Investigating the photophysical properties of novel chlorin derivatives as photosensitizer molecules for photodynamic therapy

Photodynamic therapy (PDT) is a non-invasive cancer treatment that offers several advantages over traditional methods. This successful therapy has been effectively applied in the treatment of various cancer types, especially tumors located near the body surface. However, the limitations of photosensitizer (PS) molecules, particularly for deep-seated tumors, impede the widespread clinical adoption of PDT. Consequently, there is a need for novel photosensitizer molecules to improve treatment efficacy and advance the field of cancer therapy. This study presents a comprehensive investigation into the photophysical properties of substituted chlorin derivatives as potential PS molecules to enhance PDT. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT), along with hybrid quantum mechanical/molecular mechanical methods (hybrid QM/MM), were applied to examine their photophysical properties. Moreover, the molecules are thoroughly investigated in various physiological environments, including vacuum and water phase, encapsulated with drug carriers, and on lipid membranes with molecular dynamics (MD) simulations. The results provide insights into the absorption and emission spectra, natural transition orbitals, spin-orbit coupling values, singlet-triplet energy gaps, and intersystem crossing channels of these molecules. By demonstrating the photophysical properties of these customized chlorins and their dependence on environmental factors, this research offers valuable information for the design and optimization of such molecules.