Study of the Activation Process of Isotope Exchange between Boc-Trp-Pro-Pro-Trp, Trp-Pro-Pro-Trp and Deuterated Water

The conditions for introducing deuterium into Trp-Pro-Pro-Trp and Boc-Trp-Pro-Pro-Trp by isotope exchange with D₂O in the presence of a 5% Pd/Al₂O₃ catalyst were developed. The thermal stability of Trp-Pro-Pro-Trp upon introduction of deuterium was significantly lower than that of the Boc-protected peptide. The yield of deuterated Trp-Pro-Pro-Trp did not exceed 10–15%, and the inclusion of deuterium was about 0.9–1.1 at./molecule at 125°C. The introduction of deuterium into Boc-Trp-Pro-Pro-Trp was possible at 150°C, which increased the deuterium content to 3.75 at./molecule. It was found that the tryptophan fragment of the molecule contains approximately 2 times more deuterium than the proline fragment. It was found that pretreatment of Boc-Trp-Pro-Pro-Trp with deuterium gas not only activates isotope exchange, but also promotes the removal of Boc protection. The data obtained indicate that the reason for this phenomenon is associated with the generation of deuterium cations on Boc-Trp-Pro-Pro-Trp molecules by the catalyst.