Deuterated Compounds Research Articles

Progress in the decarboxylative deuteration reaction of alkyl carboxylic acids

The application of deuterated compounds is increasingly expanding across various fields, making the development of novel deuterium labeling techniques for obtaining deuterated compounds a burgeoning research focus. Carboxylic acids and their derivatives are widely utilized as cost‐effective and readily available materials for obtaining deuterated compounds due to their stable properties. This article presents a comprehensive and concise summary of the research progress in decarboxylative deuteration reactions over the past 20 years.

K2CO3/18-Crown-6-Catalyzed Selective H/D Exchange of Heteroarenes with Bromide as a Removable Directing Group.

The K2CO3/18-crown-6-catalyzed H/D exchange of heretoarenes in high atom % deuterium incorporation is disclosed. The use of a weak base as a catalyst leads to excellent site selectivity and broad functional group tolerance. Control experiments indicated that the use of bromide, which enhances the adjacent C-H bond reactivity, as a removable directing group is essential. Moreover, conversion of bromide to other functional groups is also performed to construct other useful deuterated compounds.

Cesium Amide-Catalyzed Selective Deuteration of Benzylic C-H Bonds with D2 and Application for Tritiation of Pharmaceuticals.

Hydrogen isotope exchange (HIE) represents one of the most attractive labeling methods to synthesize deuterium- and tritium-labeled compounds. Catalytic HIE methods that enable site-selective C-H bond activation and exchange labeling with gaseous isotopes D2 and T2 are of vital importance, in particular for high-specific-activity tritiation of pharmaceuticals. As part of our interest in exploring s-block metals for catalytic transformations, we found CsN(SiMe3 )2 to be an efficient catalyst for selective HIE of benzylic C-H bonds with D2 gas. The reaction proceeds through a kinetic deprotonative equilibrium that establishes an exchange pathway between C-H bonds and D2 gas. By virtue of multiple C-H bonds activation and high activity (isotope enrichment up to 99 %), the simple cesium amide catalyst provided a very powerful and practically convenient labeling protocol for synthesis of highly deuterated compounds and high-specific-activity tritiation of pharmaceuticals.

Cesium Amide‐Catalyzed Selective Deuteration of Benzylic C‐H Bonds with D2 and Application for Tritiation of Pharmaceuticals

AbstractHydrogen isotope exchange (HIE) represents one of the most attractive labeling methods to synthesize deuterium‐ and tritium‐labeled compounds. Catalytic HIE methods that enable site‐selective C−H bond activation and exchange labeling with gaseous isotopes D2 and T2 are of vital importance, in particular for high‐specific‐activity tritiation of pharmaceuticals. As part of our interest in exploring s‐block metals for catalytic transformations, we found CsN(SiMe3)2 to be an efficient catalyst for selective HIE of benzylic C−H bonds with D2 gas. The reaction proceeds through a kinetic deprotonative equilibrium that establishes an exchange pathway between C−H bonds and D2 gas. By virtue of multiple C−H bonds activation and high activity (isotope enrichment up to 99 %), the simple cesium amide catalyst provided a very powerful and practically convenient labeling protocol for synthesis of highly deuterated compounds and high‐specific‐activity tritiation of pharmaceuticals.

Cultivation of the microalgae Chlamydomonas reinhardtii and Desmodesmus quadricauda in highly deuterated media: Balancing the light intensity.

The production of organic deuterated compounds in microalgal systems represents a cheaper and more versatile alternative to more complicated chemical synthesis. In the present study, we investigate the autotrophic growth of two microalgae, Chlamydomonas reinhardtii and Desmodesmus quadricauda, in medium containing high doses of deuterated water, D2O. The growth of such cultures was evaluated in the context of the intensity of incident light, since light is a critical factor in the management of autotrophic algal cultures. Deuteration increases the light sensitivity of both model organisms, resulting in increased levels of singlet oxygen and poorer photosynthetic performance. Our results also show a slowdown in growth and cell division processes with increasing D2O concentrations. At the same time, impaired cell division leads to cell enlargement and accumulation of highly deuterated compounds, especially energy-storing molecules. Thus, considering the specifics of highly deuterated cultures and using the growth conditions proposed in this study, it is possible to obtain highly deuterated algal biomass, which could be a valuable source of deuterated organic compounds.

