Photoactivatable Derivatives for Chemical and Biological Applications: Design, Synthesis and Mechanistic Investigation

Abstract

This thesis focuses on design, synthesis and mechanistic investigations of photoactivatable derivatives. It summarizes selected results of my Ph.D. research which have been published or submitted for publication. In the theoretical part it summarizes basic information about selected topics relevant for the studied projects, such as photoremovable protecting groups, selected visible light absorbing chromophores, biologically relevant caged ions and small molecules, and visible light photocatalysis. The part Results and Discussion is divided into eight chapters. The first chapter deals with a xanthene-based photoremovable protecting group (PPG). We managed to prepare the first PPG capable to release phosphates, carboxylates and halides by the action of green light (λmax ~ 520 nm). The second part introduces 4-hydroxyphenacyl fluoride, a caged fluoride, that can be efficiently released (Φ ~ 84%) by UV-light irradiation. The mechanism of fluoride release has been studied by picosecond pump-probe spectroscopy. The released fluoride was used for etching of silicon surfaces followed by AFM. The third project describes the first metal-free carbon monoxide-releasing molecule (CORM) activatable by visible light based on the xanthene structural motif. The fourth chapter improves the concept of visible light absorbing CORMs by using BODIPY-based chromophores. These molecules can release CO upon irradiation by light at up to 730 nm and were successfully tested in both in vitro and in vivo biological experiments. The mechanism of the photodegradation was carefully studied. The fifth chapter deals with a photocatalytic system for reduction of carbonyl compounds. It uses proflavine as a photocatalyst, rhodium mediator, and triethylamine as a sacrificial electron donor. The system selectively reduces aldehydes over ketones. Both electronic and steric effects are responsible for the selectivity which is kinetically controlled. The sixth project describes a novel photocatalytic method for generation of the nitrate radical which is further used for some synthetic applications. The mechanism of generation of the nitrate radical by photooxidation of the nitrate anion has been studied in detail. The seventh chapter discusses a new method for generation of fluorinated aryl radicals which are used in the synthesis of fluorinated biaryls as well as in late stage functionalization of some complex molecules. The transient spectroscopic study has revealed the mechanism of the aryl radical formation. The last project focuses on the synthesis of selanyl- and tellanyl-substituted BODIPY derivatives. The quantum yield of intersystem crossing (up to 60%) has been measured by transient spectroscopy. These derivatives can be used as triplet sensitizers