Molecular electronic tuning of photosensitizers to enhance photodynamic therapy: synthetic dicyanobacteriochlorins as a case study.

Photophysical, photostability, electrochemical and molecular-orbital characteristics are analyzed for a set of stable dicyanobacteriochlorins that are promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc (NC)2BC-Zn and palladium chelate (NC)2BC-Pd. The order of PDT activity against HeLa human cancer cells in vitro is (NC)2BC-Pd > (NC)2BC > (NC)2BC-Zn ≈ BC. The near-infrared absorption feature of each dicyanobacteriochlorin is bathochromically shifted 35-50 nm (748-763 nm) from that for BC (713 nm). Intersystem crossing to the PDT-active triplet excited state is essentially quantitative for (NC)2BC-Pd. Phosphorescence from (NC)2BC-Pd occurs at 1122 nm (1.1 eV). This value and the measured ground-state redox potentials fix the triplet excited-state redox properties, which underpin PDT activity via Type-1 (electron transfer) pathways. A perhaps counterintuitive (but readily explicable) result is that of the three dicyanobacteriochlorins, the photosensitizer with the shortest triplet lifetime (7 μs), (NC)2BC-Pd has the highest activity. Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins studied recently are investigated and discussed in terms of four phenomena: aggregation, reduction, oxidation and chemical reaction. Collectively, the results and analysis provide fundamental insights concerning the molecular design of PDT agents.