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Achieving precise deuterium labeling in pharmaceutical compounds presents a formidable challenge in medicinal chemistry. Herein, we introduce an innovative approach for circumventing the use of costly and environmentally unfriendly photocatalysts, enabling precise decarboxylative deuteration under mild conditions. Mechanistic investigation unveils the dual functionality of the tailored photoredox-active acid (PAC) with a photosensitive amino protecting group, serving both as a reactant and as a catalyst. This methodology not only represents a sustainable solution, eliminating the need for additional transition-metal catalysts, but also showcases exceptional regio- and chemoselectivity, successfully producing a versatile range of deuterated amines and alkanes, including complex peptides, terpenoids, and steroidal natural products. This breakthrough marks a significant advancement in the realm of photoinduced autocatalytic reaction methodologies. [ABSTRACT FROM AUTHOR]

Deuterated isohumulones can be prepared directly from humulones by an acyloin ring contraction under either magnesium-catalyzed basic conditions or by photochemical-induced reactions in deuterated solvents. Reactions of humulones with biphasic methylene chloride/aqueous NaOD and MgSO4 in D2 O leads to stereoselective formation of cis - d3-isohumulones (cis / trans ratio of 82:18) as the magnesium salts in yields of 71–83%. Greater than 95% incorporation of three deuterons is observed at the C5 position of the pentenone ring and the methylene position of the C4 acyl group. Photochemical isomerization with a 400 nm blue LED source enables stereospecific formation of deuterated trans -isohumulones in 36–82% yield with greater than 95% incorporation of deuterium at the C5 ring position. Oxidation of humulones with cumene hydroperoxide in basic D2 O gives isohumulinones with partial 55–73% incorporation of deuterium due to keto–enol isomerization of the methylene substituent of the C4 acyl group. The structural identities of the deuterated products are determined by a combination of negative-mode electrospray mass spectrometry (MS-ESI–) and 2D heteronuclear proton–carbon HMQC NMR analysis. [ABSTRACT FROM AUTHOR]

Readily accessible (PSi)Ni(II)‐benzyl complexes supported by bidentate phosphino(silyl) ligation were found to be effective pre‐catalysts for the direct hydrogenation of a variety of highly sterically hindered, unfunctionalized alkenes under relatively mild conditions (2.5‐5 mol% Ni, 10 atm H2, 50 °C) and without the need for additional additives or activator species. A range of substrates, including di‐, tri‐, and tetra‐substituted alkenes were evaluated in this regard and afforded good to moderate yields. Substrates featuring α,β‐unsaturated carbonyl functionality were also readily hydrogenated with no evidence for reduction of carbonyl or ester C−O functionalities. Deuteration experiments highlight the occurrence of chain walking which occurs in the background of the reported catalytic chemistry. [ABSTRACT FROM AUTHOR]

Molecular deuteration is a powerful diagnostic tool for probing the physical conditions and chemical processes in astrophysical environments. In this work, we focus on formaldehyde deuteration in the protobinary system NGC 1333 IRAS 4A, located in the Perseus molecular cloud. Using high-resolution (⁠|$\sim$| 100 au) ALMA (The Atacama Large Millimeter/submillimeter Array) observations, we investigate the [D |$_2$| CO]/[HDCO] ratio along the cavity walls of the outflows emanating from IRAS 4A1. Our analysis reveals a consistent decrease in the deuteration ratio (from |$\sim$| 60-20 per cent to |$\sim$| 10 per cent) with increasing distance from the protostar (from |$\sim$| 2000 to |$\sim$| 4000 au). Given the large measured [D |$_2$| CO]/[HDCO], both HDCO and D |$_2$| CO are likely injected by the shocks along the cavity walls into the gas-phase from the dust mantles, formed in the previous prestellar phase. We propose that the observed [D |$_2$| CO]/[HDCO] decrease is due to the density profile of the prestellar core from which NGC 1333 IRAS 4A was born. When considering the chemical processes at the base of formaldehyde deuteration, the IRAS 4A's prestellar precursor had a predominantly flat density profile within 3000 au and a decrease of density beyond this radius. [ABSTRACT FROM AUTHOR]

