The design and synthesis of chalcogenoxanthylium dyes for use as photosensitizers in photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT)

Photodynamic therapy (PDT) is an FDA-approved treatment of various cancers in the United States. Photodynamic antimicrobial chemotherapy (PACT) is a technique that is now being reinvestigated as a cleansing technique for the blood supply that offers several advantages to currently used techniques. Each of these treatments uses a photosensitizer (drug) that localizes in or around the tumor or blood pathogen, light and molecular oxygen to cause cell or pathogen death selectively. The currently used photosensitizers in both treatments have certain limitations including: long-term skin photosensitivity, weak absorption of light, and absorption of light of too short a wavelength for optimal penetration in tissue and red blood cell damage. New photosensitizers that overcome these deficiencies would provide clinical options for the treatment of certain types of cancer and cleansing of the blood supply.;We have synthesized structural analogues of rhodamine 123 to address the limitations of rhodamine 123 as a photosensitizer. The photophysical properties of a series of chalcogenoxanthylium dyes were studied in which the substitution of sulfur, selenium and tellurium for oxygen in the xanthylium chromophore gave a proportionally larger increases in the quantum yield for the generation of singlet oxygen and these dyes now absorb light of longer wavelengths than rhodamine. This suggests that these novel analogues are potent photosensitizers. These new analogues have given information regarding the structural components necessary for the optimization of biological and light harvesting properties of these heavy-atom rhodamine photosensitizers for use in PDT and PACT.