Clindamycin hydrochloride, an antibiotic of the lincomycin family, was crystallized as the monohydrate, namely (2S,4R)-2-(N-{(1S,2S)-2-chloro-1-[(3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylsulfanyl)perhydropyran-2-yl]propyl}aminocarbonyl)-4-propylpyrrolidinium chloride monohydrate, C18H34ClN2O5S+·Cl-·H2O, (I), and as the monohydrate ethanol solvate, C18H34ClN2O5S+·Cl-·H2O·C2H6O, (II). The conformation of the clindamycin molecule in both crystal structures is the same and is found to be similar to that in enzyme-bound clindamycin. The simultaneous presence of free chloride ions and water molecules in (I) and of additional ethanol molecules in (II) provides an interesting network of hydrogen bonds. The significance of this study lies in the interactions in these structures and the aggregations occurring via hydrogen bonds in the hydrated and solvated crystalline forms of the title compound.
Supporting information
CCDC references: 774040; 774041
Clindamycin hydrochloride (Pharmacology Department, IICT, Hyderabad) (50 mg)
was dissolved in mixture of ethanol (5 ml) and water (2 ml). After 4 d,
crystals of (I) and (II) were obtained and were distinguished by their
distinct crystal habits, needles and plates, respectively. After 8 d it was
observed that the plate-shaped crystals (II) turned opaque. Hence for (II),
data were collected on a crystal in a sealed vial with mother liquor solution.
The site-occupancy factors of disordered atoms C15/C16/C17 (propyl group) of
(I) refined to 0.760 (6) and 0.240 (6), while atoms C16/C17 (propyl group) and
C19/C20/O6 (ethanol solvent molecule) of (II) refined to 0.709 (8) and
0.291 (8). The anisotropic displacement parameters and bond distances of the
major and minor components of the disordered atoms were restrained to be
similar using SIMU and SAME instructions (SHELXL97; Sheldrick, 2008).
The C—C distances of the disordered groups were restraint to be 1.55 (1) Å
and the C—O distances to be 1.45 (1) Å. Except for the disordered ethanol
solvent molecule in (II), all N-bound H atoms, O-bound H atoms and water H
atoms of (I) and (II) were located in difference Fourier maps and their
positions were refined subject to O—H distance restraints of 0.89 (2) Å for
O1W—H1W, O1W—H2W and O3—H3O of (I) and for O1W—H1W, O1W—H2W,
O2—H2O and O4—H4O of (II), an H1W···H2W distance restraint of 1.55 (2) Å
for (I) and an N2—H2N distance restraint of 0.82 (2) Å for (II). The
isotropic displacement of these H atoms were set at Uiso(O) = 1.5Ueq(N,O).
The O-bound H atom of the disordered ethanol solvent molecule in (II) was
found in a difference Fourier map and subsequently placed in an idealized
position, with O—H = 0.82 Å and Uiso(H) = 1.5Ueq(O). All other H atoms
were located in difference density maps, positioned geometrically and included
as riding atoms, with C—H = 0.96–0.98 Å and Uiso(H) = 1.5Ueq(C) for
methyl or 1.2Ueq(C) for the other H atoms. The methyl groups were allowed to
rotate but not to tip. The absolute configuration of the procured material was
known in advance and was confirmed by unambiguous refinement of the absolute
structure parameter (Flack & Bernardinelli, 2000).
For both compounds, data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).
(I) (2
S,4
R)-2-(
N-{(1
S,2
S)-2-chloro-1-
[(3
R,4
S,5
R,6
R)-3,4,5-trihydroxy-6-
(methylsulfanyl)perhydropyran-2-yl]propyl}aminocarbonyl)-4-propylpyrrolidinium
chloride monohydrate
top
Crystal data top
C18H34ClN2O5S+·Cl−·H2O | F(000) = 512 |
Mr = 479.45 | Dx = 1.298 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 8726 reflections |
a = 9.4669 (6) Å | θ = 2.2–28.0° |
b = 9.9255 (6) Å | µ = 0.38 mm−1 |
c = 13.4949 (8) Å | T = 294 K |
β = 104.601 (1)° | Needle, colourless |
V = 1227.08 (13) Å3 | 0.15 × 0.10 × 0.06 mm |
Z = 2 | |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 4211 reflections with I > 2σ(I) |
Radiation source: sealed tube | Rint = 0.016 |
Graphite monochromator | θmax = 25.0°, θmin = 1.6° |
ω scans | h = −11→11 |
11796 measured reflections | k = −11→11 |
4321 independent reflections | l = −16→16 |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.031 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.084 | w = 1/[σ2(Fo2) + (0.0541P)2 + 0.1659P] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max = 0.001 |
4321 reflections | Δρmax = 0.26 e Å−3 |
323 parameters | Δρmin = −0.20 e Å−3 |
68 restraints | Absolute structure: Flack & Bernardinelli (1983), with XXXX Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.02 (5) |
Crystal data top
C18H34ClN2O5S+·Cl−·H2O | V = 1227.08 (13) Å3 |
Mr = 479.45 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 9.4669 (6) Å | µ = 0.38 mm−1 |
b = 9.9255 (6) Å | T = 294 K |
c = 13.4949 (8) Å | 0.15 × 0.10 × 0.06 mm |
β = 104.601 (1)° | |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 4211 reflections with I > 2σ(I) |
11796 measured reflections | Rint = 0.016 |
4321 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.031 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.084 | Δρmax = 0.26 e Å−3 |
S = 1.05 | Δρmin = −0.20 e Å−3 |
4321 reflections | Absolute structure: Flack & Bernardinelli (1983), with XXXX Friedel pairs |
323 parameters | Absolute structure parameter: 0.02 (5) |
68 restraints | |
Special details top
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell esds are taken
into account individually in the estimation of esds in distances, angles
and torsion angles; correlations between esds in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell esds is used for estimating esds involving l.s. planes. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
C1 | 0.4725 (2) | 0.67929 (18) | 0.70806 (14) | 0.0356 (4) | |
H1 | 0.5561 | 0.7033 | 0.7646 | 0.043* | |
C2 | 0.59163 (19) | 0.47578 (17) | 0.67785 (14) | 0.0365 (4) | |
H2 | 0.5732 | 0.3789 | 0.6685 | 0.044* | |
C3 | 0.61592 (19) | 0.53051 (17) | 0.57766 (14) | 0.0353 (4) | |
H3 | 0.5324 | 0.5041 | 0.5219 | 0.042* | |
