Evaluation of sulfur and selenium substituents to induce the heavy atom effect in metal-free porphyrins

The effects of the incorporation of oxygen, sulfur, selenium, and tellurium into the porphyrin core over nitrogen have been explored using density functional theory (DFT) and its time-dependent and quadratic response implementations (TDDFT and QR-TDDFT). The aim was to investigate how substitution affects the photophysical properties of these dyes and how such modifications could make them more suitable to be proposed as heavy-atom-free agents in photodynamic therapy (PDT). The photophysical properties assessed in our investigation, relevant for the PDT mechanism, allow us to establish that chalcogens trigger beneficial bathochromic shifts enabling the achievement of more biocompatible wavelengths while enhancing spin–orbit coupling and kinetic constants for intersystem crossings. Considering the higher safety profile of sulfur in biological systems and the numerous studies highlighting the role of Se-containing materials in inducing apoptosis in cancer cells with minimal side effects on normal cells, we believe that the results presented here on both the S- and Se-heterosubstitution strategies could be highly promising.