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

Abstract

Aryl-cobalamins are an ew class of organometallic structural mimics of vitamin B 12 designed as potential' antivitamins B 12 '. Here, the first cationic aryl-cobinamides are described, which were synthesized using the newly developed diaryl-iodoniumm ethod. 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.T he availability of isomers with axial attachment of the aryl group, either at the 'beta' or at the 'alpha'f ace of the cobalt-center allowed for an unprecedented comparison of the organometallic reactivity of such pairs. Theh omolytic gas-phase bond dissociation energies (BDEs)o ft he coordination-isomeric phenyl-and 4-ethylphenyl-cobinamides were determined by ESI-MS threshold CID experiments,f urnishing (CoÀC sp 2 )-BDEs of 38.4 and 40.6 kcal mol À1 ,r espectively,f or the two b-isomers, and the larger BDEs of 46.6 and 43.8 kcal mol À1 for the corresponding a-isomers.S urprisingly,t he observed (CoÀ C sp 2 )-BDEs of the Co b -aryl-cobinamides were smaller than the (CoÀC sp 3 )-BDE of Co b -methyl-cobinamide. DFT studies and the magnitudes of the experimental (CoÀC 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.

Cryogenic Ion Vibrational Predissociation (CIVP) Spectroscopy of Aryl Cobinamides in the Gas Phase: How Good Are the Calculations for Vitamin B12 Derivatives?

“…Indeed, acetamide side chains have been observed to help provide a binding interface for the fleetingly existent Ado-radical in the AdoCbl-dependent eliminating isomerases and glutamate mutase . These biostructural observations strengthen the wider implications of our recent experimental report that the Co–C bond dissociation energy in the related arylcobinamides depends on the conformational remodeling of the peripheral side chains around the corrin moiety when the central Co–C bond is cleaved …”

“…47 These biostructural observations strengthen the wider implications of our recent experimental report that the Co−C bond dissociation energy in the related arylcobinamides depends on the conformational remodeling of the peripheral side chains around the corrin moiety when the central Co−C bond is cleaved. 16 Early computational studies of vitamin B 12 and its function truncated the ligand by removing the peripheral side chains to simplify the calculation, 49,50 which, in light of our recent report, undermined an adequate description of the thermodynamics of the Co−C cleavage. More recent calculations include the side chains, but, the conformational complexity presents an immense challenge.…”

“…In our previous study, we measured bond dissociation energies (BDE) in a series of the non-natural aryl cobinamides, which have become available very recently . Through our experiments, we found that homolytic cleavage of the Co–C sp2 bonds in the β-diastereomers of phenyl- and 4-ethylphenylcobinamides results in BDEs of 38.4 and 40.6 kcal mol –1 , respectively, whereas their corresponding α-diastereomers have larger BDEs, 46.6 and 43.8 kcal mol –1 , respectively.…”

COLD ION SPECTROSCOPY OF B₁₂ DERIVATIVES: STRETCHING THE LIMITS OF THEORETICAL INTERPRETATION

“…In our previous study, we experimentally determined bond strength in a series of aryl-corrins by the threshold CID experiments and compared these BDE's with those calculated with DFT. [1] We found that the computed BDEs were very much dependent on the chosen structure. Given that aryl-cobinamides have many side chains that increase their conformational space, and that the question of a specific structure, measured in the gas phase was important for further evaluation of our T-CID experiment, we proceeded to analyze structural properties of arylcobinamides using CIVP spectroscopy.…”

Robustness of Threshold Collision-Induced Dissociation Simulations for Bond Dissociation Energies

“…We regularly perform BDE measurements with the T-CID method using L-CID for postprocessing, accompanied by quantum chemical calculations, to identify the methods that can accurately reproduce experimental bond strengths. On several occasions, we have found large discrepancies between the experimental and calculated values. − On the theoretical side, we and others have carried out extensive computational studies in an effort to resolve these discrepancies but so far with varying success. − We have also conducted experimental investigations, employing independent competition experiment approaches, , which have shown better agreement with the T-CID-derived values than the computational ones. In addition, we recently conducted a careful analysis of the rate models that are used to calculate the reaction probability in the fitting procedure, finding the BDE values to be robust with respect to differences in the rate models.…”