Triazene drug metabolites. Part 6. The interaction of N-hydroxymethyl-triazenes with lanthanide-induced shift reagents
Abstract
Paramagnetic induced chemical shifts were obtained for a series of 1-aryl-3-hydroxymethyl-3-methyltriazenes and related compounds by the addition of Pr(thd)3 or Eu(fod)3. Induced shifts were shown to be pseudo-contact in origin. Qualitative work using Pr(thd)3 inducated that the N–CH2–O proton resonances are shifted the most, followed by the N–Me resonances. Neither 1-aryl-3-methyl-nor 1-aryl-3,3-dimethyl-triazenes exhibit induced shifts of the N–Me resonances, which indicates that binding of the hydroxymethyltriazenes to the lanthanide ion occurs through the hydroxyl function. Quantitative work using Eu(fod)3 allowed values of ΔB, the paramagnetic shift of the bound hydroxymethyltriazene, and KB, the equilibrium binding constant, to be calculated. The data are consistent with 1 : 1 complex formation and values of KB, which lie between 10–60 l mol–1, are little affected by the aromatic substituent. Correlation of the pseudo-contact induced shifts, ΔB, with r3(where r is the distance between the resonating nucleus and the Eu3+ ion) occurs when the hydroxymethyltriazene is assumed to bind to Eu3+ through the hydroxyl oxygen atom. In contrast, 3-hydroxymethyl-3-methyl-1-(3′-pyridyl)triazene binds to both Pr3+ and Eu3+ through the pyridyl nitrogen atom.