On the toxicity of phenols to fast growing cells. A QSAR model for a radical-based toxicity

The cytotoxicities of a series of simple phenols as well as estrogenic phenols such as octyl and nonyl phenols, Bisphenol A, diethylstilbestrol, estradiol, estriol, equilin and equilenin were studied in a fast growing murine leukemia cell line. The use of calculated homolytic bond dissociation energies (BDE) as the electronic parameter led to the development of a Quantitative Structure–Activity Relationship model with superior results; one which established the importance of relatively low BDE values in enhancing toxicity to rapidly multiplying cells. The correlation equation that emerged is as follows: log 1/C = –0.19BDE + 0.21 log P + 3.11. It suggests that toxicity is closely related to mostly homolytic cleavage of the phenolic O–H bond and overall hydrophobicity of the phenol.