Sterically Congested Adamantylnaphthalene Quinone Methides

Five new (2-adamantyl)naphthol derivatives (5–9, quinone methide precursors, QMP) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of QMP 5 to S1 leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide QM5 which was characterized by LFP (in CH3CN–H2O, λmax = 370 nm, τ = 0.19 ms). On irradiation of QMP 5 in CH3OH–H2O (4:1), the quantum yield of methanolysis is Φ = 0.70. Excitation of naphthols QMP 6–8 to S1 in CH3CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, QMP 6–8 undergo solvent-assisted PT giving QM6 or zwitterion QM8 that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. QMP 9 in a protic solvent undergoes two competitive processes, photosolvolysis via QM9 and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. QM9 has been characterized by LFP (in CH3CN–H2O, λmax > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, QM10 and QM11 were synthesized thermally and characterized by X-ray crystallography. QM10 and QM11 do not react with H2O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of 5–9 was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with 5 to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of QM5.