C4 | 0.6237 (2) | 0.68397 (18) | 0.58082 (14) | 0.0361 (4) | |
H4 | 0.7103 | 0.7093 | 0.6345 | 0.043* | |
C5 | 0.48997 (18) | 0.74371 (17) | 0.60980 (14) | 0.0347 (4) | |
H5 | 0.5095 | 0.8397 | 0.6238 | 0.042* | |
C6 | 0.3310 (2) | 0.72023 (19) | 0.73529 (15) | 0.0409 (4) | |
H6 | 0.2498 | 0.6832 | 0.6823 | 0.049* | |
C7 | 0.3200 (3) | 0.6614 (3) | 0.8376 (2) | 0.0663 (7) | |
H7 | 0.3339 | 0.5637 | 0.8351 | 0.080* | |
C8 | 0.1736 (4) | 0.6866 (4) | 0.8611 (3) | 0.0887 (10) | |
H8A | 0.1574 | 0.7818 | 0.8639 | 0.133* | |
H8B | 0.1734 | 0.6466 | 0.9258 | 0.133* | |
H8C | 0.0973 | 0.6472 | 0.8083 | 0.133* | |
C9 | 0.1884 (2) | 0.9256 (2) | 0.68982 (15) | 0.0391 (4) | |
C10 | 0.1932 (2) | 1.0789 (2) | 0.68848 (16) | 0.0446 (4) | |
H10 | 0.2601 | 1.1095 | 0.6483 | 0.054* | |
C11 | 0.2323 (3) | 1.1447 (3) | 0.7932 (2) | 0.0736 (8) | |
H11A | 0.2874 | 1.2269 | 0.7923 | 0.088* | |
H11B | 0.2895 | 1.0842 | 0.8443 | 0.088* | |
C12 | 0.0854 (3) | 1.1751 (4) | 0.8153 (2) | 0.0746 (7) | |
H12 | 0.0454 | 1.0943 | 0.8399 | 0.090* | |
C13 | −0.0055 (3) | 1.2160 (4) | 0.7132 (2) | 0.0802 (9) | |
H13A | −0.1084 | 1.2037 | 0.7094 | 0.096* | |
H13B | 0.0114 | 1.3098 | 0.6996 | 0.096* | |
C14 | 0.0246 (3) | 1.1903 (4) | 0.5365 (2) | 0.0775 (8) | |
H14A | −0.0770 | 1.2047 | 0.5047 | 0.116* | |
H14B | 0.0653 | 1.1313 | 0.4946 | 0.116* | |
H14C | 0.0752 | 1.2750 | 0.5441 | 0.116* | |
C15 | 0.0937 (6) | 1.2941 (5) | 0.8915 (3) | 0.0791 (12) | 0.760 (6) |
H15A | 0.1644 | 1.3594 | 0.8805 | 0.095* | 0.760 (6) |
H15B | −0.0006 | 1.3383 | 0.8778 | 0.095* | 0.760 (6) |
C16 | 0.1359 (5) | 1.2494 (5) | 1.0010 (3) | 0.0819 (11) | 0.760 (6) |
H16A | 0.2279 | 1.2014 | 1.0135 | 0.098* | 0.760 (6) |
H16B | 0.0628 | 1.1869 | 1.0123 | 0.098* | 0.760 (6) |
C17 | 0.1513 (10) | 1.3634 (6) | 1.0773 (3) | 0.0920 (16) | 0.760 (6) |
H17A | 0.2311 | 1.4204 | 1.0720 | 0.138* | 0.760 (6) |
H17B | 0.1698 | 1.3272 | 1.1453 | 0.138* | 0.760 (6) |
H17C | 0.0628 | 1.4151 | 1.0629 | 0.138* | 0.760 (6) |
C151 | 0.0858 (16) | 1.2084 (12) | 0.9313 (9) | 0.078 (3) | 0.240 (6) |
H15C | −0.0124 | 1.2062 | 0.9408 | 0.094* | 0.240 (6) |
H15D | 0.1461 | 1.1448 | 0.9781 | 0.094* | 0.240 (6) |
C161 | 0.1486 (16) | 1.3478 (11) | 0.9475 (9) | 0.080 (3) | 0.240 (6) |
H16C | 0.0956 | 1.4055 | 0.8926 | 0.097* | 0.240 (6) |
H16D | 0.2495 | 1.3448 | 0.9438 | 0.097* | 0.240 (6) |
C171 | 0.142 (3) | 1.4093 (14) | 1.0491 (10) | 0.087 (4) | 0.240 (6) |
H17D | 0.0452 | 1.4412 | 1.0448 | 0.131* | 0.240 (6) |
H17E | 0.2097 | 1.4832 | 1.0649 | 0.131* | 0.240 (6) |
H17F | 0.1681 | 1.3424 | 1.1020 | 0.131* | 0.240 (6) |
C18 | 0.6901 (4) | 0.4069 (3) | 0.8801 (2) | 0.0722 (7) | |
H18A | 0.6057 | 0.4516 | 0.8916 | 0.108* | |
H18B | 0.7660 | 0.4056 | 0.9426 | 0.108* | |
H18C | 0.6650 | 0.3162 | 0.8579 | 0.108* | |
N1 | 0.31560 (19) | 0.86645 (17) | 0.73195 (13) | 0.0406 (4) | |
H1N | 0.394 (3) | 0.918 (2) | 0.7448 (16) | 0.061 (6)* | |
N2 | 0.04062 (19) | 1.12764 (19) | 0.63980 (15) | 0.0454 (4) | |
H2N | −0.008 (3) | 1.055 (3) | 0.630 (2) | 0.068 (7)* | |
O1 | 0.46370 (13) | 0.53521 (12) | 0.69777 (11) | 0.0389 (3) | |
O2 | 0.74418 (15) | 0.47869 (15) | 0.55603 (11) | 0.0446 (3) | |
H2O | 0.727 (3) | 0.400 (3) | 0.539 (2) | 0.069 (8)* | |
O3 | 0.63906 (16) | 0.74001 (14) | 0.48705 (11) | 0.0439 (3) | |
H3O | 0.574 (2) | 0.706 (3) | 0.4420 (16) | 0.066 (7)* | |
O4 | 0.36222 (15) | 0.73406 (15) | 0.52863 (11) | 0.0415 (3) | |
H4O | 0.343 (3) | 0.657 (3) | 0.520 (2) | 0.062 (8)* | |
O5 | 0.07332 (16) | 0.86606 (16) | 0.65446 (14) | 0.0571 (4) | |
S1 | 0.75350 (5) | 0.49602 (6) | 0.78280 (4) | 0.04994 (14) | |
Cl1 | 0.46173 (11) | 0.72733 (13) | 0.94037 (5) | 0.1044 (3) | |
Cl2 | 0.42970 (6) | 0.59125 (5) | 0.29038 (4) | 0.05418 (14) | |
O1W | 0.24161 (16) | 0.50065 (18) | 0.43547 (16) | 0.0594 (4) | |
H1W | 0.257 (5) | 0.511 (5) | 0.375 (2) | 0.089 (2)* | |
H2W | 0.262 (5) | 0.427 (3) | 0.473 (3) | 0.089 (15)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0383 (9) | 0.0259 (8) | 0.0456 (10) | 0.0037 (7) | 0.0162 (8) | −0.0022 (7) |
C2 | 0.0396 (9) | 0.0227 (8) | 0.0482 (10) | 0.0039 (7) | 0.0127 (7) | −0.0023 (7) |
C3 | 0.0348 (8) | 0.0273 (9) | 0.0452 (9) | 0.0027 (7) | 0.0128 (7) | −0.0040 (7) |
C4 | 0.0382 (9) | 0.0276 (8) | 0.0452 (10) | −0.0007 (7) | 0.0157 (8) | −0.0032 (7) |
C5 | 0.0378 (9) | 0.0212 (8) | 0.0465 (9) | 0.0026 (6) | 0.0134 (8) | −0.0025 (7) |
C6 | 0.0409 (10) | 0.0329 (10) | 0.0529 (10) | 0.0078 (8) | 0.0193 (8) | −0.0007 (8) |
C7 | 0.0793 (16) | 0.0557 (14) | 0.0796 (16) | 0.0196 (12) | 0.0492 (14) | 0.0146 (12) |
C8 | 0.100 (2) | 0.084 (2) | 0.111 (2) | 0.0205 (17) | 0.079 (2) | 0.0254 (18) |
C9 | 0.0372 (10) | 0.0385 (10) | 0.0445 (10) | 0.0058 (8) | 0.0156 (8) | −0.0044 (8) |
C10 | 0.0374 (9) | 0.0366 (10) | 0.0599 (12) | 0.0064 (8) | 0.0123 (9) | −0.0024 (9) |
C11 | 0.0613 (14) | 0.0560 (14) | 0.0898 (19) | 0.0174 (12) | −0.0063 (13) | −0.0306 (13) |
C12 | 0.0747 (17) | 0.0827 (19) | 0.0691 (16) | 0.0016 (15) | 0.0232 (13) | −0.0204 (14) |
C13 | 0.0599 (14) | 0.086 (2) | 0.0917 (19) | 0.0281 (15) | 0.0129 (13) | −0.0261 (16) |
C14 | 0.0527 (13) | 0.099 (2) | 0.0809 (17) | 0.0039 (14) | 0.0176 (12) | 0.0318 (17) |
C15 | 0.109 (3) | 0.067 (2) | 0.060 (2) | 0.029 (2) | 0.019 (2) | −0.0048 (19) |
C16 | 0.100 (3) | 0.081 (3) | 0.060 (2) | −0.003 (2) | 0.0128 (18) | −0.0035 (18) |
C17 | 0.120 (3) | 0.092 (4) | 0.061 (2) | 0.012 (3) | 0.017 (3) | −0.015 (2) |
C151 | 0.105 (5) | 0.071 (5) | 0.062 (5) | −0.004 (5) | 0.028 (4) | −0.005 (5) |
C161 | 0.104 (5) | 0.072 (5) | 0.062 (5) | 0.004 (5) | 0.015 (4) | −0.003 (4) |
C171 | 0.122 (6) | 0.083 (7) | 0.055 (6) | 0.006 (7) | 0.020 (6) | −0.012 (6) |
C18 | 0.094 (2) | 0.0692 (18) | 0.0524 (13) | 0.0163 (15) | 0.0173 (13) | 0.0111 (12) |
N1 | 0.0372 (8) | 0.0335 (8) | 0.0533 (9) | 0.0062 (7) | 0.0153 (7) | −0.0036 (7) |
N2 | 0.0357 (8) | 0.0389 (9) | 0.0633 (11) | 0.0073 (7) | 0.0159 (8) | 0.0058 (8) |
O1 | 0.0405 (6) | 0.0260 (6) | 0.0543 (7) | 0.0036 (5) | 0.0196 (6) | 0.0026 (5) |
