Metal complexes of benzimidazole derived sulfonamide: Synthesis, molecular structures and antimicrobial activity Adnan Ashraf a,b , Waseeq Ahmad Siddiqui a,⇑ , Jamshed Akbar a , Ghulam Mustafa c , Harald Krautscheid c , Nazif Ullah d,1 , Bushra Mirza d , Falak Sher e , Muhammad Hanif b,f,⇑ , Christian G. Hartinger b a Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan b School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand c Faculty of Chemistry and Mineralogy, University of Leipzig, Leipzig 04109, Germany d Department of Biochemistry, Quaid-e-Azam University, Islamabad 45320, Pakistan e Department of Chemistry, SSE, Lahore University of Management Sciences, Lahore 54000, Pakistan f Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan article info Article history: Received 20 October 2015 Received in revised form 18 December 2015 Accepted 28 December 2015 Available online 5 January 2016 Keywords: Sulfonamide Benzimidazole Metal complexes Antibacterial activity Carbonic anhydrase inhibitors abstract Benzimidazole and sulfonamide moieties are found in a number of pharmaceutically active molecules. By incorporating the sulfonamide pharmacophore into the benzimidazole scaffold, we prepared 2-(o-sul- famoylphenyl)benzimidazole 1 from saccharin as a precursor. Ligand 1 was coordinated to the divalent transition metals Mn(II) 2, Co(II) 3, Ni(II) 4, Cu(II) 5 and Zn(II) 6 to yield complexes of the general formula [ML 2 (H 2 O) n ](n = 2 for 2 and n = 0 for 3–6). All the compounds were characterized by elemental analysis, conductivity measurements, magnetic susceptibility, FT-IR and NMR spectroscopy. The molecular struc- tures of 1, 3 and 6 were determined by X-ray diffraction analysis. In all metal complexes, 1 behaved as a bidentate chelating ligand through the sulfonamidate nitrogen and the endocyclic nitrogen of benzimi- dazole. The molecular structures of 3 and 6 showed tetrahedral geometry around the Co(II) and Zn(II) centers, respectively. The molar conductivity data revealed the metal complexes to be non-electrolytes. The benzenesulfonamide derivative and its metal complexes were evaluated for their potential antimi- crobial activity against a range of bacterial and fungal strains. [Co(2-(o-sulfamoylphenyl)benzimidazo- late) 2 ] 3 was identified as the most active antibacterial compound, while none of the compounds exhibited antifungal activity. Ó 2016 Elsevier B.V. All rights reserved. 1. Introduction The aromatic and heterocyclic sulfonamides constitute an important class of bioactive small molecules. Some examples of clinically used sulfonamide-based drugs are acetazolamide, methazolamide, ethoxzolamide, and benzolamide (Fig. 1). These are widely used in clinics for example as antiglaucoma agents, antiepileptic, diuretic and antiobesity drugs [1–4]. In recent years, they have been extensively investigated as inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1), which is one of the most important zinc–containing metalloenzymes involved in several physiological processes [5]. Sulfonamides (RSO 2 NH 2 ) proved to be excellent inhibitors of CAs. Mechanistic studies on more than 200 CA X-ray crystal structures with inhibitors showed that sulfonamidates (RSO 2 NH À ) bind to the zinc ion of the enzyme active site and dis- rupt the catalytic process. The remaining scaffold of the drug mole- cule participates in multiple interactions with amino acid residues and water molecules, which further stabilize the enzyme–inhibitor adduct [5–7]. Metal-based drugs are widely employed for the treatment and diagnosis of a range of diseases [8–12]. For example, complexes of platinum are used as anticancer, of gold as anti-arthritic and sil- ver compounds as antimicrobial agents, whereas gadolinium and manganese derivatives play an important role as MRI contrast agents [13]. This led several research groups to prepare metal com- plexes of clinically-used heterocyclic sulfonamides and they were evaluated for their biological properties [4,5,7,14]. Sulfonamides turned out to be versatile ligands and form interesting coordina- tion complexes under basic conditions in alcoholic solutions with http://dx.doi.org/10.1016/j.ica.2015.12.031 0020-1693/Ó 2016 Elsevier B.V. All rights reserved. ⇑ Corresponding authors at: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand (M. Hanif). E-mail addresses: waseeq786@gmail.com (W.A. Siddiqui), m.hanif@ auckland.ac.nz (M. Hanif). 1 Current address: Department of Biotechnology, Abdul Wali Khan University Mardan, Pakistan. Inorganica Chimica Acta 443 (2016) 179–185 Contents lists available at ScienceDirect Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica