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The structural analysis of deacetylcephalothin [systematic name: (6
R,7
R)-3-hydroxymethyl-8-oxo-7-(2-thiophen-2-ylacetylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid], C
14H
14N
2O
5S
2, shows that the geometry of the central bicyclic moiety is close to the geometry exhibited by other biologically active cephalosporin antibiotics. The molecules are arranged in a helical chain running parallel to the 2
1 axis
via a strong O—H
O hydrogen bond. The main helices are zipped together
via N—H
O interactions, forming infinite layers. The supramolecular architecture is stabilized by O—H
S and C—H
O hydrogen bonds.
Supporting information
CCDC reference: 290566
The preparation method and properties of DACT were reported previously by Zimniak et al. (1998). Single crystals of DACT were obtained from anhydrous EtOH.
Since the absorption coefficient was comparatively low, no absorption correction was applied. The thiophene ring was found to be disordered over two positions related by rotation about the C10—C11 bond, with site-occupancy factors of 0.626 (4) and 0.374 (4) for the major and minor components, respectively. The alternative atoms C11 and C11B were fixed at the same sites with identical displacement parameters. The positions of H atoms attached to N and O atoms were refined freely but their isotropic displacement parameters were fixed to 1.2 and 1.5 times Ueq of the parent atom, respectively. The remaining H atoms were positioned geometrically and refined using a riding model, with Uiso(H) = 1.2 or 1.3Ueq(C). The absolute structure was established based on anomalous dispersion (1279 Friedel pairs) using Flack's parameter x (Flack, 1983; Flack & Bernardinelli, 1999, 2000).
Data collection: P3/P4-PC Diffractometer Program (Siemens, 1991); cell refinement: P3/P4-PC Diffractometer Program; data reduction: XDISK (Siemens, 1991); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996; Farrugia, 1997); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).
(6
R,7
R)-3-hydroxymethyl-8-oxo-7-(2-thiophen-2-ylacetylamino) −5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid]
top
Crystal data top
C14H14N2O5S2 | F(000) = 368 |
Mr = 354.36 | Dx = 1.469 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 30 reflections |
a = 9.6992 (18) Å | θ = 12–35° |
b = 6.4069 (12) Å | µ = 0.36 mm−1 |
c = 12.919 (2) Å | T = 293 K |
β = 93.974 (14)° | Prism, colourless |
V = 800.9 (2) Å3 | 0.35 × 0.25 × 0.20 mm |
Z = 2 | |
Data collection top
Siemens P3 diffractometer | Rint = 0.034 |
Radiation source: fine-focus sealed tube | θmax = 25.0°, θmin = 2.1° |
