Substituent effects on the stability of the four most stable tautomers of adenine and purine.

Substituent effects at the C2-, C8- and N-positions of adenine and purine in their four the most stable tautomers are studied by means of B97D3/aug-cc-pvdz computation applying substituents of varying electronic properties: NO 2 , CN, CHO, Cl, F, H, Me, OMe, OH and NH 2 . The substituent effect is characterized by the substituent effect stabilization energy (SESE) and substituent Hammett constant σ . For adenine, SESE is obtained with purine as the reference system. Additionally, for both adenine and purine, SESE characteristics are estimated with benzene, imidazole and amino-pyrimidine as reference systems, when possible, taking into account substitution in topologically equivalent positions. The role of a C6-NH 2 group in adenine in modifying the substitution effect is observed and discussed. Additionally, the proximity effect for some asymmetric substituents ( e.g. CHO, OMe) is recognized and meticulously analyzed.