Relative concentrations of zwitterionic and uncharged species in catecholamines and the effect of N-substituents.

The relative concentrations of zwitterionic and uncharged species for the series of N-substituted catecholamines (I, R1 = R2 = OH; R = H, Me, Et, i-Pr, t-Bu) are derived from the pKa data published in 1962 by Sinistri and Villa. The concentration ratios, represented by the tautomeric equilibrium constant Kt, show a definite trend and are respectively 1.8, 4.3, 4.7, 4.7, and 7.1. These values suggest that any mechanism of action involving proton transfer, which might transform the zwitterion into the uncharged form, would be most favorable for norepinephrine and least favorable fo the t-Bu derivative.