Study of solid-state catalytic isotope exchange of hydrogen inl-hydroxyproline under the action of spillover tritium

Abstract

Reaction of high-temperature solid-state catalytic isotope exchange (HSCIE) of hydrogen in L-hydroxyproline was studied by ab initio quantum-chemical calculations. A onecenter synchronous mechanism of isotope exchange between the amino acid and the H30 + model acidic center was considered. The structures of transition states of the reaction and the activation energies were determined. Relative reactivity of the C--H bonds in the hydroxyproline molecule under conditions of HSCIE was studied. The results obtained are in agreement with experimental data on the stereoselectivity and regioselectivity of the HSCIE reaction, viz., the lower the calculated activation energy of isotope exchange, the larger the portion of hydrogen substituted by tritium in a given position of the amino acid molecule. The enhancement of the reactivity under conditions of solid-state isotope exchange can be associated with additional interaction between the exchanging H atoms and the electrondonor O and N atoms of the amino acid molecule in transition state.Key words: ab initio quantum-chemical calculations, activation energy, hydrogen isotope exchange, hydrogen spillover.Reactions of solid-state hydrogenolysis are used to obtain organic compounds labeled with hydrogen isotopes. The reaction, based on applying high-temperature solid-state catalytic isotope exchange (HSCIE) appears to be particularly efficient for the synthesis of tritiumlabeled biologically active compounds. 1,z The reaction proceeds with retention of configuration of the asymmetric carbon atoms and in some instances it is possible to achieve virtually complete substitution of hydrogen atoms. It has been shown experimentally that the HSCIE reaction is based on the phenomenon of hydrogen spillover (HS). 3 A correlation between the local proton affinities of amino acids and the capability of hydrogen atoms to be substituted in the HSCIE reaction has been found. 4Hydrogen spillover can be considered as separate transfer of a proton and electron over the surface of an inorganic support. In this case the proton and electronic conductivity are simultaneously observed. 5 Water adsorbed on the surface of the support is a cocatalyst of HS, 6 which suggests the formation of complexes of the type H30 + on the surface. A one-center synchronous mechanism with participation of a strongly acidic proton surface center was suggested for the hydrogen exchange reaction in CH4. 7 This work is dedicated to studying the reaction of solid-state isotope exchange of hydrogen by tritium in hydroxyproline. ExperimentalSolid-state isotope exchange of hydrogen by tritium in t-hydroxyproline. Activated carbon (Norit A, Serva, 25 mg) and an aqueous solution of t,-hydroxyproline (Sigma, 0.5 mL) were mixed. Water was removed at a reduced pressure at 20 ~ Activated carbon coated with the amino acid was mixed with 5 mg of catalyst (5% Rh/AI203, Fluka). The solid mixture containing 0.5 mg of c-amino acid was placed into a 10 mL ampule. The ampule was evacuated and filled with gaseous tritium until a pressur...

The efficiency of solvent‐free catalyst systems in the synthesis of tritium‐labelled biologically active compounds

“…This concept is based on the premise that at temperatures between 50 and 200°C the activated particles of hydrogen spillover are primarily tritons. This model explains the experimental fact that the lower the electrophilic substitution energy of a specific carbon atom, the greater the degree of label inclusion in that specific location of the molecule 23. In this regard, it is obvious that in a molecule comprising a phenolic fragment and a benzoic acid fragment the isotopic exchange will be more effective in the phenolic ring.…”

Solid State Isotope Exchange with Spillover Hydrogen in Organic Compounds

“…50 The results in Table 11 are for the experimental study of isotope exchange in L-hydroxyproline (L-Hyp) and the theoretical calculations for the exchange ability of the L-Hyp H atoms. 95 The structures of the HSCIE transition states formed in L-Hyp are shown in Figure 14. The activation energy for the interaction of the model acidic center with the amino acid was found using the ab initio RHF/6-31G* method.…”

“…The results in Table are for the experimental study of isotope exchange in l -hydroxyproline ( l -Hyp) and the theoretical calculations for the exchange ability of the l -Hyp H atoms . The structures of the HSCIE transition states formed in l -Hyp are shown in Figure .…”