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Theoretical studies on sulfanilamide and derivatives with antibacterial activity: conformational and electronic analysis

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Abstract

Quantum chemical methods have been used to study the conformational and electronic properties of sulfanilamide and derivatives with antibacterial activity. Calculations at B3LYP/6-311++G(3df,2p) level of theory predict the existence of four conformers for sulfanilamide depending on the orientation of p-amino and amide groups. Focusing on the sulfonamide moiety, amide NH2 and SO2 groups could exist either in an eclipsed or staggered arrangement. Gas-phase results predict the eclipsed conformer to be most stable but opposite to what has been rationalized previously, no stabilizing hydrogen bonds between those groups has been found through NBO analysis. When solvent effect is taken into account through the IEF-PCM method, staggered conformer is preferred; in fact, eclipsed conformation changed when explicit solvent molecules were included. Conformational analysis of all derivatives has shown two global minima which are specular images. Five out of the seven derivatives studied adopted a particular minimum energy conformation with very similar geometries.

Antibacterial sulfonamides show a large conformational similarity degree.

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References

  1. Lu RJ, Tucker JA et al. (2007) Design and Synthesis of Human Immunodeficiency Virus Entry Inhibitors: Sulfonamide as an Isostere for the α-Ketoamide Group. J Med Chem 50:6535–6544. doi:10.1021/jm070650e

    Article  CAS  Google Scholar 

  2. Purushottamachar P, Khandelwal A, Vasaitis TS, Bruno RD, Gediya LK, Njar VCO (2008) Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating agent. Bioorg Med Chem 16:3519–3529. doi:10.1016/j.bmc.2008.02.031

    Article  CAS  Google Scholar 

  3. Tappe W, Zarfl C, Kummer S, Burauel P, Vereecken H, Groeneweg J (2008) Growth-inhibitory effects of sulfonamides at different pH: Dissimilar susceptibility patterns of a soil bacterium and a test bacterium used for antibiotic assays. J Chemosphere 72:836–843. doi:10.1016/j.chemosphere.2008.02.041

    Article  CAS  Google Scholar 

  4. Brown GM, Weisman RA, Molnar DA (1961) The Biosynthesis of Folic Acid: I. Substrate and Cofactor Requirements for Enzymatic Synthesis by Cell-Free.Extracts of Escherichia coli. J Biol Chem 236:2534–2543

    CAS  Google Scholar 

  5. Brown GM (1962) The biosynthesis of folic acid: II. Inhibition by sulfonamides. J Biol Chem 237:536–537

    CAS  Google Scholar 

  6. Petrov V, Petrova V, Girichev GV, Oberhammer H, Giricheva NI, Ivanov S (2006) Molecular Structure and Conformations of Benzenesulfonamide: Gas Electron Diffraction and Quantum Chemical Calculations. J Org Chem 71:2952–2956. doi:10.1021/jo0524270

    Article  CAS  Google Scholar 

  7. Petrov V, Girichev GV, Oberhammer H, Petrova V, Giricheva NI, Bardina AV, Ivanov SN (2008) Molecular Structure and Conformations of para-Methylbenzene Sulfonamide and ortho-Methylbenzene Sulfonamide: Gas Electron Diffraction and Quantum Chemical Calculations Study. J Phys Chem A 112:2969–2976. doi:10.1021/jp710532z

    Article  CAS  Google Scholar 

  8. Bharatam PV, Amita GA, Kaur D (2002) Theoretical studies on S–N interactions in sulfonamides. Tetrahedron 58:1759–1764. doi:10.1016/S0040-4020(02)00061-3

    Article  CAS  Google Scholar 

  9. .Lee PS, Du W, Boger DL, Jorgensen WL (2004) Energetic Preferences for 〈,® versus ®,© Unsaturation. J Org Chem 69:5448–5453. doi:10.1021/jo049363y

    Article  CAS  Google Scholar 

  10. Reed AE, Curtiss LA, Weinhold F (1988) Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem Rev 88:899–926. doi:10.1021/cr00088a005

    Article  CAS  Google Scholar 

  11. .Vandermeeren L, Leyssens T, Peeters D (2007) Theoretical study of the properties of sulfone and sulfoxide functional groups. J Mol Struct THEOCHEM 804:1–8. doi:10.1016/j.theochem.2006.10.006

    Article  CAS  Google Scholar 

  12. Leyssens T, Peeters D (2004) Theoretical study of the properties of phosphonate. J Mol Struct THEOCHEM 673:79–86. doi:10.1016/j.theochem.2003.12.001

    Article  CAS  Google Scholar 

  13. Riley KE, Op’t Holt BT, Merz KM Jr (2007) Critical Assessment of the performance of density functional methods for several atomic and molecular properties. J Chem Theory Comput 3:407–433. doi:10.1021/ct600185a

    Article  CAS  Google Scholar 

  14. Cossi M, Scalmani G, Rega N, Barone V (2002) New developments in the polarizable continuum model for quantum mechanical and classical calculations on molecules in solution. J Chem Phys 117:43–54. doi:10.1063/1.1480445

    Article  CAS  Google Scholar 

  15. Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3094. doi:10.1021/cr9904009

    Article  CAS  Google Scholar 

  16. Warren L. DeLano. PyMOL v.0.99. DeLano Scientific LLC. (2004).

  17. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA. (2003) Gaussian 03 Revision B.05. Gaussian Inc, Wallingford, CT

  18. .Glendening ED, Reed AE, Carpenter JE, Weinhold F (1993) NBO Version 3.1.

  19. Clark T, Murray JS, Lane P, Politzer P (2008) Why are dimethyl sulfoxide and dimethyl sulfone such good solvents? J Mol Model 14:689–697. doi:10.1007/s00894-008-0279-y

    Article  CAS  Google Scholar 

  20. Modarresi-Alam AR, Amirazizi HA, Bagheri H, Bijanzadeh H, Kleinpeter E (2009) Dynamic 1H NMR spectroscopic study of the ring inversion in N-Sulfonyl morpholines—studies on N − S interactions. J Org Chem 74:4740–4746. doi:10.1021/jo900454a

    Article  CAS  Google Scholar 

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Acknowledgments

Authors thank Universitat de València for the computational resources provided.

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Authors and Affiliations

  1. Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nac. de San Luis, Chacabuco 917, 5700, San Luis, Argentina

    Esteban G. Vega-Hissi, Matías F. Andrada, Graciela N. Zamarbide & Mario R. Estrada

  2. Departament de Química Física, Universitat de València, Campus Burjassot-Paterna, 46100, Burjassot, València, España

    Francisco Tomás-Vert

Authors
  1. Esteban G. Vega-Hissi
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  2. Matías F. Andrada
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  3. Graciela N. Zamarbide
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  4. Mario R. Estrada
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  5. Francisco Tomás-Vert
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Correspondence to Esteban G. Vega-Hissi.

Electronic supplementary materials

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894_2010_829_MOESM1_ESM.pdf

B98 and B1B95 geometric parameters and energy differences between eclipsed and staggered conformers (Tables S1 and S2). Other important interactions in SNA derivatives (Table S3). Potential energy surfaces of sulfanilamide derivatives (Figs. S1 and S2).+ (PDF 2302 kb)

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Vega-Hissi, E.G., Andrada, M.F., Zamarbide, G.N. et al. Theoretical studies on sulfanilamide and derivatives with antibacterial activity: conformational and electronic analysis. J Mol Model 17, 1317–1323 (2011). https://doi.org/10.1007/s00894-010-0829-y

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  • DOI: https://doi.org/10.1007/s00894-010-0829-y

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