Increasing complexity models for describing the generation of substrate radicals at the active site of ethanolamine ammonia-lyase/B12

Here we assess at the PCM//UB3LYP/6-31G(d,p) level how using a complete molecular description of both reactants in step b and introducing the polarizing effect of the protein/cofactor environment (mimicked through a continuum model with ε = 10) impacts on the nature and energetics of the intermediate complexes (ICs) and transition states (TSs) under three catalytic scenarios (total, partial, and no protonation). Our results show that a concerted asynchronous mechanism involving distonic radical species is at play, passing through quasi-linear early TSs displaying a C1-H cleavage slightly more advanced than formation of the new H-C bond in Ado. Whereas the enzyme's polarizing environment differentially stabilizes the TS lowering the barrier by ∼2.4-2.8 kcal/mol, a reduction of 1.4 kcal/mol in ΔG298≠ is the outcome of substrate's partial/total protonation, without a clear distinction among them, in opposition to what previously shown based upon more simplified models.