When the Surface Matters: Prebiotic Peptide-Bond Formation on the TiO2 (101) Anatase Surface through Periodic DFT-D2 Simulations

The mechanism of the peptide bond formation between two glycine (Gly) molecules has been investigated by means of PBE-D2* and PBE0-D2* periodic simulations on the TiO2 (101) anatase surface. This is a process of great relevance both in fundamental prebiotic chemistry, as the reaction univocally belongs to one of the different organizational events that ultimately led to the emergence of life on Earth, as well as from an industrial perspective, since formation of amides is a key reaction for pharmaceutical companies. The efficiency of the surface catalytic sites is demonstrated by comparing the reactions in gas phase and on the surface. At variance with the uncatalyzed gas-phase reaction, which involves a concerted nucleophilic attack and dehydration step, on the surface these two steps occur along astepwise mechanism. The presence of surface Lewis and Brönsted sites exerts some catalytic effect by lowering the free energy barrier for the peptide bond formation by about 6 kcal mol-1 compared to the gas-phase reaction. Moreover, the co-presence of molecules acting as proton transfer assistants (i.e., H2O and Gly as well) provide a more significant kinetic energy barrier decrease. The reaction on the surface is also favourable from a thermodynamic standpoint, involving very large and negative reaction energies. This is due to the fact that the anatase surface also acts as a dehydration agent during the condensation reaction, since the outermost coordinatively unsaturated Ti atoms strongly anchor the released water molecules. Our theoretical results provide a comprehensive atomistic interpretation of the experimental results of Martra et al. [Angew. Chem. Int. Ed. 2014, 53, 4671], in which polyglycine formation was obtained by successive feedings of Gly vapour on TiO2 surfaces in dry conditions and are, therefore, relevant in a prebiotic context envisaging dry and wet cycles occurring, at mineral surfaces, in small pool.