Deuteration has emerged as a significant method for investigating kinetic isotope effects in chemical reactions. In recent years, research on deuteration has revealed that this reaction often alters the pharmacokinetic or toxicological properties of drug molecules, thereby enhancing their therapeutic effect. Therefore, deuteration is considered as a potential avenue for drug research direction. Since the approval of the first deuterated drug, "deutetrabenazine," by the American Food and Drug Administration (FDA) in 2017, deuteration has been applied in the development of a variety of novel drugs. Research on deuteration technology has matured with the publication of numerous deuteration strategies. This article reviews recently reported strategies for late‐stage selective deuteration, discusses the challenges associated with current deuteration strategies, and presents future prospects for the synthesis of deuterated drugs. [ABSTRACT FROM AUTHOR]

Conjugated ladder polymers (cLPs) represent an intriguing class of macromolecules, characterized by their multi‐stranded structure, with continuous fused π‐conjugated rings forming the backbone. Isotope substitution, such as deuteration and carbon‐13 labeling, offers unique approaches to address the significant challenges associated with elucidating the structure and solution phase dynamics of these polymers. For instance, selective deuteration can highlight parts of the polymer by controlling the scattering length density of specific molecular sections, thereby enhancing the contrast for neutron scattering experiments. In this context, deuteration of side‐chains in cLPs represents a promising approach to uncover the elusive polymer physics properties of their backbone. The synthesis of two distinct types of cLPs with perdeuterated side‐chains are reported here. During the synthesis, 13C isotope labeling was also employed to verify the low levels of defects in the synthesized polymers. Demonstrating these synthetic successes lays the foundation for rigorous characterization of the defects, conformation, and dynamics of cLPs. [ABSTRACT FROM AUTHOR]

Methods are lacking that can prepare deuterium-enriched building blocks, in the full range of deuterium substitution patterns at the isotopic purity levels demanded by pharmaceutical use. To that end, this work explores the regio- and stereoselective deuteration of tetrahydropyridine (THP), which is an attractive target for study due to the wide prevalence of piperidines in drugs. A series of d0–d8 tetrahydropyridine isotopomers were synthesized by the stepwise treatment of a tungsten-complexed pyridinium salt with H−/D− and H+/D+. The resulting decomplexed THP isotopomers and isotopologues were analyzed via molecular rotational resonance (MRR) spectroscopy, a highly sensitive technique that distinguishes isotopomers and isotopologues by their unique moments of inertia. In order to demonstrate the medicinal relevance of this approach, eight unique deuterated isotopologues of erythro-methylphenidate were also prepared. Deuteration of active pharmaceutical ingredients is increasingly applied as the isosteric and isotopic replacement can modulate the pharmacokinetic profile, without necessarily having to alter the overall synthetic strategy toward the compound of interest. Here, the authors show manifold deuterations of piperidines and apply molecular rotational resonance (MRR) spectroscopy as a methodology to distinguish isotopomers within a distribution of products. [ABSTRACT FROM AUTHOR]

Chemical photoswitches have become a widely used approach for the remote control of biological functions with spatiotemporal precision. Several molecular scaffolds have been implemented to improve photoswitch characteristics, ranging from the nature of the photoswitch itself (e.g. azobenzenes, dithienylethenes, hemithioindigo) to fine‐tuning of aromatic units and substituents. Herein, we present deuterated azobenzene photoswitches as a general means of enhancing the performance of photopharmacological molecules. Deuteration can improve azobenzene performance in terms of light sensitivity (higher molar extinction coefficient), photoswitch efficiency (higher photoisomerization quantum yield), and photoswitch kinetics (faster macroscopic rate of photoisomerization) with minimal alteration to the underlying structure of the photopharmacological ligand. We report synthesized deuterated azobenzene‐based ligands for the optimized optical control of ion channel and G protein‐coupled receptor (GPCR) function in live cells, setting the stage for the straightforward, widespread adoption of this approach. [ABSTRACT FROM AUTHOR]

