The interplay between the pyramidalization of carbonyl carbons and the n → π* interactions in biomolecules

The structural preferences of biomolecules arise from a delicate balance of different forces whose identification and quantification are challenging. Studies conducted over the last two decades have shown that the n → π* interaction formed between consecutive carbonyl groups plays a crucial role in stabilizing biomolecules, which exhibit a wide range of chemical properties and structural complexities. These studies also demonstrate that the n → π* interaction relies heavily on the pyramidalization of the carbonyl group, which accepts electrons, to such an extent that pyramidalization has frequently been considered a signature of this interaction. Here, statistical surveys of different structural databases aimed at evaluating the precise relationship between the n → π* interaction and the carbonyl carbon pyramidalization (θ_C) show that the latter occurs independently of the presence of the former. Nevertheless, the n → π* interaction influences the degree of pyramidalization and affects its geometry. Importantly, our data indicate that the n → π* interaction occurs only when the local conformation of the accepting carbonyl group predisposes it for the required pyramidalization. The interplay between the n → π* interaction and θ_C pyramidalization underscores the importance of conformational pre-organization in promoting specific interactions in biomolecules.