Quantum chemical studies on clonidine and related derivatives.

The ground state geometry of the protonated form of clonidine was established by CNDO/2 (complete neglect of differential overlap) calculations. For the interplanar angle of this molecule we found a value of about 40 degrees. The interplanar angles of a number of clonidine related derivatives, both bases and protonated forms, were calculated on the basis of the results obtained for clonidine by taking into account the bond lengths and van der Waals radii of the substituents present at the ortho positions of the phenyl ring. The preferred conformations of the free bases and protonated forms were used as inputs for the semi-empirical PPP-MO (Pariser, Parr and Pople molecular orbital) calculation procedure in order to obtain several quantum chemical parameters. Excellent correlations resulted in relating some of the calculated parameters with the experimentally determined pK'a of the molecules. The results show the ability of MO-calculations to predict the basicity in this series of congeneric molecules and furthermore support the reliability of the calculation procedure in providing the quantum chemical parameters reported in this paper.