A Pd-catalyzed regioselective H/D exchange at the α-position of pyridines was achieved by employing secondary phosphine oxide as an internal base. The proposed five-membered structure enabled the reaction to overcome its conventional ortho-directing feature, allowing the efficient deuteration of pyridines and quinolines at adjacent sites of N-atoms. [ABSTRACT FROM AUTHOR]

Achieving positionally selective distal C–H functionalization remains a fundamental and longstanding challenge in the field of C–H activation. The directing template strategy has emerged as a promising solution to this problem. Herein, we disclose the development of a novel non-aromatic meta-selective directing template, which showed eminent reactivity and site-selectivity in palladium-catalyzed remote meta-C–H olefination, deuteration and acetoxylation of benzyl alcohols. [ABSTRACT FROM AUTHOR]

We report an efficient and easily available transition metal-free catalyst, barium oxide (BaO), for D/H exchange reaction between pyridine and D2. BaO enables selective deuteration at the α-position of pyridine, which is different from the reported base-mediated processes. We propose that the heterolytic dissociation of D2(H2) at the surface of BaO plays a key role in this process. [ABSTRACT FROM AUTHOR]

Herein, we report acid/base-controlled and divergent deuteration of N-unsubstituted imidazoles in an imidazole-selective manner. This protocol enabled the deuteration of not only the 4-arylimidazoles but also the 2-arylimidazoles without labelling the aromatic rings. We demonstrated the advantages of this protocol by the synthesis of deuterated pharmaceuticals, which is difficult to achieve by means of transition metals. [ABSTRACT FROM AUTHOR]

Herein, we report a facile and efficient deuteration degree controllable method for the preparation of aryl deuteromethyl ethers through dual photoredox and thiol catalysis using phenols as the starting materials and inexpensive D2O and CDCl3 as the deuterium sources. All aryl d1, d2, and d3 deuteromethyl ethers can be precisely prepared with good to excellent yields and deuteration ratios. The reaction operates under mild conditions without the need for high temperatures or high loading of transition metal catalysts, and a wide range of functional groups are well tolerated. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Deuterium labelling possesses wide applications in pharmaceuticals, chemical science and materials science. Development of efficient methodologies for the synthesis of deuterium labelled compounds, especially hydrogen isotope exchange (HIE), continued to receive an impressive attention over the years. Herein, we developed a nitrogen doped nano‐scale nickel catalyst for deuterium incorporation of a variety of nitrogen heterocycles using D2O as the isotope source. The usefulness of this approach has been demonstrated by 10 g‐scale for complex pharmaceuticals. This methodology represents a practical and scalable deuteration and the air‐ and water‐stable nanocatalyst enables efficient labelling in a straightforward manner. [ABSTRACT FROM AUTHOR]

A series of N‐alkyl‐ and N‐aryl‐viologens has been studied in alkaline solutions. In this work, we evaluated the deuteration rate of the viologens in D2O solutions of pH values ranging from 7.3 to 12.7. Kinetic experiments and computational calculations showed the high reactivity of H−C(2) bonds toward deprotonation of N‐aryl‐pyridinium moieties compared to N‐alkyl‐pyridinium moieties, even in hybrid N‐aryl/N‐alkyl dissymmetric viologens. However this high H−C(2) reactivity in liquid phase contrasted with the proton fragmentation mechanism observed in the gas phase by mass spectrometry. The H/D exchange rate of viologens in very strong alkaline conditions could be significantly reduced using cucurbit[7]uril (CB[7]) as supramolecular protecting group. Ultimately, CB[7] inclusion led to a selective protection of H−C(2) group of N‐aryl‐pyridinium of dissymmetric viologens, and induced a supramolecular regioselective deuteration. [ABSTRACT FROM AUTHOR]

A catalytic metal‐free approach for the H/D exchange in aromatic compounds using D2O as the terminal deuterating reagent has been developed. This metal‐free protocol employs a triaryl carbenium as the mediator and showcases a wide applicability in the late‐stage deuteration of various natural products and small‐molecule drugs. Gram‐scale deuteration was successfully demonstrated with β‐Estradiol, highlighting the method‘s practicability. Detailed mechanistic insights, supported by DFT calculations, unveiled the essential role of in situ generated acidic species in this electrophilic aromatic substitution process. This newly developed method offers a sustainable and versatile alternative to traditional metal‐catalyzed H/D exchange techniques, addressing challenges such as the use of expensive metals, impurity formation, and the necessity for residual metal removal from the final products. [ABSTRACT FROM AUTHOR]

Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non‐directed homogeneous Pd‐catalysis. Aromatic C−H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D2O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non‐directed homogeneous Pd‐catalysis for H/T exchange on three different pharmaceuticals by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers. [ABSTRACT FROM AUTHOR]

Constrained by a limited understanding of the structure and luminescence mechanisms of carbon dots (CDs), achieving precise enhancement of their photoluminescence (PL) performance without altering the emission wavelength and color remains a challenge. In this work, a deuterated CD is first achieved by simply replacing the reaction solvent from H2O to D2O. The substitution of D atoms for H atoms is not limited on the surface but also within the internal structure of CDs. Deuteration affects the formation of the π‐conjugated network structure by altering the content of sp2 carbon and sp3 carbon, ultimately inducing a reconstruction for energy level structure of CDs. Both the intrinsic state and surface state emission, including quantum yield, emission intensity and lifetime, are significantly enhanced after deuteration. It benefits from the reduction in non‐radiative transitions, since the lowered vibrational frequencies of D atoms and optimized local energy level distribution in CDs structure. The deuterated CDs are applied in the fabrication of white‐light‐emitting diodes to show their application potential. This work provides a highly versatile route for improving and controlling photoluminescence performance of CDs and has opportunities to guide the development of CDs for practical applications. [ABSTRACT FROM AUTHOR]

The synthesis of volicitin involved the condensation of l -(+)-glutamine with 17(S)-hydroxylinolenoic acid, derived from a Wittig reaction between the C10–C18 phosphonium salt and the C1–C9 aldehyde. The phosphonium salt was prepared through the alkynylation of a (Z)-allylic phosphate with an alkyne derived from (2 S)-but-3-yn-2-ol. The deuterated aldehyde was derived with a 96% deuteration ratio by reduction of the C1–C9 methyl ester with NaBD4 , followed by oxidation. Subsequently, 9- D1-volicitin was synthesized from the monodeuterated aldehyde by using the Wittig reaction and condensation with l -(+)-glutamine. [ABSTRACT FROM AUTHOR]

Copper-doped cadmium sulfide quantum dots (Cu-CdS QDs) were used as photocatalysts for the deuteration of halides under visible-light irradiation, with D 2 O as the deuterium source. The combined experimental and theoretical calculation results reveal that long-lived carriers are produced by rapidly capturing photoinduced holes in the Cu-doped energy levels, which is beneficial for improving photocatalytic reactivity. [Display omitted] Deuterium labeling is a highly valuable yet challenging subject of research in various scientific fields. Conventional deuteration methods often involve harsh reaction conditions and suffer from limited reactivity and selectivity. Herein, we report a visible light–driven C–X (X = halogen) to C–D (D = deuterium) exchange strategy over copper-doped cadmium sulfide quantum dots (Cu-CdS QDs) under mild conditions, eliminating the need for noble metal catalysts and expensive deuterium sources. The conversion of aryl halides into deuterated products using Cu-CdS QDs reaches up to 99%, which is four times higher than that achieved using pristine CdS QDs. The substantial enhancement in the photocatalytic activity of the QDs can be primarily attributed to the generation of long-lived charge carriers (approximately 6 μs) induced by Cu doping. Mechanistic studies reveal that the Cu dopants considerably retard the recombination of photoinduced carriers by creating intermediate energy levels that serve as hole trapping centers in CdS QDs, thereby improving the electron utilization efficiency in energetically demanding photoreduction reactions. Additionally, the introduction of Cu increases the energy offset between the conduction band of CdS QDs and molecular acceptors, facilitating the electron transfer process. Upon visible light irradiation, a series of aryl halides can be efficiently converted into the desired deuterated compounds using D 2 O as the deuterium source. This work demonstrates that regulating charge carrier dynamics in ultrasmall QD-based photocatalysts is a promising strategy for promoting organic transformations. [ABSTRACT FROM AUTHOR]

