Quantitative structure-retention relationships modeling and multivariate data analysis of lipophilicity data of new spirohydantoin derivatives

Abstract

© Akadémiai Kiadó. Modeling properties of newly synthesized compounds is important for both understanding their activity and predicting their interactions. This paper describes the evaluation of the lipophilicity of the newly synthesized cycloalkylspiro-5-hydantoins by experimental and calculation methods. The chromatographic lipophilicity (RM0) of the analyzed compounds was determined by reversed-phase liquid chromatographic system consisting of RP-18 stationary phase and methanol-water mobile phase. Correlation coefficients between RM0 values and the predicted log P were above 0.93, indicating a strong linear relationship between the variables. Multivariate data analysis applied in this study enabled the comparison of the lipophilicity and the structure of the investigated compounds using solely information obtained from thin-layer chromatography. Hierarchical clustering analysis (HCA) reveals a high similarity between RM0 and miLogP whereas squared log Ps such as ALOGP2 and MLOGP2 were distinct from RM0. HCA classifies the investigated compounds into three clusters according to lipophilicity. Principal component analysis (PCA) yields two principal components which explained >99.19% total variance. The changes in the lipophilicity of the substituents attached in the molecule are reflected in the value of PCs. An increase in the lipophilicity of spiro substituent results in a decrease of values of both PC1 and PC2. The increase in the lipophilicity of R substituent decreases the value of PC1 and increases the value of PC2. The positive value of PC1 is typical for the compounds with the electron withdrawing groups such as CN, NO2, or OCH3.