Increasing Complexity in a Conformer Space Step-by-Step: Weighing London Dispersion against Cation-? Interactions

We report an evaluation of the importance ofLondon dispersion in moderately large (up to 36 heavy atoms)organic molecules by means of a molecular torsion balance whoseconformationsweighone interaction against another in theabsence of solvents. The experimental study, with gas-phasecryogenic ion vibrational predissociation (CIVP) spectroscopy,solid-state Fourier transfer infrared (FT-IR), and single-crystal X-ray crystallography, is accompanied by density functional theorycalculations, including an extensive search and analysis ofaccessible conformations. We begin with the unsubstitutedmolecular torsion balance, and then step up the complexitysystematically by adding alkyl groups incrementally as dispersionenergy donors (DEDs) to achieve a degree of chemical complexity comparable to what is typically found in transition states formany regio- and stereoselective reactions in organic and organometallic chemistry. Wefind clear evidence for the small attractivecontribution by DEDs, as had been reported in other studies, but we alsofind that small individual contributions by Londondispersion, when they operate in opposition to other weak noncovalent interactions, produce composite effects on the structure thatare difficult to predict intuitively, or by modern quantum chemical calculations. The experimentally observed structures, togetherwith a reasonable value for a reference cation-pi interaction, indicate that the pairwise interaction between twotert-butyl groups, inthe best case, is modest. Moreover, the visualization of the conformational space, and comparison to spectroscopic indicators of thestructure, as one steps up the complexity of the manifold of noncovalent interactions, makes clear that in silico predictive ability forthe structure of moderately large,flexible, organic molecules falters sooner than one might have expected

Automated summary

This study evaluates the importance of London dispersion in moderately large organic molecules through experimental and theoretical calculations. The results show that London dispersion contributes small but significant effects on the molecular structure. However, when London dispersion operates against other weak noncovalent interactions, composite effects on the structure that are difficult to predict arise.