Synthesis of Deuterated Methylphosphonic Acid Derivatives for Use as Standard Compounds in the Analysis of Toxic Chemicals

One of the ways to ensure high reliability of detection, identification and accuracy of quantitative determination of toxic chemicals (TC) in environmental and biomedical samples by gas and liquid chromatography-mass spectrometry methods is to use internal standards (IS) as additives to the analyzed sample, which, in contrast from target TC, contain stable isotopes such as D, 13 C, 15 N, 18 O. In this case, preference is given to the most accessible stable deuterated compounds. IS labeled with stable isotopes are widely used in numerous studies to develop methods for the analysis of various toxic chemicals, in particular, alkylphosphonic acids. For the prompt and high-quality performance of the tasks assigned to the assigned laboratory, it seems necessary to have a physical bank of samples labeled with stable IS isotopes, corresponding to those TC, the appearance of which in the analyzed samples is most likely. These include, first of all, stable decomposition products of such as sarin, soman, cyclosarin, VX, VR, CVX, namely, methylphosphonic acid, its ethyl, isopropyl, butyl, isobutyl, pinacolyl and cyclohexyl esters, as well as the corresponding symmetric diesters . In accordance with the objectives of the article, we have synthesized the IS composition of deuteromethylphosphonic acid and its derivatives: acid chlorides of O-alkyl esters of deuteromethylphosphonic acids, acid O-alkyl esters of deuteromethylphosphonic acids, O, O-dialkyl esters of deuteromethylphosphonic acids, and also adducts of tyrosine and tripeptide Tyr-Thr-Lys with chlorides of O-isopropyl and O-cyclohexyl esters of deuteromethylphosphonic acid. NMR 2 Н, 31 Р, GC-MS and HPLC-MS spectral characteristics of the synthesized substances were studied

A fast SALLE GC–MS/MS multi-analyte method for the determination of 75 food packaging substances in food simulants

A simple and fast method was developed for the simultaneous determination of 75 plastic food contact material (FCM) in liquid food simulants, at levels of a few ng g−1. The method employs an optimised salt-assisted liquid–liquid extraction for all EU-regulated ethanol/H2O food simulants, in the presence of 10% NaCl (simulants A and C) or 5% NaCl (simulant D1), and dichloromethane as the extracting solvent. Gas chromatography with triple-quad MS operating in multiple reaction monitoring acquisition was used, applying isotope dilution with selected deuterated compounds. Adequate sensitivity was demonstrated for all analytes. The results also showed sufficient accuracy for the majority of substances, with recoveries of 70–120% and repeatability (expressed as relative standard deviations, RSDs) smaller than 15%. The method was applied to the analysis of FCM multilayer items after undergoing migration testing according to the specifications of the current EU legislation in force.

Nanocatalyzed Hydrogen Isotope Exchange

Recently, hydrogen isotope exchange (HIE) reactions have experienced impressive development due to the growing importance of isotope containing compounds in various fields including materials and life sciences, in addition to their classical use for mechanistic studies in chemistry and biology. Tritium-labeled compounds are also of crucial interest to study the in vivo fate of a bioactive substance or in radioligand binding assays. Over the past few years, deuterium-labeled drugs have been extensively studied for the improvement of ADME (absorption, distribution, metabolism, excretion) properties of existing bioactive molecules as a consequence of the primary kinetic isotope effect. Furthermore, in the emergent "omic" fields, the need for new stable isotopically labeled internal standards (SILS) for quantitative GC- or LC-MS analyses is increasing. Because of their numerous applications, the development of powerful synthetic methods to access deuterated and tritiated molecules with either high isotope incorporation and/or selectivities is of paramount importance.HIE reactions allow a late-stage incorporation of hydrogen isotopes in a single synthetic step, thus representing an advantageous alternative to conventional multistep synthesis approaches which are time- and resource-consuming. Moreover, HIE reactions can be considered as the most fundamental C-H functionalization processes and are therefore of great interest for the chemists' community. Depending on the purpose, HIE reactions must either be highly regioselective or allow a maximal incorporation of hydrogen isotopes, sometimes both. In this context, metal-catalyzed HIE reactions are generally performed using either homogeneous or heterogeneous catalysis which may have considerable drawbacks including an insufficient isotope incorporation and a lack of chemo- and/or regioselectivity, respectively.Over the past 6 years, we have shown that nanocatalysis can be considered as a powerful tool to access complex labeled molecules (e.g., pharmaceuticals, peptides and oligonucleotides) via regio- and chemoselective or even enantiospecific labeling processes occurring at the surface of metallic nanoclusters (Ru or Ir). Numerous heterocyclic (both saturated and unsaturated) and acyclic scaffolds have been labeled with an impressive functional group tolerance, and highly deuterated compounds or high molar activity tritiated drugs have been obtained. An insight into mechanisms has also been provided by theoretical calculations to explain the regioselectivities of the isotope incorporation. Our studies have suggested that undisclosed key intermediates, including 4- and 5-membered dimetallacycles, account for the particular regioselectivities observed during the process, in contrast to the 5- or 6-membered metallacycle key intermediates usually encountered in homogeneous catalysis. These findings together with the important number of available coordination sites explain the compelling reactivity of metal nanoparticles, in between homogeneous and heterogeneous catalysis. They represent innovative tools combining the advantages of both methods for the isotopic labeling and activation of C-H bonds of complex molecules.