Graphite monochromator | h = −11→11 |
profile data from ω/2θ scans | k = −7→7 |
3986 measured reflections | l = −15→15 |
2834 independent reflections | 2 standard reflections every 70 reflections |
2623 reflections with I > 2σ(I) | intensity decay: 4.8% |
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)] = 0.038 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.090 | w = 1/[σ2(Fo2) + (0.0457P)2 + 0.2079P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max < 0.001 |
2834 reflections | Δρmax = 0.18 e Å−3 |
254 parameters | Δρmin = −0.18 e Å−3 |
101 restraints | Absolute structure: Flack (1983), with 1279 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.02 (9) |
Crystal data top
C14H14N2O5S2 | V = 800.9 (2) Å3 |
Mr = 354.36 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 9.6992 (18) Å | µ = 0.36 mm−1 |
b = 6.4069 (12) Å | T = 293 K |
c = 12.919 (2) Å | 0.35 × 0.25 × 0.20 mm |
β = 93.974 (14)° | |
Data collection top
Siemens P3 diffractometer | Rint = 0.034 |
3986 measured reflections | 2 standard reflections every 70 reflections |
2834 independent reflections | intensity decay: 4.8% |
2623 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.038 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.090 | Δρmax = 0.18 e Å−3 |
S = 1.08 | Δρmin = −0.18 e Å−3 |
2834 reflections | Absolute structure: Flack (1983), with 1279 Friedel pairs |
254 parameters | Absolute structure parameter: −0.02 (9) |
101 restraints | |
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. The final INS file consists the following commands used for the disorder modeling:.. FVAR 0.74006 0.62590.. EXYZ C11 C11B EADP C11 C11B SIMU 0.01 C12 > C14B PART 1 C11 1 0.248025 0.535527 0.048752 21.00000 0.04728 0.06776 = 0.03732 0.00464 0.01135 − 0.01780 S2 5 0.187420 0.399948 − 0.056591 21.00000 0.06606 0.09550 = 0.05519 − 0.01974 − 0.00492 − 0.01144 C12 1 0.321358 0.223034 − 0.038721 21.00000 0.07422 0.08112 = 0.05731 − 0.00069 0.01855 0.00386 AFIX 43 H12 2 0.331184 0.109531 − 0.082476 21.00000 − 1.20000 AFIX 0 C13 1 0.409962 0.262301 0.043170 21.00000 0.07112 0.08522 = 0.05287 0.00329 0.00702 0.00212 AFIX 43 H13 2 0.487275 0.183635 0.064720 21.00000 − 1.20000 AFIX 0 C14 1 0.362088 0.452475 0.092339 21.00000 0.07120 0.09576 = 0.05398 0.00910 0.00259 0.00420 AFIX 43 H14 2 0.409082 0.510841 0.150511 21.00000 − 1.20000 AFIX 0 PART 2 SAME 0.01 0.01 C11 > C14 C11B 1 0.248025 0.535527 0.048752 − 21.00000 0.04728 0.06776 = 0.03732 0.00464 0.01135 − 0.01780 S2B 5 0.380840 0.429973 0.119799 − 21.00000 0.06099 0.08744 = 0.05530 0.01098 0.00766 0.01385 C12B 1 0.390183 0.230218 0.029443 − 21.00000 0.07166 0.08192 = 0.05190 − 0.00032 0.01524 0.00246 