Does Silica Surface Catalyse Peptide Bond Formation? New Insights from First‐Principles Calculations

The role that silica surface could have played in prebiotic chemistry as a catalyst for peptide bond formation has been addressed at the B3LYP/6‐31+G(d,p) level for a model reaction involving glycine and ammonia on a silica cluster mimicking an isolated terminal silanol group present at the silica surface. Hydrogen‐bond complexation between glycine and the silanol is followed by the formation of the mixed surface anhydride Si surf OC(O)R, which has been suggested in the literature to activate the CO bond towards nucleophilic attack by a second glycine molecule, here simulated by the simpler NH 3 molecule. However, B3LYP/6‐31+G(d,p) calculations show that formation of the surface mixed anhydride Si surf OC(O)R is disfavoured (Δ r G 298 ≈6 kcal mol −1 ), and that the surface bond only moderately lowers the free‐energy barrier of the nucleophilic attack responsible for peptide bond formation (Δ G ${{{{\ne}\hfill \atop 298\hfill}}}$ ≈48 kcal mol −1 ) in comparison with the uncatalysed reaction (Δ G ${{{{\ne}\hfill \atop 298\hfill}}}$ ≈52 kcal mol −1 ). A further decrease of the free‐energy barrier of peptide bond formation (Δ G ${{{{\ne}\hfill \atop 298\hfill}}}$ ≈41 kcal mol −1 ) is achieved by a single water molecule close to the reaction centre acting as a proton‐transfer helper in the activated complex. A possible role of strained silica surface defects on the formation of the surface mixed anhydride Si surf OC(O)R has also been addressed.