Spectroscopy and photophysics of styrylquinoline-type HIV-1 integrase inhibitors and its oxidized forms studied by steady state and time resolved absorption and fluorescence

Abstract

The geometric and electronic structure in solution of a new 2-styrylquinoline-type inhibitor of the HIV1-integrase was examined for the first time by following changes in the photophysical properties of the chromophore using steady state as well as time resolved absorption and fluorescence methods. The results obtained under different conditions of pH and solvent revealed that there are at least two rotamers in the ground state which exhibit different photophysical and photochemical properties. Picosecond fluorescence and absorption measurements gave evidence for a very short (∽20–30 ps) singlet excited state lifetime for one conformer and a much longer one for the other conformer, from a few hundreds of picoseconds up to nanoseconds, depending on the solvent characteristics. At physiological pH, the longer lived conformer can also undergo oxygen oxidation or photooxidation giving rise to the formation of the semiquinone radical and ultimately to a stable orthoquinone species. The role played by the singlet excited state of the rotamer on the photooxidation process is also detailed using picosecond and nanosecond absorption measurements.