Phenol-based lipophilic fluorescent antioxidant indicators: a rational approach.
The reactivity, electrochemistry, and photophysics of the novel antioxidant indicator B-TOH, a BODIPY-alpha-tocopherol adduct, were investigated. We also studied a newly prepared BODIPY-3,5-di-tert-butyl-4-hydroxybenzoic acid adduct (B-BHB) and compared the results for both sets of probes. Our results highlight the potential of B-TOH as a fluorescent antioxidant indicator and help illustrate the considerations to be taken into account in preparing a receptor-reporter-type fluorescent antioxidant indicator. Based on the experimental values of the redox potentials for the reporter BODIPY and from the redox potentials estimated for the phenol receptor segment, the off-to-on emission enhancement recently reported for B-TOH upon peroxyl radical scavenging can be unequivocally assigned to the deactivation of an intramolecular photoinduced electron transfer (PeT) which operates in the reduced form of B-TOH. Theoretical calculations performed at the B3LYP/6-31G(d) level on HOMO energy levels relative to vacuum further support the deactivation of a PeT mechanism upon peroxyl radical scavenging by B-TOH. Fluorescence lifetimes and fluorescence quantum yields measured in a range of solvent polarities, from hexane to acetonitrile, for B-TOH, B-BHB, and their BODIPY precursors PM605 or PMOH, are consistent with an intramolecular nonradiative decay pathway operative in B-TOH. This pathway is not operative in B-BHB where PeT is deemed highly endergonic based on electrochemical studies. A subsequent analysis on the antioxidant properties of both fluorophore-phenol adducts studied herein indicates that B-TOH antioxidant activity is on par with that of alpha-tocopherol, the most potent naturally occurring lipid soluble antioxidant, whereas B-BHB is a poor antioxidant. Oxygen uptake studies upon peroxyl radical initiated styrene autoxidation and laser flash photolysis studies on the rate of H-atom abstraction by cumyloxyl radicals reveal similar reactivity patterns for B-TOH and 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC), an alpha-tocopherol analogue lacking the phytil tail. Analogous reactivity studies on B-BHB underscore its poor antioxidant activity. In general, this work provides substantial amount of information useful in designing off/on lipid soluble fluorescent antioxidant indicators based on phenol moieties.
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 2K6, Canada.
Katerina
K
Krumova
Paul
P
Oleynik
Pierre
P
Karam
Gonzalo
G
Cosa
D000975:Antioxidants / Q000737:chemistry*; D015195:Drug Design; D004563:Electrochemistry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D010545:Peroxides / Q000032:analysis; D019800:Phenol / Q000737:chemistry*; D012995:Solubility; D013057:Spectrum Analysis; D013696:Temperature; D013997:Time Factors
D000975:Antioxidants; D005456:Fluorescent Dyes; D010545:Peroxides; C049375:perhydroxyl radical; D019800:Phenol; D010100:Oxygen