Application of TD-DFT Theory to Studying Porphyrinoid-Based Photosensitizers for Photodynamic Therapy: A Review

Abstract

An important focus for innovation in photodynamic therapy (PDT) is theoretical investigations. They employ mostly methods based on Time-Dependent Density Functional Theory (TD-DFT) to study the photochemical properties of photosensitizers. In the current article we review the existing state-of-the-art TD-DFT methods (and beyond) which are employed to study the properties of porphyrinoid-based systems. The review is organized in such a way that each paragraph is devoted to a separate aspect of the PDT mechanism, e.g., correct prediction of the absorption spectra, determination of the singlet-triplet intersystem crossing, and interaction with molecular oxygen. Aspects of the calculation schemes are discussed, such as the choice of the most suitable functional and inclusion of a solvent. Finally, quantitative structure-activity relationship (QSAR) methods used to explore the photochemistry of porphyrinoid-based systems are discussed.

Keywords: photodynamic therapy (PDT); porphyrinoids; time-dependent density functional theory (TD-DFT).

Scheme 1

The scheme of photodynamic therapy.

Scheme 2

Gouterman’s model of porphyrinoids’ main absorption bands (note that substitution or other modifications in the porphyrin skeleton may result in modification of orbital levels, causing changes in the band assignment).