High temperature solid state catalytic isotope exchange with deuterium and tritium

Abstract

A method for synthesizing tritium- or deuterium-labeled amino acids, peptides and biogenic amines through high temperature solid state catalytic isotope exchange (HSCIE) is proposed. The dependence of the degree of isotope exchange in HSCIE on the structure of the compound, the reactivity of hydrogen at different carbon atoms and the conditions of the process has been examined. If HSCIE is performed in the temperature range of 373 to 413K, the selectivity of isotopic label incorporation comes to 70% or higher. When the tritium label is introduced into peptides, they retain the configuration of asymmetric atoms, even upon the substitution of tritium for hydrogen at the α-carbon atoms of the amino acid residues. HSCIE at 453–513K leads to an even distribution of the isotopic label over the organic compound molecule. The results of³H NMR spectroscopy highlighting the distribution of the tritium label in the organic compound molecules are presented. The configuration of asymmetric atoms in amino acids is preserved to a high extent upon 80–90% substitution of isotopes for hydrogen atoms.