Abstract
Carbonyl-carbonyl n→π* interactions where a lone pair (n) of the oxygen atom of a carbonyl group is delocalized over the π* orbital of a nearby carbonyl group have attracted a lot of attention in recent years due to their ability to affect the 3D structure of small molecules, polyesters, peptides, and proteins. In this paper, we report the discovery of a “reciprocal” carbonyl-carbonyl interaction with substantial back and forth n→π* and π→π* electron delocalization between neighboring carbonyl groups. We have carried out experimental studies, analyses of crystallographic databases and theoretical calculations to show the presence of this interaction in both small molecules and proteins. In proteins, these interactions are primarily found in polyproline II (PPII) helices. As PPII are the most abundant secondary structures in unfolded proteins, we propose that these local interactions may have implications in protein folding.
Highlights
Carbonyl-carbonyl n→π* interactions where a lone pair (n) of the oxygen atom of a carbonyl group is delocalized over the π* orbital of a nearby carbonyl group have attracted a lot of attention in recent years due to their ability to affect the 3D structure of small molecules, polyesters, peptides, and proteins
We carried out Cambridge Structural Database (CSD)[33] and Protein Data Bank (PDB)[34] analyses to show that these interactions are widely present in small molecules and proteins
We propose that due to the repulsion between the nitrogen lone pairs, the N,N-diacylhydrazines should be nonplanar with the carbonyl groups orientated favorably for reciprocal n→π* interactions
Summary
Carbonyl-carbonyl n→π* interactions where a lone pair (n) of the oxygen atom of a carbonyl group is delocalized over the π* orbital of a nearby carbonyl group have attracted a lot of attention in recent years due to their ability to affect the 3D structure of small molecules, polyesters, peptides, and proteins. NBO analyses of crystal geometries of 30 randomly chosen molecules (Supplementary Fig. 4) having d1 and d2 ≤ 3.20 Å and covering the range of observed ∠O···C = O angles (θ) values (70–100°) showed the presence of reciprocal interactions in them (Table 2).
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