Journal of Chromatography, 403 (1987) 19-26 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands CHROM. 19 637 SOME PROBLEMS IN THE CORRELATION OF MOLECULAR PARAM- ETERS AND THE CONNECTIVITY INDEX 0. PAPP* and Gy. SZASZ Institute qf Pharmaceutical Chemistry, Semmelwei,~ Mrdical C’niversity, H-1092 Budapest (Hungary) M. FARKAS and G. SIMON Sqftwurehouse and Data Center qf Semmelweis Medical C’ninirersity, Budapest (Hungary) and I. HERMECZ Chinoin Pharmaceutical Works, Budapest (Hungary) (Received February 10th. 1987) SUMMARY A study was made of 28 heterocyclic nitrogen-containing compounds and 68 of their alkyl derivatives. Their retention indices were determined on the stationary phases OV-1, OV-25, OV-225 and Carbowax 20M, and their molecular connectivity indices were obtained by the method of Kier. It was found that the four groups of compounds distinguished by cluster analysis corresponded to certain molecular prop- erties, even without a regression correlation. A tree-graph produced from the data revealed those pairs of compounds and those structural differences which are not (or only slightly) differentiated by the connectivity index. The effect of the mean polarity of the stationary phase was used to evaluate the fit of the regression. By comparison of the statistical parameters of the various regression equations, a study was made of the roles played by the simple, valence, path and path-cluster indices in the value of the dependent variable. INTRODUCTION Randic’ made use of graph theory to describe various properties of isomeric hydrocarbons by means of the branching index. This method was developed by Kier and Ha112-“, who also reported a structure-effect correlation for halogenated phenol derivatives7. The correlation coefficient, Y, for the correlation between the bacterio- static effect of phenol derivatives and the connectivity, x, was 0.975. DiPaolo et aL8 found a correlation between the volatility and the connectivity in terms of the indices 2x and 3xpc, with r = 0.821. Kier and Hall” characterized the hallucinogenic effect of amphetamine derivatives by means of a correlation with Y = 0.920. Besides the index 6xp, the reciprocals of the indices “x& and 3xp were featured in this correlation (for the meaning of the symbols see ref. 6). Even closer correlations have been demonstrated with various physico-chem- 0021-9673/87,/%03.59 c 1987 Elsevier Science Publishers B.V.