Mutual prodrug of cephazolin and benzydamin: 3-[(1-benzyl-1H-indazol-3-yl)­oxy]-N,N-dimethyl­propan-1-aminium 3-{[(5-methyl-1,3,4-thia­diazol-2-yl)sulfan­yl]meth­yl}-8-oxo-7-[(1H-tetra­zol-1-yl)acetamido]-5-thia-1-aza­bicyclo­[4.2.0]octane-2-carboxyl­ate (benzydaminium cephazolinate)

Asghar, A.; Iqbal, M.S.; Tahir, M.N.

doi:10.1107/S1600536809047941

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 12| December 2009| Pages o3132-o3133

doi:10.1107/S1600536809047941

Open

access

Mutual prodrug of cephazolin and benzydamin: 3-[(1-benzyl-1H-indazol-3-yl)oxy]-N,N-dimethylpropan-1-aminium 3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1H-tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylate (benzydaminium cephazolinate)

Amina Asghar,^a Mohammad S. Iqbal ^a and M. Nawaz Tahir ^b ^*

^aDepartment of Chemistry, Government College University, Lahore, Pakistan, and ^bDepartment of Physics, University of Sargodha, Sargodha, Pakistan
^*Correspondence e-mail: dmntahir_uos@yahoo.com

(Received 7 November 2009; accepted 12 November 2009; online 21 November 2009)

In the crystal of the title molecular salt, C₁₉H₂₄N₃O⁺·C₁₄H₁₃N₈O₄S₃⁻, the cations and anions are linked by N—H⋯O hydrogen bonds. Short intramolecular C—H⋯O contacts occur within the anion and intermolecular C—H⋯O and C—H⋯π bonds help to establish the packing.

Related literature

Cephazolin, is a first generation cefalosporin antibiotic and benzydamin hydrochloride is a locally acting non-steroidal anti-inflammatory drug with local anaesthetic and analgesic properties. The title compound was prepared as a mutual prodrug for the treatment of infections and inflamatory conditions. For medicinal background to cephazolin, see: Turnbull (1995 ). For ring-puckering analysis, see: Cremer & Pople (1975 ). For graph-set theory, see: Bernstein et al. (1995 ).

Experimental

Crystal data

C₁₉H₂₄N₃O⁺·C₁₄H₁₃N₈O₄S₃⁻
M_r = 763.92
Monoclinic, C 2
a = 44.409 (3) Å
b = 7.1777 (5) Å
c = 11.2683 (8) Å
β = 90.587 (8)°
V = 3591.6 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.27 mm⁻¹
T = 296 K
0.24 × 0.14 × 0.12 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ) T_min = 0.957, T_max = 0.968
34321 measured reflections
6750 independent reflections
4092 reflections with I > 2σ(I)
R_int = 0.088

Refinement

R[F² > 2σ(F²)] = 0.050
wR(F²) = 0.095
S = 1.00
6750 reflections
475 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.23 e Å⁻³
Absolute structure: Flack (1983 ), 2918 Friedel Pairs
Flack parameter: −0.07 (7)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3N⋯O3ⁱ	0.96 (4)	1.70 (4)	2.660 (4)	174 (3)
N7—H7N⋯O2ⁱⁱ	0.86	2.02	2.868 (3)	167
C18—H18C⋯O4ⁱⁱⁱ	0.96	2.52	3.303 (5)	139
C24—H24A⋯N4	0.97	2.41	2.961 (5)	116
C24—H24B⋯O3	0.97	2.38	2.882 (4)	112
C32—H32A⋯O2^iv	0.97	2.28	3.218 (4)	164
C32—H32B⋯O2ⁱⁱ	0.97	2.50	3.318 (4)	142
C19—H19B⋯CgA	0.96	2.91	3.869 (6)	174
C20—H20B⋯CgD	0.97	2.72	3.642 (4)	158
C29—H29⋯CgAⁱⁱ	0.98	2.99	3.861 (4)	149
Symmetry codes: (i) x, y-1, z+1; (ii) x, y-1, z; (iii) x, y, z+1; (iv) -x, y-1, -z+1. CgA and CgD are the centroids of the C1–C6 and N8–N11/C33 rings, respectively.

Data collection: APEX2 (Bruker, 2007 ); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ) and PLATON (Spek, 2009 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ) and PLATON.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809047941/hb5219sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809047941/hb5219Isup2.hkl

checkCIF report

Comment top

Cephazolin, is a first generation cefalosporin antibiotic and benzydamin hydrochloride is a locally acting nonsteroidal anti-inflammatory drug with local anaesthetic and analgesic properties providing both rapid and extended pain relief as well as a significant anti-inflammatory treatment for the painful inflammatory conditions of mouth and throat (Turnbull, 1995). The title compound (I, Fig. 1) was prepared as a mutual prodrug for the treatment of infections and inflamatory conditions.

No crystal structure has been found related to cation. In the cation the indazol moiety A (C1–C6/N2/N1/C14) and the benzene ring B (C8–C13) are planar with r.m.s. deviations of 0.0258 and 0.0031 Å respectively, from the respective mean square planes. The dihedral angle between A/B is 71.06 (12)°. In this cation, there exist an intramolecular H-bonding of C—H···O type (Table 1, Fig. 1) forming S(5) ring motif (Bernstein et al., 1995) in the envelop form.

In the anion, two five membered heterocyclic rings C (C25/S3/C26/N5/N4) and D (N8—N9/C33) are planar with r. m. s. deviations of 0.0025 and 0.0014 Å respectively, from the respective mean square planes and the dihedral angle between C/D is 38.58 (14)°. The heterocyclic six membered E (C20/C21/C22/N6/C28/S1) is in the twisted form, with the maximum puckering amplitude Q_T = 0.623 (4) Å (Cremer & Pople, 1975) and the four membered ring F (N6/C28–C30) is not planar also. In anion, there exist two S(5) and a S(6) ring motifs (Table 1, Fig. 1). The molecules are stabilized in the form of polymeric chains forming R₂¹(6), R₄²(8), R₂²(10) and other ring motifs (Fig. 2 & Fig. 3).

Related literature top

For medicinal background to cephazolin, see: Turnbull (1995). For ring-puckering analysis, see: Cremer & Pople (1975). For graph-set theory, see: Bernstein et al. (1995).CgA and CgD are the centroids of the C1–C6 and N8–N11/C33 rings, respectively.

Experimental top

Cefazolin sodium (0.238 g; 0.1 mol) and benzydamine hydrochloride (0.173 g; 0.01 mol) were dissolved separately in distilled water (50 ml). Ten milliliter of each solution were mixed and left for two days. The colourless needles of (I) thus obtained were filtered out by suction, washed with distilled water and dried under vacuum.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and PLATON (Spek, 2009); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2009).

Figures top

	Fig. 1. View of (I) with displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. The partial packing of (I), which shows that molecules form polymeric chains and ring motifs.
	Fig. 3. The partial packing of (I), which shows that molecules form polymeric networks with various ring motifs.

3-[(1-Benzyl-1H-indazol-3-yl)oxy]-N,N-dimethylpropan-1-aminium 3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1H-tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylate top

Crystal data top

C₁₉H₂₄N₃O⁺·C₁₄H₁₃N₈O₄S₃⁻	F(000) = 1600
M_r = 763.92	D_x = 1.413 Mg m⁻³
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2y	Cell parameters from 3824 reflections
a = 44.409 (3) Å	θ = 2.6–26.0°
b = 7.1777 (5) Å	µ = 0.27 mm⁻¹
c = 11.2683 (8) Å	T = 296 K
β = 90.587 (8)°	Cut needle, colourless
V = 3591.6 (4) Å³	0.24 × 0.14 × 0.12 mm
Z = 4

Data collection top

Bruker Kappa APEXII CCD diffractometer	6750 independent reflections
Radiation source: fine-focus sealed tube	4092 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.088
Detector resolution: 7.60 pixels mm^-1	θ_max = 26.0°, θ_min = 2.6°
ω scans	h = −54→54
Absorption correction: multi-scan (SADABS; Bruker, 2005)	k = −8→8
T_min = 0.957, T_max = 0.968	l = −13→13
34321 measured reflections

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) = 0.095	w = 1/[σ²(F_o²) + (0.0342P)²] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max < 0.001
6750 reflections	Δρ_max = 0.36 e Å⁻³
475 parameters	Δρ_min = −0.23 e Å⁻³
1 restraint	Absolute structure: Flack (1983), 2918 Friedal Pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.07 (7)

Crystal data top

C₁₉H₂₄N₃O⁺·C₁₄H₁₃N₈O₄S₃⁻	V = 3591.6 (4) Å³
M_r = 763.92	Z = 4
Monoclinic, C2	Mo Kα radiation
a = 44.409 (3) Å	µ = 0.27 mm⁻¹
b = 7.1777 (5) Å	T = 296 K
c = 11.2683 (8) Å	0.24 × 0.14 × 0.12 mm
β = 90.587 (8)°

Data collection top

Bruker Kappa APEXII CCD diffractometer	6750 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2005)	4092 reflections with I > 2σ(I)
T_min = 0.957, T_max = 0.968	R_int = 0.088
34321 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.050	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.095	Δρ_max = 0.36 e Å⁻³
S = 1.00	Δρ_min = −0.23 e Å⁻³
6750 reflections	Absolute structure: Flack (1983), 2918 Friedal Pairs
475 parameters	Absolute structure parameter: −0.07 (7)
1 restraint

Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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	U_iso*/U_eq
O1	0.14103 (6)	0.2863 (4)	0.9240 (3)	0.0552 (11)
N1	0.18241 (7)	0.2542 (4)	0.7971 (3)	0.0420 (12)
N2	0.19416 (7)	0.3698 (5)	0.7111 (3)	0.0433 (12)
N3	0.06627 (7)	0.0749 (5)	1.1012 (3)	0.0372 (11)
C1	0.15436 (8)	0.5181 (5)	0.7788 (3)	0.0340 (12)
C2	0.13236 (9)	0.6570 (6)	0.7813 (4)	0.0510 (17)
C3	0.13442 (11)	0.8000 (7)	0.7038 (4)	0.0640 (17)
C4	0.15844 (11)	0.8115 (6)	0.6251 (4)	0.0610 (19)
C5	0.18016 (10)	0.6769 (6)	0.6189 (3)	0.0490 (17)
C6	0.17762 (8)	0.5263 (5)	0.6969 (3)	0.0370 (12)
C7	0.21920 (9)	0.3080 (6)	0.6398 (3)	0.0463 (17)
C8	0.24923 (8)	0.3866 (5)	0.6760 (3)	0.0353 (12)
C9	0.25878 (9)	0.3855 (6)	0.7933 (4)	0.0466 (17)
C10	0.28704 (10)	0.4478 (6)	0.8244 (4)	0.0520 (17)
C11	0.30587 (9)	0.5147 (6)	0.7391 (4)	0.0484 (17)
C12	0.29672 (9)	0.5182 (6)	0.6231 (4)	0.0492 (17)
C13	0.26851 (9)	0.4546 (6)	0.5911 (3)	0.0450 (17)
C14	0.15916 (9)	0.3469 (5)	0.8366 (3)	0.0393 (16)
C15	0.14483 (9)	0.1004 (6)	0.9660 (4)	0.0546 (17)
C16	0.12086 (10)	0.0662 (8)	1.0548 (4)	0.0699 (19)
C17	0.09024 (9)	0.0869 (7)	1.0079 (4)	0.0636 (19)
C18	0.06411 (12)	0.2420 (7)	1.1765 (4)	0.089 (3)
C19	0.03700 (9)	0.0436 (8)	1.0420 (4)	0.0718 (19)
S1	0.10575 (2)	0.19304 (14)	0.49823 (9)	0.0428 (3)
S2	0.14745 (2)	0.56694 (16)	0.18123 (9)	0.0463 (4)
S3	0.20738 (2)	0.44836 (15)	0.08659 (9)	0.0456 (4)
O2	0.05024 (6)	0.8249 (3)	0.3777 (2)	0.0384 (9)
O3	0.08047 (6)	0.7715 (4)	0.2253 (2)	0.0547 (11)
O4	0.02066 (6)	0.4136 (4)	0.3861 (2)	0.0405 (9)
O5	0.02552 (7)	0.0728 (4)	0.7592 (2)	0.0587 (13)
N4	0.19862 (7)	0.4956 (4)	0.3076 (3)	0.0406 (12)
N5	0.22865 (7)	0.4435 (4)	0.2966 (3)	0.0427 (12)
N6	0.06812 (6)	0.4815 (4)	0.4717 (2)	0.0279 (10)
N7	0.03965 (6)	0.0819 (4)	0.5676 (2)	0.0315 (10)
N8	0.02949 (7)	−0.3125 (4)	0.7545 (3)	0.0325 (11)
N9	0.05801 (8)	−0.3400 (5)	0.7855 (3)	0.0603 (16)
N10	0.05818 (10)	−0.4303 (7)	0.8833 (4)	0.0751 (17)
N11	0.02978 (11)	−0.4641 (5)	0.9184 (3)	0.0663 (16)
C20	0.13044 (8)	0.3791 (5)	0.4529 (3)	0.0440 (14)
C21	0.11584 (8)	0.5428 (5)	0.3900 (3)	0.0317 (12)
C22	0.08645 (8)	0.5831 (5)	0.3948 (3)	0.0293 (12)
C23	0.07099 (9)	0.7410 (5)	0.3273 (3)	0.0330 (12)
C24	0.13782 (8)	0.6622 (5)	0.3251 (3)	0.0396 (14)
C25	0.18490 (8)	0.5045 (5)	0.2061 (3)	0.0376 (12)
C26	0.23635 (9)	0.4134 (5)	0.1884 (3)	0.0407 (14)
C27	0.26722 (9)	0.3571 (6)	0.1520 (4)	0.0570 (17)
C28	0.07883 (8)	0.3496 (5)	0.5621 (3)	0.0347 (12)
C29	0.04609 (8)	0.2771 (5)	0.5704 (3)	0.0323 (12)
C30	0.04024 (8)	0.3968 (5)	0.4591 (3)	0.0289 (12)
C31	0.02943 (8)	−0.0044 (5)	0.6644 (3)	0.0340 (12)
C32	0.02179 (8)	−0.2078 (5)	0.6480 (3)	0.0337 (12)
C33	0.01254 (10)	−0.3891 (5)	0.8368 (4)	0.0479 (17)
H2	0.11664	0.65124	0.83513	0.0612*
H3	0.11965	0.89190	0.70279	0.0762*
H3N	0.0701 (8)	−0.035 (5)	1.148 (3)	0.0446*
H4	0.15971	0.91434	0.57520	0.0732*
H5	0.19589	0.68514	0.56533	0.0588*
H7A	0.21521	0.34164	0.55778	0.0555*
H7B	0.22030	0.17314	0.64381	0.0555*
H9	0.24592	0.34200	0.85174	0.0560*
H10	0.29334	0.44458	0.90336	0.0622*
H11	0.32494	0.55774	0.76019	0.0578*
H12	0.30960	0.56374	0.56540	0.0593*
H13	0.26244	0.45759	0.51190	0.0541*
H15A	0.16458	0.08557	1.00236	0.0653*
H15B	0.14299	0.01281	0.90075	0.0653*
H16A	0.12321	−0.05902	1.08589	0.0837*
H16B	0.12364	0.15230	1.12035	0.0837*
H17A	0.08661	−0.00932	0.94905	0.0766*
H17B	0.08860	0.20648	0.96821	0.0766*
H18A	0.05950	0.34834	1.12796	0.1331*
H18B	0.08295	0.26181	1.21710	0.1331*
H18C	0.04846	0.22478	1.23366	0.1331*
H19A	0.03248	0.14682	0.99069	0.1076*
H19B	0.02159	0.03237	1.10070	0.1076*
H19C	0.03785	−0.06890	0.99605	0.1076*
H7N	0.04237	0.01975	0.50338	0.0378*
H20A	0.14087	0.42565	0.52288	0.0529*
H20B	0.14552	0.32694	0.40083	0.0529*
H24A	0.15602	0.67492	0.37270	0.0474*
H24B	0.12927	0.78543	0.31426	0.0474*
H27A	0.27708	0.29376	0.21663	0.0852*