O2 | 0.0431 (7) | 0.0328 (7) | 0.0623 (8) | 0.0029 (6) | 0.0217 (6) | −0.0101 (7) |
O3 | 0.0484 (8) | 0.0371 (7) | 0.0511 (8) | −0.0008 (6) | 0.0217 (7) | 0.0027 (6) |
O4 | 0.0438 (7) | 0.0296 (7) | 0.0496 (7) | 0.0057 (6) | 0.0087 (6) | 0.0020 (6) |
O5 | 0.0410 (8) | 0.0435 (8) | 0.0838 (10) | 0.0016 (6) | 0.0099 (7) | −0.0110 (8) |
S1 | 0.0473 (3) | 0.0488 (3) | 0.0500 (3) | 0.0105 (2) | 0.0053 (2) | 0.0029 (2) |
Cl1 | 0.1098 (6) | 0.1549 (9) | 0.0513 (3) | 0.0394 (6) | 0.0256 (4) | 0.0028 (5) |
Cl2 | 0.0579 (3) | 0.0430 (3) | 0.0619 (3) | 0.0056 (2) | 0.0157 (2) | 0.0045 (2) |
O1W | 0.0429 (7) | 0.0453 (9) | 0.0910 (13) | −0.0017 (7) | 0.0186 (8) | −0.0082 (9) |
Geometric parameters (Å, º) top
C1—O1 | 1.437 (2) | C12—H12 | 0.9800 |
C1—C5 | 1.518 (3) | C13—N2 | 1.470 (3) |
C1—C6 | 1.531 (2) | C13—H13A | 0.9700 |
C1—H1 | 0.9800 | C13—H13B | 0.9700 |
C2—O1 | 1.432 (2) | C14—N2 | 1.498 (3) |
C2—C3 | 1.527 (3) | C14—H14A | 0.9600 |
C2—S1 | 1.8167 (18) | C14—H14B | 0.9600 |
C2—H2 | 0.9800 | C14—H14C | 0.9600 |
C3—O2 | 1.415 (2) | C15—C16 | 1.497 (5) |
C3—C4 | 1.525 (2) | C15—H15A | 0.9700 |
C3—H3 | 0.9800 | C15—H15B | 0.9700 |
C4—O3 | 1.423 (2) | C16—C17 | 1.511 (5) |
C4—C5 | 1.535 (2) | C16—H16A | 0.9700 |
C4—H4 | 0.9800 | C16—H16B | 0.9700 |
C5—O4 | 1.416 (2) | C17—H17A | 0.9600 |
C5—H5 | 0.9800 | C17—H17B | 0.9600 |
C6—N1 | 1.458 (2) | C17—H17C | 0.9600 |
C6—C7 | 1.526 (3) | C151—C161 | 1.500 (6) |
C6—H6 | 0.9800 | C151—H15C | 0.9700 |
C7—C8 | 1.519 (4) | C151—H15D | 0.9700 |
C7—Cl1 | 1.793 (3) | C161—C171 | 1.515 (7) |
C7—H7 | 0.9800 | C161—H16C | 0.9700 |
C8—H8A | 0.9600 | C161—H16D | 0.9700 |
C8—H8B | 0.9600 | C171—H17D | 0.9600 |
C8—H8C | 0.9600 | C171—H17E | 0.9600 |
C9—O5 | 1.226 (3) | C171—H17F | 0.9600 |
C9—N1 | 1.331 (3) | C18—S1 | 1.807 (3) |
C9—C10 | 1.523 (3) | C18—H18A | 0.9600 |
C10—N2 | 1.507 (3) | C18—H18B | 0.9600 |
C10—C11 | 1.516 (3) | C18—H18C | 0.9600 |
C10—H10 | 0.9800 | N1—H1N | 0.88 (2) |
C11—C12 | 1.524 (4) | N2—H2N | 0.85 (3) |
C11—H11A | 0.9700 | O2—H2O | 0.82 (3) |
C11—H11B | 0.9700 | O3—H3O | 0.822 (17) |
C12—C13 | 1.485 (4) | O4—H4O | 0.78 (3) |
C12—C15 | 1.556 (5) | O1W—H1W | 0.870 (18) |
C12—C151 | 1.600 (10) | O1W—H2W | 0.888 (18) |
| | | |
O1—C1—C5 | 110.55 (15) | C13—C12—H12 | 110.8 |
O1—C1—C6 | 104.73 (14) | C11—C12—H12 | 110.8 |
C5—C1—C6 | 113.10 (15) | C15—C12—H12 | 110.8 |
O1—C1—H1 | 109.4 | C151—C12—H12 | 75.1 |
C5—C1—H1 | 109.4 | N2—C13—C12 | 105.1 (2) |
C6—C1—H1 | 109.4 | N2—C13—H13A | 110.7 |
O1—C2—C3 | 110.05 (14) | C12—C13—H13A | 110.7 |
O1—C2—S1 | 113.28 (12) | N2—C13—H13B | 110.7 |
C3—C2—S1 | 111.42 (12) | C12—C13—H13B | 110.7 |
O1—C2—H2 | 107.3 | H13A—C13—H13B | 108.8 |
C3—C2—H2 | 107.3 | N2—C14—H14A | 109.5 |
S1—C2—H2 | 107.3 | N2—C14—H14B | 109.5 |
O2—C3—C4 | 109.33 (15) | H14A—C14—H14B | 109.5 |
O2—C3—C2 | 112.44 (15) | N2—C14—H14C | 109.5 |
C4—C3—C2 | 110.32 (15) | H14A—C14—H14C | 109.5 |
O2—C3—H3 | 108.2 | H14B—C14—H14C | 109.5 |
C4—C3—H3 | 108.2 | C16—C15—C12 | 112.6 (3) |
C2—C3—H3 | 108.2 | C16—C15—H15A | 109.1 |
O3—C4—C3 | 112.36 (16) | C12—C15—H15A | 109.1 |
O3—C4—C5 | 110.58 (15) | C16—C15—H15B | 109.1 |
C3—C4—C5 | 110.86 (15) | C12—C15—H15B | 109.1 |
O3—C4—H4 | 107.6 | H15A—C15—H15B | 107.8 |
C3—C4—H4 | 107.6 | C15—C16—C17 | 114.0 (4) |
C5—C4—H4 | 107.6 | C15—C16—H16A | 108.8 |
O4—C5—C1 | 112.80 (14) | C17—C16—H16A | 108.8 |
O4—C5—C4 | 112.04 (14) | C15—C16—H16B | 108.8 |
C1—C5—C4 | 109.76 (14) | C17—C16—H16B | 108.8 |
O4—C5—H5 | 107.3 | H16A—C16—H16B | 107.7 |
C1—C5—H5 | 107.3 | C161—C151—C12 | 103.7 (8) |
C4—C5—H5 | 107.3 | C161—C151—H15C | 111.0 |
N1—C6—C7 | 112.33 (17) | C12—C151—H15C | 111.0 |
N1—C6—C1 | 110.08 (15) | C161—C151—H15D | 111.0 |
C7—C6—C1 | 112.25 (17) | C12—C151—H15D | 111.0 |
N1—C6—H6 | 107.3 | H15C—C151—H15D | 109.0 |
C7—C6—H6 | 107.3 | C151—C161—C171 | 113.5 (6) |
C1—C6—H6 | 107.3 | C151—C161—H16C | 108.9 |
C8—C7—C6 | 113.5 (2) | C171—C161—H16C | 108.9 |
C8—C7—Cl1 | 108.8 (2) | C151—C161—H16D | 108.9 |
C6—C7—Cl1 | 110.59 (18) | C171—C161—H16D | 108.9 |
C8—C7—H7 | 107.9 | H16C—C161—H16D | 107.7 |
C6—C7—H7 | 107.9 | C161—C171—H17D | 109.5 |
Cl1—C7—H7 | 107.9 | C161—C171—H17E | 109.5 |
C7—C8—H8A | 109.5 | H17D—C171—H17E | 109.5 |
C7—C8—H8B | 109.5 | C161—C171—H17F | 109.5 |
H8A—C8—H8B | 109.5 | H17D—C171—H17F | 109.5 |
C7—C8—H8C | 109.5 | H17E—C171—H17F | 109.5 |
H8A—C8—H8C | 109.5 | S1—C18—H18A | 109.5 |
H8B—C8—H8C | 109.5 | S1—C18—H18B | 109.5 |
O5—C9—N1 | 125.00 (19) | H18A—C18—H18B | 109.5 |
O5—C9—C10 | 120.19 (18) | S1—C18—H18C | 109.5 |
N1—C9—C10 | 114.81 (18) | H18A—C18—H18C | 109.5 |
N2—C10—C11 | 104.49 (17) | H18B—C18—H18C | 109.5 |
N2—C10—C9 | 107.34 (17) | C9—N1—C6 | 121.63 (18) |
C11—C10—C9 | 114.9 (2) | C9—N1—H1N | 117.1 (15) |
N2—C10—H10 | 110.0 | C6—N1—H1N | 119.9 (15) |
C11—C10—H10 | 110.0 | C13—N2—C14 | 113.7 (2) |
C9—C10—H10 | 110.0 | C13—N2—C10 | 108.21 (18) |
C10—C11—C12 | 104.3 (2) | C14—N2—C10 | 113.56 (17) |
C10—C11—H11A | 110.9 | C13—N2—H2N | 111.8 (17) |
C12—C11—H11A | 110.9 | C14—N2—H2N | 106.4 (18) |
C10—C11—H11B | 110.9 | C10—N2—H2N | 102.7 (18) |
C12—C11—H11B | 110.9 | C2—O1—C1 | 113.37 (13) |
H11A—C11—H11B | 108.9 | C3—O2—H2O | 107 (2) |
C13—C12—C11 | 102.5 (2) | C4—O3—H3O | 105.6 (18) |
C13—C12—C15 | 109.1 (3) | C5—O4—H4O | 108 (2) |
C11—C12—C15 | 112.5 (3) | C18—S1—C2 | 98.23 (12) |
C13—C12—C151 | 135.2 (6) | H1W—O1W—H2W | 125 (3) |
C11—C12—C151 | 117.1 (6) | | |
| | | |
O1—C2—C3—O2 | 177.86 (14) | C10—C11—C12—C13 | −37.7 (3) |
S1—C2—C3—O2 | 51.34 (17) | C10—C11—C12—C15 | −154.7 (3) |
O1—C2—C3—C4 | 55.52 (19) | C10—C11—C12—C151 | 164.0 (5) |
S1—C2—C3—C4 | −71.00 (16) | C11—C12—C13—N2 | 37.6 (3) |
O2—C3—C4—O3 | 58.7 (2) | C15—C12—C13—N2 | 157.0 (3) |
C2—C3—C4—O3 | −177.11 (14) | C151—C12—C13—N2 | −170.2 (6) |
O2—C3—C4—C5 | −176.96 (14) | C13—C12—C15—C16 | 159.8 (4) |
C2—C3—C4—C5 | −52.8 (2) | C11—C12—C15—C16 | −87.1 (5) |
O1—C1—C5—O4 | 69.97 (18) | C151—C12—C15—C16 | 18.5 (9) |
C6—C1—C5—O4 | −47.1 (2) | C12—C15—C16—C17 | 177.5 (5) |
