Core Electron Binding Energy (CEBE) as Descriptors in Quantitative Structure–Activity Relationship (QSAR) Analysis of Cytotoxicities of a Series of Simple Phenols

Abstract

Core Electron Binding Energies (CEBEs) of ring carbon atoms in 4-X-phenols were calculated using density-functional theory with the scheme ΔEKS (PW86-PW91)/TZP//HF/6-31G*. The phenols show toxicity to fast growing cells. Using CEBEs of four distinguished carbon atoms in the phenyl ring and oxygen atom in OH of the phenols, the compounds were well separated and grouped by Principal Component Analysis (PCA). Using three out of the five CEBEs, together with σ+ and log P of the phenols as descriptor, we established a QSAR model with Partial Least Squares (PLS) regression which resulted in Q2=0.914. CEBE values when used together with traditionally used descriptors such as log P and σ+ turned out to be useful descriptors in modeling the activity (QSAR) of the compounds with PLS.