On the Substituent Effect of tert-Butylaminoxyl Group for the Acid-dissociation Equilibria of α-Substituted Acetic Acids

Abstract

α-Substituted acetic acids with tert-butylaminoxyl groups, t-BuN(O•)–CHX–COOH, were produced as spin adducts in gamma-irradiated aqueous solutions of amino acids and peptides with a spin trap, 2-methyl-2-nitrosopropane. The spin adducts were isolated and characterized by means of high-performance liquid chromatography and EPR spectroscopy. Their EPR spectra in acidic region changed reversibly with pH through the acid-dissociation of the carboxyl groups. The spectra at pH around the pK value were weighted averages of acid forms and conjugate base forms. The pK_COOH values for the dissociation were determined to be 3.0, 3.2, 2.0, 1.8, and 1.6 for t-BuN(O•)–CH₂COOH, t-BuN(O•)–CH(CH₃)COOH, NH₃⁺CH₂CONHCH(COOH)N(O•)–t-Bu, and NH₃⁺–^∗CH(CH₃)–CONH–^∗CH(COOH)N(O•)–t-Bu [a pair of diastereomers], respectively. The electron-withdrawing character of the aminoxyl group is responsible for the observation that the pK_COOH values are lower than those of X–CH₂–COOH. The substituent effect of the tert-butylaminoxyl group on the acid-dissociation equilibria of alpha-substituted acetic acids was investigated in relation to the Taft equation. The aliphatic polar substituent constant (σ^∗) has been evaluated to be approximately +0.9 for the t-BuN(O•)CH₂ group [or the inductive substituent constant σ₁ approximately +0.4 for the t-BuN(O•) group].

Key Words:

• spin trapping
• aminoxyl radical
• acid-dissociation of free radical
• pK of α-substituted acetic acid
• aliphatic substituent constant
• HPLC-EPR method