Effect of Substituents on the Photodynamic Action of Anthraquinones: EPR, Computational and In Vitro Studies

Anthraquinone class of compounds possesses a broad spectrum of therapeutic applications. Cancer cell targeting ability, together with photogeneration of reactive oxygen species, renders anthraquinones an interesting class of photosensitizers for photodynamic therapy (PDT). Screening of newer compounds for better singlet oxygen generation is of current interest to improve the practical usability in PDT. In this study, we investigate the photodynamic activity of nine commercially available anthraquinones, using EPR spectroscopy and computational techniques, to identify the role of substituents on singlet oxygen yield. Three anthraquinone derivatives, 1,5-diaminoanthraquinone, 15-dihydroxyanthraquinone and 1,2,7-trihydroxyanthraquinone, showed highest singlet oxygen quantum yield (0.21, 0.18 and 0.15, respectively) relative to Rose Bengal. Time-dependent density functional theory calculations indicate the singlet oxygen quantum yield of anthraquinones inversely correlate well with the excited singlet-triplet (S1-T1) energy gap. Electron-donating substituents present at positions 1, 2 and 5 of anthraquinone seem to reduce the S1-T1 energy gap, facilitating inter-system crossing and the production of singlet oxygen. This would greatly aid in the design of newer anthraquinone-based photosensitizers. This study also highlights the suitability of 1,5-diaminoanthraquinone for PDT applications as demonstrated by in vitro experiments of photoinduced DNA cleavage and photocytotoxicity in Dalton's lymphoma ascites.