Electronic Structure of Tetrahydropteridine Derivatives

Abstract

Recently; the 4-amino analogue of tetrahydrobiopterin was found to be a strong inhibitor of nitric oxide synthase while being bound to the enzyme in a manner similar to the natural cofactor tetrahydrobiopterin. We were interested in the electronic properties of these and similar compounds and studied therefore the following model tetrahydropteridine structures: tetrahydrolumazine, tetrahydropterin, 4-amino-analogue of tetrahydropterin and N5-methyl-tetrahydropterin. Ab initio quantum chemical computations used the Hartree- Fode method with basis set 6-31G** after geometry optimization with basis set 3-21G*. Results reveal dramatic differences in distribution of electronic charge and all the molecular properties derived thereof~ between a) the lumazine system, b) the normal pterin system, and c) the 4-amino analogue. In contrast, differences of electronic properties between tetrahydropterin and its N5-methyl-derivative are negligible. Our results are compatible with recent speculations that the striking differences between the effects of the tetrahydropterin struculrc and its 4-amino analogue on cnznllatic activity may be due to electronic interaction between the pyrimidine moiety of the ptcrin ring systcm and the heme group.

Keywords

• ab initio
• quanulm chemistry
• visualization
• pteridines
• nitric oxide synthase