Nature of π-interactions inn nitrogen-containing heterocyclic systems:: A structural database analysis

Noncovalent interactions involving heteroaromatic ring systems play a major role in determining the function of many chemical as well as biological molecules. Therefore, detailed quantitative analyses of the pi-interactions (X-H---pi and pi---pi) were carried out for nitrogen-containing pi-systems (isoxazole, imidazole, and indole moieties). Statistical analysis of the geometrical properties for the oxygen, nitrogen, and carbon atom donors with the heterocyclic pi-system acceptors showed that carbon donors participate in relatively large numbers for X-H---pi interactions, and they adopt T-shaped geometry. The pi-pi interaction analysis was categorized into three types based on the involvement of the heterocyclic at-systems with themselves, with any other benzene ring present in that particular structure, and their influence on the formation of pi-interactions between benzene-benzene rings found in that particular compound. The pi-systems in all the three categories prefer to form offset stacking pi---pi interaction geometry. The benzene rings which normally favor the formation of T-shaped geometry are found to prefer offset stacking geometry, which may be due to the influence of the heteroatom. The pi-systems in these heterocyclic structures behave similar to the phenylalaninephenylalanine interactions in proteins, and therefore this quantitative analysis can serve as a guide for structural and biological studies.