Synthesis, spectroscopic characterization, antimicrobial activity and crystal structure of [Ag2(C10H10N3O3S)2(C5H5N)3]

Journal of Molecular Structure 1088 (2015) 161–168

Contents lists available at ScienceDirect

Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc

Synthesis, spectroscopic characterization, antimicrobial activity and crystal structure of [Ag2(C10H10N3O3S)2(C5H5N)3] Sanjay M. Tailor ⇑, Urmila H. Patel 1 X-ray Crystallography Laboratory, Department of Physics, Sardar Patel University, Vallabh Vidyanagar 388 120, Gujarat, India

h i g h l i g h t s

g r a p h i c a l a b s t r a c t

 A new silver complex of

ORTEP view of the title compound shows two silver atoms leading to distorted tetrahedral and square pyramid geometry.

sulfamethoxazole is synthesized by reflux method.  Silver (two) forms distorted tetrahedral and square pyramid geometry.  Characterized by X-ray crystallography, IR, NMR and UV spectra, CHN and TG analysis.  The molecular structure of [Ag2(C10H10N3O3S)2(C5H5N)3] is investigated.  Ag-SMX shows high antibacterial activity than free ligand against gram +ve bacteria.

a r t i c l e

i n f o

Article history: Received 1 November 2014 Received in revised form 27 January 2015 Accepted 5 February 2015 Available online 12 February 2015 Keywords: Ag complex Sulfamethoxazole Spectroscopic analysis Crystal structure Thermogravimetric study Antimicrobial activity

a b s t r a c t Silver complex of 4-Amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide (sulfamethoxazole) (SMX) has been synthesized and characterized by elemental analysis, infrared, UV and NMR spectroscopy. The title compound, [Ag2(C10H10N3O3S)2(C5H5N)3] crystallizes in the orthorhombic space group Pna21 with lattice parameters a = 17.9527(5), b = 8.6529(3), c = 25.1621(7) Å and Z = 4. The structure is solved by direct method and refined to a final R = 0.0567 for 6732 reflections with I P 2r(I). The results of IR, 1H NMR and 13C NMR spectral data suggest the binding of silver atom to the sulfonamide ligand which is in agreement with the crystal structure determination. X-ray analysis revealed that in the title compound, one silver atom is surrounded by three N atoms and one Ag atom leading to a distorted tetrahedral geometry and another silver atom is surrounded by four N atoms and one Ag atom leading to a slightly distorted square pyramid geometry with Ag  Ag separation distance of 3.026 Å. The dihedral angle between phenyl and isoxazole ring is 85.7(4)°. In the crystal structure, the molecules are linked via NAH  O, CAH  O intermolecular and CAH  O intramolecular interactions. Silver complex of sulfamethoxazole has been studied by electrical and thermal analysis. Silver sulfamethoxazole presents different antibacterial behavior against Escherichia coli and Staphylococcus aureus strains. Ó 2015 Elsevier B.V. All rights reserved.

Introduction ⇑ Corresponding author. Tel.: +91 9824741619. E-mail addresses: [email protected] (S.M. Tailor), u_h_patel@yahoo. com (U.H. Patel). 1 Tel.: +91 9898399054, +91 2692 236844. http://dx.doi.org/10.1016/j.molstruc.2015.02.014 0022-2860/Ó 2015 Elsevier B.V. All rights reserved.

During the past two decades the frequencies and types of life-threatening infections have increased. Besides the usual cases, there is an increase of immunocompromised patients (HIV infections, antitumoral treatments, organ transplant-associated

162

S.M. Tailor, U.H. Patel / Journal of Molecular Structure 1088 (2015) 161–168

immunosuppressive therapy) as well as patients undergoing more invasive medical procedures (extensive surgery, prosthetic implants) among others [1]. Sulfonamides and their different derivatives are extensively used in medicine due to their pharmacological properties such as antibacterial activity. They interfere with the use of p-aminobenzoic acid (PABA) in the biosynthesis of tetrahydrofolic acid, which is an essential growth factor that is vital to the bacteria’s metabolism. A number of activities some of which have been recently observed include endothelin antagonism, antiinflammatory activity, tubular transport inhibition, insulin release, carbonic anhydrase and saluretic action among others [2]. Our interests have been in the synthesis and characterization of metallic complexes bearing sulfonamide ligands. The heterocyclic compounds with both sulfur and nitrogen atoms in the ring system have frequently been used in the synthesis of biologically active complexes. It is, however, noteworthy that the biological activity gets enhanced on undergoing complexation with metals [3,4]. Several sulfonamide metal complexes showed more activity than free ligand [5–7]. In particular, Ag(I)–sulfadiazine [8] and Zn(II)– sulfadiazine [9] are used in preventing bacterial infection in burn treatment. Literature survey reveals that Ag–sulfonamide complexes have not been well studied and so far only the crystal structure of Ag(I)–sulfadiazine is reported in literature. Although ‘‘coulombic’’ repulsion is expected between silver(I)–silver(I) metal center, quite a good number of structures with such contacts have been characterized [10] and it is also well documented that the stereochemistry of the silver complexes and the geometry of metal co-ordination gets modified with change of ligand, solvents and the condition of crystallization. To understand the drug metal ion properties and to investigate silver complexes containing a close Ag(I)AAg(I) separation, we have synthesized four and five coordinated Ag(I) ligand inter connected through imido, isoxazole and pyridine solvent nitrogens and Ag(I) with Ag(I)AAg(I) separation distance of 3.026 Å. Sulfamethoxazole, a well-known antibacterial sulfa drug, contains several groups with donor atoms those are able to interact with metal ions: ArANH2, NH sulfonamide, SO2AR and N and O heterocyclic atoms (Fig. 1). Sulfamethoxazole can act as a monodentate or a bidentate ligand. Some metal complexes of sulfamethoxazole have been reported [11,12]. Further the study of silver sulfonamide complexes is attractive in relation to coordination chemistry area.

