A new quantum chemical approach in QSAR-analysis. Parametrisation of conformational energies into molecular descriptors JMn (steric) and JSn (electronic).

Two new types of structure-related molecular descriptors, JMn and JSn, have been developed using conformational energies from quantum chemical calculations. For this purpose propipocaine (CAS 3670-68-6) was chosen as a model and 42 analogues were studied. The quantum chemical calculations were performed applying AM1 and PCILO approximation methods. Appropriate mathematical models were designed to calculate steric parameter log JM1 and electronic parameters JS1 to JS6. The values obtained for these parameters were used in multiple linear regression analysis for the evaluation of the structure-activity relationship. Furthermore, a comparison between electronic parameters JSn and sigma (Hammett) was made. The results show, that these parameters can be used successfully in predicting the biological activity of compounds in this model. Although, JS5 values are comparable to sigma-Hammett, the electronic parameter JS2 gives a better correlation in QSAR-analysis involving two parameters JS2 and log JM1.