Mechanistic studies of selected photochemical cleavage reactions using transient spectroscopic experiments and theoretical calculations

Abstract

In this thesis, time-resolved spectroscopic techniques including transient absorption spectroscopy, fluorescence spectroscopy and resonance Raman spectroscopy were used to investigate the photochemical and photophysical processes for: 1) the photo-release reactions of 8-cyano-7-hydroxyquinoline (CyHQ) caged tertiary amines; 2) the photo-rearrangement reactions of quaternary CyHQ-protected anilines; and 3) the generation and characterization of a halogenated diarylnitrenium ion. The interpretation of these experimental results was assisted by results from density functional theory calculations performed for relevant excited-state intermediates thought to be possibly involved in the reactions examined in this thesis.

Unlike traditional photoremovable protecting groups (PPGs) that release bioagents after UV irradiation, the CyHQ-caged systems can enable the release of the bioagent of interest by using two-photon excitation of near-IR or IR light. Although PPGs have been broadly studied in synthetic protection and photoactivation of various functional chemical species, there are very few researches reporting efficient photoinduced uncaging for tertiary amines and its applications for use in biological systems. In this research, the photolysis of CyHQ-caged triethylamine (CyHQ-TEA) in a neutral buffer solution has been demonstrated to proceed through the rapid release of a caged amine from a singlet state intermediate with a very fast time constant of 70 ± 19 ps, which is 70 times faster than the photorelease of a acetate caged by another similar PPG from a triplet state. This faster release from a singlet state after photolysis of CyHQ-TEA means that controlling the release of tertiary amines conjugated to CyHQ upon one or two photon excitation could be very useful to more precisely localize the activation of amine-derivative bioagents in physiology environments. It is also very promising to develop these new types of PPGs for applications in polymer synthesis and materials science.

In addition, the time-resolved spectroscopic and theoretical quantum calculation results have also demonstrated that the photolysis of the CyHQ-caged dimethylaniline gives the ortho-alkylated aniline as a primary product through an unconventional Hofmann-Martius rearrangement reaction. This primary product is very different with that of the conventional one, which usually requires an acid catalyst and produces a para-alkylated aniline as a primary product. This finding is very interesting and inspirational for organic synthesis scientists, because this novel reaction model is potentially useful for obtaining ortho-substituted alkyl aniline from the photolysis of the corresponding N-α-alkylaniline under much milder reaction conditions.

Finally, this thesis presents direct observation of a halogenated diarylnitrenium ion generated within 4 ps by the photolysis of the N-(4,4’-dibromodiphenylamino)-2,4,6-trimethylpyridinium BF4- salt (DN) in pure MeCN, and this nitrenium ion can undergo a nucleophilic adduct reaction with H2O in aqueous solution conditions. These results provide a new benchmark characterization of a diarylnitrenium ion that can be useful to guide next time-resolved spectroscopic studies of the covalent addition reactions between diarylnitrenium ions and DNA nucleosides or oligomers.