Investigation of the solvent-dependent photolysis of a nonnucleoside reverse-transcriptase inhibitor, antiviral agent efavirenz.

Abstract

This study sought to investigate the solvent-dependency on the photolysis of efavirenz to gain insight into the photoprocesses involved. The primary mechanisms were firstly the excited-state intramolecular proton transfer (i.e. phototautomerization), which generated the imidic acid phototautomer observed as [M-H]^- quasimolecular ion at m/z 314.0070 in the high-performance liquid chromatography-electrospray ionization-time-of-flight mass spectrometry in the negative mode. Secondly, the photoinduced α-cleavage with the loss of a carbonyl group occurred (i.e. photodecarbonylation) to form the photoproduct at m/z 286.0395. The ultraviolet-visible spectra illustrated a large, hyperchromic, and slight bathochromic effect in both the π→π* and n→π* electronic transitions. The largest bathochromic effect was prevalent in the chloroform solvent, i.e. chloroform (π* = 0.58; β = 0.00; α = 0.44) > methanol (π* = 0.60; β = 0.66; α = 0.98) > acetonitrile (π* = 0.75; β = 0.40; α = 0.19). This is due to the significant interaction of the amino group with the excited carbonyl moiety which is attributed to intramolecular phototautomerization resulting in a larger energy shift of the electronic state. A plausible explanation is due to the hydrogen bond donor ability of the polar methanol and nonpolar chloroform solvents, which stabilized the polarized imidic acid phototautomer by means of hydrogen bonding interactions, as opposed to the aprotic acetonitrile which exhibits no hydrogen bonding interactions. The study would form the basis for further photolytic analyses and syntheses to generate a plethora of novel photoproducts with anti-HIV activity based on the biologically active benzoxazinone framework of efavirenz.