title: Structure-activity relationships in nitrothiophenes.
abstract: The structure and electronic properties of a series of biologically active 2-nitrothiophenes (1) have been calculated using both semi-empirical and ab initio molecular orbital methods. Multi-linear regression analysis suggests that there is a reasonable correlation between the experimental activity of the derivatives against either Escherichia coli or Micrococcus luteus and calculated properties such as the HOMO energies, the total atomic charges and ring angles at the heterocyclic sulfur atom, but there is no correlation with the calculated solvation energies or dipole moments. The presence or absence of an additional nitro group at the 3-position of the ring also has a significant effect on the activity. From the derived QSAR equations, the 2-chloro- or 2-bromo-3,5-dinitrothiophenes (1a and 1c) are predicted to show the highest activity against both bacteria, while 2-nitrothiophene (1n) is predicted to be the least active, in line with the experimental results.
authors.affiliation: Chemistry Department, University of Wales Swansea, Singleton Park, Swansea, Swansea SA2 8PP, UK. j.o.morley@swansea.ac.uk
authors.forename: John O
authors.initials: JO
authors.lastname: Morley
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Matthews
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D004583:Electrons; D004926:Escherichia coli / Q000187:drug effects; D016982:Micrococcus luteus / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D009574:Nitro Compounds; D013876:Thiophenes