H27B	0.27858	0.46598	0.13134	0.0852*
H27C	0.26590	0.27544	0.08474	0.0852*
H28	0.08607	0.41003	0.63503	0.0418*
H29	0.03622	0.33403	0.63884	0.0385*
H32A	0.00044	−0.22075	0.63099	0.0402*
H32B	0.03281	−0.25736	0.58121	0.0402*
H33	−0.00840	−0.38952	0.83662	0.0575*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.058 (2)	0.0430 (17)	0.065 (2)	0.0076 (15)	0.0274 (16)	0.0174 (15)
N1	0.036 (2)	0.044 (2)	0.046 (2)	0.0012 (17)	0.0080 (18)	0.0076 (17)
N2	0.031 (2)	0.052 (2)	0.047 (2)	0.0036 (18)	0.0123 (17)	0.0080 (18)
N3	0.039 (2)	0.043 (2)	0.0295 (19)	0.0030 (18)	0.0015 (16)	0.0090 (17)
C1	0.030 (2)	0.037 (2)	0.035 (2)	−0.0035 (19)	−0.0037 (19)	0.0030 (19)
C2	0.049 (3)	0.050 (3)	0.054 (3)	0.008 (2)	0.007 (2)	0.009 (2)
C3	0.070 (3)	0.064 (3)	0.058 (3)	0.021 (3)	0.005 (3)	0.014 (3)
C4	0.082 (4)	0.048 (3)	0.053 (3)	0.003 (3)	0.002 (3)	0.013 (2)
C5	0.054 (3)	0.054 (3)	0.039 (3)	−0.015 (3)	0.001 (2)	0.010 (2)
C6	0.034 (2)	0.040 (2)	0.037 (2)	−0.006 (2)	−0.004 (2)	0.002 (2)
C7	0.042 (3)	0.051 (3)	0.046 (3)	−0.002 (2)	0.006 (2)	−0.003 (2)
C8	0.034 (2)	0.036 (2)	0.036 (2)	0.0023 (19)	0.005 (2)	0.003 (2)
C9	0.049 (3)	0.049 (3)	0.042 (3)	−0.007 (2)	0.008 (2)	0.001 (2)
C10	0.059 (3)	0.056 (3)	0.041 (3)	−0.008 (3)	−0.005 (2)	−0.002 (2)
C11	0.040 (3)	0.042 (3)	0.063 (3)	0.007 (2)	−0.003 (2)	0.000 (2)
C12	0.041 (3)	0.052 (3)	0.055 (3)	0.004 (2)	0.014 (2)	0.009 (2)
C13	0.042 (3)	0.051 (3)	0.042 (3)	0.004 (2)	0.006 (2)	0.004 (2)
C14	0.031 (2)	0.047 (3)	0.040 (3)	−0.006 (2)	0.006 (2)	0.009 (2)
C15	0.042 (3)	0.054 (3)	0.068 (3)	0.005 (2)	0.010 (2)	0.015 (3)
C16	0.054 (3)	0.071 (3)	0.085 (4)	0.004 (3)	0.023 (3)	0.042 (3)
C17	0.051 (3)	0.082 (4)	0.058 (3)	−0.010 (3)	0.006 (3)	0.024 (3)
C18	0.128 (5)	0.061 (4)	0.077 (4)	0.019 (3)	−0.010 (4)	−0.030 (3)
C19	0.052 (3)	0.101 (4)	0.062 (3)	−0.009 (3)	−0.015 (2)	0.006 (3)
S1	0.0374 (6)	0.0314 (5)	0.0596 (7)	0.0060 (5)	0.0004 (5)	0.0109 (5)
S2	0.0375 (6)	0.0565 (7)	0.0448 (7)	−0.0009 (6)	0.0007 (5)	0.0019 (6)
S3	0.0463 (7)	0.0527 (7)	0.0380 (6)	0.0001 (6)	0.0054 (5)	−0.0031 (5)
O2	0.0384 (16)	0.0316 (15)	0.0452 (17)	0.0089 (13)	0.0084 (14)	0.0012 (13)
O3	0.067 (2)	0.0582 (19)	0.0393 (17)	0.0184 (16)	0.0200 (16)	0.0246 (15)
O4	0.0324 (15)	0.0485 (17)	0.0406 (16)	−0.0028 (13)	−0.0041 (14)	0.0086 (14)
O5	0.106 (3)	0.0393 (17)	0.0313 (16)	−0.0094 (17)	0.0191 (16)	−0.0010 (15)
N4	0.037 (2)	0.046 (2)	0.039 (2)	0.0003 (16)	0.0038 (16)	0.0039 (16)
N5	0.038 (2)	0.047 (2)	0.043 (2)	0.0016 (18)	0.0012 (17)	0.0032 (18)
N6	0.0282 (18)	0.0253 (17)	0.0302 (17)	−0.0001 (14)	0.0004 (14)	0.0099 (14)
N7	0.0414 (19)	0.0239 (17)	0.0293 (18)	−0.0033 (15)	0.0101 (15)	0.0011 (15)
N8	0.038 (2)	0.0287 (16)	0.0308 (19)	−0.0024 (16)	0.0055 (16)	0.0022 (16)
N9	0.044 (2)	0.080 (3)	0.057 (3)	0.010 (2)	0.000 (2)	0.016 (2)
N10	0.074 (3)	0.090 (3)	0.061 (3)	0.028 (3)	−0.009 (2)	0.022 (3)
N11	0.096 (3)	0.059 (3)	0.044 (2)	0.001 (3)	0.003 (2)	0.020 (2)
C20	0.036 (2)	0.043 (2)	0.053 (3)	−0.003 (2)	0.000 (2)	0.011 (2)
C21	0.031 (2)	0.027 (2)	0.037 (2)	−0.0021 (18)	0.0007 (18)	0.0008 (18)
C22	0.030 (2)	0.028 (2)	0.030 (2)	−0.0067 (18)	0.0040 (17)	0.0024 (18)
C23	0.036 (2)	0.028 (2)	0.035 (2)	−0.0032 (18)	−0.005 (2)	0.0028 (19)
C24	0.035 (2)	0.034 (2)	0.050 (3)	−0.0034 (19)	0.0070 (19)	0.004 (2)
C25	0.040 (2)	0.035 (2)	0.038 (2)	−0.0023 (19)	0.007 (2)	0.0035 (19)
C26	0.037 (2)	0.041 (2)	0.044 (3)	−0.001 (2)	0.003 (2)	−0.003 (2)
C27	0.044 (3)	0.062 (3)	0.065 (3)	0.006 (2)	0.008 (2)	0.001 (2)
C28	0.039 (2)	0.035 (2)	0.030 (2)	0.0001 (19)	0.0014 (19)	0.0055 (18)
C29	0.039 (2)	0.029 (2)	0.029 (2)	0.0000 (19)	0.0081 (18)	0.0008 (18)
C30	0.029 (2)	0.029 (2)	0.029 (2)	0.0037 (19)	0.0095 (19)	−0.0001 (18)
C31	0.036 (2)	0.036 (2)	0.030 (2)	−0.0018 (19)	0.0035 (19)	0.0063 (19)
C32	0.036 (2)	0.033 (2)	0.032 (2)	−0.0091 (18)	0.0000 (18)	0.0061 (18)
C33	0.055 (3)	0.048 (3)	0.041 (3)	−0.007 (2)	0.009 (2)	0.008 (2)

