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.
Supporting information
CCDC references: 672552; 672553
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.
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 [Uiso(H) =
1.2Ueq(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 Uiso(H) = 1.2Ueq(C,O) or
1.5Ueq(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.
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).
(I) 4-(3-carboxy-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolyl)piperazinium
dihydrogen phosphate monohydrate
top
Crystal data top
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) Å3 | |
Data collection top
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 top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.048 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.146 | H-atom parameters constrained |
S = 1.10 | w = 1/[σ2(Fo2) + (0.0744P)2 + 0.5378P] where P = (Fo2 + 2Fc2)/3 |
5425 reflections | (Δ/σ)max = 0.001 |
263 parameters | Δρmax = 0.65 e Å−3 |
0 restraints | Δρmin = −0.94 e Å−3 |
Crystal data top
C16H19FN3O3+·H2PO4−·H2O | γ = 106.51 (3)° |
Mr = 435.34 | V = 934.9 (4) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.1918 (14) Å | Mo Kα radiation |
b = 8.9400 (18) Å | µ = 0.21 mm−1 |
c = 15.792 (3) Å | T = 100 K |
α = 103.81 (3)° | 0.25 × 0.20 × 0.08 mm |
β = 94.01 (3)° | |
Data collection top
Nonius KappaCCD diffractometer | 4398 reflections with I > 2σ(I) |
10002 measured reflections | Rint = 0.030 |
5425 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.048 | 0 restraints |
wR(F2) = 0.146 | H-atom parameters constrained |
S = 1.10 | Δρmax = 0.65 e Å−3 |
5425 reflections | Δρmin = −0.94 e Å−3 |
263 parameters | |
Special details top
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 (Å2) top | 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 (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
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) top
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) top
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···O2i | 0.84 | 2.04 | 2.807 (2) | 151 |
O6—H6···O4ii | 0.84 | 1.99 | 2.566 (2) | 125 |
O7—H7···O8iii | 0.84 | 2.21 | 2.623 (2) | 110 |
N1—H1B···O5 | 0.88 | 1.83 | 2.706 (2) | 172 |
N1—H1A···O4iv | 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
top
Crystal data top
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) Å3 | |
Data collection top
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 top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.075 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.242 | H-atom parameters constrained |
S = 1.12 | w = 1/[σ2(Fo2) + (0.1168P)2 + 1.9184P] where P = (Fo2 + 2Fc2)/3 |
5568 reflections | (Δ/σ)max < 0.001 |
271 parameters | Δρmax = 1.22 e Å−3 |
0 restraints | Δρmin = −0.84 e Å−3 |
Crystal data top
C17H19FN3O3+·H2PO4−·H2O | γ = 105.74 (3)° |
Mr = 447.35 | V = 956.4 (4) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.2582 (15) Å | Mo Kα radiation |
b = 8.9979 (18) Å | µ = 0.21 mm−1 |
c = 15.712 (3) Å | T = 100 K |
α = 100.93 (3)° | 0.26 × 0.22 × 0.05 mm |
β = 96.00 (3)° | |
Data collection top
Nonius KappaCCD diffractometer | 4311 reflections with I > 2σ(I) |
9764 measured reflections | Rint = 0.041 |
5568 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.075 | 0 restraints |
wR(F2) = 0.242 | H-atom parameters constrained |
S = 1.12 | Δρmax = 1.22 e Å−3 |
5568 reflections | Δρmin = −0.84 e Å−3 |
271 parameters | |
Special details top
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 (Å2) top | 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 (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
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) top
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) top
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···O4i | 0.84 | 1.96 | 2.556 (3) | 128 |
O8—H8A···O2 | 0.86 | 2.08 | 2.881 (3) | 154 |
O8—H8B···O5ii | 0.86 | 1.83 | 2.681 (3) | 171 |
N1—H1A···O5iii | 0.86 | 1.84 | 2.695 (3) | 169 |
N1—H1B···O4iv | 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. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C16H19FN3O3+·H2PO4−·H2O | C17H19FN3O3+·H2PO4−·H2O |
Mr | 435.34 | 447.35 |
Crystal system, space group | Triclinic, P1 | Triclinic, P1 |
Temperature (K) | 100 | 100 |
a, b, c (Å) | 7.1918 (14), 8.9400 (18), 15.792 (3) | 7.2582 (15), 8.9979 (18), 15.712 (3) |
α, β, γ (°) | 103.81 (3), 94.01 (3), 106.51 (3) | 100.93 (3), 96.00 (3), 105.74 (3) |
V (Å3) | 934.9 (4) | 956.4 (4) |
Z | 2 | 2 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.21 | 0.21 |
Crystal size (mm) | 0.25 × 0.20 × 0.08 | 0.26 × 0.22 × 0.05 |
|
Data collection |
Diffractometer | Nonius KappaCCD diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 10002, 5425, 4398 | 9764, 5568, 4311 |
Rint | 0.030 | 0.041 |
(sin θ/λ)max (Å−1) | 0.704 | 0.705 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.146, 1.10 | 0.075, 0.242, 1.12 |
No. of reflections | 5425 | 5568 |
No. of parameters | 263 | 271 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.65, −0.94 | 1.22, −0.84 |
Hydrogen-bond geometry (Å, º) for (I) top
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···O2i | 0.84 | 2.04 | 2.807 (2) | 151 |
O6—H6···O4ii | 0.84 | 1.99 | 2.566 (2) | 125 |
O7—H7···O8iii | 0.84 | 2.21 | 2.623 (2) | 110 |
N1—H1B···O5 | 0.88 | 1.83 | 2.706 (2) | 172 |
N1—H1A···O4iv | 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. |
Hydrogen-bond geometry (Å, º) for (II) top
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···O4i | 0.84 | 1.96 | 2.556 (3) | 128 |
O8—H8A···O2 | 0.86 | 2.08 | 2.881 (3) | 154 |
O8—H8B···O5ii | 0.86 | 1.83 | 2.681 (3) | 171 |
N1—H1A···O5iii | 0.86 | 1.84 | 2.695 (3) | 169 |
N1—H1B···O4iv | 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. |
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···O4iv 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.