Computed libraries of avobenzone derivatives with sulfur groups as enhanced UVA filters

Abstract

Context

Sunscreen formulations often contain avobenzone as a UVA filter to combat the deleterious effects of solar UV radiation. Avobenzone has notable drawbacks: (1) photounstability under UV radiation/sunlight and (2) tendency for skin penetration. The current report aims to improve both the intrinsic photostability and decrease the skin permeability of avobenzone through skeleton structure modification. The electron-donating -OMe group of avobenzone was replaced with diverse groups to compute molecular libraries of avobenzone derivatives. The studies were focused on the sulfur electron-withdrawing groups of avobenzone derivatives as the photostable UV filters contain –SO₃H groups. The UV spectra and bond dissociation energy of Norrish type I cleavages were computed using density functional theory (DFT). The tendency for skin permeability was evaluated by calculating transdermal transportation rate and membrane permeability.

Methods

A total of 2468 avobenzone derivatives were computed using the enumeration tool of the Schrödinger Material Suite platform. Searching for sulfur-containing derivatives yielded a total of 72 molecules, 23 of which exhibited electron-withdrawing properties. These molecules were evaluated for their UVA spectra using TDDFT with the B3LYP functional and a 6-311G + ** basis set. The bond dissociation energy for putative Norrish type I cleavages was calculated using the B3LYP functional in combination with the LACV3P** basis set. The membrane dG insert was calculated using the membrane permeability panel. The maximum transdermal transportation rate (Jm) was derived using the QikProp tool. These results indicate that avobenzone derivatives with sulfonic acid, sulfuric diamide, and sulfonamide functional groups demonstrated improved photochemical properties with a significant reduction in skin permeability compared to the native avobenzone.

Graphical Abstract