.388 (8)
C2—N2	1.489 (8)	C18—C24	1.430 (8)
C2—C5	1.513 (9)	C19—C20	1.380 (8)
C2—H2	0.9800	C19—H19	0.9300
C3—C4	1.430 (10)	C20—C21	1.388 (9)
C3—N2	1.485 (7)	C20—C25	1.518 (8)
C3—H3A	0.9700	C21—C22	1.335 (8)
C3—H3B	0.9700	C21—H21	0.9300
C4—N1	1.462 (8)	C22—C23	1.441 (9)
C4—H4A	0.9700	C22—H22	0.9300
C4—H4B	0.9700	C23—H23	0.9300
C5—H5A	0.9600	C24—O5	1.246 (7)
C5—H5B	0.9600	C24—O4	1.356 (7)
C5—H5C	0.9600	C25—O6	1.235 (8)
C6—C7	1.385 (8)	C25—O7	1.280 (8)
C6—C11	1.384 (9)	C26—O9	1.218 (7)
C6—N1	1.395 (7)	C26—N6	1.378 (8)
C7—F1	1.335 (7)	C26—N4	1.360 (7)
C7—C8	1.429 (8)	N4—C28	1.374 (7)
C8—N3	1.395 (7)	N4—H4	0.8600
C8—C9	1.395 (8)	C28—O10	1.270 (6)
C9—C10	1.411 (9)	C28—C27	1.382 (8)
C9—C12	1.470 (8)	C29—O8	1.272 (7)
C10—C11	1.324 (9)	C29—N6	1.357 (8)
C10—H10	0.9300	C29—C27	1.401 (8)
C11—F2	1.367 (7)	C30—O14	1.401 (8)
C12—O1	1.255 (7)	C30—H30A	0.9600
C12—C13	1.432 (9)	C30—H30B	0.9600
C13—C14	1.343 (9)	C30—H30C	0.9600
C13—C15	1.534 (9)	N2—H2A	0.9000
C14—N3	1.352 (7)	N2—H2B	0.9000
C14—H14	0.9300	C27—H27	0.9300
C15—O3	1.202 (9)	N6—H6	0.8600
C15—O2	1.258 (9)	O2—H2C	0.8200
C16—N3	1.500 (8)	O4—H4C	0.8200
C16—C17	1.504 (9)	O7—H7	0.8200
C16—H16A	0.9700	O12—H12A	0.8201
C16—H16B	0.9700	O12—H12B	0.8201
C17—H17A	0.9600	O14—H14A	0.8200
C2—C1—N1	114.6 (6)	C16—C17—H17C	109.5
C2—C1—H1A	108.6	H17A—C17—H17C	109.5
N1—C1—H1A	108.6	H17B—C17—H17C	109.5
C2—C1—H1B	108.6	C23—C18—C19	119.8 (6)
N1—C1—H1B	108.6	C23—C18—C24	122.6 (5)
H1A—C1—H1B	107.6	C19—C18—C24	117.6 (6)
C1—C2—N2	111.9 (6)	C20—C19—C18	120.5 (6)
C1—C2—C5	117.1 (6)	C20—C19—H19	119.8
N2—C2—C5	110.2 (6)	C18—C19—H19	119.8
C1—C2—H2	105.6	C19—C20—C21	119.1 (5)
N2—C2—H2	105.6	C19—C20—C25	119.5 (6)
C5—C2—H2	105.6	C21—C20—C25	121.4 (6)
C4—C3—N2	113.8 (6)	C22—C21—C20	122.6 (6)
C4—C3—H3A	108.8	C22—C21—H21	118.7
N2—C3—H3A	108.8	C20—C21—H21	118.7
C4—C3—H3B	108.8	C21—C22—C23	118.5 (6)
N2—C3—H3B	108.8	C21—C22—H22	120.7
H3A—C3—H3B	107.7	C23—C22—H22	120.7
C3—C4—N1	110.2 (7)	C18—C23—C22	119.5 (6)
C3—C4—H4A	109.6	C18—C23—H23	120.3
N1—C4—H4A	109.6	C22—C23—H23	120.3
C3—C4—H4B	109.6	O5—C24—O4	116.9 (6)
N1—C4—H4B	109.6	O5—C24—C18	124.8 (5)
H4A—C4—H4B	108.1	O4—C24—C18	118.3 (6)
C2—C5—H5A	109.5	O6—C25—O7	126.1 (6)
C2—C5—H5B	109.5	O6—C25—C20	117.8 (6)