AFIX 43 H12B 2 0.452711 0.120532 0.038175 − 21.00000 − 1.20000 AFIX 0 C13B 1 0.300204 0.246551 − 0.053861 − 21.00000 0.07040 0.08684 = 0.05072 − 0.00687 0.01591 − 0.00218 AFIX 43 H13B 2 0.291940 0.156371 − 0.110360 − 21.00000 − 1.20000 AFIX 0 C14B 1 0.217613 0.433737 − 0.038580 − 21.00000 0.07083 0.08563 = 0.05678 − 0.00125 0.00919 − 0.01386 AFIX 43 H14B 2 0.148441 0.477886 − 0.087109 − 21.00000 − 1.20000 PART 0 |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
S1 | 0.34512 (6) | 0.42171 (10) | 0.39715 (5) | 0.03643 (17) | |
O1 | 0.5993 (2) | 0.4588 (3) | 0.70333 (18) | 0.0502 (6) | |
H1O | 0.616 (4) | 0.584 (7) | 0.687 (3) | 0.075* | |
O2 | 0.3286 (2) | 0.8445 (5) | 0.7476 (2) | 0.0753 (8) | |
O3 | 0.1076 (2) | 0.7683 (4) | 0.70668 (17) | 0.0507 (6) | |
H3O | 0.073 (4) | 0.856 (7) | 0.748 (3) | 0.076* | |
O4 | 0.1383 (2) | 0.9813 (3) | 0.48534 (17) | 0.0437 (5) | |
O5 | −0.0068 (2) | 0.5487 (4) | 0.17060 (16) | 0.0589 (7) | |
N1 | 0.1820 (2) | 0.6264 (3) | 0.52097 (18) | 0.0318 (5) | |
N2 | 0.1509 (2) | 0.7267 (4) | 0.27214 (18) | 0.0365 (5) | |
H2N | 0.223 (3) | 0.787 (5) | 0.274 (2) | 0.044* | |
C1 | 0.4577 (3) | 0.4143 (6) | 0.7132 (2) | 0.0461 (7) | |
H1A | 0.4249 | 0.4966 | 0.7695 | 0.060* | |
H1B | 0.4477 | 0.2681 | 0.7308 | 0.060* | |
C2 | 0.3705 (2) | 0.4607 (4) | 0.6154 (2) | 0.0348 (6) | |
C3 | 0.3997 (3) | 0.3232 (5) | 0.5248 (2) | 0.0411 (6) | |
H3A | 0.3549 | 0.1897 | 0.5338 | 0.053* | |
H3B | 0.4984 | 0.2979 | 0.5271 | 0.053* | |
C4 | 0.1724 (3) | 0.4853 (4) | 0.4323 (2) | 0.0314 (6) | |
H4 | 0.1139 | 0.3630 | 0.4418 | 0.041* | |
C5 | 0.2702 (3) | 0.6060 (4) | 0.6110 (2) | 0.0325 (6) | |
C6 | 0.2409 (3) | 0.7540 (5) | 0.6961 (2) | 0.0396 (7) | |
C7 | 0.1386 (2) | 0.7990 (4) | 0.4636 (2) | 0.0311 (6) | |
C8 | 0.0983 (3) | 0.6634 (4) | 0.3685 (2) | 0.0329 (6) | |
H8 | −0.0018 | 0.6405 | 0.3608 | 0.043* | |
C9 | 0.0966 (3) | 0.6594 (5) | 0.1809 (2) | 0.0407 (7) | |
C10 | 0.1737 (3) | 0.7210 (6) | 0.0870 (2) | 0.0525 (8) | |
H10A | 0.1089 | 0.7732 | 0.0325 | 0.068* | |
H10B | 0.2393 | 0.8311 | 0.1058 | 0.068* | |
C11 | 0.2480 (3) | 0.5355 (6) | 0.0488 (2) | 0.0504 (8) | 0.626 (4) |
S2 | 0.1874 (3) | 0.3999 (5) | −0.0566 (2) | 0.0727 (8) | 0.626 (4) |
C12 | 0.3214 (16) | 0.223 (2) | −0.0387 (10) | 0.070 (2) | 0.626 (4) |
H12 | 0.3312 | 0.1095 | −0.0825 | 0.084* | 0.626 (4) |
C13 | 0.4100 (15) | 0.262 (2) | 0.0432 (10) | 0.070 (2) | 0.626 (4) |
H13 | 0.4873 | 0.1836 | 0.0647 | 0.084* | 0.626 (4) |
C14 | 0.3621 (14) | 0.452 (3) | 0.0923 (9) | 0.074 (3) | 0.626 (4) |
H14 | 0.4091 | 0.5108 | 0.1505 | 0.088* | 0.626 (4) |
C11B | 0.2480 (3) | 0.5355 (6) | 0.0488 (2) | 0.0504 (8) | 0.374 (4) |