Isotope Effects on Hydrogen Bonding and CH/CD−π Interaction

We study the isotope effect by liquid chromatography (LC) with a variety of separation media under reversed and normal phase conditions using the protiated and/or deuterated compounds as the solutes. Results of reversed phase LC (RPLC) suggested that the protiated compounds were more hydrophobic than that of deuterated compounds due to the isotope effect based on the hydrogen bonding between hydrogen atoms of isotopologues and hydroxy groups in the mobile phase. The importance of the hydrogen bonding was also supported by the separation of isotopologues with a silica stationary phase on normal phase LC (NPLC), where the deuterated compounds showed stronger hydrogen bonding to hydroxy groups on silanol. Additionally, we investigated the difference of the strength between CH−π and CD−π interactions. Comparison of free energies of isotopologues by RPLC suggested that the CH−π interaction was slightly stronger than CD−π interaction. Finally, we demonstrated the separation of a few isotopologues on NPLC using ...

Performance of a zeolite-containing catalyst and catalysts based on noble metals in intermolecular hydrogen transfer between С6 hydrocarbons

The activities of a zeolite-containing catalyst and catalysts containing a noble metal in intermolecular hydrogen transfer between С6 hydrocarbons are compared. The zeolite-containing catalyst is ineffective in hydrogen transfer from cyclohexane to 1-hexene and in cyclohexene conversion at <400°С. Cyclohexene disproportionation at Т < 200°С takes place only over catalysts containing a noble metal. The cyclohexene conversion selectivity depends strongly on the support type. Using deuterated compounds, it has been demonstrated that intermolecular hydrogen transfer via the dehydrogenation–hydrogenation mechanism involves only the initial cyclohexene.

Using mass spectrometry to highlight structures of degradation compounds obtained by photolysis of chloroacetamides: Case of acetochlor

The photooxidation of acetochlor (a pesticide belonging to the acetamides group) using a polychromatic UV irradiation in ultrapure water was studied. This study reports the efficiency of mass spectrometry for the characterization of photodegradation products of acetochlor. Decompositions of protonated ions MH+ are proposed in electrospray (ESI) mode for LC–MS, while electron ionization (EI) and chemical ionization modes (CI) are used for GC–MS. The knowledge of fragmentation and the use of a combination of experiments (MS/MS, high resolution) allow the characterization of photoproducts. Structural elucidation is assisted by the use of photolysed deuterated compounds. Fifteen major degradation products have been characterized, five by LC-QTOF, six photoproducts by GC-ITMS, and four are observed by both techniques. In vitro bioassays based on the quantification of receptor-mediated activity demonstrated that acetochlor photolysis engenders a moderate but significant estrogenic activity. Moreover, a quantitative structure–activity relationship (QSAR) approach was used to assess the potential toxicity effect of acetochlor and its by-products. The predictions were analyzed showing a variety of toxicity profiles of acetochlor photoproducts depending on the toxicological investigated endpoint.

