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

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.