Perkin Elmer Spectrum GX FT-IR Spectrometer using KBr pellet technique. UV spectra (200–400 nm) are recorded on a Shimadzu UV-160 in DMSO. 1H NMR and 13C NMR spectra are recorded on a Bruker Avance DPX-200 spectrometer. Electrical conductivity is measured using EQ-660A conductivity meter. Thermogravimetric analyses are carried out in nitrogen atmosphere using Seiko SII-EXSTAR TG/DTA-7200. Synthesis of the complex The solution of silver nitrate (1 mmol) in distilled water is added in the solution of sulfamethoxazole (SMX) (1 mmol) in 25 ml methanol and the mixture is refluxed for 2 h. A white precipitate is formed, filtered and washed with hot distilled water and methanol successively and dried in a desiccator over anhydrous CaCl2. The yield at the end of reaction for the complex is around 40%. The results for [C20H20N6Ag2O6S2] are: Anal. Calcd. (%): C, 33.35; H, 2.78; N, 11.66. Found (%): C, 34.95; H, 2.66; N, 11.48. The complex is insoluble in water and in most of the common solvents but soluble in Dimethyl sulfoxide (DMSO), Dimethylformamide (DMF) and pyridine. After several unsuccessful attempts, it is possible to grow a few numbers of tiny colorless single crystals adequate for X-ray structure analysis from pyridine. X-ray crystallography Crystallographic data are collected on a Bruker Kappa APEX-II CCD diffractometer with graphite monochromated Mo Ka radia0

tion (k = 0.71703 Å A) at T = 296.15 K. The structure is solved by direct methods with SHELXS-97 [13] and anisotropic thermal parameters for all non hydrogen atoms are refined by full-matrix least squares procedure against F2 with SHELXL-97 [14]. The H 0

atoms are positioned geometrically with NAH = 0.90 Å A (for NH2), 0

0

CAH = 0.96 Å A (for CH3), and CAH = 0.93 Å A for aromatic H atoms respectively. In addition they are constrained to ride on their parent atoms with Uiso(H) = 1.2 Ueq (carrier atoms of CH, NH) and Uiso(H) = 1.5 Ueq (carrier atoms of CH3). The program PLATON [15] and ORTEP-3 [16] within WinGX [17] are used to prepare materials for publication.

Experimental

Microbiological assays

Chemicals

Micro broth dilution method is used to determine the minimal inhibitory concentration (MIC) of the antimicrobial agent against gram negative (Escherichia coli) and gram positive (Staphylococcus aureus). The steps for performing the Micro broth dilution method are based on recommendations from the National Committee for Clinical Laboratory Standards [18]. The standard strains used are E. coli MTCC 422 and S. aureus MTCC 96. Mueller Hinton Broth is used as Nutrient medium at 37 °C to grow and dilute the drug suspension for the test bacteria. The solvent DMSO is used as diluent to get desired concentration of drugs to test upon standard bacterial strains. Serial dilutions are prepared in primary and secondary screening. Each synthesized compound and standard drugs are diluted obtaining 2000 lg/mL concentration, as a stock solution. In primary screening 1000, 500, and 250 lg/mL concentrations of the synthesized drugs are taken. The active synthesized compounds found in this primary screening are further diluted to obtain 200, 125, 100, 62.5, 50, 25, 12.5, and 6.250 lg/mL concentrations for secondary screening. Inoculum’s size for test strain is adjusted to 108 CFU ml1 by comparing the turbidity. MIC is the lowest concentration of a compound in DMSO that exhibited no visual growth of the organisms

Sulfamethoxazole (Sigma, >99%), silver (I) nitrate and all other reagents are of the highest grade commercially available and used without further purification. Physical measurements Elemental analyses (C, H, N) is carried out using a Perkin Elmer 2400-II CHN elemental analyzer. IR spectra are recorded on a

Fig. 1. Chemical structure of sulfamethoxazole.

