Finally, the FC reaction pathway of Cu(II)-bound SCP_Q111CBpy was explored, using ReproS,C and ReproR,C reactants as the starting structures. The calculated potential energy landscape for the conjugate coupling reaction for model C is represented, along with the optimized geometric structures of these transition states, in Figure . The lowest energy barrier (13.6 kcal mol -1 ) was obtained for the proR C-C coupling transition state (TS1proR,C) while the energy barrier for the proS transition state (TS1proS,C) was higher (15.4 kcal mol -1 ). The transition are characterized by the presence of an imaginary frequencies i288 cm -1 and i273 cm -1 for TS1proR,C and TS1proS,C respectively. Furthermore, in the TS1proR,C transition state a hydrophobic interaction from M105 was observed with 3, while no such interaction of 3 was observed in TS1proS,C. The system then relaxed to the low energy state intermediates Int1proR,C and Int1proS,C, which are characterized in the local minima state by the presence of all real frequency values indicating stable structures. The Int1proR,C has lower energy (6.7 kcal mol -1 ) than the Int1proS,C configuration (9.8 kcal mol -1 ), which favours the proR configuration pathway over the proS pathway. This is consistent with the experimentally observed preference to produce the R enantiomer by SCP_Q111CBpy (Table ).