H5A—C5—H5B	109.5	O7—C25—C20	115.9 (6)
C2—C5—H5C	109.5	O9—C26—N6	123.3 (5)
H5A—C5—H5C	109.5	O9—C26—N4	123.0 (6)
H5B—C5—H5C	109.5	N6—C26—N4	113.7 (6)
C7—C6—C11	116.5 (6)	C26—N4—C28	125.3 (5)
C7—C6—N1	120.8 (6)	C26—N4—H4	117.3
C11—C6—N1	122.6 (6)	C28—N4—H4	117.3
F1—C7—C6	118.0 (5)	O10—C28—C27	126.6 (6)
F1—C7—C8	119.4 (6)	O10—C28—N4	115.9 (5)
C6—C7—C8	122.6 (6)	C27—C28—N4	117.5 (5)
N3—C8—C9	120.0 (5)	O8—C29—N6	119.3 (5)
N3—C8—C7	123.7 (6)	O8—C29—C27	124.0 (6)
C9—C8—C7	116.2 (6)	N6—C29—C27	116.7 (6)
C8—C9—C10	120.9 (6)	O14—C30—H30A	109.5
C8—C9—C12	121.7 (6)	O14—C30—H30B	109.5
C10—C9—C12	117.4 (6)	H30A—C30—H30B	109.5
C11—C10—C9	119.3 (7)	O14—C30—H30C	109.5
C11—C10—H10	120.4	H30A—C30—H30C	109.5
C9—C10—H10	120.4	H30B—C30—H30C	109.5
C10—C11—F2	119.3 (7)	C6—N1—C1	122.1 (5)
C10—C11—C6	124.3 (6)	C6—N1—C4	121.4 (5)
F2—C11—C6	116.2 (6)	C1—N1—C4	115.3 (5)
O1—C12—C13	123.0 (6)	C3—N2—C2	113.1 (5)
O1—C12—C9	123.4 (6)	C3—N2—H2A	109.0
C13—C12—C9	113.6 (6)	C2—N2—H2A	109.0
C14—C13—C12	121.7 (5)	C3—N2—H2B	109.0
C14—C13—C15	118.6 (6)	C2—N2—H2B	109.0
C12—C13—C15	119.7 (6)	H2A—N2—H2B	107.8
C13—C14—N3	124.6 (6)	C14—N3—C8	118.3 (5)
C13—C14—H14	117.7	C14—N3—C16	116.8 (5)
N3—C14—H14	117.7	C8—N3—C16	124.7 (5)
O3—C15—O2	124.6 (7)	C28—C27—C29	120.5 (6)
O3—C15—C13	120.6 (8)	C28—C27—H27	119.8
O2—C15—C13	114.7 (7)	C29—C27—H27	119.8
N3—C16—C17	110.8 (5)	C29—N6—C26	126.1 (5)
N3—C16—H16A	109.5	C29—N6—H6	117.0
C17—C16—H16A	109.5	C26—N6—H6	117.0
N3—C16—H16B	109.5	C15—O2—H2C	101.8
C17—C16—H16B	109.5	C24—O4—H4C	109.5
H16A—C16—H16B	108.1	C25—O7—H7	114.4
C16—C17—H17A	109.5	H12A—O12—H12B	121.3
C16—C17—H17B	109.5	C30—O14—H14A	109.5
H17A—C17—H17B	109.5
N1—C1—C2—N2	−47.3 (10)	C20—C21—C22—C23	−2.1 (10)
N1—C1—C2—C5	−175.9 (7)	C19—C18—C23—C22	1.2 (9)
N2—C3—C4—N1	50.8 (10)	C24—C18—C23—C22	−178.4 (6)
C11—C6—C7—F1	−174.7 (5)	C21—C22—C23—C18	0.7 (10)
N1—C6—C7—F1	4.8 (8)	C23—C18—C24—O5	170.8 (6)
C11—C6—C7—C8	5.1 (9)	C19—C18—C24—O5	−8.8 (9)
N1—C6—C7—C8	−175.4 (5)	C23—C18—C24—O4	−7.0 (9)
F1—C7—C8—N3	−3.2 (8)	C19—C18—C24—O4	173.4 (5)
C6—C7—C8—N3	177.0 (5)	C19—C20—C25—O6	−0.6 (10)
F1—C7—C8—C9	174.8 (5)	C21—C20—C25—O6	179.4 (7)
C6—C7—C8—C9	−5.0 (8)	C19—C20—C25—O7	175.9 (6)
N3—C8—C9—C10	−178.5 (5)	C21—C20—C25—O7	−4.2 (9)
C7—C8—C9—C10	3.4 (8)	O9—C26—N4—C28	178.2 (6)