Multiple‐resonance thermally activated delayed fluorescence (MR‐TADF) emitters have garnered significant attention in recent years due to their remarkable properties, such as high luminescent quantum yield, robustness, and their compliance with the Broadcast Television 2020 standard for the new generation of ultrahigh‐definition. Despite these advancements, the operational lifetimes of organic light‐emitting diodes (OLEDs) relying on MR‐TADF emitters still fall short for practical application. It is believed that the enhancement of the intrinsic molecular stability of tBu‐DABNA, a fundamental backbone of MR‐TADF emitters, holds great promise to be a universal strategy for all MR‐TADF emitters improving the operational lifetimes of OLEDs. Herein, the design and synthesis of targeted deuteration are reported on donor and/or backbone of MR‐TADF emitters, where the structure‐property relationship between intrinsic molecular stability upon isotopic effect and device operational stability are examined. The isotopic analogs show a gradual increase in the device operational stability and achieve long‐lifetime LT80 (80% of the initial luminance of 1000 cd m−2) of 24.3 h for TADF‐sensitized fluorescence OLED, representing a sevenfold enhancement when compared with the undeuterated counterpart. This strategic deuteration approach underlines the importance of structural modification on materials toward device operational stability. [ABSTRACT FROM AUTHOR]

The development of green and efficient deuteration methods is of great significance for various fields such as organic synthesis, analytical chemistry, and medicinal chemistry. Herein, we have developed a dehalogenative deuteration strategy using piezoelectric materials as catalysts in a solid‐phase system under ball‐milling conditions. This non‐spontaneous reaction is induced by mechanical force. D2O can serve as both a deuterium source and an electron donor in the transformation, eliminating the need for additional stoichiometric exogenous reductants. A series of (hetero)aryl iodides can be transformed into deuterated products with high deuterium incorporation. This method not only effectively overcomes existing synthetic challenges but can also be used for deuterium labelling of drug molecules and derivatives. Bioactivity experiments with deuterated drug molecule suggest that the D‐ipriflavone enhances the inhibitory effects on osteoclast differentiation of BMDMs in vitro. [ABSTRACT FROM AUTHOR]

The elucidation of the ring–opening reaction mechanism is a critical step towards improving the catalytic performance for the conversion of biomass into value–added chemicals. Herein, we focused on the stepwise C−O bond hydrogenolysis mechanism of oxygen–containing heterocycles (O‐heterocycles) into α,ω‐diols, in particular THFA to 1,5‐PeD, over selective Ni−La(OH)3 in hydrogen–donor isopropanol. A mechanistic study was carried out on a structurally well–defined Ni−La(OH)3, where the mechanism was elucidated using a combination of kinetic and 13C NMR isotope labeling experiments. It was suggested that both Ni nanoparticles and La(OH)3 support play a critical role in the reaction mechanism, where basic hydroxide species of the support initially deprotonate the CH2OH and −OH modified furan, tetrahydrofuran and tetrahydropyran rings, adsorbing them chemically on the catalyst surface. This step is followed by a direct hydride attack on the second carbon atom of these rings, which is proposed to be the key step for ring cleavage, as indicated by the increased deuteration at this position. In addition to the direct hydrogenolysis using gaseous H2, it is assumed that a catalytic transfer hydrogenolysis reaction (CTH) reaction of THFA is proposed to proceed via the dehydrogenation of isopropanol over isolated Ni species, forming hydrogen species that can be adsorbed on the Ni surface or desorb as H2 molecules. [ABSTRACT FROM AUTHOR]

The importance of deuterium labelling in a variety of applications, ranging from mechanistic studies to drug‐discovery, has spurred immense interest in the development of new methods for its efficient incorporation in organic, and especially in bioactive molecules. The five‐membered heteroarenes at the center of this work are ubiquitous motifs in bioactive molecules and efficient methods for the deuterium labelling of these compounds are therefore highly desirable. However, the profound differences in chemical properties encountered between different heteroarenes hamper the development of a single set of broadly applicable reaction conditions, often necessitating a separate optimization campaign for a given type of heteroarene. In this study we describe the use of a multi‐substrate screening approach to identify optimal reaction conditions for different classes of heteroarenes from a minimal number of screening reactions. Using this approach, four sets of complementary reaction conditions derived from our dual ligand‐based palladium catalysts for nondirected C(sp2)−H activation were identified, that together enable the deuteration of structurally diverse heteroarenes, including bioactive molecules. [ABSTRACT FROM AUTHOR]