Geometric parameters (Å, º) top

S1—C20	1.805 (4)	C11—C12	1.365 (6)
S1—C28	1.797 (4)	C12—C13	1.378 (6)
S2—C24	1.815 (4)	C15—C16	1.489 (6)
S2—C25	1.742 (4)	C16—C17	1.461 (6)
S3—C26	1.733 (4)	C2—H2	0.9300
S3—C25	1.732 (4)	C3—H3	0.9300
O1—C15	1.425 (5)	C4—H4	0.9300
O1—C14	1.350 (5)	C5—H5	0.9300
O2—C23	1.243 (5)	C7—H7B	0.9700
O3—C23	1.247 (4)	C7—H7A	0.9700
O4—C30	1.197 (4)	C9—H9	0.9300
O5—C31	1.217 (4)	C10—H10	0.9300
N1—N2	1.382 (5)	C11—H11	0.9300
N1—C14	1.310 (5)	C12—H12	0.9300
N2—C7	1.448 (5)	C13—H13	0.9300
N2—C6	1.351 (5)	C15—H15B	0.9700
N3—C17	1.506 (5)	C15—H15A	0.9700
N3—C18	1.473 (6)	C16—H16A	0.9700
N3—C19	1.472 (5)	C16—H16B	0.9700
N3—H3N	0.96 (4)	C17—H17A	0.9700
N4—N5	1.392 (4)	C17—H17B	0.9700
N4—C25	1.292 (5)	C18—H18B	0.9600
N5—C26	1.288 (5)	C18—H18A	0.9600
N6—C28	1.466 (4)	C18—H18C	0.9600
N6—C30	1.385 (4)	C19—H19C	0.9600
N6—C22	1.400 (4)	C19—H19B	0.9600
N7—C31	1.338 (4)	C19—H19A	0.9600
N7—C29	1.430 (5)	C20—C21	1.515 (5)
N8—N9	1.325 (5)	C21—C24	1.496 (5)
N8—C33	1.320 (5)	C21—C22	1.339 (5)
N8—C32	1.454 (5)	C22—C23	1.524 (5)
N9—N10	1.279 (6)	C26—C27	1.491 (6)
N10—N11	1.348 (7)	C28—C29	1.548 (5)
N11—C33	1.307 (6)	C29—C30	1.540 (5)
N7—H7N	0.8600	C31—C32	1.510 (5)
C1—C14	1.406 (5)	C20—H20A	0.9700
C1—C2	1.396 (5)	C20—H20B	0.9700
C1—C6	1.393 (5)	C24—H24A	0.9700
C2—C3	1.351 (7)	C24—H24B	0.9700
C3—C4	1.397 (7)	C27—H27A	0.9600
C4—C5	1.368 (6)	C27—H27B	0.9600
C5—C6	1.399 (5)	C27—H27C	0.9600
C7—C8	1.501 (5)	C28—H28	0.9800
C8—C9	1.384 (6)	C29—H29	0.9800
C8—C13	1.380 (5)	C32—H32A	0.9700
C9—C10	1.374 (6)	C32—H32B	0.9700
C10—C11	1.368 (6)	C33—H33	0.9300

