While reducing the C-C RPF in the range 2.3-2.7 Å could potentially decrease the repulsion between C4 and Cβ near the TS, this effect is moderated by the modifications made to the C-H RPFs. Therefore, we focused on finding the optimal combination of C-H and C-C RPF modifications that would improve the overall energetics of the reaction, that is the relative energies between the reactant, transition state, and enolate intermediate. Among the possible combinations of the modified RPFs for C-H and C-C pairwise distances, we found that the configurations combining CH_4 with CC_1 to CC_9 were the ones showing more agreement in the potential energy profiles for the IRC geometries between the corrected DFTB3 and M06-2X/def2-TZVP Hamiltonians (see Figure ). Validation of the improved DFTB3 Hamiltonian using QM/MM sim-