Electron-rich heteroaromatics, such as furan, thiophene and pyrrole, as well as their benzo-condensed derivatives, are of great interest as components of natural products and as starting substances for various products including high-tech materials. Although their reactions with Brønsted and Lewis acids play important roles, in particular as the primary step of various transformations, they are often disregarded and mechanistically not understood. The present publication gives a first overview about this chemistry focusing on the parent compounds. It comprises reactions with strong Brønsted acids forming adducts that can undergo intramolecular proton and/or substituent transfer reactions, ring openings or ring transformations into other heterocycles, depending on their structure. Interactions with weak Brønsted acids usually initiate oligomerizations/polymerizations. A similar behaviour is observed in reactions of these heteroaromatics with Lewis acids. Special effects are achieved when the Lewis acids are activated through primary protonation. Deuterated Brønsted acids allow straight forward deuteration of electron-rich heteroaromatics. Mercury salts as extremely weak Lewis acids cause direct metalation in a straight forward way replacing ring H-atoms yielding organomercury heterocycles. This review will provide comprehensive information about the chemistry of adducts of such heterocycles with Brønsted and Lewis acids enabling chemists to understand the mechanisms and the potential of this field and to apply the findings in future syntheses. [ABSTRACT FROM AUTHOR]

An efficiently aerobic dehydrazination of arylhydrazines promoted by potassium tert‐butoxide (tBuOK) is detailed in this study. This method smoothly produces aromatics analogues from arylhydrazines using catalytic amount of tBuOK under practical conditions, exhibiting excellent functional group tolerance and a broad substrate scope. The application potential of this approach is further demonstrated through the preparation of deuterated, iodinated and brominated aromatics. Moreover, it shows that this aerobic base‐mediated dehydrazination could be utilized to prepare unsymmetrical aryl sulfides, selenides and tellurides with high efficiency. [ABSTRACT FROM AUTHOR]

This article explores the use of chromium-promoted dearomative hydrocyanoalkylation in organic synthesis. The authors emphasize the versatility of the cyano group and the potential for using simple alkylnitriles as cost-effective sources. They also discuss the challenges and limitations of current methods. The authors present their own research on the efficient dearomative hydrocyanoalkylation of chromium-bound (hetero)arenes using simple alkylnitriles, focusing on optimizing reaction conditions. This research has the potential to expand the scope of dearomative hydrocyanoalkylation reactions and provide new synthetic building blocks. Additionally, the article discusses a new method for synthesizing complex cyclohexadiene compounds using a chromium-mediated reaction. The authors demonstrate the broad applicability of the reaction by successfully synthesizing various arenes and heteroarenes with different substituents and functional groups. They also explore the synthesis of deuterated cyclohexadienes and the transformation of the products into more structurally complex compounds. The authors highlight the potential applications of this method in the synthesis of bioactive natural products and alkaloids. [Extracted from the article]

The high Faradaic efficiency (FE) of the electrocatalytic deuteration of organics with D2O at a large current density is significant for deuterated electrosynthesis. However, the FE and current density are the two ends of a seesaw because of the severe D2 evolution side reaction at nearly industrial current densities. Herein, we report a combined scenario of a nanotip-enhanced electric field and surfactant-modified interface microenvironment to enable the electrocatalytic deuteration of arylacetonitrile in D2O with an 80% FE at −100 mA cm−2. The increased concentration with low activation energy of arylacetonitrile due to the large electric field along the tips and the accelerated arylacetonitrile transfer and suppressed D2 evolution by the surfactant-created deuterophobic microenvironment contribute to breaking the trade-off between a high FE and large current density. Furthermore, the application of our strategy in other deuteration reactions with improved Faradaic efficiencies at −100 mA cm−2 rationalizes the design concept. Achieving a high Faradaic efficiency in the electrocatalytic deuteration of organics with D2O at large current densities is challenging due to the competing D2 evolution side reaction. Here the authors report the combined nanotip-enhanced electric field and surfactant-modified interface microenvironment enabled electrocatalytic deuteration of organics in D2O with an 80% FE at −100 mA cm−2. [ABSTRACT FROM AUTHOR]

