Flow microcalorimetricstudies of phenol and its chlorinated derivatives and a theoretical evaluation of their possible inhibition mode on Chromobacterium violaceum respiration

The general belief that chemical structure determines the biological effect of drugs has led to several techniques to establish structure-activity relationships (SAR) that is useful in the development of more active compounds. Predicting toxic effects based on SAR, one can obtain toxicological data with a low cost-benefit ratio. Chlorophenols that represent a class of toxic agents frequently used in industrial processes are not satisfactorily described in the literature in relation to their toxicity. The main objective of this work is to relate the microbial activities of phenol, anisole and their chlorinated derivatives on Chromobacterium violaceum respiration with their physicochemical properties. Anisole and its chlorinated derivatives were used to evaluate the influence of phenol acidity on biological activity. The calculations were carried out at the semi-empirical AM I and ab initio DFT levels employing the basis sets CEP-31G, CEP-31+Ge CEP-31G** that were parameterized using the continuum-solvation model COSMO for solvent contribution. Both empirical and theoretical properties were evaluated by chemometric analyses (hierarchical Cluster analysis (HCA) and principal component analysis (PCA)), to correlate the physicochemical properties of the phenol, anisole and their chlorinated derivatives with their biological activities. The results obtained for the current work indicate that the biological activities of these Compounds increase as the n-octanol/water (log P) partition coefficients, ionization energies (IP), melting points (mp) and dissociation constants increase and the solvent effects (SE), enthalpies of formation (Delta(f)Hdegrees) and proton affinities (PA) decrease. (C) 2004 Elsevier B.V. All rights reserved.