Indotricarbocyanine dyes relevant for photodynamic therapy and their radicals: Substituent effects studied by optical and electrochemical methods

Abstract

Photodynamic therapy is an effective and minimally invasive treatment method for cancer. A deeper understanding of the photocytotoxicity mechanism of cyanine dyes is necessary for the development of more efficient photosensitizers. We combine electrochemistry, optical and ESR spectroscopy, and quantum chemical calculations to study indotricarbocyanine dyes relevant for photodynamic therapy. The incorporation of 4-meso-chloride and a 3,5-o-phenylene bridge into the polymethine chain results in a hypsochromic shift of the absorption spectrum by ca. 30 nm and in a downward shift of the frontier orbitals energy levels by 0.1–0.3 eV. In addition, such substitution imparts stability to the electrogenerated radical dications of the dyes. The presence of 4-meso-chloride and a 3,5-trimethylene bridge in the polymethine chain causes the absorption spectrum to shift bathochromically by almost 40 nm and the HOMO–LUMO energy gap to decrease by ca. 0.1 eV. The radical dication of the dye with such substitution is particularly stable and exhibits improved electron delocalization. The radical dication of the dye with an unsubstituted polymethine chain is unstable due to its propensity to form dimers. The substituents at the nitrogen atoms are shown to have almost no influence on the optical and electrochemical properties of the indotricarbocyanine dyes. The radical dications of the dyes with an o-phenylene bridge can oxidize bromide ions, unlike the radical dications of the dyes with an unsubstituted polymethine chain or with a trimethylene bridge. The reported data can be used to develop new indotricarbocyanine dyes with desired characteristics.