S2B | 0.3808 (6) | 0.4300 (10) | 0.1198 (3) | 0.0677 (11) | 0.374 (4) |
C12B | 0.390 (2) | 0.230 (3) | 0.0294 (15) | 0.068 (3) | 0.374 (4) |
H12B | 0.4527 | 0.1205 | 0.0382 | 0.082* | 0.374 (4) |
C13B | 0.300 (3) | 0.247 (4) | −0.0539 (15) | 0.069 (3) | 0.374 (4) |
H13B | 0.2919 | 0.1564 | −0.1104 | 0.083* | 0.374 (4) |
C14B | 0.2176 (18) | 0.434 (3) | −0.0386 (12) | 0.071 (3) | 0.374 (4) |
H14B | 0.1484 | 0.4779 | −0.0871 | 0.085* | 0.374 (4) |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.0332 (3) | 0.0313 (3) | 0.0456 (3) | 0.0019 (3) | 0.0093 (3) | −0.0051 (3) |
O1 | 0.0355 (10) | 0.0390 (13) | 0.0746 (14) | 0.0064 (9) | −0.0067 (9) | 0.0086 (11) |
O2 | 0.0499 (13) | 0.094 (2) | 0.0802 (17) | 0.0075 (13) | −0.0043 (12) | −0.0445 (16) |
O3 | 0.0378 (11) | 0.0636 (15) | 0.0512 (13) | 0.0176 (10) | 0.0072 (9) | −0.0119 (11) |
O4 | 0.0472 (11) | 0.0259 (11) | 0.0587 (12) | 0.0033 (8) | 0.0080 (10) | 0.0006 (9) |
O5 | 0.0539 (13) | 0.0796 (17) | 0.0425 (12) | −0.0323 (12) | −0.0012 (10) | 0.0130 (11) |
N1 | 0.0270 (10) | 0.0277 (11) | 0.0408 (12) | 0.0053 (9) | 0.0038 (9) | −0.0028 (10) |
N2 | 0.0265 (11) | 0.0404 (13) | 0.0430 (13) | −0.0067 (10) | 0.0059 (10) | 0.0047 (11) |
C1 | 0.0392 (14) | 0.0505 (16) | 0.0489 (15) | 0.0119 (16) | 0.0043 (12) | 0.0085 (17) |
C2 | 0.0283 (12) | 0.0329 (16) | 0.0439 (14) | 0.0031 (10) | 0.0083 (10) | 0.0048 (12) |
C3 | 0.0357 (14) | 0.0327 (14) | 0.0548 (17) | 0.0075 (12) | 0.0021 (12) | −0.0001 (13) |
C4 | 0.0283 (12) | 0.0254 (13) | 0.0410 (14) | −0.0011 (10) | 0.0050 (10) | −0.0027 (11) |
C5 | 0.0269 (13) | 0.0309 (14) | 0.0401 (14) | 0.0014 (11) | 0.0060 (11) | 0.0006 (12) |
C6 | 0.0357 (15) | 0.0418 (16) | 0.0413 (16) | 0.0074 (13) | 0.0012 (12) | −0.0026 (13) |
C7 | 0.0200 (12) | 0.0295 (15) | 0.0444 (15) | 0.0005 (10) | 0.0063 (10) | 0.0025 (12) |
C8 | 0.0291 (13) | 0.0318 (14) | 0.0383 (14) | −0.0037 (11) | 0.0058 (11) | 0.0017 (12) |
C9 | 0.0347 (15) | 0.0457 (17) | 0.0416 (16) | −0.0066 (13) | 0.0022 (12) | 0.0106 (13) |
C10 | 0.0539 (19) | 0.060 (2) | 0.0447 (18) | −0.0158 (16) | 0.0084 (14) | 0.0123 (16) |
C11 | 0.0473 (17) | 0.068 (2) | 0.0373 (15) | −0.0178 (15) | 0.0114 (13) | 0.0046 (15) |
S2 | 0.0661 (13) | 0.0955 (17) | 0.0552 (11) | −0.0114 (12) | −0.0049 (8) | −0.0197 (11) |
C12 | 0.074 (5) | 0.081 (4) | 0.057 (4) | 0.004 (3) | 0.019 (4) | −0.001 (4) |
C13 | 0.071 (4) | 0.085 (4) | 0.053 (4) | 0.002 (4) | 0.007 (3) | 0.003 (3) |
C14 | 0.071 (4) | 0.096 (5) | 0.054 (5) | 0.004 (4) | 0.003 (4) | 0.009 (4) |
C11B | 0.0473 (17) | 0.068 (2) | 0.0373 (15) | −0.0178 (15) | 0.0114 (13) | 0.0046 (15) |
S2B | 0.0610 (19) | 0.087 (2) | 0.055 (2) | 0.0139 (18) | 0.0077 (15) | 0.011 (2) |
