Theoretical investigation of F430-catalyzed dehalogenation of chloro-alkanes. A comprehensive DFT benchmark

Abstract

We conducted a comprehensive benchmarking study to assess the performance of 40 theoretical levels for modeling the mechanism of dehalogenation of chloromethane by octaethylisobacteriochlorin (OEtiBCh-Ni), a simplified model of the F₄₃₀ cofactor. Our research has demonstrated a substantial impact of dispersion on the reaction barrier. Additionally, we have identified a correlation between the deformation of the isobacteriochlorin ring and the relative stability of the system. We observe relatively sizeable kinetic isotope effect (KIE) values in the range of 1.010–1.011, which is above the expected values for typical S_N2 reactions. The optimal choice for modeling of this reaction is the MN15-L functional with the def2-TZVP basis set, which yields a relative error of less than 3% while exhibiting a high level of computational efficiency. The combination of M06-D3(0), PBE0-D3(BJ), and HSE06-D3(BJ) with 6-31+G(d) also represents a viable option, offering a computational cost comparable to MN15-L/def2TZVP. Calculations using the low-cost def2-SVP basis set are the fastest, but the resulting geometries are questionable.