The largest energetic effects (highest ∆E total ) usually correspond to breaking of strong non-bonded intramolecular interactions, such as intramolecular hydrogen bonds or stabilising interactions from folding of long, flexible molecules, that are present in the most stable geometry of the isolated molecule. In the absence of such effects, molecules in CS structures usually adopt a geometry that is energetically close to one of their lowest energy conformers, although this is often not the lowest possible conformer of the isolated molecule.