Synthesis, characterization, and crystal structures of n-alkyldiorganodithiophosphates RS2P(OC6H4)2

Cation-pi interactions occur between cations and electron-rich species such as double bonds, triple bonds, and arenes. The pi-electron system may be neutral or anionic, but the latter are less relevant to biology, at least so far as is currently known. Among the 20 essential amino acids, there are four aromatic residues. These are benzene, phenol, indole, and imidazole, on the side chains of phenylalanine, tyrosine, tryptophan, and histidine, respectively. Of these, imidazole is expected to be a sigma-donor, and benzene, phenol, and indole are antipicated to serve as pi-donors. Sodium and potassium are the most abundant cations in living systems. This Account describes an experimental system that has been developed to probe, especially by X-ray crystallography, the interactions that occur between Na(+) or K(+) and the neutral arenes of particular biological significance.

Recent X-ray crystallographic and NMR evidence indicates that relatively weak intramolecular edge-to-face interactions between aromatic rings can affect or determine the conformation of organic molecules in the solid state and in solution. Experimental estimates indicate that these interactions are energetically attractive by ca. 1.5 kcal mol(-1) but disfavored in solution by entropic factors due to the restricted internal mobility. Hence, these interactions are more manifest at low temperature in solution or in crystal structures where conformational entropy effects are negligible.