Complexation of NADH analogs with divalent metal ions: Dependence on the 3-substituent of 1-benzyl-1,4-dihydropyridines

Abstract

In light of the critical role of divalent metal ions in the chemistry of coenzyme NADH analogs, complexation of 1-benzyl-3-substituted(X)-1,4-dihydropyridines (1, X=CONH2; 2, X=CSNH2; 3, X=COOCH3; 4, X=COCH3) with divalent metal ions (Mg2+, Zn2+, and Co2+) in dry acetonitrile was studied spectroscopically and kinetically. Presence of the metal ions causes red-shift of absorption band of NADH analogs and the rate retardation for the reaction between NADH analogs and N-methylacridinium ion. Analysis of the spectroscopic and kinetic data indicates that the NADH analogs form 1 : 1 complexes with the metal ions. The decreasing order of the magnitude of the association constants, K, is 1 ≅ 2 ≫ 4 ≫ 3 for a given metal ion, and Mg2+ ≫ Zn2+ > Co2+ for a given NADH analog. The results strongly suggest that the primary binding site for the metal ions is the carbonyl oxygen (or thiocarbonyl sulfur) of the 3-substituent and that the amide nitrogen atom of the 3-substituent of 1 and 2 also ligates the metal ions, forming a bidentate structure and providing extra stability to the complexes of 1 and 2. Inhibition of reaction between NADH analogs and N-methylacridinium ion by the metal ions is attributed to inaccessibility of N-methylacridinium ion to the NADH analogs complexed with metal ions due to electrostatic repulsion.