163

S.M. Tailor, U.H. Patel / Journal of Molecular Structure 1088 (2015) 161–168

in the culture tubes. Each of thrice along with a control obtained for three individual the growth inhibition zone of

the above experiments is repeated set using DMSO. The mean value replicates is then used to calculate each sample.

Results and discussion Crystal structure of [Ag2(C10H10N3O3S)2(C5H5N)3] Suitable single crystals grown by slow evaporation from a pyridine solvent of the complex is used for X-ray crystal structure determination. The single crystal data and refinement details for the title compound [Ag2(C10H10N3O3S)2(C5H5N)3] are summarized in Table 1. The fractional atomic coordinates and equivalent isotropic thermal parameters are shown in Table 2. The selected bond lengths and bond angles are shown in Table 3. Fig. 2 shows an ORTEP view of the title compound with atomic numbering scheme. Hydrogen bond geometry and symmetry code for title compound are given in Table 4. Crystal structure of the title compound contains two silver atoms in which one is four coordinated silver(I) ion and another is five coordinated silver(I) ion. One silver atom is four coordinated with a distorted tetrahedral geometry by one Ag(I) ion, two nitrogen atoms from two sulfamethoxazole ligands and one nitrogen atom from pyridine solvent molecules. Another silver atom is five coordinated with a distorted pentadented geometry by one Ag(I) ion, two nitrogen atoms from two sulfamethoxazole ligands and two nitrogen atoms from two pyridine solvent molecules. The bond lengths involving silver represents a distorted tetrahedral configuration but are compatible to those (2.354–2.689 Å) reported in other silver complexes (Table 3). The distance between first silver cation and the nitrogen atoms adjacent to the sulfonyl group of a 0

symmetry related ligand is Ag1AN1A = 2.229(6) Å A. Second bond involves the isoxazole nitrogen atom Ag1AN2B = 2.249(7) Å, while the third bond occurs along the lone electron pair of the N-atom of 0

the pyridine molecule [Ag1AN4A = 2.403(7) Å A]. The fourth bond is due to each ligand bridges two different silver atoms

Table 1 Crystal data and refinement of [Ag2(C10H10N3O3S)2(C5H5N)3]. Empirical formula

C35H35N9Ag2O6S2

Formula weight Crystal system Space group a (Å) b (Å) c (Å) Volume (Å3) Z Temperature (K) Crystal size (mm3) Calculated density (Mg m3), Absorption coefficient (mm1) F(0 0 0) h range for data collection (°) Index ranges Reflections collected Unique reflections Rint Goodness-of-fit on F2 Absorption correction Refinement method Data/parameters Final R indices [I P 2r(I)] R indices (all data) Largest diff. peak and hole (e Å3)

957.6 Orthorhombic Pna21 17.9527(5) 8.6529(3) 25.1621(15) 3908.75(2) 4 296.15 0.08  0.04  0.02 1.63 1.165 1928 2.3–27.6 13 6 h 6 23; 11 6 k 6 7; 18 6 l 6 32 19,781 6732 0.0419 1.0060 NA Full Matrix Least Square of |F|2 6732/488 R1 = 0.038, wR2 = 0.066 R1 = 0.076, wR2 = 0.080 0.49 and 0.71

Table 2 Fractional atomic coordinates and equivalent isotropic displacement parameters (Å2).

Ag1 Ag2 S1A S1B O1A O1B O2A O2B O3A O3B N1A N1B N2A N2B N3A N3B N4A N4B N5B C1A C1B C2A C2B C3A C3B C4A C4B C5A C5B C6A C6B C7A C7B C8A C8B C9A C9B C10A C10B C11A C11B C12A C12B C13A C13B C14A C14B C15A C15B C16B C17B C18B C19B C20B

x

y

z

Ueq(Å2)

0.55490 (3) 0.67391 (3) 0.62908 (13) 0.60720 (15) 0.6730 (3) 0.5647 (4) 0.5494 (3) 0.6871 (4) 0.8164 (3) 0.4158 (3) 0.6481 (4) 0.5855 (4) 0.7375 (3) 0.4950 (4) 0.7076 (5) 0.5532 (5) 0.4495 (4) 0.7834 (5) 0.6110 (5) 0.6512 (5) 0.5863 (4) 0.7043 (5) 0.5450 (5) 0.7217 (5) 0.5337 (5) 0.6886 (5) 0.5630 (5) 0.6368 (5) 0.6035 (4) 0.6190 (4) 0.6147 (4) 0.7224 (5) 0.5113 (5) 0.7891 (5) 0.4453 (5) 0.9274 (5) 0.3063 (5) 0.8441 (5) 0.3893 (5) 0.4110 (5) 0.7633 (6) 0.3481 (6) 0.8061 (9) 0.3231 (6) 0.8749 (9) 0.3603 (6) 0.8969 (7) 0.4244 (6) 0.8490 (8) 0.5691 (5) 0.5656 (5) 0.6059 (8) 0.6480 (7) 0.6490 (5)

