Exploring the consistency of logP estimation for substituted coumarins

Abstract

AbstractThe lipophilicity of a series of substituted coumarins was investigated by experimental and calculative approaches. The compounds contain substituted amidoximes, or substituted heterocycles directly attached at position 4 of the coumarinic skeleton. The reliability of the predictions produced by 8 different calculation systems was evaluated considering the absolute differences and the correlation between experimental and calculated logP values. The calculation procedure based on electrotopological state indices provided better results than the fragmental and atomic contribution systems applied. The consistency of the predictions based on the fragmental or atomic contribution systems was further explored by comparing the contribution of certain structural characteristics, defined as special π constants, in the experimental and estimated logP values. Differences between the heterocyclic and the original benzene π constants were found to affect the predictions. They might be attributed to the contribution of electronic effects as further supported by the factorization of logP in bulk and electronic terms. The same factors were found to be significant for the calculated logP values derived on the basis of the Electrotopological State Indices.