Determination of solute descriptors of tripeptide derivatives based on high-throughput gradient high-performance liquid chromatography retention data

Recently proposed chromatographic hydrophobicity indices (CHIs) have been calculated from the correlation of fast gradient HPLC retention times with rho(0) values from isocratic HPLC measurements for 30 oligopeptide derivatives. Measurements were performed on five HPLC columns; an Inertsil ODS (In), a Prodigy ODS (Pro), an immobilised artificial membrane (IAM), a permethylated beta-cylcodextrin (CD) and a cyanopropyl (CN) stationary phase. The ranking of CHI values of the tripeptide derivative of the type Z-Ala-Xaa-Val-OMe for the CD, IAM and CN phases is comparable with other amino acid hydrophobicity scales. The CHI values were used for the determination of three molecular descriptors of the solvation equation established by Abraham; these are the effective hydrogen-bond acidity Sigma alpha(2)(H), the effective hydrogen-bond basicity Sigma beta(2)(H) and the solute dipolarity/polarisability pi(2)(H). The comparison of the solute descriptors of the tripeptide derivatives in terms of the change of the sequence and the chirality of the amino acids shows a strong influence on Sigma alpha(2)(H), Sigma beta(2)(H) and pi(2)(H). (C) 1998 Elsevier Science B.V.