0.43510 (7) 0.45918 (7) 0.3295 (2) 0.3881 (2) 0.2115 (6) 0.4993 (6) 0.3098 (6) 0.4051 (7) 0.3995 (7) 0.3682 (7) 0.3471 (7) 0.3848 (7) 0.3963 (7) 0.3814 (7) 0.9324 (7) 0.2246 (7) 0.5691 (8) 0.6171 (9) 0.7111 (7) 0.5057 (9) 0.2059 (8) 0.5174 (9) 0.1925 (9) 0.6594 (8) 0.0487 (9) 0.7938 (8) 0.0838 (9) 0.7821 (9) 0.0683 (9) 0.6424 (9) 0.0742 (8) 0.3585 (8) 0.3758 (8) 0.3368 (9) 0.3601 (9) 0.3706 (13) 0.3476 (13) 0.3643 (10) 0.3571 (10) 0.6598 (10) 0.7267 (12) 0.7347 (12) 0.7837 (15) 0.7199 (13) 0.7269 (17) 0.6290 (16) 0.6107 (16) 0.5541 (12) 0.5604 (14) 0.7934 (10) 0.9514 (10) 1.0247 (10) 0.9418 (11) 0.7855 (9)

0.05068 (2) 0.03410 (3) 0.16255 (8) 0.15194 (8) 0.1884 (2) 0.1814 (2) 0.1646 (2) 0.1523 (2) 0.0340 (2) 0.0223 (2) 0.1007 (2) 0.0900 (2) 0.0380 (2) 0.0255 (3) 0.2567 (3) 0.2482 (3) 0.0873 (3) 0.0728 (3) 0.0038 (3) 0.1927 (3) 0.1791 (3) 0.2323 (3) 0.2247 (3) 0.2541 (3) 0.2479 (3) 0.2361 (3) 0.2257 (3) 0.1951 (3) 0.1785 (3) 0.1741 (3) 0.1556 (3) 0.0869 (3) 0.0768 (3) 0.1161 (3) 0.1073 (4) 0.0871 (4) 0.0759 (4) 0.0834 (4) 0.0721 (5) 0.0563 (5) 0.1028 (4) 0.0717 (5) 0.1433 (5) 0.1217 (5) 0.1529 (5) 0.1545 (5) 0.1222 (5) 0.1361 (4) 0.0809 (5) 0.0282 (4) 0.0263 (5) 0.0105 (6) 0.0448 (5) 0.0407 (4)

0.05810 (18) 0.05927 (18) 0.0525 (5) 0.0574 (6) 0.0702 (18) 0.081 (2) 0.0643 (16) 0.0804 (19) 0.0629 (16) 0.0664 (16) 0.0474 (16) 0.0476 (16) 0.0486 (17) 0.0537 (17) 0.083 (3) 0.088 (3) 0.066 (2) 0.073 (2) 0.0666 (19) 0.0476 (19) 0.0451 (19) 0.058 (2) 0.063 (3) 0.063 (2) 0.070 (3) 0.050 (2) 0.056 (2) 0.059 (2) 0.054 (2) 0.055 (2) 0.051 (2) 0.0410 (19) 0.050 (2) 0.058 (2) 0.063 (2) 0.091 (3) 0.098 (4) 0.060 (2) 0.069 (3) 0.080 (3) 0.089 (3) 0.099 (4) 0.127 (5) 0.093 (3) 0.123 (5) 0.109 (4) 0.120 (4) 0.091 (3) 0.111 (4) 0.071 (3) 0.077 (3) 0.097 (3) 0.098 (3) 0.072 (3)

0

[Ag1AAg2 = 3.0264(8) Å A], while the distance between second silver cation and the nitrogen atoms adjacent to the sulfonyl group of a 0

symmetry related ligand is Ag2AN1B = 2.216(6) Å A. Second bond involves the isoxazole nitrogen atom Ag2AN2A = 2.212(5) Å, while the third and fourth bond occurs along the lone electron pairs of the two nitrogen atoms of the two pyridine molecules 0

0

[Ag2AN4B = 2.584(8) Å A and Ag2AN5B = 2.634(7) Å A]. The fifth bond is due to each ligand bridges two different silver atoms 0

[Ag1AAg2 = 3.0264(8) Å A]. The bond lengths and angles of the phenyl ring confirm well to those found in the free sulfamethoxazole [19], whereas distances S1AN1 (1.598(6) Å for molecule A and 1.607(6) Å for molecule B) and N1AC10 (1.383(11) Å for molecule A and 1.375(11) Å for

