title: Toward the Design of Photoresponsive Conditional Antivitamins B12: A Transient Absorption Study of an Arylcobalamin and an Alkynylcobalamin.
abstract: Cobalamins are of widespread importance in biology. Both of the cofactors essential for human metabolism, the organocobalamins coenzyme B12and methylcobalamin, are highly photolabile, as are other alkylcobalamins. The alkynylcobalamin phenylethynylcobalamin (PhEtyCbl) and the arylcobalamin 4-ethylphenylcobalamin (EtPhCbl) with "atypical" Co-C-bonds to unsaturated carbons, were recently designed as metabolically inert cobalamins, classified as "antivitamins B12". The further development of an ideal light-activated or "conditional" antivitamin B12would require it to be readily converted by light into an active B12vitamin form. Very photolabile "antivitamins B12" would also represent particularly useful scaffolds for therapeutic light-activated reagents. Here, the photoactive arylcobalamin EtPhCbl and the remarkably photostable alkynylcobalamin PhEtyCbl are examined using femtosecond to picosecond UV-visible transient absorption spectroscopy. PhEtyCbl undergoes internal conversion to the ground state with near unit quantum yield on a time scale < 100 ps and an activation energy of 12.6 ± 1.4 kJ/mol. The arylcobalamin EtPhCbl forms an excited state with a ca. 247 ps lifetime. This excited state branches between internal conversion to the ground state and formation of a long-lived base-off species with a quantum yield of ∼9%. Anaerobic steady state photolysis of "light-sensitive" EtPhCbl results in the formation of cob(II)alamin, but only with quantum yield <1%. Hence, our studies suggest that suitably modified arylcobalamins may be a rational basis for the design of photoresponsive "antivitamins B12".
authors: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109-1055, United States.
authors: Nicholas A
authors: NA
authors: Miller
authors: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109-1055, United States.
authors: Theodore E
authors: TE
authors: Wiley
authors: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109-1055, United States.
authors: Kenneth G
authors: KG
authors: Spears
authors: Institute of Organic Chemistry & Center for Molecular Biosciences, University of Innsbruck , Innrain 80/82, A-6020 Innsbruck, Austria.
authors: Markus
authors: M
authors: Ruetz
authors: Institute of Organic Chemistry & Center for Molecular Biosciences, University of Innsbruck , Innrain 80/82, A-6020 Innsbruck, Austria.
authors: Christoph
authors: C
authors: Kieninger
authors: Institute of Organic Chemistry & Center for Molecular Biosciences, University of Innsbruck , Innrain 80/82, A-6020 Innsbruck, Austria.
authors: Bernhard
authors: B
authors: Kräutler
authors: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109-1055, United States.
authors: Roseanne J
authors: RJ
authors: Sension
mesh_terms: D065966:Absorption, Physicochemical; D000480:Alkynes / Q000737:chemistry*; D003038:Cobamides / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D055668:Photochemical Processes
chemical_list: D000480:Alkynes; D003038:Cobamides; C000913:cobamamide