New Development in the Solid-State Isotope Exchange with Spillover Hydrogen in Organic Compounds

Abstract

Solid-state catalytic isotope exchange of hydrogen under the action of spillover hydrogen in organic compounds applied on a nonorganic carrier has been studied. The deuterium-labeled peptide [D]dalargin containing 14 deuterium atoms, [D]melatonin, and [D]histamine with the 72–92% substitution degree of all C–H bonds were prepared by this reaction. The activation energy of hydrogen isotope exchange with T2 and D2 in glycine and α-aminoisobutyric acid was obtained experimentally. It was shown that for the studied reaction the kinetic isotopic effect is 1.2–1.4 by the Hartree–Fock method, which is several times smaller than one in the liquid-phase reactions. Quantum chemical calculations of the isotope shift values in the electronic spectra of deuterium-labeled metal ion complexes were performed using the RB3LYP/LanL2DZ and CIS/LanL2DZ methods for calculation of the ground and the excited states. It was shown for deuterium-labeled histamine complexes [D12]Pd(him)2Cl2 and [D12]Cu(him)2Cl that the isotopic effect of UV spectra was 1600 and 1800 cal/mol, respectively. The measurement of isotopic shifts for electronic transitions potentially can be utilized as a new informative method for the investigation of complex formation. The deuterium-labeled compounds were shown to be useful as internal standards for quantitative mass spectroscopy (MS) analysis.

Use of deuterium labeling by high‐temperature solid‐state hydrogen‐exchange reaction for mass spectrometric analysis of bradykinin biotransformation

“…Deuterated BK was obtained using the HSCIE reaction . Figure shows that deuterated BK was detected as an ion with m / z = 533.30011 corresponding to the doubly charged state ion of the peptide.…”

“…This approach is potentially applicable for kinetic studies, structural analysis as well as analysis of protein‐protein interactions and supramolecular complex formation. In contrast to deuterium labeling of selected moieties of various substances, the deuteration allows analysis of the metabolic transformation of all fragments of peptides or organic compounds of interest …”

“…To produce such peptides, we have recently proposed a method using high‐temperature solid‐state hydrogen exchange (HSCIE) . Using this method it is possible to substitute hydrogen atoms for deuterium atoms at the asymmetric carbon atoms and this substitution does not affect the asymmetric configuration of the carbon atoms . In the HSCIE reaction isotope exchange follows single‐centric synchronic mechanism with spillover hydrogen.…”

“…The main features of the solid‐state reaction of the hydrogen isotope exchange of organic compounds on hydrogen spillover have been recently reviewed . This reaction is also characterized by an extremely low kinetic isotope effect, which causes substitution of hydrogen for deuterium or tritium atoms at basically the same velocities and generation of uniform distribution of the label within the molecule . An important feature of the HSCIE reaction is that the isotopic exchange in peptides and proteins occurs with preservation of their physiological activity .…”

“…[17] Using this method it is possible to substitute hydrogen atoms for deuterium atoms at the asymmetric carbon atoms and this substitution does not affect the asymmetric configuration of the carbon atoms. [18] In the HSCIE reaction isotope exchange follows single-centric synchronic mechanism with spillover hydrogen. The main features of the solid-state reaction of the hydrogen isotope exchange of organic compounds on hydrogen spillover have been recently reviewed.…”