Synthesis, crystal structure, antibacterial activities, and electrochemical studies of new N,N 0 -polymethylene bis-sulfonamides Neslihan Özbek a , Saliha Alyar b , Serhat Mamas ß c , Ertan S ßahin d , Nurcan Karacan c,⇑ a Department of Primary Education, Faculty of Education, Ahi Evran University, TR-40100 Kırs ßehir, Turkey b Department of Chemistry, Science and Art Faculty, Karatekin University, TR-18100 Çankırı, Turkey c Department of Chemistry, Faculty of Science, Gazi University, TR-06500 Ankara, Turkey d Department of Chemistry, Faculty of Science and Art, Atatürk University, TR-25240 Erzurum, Turkey article info Article history: Received 2 August 2011 Received in revised form 19 October 2011 Accepted 20 October 2011 Available online 11 November 2011 Keywords: Bis-sulfonamides Antimicrobial activity Cyclic voltammetry X-ray structure abstract Four disulfonamide derivatives (C 2 H 5 SO 2 NH) 2 (CH 2 ) n (n = 2, 3, 4, 5) were synthesized and characterized by FTIR, 1 H NMR, 13 C NMR, HETCOR, LCMS and elemental analysis. Ethanesulfonamide-N,N 0 -pentamethylene bis was also characterized by X-ray single crystal diffraction measurement. The electrochemical characteristics of the disulfonamide derivatives were performed by cyclic voltammetry and chronoamperometry. 1 H and 13 C NMR chemical shifts of the compounds were calculated by using DFT/B3LYP methods with a 6-311++G (d,p) basis set. Antibacterial activity and the structural relationship of the compounds showed that activity decreases proportionately to the increasing length of the carbon chain between NH groups, log P values, hydration energy and molecular volumes. Anodic peak potentials and HOMO values do not correlate with the activity, but reduction potential and LUMO decrease weakly with increasing activity. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Sulfonamides were the first effective chemotherapeutic agents employed systematically for the prevention and cure of bacterial infections in humans and other animal systems [1–3]. Despite the loss of value in the development of antimicrobial therapy over time, the synergetic action of sulfonamides with trimethoprim has brought about widespread usage over the last decade [4]. The dis- covery of novel antimicrobial agents with better pharmacological profiles is still highly desirable, due to the evolution of drug resis- tance [5,6] and the threat of bioterrorism [7]. Knowledge on the antimicrobial activity of bis-sulfonamides appears to be limited in the literature [8,9]. Wilkinson et al. showed that a bis-arylsulfonamide exhibits moderate growth inhi- bition against Mycobacterium smegmatis [10]. Asundaria et al. re- ported that 4-sulfonamides substituted novel sydnones show excellent antibacterial activity against Gram pos. Staphylococcus pneumoniae and Staphylococcus aureus, and Gram neg. bacteria Escherichia coli and Pseudomonas aeruginosa [11]. In our previous studies, aliphatic/aromatic bis sulfonamides were synthesized and tested for antimicrobial activity [12–16]. Continuing our studies, in this paper a series of new N,N 0 -polymeth- ylene bis-sulfonamide derivatives (indicated as n = 2: ESEN, n = 3: ESPR, n = 4: ESBUT, and n = 5: ESPEN) (Fig. 1) were synthesized and characterized by elemental analysis, and FT-IR, 1 H NMR, 13 C NMR, 2D-HETCOR and LC–MS methods. Electrochemical properties of the compounds were studied by cyclic voltammetry and chrono- amperometry. Their antibacterial activities were evaluated against Gram-positive bacteria (S. aureus ATCC 25923, Bacillus cereus RSKK 863, Bacillus subtilis ATCC 6633, Listeria monocytogenes ATCC Li6 (izolate) and Gram-negative bacteria (E. coli ATCC 11230, Salmonella enterititis ATCC 13076, P. aeruginosa ATCC 27853 and Yersinia enterocol- itica O:3) by both disc diffusion and micro dilution methods. The crystal structure of ESPEN was investigated by X-ray analysis. Theoretical chemical shifts of the compounds were calculated by using DFT/B3LYP methods with a 6-311++G (d,p) basis set to support the examination. 2. Experimental 2.1. Chemistry The elemental analyses (C, H, N and S) were performed on a LECO–CHSNO – 9320 type elemental analyzer. The IR spectra (4000–400 cm 1 ) were recorded on a Mattson-1000 FT-IR spectro- photometer with samples prepared as KBr pellets. NMR spectra were recorded on a Bruker-Spectrospin Avance DPX – 400 Ultra – Shield (400 MHz) by using DMSO as a solvent and TMS as an inter- nal standard. LC/MS-APCl was recorded on the AGILENT 1100. The melting point was recorded on Opti Melt apparatus. TLC was con- ducted on 0.25 mm silica gel plates (60F254, Merck). Visualization was made by using ultraviolet light. All extracted solvents (all from 0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2011.10.040 ⇑ Corresponding author. Tel.: +90 312 2021117; fax: +90 312 2122279. E-mail address: nozbek@gazi.edu.tr (N. Karacan). Journal of Molecular Structure 1010 (2012) 1–7 Contents lists available at SciVerse ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc