Influence of PKa on the methylation of arylalkylamines by rabbit lung N-methyltransferase.

Substitution of one or two fluorine atoms on the B carbon of phenethylamine progressively reduced the pKa of the amine and increased its rate of methylation by N-methyltransferase from rabbit lung. The methylation of other amines (amphetamine and benzylamine) was similarly increased by decreases in pKa. The results suggest that the neutral nonprotonated amine is the molecular species attacked or preferred by this enzyme.