QSAR STUDY OF 4-HYDROXYPYRIDINE DERIVATIVES AS INHIBITORS OF THE HILLREACTION

QSAR analysis has been performed for two sets of 4-hydroxypyridine der ivatives, i.e. phenol type inhibitors of photosystem II, to find accur ate quantitative models for their inhibitory potency in the Hill react ion. Separate QSAR models based either on the structural descriptors ( molecular connectivity indices and other topological features) or on t he physicochemical constants (pi, V-w, sigma) have been developed for the two sets of 4-hydroxypyridine derivatives. It was found that the s ize and lipophilicity of substituents at positions 2 and 5 are the mos t important for the activity of derivatives with a long side chain. Th e electron-attracting capacity of these substituents might be an addit ional factor which increases the activity of 4-hydroxypyridines in the Hill reaction. However, the inhibitory potency of tetrahalogenated 4- hydroxpyridines depends on the type of halogen atom on the pyridine ri ng. The iodine substituent meets the receptor requirements best. The s tudy suggests that the two groups of 4-hydroxypyridines analyzed have overlapping binding sites on the receptor protein.