164

S.M. Tailor, U.H. Patel / Journal of Molecular Structure 1088 (2015) 161–168

Table 3 Selected bond lengths and bond angles for [Ag2(C10H10N3O3S)2(C5H5N)3]. Bond distances (Å) Ag1AN1A Ag1AN2B Ag1AN4A Ag1AAg2 Ag2AN2A Ag2AN1B Ag2AN4B Ag2AN5B

Bond angles (°) 2.229 (6) 2.247 (7) 2.402 (7) 3.0263 (9) 2.211 (6) 2.215 (6) 2.585 (8) 2.634 (7)

N1AAAg1AN2B N1AAAg1AN4A N2BAAg1AN4A N1AAAg1AAg2 N2BAAg1AAg2 N4AAAg1AAg2 N2AAAg2AN1B N2AAAg2AN4B N1BAAg2AN4B N2AAAg2AN5B N1BAAg2AN5B N4BAAg2AN5B N2AAAg2AAg1 N1BAAg2AAg1 N4BAAg2AAg1 N5BAAg2AAg1

Table 4 Hydrogen bond geometry and symmetry code for [Ag2(C10H10N3O3S)2(C5H5N)3]. DAH  A

140.5 (2) 122.6 (3) 92.9 (2) 83.80 (17) 75.56 (17) 142.47 (19) 145.0 (2) 92.7 (2) 117.3 (2) 97.4 (2) 99.4 (2) 91.4 (3) 76.68 (17) 85.49 (17) 147.04 (18) 59.95 (18)

molecule B) are shorter in the Ag(I) complex than those in free ligand. The stereochemistry about the sulfur atom is as usual a slightly distorted tetrahedral geometry with the bond lengths and bond angles involving sulfur lying within the range quoted in the literature [20–22]. The maximum and minimum values of angles around the sulfur atom are for O1AS1AO2 (116.2(3) Å for molecule A and 117.2(4) Å for molecule B) and for O2AS1AN1 (105.0(3) Å for molecule A and 104.4(4) Å for molecule B) and the SAN bond length is similar to that found in Ag–sulfadiazine. Molecular conformation of the sulfonamide group described about S1AN1 bond is 68.9(6)° for molecule A and 68.4(6)° for molecule B, values in the brackets are those of the reported in free molecule (65.1(2)° for molecule A and 59.4(3)° for molecule B) [23].

i

N3AAH3A1  O2B N3AAH3A2  O1Aii N3BAH3B1  O2Aiii N3BAH3B2  O1Biv C8AAH8A  O1A C9AAH9A2  O2Av C12AAH12A  O3Avi C15AAH15A  O2A C15BAH15B  O3A

DAH(Å)

H  A(Å)

DAA (Å)

\DAH  A (°)

0.86 0.86 0.86 0.86 0.93 0.96 0.93 0.93 0.93

2.13 2.23 2.13 2.14 2.49 2.58 2.66 2.37 2.59

2.979 3.028 2.959 2.929 2.971 3.321 3.352 3.164 3.263

168 154 162 152 112 134 132 143 130

(9) (9) (8) (9) (11) (11) (12) (12) (13)

Symmetry codes: (i) x + 3/2, y + 1/2, z + 1/2; (ii) x, y + 1, z; (iii) x + 1, y, z  1/2; (iv) x, y  1, z; (v) x + 1/2, y + 1/2, z; (vi) x  1/2, y + 3/2, z.

Figs. 3 and 4 are the molecular packing diagram of intermolecular and intramolecular interactions in the title compound, respectively. Two of these intermolecular interactions are NAH  O hydrogen bonds formed by the terminal amino nitrogen and sulfonyl oxygen and one CAH  O interactions are formed by terminal methyl carbon of isoxazole ring and the sulfonyl oxygen. IR spectra The infrared spectra (IR) of the complex taken in the region 4000–400 cm1 are compared with those of the free ligand. Based on some general references [24–26] and previous studies of complexes with sulfonamides [27–30], a tentative assignment of the most important bands is given in Table 5. The positions of the characteristic vibrations of free sulfamethoxazole and its silver complex is compared in Table 5. The

Fig. 2. ORTEP diagram of the title compound showing thermal displacement ellipsoids are drawn at 50% probability level.

S.M. Tailor, U.H. Patel / Journal of Molecular Structure 1088 (2015) 161–168

Fig. 3. Molecular packing of title compound showing intermolecular NAH  O interaction.

Fig. 4. Molecular packing of title compound showing intramolecular CAH  O interaction.

