Synthesıs of some disulfonamide derivatives and their Cu(II) complexes, examination of antimicrobial activities, evaluation of quantitative structure-activity relationship (QSAR)

In this study, eight symmetric aromatic disulfonamides (ptspr, ptsbut, ptspen, mtsen, mtsbut, otsen, otsbut, otspen) with general formula X-ph-SO2-NH-(CH2)n-NH-SO2-ph-X ( where n = 2, 3, 4, 5 and X= o-, m-, p-CH3) were synthesized by the reaction of o-, m-, p-toluenesulfonyl chloride with a series of diamines. Their structures were investigated by elemental analysis, LCMS, 1H-NMR, 13C-NMR, COSY, HETCOR and IR techniques. Structure of N,N'-dimethylenebis(m-toluenesulfonamide) (mtsen) and N,N'-trimethylenebis(p-toluenesulfonamide) (ptspr) were also examined by single crystal X-ray analysis.[Cu(phen)2]L (L= (L= n=3, X=p-CH3; n=4, X=p-CH3; n=5, X=p-CH3; n=2, X=m-CH3; n=4, X=m-CH3; n=2, X=o-CH3) complexes were synthezised and their structure were characterized by LCMS, FTIR, conductivity and magnetic susceptibility techniques. Structure of [Cu(phen)2](mtsen) and [Cu(phen)2](otsen) complexes were also examined by single crystal X-ray analysis.Antimicrobial activity of disulfonamide derivatives were evaluated in vitro against Escherichia coli ATCC 11230, Salmonella enterititis ATCC 13076, Bacillus magaterium RSKK 5117, Bacillus cereus ATCC 6633, Staphylococcus aureus ATCC 25953 by paper disc diffusion and microdilution methods.The compounds exhibit a broad spectrum of activity against Gram-negative and Gram-positive bacteria. It shows relatively better activity against Gram-negative than Gram-positive bacteria. n=2, X=o-CH3 shows higher antibacterial activity with a MIC of 74 µg/mL against Escherichia coli. All compounds possess poor activity against Bacillus magaterium and n=5, X=p-CH3 exhibit the lowest inhibitory activity with a MIC of 440 µg/mL.The QSAR study on a series of symmetric disulfonamides (26 compounds) were carried out to find out the correlation between antimicrobial activities with physicochemical properties and different topological indices using Hansch analysis for Bacillus cereus ATCC 6633, Staphylococcus aureus ATCC and Escherichia coli ATCC 1123. The QSAR reveals that average connectivity indice among topological parameters was found to have overall significant correlation. QSAR models were obtained by cross validated and leave-one-out technique.