Evaluating the polar organic chemical integrative sampler for the monitoring of beta‐blockers and hormones in wastewater treatment plant effluents and receiving surface waters

Wastewater treatment plants (WWTP) are known to be a source of surface water contamination by organic compounds such as pharmaceuticals. The objective of the present work was to study the suitability of the polar organic chemical integrative sampler (POCIS) to monitor beta-blockers and hormones in effluents and surface waters. Four sampling campaigns were carried out in French rivers (the Saône, the Ardières, the Bourbre, and the Seine) between November 2007 and September 2008. Passive samplers were exposed in surface waters, upstream and downstream of WWTP outflows, and in effluents. Exposures lasted for up to 24 d to study the uptake kinetics directly in situ, and repeatability was assessed by exposure of triplicates. A good agreement was found between POCIS and water samples. With the exception of atenolol, beta-blockers showed a linear uptake during at least three weeks, and their sampling rates could be determined in situ. These sampling rates were then used to calculate time-weighted average concentrations of beta-blockers in the Seine River with an overall good accuracy and repeatability. Such calculations could not be performed for hormones because of their variable occurrences and low concentrations in water and POCIS. Polar organic chemical integrative sampler therefore seems to be a suitable tool for monitoring beta-blockers in surface waters impacted by WWTP effluents. Longer exposure durations would be necessary to determine the suitability of POCIS for monitoring hormones. Finally, preliminary assays on the use of several deuterated compounds as performance reference compounds showed promising results for deuterated atenolol.

Competitive Pathways in the Reaction of Lithium Oxy‐ortho‐quinodimethanes and Fischer Alkoxy Alkynyl Carbene Complexes: Synthesis of Highly Functionalised Seven‐Membered Benzocarbocycles

Up to four different outcomes have been found for the reaction between 1-oxy-ortho-quinodimethanes (oQDMs) and alkoxy alkynyl Fischer carbene complexes (FCCs). The product formed depends on the structure of both reagents and on the reaction solvent. The pathways can be topologically classified as a [4C+2C], a [3(2C+O)+3C], and two different [4C+3C] processes and, in all these sequences, 1-oxy-oQDMs behave as enolates or as vinylogous enolates. The reaction of Choy and Yang's unsubstituted oQDM 1 with tungsten alkynyl FCCs is solvent controlled; thus, selective formation of benzocycloheptenones can be achieved in THF, whereas exclusive synthesis of benzocycloheptene ketals is reached in diethyl ether. On the other hand, THF is the solvent of choice to form benzocycloheptene ketals when an alkyl or aryl group is placed at position 1 of the oQDM in its reaction with tungsten carbene complexes; however, a pyranylidene carbene complex is formed when a chromium carbene complex is used. Alternatively, the presence of bulky alkoxy groups in the FCC component favours a Diels-Alder aromatisation sequence, which leads to 1-naphthyl FCCs. Furthermore, the isolation and the characterisation of several deuterated compounds by labelling experiments have provided some insight into the reaction pathways, and mechanisms consistent with those findings have been established and several reaction intermediates have been identified.

Palythine–threonine, a major novel mycosporine-like amino acid (MAA) isolated from the hermatypic coral Pocillopora capitata

Using a high-resolution reverse-phase liquid chromatography method we found that the tissues of the hermatypic coral Pocillopora capitata (collected in Santiago Bay, Mexico) contain a high diversity of primary and secondary mycosporine-like amino acids (MAAs) typical of some reef-building coral species: mycosporine–glycine, shinorine, porphyra-334, mycosporine–methylamine–serine, mycosporine–methylamine–threonine, palythine–serine, palythine and one additional novel predominant MAA, with an absorbance maximum of 320 nm. Here we document the isolation and characterization of this novel MAA from the coral P. capitata. Using low multi-stage mass analyses of deuterated and non deuterated compounds, high-resolution mass analyses (Time of Flight, TOF) and other techniques, this novel compound was characterized as palythine–threonine. Palythine–threonine was also present in high concentrations in the corals Pocillopora eydouxi and Stylophora pistillata indicating a wider distribution of this MAA among reef-building corals. From structural considerations we suggest that palythine–threonine is formed by decarboxylation of porphyra-334 followed by demethylation of mycosporine–methylamine–threonine.

Isotope Effects in the Electrochemical Reduction of Oxalic Acid-D2 and Benzoic Acid-D

Abstract The electrochemical reduction of model carboxylic acid at lead cathodes in deuterated media was studied for potential use in the synthesis of special deuterated compounds. Oxalic acid-d2 in D2O gives good yields of glyoxylic acid-d2. An unexpected large isotope effect of 5.3 ± 1.7 was found in this reaction, leading to significant depletion of deuterium content in the aldehyde group. Benzoic acid-d in CD3OD/diluted D2SO4 yields benzyl alcohol-d, 7,7-d2. The isotope effect of 2.4 ± 1.0 is within the expected range. No deuterium is incorporated into the aromatic nucleus. Essentially unlabelled benzyl alcohol is obtained in CD3OH/dil. H2SO4.