C12B | 0.072 (5) | 0.082 (5) | 0.052 (5) | 0.002 (5) | 0.015 (5) | 0.000 (4) |
C13B | 0.070 (6) | 0.087 (5) | 0.051 (5) | −0.002 (4) | 0.016 (5) | −0.007 (5) |
C14B | 0.071 (6) | 0.086 (6) | 0.057 (6) | −0.014 (5) | 0.009 (5) | −0.001 (5) |
Geometric parameters (Å, º) top
S1—C3 | 1.810 (3) | C4—H4 | 0.9800 |
S1—C4 | 1.813 (3) | C5—C6 | 1.494 (4) |
O1—C1 | 1.417 (3) | C7—C8 | 1.533 (4) |
O1—H1O | 0.85 (5) | C8—H8 | 0.9800 |
O2—C6 | 1.193 (4) | C9—C10 | 1.521 (4) |
O3—C6 | 1.312 (3) | C10—C11 | 1.491 (5) |
O3—H3O | 0.85 (4) | C10—H10A | 0.9700 |
O4—C7 | 1.201 (3) | C10—H10B | 0.9700 |
O5—C9 | 1.228 (3) | C11—C14 | 1.318 (12) |
N1—C7 | 1.381 (3) | C11—S2 | 1.686 (4) |
N1—C5 | 1.402 (3) | S2—C12 | 1.727 (11) |
N1—C4 | 1.457 (3) | C12—C13 | 1.340 (8) |
N2—C9 | 1.329 (4) | C12—H12 | 0.9300 |
N2—C8 | 1.437 (4) | C13—C14 | 1.464 (18) |
N2—H2N | 0.80 (3) | C13—H13 | 0.9300 |
C1—C2 | 1.501 (4) | C14—H14 | 0.9300 |
C1—H1A | 0.9700 | S2B—C12B | 1.739 (14) |
C1—H1B | 0.9700 | C12B—C13B | 1.342 (9) |
C2—C5 | 1.344 (4) | C12B—H12B | 0.9300 |
C2—C3 | 1.508 (4) | C13B—C14B | 1.46 (2) |
C3—H3A | 0.9700 | C13B—H13B | 0.9300 |
C3—H3B | 0.9700 | C14B—H14B | 0.9300 |
C4—C8 | 1.554 (4) | | |
| | | |
C3—S1—C4 | 93.86 (12) | O4—C7—C8 | 137.2 (3) |
C1—O1—H1O | 115 (3) | N1—C7—C8 | 91.6 (2) |
C6—O3—H3O | 123 (3) | N2—C8—C7 | 116.6 (2) |
C7—N1—C5 | 131.8 (2) | N2—C8—C4 | 119.2 (2) |
C7—N1—C4 | 94.3 (2) | C7—C8—C4 | 84.77 (19) |
C5—N1—C4 | 126.7 (2) | N2—C8—H8 | 111.3 |
C9—N2—C8 | 122.3 (2) | C7—C8—H8 | 111.3 |
C9—N2—H2N | 119 (2) | C4—C8—H8 | 111.3 |
C8—N2—H2N | 118 (2) | O5—C9—N2 | 123.7 (3) |
O1—C1—C2 | 112.2 (2) | O5—C9—C10 | 120.4 (3) |
O1—C1—H1A | 109.2 | N2—C9—C10 | 115.9 (2) |
C2—C1—H1A | 109.2 | C11—C10—C9 | 109.5 (3) |
O1—C1—H1B | 109.2 | C11—C10—H10A | 109.8 |
C2—C1—H1B | 109.2 | C9—C10—H10A | 109.8 |
H1A—C1—H1B | 107.9 | C11—C10—H10B | 109.8 |
C5—C2—C1 | 122.5 (3) | C9—C10—H10B | 109.8 |
C5—C2—C3 | 123.1 (2) | H10A—C10—H10B | 108.2 |
C1—C2—C3 | 114.4 (2) | C14—C11—C10 | 126.2 (7) |
C2—C3—S1 | 116.4 (2) | C14—C11—S2 | 111.9 (6) |
C2—C3—H3A | 108.2 | C10—C11—S2 | 121.9 (3) |
S1—C3—H3A | 108.2 | C11—S2—C12 | 90.8 (5) |
C2—C3—H3B | 108.2 | C13—C12—S2 | 114.7 (13) |
S1—C3—H3B | 108.2 | C13—C12—H12 | 122.7 |
H3A—C3—H3B | 107.3 | S2—C12—H12 | 122.7 |
N1—C4—C8 | 87.91 (19) | C12—C13—C14 | 107.1 (13) |
N1—C4—S1 | 109.03 (17) | C12—C13—H13 | 126.5 |
C8—C4—S1 | 115.72 (18) | C14—C13—H13 | 126.5 |
N1—C4—H4 | 113.8 | C11—C14—C13 | 115.6 (11) |
C8—C4—H4 | 113.8 | C11—C14—H14 | 122.2 |
S1—C4—H4 | 113.8 | C13—C14—H14 | 122.2 |
C2—C5—N1 | 119.8 (2) | C13B—C12B—S2B | 114.8 (15) |
C2—C5—C6 | 125.6 (2) | C13B—C12B—H12B | 122.6 |
