Ana M. S. Soares

Light triggering of 5-aminolevulinic acid from fused coumarin ester cages

The evaluation of the photorelease of 5-aminolevulinic acid (5-ALA), a small molecule which has considerable interest in the area of medicine as a photosensitizer prodrug in PDT and cosmetic treatments, and in agriculture as a herbicide/insecticide, was carried out by using a series of fused coumarin derivatives with different substituents and ring fusions in the preparation of 5-ALA photosensitive ester cages, in order to tune the photophysical and photolytic properties of the resulting conjugates. This study was intended to assess the viability of the photorelease of 5-ALA from lipophilic conjugates since it has hydrophilic character, does not penetrate efficiently through the skin or cell membranes and appropriate derivatisation can enhance its lipophilicity and its application scope in biological environment. Photolytic studies were performed on the ester cages by irradiation in a photochemical reactor at 254, 300, 350 and 419 nm, using methanol/HEPES buffer 80u2006:u200620 solutions as solvent. The data obtained confirmed the suitability of the tested photosensitive moieties for the release of 5-aminolevulinic acid at the various wavelengths of irradiation. As well as the photolysis, the photophysics of the compounds was characterised by both steady state and time-resolved methods which uncovered the presence of different fluorescing species. Additionally, an on–off experiment was carried out by using two excitation sources (cleave and probe) to enable fluorescence to follow the kinetics of the process and to ascertain optical control over the bond scission.

Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages

Ala–Ala–Pro–Val (AAPV) is a bioactive tetrapeptide that inhibits human neutrophil elastase, an enzyme involved in skin chronic inflammatory diseases like psoriasis. Caged derivatives of this peptide were prepared by proper N- and C-terminal derivatisation through a carbamate or ester linkage, respectively, with two photoactive moieties, namely 7-methoxycoumarin-2-ylmethyl and pyren-2-ylmethyl groups. These groups were chosen to assess the influence of the photosensitive group and the type of linkage in the controlled photo release of the active molecule. The caged peptides were irradiated at selected wavelengths of irradiation (254, 300, and 350xa0nm), and the photolytic process was monitored by HPLC–UV. The results established the applicability of the tested photoactive groups for the release of AAPV, especially for the derivative bearing the carbamate-linked pyrenylmethyl group, which displayed the shortest irradiation times for the release at the various wavelengths of irradiation (ca. 4xa0min at 254xa0nm, 8xa0min at 300xa0nm and 46xa0min at 350xa0nm).