Nucleophilicities of amino acids and peptides

Abstract

The kinetics of the reactions of amino acids with stabilized diarylcarbenium ions (Ar₂CH⁺) have been studied photometrically in aqueous solution at variable pH. In the range of 10.5 < pH < 12, the amino acids react much faster than the competing nucleophiles hydroxide and water. Though the pK_aH values of the amino acids vary by almost four units, the nucleophilic reactivities of all primary amino groups differ by less than a factor of 4. The secondary amino group of proline is 10² times more reactive, and the thiolate site in cysteine exceeds the reactivities of the primary amino groups by a factor of 10⁴. Nucleophilicity parameters N as defined by the correlation log k_20 °C = s(N + E) have been determined in order to include amino acids into the most comprehensive nucleophilicity scales presently available, which provide a direct comparison of n-, π-, and σ-nucleophiles.