C20—S1—C28	93.40 (17)	C15—C16—H16B	109.00
C24—S2—C25	100.75 (17)	C17—C16—H16B	109.00
C25—S3—C26	87.07 (17)	H16A—C16—H16B	108.00
C14—O1—C15	118.3 (3)	C17—C16—H16A	109.00
N2—N1—C14	103.8 (3)	C16—C17—H17A	109.00
C6—N2—C7	127.5 (3)	C16—C17—H17B	109.00
N1—N2—C6	111.9 (3)	H17A—C17—H17B	108.00
N1—N2—C7	120.2 (3)	N3—C17—H17B	109.00
C17—N3—C18	114.0 (4)	N3—C17—H17A	109.00
C17—N3—C19	108.6 (3)	N3—C18—H18B	109.00
C18—N3—C19	108.8 (4)	N3—C18—H18A	110.00
C17—N3—H3N	108 (2)	H18A—C18—H18C	109.00
C18—N3—H3N	111 (2)	N3—C18—H18C	109.00
C19—N3—H3N	106 (2)	H18A—C18—H18B	109.00
N5—N4—C25	112.2 (3)	H18B—C18—H18C	109.00
N4—N5—C26	113.2 (3)	N3—C19—H19B	109.00
C22—N6—C30	133.6 (3)	N3—C19—H19C	109.00
C22—N6—C28	125.4 (3)	H19A—C19—H19C	109.00
C28—N6—C30	94.1 (3)	H19B—C19—H19C	109.00
C29—N7—C31	120.3 (3)	H19A—C19—H19B	109.00
N9—N8—C32	120.7 (3)	N3—C19—H19A	109.00
C32—N8—C33	131.6 (3)	S1—C20—C21	116.6 (3)
N9—N8—C33	107.6 (3)	C22—C21—C24	122.5 (3)
N8—N9—N10	107.5 (3)	C20—C21—C22	124.2 (3)
N9—N10—N11	110.3 (4)	C20—C21—C24	113.3 (3)
N10—N11—C33	105.2 (4)	N6—C22—C23	115.8 (3)
C29—N7—H7N	120.00	N6—C22—C21	119.1 (3)
C31—N7—H7N	120.00	C21—C22—C23	125.1 (3)
C6—C1—C14	103.5 (3)	O2—C23—C22	117.7 (3)
C2—C1—C6	120.5 (3)	O2—C23—O3	126.5 (3)
C2—C1—C14	135.8 (4)	O3—C23—C22	115.8 (3)
C1—C2—C3	118.5 (4)	S2—C24—C21	112.5 (2)
C2—C3—C4	120.8 (4)	S2—C25—N4	126.6 (3)
C3—C4—C5	122.3 (4)	S2—C25—S3	119.5 (2)
C4—C5—C6	116.9 (4)	S3—C25—N4	114.0 (3)
N2—C6—C1	107.0 (3)	S3—C26—C27	122.4 (3)
C1—C6—C5	120.9 (3)	S3—C26—N5	113.6 (3)
N2—C6—C5	132.1 (3)	N5—C26—C27	124.0 (4)
N2—C7—C8	114.8 (3)	N6—C28—C29	87.8 (2)
C7—C8—C9	121.4 (3)	S1—C28—C29	116.3 (2)
C7—C8—C13	120.0 (3)	S1—C28—N6	109.8 (2)
C9—C8—C13	118.6 (3)	N7—C29—C28	121.0 (3)
C8—C9—C10	120.8 (4)	N7—C29—C30	119.8 (3)
C9—C10—C11	119.9 (4)	C28—C29—C30	85.1 (3)
C10—C11—C12	120.1 (4)	O4—C30—N6	132.0 (3)
C11—C12—C13	120.4 (4)	N6—C30—C29	91.0 (3)
C8—C13—C12	120.3 (3)	O4—C30—C29	137.0 (3)
N1—C14—C1	113.8 (3)	O5—C31—C32	120.9 (3)
O1—C14—N1	124.2 (3)	O5—C31—N7	123.9 (3)
O1—C14—C1	122.1 (3)	N7—C31—C32	115.2 (3)
O1—C15—C16	107.1 (4)	N8—C32—C31	110.4 (3)
C15—C16—C17	114.2 (4)	N8—C33—N11	109.4 (4)
N3—C17—C16	113.8 (4)	S1—C20—H20A	108.00
C1—C2—H2	121.00	S1—C20—H20B	108.00
C3—C2—H2	121.00	C21—C20—H20A	108.00
C4—C3—H3	120.00	C21—C20—H20B	108.00
C2—C3—H3	120.00	H20A—C20—H20B	107.00
C3—C4—H4	119.00	S2—C24—H24A	109.00
C5—C4—H4	119.00	S2—C24—H24B	109.00
C6—C5—H5	122.00	C21—C24—H24A	109.00
C4—C5—H5	122.00	C21—C24—H24B	109.00
N2—C7—H7A	109.00	H24A—C24—H24B	108.00
C8—C7—H7B	109.00	C26—C27—H27A	109.00
N2—C7—H7B	109.00	C26—C27—H27B	109.00
C8—C7—H7A	109.00	C26—C27—H27C	110.00
H7A—C7—H7B	108.00	H27A—C27—H27B	109.00
C10—C9—H9	120.00	H27A—C27—H27C	109.00
C8—C9—H9	120.00	H27B—C27—H27C	109.00
C9—C10—H10	120.00	S1—C28—H28	113.00
C11—C10—H10	120.00	N6—C28—H28	113.00
C12—C11—H11	120.00	C29—C28—H28	113.00
C10—C11—H11	120.00	N7—C29—H29	110.00
C13—C12—H12	120.00	C28—C29—H29	110.00
C11—C12—H12	120.00	C30—C29—H29	110.00
C8—C13—H13	120.00	N8—C32—H32A	110.00
C12—C13—H13	120.00	N8—C32—H32B	110.00
O1—C15—H15B	110.00	C31—C32—H32A	110.00
C16—C15—H15A	110.00	C31—C32—H32B	110.00
O1—C15—H15A	110.00	H32A—C32—H32B	108.00
H15A—C15—H15B	109.00	N8—C33—H33	125.00
C16—C15—H15B	110.00	N11—C33—H33	125.00
C15—C16—H16A	109.00

