Surprising Homolytic Gas Phase Co-C Bond Dissociation Energies of Organometallic Aryl-Cobinamides Reveal Notable Non-Bonded Intramolecular Interactions.

Aryl-cobalamins are a new class of organometallic structural mimics of vitamin B12 designed as potential 'antivitamins B12 '. Here, the first cationic aryl-cobinamides are described, which were synthesized using the newly developed diaryl-iodonium method. The aryl-cobinamides were obtained as pairs of organometallic coordination isomers, the stereo-structure of which was unambiguously assigned based on homo- and heteronuclear NMR spectra. The availability of isomers with axial attachment of the aryl group, either at the 'beta' or at the 'alpha' face of the cobalt-center allowed for an unprecedented comparison of the organometallic reactivity of such pairs. The homolytic gas-phase bond dissociation energies (BDEs) of the coordination-isomeric phenyl- and 4-ethylphenyl-cobinamides were determined by ESI-MS threshold CID experiments, furnishing (Co-C sp 2 )-BDEs of 38.4 and 40.6 kcal mol-1 , respectively, for the two ß-isomers, and the larger BDEs of 46.6 and 43.8 kcal mol-1 for the corresponding α-isomers. Surprisingly, the observed (Co-C sp 2 )-BDEs of the Coß -aryl-cobinamides were smaller than the (Co-C sp 3 )-BDE of Coß -methyl-cobinamide. DFT studies and the magnitudes of the experimental (Co-C sp 2 )-BDEs revealed relevant contributions of non-bonded interactions in aryl-cobinamides, notably steric strain between the aryl and the cobalt-corrin moieties and non-bonded interactions with and among the peripheral sidechains.

A Nickel(II)-Containing Vitamin†B12 Derivative with a Cofactor-F430-type π-System.

F430 is a unique enzymatic cofactor in the production and oxidation of methane by strictly anaerobic bacteria. The key enzyme methyl coenzyme M reductase (MCR) contains a hydroporphinoid nickel complex with a characteristic absorption maximum at around 430 nm in its active site. Herein, the three-step semisynthesis of a hybrid NiII -containing corrinoid that partly resembles F430 in its structural and spectroscopic features from vitamin B12 is presented. A key step of the route is the simultaneous demetalation and ring closure reaction of a 5,6-secocobalamin to metal-free 5,6-dihydroxy-5,6-dihydrohydrogenobalamin with cobaltocene and KCN under reductive conditions. Studies on the coordination chemistry of the novel compound support an earlier hypothesis why nature carefully selected a corphin over a corrin ligand in F430 for challenging nickel-catalyzed biochemical reactions.

Alpha- and Beta-Diastereoisomers of Phenylcobalamin from Cobalt-Arylation with Diphenyliodonium Chloride.

Organometallic aryl-cobalamins are B12 -derivatives featuring properties of potential 'B12 antivitamins'. Herein, we describe a new method for the preparation of aryl-cobalamins using versatile diaryliodonium salts as arylation agents. Formate or sodium borohydride reduction of aquocobalamin in presence of diphenyliodonium chloride furnished Coß -phenyl-cobalamin PhCbl in a roughly 3:1 to 1:1 ratio with its coordination isomer αPhCbl, a first representative 'base-off' Coα -aryl-cobalamin. The new structures were secured by detailed spectroscopic analysis, supplemented by an X-ray crystal structure analysis of PhCbl. Both types of coordination isomers of the aryl-cobalamins promise to be useful molecular tools in biomedical and biological studies.

Functionalisation of vitamin B12 derivatives with a cobalt ß-phenyl ligand boosters antimetabolite activity in bacteria.

This study describes the syntheses of four singly- and two doubly-modified vitamin B12 derivatives for generating antimetabolites of Lactobacillus delbrueckii (L. delbrueckii). The two most potent antagonists, a Coß-phenyl-cobalamin-c,8-lactam and a 10-bromo-Coß-phenylcobalamin combine a c-lactam or 10-bromo modification at the "eastern" site of the corrin ring with an artificial organometallic phenyl group instead of a cyano ligand at the ß-site of the cobalt center. These two doubly-modified B12 antagonists (10 nM) inhibit fully B12-dependent (0.1 nM) growth of L. delbrueckii. In contrast to potent 10-bromo-Coß-phenylcobalamin, single modified 10-bromo-Coß-cyanocobalamin lacking the artificial organometallic phenyl ligand does not show any inhibitory effect. These results suggest, that the organometallic ß-phenyl ligand at the Co center ultimately steers the metabolic effect of the 10-bromo-analogue.

Reversible metal-centered reduction empowers a Ni-Corrin to mimic F430.

This communication presents a novel truncated NiII-containing metbalamin and describes its reversible one electron reduction to a catalytically active NiI species, that features cofactor F430 model character. Our results strikingly demonstrate that stabilization of NiI is not restricted to the related hydroporhyrinoid ligands and is of relevance to the application of metallocorrins in (biomimetic) catalysis.