165

166

S.M. Tailor, U.H. Patel / Journal of Molecular Structure 1088 (2015) 161–168

Table 5 Characteristics IR bands (cm1) of the spectra of sulfamethoxazole and the Ag– sulfamethoxazole complex. Assignment

Sulfamethoxazole

Ag–sulfamethoxazole

mas(NH2) ms(NH2) m(NH)amide m (@CH)isoxazole ring d(NH2) + m(isoxazole ring) m(C@C) aromatic m(isoxazole ring) mas(SO2) m(CAN) ms(SO2)

3467 (s) 3378 (s) 3299 (s) 3144 (s) 1621 (s) 1596 (s) 1503 (s), 1471 (s) 1305 (s) 1266 (s) 1157 (s) 1091 (s) 885 (s)

3436 (m) 3376 (m) – 3245 (w) 1613 (s) 1598 (sh) 1502 (s), 1468 (s) 1300 (s) 1244 (s) 1164 (s) 1090 (m) 946 (s)

d(CH) aromatic

q(isoxazole ring)

symmetric and antisymmetric bands assigned to m(NH2) in the ligand (3467 and 3378 cm1) are shifted to lower frequencies in the complex (3436 and 3376 cm1), indicating the consequences of the change in their hydrogen bonding scheme. The peak for the sulfonamide (NAH) group in the free ligand at around 3299 cm1, is not present in the spectra of the complex, confirming the deprotonation of the ASO2NHA moiety. Although the SO2 group did not participate in coordination, the ms(SO2) shifted by 7 cm1, probably because of the different spatial orientation of the S@O group in the complex, while the mas(SO2) remained almost unchanged. This behavior is frequently observed in other metal complexes of sulfonamides [27,31,32]. The vibrational spectrum of isoxazole has been described by several authors [29,30]. Because of the rigidity of the penta atomic ring, the spectrum cannot be interpreted in terms of localized vibrations. Similar to other simple metal complexes with isoxazole, in [Ag2(C10H10N3O3S)2(C5H5N)3] only three isoxazole bands showed significant shifts. The bands of the ligands at 3144, 1503 and 885 cm1 shifted to 3245, 1502 and 946 cm1, respectively, after coordination. Most of the other shifts were small. 1

H NMR and

13

C NMR

ligand shows a broad singlet at 10.92 ppm, which may be assigned to the sulfonamide NH proton. The absence of this proton signal in the spectra of the silver complex indicate that the sulfonamide NH group is deprotonated during complex formation. UV spectra The UV spectra of free sulfamethoxazole and its silver complex recorded in DMSO solution are shown in Fig. 5. The electronic spectrum of SMX gave absorption band at 274.2 nm which is assigned to p ? p⁄. The silver ion has completely vacant 5d orbital consequently ligand to metal (L ? M) binding can take place by the acceptance of one pair of electron from the donor nitrogen atom of the ligand. The same transition is observed for silver complex of sulfamethoxazole with 1S spectroscopic term. According to literature [33], no d–d transition is expected for silver complex. The absorbance value of sulfamethoxazole (SMX) and its silver complex are listed in Table 7. Thermogravimetric analysis Sulfamethoxazole (SMX) and its silver complex (Ag-SMX) are studied by thermogravimetric analysis from ambient temperature to 1000 °C in nitrogen atmosphere. The TGA curves are shown as % mass loss versus temperature, the DTG curves are as the rate of loss of mass versus temperature. The thermal decomposition of silver complex of sulfamethoxazole occurs with DTG curve maxima showing endothermic peak at 281.03 °C (DH = 99.6582 kJ mol1) while in free SMX endothermic peak are observed at 262.73 °C (DH = 73.5307 kJ mol1). The final residual mass left at 998 °C correspond to 57.83% for silver complex and 35.81% for free SMX. The thermogravimetric (TG) and differential thermogravimetric (DTG) curves for free sulfamethoxazole (SMX) and its silver complex are depicted in Figs. 6 and 7. Thermodynamic parameters of the synthesized silver complex of sulfamethoxazole and ligand (SMX) itself have been evaluated by Broido’s graphical method [34] for straight line decomposition portion of the thermodynamic analytical curve. Activation Energy (Ea) is calculated by the slope of ln(ln 1/y) versus 1/T, where y is

Due to this complex being insoluble in less polar solvents, 1H NMR and 13C NMR spectra are recorded from a solution of the complex in d6-DMSO. The chemical shifts are expressed in ppm relative to internal TMS. The NMR data is presented in Table 6. The data shows that while the ligand is present in the complex, they only display very small shifts in comparison to the free ligand. The most notable feature is the proton magnetic resonance spectrum of the

Table 6 H NMR and 13C NMR shift assignments of sulfamethoxazole (1) and its Ag complex (2) in DMSO-d6a. 1

a b

Assignment

1

N(1)AH C(1) C(2)AH/C(6)AH C(3)AH/C(5)AH C(4) C(7) C(8)AH N(3)H2 C(9)H3 C(10)

10.921

H(1)

1

H(2)

7.47 6.58

7.55 6.56

6.08 6.07 2.28

6.19 5.78 2.27

13

C(1)

13

C(2)

124.24 128.93 112.70 153.35 158.04 95.38

128.26 128.61 112.61 151.82 165.25 95.74

12.09 169.98

12.41 170.54

Dd(H)b

Dd(C)b +4.02 0.32 0.09 1.53 +7.21 +0.36

+0.08 0.02

+0.11 0.29 0.01

Relative to TMS with DMSO-d6 peak as reference (1H, 2.60 ppm, Dd = d(sulfonamide complex)–d(sulfonamide).

