Design, synthesis and characterization of photocage molecules for light-activated release: Applications in polymer chemistry and phototherapeutics

ABSTRACT Photocages are photo-protecting groups that can release a covalently linked cargo on irradiation with a light of a particular wavelength. This characteristic of the photocages allows them to have precise spatial and temporal control over the release of substrates over time. But most of the available photocages absorbed in the UV light region and hence showed cytotoxicity and poor tissue penetration. Therefore, there was always the need for photocages that will absorb in the wavelength range of 600-1000 nm, also known as the biological window with minimum cell toxicity and higher penetration ability within the tissue. The work contained in this dissertation involves the development of new BODIPY photocages, advancing the properties of those photocages with structural modifications and extending the scope of those photocages with different leaving groups uncaging for better activity and releasing ability within the living cells. In chapter 2, a new class of BODIPY photocages were developed to absorb light within the far-red/near IR region with improved releasing efficiency by blocking the unproductive decay channels. Conformationally restricted structures were synthesized to minimize energy loss via internal conversion pathways like cis-trans isomerization, and charge transfer. Similarly, aryl groups with or without substitutions were introduced at proximity to trap the formed carbocation intermediate and prevent ion-pair recombination. This strategy led to new highly efficient second-generation BODIPY photocages that absorb light at an wavelength around 700 nm, which is a 50-fold improvement from the best known previously reported photocage absorbing >600 nm. In chapter 3, second-generation green-light and red-light absorbing photocages were used to release various functional groups like carboxylic acid, amines, alcohol, phenol, phosphate, and halide. Both the photocages showed excellent chemical yields and good quantum yield of photorelease. But the releasing efficiency of the photocages with an array of leaving groups were also found to be dependent on the nature of the leaving group, any of the linker used and the photocages. The plot of pKa against the quantum yield of release was linear for green-light absorbing photocages, but there was no correlation for red-light absorbing photocages. In chapter 5, the first generation green-light absorbing BODIPY photocage was modified to develop a new photocage with alkenyl chains attached to it. The alkenylated BODIPY was introduced into a polymeric chain along with thiol moieties and a novel highly cross-linked hydrogel was synthesized. The work extended to explore the use of different concentrations of the BODIPY molecules in the polymer as well as their formation in different light sources – UV or visible light. Quantum yield of photorelease showed good releasing efficiency with minimum dependency on the cross-linking density and was comparable for all the samples. Visco-elastic properties were measured by dynamic mechanical analysis and were found to become better with increased BODIPY concentrations. All of the synthesized hydrogels showed 100% release within a maximum of 3 h of irradiation and thereby showed excellent photouncaging abilities. In chapter 6, previously reported BODIPY photocages were structurally modified by deuterium incorporation to enhance their releasing ability. Deuteration improves the photoreleasing ability from the excited singlet state by minimizing the internal conversions and allowing longer fluorescence lifetimes. Quantum yield of photorelease were better for all the deuterated compounds in comparison to their non-deuterated analogs with 25-93% increase. The deuterated samples had extended fluorescence lifetimes as observed by time correlated single photon counting (TCSPC) experiments, even though no correlation was observed between the amount of deuterium incorporation and the increase in fluorescent lifetime.