RESUMEN
In recent years, methodologies that rely on water as the reaction medium have gained considerable attention. The unique properties of micellar solutions were shown to improve the regio-, stereo-, and chemoselectivity of different transformations. Herein, we demonstrate that the aqueous environment is a suitable medium for a visible light driven cobalt-catalyzed reaction involving radical species. In this system, reduced vitamin B12 reacts with alkyl halides, generating radicals that are trapped by the lipophilic olefin present in the Stern layer. A series of NMR measurements and theoretical studies revealed the location of reaction components in the micellar system.
RESUMEN
Gram-negative bacteria develop specific systems for the uptake of scarce nutrients, including vitaminâ B12 . These uptake pathways may be utilized for the delivery of biologically relevant molecules into cells. Indeed, it was recently reported that vitaminâ B12 transported an antisense peptide nucleic acid (PNA) into Escherichia coli and Salmonella Typhimurium cells. The present studies indicate that the conjugation site of PNA to vitaminâ B12 has an impact on PNA transport into bacterial cells. Toward this end, a specifically designed PNA oligomer has been tethered at various positions of vitaminâ B12 (central Co, R5' -OH, c and e amide chains, meso position, and at the hydroxy group of cobinamide) by using known or newly developed methodologies and tested for the uptake of the synthesized conjugates by E. coli. Compounds in which the PNA oligonucleotide was anchored at the R5' -OH position were transported more efficiently than that of other compounds tethered at the peripheral positions around the corrin ring. Of importance is the fact that, contrary to mammalian organisms, E. coli also takes up cobinamide, which is an incomplete corrinoid. This selectivity opens up ways to fight bacterial infections.
Asunto(s)
Escherichia coli/metabolismo , Ácidos Nucleicos de Péptidos/química , Salmonella typhimurium/metabolismo , Vitamina B 12/química , Alquinos/química , Azidas/química , Transporte Biológico , Catálisis , Cobre/química , Reacción de Cicloadición , Portadores de Fármacos/química , Vitamina B 12/metabolismoRESUMEN
Vitamin B12 and its derivatives present excellent paradigms for bioinspired catalysis. The inherent challenges for derivatizing cobalamins, such as vitaminâ B12 , to incorporate them in supramolecular designs and materials, limit the range of their utility and applications. Herein, we present a synthetic approach toward derivatives of vitaminâ B12 possessing electron-donating and -withdrawing substituents at the meso position (C10). Spectroscopic and cyclic voltammetry studies reveal that changes in the substitution pattern on the equatorial ligand have a significant impact on the electronic and optical properties of the cobalamin. These synthetic methods, therefore, provide invaluable routes not only for covalent linking to other structures, but also for attaining a wide range of functionalities for the derivatives of vitamin B12 .