Molecular orbital studies on m- and p-methylation of substituted catechols by catechol O-methyltransferase

Abstract

The electronic structures of catechol derivatives, 3,4-dihydroxy-1-substituted benzenes, including epinephrine and norepinephrine, were calculated by means of CNDO/2 and MINDO/3 methods. Correlation between the ratio (meta:para) of O-methylated products of catechols catalyzed by catechol O-methyltransferase and the reaction indices calculated from molecular orbital parameters was found. The regression analysis showed that the electron donative indices at C2 and para O position and the electron acceptable index at C6 position in the catechols by CNDO/2 calculation represented the best correlation with the meta:para ratio. The correlation coefficient between the meta:para ratio predicted by regression equation and the observed one was 0.900. By means of MINDO/3 calculations, the regression equation from the electron donative indices at C2, C4, and C6 positions in catechols exhibited the correlation coefficient 0.798.