O1—C1—C5—C4 | −55.74 (18) | C13—C12—C151—C161 | −75.7 (12) |
C6—C1—C5—C4 | −172.81 (15) | C11—C12—C151—C161 | 73.6 (11) |
O3—C4—C5—O4 | 51.98 (19) | C15—C12—C151—C161 | −18.8 (7) |
C3—C4—C5—O4 | −73.33 (19) | C12—C151—C161—C171 | 172.6 (14) |
O3—C4—C5—C1 | 178.11 (15) | O5—C9—N1—C6 | 3.2 (3) |
C3—C4—C5—C1 | 52.8 (2) | C10—C9—N1—C6 | −177.36 (17) |
O1—C1—C6—N1 | −171.00 (16) | C7—C6—N1—C9 | −97.0 (2) |
C5—C1—C6—N1 | −50.6 (2) | C1—C6—N1—C9 | 137.17 (18) |
O1—C1—C6—C7 | 63.1 (2) | C12—C13—N2—C14 | −150.6 (3) |
C5—C1—C6—C7 | −176.47 (18) | C12—C13—N2—C10 | −23.5 (3) |
N1—C6—C7—C8 | 62.0 (3) | C11—C10—N2—C13 | −0.4 (3) |
C1—C6—C7—C8 | −173.3 (2) | C9—C10—N2—C13 | 122.0 (2) |
N1—C6—C7—Cl1 | −60.7 (2) | C11—C10—N2—C14 | 126.8 (3) |
C1—C6—C7—Cl1 | 64.0 (2) | C9—C10—N2—C14 | −110.8 (2) |
O5—C9—C10—N2 | 0.3 (3) | C3—C2—O1—C1 | −60.68 (19) |
N1—C9—C10—N2 | −179.24 (16) | S1—C2—O1—C1 | 64.78 (18) |
O5—C9—C10—C11 | 116.0 (2) | C5—C1—O1—C2 | 61.28 (19) |
N1—C9—C10—C11 | −63.5 (2) | C6—C1—O1—C2 | −176.59 (14) |
N2—C10—C11—C12 | 23.4 (3) | O1—C2—S1—C18 | 60.84 (16) |
C9—C10—C11—C12 | −93.9 (3) | C3—C2—S1—C18 | −174.43 (14) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···Cl2i | 0.88 (2) | 2.53 (2) | 3.3540 (19) | 157.2 (19) |
N2—H2N···O1Wii | 0.85 (3) | 2.23 (3) | 2.897 (3) | 136 (2) |
N2—H2N···O5 | 0.85 (3) | 2.02 (3) | 2.616 (2) | 126 (2) |
O2—H2O···O4iii | 0.82 (3) | 1.97 (3) | 2.763 (2) | 164 (3) |
O3—H3O···Cl2 | 0.82 (2) | 2.44 (2) | 3.2403 (17) | 166 (2) |
O4—H4O···O1W | 0.78 (3) | 2.02 (3) | 2.744 (2) | 153 (3) |
O1W—H1W···Cl2 | 0.87 (2) | 2.36 (3) | 3.094 (2) | 142 (4) |
O1W—H2W···O3iii | 0.89 (2) | 2.08 (3) | 2.910 (2) | 155 (4) |
C5—H5···Cl2i | 0.98 | 2.75 | 3.712 (2) | 167 |
C14—H14B···O2i | 0.96 | 2.58 | 3.484 (4) | 158 |
C15—H15B···S1iv | 0.97 | 2.83 | 3.763 (5) | 162 |
Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) −x, y+1/2, −z+1; (iii) −x+1, y−1/2, −z+1; (iv) x−1, y+1, z. |
(II) (2
S,4
R)-2-(
N-{(1
S,2
S)-2-chloro-1-
[(3
R,4
S,5
R,6
R)-3,4,5-trihydroxy-6-
(methylsulfanyl)perhydropyran-2-yl]propyl}aminocarbonyl)-4-propylpyrrolidinium
chloride monohydrate ethanol solvate
top
Crystal data top
C18H34ClN2O5S+·Cl−·H2O·C2H6O | F(000) = 1128 |
Mr = 525.52 | Dx = 1.244 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 5339 reflections |
a = 9.9630 (16) Å | θ = 2.2–25.2° |
b = 10.6998 (17) Å | µ = 0.34 mm−1 |
c = 26.324 (4) Å | T = 294 K |
V = 2806.2 (8) Å3 | Plates, colourless |
Z = 4 | 0.13 × 0.11 × 0.05 mm |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 4748 reflections with I > 2σ(I) |
Radiation source: sealed tube | Rint = 0.027 |
Graphite monochromator | θmax = 25.0°, θmin = 1.6° |
ω scans | h = −11→11 |
27108 measured reflections | k = −12→12 |
4937 independent reflections | l = −31→31 |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.050 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.119 | w = 1/[σ2(Fo2) + (0.0537P)2 + 1.0157P] where P = (Fo2 + 2Fc2)/3 |
S = 1.18 | (Δ/σ)max < 0.001 |
4937 reflections | Δρmax = 0.45 e Å−3 |
364 parameters | Δρmin = −0.19 e Å−3 |
125 restraints | Absolute structure: Flack & Bernardinelli (1983), with XXXX Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.00 (7) |
Crystal data top
C18H34ClN2O5S+·Cl−·H2O·C2H6O | V = 2806.2 (8) Å3 |
Mr = 525.52 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 9.9630 (16) Å | µ = 0.34 mm−1 |
b = 10.6998 (17) Å | T = 294 K |
c = 26.324 (4) Å | 0.13 × 0.11 × 0.05 mm |
Data collection top
Bruker SMART APEX CCD area-detector diffractometer | 4748 reflections with I > 2σ(I) |
27108 measured reflections | Rint = 0.027 |
4937 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.050 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.119 | Δρmax = 0.45 e Å−3 |
S = 1.18 | Δρmin = −0.19 e Å−3 |
4937 reflections | Absolute structure: Flack & Bernardinelli (1983), with XXXX Friedel pairs |
364 parameters | Absolute structure parameter: 0.00 (7) |
125 restraints | |
Special details top
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell esds are taken
into account individually in the estimation of esds in distances, angles
and torsion angles; correlations between esds in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell esds is used for estimating esds involving l.s. planes. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
C1 | −0.0068 (3) | −0.1469 (3) | 0.10524 (11) | 0.0366 (6) | |
H1 | 0.0230 | −0.2073 | 0.1309 | 0.044* | |
C2 | −0.2203 (3) | −0.2497 (3) | 0.09578 (12) | 0.0447 (7) | |
H2 | −0.3161 | −0.2294 | 0.0943 | 0.054* | |
C3 | −0.1809 (3) | −0.3007 (3) | 0.04361 (12) | 0.0421 (7) | |
H3 | −0.2115 | −0.2420 | 0.0175 | 0.050* | |
C4 | −0.0298 (3) | −0.3137 (3) | 0.03970 (11) | 0.0413 (7) | |
H4 | 0.0001 | −0.3780 | 0.0637 | 0.050* | |
C5 | 0.0386 (3) | −0.1897 (3) | 0.05313 (10) | 0.0362 (6) | |
H5 | 0.1353 | −0.2060 | 0.0552 | 0.043* | |
C6 | 0.0427 (3) | −0.0163 (3) | 0.11971 (11) | 0.0362 (6) | |
H6 | −0.0071 | 0.0431 | 0.0985 | 0.043* | |
C7 | 0.0112 (3) | 0.0165 (3) | 0.17472 (12) | 0.0521 (8) | |
H7 | −0.0847 | 0.0020 | 0.1805 | 0.062* | |
C8 | 0.0419 (4) | 0.1511 (4) | 0.18828 (16) | 0.0739 (12) | |
H8A | 0.1361 | 0.1666 | 0.1839 | 0.111* | |
H8B | 0.0174 | 0.1662 | 0.2230 | 0.111* | |
H8C | −0.0084 | 0.2058 | 0.1665 | 0.111* | |
C9 | 0.2263 (3) | 0.0992 (2) | 0.08183 (11) | 0.0368 (6) | |
C10 | 0.3742 (3) | 0.0975 (3) | 0.06618 (12) | 0.0403 (6) | |
H10 | 0.3932 | 0.0216 | 0.0466 | 0.048* | |
C11 | 0.4740 (3) | 0.1088 (4) | 0.11017 (14) | 0.0597 (9) | |
H11A | 0.4315 | 0.0876 | 0.1422 | 0.072* | |
H11B | 0.5503 | 0.0540 | 0.1050 | 0.072* | |
C12 | 0.5178 (3) | 0.2451 (3) | 0.10987 (14) | 0.0565 (8) | |
H12 | 0.4482 | 0.2957 | 0.1263 | 0.068* | |
C13 | 0.5203 (3) | 0.2749 (3) | 0.05441 (14) | 0.0533 (8) | |
H13A | 0.6013 | 0.2430 | 0.0386 | 0.064* | |
H13B | 0.5155 | 0.3644 | 0.0489 | 0.064* | |
C14 | 0.4057 (3) | 0.1843 (3) | −0.02158 (12) | 0.0518 (8) | |
H14A | 0.4092 | 0.2616 | −0.0401 | 0.078* | |
H14B | 0.3277 | 0.1379 | −0.0318 | 0.078* | |
