A Chemical Model of Catechol-O-methyltransferase. Methylation of 3,4-Dihydroxybenzaldehyde in Methanol Solution

The reaction of 3,4-dihydroxybenzaldehyde (LH₂) and dimethyl sulfate (DMS) in forming m- and p-O-methylated products (vanillin and isovanillin, respectively) in a methanol buffer solution was studied kinetically as a chemical model of catechol-O-methyltransferase (COMT). The O-methylations, especially m-O-methylations, were catalyzed by divalent metal ions such as Cu(II), Mg(II) and Zn(II). A clear Mg(II) catalysis was observed for the first time in this medium. As Mg(II) is an important metal in the COMT catalyzed reaction in vivo, this observation is very interesting. Kinetic analyses of the present data and recalculation of a part of the previous data offered the following evidence. In Cu(II) catalysis, a 1:2 complex(CuL₂) was more active than the 1:1 complex (CuL). On the other hand, in Mg(II) catalysis and Zn(II) catalysis, ML was more active than ML₂. These facts show that ML₂ is not always more active than ML, contrary to previous reports. Methanolysis of DMS, a significant side reaction of this model reaction, and dissociation of LH₂ were studied thoroughly as bases for these kinetic analyses.