C20—S1—C28—C29	155.3 (3)	N8—N9—N10—N11	0.1 (5)
C20—S1—C28—N6	57.8 (3)	N9—N10—N11—C33	−0.1 (5)
C28—S1—C20—C21	−47.1 (3)	N10—N11—C33—N8	0.2 (5)
C24—S2—C25—N4	12.6 (4)	C2—C1—C6—N2	−176.6 (3)
C24—S2—C25—S3	−167.0 (2)	C2—C1—C6—C5	2.6 (6)
C25—S2—C24—C21	−111.3 (3)	C14—C1—C2—C3	−175.0 (4)
C25—S3—C26—C27	−179.3 (3)	C14—C1—C6—C5	178.4 (3)
C26—S3—C25—N4	−0.1 (3)	C2—C1—C14—O1	−5.2 (7)
C25—S3—C26—N5	−0.4 (3)	C14—C1—C6—N2	−0.8 (4)
C26—S3—C25—S2	179.6 (2)	C6—C1—C2—C3	−0.9 (6)
C14—O1—C15—C16	−176.1 (3)	C6—C1—C14—N1	−0.5 (4)
C15—O1—C14—C1	171.1 (3)	C2—C1—C14—N1	174.4 (4)
C15—O1—C14—N1	−8.4 (5)	C6—C1—C14—O1	179.9 (3)
N2—N1—C14—C1	1.4 (4)	C1—C2—C3—C4	−1.7 (7)
C14—N1—N2—C7	−175.3 (3)	C2—C3—C4—C5	2.7 (7)
N2—N1—C14—O1	−179.0 (3)	C3—C4—C5—C6	−1.0 (6)
C14—N1—N2—C6	−1.9 (4)	C4—C5—C6—C1	−1.6 (6)
N1—N2—C6—C5	−177.3 (4)	C4—C5—C6—N2	177.3 (4)
C7—N2—C6—C5	−4.6 (7)	N2—C7—C8—C9	48.2 (5)
N1—N2—C7—C8	−102.2 (4)	N2—C7—C8—C13	−134.6 (4)
C6—N2—C7—C8	85.6 (5)	C7—C8—C13—C12	−176.7 (4)
C7—N2—C6—C1	174.5 (3)	C9—C8—C13—C12	0.6 (6)
N1—N2—C6—C1	1.7 (4)	C13—C8—C9—C10	−1.1 (6)
C19—N3—C17—C16	−164.0 (4)	C7—C8—C9—C10	176.1 (4)
C18—N3—C17—C16	74.5 (5)	C8—C9—C10—C11	1.1 (6)
C25—N4—N5—C26	−0.7 (4)	C9—C10—C11—C12	−0.5 (7)
N5—N4—C25—S3	0.4 (4)	C10—C11—C12—C13	0.0 (7)
N5—N4—C25—S2	−179.2 (3)	C11—C12—C13—C8	0.0 (6)
N4—N5—C26—S3	0.6 (4)	O1—C15—C16—C17	59.5 (5)
N4—N5—C26—C27	179.6 (3)	C15—C16—C17—N3	−173.0 (4)
C30—N6—C22—C21	−133.6 (4)	S1—C20—C21—C22	19.2 (5)
C30—N6—C22—C23	49.7 (5)	S1—C20—C21—C24	−163.3 (2)
C28—N6—C22—C23	−167.3 (3)	C20—C21—C22—N6	6.9 (5)
C30—N6—C28—C29	−11.3 (3)	C20—C21—C22—C23	−176.7 (3)
C22—N6—C28—S1	−48.2 (4)	C20—C21—C24—S2	81.3 (3)
C22—N6—C28—C29	−165.4 (3)	C22—C21—C24—S2	−101.2 (4)
C22—N6—C30—O4	−16.5 (7)	C24—C21—C22—N6	−170.3 (3)
C28—N6—C22—C21	9.4 (5)	C24—C21—C22—C23	6.0 (6)
C30—N6—C28—S1	106.0 (2)	N6—C22—C23—O2	32.8 (5)
C22—N6—C30—C29	161.9 (4)	C21—C22—C23—O3	37.0 (5)
C28—N6—C30—O4	−167.1 (4)	N6—C22—C23—O3	−146.5 (3)
C28—N6—C30—C29	11.3 (3)	C21—C22—C23—O2	−143.7 (4)
C29—N7—C31—O5	−1.4 (5)	S1—C28—C29—N7	21.1 (4)
C31—N7—C29—C30	−145.3 (3)	S1—C28—C29—C30	−100.9 (3)
C29—N7—C31—C32	176.6 (3)	N6—C28—C29—N7	132.1 (3)
C31—N7—C29—C28	111.5 (4)	N6—C28—C29—C30	10.1 (2)
N9—N8—C32—C31	−69.8 (4)	N7—C29—C30—O4	44.4 (6)
N9—N8—C33—N11	−0.1 (4)	N7—C29—C30—N6	−133.9 (3)
C32—N8—C33—N11	−177.9 (3)	C28—C29—C30—O4	167.5 (5)
C33—N8—N9—N10	0.0 (4)	C28—C29—C30—N6	−10.7 (3)
C32—N8—N9—N10	178.1 (4)	O5—C31—C32—N8	−38.1 (5)
C33—N8—C32—C31	107.8 (4)	N7—C31—C32—N8	143.9 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3N···O3ⁱ	0.96 (4)	1.70 (4)	2.660 (4)	174 (3)
N7—H7N···O2ⁱⁱ	0.8600	2.0200	2.868 (3)	167.00
C18—H18C···O4ⁱⁱⁱ	0.9600	2.5200	3.303 (5)	139.00
C24—H24A···N4	0.9700	2.4100	2.961 (5)	116.00
C24—H24B···O3	0.9700	2.3800	2.882 (4)	112.00
C32—H32A···O2^iv	0.9700	2.2800	3.218 (4)	164.00
C32—H32B···O2ⁱⁱ	0.9700	2.5000	3.318 (4)	142.00
C19—H19B···CgA	0.96	2.91	3.869 (6)	174
C20—H20B···CgD	0.97	2.72	3.642 (4)	158
C29—H29···CgAⁱⁱ	0.98	2.99	3.861 (4)	149

