Reconciling Electrostatic and n→π* Orbital Contributions in Carbonyl Interactions

Abstract

Interactions between carbonyl groups are prevalent in protein structures. Earlier investigations identified dominant electrostatic dipolar interactions, while others implicated lone pair n→π* orbital delocalisation. Here these observations are reconciled. A combined experimental and computational approach confirmed the dominance of electrostatic interactions in a new series of synthetic molecular balances, while also highlighting the distance‐dependent observation of inductive polarisation manifested by n→π* orbital delocalisation. Computational fiSAPT energy decomposition and natural bonding orbital analyses correlated with experimental data to reveal the contexts in which short‐range inductive polarisation augment electrostatic dipolar interactions. Thus, we provide a framework for reconciling the context dependency of the dominance of electrostatic interactions and the occurrence of n→π* orbital delocalisation in C=O⋅⋅⋅C=O interactions.

Enabling three-dimensional porous architectures via carbonyl functionalization and molecular-specific organic-SERS platforms

“…The minimum ( Ar ) C-H···π/S···S interaction distances were found to be ~0.2 Å smaller than those in C 8 -BTBT , which is undoubtedly owing to the electronic effect of carbonyl presence (i.e., deshielding on the aromatic π-system and increased acidity for the α-methylene hydrogens) 26 . On the basis of the measured distance, carbonyl···carbonyl interactions in D(C 7 CO)-BTBT film is found to be of dipolar nature 30 , 32 , 38 , rather than n-π* interactions (typical distances <3.1–3.2 Å) 4 , 31 . These dipolar head-to-tail carbonyl interactions were reported to be strong noncovalent interactions that could indeed be competitive with hydrogen bonds in some biological molecules 30 – 32 .…”

Analysis of the Orbital and Electrostatic Contributions to the Lone Pair–Aromatic Interaction Using Molecular Rotors

“…25 However, this is different than what was observed for the CO•••CO interaction, where the orbital delocalization component was greatly accentuated at shorter distances. 24 This provides additional support for the fundamental differences between the CO•••Ar and CO•••π interactions. Both have strong electrostatic components.…”

“…A characteristic of interactions with a large orbital delocalization component is a strong correlation between an increasing interaction strength and decreasing atom−atom distances. 23,24 In rotors 1, a poor correlation (R 2 = 0.237) was observed between ΔG CO•••Ar and CO•••C(1) atom distances (Figure 4d, red squares). The atom distances spanned a narrow range (2.53−2.57 Å) despite significant variations in the interaction energies (0.25−4.49 kcal/mol).…”

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

“…The effect occurs indirectly due to the impact onto the side-chain envelope conformation: the C 4 - exo conformation creates a favorable relative arrangement of the main-chain groups. This energetic favorability is typically attributed to the n→π* donative interaction between the carbonyl groups, although the exact nature of this interaction (orbital or dipolar) is debatable [ 82 ]. Result of this effect though, is that the trans -fluoroproline shifts the equilibrium towards a higher abundance of the trans -amide, while cis -fluoroproline promotes the cis -amide ( Fig.…”