H14C | 0.4848 | 0.1362 | −0.0287 | 0.078* | |
C15 | 0.6524 (4) | 0.2703 (5) | 0.13607 (16) | 0.0813 (12) | |
H15A | 0.7188 | 0.2136 | 0.1221 | 0.098* | |
H15B | 0.6805 | 0.3547 | 0.1279 | 0.098* | |
C16 | 0.6518 (11) | 0.2559 (9) | 0.1929 (3) | 0.099 (2) | 0.709 (8) |
H16A | 0.7432 | 0.2641 | 0.2052 | 0.119* | 0.709 (8) |
H16B | 0.6214 | 0.1722 | 0.2012 | 0.119* | 0.709 (8) |
C17 | 0.5644 (11) | 0.3489 (12) | 0.2210 (4) | 0.122 (3) | 0.709 (8) |
H17A | 0.5740 | 0.3365 | 0.2569 | 0.183* | 0.709 (8) |
H17B | 0.4723 | 0.3368 | 0.2115 | 0.183* | 0.709 (8) |
H17C | 0.5916 | 0.4323 | 0.2124 | 0.183* | 0.709 (8) |
C161 | 0.663 (3) | 0.206 (2) | 0.1884 (7) | 0.095 (3) | 0.291 (8) |
H16C | 0.6395 | 0.1182 | 0.1851 | 0.114* | 0.291 (8) |
H16D | 0.7542 | 0.2113 | 0.2008 | 0.114* | 0.291 (8) |
C171 | 0.569 (2) | 0.268 (3) | 0.2259 (9) | 0.108 (4) | 0.291 (8) |
H17D | 0.5811 | 0.2319 | 0.2590 | 0.161* | 0.291 (8) |
H17E | 0.4776 | 0.2561 | 0.2152 | 0.161* | 0.291 (8) |
H17F | 0.5880 | 0.3560 | 0.2274 | 0.161* | 0.291 (8) |
C18 | −0.2795 (7) | −0.2858 (6) | 0.19514 (19) | 0.121 (2) | |
H18A | −0.2260 | −0.2148 | 0.2045 | 0.181* | |
H18B | −0.2895 | −0.3400 | 0.2240 | 0.181* | |
H18C | −0.3664 | −0.2581 | 0.1841 | 0.181* | |
N1 | 0.1844 (2) | −0.0006 (2) | 0.10731 (9) | 0.0365 (5) | |
H1N | 0.232 (3) | −0.060 (3) | 0.1134 (10) | 0.055 (7)* | |
N2 | 0.3984 (2) | 0.2109 (2) | 0.03358 (10) | 0.0419 (6) | |
H2N | 0.332 (2) | 0.258 (3) | 0.0393 (11) | 0.063 (9)* | |
O1 | −0.15067 (18) | −0.13643 (19) | 0.10683 (8) | 0.0410 (5) | |
O2 | −0.2394 (2) | −0.4187 (2) | 0.03415 (10) | 0.0563 (6) | |
H2O | −0.320 (2) | −0.404 (4) | 0.0228 (14) | 0.085 (13)* | |
O3 | 0.0063 (2) | −0.3507 (2) | −0.01022 (9) | 0.0531 (6) | |
H3O | 0.070 (4) | −0.397 (3) | −0.0075 (13) | 0.080 (11)* | |
O4 | 0.0195 (2) | −0.0974 (2) | 0.01531 (8) | 0.0434 (5) | |
H4O | −0.061 (2) | −0.071 (3) | 0.0118 (14) | 0.065 (11)* | |
O5 | 0.1569 (2) | 0.1880 (2) | 0.07070 (10) | 0.0566 (6) | |
S1 | −0.19946 (11) | −0.36814 (9) | 0.14507 (4) | 0.0695 (3) | |
Cl1 | 0.10480 (14) | −0.08464 (12) | 0.21702 (4) | 0.0833 (3) | |
Cl2 | 0.24523 (8) | −0.52857 (7) | 0.00714 (4) | 0.0637 (3) | |
C19 | −0.2848 (14) | −0.0397 (10) | −0.1987 (3) | 0.147 (3) | 0.709 (8) |
H19A | −0.3207 | 0.0173 | −0.2234 | 0.221* | 0.709 (8) |
H19B | −0.3312 | −0.1181 | −0.2010 | 0.221* | 0.709 (8) |
H19C | −0.1910 | −0.0524 | −0.2051 | 0.221* | 0.709 (8) |
C20 | −0.3026 (11) | 0.0123 (8) | −0.1480 (3) | 0.125 (3) | 0.709 (8) |
H20A | −0.2667 | 0.0965 | −0.1462 | 0.150* | 0.709 (8) |
H20B | −0.3969 | 0.0144 | −0.1389 | 0.150* | 0.709 (8) |
O6 | −0.2297 (10) | −0.0699 (9) | −0.1153 (3) | 0.135 (3) | 0.709 (8) |
H6A | −0.2413 | −0.0489 | −0.0856 | 0.203* | 0.709 (8) |
C191 | −0.313 (3) | 0.046 (2) | −0.1873 (10) | 0.143 (4) | 0.291 (8) |
H19D | −0.4077 | 0.0616 | −0.1841 | 0.214* | 0.291 (8) |
H19E | −0.2915 | 0.0319 | −0.2224 | 0.214* | 0.291 (8) |
H19F | −0.2643 | 0.1179 | −0.1752 | 0.214* | 0.291 (8) |
C201 | −0.276 (3) | −0.0634 (19) | −0.1573 (10) | 0.138 (3) | 0.291 (8) |
H20C | −0.3532 | −0.0911 | −0.1377 | 0.166* | 0.291 (8) |
H20D | −0.2499 | −0.1308 | −0.1798 | 0.166* | 0.291 (8) |
O61 | −0.169 (2) | −0.0347 (19) | −0.1238 (8) | 0.121 (4) | 0.291 (8) |
H6B | −0.1977 | −0.0254 | −0.0949 | 0.181* | 0.291 (8) |
O1W | −0.1143 (3) | −0.3016 (3) | −0.10692 (12) | 0.0701 (7) | |
H1W | −0.089 (4) | −0.303 (4) | −0.0761 (9) | 0.105 (12)* | |
H2W | −0.133 (5) | −0.224 (3) | −0.1162 (19) | 0.105 (18)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0247 (13) | 0.0382 (14) | 0.0468 (15) | 0.0004 (11) | −0.0032 (12) | 0.0061 (12) |
C2 | 0.0233 (14) | 0.0499 (17) | 0.0610 (19) | −0.0052 (12) | −0.0027 (12) | 0.0028 (14) |
C3 | 0.0306 (15) | 0.0381 (14) | 0.0574 (18) | −0.0009 (12) | −0.0107 (13) | 0.0004 (13) |
C4 | 0.0308 (14) | 0.0420 (15) | 0.0510 (17) | 0.0072 (12) | −0.0056 (13) | −0.0030 (13) |
C5 | 0.0203 (13) | 0.0450 (16) | 0.0434 (15) | −0.0007 (11) | −0.0037 (11) | −0.0006 (13) |
C6 | 0.0279 (13) | 0.0355 (14) | 0.0453 (15) | −0.0021 (11) | 0.0002 (11) | 0.0059 (12) |
C7 | 0.0443 (17) | 0.0545 (18) | 0.0575 (18) | −0.0084 (15) | 0.0051 (15) | −0.0077 (16) |
C8 | 0.076 (3) | 0.067 (2) | 0.078 (3) | −0.007 (2) | 0.011 (2) | −0.031 (2) |
C9 | 0.0314 (15) | 0.0327 (14) | 0.0462 (15) | 0.0003 (12) | −0.0023 (11) | 0.0000 (12) |
C10 | 0.0305 (14) | 0.0330 (14) | 0.0573 (17) | −0.0004 (11) | 0.0009 (12) | 0.0045 (13) |
C11 | 0.0335 (16) | 0.071 (2) | 0.074 (2) | −0.0087 (16) | −0.0066 (16) | 0.0197 (19) |
C12 | 0.0358 (16) | 0.064 (2) | 0.070 (2) | −0.0051 (16) | 0.0000 (16) | −0.0068 (17) |
C13 | 0.0387 (16) | 0.0376 (16) | 0.084 (2) | −0.0083 (13) | 0.0003 (16) | 0.0031 (16) |
C14 | 0.0431 (17) | 0.0518 (18) | 0.061 (2) | 0.0039 (15) | 0.0046 (15) | 0.0097 (15) |
C15 | 0.051 (2) | 0.111 (3) | 0.082 (3) | −0.021 (2) | −0.0106 (19) | −0.016 (3) |
C16 | 0.065 (4) | 0.141 (6) | 0.090 (4) | −0.023 (5) | −0.016 (3) | −0.024 (4) |
C17 | 0.100 (5) | 0.169 (8) | 0.097 (5) | −0.022 (7) | −0.003 (4) | −0.023 (6) |
C161 | 0.059 (5) | 0.136 (8) | 0.091 (6) | −0.016 (7) | −0.015 (5) | −0.024 (6) |
C171 | 0.079 (6) | 0.150 (8) | 0.094 (6) | −0.015 (8) | −0.009 (5) | −0.020 (7) |
C18 | 0.135 (5) | 0.158 (5) | 0.070 (3) | 0.003 (5) | 0.024 (3) | 0.015 (3) |
N1 | 0.0277 (12) | 0.0314 (12) | 0.0504 (14) | 0.0020 (10) | −0.0031 (10) | 0.0019 (11) |
N2 | 0.0301 (12) | 0.0338 (12) | 0.0619 (15) | −0.0006 (11) | 0.0037 (12) | 0.0035 (11) |
O1 | 0.0245 (9) | 0.0428 (10) | 0.0556 (11) | −0.0007 (8) | 0.0032 (8) | −0.0032 (9) |
O2 | 0.0378 (12) | 0.0461 (11) | 0.0848 (16) | 0.0000 (10) | −0.0199 (12) | −0.0093 (12) |
O3 | 0.0397 (12) | 0.0591 (13) | 0.0603 (14) | 0.0133 (11) | −0.0084 (11) | −0.0177 (11) |
O4 | 0.0309 (10) | 0.0517 (12) | 0.0478 (11) | 0.0038 (9) | 0.0043 (9) | 0.0081 (10) |
O5 | 0.0321 (11) | 0.0429 (12) | 0.0947 (17) | 0.0085 (10) | 0.0092 (11) | 0.0197 (12) |
S1 | 0.0670 (6) | 0.0635 (5) | 0.0780 (6) | −0.0195 (5) | 0.0064 (5) | 0.0195 (5) |
