title: Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy.
abstract: Here we show the design, preparation, and characterization of a dormant singlet oxygen ((1)O2) photosensitizer that is activated upon its reaction with reactive oxygen species (ROS), including (1)O2 itself, in what constitutes an autocatalytic process. The compound is based on a two segment photosensitizer-trap molecule where the photosensitizer segment consists of a Br-substituted boron-dipyrromethene (BODIPY) dye. The trap segment consists of the chromanol ring of α-tocopherol, the most potent naturally occurring lipid soluble antioxidant. Time-resolved absorption, fluorescence, and (1)O2 phosphorescence studies together with fluorescence and (1)O2 phosphorescence emission quantum yields collected on Br2B-PMHC and related bromo and iodo-substituted BODIPY dyes show that the trap segment provides a total of three layers of intramolecular suppression of (1)O2 production. Oxidation of the trap segment with ROS restores the sensitizing properties of the photosensitizer segment resulting in ∼40-fold enhancement in (1)O2 production. The juxtaposed antioxidant (chromanol) and prooxidant (Br-BODIPY) antagonistic chemical activities of the two-segment compound enable the autocatalytic, and in general ROS-mediated, activation of (1)O2 sensitization providing a chemical cue for the spatiotemporal control of (1)O2.The usefulness of this approach to selectively photoactivate the production of singlet oxygen in ROS stressed vs regular cells was successfully tested via the photodynamic inactivation of a ROS stressed Gram negative Escherichia coli strain.
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures (CSACS-CRMAA), McGill University , 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
authors.forename: Andrés M
authors.initials: AM
authors.lastname: Durantini
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures (CSACS-CRMAA), McGill University , 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
authors.forename: Lana E
authors.initials: LE
authors.lastname: Greene
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures (CSACS-CRMAA), McGill University , 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Lincoln
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures (CSACS-CRMAA), McGill University , 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.|Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET, and Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , Córdoba X5000HUA, Argentina.
authors.forename: Sol R
authors.initials: SR
authors.lastname: Martínez
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures (CSACS-CRMAA), McGill University , 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Cosa
mesh_terms: D001896:Boron Compounds / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry*
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen