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 Δ_B, the paramagnetic shift of the bound hydroxymethyltriazene, and K_B, the equilibrium binding constant, to be calculated. The data are consistent with 1 : 1 complex formation and values of K_B, which lie between 10–60 l mol^–1, are little affected by the aromatic substituent. Correlation of the pseudo-contact induced shifts, Δ_B, 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.