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

Experimental details

Crystal data
Chemical formula	C₁₉H₂₄N₃O⁺·C₁₄H₁₃N₈O₄S₃⁻
M_r	763.92
Crystal system, space group	Monoclinic, C2
Temperature (K)	296
a, b, c (Å)	44.409 (3), 7.1777 (5), 11.2683 (8)
β (°)	90.587 (8)
V (Å³)	3591.6 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.27
Crystal size (mm)	0.24 × 0.14 × 0.12

Data collection
Diffractometer	Bruker Kappa APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2005)
T_min, T_max	0.957, 0.968
No. of measured, independent and observed [I > 2σ(I)] reflections	34321, 6750, 4092
R_int	0.088
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.050, 0.095, 1.00
No. of reflections	6750
No. of parameters	475
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.36, −0.23
Absolute structure	Flack (1983), 2918 Friedal Pairs
Absolute structure parameter	−0.07 (7)

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997) and PLATON (Spek, 2009), WinGX (Farrugia, 1999) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3N···O3ⁱ	0.96 (4)	1.70 (4)	2.660 (4)	174 (3)
N7—H7N···O2ⁱⁱ	0.8600	2.0200	2.868 (3)	167.00
C18—H18C···O4ⁱⁱⁱ	0.9600	2.5200	3.303 (5)	139.00
C24—H24A···N4	0.9700	2.4100	2.961 (5)	116.00
C24—H24B···O3	0.9700	2.3800	2.882 (4)	112.00
C32—H32A···O2^iv	0.9700	2.2800	3.218 (4)	164.00
C32—H32B···O2ⁱⁱ	0.9700	2.5000	3.318 (4)	142.00
C19—H19B···CgA	0.96	2.91	3.869 (6)	174
C20—H20B···CgD	0.97	2.72	3.642 (4)	158
C29—H29···CgAⁱⁱ	0.98	2.99	3.861 (4)	149

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

Acknowledgements

AA gratefully acknowledges the Higher Education Commision, Islamabad, Pakistan, for providing a Scholaship under the Indigenous PhD Program.

References

Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573. CrossRef CAS Web of Science Google Scholar
Bruker (2005). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Turnbull, R. S. (1995). J. Can. Dent. Assoc. 61, 127–134. CAS PubMed Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 12| December 2009| Pages o3132-o3133

doi:10.1107/S1600536809047941

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Mutual prodrug of cephazolin and benzydamin: 3-[(1-benzyl-1H-indazol-3-yl)­­oxy]-N,N-di­methyl­propan-1-aminium 3-{[(5-methyl-1,3,4-thia­diazol-2-yl)sulfan­yl]meth­yl}-8-oxo-7-[(1H-tetra­zol-1-yl)acetamido]-5-thia-1-aza­bi­cyclo­[4.2.0]octane-2-carboxyl­ate (benzydaminium cephazolinate)

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

Mutual prodrug of cephazolin and benzydamin: 3-[(1-benzyl-1H-indazol-3-yl)oxy]-N,N-dimethylpropan-1-aminium 3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1H-tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylate (benzydaminium cephazolinate)