Correlation of di- and tripeptide distribution coefficients with structure via unitary molecular indices

Abstract

The unitary molecular structure indices, viz., the integrated molecular transform (FTm), the integrated electronic transform (FTe), the integrated charge transform (FTc), the normalized molecular moment (Mn), and the normalized electronic moment (Me) were used in separate trials to model the reported apparent distribution coefficients (log P′) of 25 dipeptides and 34 tripeptides. Linear regressions indicated that the two series should be considered separately as shown by the correlation coefficients and F statistics. In these cases, the former exceeded 0.75 generally and reached 0.795 for the FTe. The correlation coefficients for the FTc index were 0.692 and 0.380, respectively, for the two series and thus indicative of its inadequacy as a descriptor for this model. A bivariant regression of log P′ against Mn and Me did not improve on the monovariant models. The molecular weight as a structure surrogate gave adequate correlation coefficients but is not recommended as structure parameters are implicit rather than explicit. The Mn or Me correlations may be used to estimate log P′ for compounds similar to those in the dipeptide series, and FTe, likewise in the tripeptide series. The possible requirement for an amide group descriptor is discussed. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 49–56, 1998