title: Monitoring Chemical and Biological Electron Transfer Reactions with a Fluorogenic Vitamin K Analogue Probe.
abstract: We report herein the design, synthesis, and characterization of a two-segment fluorogenic analogue of vitamin K, B-VKQ, prepared by coupling vitamin K3, also known as menadione (a quinone redox center), to a boron-dipyrromethene (BODIPY) fluorophore (a lipophilic reporter segment). Oxidation-reduction reactions, spectroelectrochemical studies, and enzymatic assays conducted in the presence of DT-diaphorase illustrate that the new probe shows reversible redox behavior on par with that of vitamin K, provides a high-sensitivity fluorescence signal, and is compatible with biological conditions, opening the door to monitor remotely (i.e., via imaging) redox processes in real time. In its oxidized form, B-VKQis non-emissive, while upon reduction to the hydroquinone form, B-VKQH2, BODIPY fluorescence is restored, with emission quantum yield values of ca. 0.54 in toluene. Density functional theory studies validate a photoinduced electron transfer intramolecular switching mechanism, active in the non-emissive quinone form and deactivated upon reduction to the emissive dihydroquinone form. Our results highlight the potential of B-VKQas a fluorogenic probe to study electron transfer and transport in model systems and biological structures with optimal sensitivity and desirable chemical specificity. Use of such a probe may enable a better understanding of the role that vitamin K plays in biological redox reactions ubiquitous in key cellular processes, and help elucidate the mechanism and pathological significance of these reactions in biological systems.
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures, McGill University , 801 Sherbrooke Street West, Montréal, Québec H3A 0B8, Canada.
authors.forename: Mei-Ni
authors.initials: MN
authors.lastname: Belzile
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures, McGill University , 801 Sherbrooke Street West, Montréal, Québec H3A 0B8, Canada.
authors.forename: Robert
authors.identifier: 0000-0001-7945-8548
authors.initials: R
authors.lastname: Godin
authors.affiliation: Department of Chemistry and Center for Self-Assembled Chemical Structures, McGill University , 801 Sherbrooke Street West, Montréal, Québec 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, McGill University , 801 Sherbrooke Street West, Montréal, Québec H3A 0B8, Canada.
authors.forename: Gonzalo
authors.identifier: 0000-0003-0064-1345
authors.initials: G
authors.lastname: Cosa
mesh_terms: D004563:Electrochemistry; D004579:Electron Transport; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D014812:Vitamin K / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D014812:Vitamin K; D016660:NAD(P)H Dehydrogenase (Quinone)