N1—C5—C6 | 114.5 (2) | S2B—C12B—H12B | 122.6 |
O2—C6—O3 | 125.3 (3) | C12B—C13B—C14B | 106.7 (15) |
O2—C6—C5 | 123.6 (3) | C12B—C13B—H13B | 126.6 |
O3—C6—C5 | 111.1 (2) | C14B—C13B—H13B | 126.6 |
O4—C7—N1 | 131.2 (3) | C13B—C14B—H14B | 122.3 |
| | | |
O1—C1—C2—C5 | −117.2 (3) | C9—N2—C8—C7 | −161.9 (2) |
O1—C1—C2—C3 | 66.0 (4) | C9—N2—C8—C4 | 98.7 (3) |
C5—C2—C3—S1 | 23.6 (4) | O4—C7—C8—N2 | 49.6 (4) |
C1—C2—C3—S1 | −159.6 (2) | N1—C7—C8—N2 | −129.2 (2) |
C4—S1—C3—C2 | −49.3 (2) | O4—C7—C8—C4 | 169.7 (3) |
C7—N1—C4—C8 | −9.60 (19) | N1—C7—C8—C4 | −9.13 (18) |
C5—N1—C4—C8 | −162.3 (2) | N1—C4—C8—N2 | 126.3 (2) |
C7—N1—C4—S1 | 106.94 (18) | S1—C4—C8—N2 | 16.2 (3) |
C5—N1—C4—S1 | −45.7 (3) | N1—C4—C8—C7 | 8.65 (17) |
C3—S1—C4—N1 | 56.49 (19) | S1—C4—C8—C7 | −101.50 (19) |
C3—S1—C4—C8 | 153.6 (2) | C8—N2—C9—O5 | 4.4 (5) |
C1—C2—C5—N1 | −172.9 (3) | C8—N2—C9—C10 | −173.4 (3) |
C3—C2—C5—N1 | 3.7 (4) | O5—C9—C10—C11 | −71.8 (4) |
C1—C2—C5—C6 | 6.7 (4) | N2—C9—C10—C11 | 106.1 (3) |
C3—C2—C5—C6 | −176.7 (3) | C9—C10—C11—C14 | −74.9 (9) |
C7—N1—C5—C2 | −132.7 (3) | C9—C10—C11—S2 | 102.4 (3) |
C4—N1—C5—C2 | 9.4 (4) | C14—C11—S2—C12 | 0.8 (11) |
C7—N1—C5—C6 | 47.7 (4) | C10—C11—S2—C12 | −176.8 (7) |
C4—N1—C5—C6 | −170.2 (2) | C11—S2—C12—C13 | −0.2 (14) |
C2—C5—C6—O2 | 43.0 (5) | S2—C12—C13—C14 | −0.4 (18) |
N1—C5—C6—O2 | −137.4 (3) | C10—C11—C14—C13 | 176.3 (9) |
C2—C5—C6—O3 | −136.4 (3) | S2—C11—C14—C13 | −1.2 (15) |
N1—C5—C6—O3 | 43.2 (3) | C12—C13—C14—C11 | 1.1 (19) |
C5—N1—C7—O4 | −18.8 (5) | S2B—C12B—C13B—C14B | −2 (3) |
C4—N1—C7—O4 | −169.2 (3) | O4—N1—C5—C6 | 40.1 (3) |
C5—N1—C7—C8 | 160.1 (3) | C4—C8—N1—C7 | 166.9 (3) |
C4—N1—C7—C8 | 9.73 (19) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3O···O5i | 0.86 (4) | 1.77 (4) | 2.629 (3) | 177 (4) |
N2—H2N···O1ii | 0.80 (3) | 2.05 (3) | 2.841 (3) | 172 (2) |
O1—H1O···S1ii | 0.85 (4) | 2.46 (4) | 3.297 (2) | 168 (4) |
C3—H3A···O4iii | 0.97 | 2.53 | 3.362 (4) | 144 |
C4—H4···O4iii | 0.98 | 2.52 | 3.322 (3) | 139 |
C1—H1A···O2 | 0.97 | 2.43 | 3.072 (5) | 124 |
Symmetry codes: (i) −x, y+1/2, −z+1; (ii) −x+1, y+1/2, −z+1; (iii) x, y−1, z. |
Experimental details
Crystal data |
Chemical formula | C14H14N2O5S2 |
Mr | 354.36 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 293 |
a, b, c (Å) | 9.6992 (18), 6.4069 (12), 12.919 (2) |
β (°) | 93.974 (14) |
V (Å3) | 800.9 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.36 |
Crystal size (mm) | 0.35 × 0.25 × 0.20 |
|
Data collection |
Diffractometer | Siemens P3 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3986, 2834, 2623 |
Rint | 0.034 |
(sin θ/λ)max (Å−1) | 0.595 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.038, 0.090, 1.08 |
No. of reflections | 2834 |
No. of parameters | 254 |
No. of restraints | 101 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.18, −0.18 |
Absolute structure | Flack (1983), with 1279 Friedel pairs |
Absolute structure parameter | −0.02 (9) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3O···O5i | 0.86 (4) | 1.77 (4) | 2.629 (3) | 177 (4) |
N2—H2N···O1ii | 0.80 (3) | 2.05 (3) | 2.841 (3) | 172 (2) |
O1—H1O···S1ii | 0.85 (4) | 2.46 (4) | 3.297 (2) | 168 (4) |
C3—H3A···O4iii | 0.97 | 2.53 | 3.362 (4) | 144 |
C4—H4···O4iii | 0.98 | 2.52 | 3.322 (3) | 139 |
C1—H1A···O2 | 0.97 | 2.43 | 3.072 (5) | 124 |
Symmetry codes: (i) −x, y+1/2, −z+1; (ii) −x+1, y+1/2, −z+1; (iii) x, y−1, z. |
Selected geometric parameters for DACT and the mean values for other cephalosporins retrieved from the CSD (Å,°) top | DACT | mean CSDa |
S1—C3 | 1.810 (3) | 1.82 (2) |
S1—C4 | 1.813 (3) | 1.797 (7) |
O4—C7 | 1.201 (3) | 1.208 (9) |
N1—C4 | 1.457 (3) | 1.47 (1) |
N1—C5 | 1.402 (3) | 1.41 (1) |
N1—C7 | 1.381 (3) | 1.37 (2) |
C2—C5 | 1.344 (4) | 1.34 (1) |
C3—S1—C4 | 93.86 (12) | 94 (2) |
S1—C4—C8 | 115.72 (18) | 116 (1) |
C4—N1—C5 | 126.7 (2) | 126 (1) |
C4—N1—C7 | 94.3 (2) | 95.0 (9) |
C5—N1—C7 | 131.8 (2) | 133 (2) |
C3—S1—C4—N1 | 56.49 (19) | 55 (4) |
C4—C8—N1—C7 | 166.9 (3) | 172 (4) |
(a) Based on data for 27 structures with an R-factor below 0.075 (36 Δ3-cephem fragments) (CSD, version 5.26, August 2005; Allen, 2002). |
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The cephalosporins are widely used broad-spectrum antibiotics, exhibiting antibacterial activity against both Gram-positive and Gram-negative bacteria (Dollery, 1999). In humans and animals, after parenteral administration of cephalothin [systematic name: (6R,7R)-3-acetoxymethyl-8-oxo-7-(2-thiophen-2-ylacetylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid], the metabolite deacetylcephalothin, DACT, (I), is formed (Katzung, 2001). Microbiological tests showed that DACT exhibits lower activity than the parent drug (Lee et al., 1963). In general, the decrease of biological activity was attributed to the blocking of the carboxyl substituent (Flynn, 1972). On the basis of NMR and IR studies, it was proposed that, in solution, the O1—H hydroxyl group in DACT can form an intramolecular hydrogen bond with the O2 carbonyl atom and in this manner protect the COOH group (Zimniak et al., 1998). In order to elucidate the nature of the hydrogen bonds in DACT in the solid state, this crystallographic study has been performed. The structure of the sodium salt of cephalothin was determined by van Meerssche et al. (1979).