+0.32 +0.56

13

C,43.5 ppm). Fig. 5. UV spectra.

167

S.M. Tailor, U.H. Patel / Journal of Molecular Structure 1088 (2015) 161–168 Table 7 Absorbance, wavelength and assignment of sulfamethoxazole and its silver complex. Ligand/complex

Wavelength (nm)

Energy (cm1)

Assignment

SMX Ag-SMX

274.2 271

36,469 36,900

p ? p⁄/n ? p⁄overlap 1.206 p ? p⁄ 1.995

Absorbance (A)

Table 9 Electrical conductivity and Molar conductance of SMX and its silver complex. Concentration (mM)

1 2 3 4 5

Molar conductance (ohm1 cm2 mol1)

Electrical conductivity (ohm1 cm1) SMX

Ag-SMX

SMX

Ag-SMX

0.78 0.93 1.07 1.24 1.34

4.75 6.74 8.33 9.40 10.63

0.78 0.46 0.35 0.31 0.26

4.75 3.37 2.77 2.35 2.12

Table 10 MIC value (lg/ml) of sulfamethoxazole and its silver complex. Sulfa drug

MIC for Escherichia coli MTCC 442

MIC for Staphylococcus aureus MTCC 96

SMX Ag-SMX

62.5 125

250 200

are calculated using the standard equations [35,36] and data are presented in Table 8. Electrical conductivity measurement The electrical conductivity of millimolar solution of sulfamethoxazole and its silver complex in pyridine are measured at room temperature. The calculated molar conductance (Km) values are given in Table 9. The molar conductance values of the complex range from 2.12 to 4.75 ohm1 cm2 mol1 indicating their nonelectrolytic nature [37]. The result indicates that no anion is present outside the coordination sphere. The very low molar conductivity values in the case of Ag-SMX indicate that complex remain neutral in solution.

Fig. 6. TGAcurve.

Microbiological assays Sulfamethoxazole and its silver complex exhibited varying inhibitory effect toward the bacterial strains. The complex is sensitive toward gram positive bacteria (S. aureus) while it is not active against gram negative bacteria (E. coli). The minimum inhibitory concentration (MIC) values of sulfamethoxazole and its silver complex against S. aureus and E. coli are shown in Table 10. Our observations reveal that the MIC for silver complex changes according to the target bacteria. It is known that S. aureus and E. coli have different cell wall constitution. E. coli has an outer lipidic membrane layer while S. aureus does not have one. Conclusion

Fig. 7. DTG curve.

the fraction of the number of initial molecules not yet decomposed. The thermodynamic parameters like change in enthalpy (DH), entropy (DS), Gibb’s free energy (DG) and Arrhenius constant (A)

Silver complex with different stoichiometries and coordination environments are synthesized, characterized and tested as antimicrobial agents. Single crystals of silver sulfamethoxazole are successfully grown from pyridine solution by slow evaporation technique. The spectroscopic data are in good agreement with

Table 8 Thermodynamic parameters of sulfamethoxazole and its silver complex. Ligand/complex

Decomposition temperature range (K)

Activation energy (kJ mol1)

Arrhenius constant

DH (kJ mol1)

DS (J K1 mol1)

DG (kJ mol1)

SMX Ag-SMX

515.73–555.73 534.03–574.03

77.98 104.26

16.07 21.19

73.53 99.65

226.73 224.70

194.99 224.15

168

S.M. Tailor, U.H. Patel / Journal of Molecular Structure 1088 (2015) 161–168

the crystal structure. Ag-SMX shows higher antibacterial activity than free ligand against gram positive bacteria. Acknowledgement We are thankful to DST- FIST, New Delhi for funding towards the single crystal diffractometer facility at Department of Physics, Sardar Patel University, Vallabh Vidyanagar. One of the authors (SMT) is thankful to UGC for RFSMS fellowship. We are also thankful to Central Salt and Marine Chemicals Research Institute, CSMCRI, Bhavnagar for collecting NMR and TGA data. We also acknowledge the help received from SICART, Vallabh Vidyanagar for CHN and IR data. Appendix A. Supplementary material Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.molstruc.2015.02. 014. These data include MOL files and InChiKeys of the most important compounds described in this article. References [1] N.H. Georgopapadakou, T.J. Walsh, Antimicrob. Agents Chemother. 40 (1996) 279. [2] , fifth ed.M.E. Wolff (Ed.), Burger’s Medicinal Chemistry and Drug Discovery, vol. 2, Wiley, Laguna Beach, 1996. [3] A. Bult, H. Sigel (Eds.), Metal Ions in Biological Systems, vol. 16, Marcel Dekker, New York, 1983. [4] J.E.F. Reynolds (Ed.), Martindale, the Extra Pharmacopoeia, Royal Pharmaceutical Society, London, 1996. [5] E. Kremer, G. Facchin, E. Estevez, P. Albores, E.J. Baran, J. Ellena, M.H. Torre, J. Inorg. Biochem. 100 (2006) 1167. [6] J. Casanova, G. Alzuet, J. Borras, J. Timoneda, S. Garcıa-Granda, I. CandanoGonzalez, J. Inorg. Biochem. 56 (1994) 65. [7] Z.H. Chohan, K. Mahmood-Ul-Hassan, M. Khan, C.T. Supuran, J. Enzym. Inhib. Med. Chem. 20 (2005) 183. [8] D.S. Cook, M.F. Turner, J. Chem. Soc. Perkin Trans. 2 (1975) 1021. [9] C.J. Brown, D.S. Cook, L. Sengier, Acta Cryst. C41 (1985) 718.

