QUANTUM CHEMICAL STUDY OF THE ELECTRONIC AND CONFORMATIONAL CHARACTERISTICS OF ADENOSINE AND 8-SUBSTITUTED DERIVATIVES - FUNCTIONAL IMPLICATIONS IN THE MECHANISM OF REACTION OF ADENOSINE-DEAMINASE

A quantum chemical study of 10 substrates of adenosine deaminase is performed. The conformational preference around the glycosidic bond of several 8‐substituted derivatives of adenosine is studied using semiempirical modified neglect of diatomic overlap (MNDO) and Austin model 1 (AM1) methods. All the compounds studied show preference for the anti conformation; the syn – anti energetic differences calculated are small and in excellent agreement with experimental data. A relationship between the ab initio molecular electrostatic potential minimum energy of N3 and the syn – anti energetic difference is found. A highly significant relationship is also found between the ab initio net charge over the purine and pyrimidine rings and the logarithm of the maximum rate of deamination (log Vm) of the nucleosides by adenosine deaminase. In contrast, no significant relationship is found between the anti preference of 8‐substituted derivatives of adenosine and their log Vm of deamination. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company