Amide and Peptide Bond Formation: Interplay between Strained Ring Defects and Silanol Groups at Amorphous Silica Surfaces

Formation of amide and peptide bonds on plain amorphous silica surfaces is studied by DFT-D3 methods on cluster silica surface models envisaging strained Si-O rings as sources of reactivity. The amide/peptide bond formation reaction resulted thermodynamically and kinetically favored compared to the gas-phase processes due to the co-presence of surface (SiO)2/(SiO)3 strained ring defects, which result from high temperature treatment of silica, and spatially close SiOH silanol groups. Preliminary extended calculations involving ammonia and formic acid give the insights for the most promising reaction paths for the amide bond formation on the defective silica surfaces. These paths were also adopted to study the glycine di-peptide formation. The reactions proceed through two steps: i) silica ring opening by reaction with carboxylic acids forming a Si-O-C(=O)- surface mixed anhydride (SMA); and ii) reaction of SMA with amines to form the amide product. The key point of the overall reaction is the synergy between the strained Si-O rings and spatially close silanol groups: SMA formation forces carboxylic acids to be immobilized on the surface, whereas SiOH groups are effective mild Brønsted catalytic acidic sites through a silanol-assisted proton relay mechanism in the second step. These results provide some atomistic insights of recent experimental findings on the formation of amides catalyzed by bare silica surfaces.