[10] C.-X. Ren, B.-H. Ye, H.-L. Zhu, J.-X. Shi, X.-M. Chen, Inorg. Chim. Acta 357 (2004) 443. [11] A. Garcı´a-Raso, J.J. Fiol, S. Rigo, A. Lo´ pez-Lo´ pez, E. Molins, E. Espinosa, E. ~ eiras, Polyhedron 19 (2000) 991. Borra´s, G. Alzuet, J. Borra´s, A. Castin [12] B. Kesimli, A. Topacli, Spectrochim. Acta Part A 57 (2001) 1031. [13] G.M. Sheldrick, SHELXS2013: Program for Crystal Structure Solution, University of Göttingen, Germany, 2013. [14] G.M. Sheldrick, SHELXL2013: Program for Crystal Structure Refinement, University of Göttingen, Germany, 2013. [15] A.L. Spek, PLATON: A Multipurpose Crystallographic Tool, Utrecht University, The Netherlands, 2003. [16] L.J. Farrugia, J. Appl. Cryst. 30 (1997) 565. [17] L.J. Farrugia, J. Appl. Cryst. 32 (1999) 837. [18] National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that grow aerobically, approved standard (M7A5), fifth ed., National Committee for Clinical Laboratory Standards: Wayne, PA, 2000. [19] G.P. Bettinetti, F. Giordano, A. Lamanna, C. Giuseppetti, C. Tadini, Cryst. Struct. Commun. 11 (3) (1982) 821. [20] U.H. Patel, S.A. Gandhi, Indian J. Pure Appl. Phys. 49 (2011) 263. [21] U.H. Patel, B.H. Patel, B.N. Patel, Cryst. Res. Technol. 36 (2001) 1445. [22] U.H. Patel, Cryst. Res. Technol. 30 (1995) 381. [23] M. Takasuka, H. Nakai, Vib. Spec. 25 (2001) 197. [24] D. Lin-Vien, N.B. Colthup, W.G. Fately, J.G. Grasselli, The Handbook of Infrared and Raman Characteristic Frequencies of Organic Molecules, Academic Press, San Diego, 1991. [25] K. Nakamoto, Infrared and Raman Spectra of Inorganic and Coordination Compounds, John Wiley & Sons, USA, 1997. [26] K. Nakanishi, IR-Absorption Spectroscopy – Practical, Holden-Day Inc., San Francisco, 1962. ~ eiras, F. Sanz, Polyhedron 21 [27] B. Macı´as, I. Garcı´a, M.V. Villa, J. Borra´s, A. Castin (2002) 1229. [28] F. Blasco, L. Perello´, J. Latorre, J. Borra´s, S. Garcı´a-Granda, J. Inorg. Biochem. 61 (1996) 143. [29] W.L. Driessen, P.H. van der Voort, Inorg. Chim. Acta 21 (1977) 217. [30] G. Adembri, G. Speroni, S. Califano, Spectrochim. Acta 19 (1963) 1145. ~ eiras, M. Liu-Gonza´lez, F. [31] E. Borra´s, G. Alzuet, J. Borra´s, J. Server-Carrio´, A. Castin Sanz-Ruiz, Polyhedron 19 (2000) 1859. [32] E.E. Chufa´n, J.C. Pedregosa, S. Ferrer, J. Borra´s, Vib. Spectrosc. 15 (1997) 191. [33] A.D. Tella, J.A. Obaleye, Bull. Chem. Soc. Ethiop. 25 (2011) 371. [34] K.R. Venugopala Reddy, J. Keshavayya, J. Seetharamappa, Dyes Pigments 59 (2003) 237. [35] A. Broido, J. Polym. Sci. 7 (1969) 1761. [36] A.W. Coats, J.P. Redfern, Nature 201 (1964) 68. [37] T. Vogel, Textbook of Practical Organic Chemistry, fourth ed., John Wiley Inc., England, 1989.