Application of tritium high resolution NMR spectroscopy to analysis of tritium-labelled amino acids and peptides

Rosenberg, Steven; Zolotarev, Yu. A.; Myasoedov, N. F.

doi:10.1007/bf00806011

Cited by 11 publications

(14 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tritium distribution in a number of labeled amino acids and peptides obtained by the HSCIE reaction was analyzed by 3 H NMR [61,62]. Some results of this study obtained in amino acids at 150°ë are given in Table 4.…”

Section: Solid Phase Catalytic Isotope Exchange Using Gaseous Deuterimentioning

confidence: 99%

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

2005

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Solid Phase Catalytic Isotope Exchange Using Gaseous Deuterimentioning

confidence: 99%

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

2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…The tritium-labeled amino acid (50 mCi) dissolved in D20 (500 mL) was used for measurements. 7 The refined data on stereochemistry of the isotope label distribution were obtained by a procedure described previousiy. 8 Calculation methods.…”

Section: Synthesis Of (R)-4-tert-butoxy-alpyrrolin-2-carboxytie Acidmentioning

confidence: 99%

Stereoselective effects in the solid-phase hydrogenation of unsaturatedl-hydroxyproline derivatives

et al. 1997

Self Cite

View full text Add to dashboard Cite

The solid-phase catalytic hydrogenation of (R)-4-tert-butoxy-~XLpyrroline-2-carboxylic acid under the action of hydrogen spillover was studied. The reaction proceeds stereoselectively with the predominant formation of the L-amino acid. The configuration of the asymmetric center formed is determined by that of the asymmetric C(4) atom. The major portion of the isotope label is incorporated into the allylic C(3) and C(5) positions, and the ~-[-t atoms are more mobile. Using quantum-chemical calculations, the geometric structure of the L-hydroxyproline molecule was calculated, and the spin-spin coupling constants for this tritium-!abeled amino acid were determined.Key words: solid-phase hydrogenation; quantum-chemical calculation; stereochemist~ of addition; 3H NMR; hydrogen spillover.Tritium labeling of amino acids is widely used in medical biological studies. A multiple tritium label, which decreases the limits of determination of labeled compounds, is especially valuable. Liquid-phase catalytic reduction of unsaturated compounds-precursors is the main method for the incorporation of tritium into aliphatic amino acids) If this reaction is carried out in a solid mixture of a finely dispersed platinum group metal, an inorganic support, and an unsaturated amino acid derivative, the degree of incorporation of tritium into the amino acid increases. 2,3 Solid-phase catalytic hydrogenation (SCH) can be performed in the absence of a direct contact between the catalyst and the substrate. The transfer of hydrogen activated on the catalyst to the reaction zone is called hydrogen spillover. 4 Asymmetric cyclohexanols were obtained by the reaction of hydrogen spillover (HS) with asymmetric crystals of substituted phenol. 5 In this work, the stereochemistry of the solid-phase hydrogenation of the diastereotropic multiple bond in (R)-4-tert-butoxy-M-pyrroline-2-carboxylic acid under the action of HS was studied. ExperimentalThe studied transformations of L-hydroxyproline derivatives are presented in Scheme 1. Synthesis of (R)-4-tert-butoxy-ALpyrrolin-2-carboxytie acid(2). (R)-4-tert-Butoxy-L-proline 1 (0.56 g, Bachem) was added to a 0.3 M solution of CuSO 4 (5 mL). 7"lien 5 M KOH

show abstract

“…The purification of L-Hyp was performed by ligand exchange chromatography using chiral sorbents, s The tritium distribution in the labeled amino acid was determined by 3H NMR spectroscopy. 9 The extent of tritium incorporation into the amino acid was established by liquid scintillation analysis.…”

Section: Methodsmentioning

confidence: 99%

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

Zolotarev

Borisov

1999

Russ Chem Bull

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Application of tritium high resolution NMR spectroscopy to analysis of tritium-labelled amino acids and peptides

Cited by 11 publications

References 3 publications

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

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

Stereoselective effects in the solid-phase hydrogenation of unsaturatedl-hydroxyproline derivatives

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

Contact Info

Product

Resources

About