Cl1 | 0.1103 (9) | 0.0914 (7) | 0.0480 (5) | −0.0012 (7) | −0.0112 (5) | 0.0074 (5) |
Cl2 | 0.0366 (4) | 0.0415 (4) | 0.1129 (8) | −0.0002 (3) | 0.0096 (5) | 0.0166 (4) |
C19 | 0.202 (7) | 0.128 (6) | 0.113 (5) | 0.001 (6) | −0.035 (6) | 0.003 (5) |
C20 | 0.171 (6) | 0.097 (5) | 0.108 (4) | 0.004 (5) | −0.028 (5) | 0.009 (4) |
O6 | 0.186 (7) | 0.119 (5) | 0.100 (4) | 0.045 (5) | −0.026 (5) | 0.017 (3) |
C191 | 0.192 (8) | 0.116 (7) | 0.120 (7) | 0.008 (7) | −0.032 (7) | 0.009 (7) |
C201 | 0.185 (7) | 0.117 (6) | 0.113 (5) | 0.010 (6) | −0.025 (6) | 0.010 (6) |
O61 | 0.162 (8) | 0.093 (7) | 0.107 (6) | 0.000 (6) | −0.026 (6) | 0.019 (5) |
O1W | 0.0680 (18) | 0.0633 (17) | 0.079 (2) | −0.0137 (14) | −0.0106 (15) | 0.0138 (15) |
Geometric parameters (Å, º) top
C1—O1 | 1.438 (3) | C15—C16 | 1.504 (9) |
C1—C5 | 1.515 (4) | C15—C161 | 1.544 (17) |
C1—C6 | 1.531 (4) | C15—H15A | 0.9700 |
C1—H1 | 0.9800 | C15—H15B | 0.9700 |
C2—O1 | 1.427 (4) | C16—C17 | 1.515 (9) |
C2—C3 | 1.529 (4) | C16—H16A | 0.9700 |
C2—S1 | 1.825 (3) | C16—H16B | 0.9700 |
C2—H2 | 0.9800 | C17—H17A | 0.9600 |
C3—O2 | 1.413 (4) | C17—H17B | 0.9600 |
C3—C4 | 1.515 (4) | C17—H17C | 0.9600 |
C3—H3 | 0.9800 | C161—C171 | 1.515 (9) |
C4—O3 | 1.419 (4) | C161—H16C | 0.9700 |
C4—C5 | 1.533 (4) | C161—H16D | 0.9700 |
C4—H4 | 0.9800 | C171—H17D | 0.9600 |
C5—O4 | 1.415 (3) | C171—H17E | 0.9600 |
C5—H5 | 0.9800 | C171—H17F | 0.9600 |
C6—N1 | 1.459 (4) | C18—S1 | 1.775 (6) |
C6—C7 | 1.523 (4) | C18—H18A | 0.9600 |
C6—H6 | 0.9800 | C18—H18B | 0.9600 |
C7—C8 | 1.515 (5) | C18—H18C | 0.9600 |
C7—Cl1 | 1.811 (4) | N1—H1N | 0.81 (3) |
C7—H7 | 0.9800 | N2—H2N | 0.843 (18) |
C8—H8A | 0.9600 | O2—H2O | 0.868 (19) |
C8—H8B | 0.9600 | O3—H3O | 0.81 (4) |
C8—H8C | 0.9600 | O4—H4O | 0.852 (19) |
C9—O5 | 1.211 (3) | C19—C20 | 1.456 (10) |
C9—N1 | 1.329 (4) | C19—H19A | 0.9600 |
C9—C10 | 1.530 (4) | C19—H19B | 0.9600 |
C10—N2 | 1.506 (4) | C19—H19C | 0.9600 |
C10—C11 | 1.531 (4) | C20—O6 | 1.430 (9) |
C10—H10 | 0.9800 | C20—H20A | 0.9700 |
C11—C12 | 1.522 (5) | C20—H20B | 0.9700 |
C11—H11A | 0.9700 | O6—H6A | 0.8200 |
C11—H11B | 0.9700 | C191—C201 | 1.463 (14) |
C12—C13 | 1.495 (5) | C191—H19D | 0.9600 |
C12—C15 | 1.532 (5) | C191—H19E | 0.9600 |
C12—H12 | 0.9800 | C191—H19F | 0.9600 |
C13—N2 | 1.498 (4) | C201—O61 | 1.421 (14) |
C13—H13A | 0.9700 | C201—H20C | 0.9700 |
C13—H13B | 0.9700 | C201—H20D | 0.9700 |
C14—N2 | 1.481 (4) | O61—H6B | 0.8200 |
C14—H14A | 0.9600 | O1W—H1W | 0.850 (19) |
C14—H14B | 0.9600 | O1W—H2W | 0.89 (2) |
C14—H14C | 0.9600 | | |
| | | |
O1—C1—C5 | 110.4 (2) | C16—C15—C12 | 115.2 (5) |
O1—C1—C6 | 104.0 (2) | C12—C15—C161 | 112.4 (11) |
C5—C1—C6 | 113.9 (2) | C16—C15—H15A | 108.5 |
O1—C1—H1 | 109.5 | C12—C15—H15A | 108.5 |
C5—C1—H1 | 109.5 | C161—C15—H15A | 90.8 |
C6—C1—H1 | 109.5 | C16—C15—H15B | 108.5 |
O1—C2—C3 | 111.2 (2) | C12—C15—H15B | 108.5 |
O1—C2—S1 | 112.9 (2) | C161—C15—H15B | 126.5 |
C3—C2—S1 | 111.2 (2) | H15A—C15—H15B | 107.5 |
O1—C2—H2 | 107.1 | C15—C16—C17 | 114.9 (8) |
C3—C2—H2 | 107.1 | C15—C16—H16A | 108.5 |
S1—C2—H2 | 107.1 | C17—C16—H16A | 108.5 |
O2—C3—C4 | 108.4 (2) | C15—C16—H16B | 108.5 |
O2—C3—C2 | 111.8 (3) | C17—C16—H16B | 108.5 |
C4—C3—C2 | 110.4 (2) | H16A—C16—H16B | 107.5 |
O2—C3—H3 | 108.7 | C16—C17—H17A | 109.5 |
C4—C3—H3 | 108.7 | C16—C17—H17B | 109.5 |
C2—C3—H3 | 108.7 | H17A—C17—H17B | 109.5 |
O3—C4—C3 | 109.9 (2) | C16—C17—H17C | 109.5 |
O3—C4—C5 | 110.0 (2) | H17A—C17—H17C | 109.5 |
C3—C4—C5 | 110.3 (2) | H17B—C17—H17C | 109.5 |
O3—C4—H4 | 108.9 | C171—C161—C15 | 110.1 (17) |
C3—C4—H4 | 108.9 | C171—C161—H16C | 109.6 |
C5—C4—H4 | 108.9 | C15—C161—H16C | 109.6 |
O4—C5—C1 | 112.7 (2) | C171—C161—H16D | 109.6 |
O4—C5—C4 | 112.4 (2) | C15—C161—H16D | 109.6 |
C1—C5—C4 | 109.7 (2) | H16C—C161—H16D | 108.1 |
O4—C5—H5 | 107.2 | C161—C171—H17D | 109.5 |
C1—C5—H5 | 107.2 | C161—C171—H17E | 109.5 |
C4—C5—H5 | 107.2 | H17D—C171—H17E | 109.5 |
N1—C6—C7 | 112.7 (2) | C161—C171—H17F | 109.5 |
N1—C6—C1 | 111.2 (2) | H17D—C171—H17F | 109.5 |
C7—C6—C1 | 112.4 (2) | H17E—C171—H17F | 109.5 |
N1—C6—H6 | 106.7 | S1—C18—H18A | 109.5 |
C7—C6—H6 | 106.7 | S1—C18—H18B | 109.5 |
C1—C6—H6 | 106.7 | H18A—C18—H18B | 109.5 |
C8—C7—C6 | 113.7 (3) | S1—C18—H18C | 109.5 |
C8—C7—Cl1 | 108.6 (3) | H18A—C18—H18C | 109.5 |
C6—C7—Cl1 | 109.9 (2) | H18B—C18—H18C | 109.5 |
C8—C7—H7 | 108.1 | C9—N1—C6 | 120.7 (2) |
C6—C7—H7 | 108.1 | C9—N1—H1N | 123 (2) |
Cl1—C7—H7 | 108.1 | C6—N1—H1N | 115 (2) |
C7—C8—H8A | 109.5 | C14—N2—C13 | 114.0 (3) |
C7—C8—H8B | 109.5 | C14—N2—C10 | 114.3 (2) |
H8A—C8—H8B | 109.5 | C13—N2—C10 | 106.8 (2) |
C7—C8—H8C | 109.5 | C14—N2—H2N | 109 (2) |
H8A—C8—H8C | 109.5 | C13—N2—H2N | 107 (2) |
H8B—C8—H8C | 109.5 | C10—N2—H2N | 105 (2) |
O5—C9—N1 | 124.9 (3) | C2—O1—C1 | 114.3 (2) |
O5—C9—C10 | 119.6 (3) | C3—O2—H2O | 106 (3) |
N1—C9—C10 | 115.4 (2) | C4—O3—H3O | 107 (3) |
N2—C10—C9 | 107.3 (2) | C5—O4—H4O | 116 (3) |
N2—C10—C11 | 105.3 (2) | C18—S1—C2 | 97.6 (2) |
C9—C10—C11 | 114.9 (3) | C20—C19—H19A | 109.5 |
N2—C10—H10 | 109.7 | C20—C19—H19B | 109.5 |
C9—C10—H10 | 109.7 | H19A—C19—H19B | 109.5 |
C11—C10—H10 | 109.7 | C20—C19—H19C | 109.5 |
C12—C11—C10 | 104.9 (3) | H19A—C19—H19C | 109.5 |
C12—C11—H11A | 110.8 | H19B—C19—H19C | 109.5 |
C10—C11—H11A | 110.8 | O6—C20—C19 | 104.8 (8) |
C12—C11—H11B | 110.8 | O6—C20—H20A | 110.8 |
C10—C11—H11B | 110.8 | C19—C20—H20A | 110.8 |
H11A—C11—H11B | 108.8 | O6—C20—H20B | 110.8 |
C13—C12—C11 | 102.4 (3) | C19—C20—H20B | 110.8 |
C13—C12—C15 | 112.8 (3) | H20A—C20—H20B | 108.9 |
C11—C12—C15 | 114.6 (3) | C20—O6—H6A | 109.5 |
C13—C12—H12 | 108.9 | C201—C191—H19D | 109.5 |
C11—C12—H12 | 108.9 | C201—C191—H19E | 109.5 |
C15—C12—H12 | 108.9 | H19D—C191—H19E | 109.5 |
C12—C13—N2 | 104.3 (3) | C201—C191—H19F | 109.5 |
C12—C13—H13A | 110.9 | H19D—C191—H19F | 109.5 |
N2—C13—H13A | 110.9 | H19E—C191—H19F | 109.5 |
C12—C13—H13B | 110.9 | O61—C201—C191 | 110.5 (19) |
N2—C13—H13B | 110.9 | O61—C201—H20C | 109.5 |
H13A—C13—H13B | 108.9 | C191—C201—H20C | 109.5 |
