Stereoelectronic Interactions in Molecular Systems

Stereoelectronic interactions are a class of orbital-driven forces that govern the shape, stability and reactivity of molecular systems. They emerge when filled and vacant molecular orbitals adopt specific spatial alignments, permitting stabilising donor–acceptor overlap or, conversely, destabilising interactions when filled orbitals clash. Classic examples include hyperconjugation, whereby electrons in σ-bonds interact with adjacent antibonding orbitals to influence bond lengths and rotational barriers, and the anomeric effect, in which lone-pair donation to σ* orbitals stabilises certain ring conformations in carbohydrates and heterocycles. The balance between these attractive orbital overlaps and repulsive forces such as Pauli repulsion shapes conformational equilibria in organic frameworks, guiding selectivity in synthesis and catalysis. Advances in computational methods, including natural bond orbital analysis and energy decomposition, have enabled quantitative elucidation of these effects, while spectroscopic techniques offer experimental validation. Through careful stereoelectronic tuning, chemists have achieved precise control over reaction pathways, engineered novel catalysts and designed functional materials. At a global level, understanding stereoelectronic principles underpins the development of pharmaceuticals with optimal binding geometries, next-generation polymers with tailored mechanical properties and efficient catalytic processes that reduce energy demands and waste.

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Stereoelectronic Interactions in Molecular Systems publication trend

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Technical terms

Stereoelectronic interactions: Electronic stabilisation or destabilisation arising from the directional overlap of filled and vacant orbitals.

Hyperconjugation: Delocalisation of electrons from a filled σ-bonding orbital into an adjacent antibonding orbital.

Anomeric effect: Preference for an electronegative substituent on a cyclic system to adopt an axial orientation due to lone-pair donation into a σ* orbital.

Pauli repulsion: Destabilising interaction between filled orbitals that cannot occupy the same spatial region.

References

1. Exploring and Re-Assessing Reverse Anomeric Effect in 2-Iminoaldoses Derived from Mono- and Polynuclear Aromatic Aldehydes. Molecules (2024).
2. The Gauche Effect in XCH2CH2X Revisited. ChemPhysChem (2021).
3. In silico modelling of chelate stabilized tetrylene derivatives. RSC Advances (2024).