Theoretical studies on sulfanilamide and derivatives with antibacterial activity: conformational and electronic analysis.
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 NH(2) and SO(2) 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.
Vega-Hissi
Esteban G
EG
Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nac. de San Luis, San Luis, Argentina. egvega@unsl.edu.ar
Andrada
Matías F
MF
Zamarbide
Graciela N
GN
Estrada
Mario R
MR
Tomás-Vert
Francisco
F
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003198:Computer Simulation; D004563:Electrochemistry; D004583:Electrons; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D013424:Sulfanilamides / Q000737:chemistry*; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D013424:Sulfanilamides
J Biol Chem. 1962 Feb;237:536-40
13873645
J Org Chem. 2006 Apr 14;71(8):2952-6
16599587
J Mol Model. 2008 Aug;14(8):689-97
18458968
J Org Chem. 2004 Aug 6;69(16):5448-53
15287795
Bioorg Med Chem. 2008 Apr 1;16(7):3519-29
18316193
J Med Chem. 2007 Dec 27;50(26):6535-44
18052117
J Chem Theory Comput. 2007;3(2):407-433
19002267
J Phys Chem A. 2008 Apr 3;112(13):2969-76
18302350
Chem Rev. 2005 Aug;105(8):2999-3093
16092826
J Org Chem. 2009 Jul 3;74(13):4740-6
19558179
Chemosphere. 2008 Jun;72(5):836-43
18396316