N2—C14—H14A | 109.5 | O61—C201—H20D | 109.5 |
N2—C14—H14B | 109.5 | C191—C201—H20D | 109.5 |
H14A—C14—H14B | 109.5 | H20C—C201—H20D | 108.1 |
N2—C14—H14C | 109.5 | C201—O61—H6B | 109.5 |
H14A—C14—H14C | 109.5 | H1W—O1W—H2W | 110 (4) |
H14B—C14—H14C | 109.5 | | |
| | | |
O1—C2—C3—O2 | 174.5 (2) | C9—C10—C11—C12 | −100.3 (3) |
S1—C2—C3—O2 | 47.7 (3) | C10—C11—C12—C13 | −35.7 (3) |
O1—C2—C3—C4 | 53.7 (3) | C10—C11—C12—C15 | −158.2 (3) |
S1—C2—C3—C4 | −73.1 (3) | C11—C12—C13—N2 | 40.4 (3) |
O2—C3—C4—O3 | 62.3 (3) | C15—C12—C13—N2 | 164.1 (3) |
C2—C3—C4—O3 | −175.0 (2) | C13—C12—C15—C16 | 173.4 (5) |
O2—C3—C4—C5 | −176.3 (2) | C11—C12—C15—C16 | −70.0 (6) |
C2—C3—C4—C5 | −53.5 (3) | C13—C12—C15—C161 | −163.7 (10) |
O1—C1—C5—O4 | 69.5 (3) | C11—C12—C15—C161 | −47.1 (10) |
C6—C1—C5—O4 | −47.0 (3) | C12—C15—C16—C17 | −64.9 (9) |
O1—C1—C5—C4 | −56.6 (3) | C161—C15—C16—C17 | −152 (4) |
C6—C1—C5—C4 | −173.1 (2) | C16—C15—C161—C171 | 33 (3) |
O3—C4—C5—O4 | 50.4 (3) | C12—C15—C161—C171 | −69.6 (19) |
C3—C4—C5—O4 | −71.0 (3) | O5—C9—N1—C6 | 6.4 (4) |
O3—C4—C5—C1 | 176.7 (2) | C10—C9—N1—C6 | −173.5 (2) |
C3—C4—C5—C1 | 55.3 (3) | C7—C6—N1—C9 | −101.9 (3) |
O1—C1—C6—N1 | −165.1 (2) | C1—C6—N1—C9 | 131.0 (3) |
C5—C1—C6—N1 | −45.0 (3) | C12—C13—N2—C14 | −157.3 (3) |
O1—C1—C6—C7 | 67.5 (3) | C12—C13—N2—C10 | −30.1 (3) |
C5—C1—C6—C7 | −172.3 (2) | C9—C10—N2—C14 | −102.7 (3) |
N1—C6—C7—C8 | 61.2 (4) | C11—C10—N2—C14 | 134.5 (3) |
C1—C6—C7—C8 | −172.2 (3) | C9—C10—N2—C13 | 130.2 (3) |
N1—C6—C7—Cl1 | −60.8 (3) | C11—C10—N2—C13 | 7.4 (3) |
C1—C6—C7—Cl1 | 65.7 (3) | C3—C2—O1—C1 | −57.3 (3) |
O5—C9—C10—N2 | −5.6 (4) | S1—C2—O1—C1 | 68.5 (3) |
N1—C9—C10—N2 | 174.4 (2) | C5—C1—O1—C2 | 59.1 (3) |
O5—C9—C10—C11 | 111.1 (3) | C6—C1—O1—C2 | −178.4 (2) |
N1—C9—C10—C11 | −68.9 (3) | O1—C2—S1—C18 | 63.6 (3) |
N2—C10—C11—C12 | 17.5 (3) | C3—C2—S1—C18 | −170.6 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O1Wi | 0.81 (3) | 2.14 (3) | 2.917 (4) | 161 (3) |
N2—H2N···Cl2ii | 0.84 (2) | 2.59 (2) | 3.253 (3) | 137 (3) |
O2—H2O···O4iii | 0.87 (2) | 1.89 (2) | 2.738 (3) | 165 (4) |
O3—H3O···Cl2 | 0.81 (4) | 2.28 (4) | 3.082 (3) | 175 (3) |
O4—H4O···Cl2iii | 0.85 (2) | 2.26 (2) | 3.104 (2) | 169 (4) |
O6—H6A···Cl2iii | 0.82 | 2.23 | 3.046 (9) | 173 |
O61—H6B···Cl2iii | 0.82 | 2.45 | 3.26 (3) | 170 |
O1W—H1W···O3 | 0.85 (2) | 2.04 (2) | 2.863 (4) | 163 (4) |
O1W—H2W···O6 | 0.89 (2) | 1.91 (3) | 2.741 (9) | 156 (5) |
O1W—H2W···O61 | 0.89 (2) | 2.07 (3) | 2.94 (2) | 169 (5) |
C10—H10···O3i | 0.98 | 2.35 | 3.298 (4) | 162 |
C14—H14B···O2i | 0.96 | 2.44 | 3.206 (4) | 137 |
Symmetry codes: (i) x+1/2, −y−1/2, −z; (ii) x, y+1, z; (iii) x−1/2, −y−1/2, −z. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C18H34ClN2O5S+·Cl−·H2O | C18H34ClN2O5S+·Cl−·H2O·C2H6O |
Mr | 479.45 | 525.52 |
Crystal system, space group | Monoclinic, P21 | Orthorhombic, P212121 |
Temperature (K) | 294 | 294 |
a, b, c (Å) | 9.4669 (6), 9.9255 (6), 13.4949 (8) | 9.9630 (16), 10.6998 (17), 26.324 (4) |
α, β, γ (°) | 90, 104.601 (1), 90 | 90, 90, 90 |
V (Å3) | 1227.08 (13) | 2806.2 (8) |
Z | 2 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.38 | 0.34 |
Crystal size (mm) | 0.15 × 0.10 × 0.06 | 0.13 × 0.11 × 0.05 |
|
Data collection |
Diffractometer | Bruker SMART APEX CCD area-detector diffractometer | Bruker SMART APEX CCD area-detector diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 11796, 4321, 4211 | 27108, 4937, 4748 |
Rint | 0.016 | 0.027 |
(sin θ/λ)max (Å−1) | 0.595 | 0.595 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.031, 0.084, 1.05 | 0.050, 0.119, 1.18 |
No. of reflections | 4321 | 4937 |
No. of parameters | 323 | 364 |
No. of restraints | 68 | 125 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.26, −0.20 | 0.45, −0.19 |
Absolute structure | Flack & Bernardinelli (1983), with XXXX Friedel pairs | Flack & Bernardinelli (1983), with XXXX Friedel pairs |
Absolute structure parameter | 0.02 (5) | 0.00 (7) |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···Cl2i | 0.88 (2) | 2.53 (2) | 3.3540 (19) | 157.2 (19) |
N2—H2N···O1Wii | 0.85 (3) | 2.23 (3) | 2.897 (3) | 136 (2) |
N2—H2N···O5 | 0.85 (3) | 2.02 (3) | 2.616 (2) | 126 (2) |
O2—H2O···O4iii | 0.82 (3) | 1.97 (3) | 2.763 (2) | 164 (3) |
O3—H3O···Cl2 | 0.822 (17) | 2.436 (18) | 3.2403 (17) | 166 (2) |
O4—H4O···O1W | 0.78 (3) | 2.02 (3) | 2.744 (2) | 153 (3) |
O1W—H1W···Cl2 | 0.870 (18) | 2.36 (3) | 3.094 (2) | 142 (4) |
O1W—H2W···O3iii | 0.888 (18) | 2.08 (3) | 2.910 (2) | 155 (4) |
C5—H5···Cl2i | 0.98 | 2.75 | 3.712 (2) | 167 |
C14—H14B···O2i | 0.96 | 2.58 | 3.484 (4) | 158 |
C15—H15B···S1iv | 0.97 | 2.83 | 3.763 (5) | 162 |
Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) −x, y+1/2, −z+1; (iii) −x+1, y−1/2, −z+1; (iv) x−1, y+1, z. |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O1Wi | 0.81 (3) | 2.14 (3) | 2.917 (4) | 161 (3) |
N2—H2N···Cl2ii | 0.843 (18) | 2.59 (2) | 3.253 (3) | 137 (3) |
O2—H2O···O4iii | 0.868 (19) | 1.89 (2) | 2.738 (3) | 165 (4) |
O3—H3O···Cl2 | 0.81 (4) | 2.28 (4) | 3.082 (3) | 175 (3) |
O4—H4O···Cl2iii | 0.852 (19) | 2.26 (2) | 3.104 (2) | 169 (4) |
O6—H6A···Cl2iii | 0.82 | 2.23 | 3.046 (9) | 172.6 |
O61—H6B···Cl2iii | 0.82 | 2.45 | 3.26 (3) | 170.3 |
O1W—H1W···O3 | 0.850 (19) | 2.04 (2) | 2.863 (4) | 163 (4) |
O1W—H2W···O6 | 0.89 (2) | 1.91 (3) | 2.741 (9) | 156 (5) |
O1W—H2W···O61 | 0.89 (2) | 2.07 (3) | 2.94 (2) | 169 (5) |
C10—H10···O3i | 0.98 | 2.35 | 3.298 (4) | 162 |
C14—H14B···O2i | 0.96 | 2.44 | 3.206 (4) | 137 |
Symmetry codes: (i) x+1/2, −y−1/2, −z; (ii) x, y+1, z; (iii) x−1/2, −y−1/2, −z. |