N3—C8—C9—C12	−0.9 (9)	N6—C26—N4—C28	−3.5 (8)
C7—C8—C9—C12	−179.0 (5)	C26—N4—C28—O10	−178.5 (5)
C8—C9—C10—C11	−2.1 (9)	C26—N4—C28—C27	0.0 (9)
C12—C9—C10—C11	−179.9 (6)	C7—C6—N1—C1	−125.2 (7)
C9—C10—C11—F2	176.8 (5)	C11—C6—N1—C1	54.2 (9)
C9—C10—C11—C6	2.3 (10)	C7—C6—N1—C4	42.0 (9)
C7—C6—C11—C10	−3.7 (10)	C11—C6—N1—C4	−138.6 (7)
N1—C6—C11—C10	176.8 (6)	C2—C1—N1—C6	−141.4 (7)
C7—C6—C11—F2	−178.4 (5)	C2—C1—N1—C4	50.7 (10)
N1—C6—C11—F2	2.1 (9)	C3—C4—N1—C6	141.0 (7)
C8—C9—C12—O1	176.6 (6)	C3—C4—N1—C1	−51.0 (9)
C10—C9—C12—O1	−5.6 (9)	C4—C3—N2—C2	−50.6 (10)
C8—C9—C12—C13	−1.0 (8)	C1—C2—N2—C3	47.3 (9)
C10—C9—C12—C13	176.7 (5)	C5—C2—N2—C3	179.4 (6)
O1—C12—C13—C14	−175.5 (6)	C13—C14—N3—C8	−0.6 (9)
C9—C12—C13—C14	2.2 (9)	C13—C14—N3—C16	175.4 (6)
O1—C12—C13—C15	5.4 (10)	C9—C8—N3—C14	1.7 (8)
C9—C12—C13—C15	−176.9 (5)	C7—C8—N3—C14	179.7 (5)
C12—C13—C14—N3	−1.4 (10)	C9—C8—N3—C16	−173.9 (5)
C15—C13—C14—N3	177.7 (6)	C7—C8—N3—C16	4.0 (8)
C14—C13—C15—O3	−2.5 (10)	C17—C16—N3—C14	−93.5 (6)
C12—C13—C15—O3	176.6 (7)	C17—C16—N3—C8	82.2 (7)
C14—C13—C15—O2	177.5 (6)	O10—C28—C27—C29	−177.9 (6)
C12—C13—C15—O2	−3.4 (10)	N4—C28—C27—C29	3.8 (9)
C23—C18—C19—C20	−1.8 (9)	O8—C29—C27—C28	174.9 (6)
C24—C18—C19—C20	177.8 (5)	N6—C29—C27—C28	−3.6 (9)
C18—C19—C20—C21	0.4 (9)	O8—C29—N6—C26	−178.9 (6)
C18—C19—C20—C25	−179.6 (6)	C27—C29—N6—C26	−0.3 (9)
C19—C20—C21—C22	1.6 (10)	O9—C26—N6—C29	−178.0 (6)
C25—C20—C21—C22	−178.4 (6)	N4—C26—N6—C29	3.7 (9)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O9^i	0.90	2.54	3.013 (8)	114
N2—H2A···O10^ii	0.90	2.09	2.904 (7)	150
N2—H2B···O12^iii	0.90	1.99	2.846 (8)	159
O2—H2C···O1	0.82	1.84	2.511 (7)	138
N4—H4···O9^iv	0.86	1.96	2.820 (7)	176
O4—H4C···O10^v	0.82	1.80	2.574 (7)	156
N6—H6···O6	0.86	2.03	2.888 (6)	171
O7—H7···O8	0.82	1.76	2.581 (6)	176
O12—H12A···O3^vi	0.82	2.03	2.731 (7)	143
O12—H12B···O14	0.82	1.98	2.773 (9)	164
O14—H14A···O8^iii	0.82	1.98	2.795 (8)	172
C1—H1A···F2	0.97	2.37	2.923 (9)	115
C2—H2···O5^vii	0.98	2.48	3.390 (9)	155
C10—H10···F2^vii	0.93	2.49	3.181 (9)	131
C14—H14···O14	0.93	2.59	3.453 (8)	154
C16—H16A···F1	0.97	2.14	2.696 (7)	115
C17—H17B···O7^iii	0.96	2.51	3.308 (10)	140

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