The asymmetric unit of the title compound contains one DACT molecule, confirmed as the (R,R) isomer (Fig. 1). The analysis of the bicyclic [4.2.0] ring shows that the dihydrothiazine six-membered ring displays an envelope conformation, with atom S1 lying 0.9027 (6) Å out of the plane defined by the remaining atoms of the ring, and the C3—S1—C4—N1 torsion angle being 56.5 (2)°. The β-lactam four-membered ring is folded along the C8—N1 line, and the C4—C8—N1—C7 torsion angle is 166.9 (3)°. The geometry of the Δ3-cephem core (cephem is 5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-8-one) in DACT was compared with that observed for other structurally characterized active cephalosporins derived from the Cambridge Structural Database (CSD, Version 5.26, August 2005; Allen, 2002). It was found that the overall geometry and conformation of the Δ3-cephem core in DACT are close to those in retrieved structures (Table 1).
Some geometric parameters were found to correlate with the antimicrobial activity of cephalosporins. The most commonly reported are the pyramidality of atom N1 (Woodward, 1980), the distance between atom C6 of the carboxyl group and the β-lactam atom O4 (Cohen, 1983) and the O4—N1—C5—C6 torsion angle (Nangia et al., 1996). In the DACT molecule, atom N1 is displaced from the plane defined by atoms C4/C5/C8 by 0.214 (3) Å and Cohen's and Nangia's parameters are 3.186 (4) Å and 40.1 (3)°, respectively. These values are within the ranges postulated for active cephalosporins of 0.15–0.25 Å, 3.1–3.6 Å and 30–160°, respectively (Nangia et al., 1996).
The molecular packing of DACT involves strong intermolecular hydrogen bonds (Table 2), resulting in a two-dimensional supramolecular structure that has been examined using graph-set descriptors (Etter, 1990; Bernstein et al., 1995). The molecules of DACT are linked head-to-tail via strong O3—H3O···O5i hydrogen bonds, forming a helix with a C(10) pattern around the 21 screw axis [symmetry code: (i) −x, y + 1/2, 1 − z Please check added symmetry code; motif a in Fig. 2]. These main helices are further zipped together via the hydroxymethyl group, acting as both hydrogen-bond acceptor and donor. An O1ii···H—N1 [O1ii···H2N—N2 in Table 2?] bond [the C(9) motif b] is formed by the peptide N1—H [N2—H2N?] group and, simultaneously, the O1—H1O group is engaged in a hydrogen bond with atom S1ii of the dihydrothiazine ring, resulting in the C(6) motif c [symmetry code: (ii) 1 − x, y + 1/2, 1 − z Please check added symmetry code]. Motif a and motifs b or c combine to form layers of fused rings parallel to the (001) plane, with the second-level graph descriptors N2(ab) = C22(11)[R44(38)] and N2(ac) = C22(14)[R44(30)].
The two-dimensional structure is additionally stabilized by weak C—H···O hydrogen bonds between molecules related by translation symmetry in the [010] direction, as shown schematically in Fig. 3 (motifs d and e) (Steiner, 2002). These bonds are formed by two H atoms of the dihydrothiazine ring (H3A and H4) and the lactam atom O4iii [symmetry code: (iii) x, y − 1, z Please check added symmetry code], acting as a double acceptor, and tighten the helix, joining consecutive coils. Adjacent sheets are linked by very weak hydrogen-bond type interactions between aromatic C—H donors of the thiophene ring and atom O2 of the carboxyl group, leading to a three-dimensional supramolecular network (Fig. 3).
Thus, in the solid state, all the potential strong hydrogen-bonding donor centres of DACT are engaged in the intermolecular interactions that are decisive for supramolecular assembly. They do not form the O—H···O intramolecular bonds that were previously postulated for solutions (Zimniak et al., 1998). The only intramolecular interaction observed in DACT is the weak C1—H1A···O2 interaction, depicted as motif f in Fig. 1.