Functional group substitutions influence the binding of benzophenone-type UV filters with DNA

Abstract

As a class of possible carcinogens, benzophenone-type UV filters (BPs) widely exist in natural environments and organisms. The crucial step of the carcinogenic process induced by cancerous toxins is binding with DNA to form adducts. Here, the binding of 10 typical BPs, i.e., benzophenone (BP1), 2-hydroxyl benzophenone (BP2), 4-hydroxyl benzophenone (BP3), 2,2'-dihydroxyl benzophenone (BP4), 2,4-dihydroxyl benzophenone (BP5), 4,4'-dihydroxyl benzophenone (BP6), 2,4,4'-trihydroxyl benzophenone (BP7), 2,2',4,4'-tetrahydroxyl benzophenone (BP8), 2-hydroxyl-4-methoxyl benzophenone (BP9), and 2,2'-dihydroxyl-4-methoxyl benzophenone (BP10), with DNA was tested via fluorescence quenching experiments. Only hydroxyl group-substituted BPs could bind to DNA by groove binding mode, and the quenching constants were 0.93 × 10³-5.89 × 10³ L/mol. Substituted BPs were preferentially bound to thymine. Circular dichroism analysis confirmed that BPs could affect DNA base stacking but could not transform its B-form. Based on molecular electrostatic surface potential analyses, molecular dynamics simulations, and energy decomposition calculations, it could be found that the site and number of hydroxyl substitution changed the molecular polarity of BPs, thereby affecting the number and strength of hydrogen bonds between BPs and DNA. The hydroxyl substitution at site 2 was more conducive to binding than at site 4. This study is beneficial in comprehending the carcinogenic mechanisms of BPs.

Keywords: Genetic materials; Groove binding; Hydrogen bond; Hydroxyl group; Sunscreen.