A comprehensive investigation of the partitioning and hydrogen bonding behavior of indole containing derivatives of 1,3,4-thiadiazole and 1,2,4-triazole by means of experimental and calculative approaches

The lipophilicity and hydrogen bonding capability of the title compounds wa s investigated. HPLC lipophilicity indices proved to be appropriate substit utes of directly measured octanol-water partition coefficients and were use d to evaluate the predictive power of 7 different calculative approaches. C onformation effects as well as particularities in the way the triazole and thiadiazolyl-amine moieties are treated by the different calculation system s need to be taken into account in order to establish sound correlations wi th experimental data. Cyclohexane-water partition coefficients were determi ned and used to derive Delta logP values as a measure of hydrogen bonding a bility. Exploration of the Delta logP parameter unraveled particular featur es of the hydrogen bond capability pattern of the compounds. Thermodynamica lly derived hydrogen bonding parameters Sigma c(a) and Sigma c(d) were used for the analysis of all lipophilicity data. A negative contribution of the hydrogen bond acceptor capability, much stronger in the case of the cycloh exane-water partition coefficients, was found while the hydrogen bond donor factor proved not essential. Similar analysis of the Delta logP values rev ealed a more complex nature of that parameter than being a pure hydrogen bo nd measure.