Clindamycin is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoan diseases, such as malaria. It is a common topical treatment for acne, and can be useful against some methicillin-resistant Staphylococcus aureus (MRSA) infections (Daun, 2007). Clindamycin is also used in veterinary medications. It is marketed under various trade names, including Dalacin, Clindacin, Cleocin, and Evovlin (clindamycin by itself), Duac, BenzaClin and Arcanya (in combination with benzoyl peroxide), and Ziana (with tretinoin). Clindamycin is a semisynthetic derivative of lincomycin, a natural antibiotic produced by the actinobacterium Streptomyces lincolnensis. It is obtained by 7(S)-chloro-substitution of the 7(R)-hydroxyl group of lincomycin. We report here the crystal structures of clindamycin hydrochloride monohydrate, (I), and its ethanol solvate, (II), as a part of our ongoing studies of the structural characterization of drug molecules.
The clindamycin molecule consists of a derivative of the amino acid trans-L-4-n-propyl-hygrinic acid joined to a sulfur-containing octose derivative. Views of the molecules of (I) and (II), showing the atom-labelling, are presented in Fig. 1(a) and (b). The bond distances and angles in (I) and (II) are in the normal ranges (Allen et al., 1987) and are comparable with the corresponding values observed in lincomycin hydrochloride (Rajeswaran & Srikrishnan, 2004) and clindamycin 2-phosphate hydrate (Leban et al., 1994). An earlier initial study of clindamycin hydrochloride monohydrate in which only the unit-cell dimensions were reported [a = 9.47 Å, b = 9.91 Å, c = 13.50 Å, β = 104.5° and V = 1226.589 Å3, monoclinic space group P21; Cambridge Structural Database (CSD; Allen, 2002) refcode DECLMY (Duchamp, 1967)], is similar to (I).
In both (I) and (II), the propyl side chain is disordered; in (I), atoms C15/C16/C17 are disordered over two sites with occupancies of 0.760 (6) and 0.240 (6), and in (II), atoms C16/C17 are disordered over two sites with occupancies of 0.709 (8) and 0.291 (8). Additionally, the ethanoll solvent molecule (atoms C19/C20/O6) in (II) is disordered over two sites with occupancies of 0.709 (8) and 0.291 (8).
The central amide linkage plays an active role in the solid-state conformation and governs the overall shape of the clindamycin molecule in (I) and (II). It is planar and in an extended conformation (Fig. 2). Atom N2 of the terminal pyrrolidine ring is protonated to form the pyrrolidinium cation in both (I) and (II). Fig. 2 shows an overlay of the clindamycin molecules of (I) and (II) with the extracted clindamycin ligand from the crystal structure of the complex of clindamycin bound to the G2099A mutant 50S ribosomal subunit of Haloarcula marismortul [Tu et al., 2005; Protein Data Bank (PDB; Berman et al., 2000) entry 1YJN], clindamycin 2-phosphate hydrate and lincomycin. It can be seen that the clindamycin molecules prefer to adopt the same configuration and similar conformations in spite of having significant sites for drug activation.
In structures of both (I) and (II), the pyranoside ring is of the galactopyranose stereochemistry with a 4C1 chair form, with configuration 1a2e3e4a5e (a = axial and e = equatorial), where 1,2,3,4 and 5 represent atoms C2, C3, C4, C5 and C1, respectively. A similar conformation has been observed in the structures of lincomycin hydrochloride and clindamycin 2-phosphate hydrate.
The pyrrolidinium ring in both structures is in an envelope conformation with C12 being the flip atom. The flip angle of the envelope, defined as the dihedral angle between the planes of atoms N2/C10/C11/C13 and C11/C12/C13, is 38.0 (2)° in (I) and 38.7 (2)° in (II). On the other hand, even though the pyrrolidine ring is in an envelope conformation in the structures of lincomycin hydrochloride, clindamycin 2-phosphate hydrate and 1YJN, it is observed that the atom corresponding to C13 occupies the flip position. The sum of the bond angles around the pyrrolidinium N2 atom (ΣN2) is 335.5 (2)° in (I) and 335.1 (2)° in (II) and this atom tends to be coplanar with the central carboxamide plane [deviation of N2 = 0.001 (2) Å in (I) and 0.182 (3) Å in (II)]. We believe that this tendency towards coplanarity of atom N2 may be related to the antibacterial activity, since N2 bears a positive charge facilitating binding at the active site. The corresponding deviations of N2 found in lincomycin hydrochloride, clindamycin 2-phosphate hydrate and 1YJN are 0.173, 0.068/0.802/0.087 (three molecules in the asymmetric unit) and 0.035 Å, respectively.
The crystal packing in (I) and (II) is influenced by the presence of the free Cl- ion and the single water molecule, which appears to be crucial for crystal formation. As observed in the crystal structures of small-molecule hydrates (Jeffrey & Saenger, 1991), the water molecule in (I) is four-coordinated, with each molecule acting as a donor in two hydrogen bonds and an acceptor in two (Table 1). Thus, the water molecules and the free Cl2- ions connect the three moieties (pyrrolidinium, amide and pyranoside) of the clindamycin molecules and form an intricate three-dimensional intermolecular hydrogen-bond network (Fig.3). The presence of an additional ethanol molecule in (II) supports the water molecule in hydrogen bonding (Table 2). The water molecule of (II) is three-coordinated, with each molecule acting as a donor to two hydrogen bonds and an acceptor to just one. Similarly, the ethanol molecule also acts as a donor and an acceptor. Thus, the water molecules, mediated by the ethanol molecules and free Cl2- ions, connect the three moieties of the clindamycin molecules to form a complex three-dimensional intermolecular hydrogen-bond network (Fig. 4). It is interesting to note that the pyranoside atom O1, the bonded atom Cl1 and the carboxamide atom O5 (excluding its intramolecular hydrogen bonding) do not participate in the hydrogen-bonding network in either structure. This may provide some insight into the nature of drug-binding interactions at the enzyme active site. In (I), non-classical C—H···O, C—H···Cl and C—H···S interactions are observed, while in (II) only a C—H···O interaction is observed.
In conclusion, this structural analysis can facilitate in understanding the solid-state features of the drug and its hydrogen-bonding interactions in the hydrated and solvated environments.