Lipophilicity Determination using Both TLC and Calculations

Abstract

Lipophilicity of four different groups of organic compounds was both measured and calculated. Measurements were done using reversed-phase thin-layer chromatography and lipophilicity was considered as the RM,0 values of their RM versus the percentage of the organic modifier. Calculation was performed using a recent version of the Pallas program of CompuDrug, Inc. Between RM,0 and logP, a surprising deviation was found in case of cyasterone having an extra ring. Other ecdysteroids gave a well arranged group determining a straight line. RP-TLC-measured lipophilicity values of about 30 phenylalkyl compounds also showed good correlation with those of the calculated logP values. Deviations were found in the case of J-508 (having an indol ring instead of a phenyl ring). Positive differences were found in cases of para-halogen substituted compounds, where the calculated values were higher than those predicted by the corresponding straight line of the experimentally found RM,0 versus calculated logP. RM,0 values versus calculated logP series of dermorphine derivatives were also gathered in a cluster. The consequence of consistent substitution gave a larger impetus to lipophilicity experimentally than by calculation. Experimental determination of RM,0 values of pyridinium aldoximes was not possible using a reversed-phase stationary phase. Calculated hydrophilicity did not correlate with logP.