title: Modulation of reactive oxygen species photogeneration of bacteriopheophorbide a derivatives by exocyclic E-ring opening and charge modifications.
abstract: With the knowledge that the dominant photodynamic therapy (PDT) mechanism of 1a (WST09) switched from type 2 to type 1 for 1b (WST11) upon taurine-driven E-ring opening, we hypothesized that taurine-driven E-ring opening of bacteriochlorophyll derivatives and net-charge variations would modulate reactive oxygen species (ROS) photogeneration. Eight bacteriochlorophyll a derivatives were synthesized with varying charges that either contained the E ring (2a-5a) or were synthesized by taurine-driven E-ring opening (2b-5b). Time-dependent density functional theory (TDDFT) modeling showed that all derivatives would be type 2 PDT-active, and ROS-activated fluorescent probes were used to investigate the photogeneration of a combination of type 1 and type 2 PDT ROS in organic- and aqueous-based solutions. These investigations validated our predictive modeling calculations and showed that taurine-driven E-ring opening and increasing negative charge generally enhanced ROS photogeneration in aqueous solutions. We propose that these structure-activity relationships may provide simple strategies for designing bacteriochlorins that efficiently generate ROS upon photoirradiation.
authors: Department of Pharmaceutical Sciences, Leslie L. Dan Faculty of Pharmacy, University of Toronto , 144 College Street, Toronto, Ontario M5S 3M2, Canada.
authors: Áron
authors: Á
authors: Roxin
authors: Juan
authors: J
authors: Chen
authors: Andrew S
authors: AS
authors: Paton
authors: Timothy P
authors: TP
authors: Bender
authors: Gang
authors: G
authors: Zheng
mesh_terms: D001429:Bacteriochlorophylls / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D055668:Photochemical Processes; D010778:Photochemotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001429:Bacteriochlorophylls; D017382:Reactive Oxygen Species