Zinc(II) and cadmium(II) metal complexes of thiamine pyrophosphate and 2-(alpha-hydroxyethyl)thiamine pyrophosphate: models for activation of pyruvate decarboxylase.

Metal complexes of thiamine pyrophosphate (TPP) of the general formula [M2(TPPH)2Cl2]x4H2O (M = Zn2+, Cd2+) were isolated from methanolic solutions and characterized by elemental analysis, FT-IR, and multinuclear NMR spectroscopies. The data provide evidence for the bonding of the metals to the N(1') atom of the pyrimidine ring and to the pyrophosphate group. The stability constant measurements of TPP and 2-(alpha-hydroxyethyl)thiamine pyrophosphate (HETPP) metal complexes in aqueous solution imply the formation of dimeric complex species similar to the isolated solid products. They indicate also that HETPP forms more stable metal complexes than does TPP. To evaluate the coenzyme action of TPP and HETPP metal complexes, enzymic studies have been done using pyruvate decarboxylase apoenzyme. TPP metal complexes do not bind to the apoenzyme, unlike the Zn(II)-HETPP complex which can act as coenzyme. Considering these results, possible functional implications for thiamine involvement in catalysis are discussed.