Seeing through solvent effects using molecular balances

Abstract

The study of molecular interactions is often complicated by solvent effects. Here we have used a series of 11 synthetic molecular balances to measure solvent and substituent effects on the positions of conformational equilibria in 13 different solvents. Despite the simplicity of the model system, surprisingly complicated behaviour was seen to emerge from the interplay of conformational, intramolecular and solvent effects. Nonetheless, 138 experimental conformational free energies were analysed using a simple solvent model, which was able to account for both the major and more unusual patterns observed. The success of the solvent model can be attributed to its ability to facilitate consideration of individual intramolecular and solute–solvent interactions, as confirmed by comparison with NMR chemical shifts and DFT calculations. The approach provides a means of dissecting electrostatic and solvent effects to reveal pseudo gas-phase behaviour from experimental data obtained in solution. For example, the method facilitated the identification of an unexpected, but highly favourable CO⋯NO₂ interaction worth up to 3.6 kJ mol⁻¹, which was shown not to be driven by solvent effects.