Negative ion tandem mass spectrometry of leukotriene E 4 and LTE 4 metabolites: identification of LTE 4 in human urine

The sulfidopeptide leukotrienes, leukotriene E 4 (LTE 4) and its N-acetyl derivative and several ω- and β-oxidized metabolites of LTE 4, have been analyzed by tandem mass spectrometry. [M-H] − ions were produced by continuous flow fast atom bombardment, and collision-induced dissociation of these ions was studied by using a triple quadrupole instrument. The product ion spectra obtained were characteristic of the structure of LTE 4, and mechanisms of ion formation were investigated by using deuterated compounds. β-Elimination of the peptide portion of LTE 4 by loss of CO 2 and ethylene amine leaves the C-1 carboxyl group ionized in the most abundant fragment ion for LTE 4 and all metabolites. Tandem mass spectrometry of fast atom bombardment-generated anions from ω- and β-oxidized metabolites of LTE 4 produced similar ions with only a minor influence of the third carboxyl group at the omega terminus evident. Tandem mass spectrometry was used to identify unequivocally the presence of unmodified LTE 4 in a high performance liquid chromatography-purified fraction of urine from a normal healthy volunteer after infusion with LTE 4.

ChemInform Abstract: PHYSICOCHEMICAL PROPERTIES OF DEUTERATED COMPOUNDS. 7. THE HYDROGEN/DEUTERIUM M EXCHANGE BETWEEN HYDROGEN AND METHANE OVER NICKEL CATALYST

Chemischer InformationsdienstVolume 16, Issue 46 Preparative Organic Chemistry ChemInform Abstract: PHYSICOCHEMICAL PROPERTIES OF DEUTERATED COMPOUNDS. 7. THE HYDROGEN/DEUTERIUM M EXCHANGE BETWEEN HYDROGEN AND METHANE OVER NICKEL CATALYST M. PORETTI, M. PORETTISearch for more papers by this authorT. + GAEUMANN, T. + GAEUMANNSearch for more papers by this author M. PORETTI, M. PORETTISearch for more papers by this authorT. + GAEUMANN, T. + GAEUMANNSearch for more papers by this author First published: November 19, 1985 https://doi.org/10.1002/chin.198546094Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume16, Issue46November 19, 1985 RelatedInformation

Sensitive mass fragmentographic determination of acidic catecholamine metabolites in human body fluids

A sensitive and simple method for the simultaneous quantitation of homovanillic acid and vanilmandelic acid in small samples (0.1–1.0 ml) of urine, serum, plasma and cerebrospinal fluid is described. The stable dimethylthiophosphinyl methyl ester derivatives are detected specifically by mass fragmentography using the respective deuterated compounds as internal standards. Gas chromatographic separation is performed on a fused-silica DB-1 capillary column combined with a cold injection system for large sample volumes. Linear response curves and a detection limit of 1 ng/ml are obtained. The method has been applied to the localization of pheochromocytoma by selective determination of venous vanilmandelic acid.

Kurze Originalmitteilungen Zur Darstellung deuterierter heterocyclischer Fünfringverbindungen vom Typ Furan, Thiophen und Pyrrol durch basenkatalysierten Wasserstoffisotopenaustausch mit Deuteriumoxid

Several deuterated heterocyclic compounds of the type of furane, thiophene and pyrrole were prepared by base catalyzed proton exchange with deuteriumoxide at temperatures above 423 K in a closed system. The determination of the deuterium and its distribution within the molecules was carried out by mass spectrometry and 1h-nmr spectrometry.

Synthesis of deuterium and carbon-13 labelled lipids

Methods of preparing deuterated fatty acids by exchange and reduction, reaction with small deuterated compounds and synthesis using deuterated intermediates and biological synthesis are discussed. About 100 deuterated fatty acids are listed. Synthesis of a number of deuterated glycerides and phospholipids are also described. Preparations of twenty [ 13C]fatty acids and a few [ 13C]phospholipids are considered.