Solid phase isotope exchange with spillover hydrogen in amino acids, peptides, and proteins

Abstract

We summarize here information on the theoretical and experimental study of high-temperature (150-200 degrees C) solid phase catalytic isotope exchange (HTSPCIE) carried out with amino acids, peptides, and proteins under the action of spillover hydrogen. Main specific features of the HTSPCIE reaction, its mechanism, and its use for studying spatial interactions in polypeptides are discussed. A virtually complete absence of racemization makes this reaction a valuable preparative method. The main regularities of the HTSPCIE reaction with the participation of spillover tritium have been revealed in the case of peptides and proteins, and the dependence of reactivity of peptide fragments on the spatial organization of their molecules has been studied. An important peculiarity of this reaction is that HTSPCIE proceeds at 150-200 degrees C with a high degree of chirality retention in amino acids and peptides. This is provided by its reaction mechanism, which consists in a synchronous one-center substitution at the saturated carbon atom characterized by the formation of pentacoordinated carbon and a three-center bond between the carbon and the incoming and outgoing hydrogen atoms.

Preparation of Tritium‐Labeled Compounds by Isotope Exchange Reactions

“…It involves exposing a mixture of substrate, support and a metal catalyst to tritium gas and heat for a short period of time. This is consistent with observations that Ca labeling of amino acids usually proceeds with retention of configuration 232,233 . Tritium activated by the metal catalyst migrates ('spillover hydrogen' phenomenon 230 ) to the support material and thence to the substrate with which it then interacts.…”

Hydrogen Spillover. Facts and Fiction

“…Zolotarev et al have applied spillover to replace H atoms in organic molecules by deuterium (D) or tritium (T) atoms. The results of their extensive studies are described in two recent reviews. , They brought D 2 or T 2 gas in contact with a solid mixture of an inorganic support (such as barium sulfate or calcium carbonate), a Rh, Pd, or Pt salt, and a small amount of amino acid, peptide, carbohydrate, nucleoside, or heterocyclic acid at 100–240 °C during 20–200 min. An exchange of D or T atoms for H atoms took place in the organic molecule.…”

Solid State Isotope Exchange with Spillover Hydrogen in Organic Compounds

“…43,44 At temperatures of 180s200 °C and higher, isotope exchange at all H-C bonds proceeds evenly and leads to uniformly labeled compounds. 45 The distribution analysis of isotopomers is an effective method in solid state reactions investigation. Data on the isotopomeric distribution in the methyl groups of amino acids and peptides make it possible to determine the ratio of isotopomers in the reaction zone at a chosen temperature.…”

“…An interesting fact about HSCIE reactions is that they proceed regioselectively in the 100−150 °C temperature range, leading to the formation of selectively labeled compounds. The correlation between the structure of the α-amino acids and their reactivity has been studied. , At temperatures of 180200 °C and higher, isotope exchange at all H−C bonds proceeds evenly and leads to uniformly labeled compounds …”