This article explores the electrochemical hydro- and deuterocarboxylation of allenes using carbon dioxide (CO2) and deuterium oxide (D2O) as starting materials. The authors discuss the challenges of activating CO2 and propose photochemical and electrochemical methods as potential solutions. They present their own findings on the electrochemical hydrocarboxylation and deuterocarboxylation of allenes, demonstrating good regioselectivity and high yields of carboxylic acids. The authors suggest possible mechanisms for these reactions and highlight their potential applications in reaction mechanism studies and drug development. The article also provides detailed experimental procedures and results, including information on the synthesis and characterization of various compounds. [Extracted from the article]

Development of the efficient and practical method for the synthesis of deuterated compounds which occupies the broadest area among stable isotopes is one of the most essential issues toward the industrial advance and building a sustainable society. This review describes recent advances in deuteration reactions, where the continuous flow chemistry plays pivotal roles for the successful installation of deuterium atom into diverse organic frameworks, opening new fields of isotope‐based synthetic chemistry. [ABSTRACT FROM AUTHOR]

Glycine silver nitrate (GSN) and fully deuterated GSN (FDGSN) form two isotopic polymorphs. The effect of full deuteration brought about the isotopic polymorph of GSN. In order to study the effect of partial deuteration on isotopic polymorphs, crystals of C-deuterated GSN (CDGSN) and N-deuterated GSN (NDGSN) were grown. The crystal structure of C deuteration was similar to FDGSN forming 2-dimensional polymeric structures extended along the c-axis. In CDGSN, the silver ion is mononuclear similar to that in FDGSN with no Ag-Ag coordination. N deuteration had similar crystal structure to that of GSN. The nitrate ion, the silver ion and the zwitterionic glycine form a three-dimensional network unlike the case in CDGSN. The silver ion is binuclear with Ag-Ag coordination similar to that in GSN. In both crystal structures, the silver ion has an oxidation state of +1. The Hirshfeld surface analysis of all the above structures was carried out using the X-ray data. The globularity parameter is similar in all the structures. For the entire complex, it is observed that FDGSN and CDGSN have similar values, which are lower than that of GSN and NDSN. The asphericity for the entire complex in the case of NDGSN and GSN is close to 0 indicating the isotropic nature whereas for FDGSN and CDGSN, it is near 0.36 indicating oblate nature. NDGSN and GSN have higher Ag···O interactions compared to that of CDGSN and FDGSN. NDGSN and GSN have Ag···Ag interaction, which is totally absent in CDGSN and FDGSN. Raman measurements showed the partial deuteration of the compounds. The lattice modes of GSN and NDGSN are similar, and FDGSN and CDGSN are similar. The C deuteration changes the coordination of the silver. In FDGSN and CDGSN, Ag ion coordinates to the hydrogen which is covalently bonded to carbon of zwitterionic glycine whereas in NDGSN and GSN, this coordination of Ag ion with hydrogen is absent. [ABSTRACT FROM AUTHOR]

The conjugation of proteins with polymers offers immense biotechnological potential by creating novel macromolecules. This article presents experimental findings on the structural properties of maltose‐binding protein (MBP) conjugated with linear biodegradable polyphosphoester polymers with different molecular weights. We studied isotopic effects on both proteins and polymers. Circular dichroism and fluorescence spectroscopy and small‐angle neutron scattering reveal that the conjugation process destabilizes the protein, affecting the secondary more than the tertiary structure, even at room temperature, and that the presence of two domains in the MBP may contribute to its observed instability. Notably, unfolding temperatures differ between native MBP and the conjugates. In particular, this study sheds light on the complex interplay of factors such as the deuteration influencing protein stability and conformational changes in the conjugation processes. The perdeuteration influences the hydrogen bond network and hydrophobic interactions in the case of the MBP protein. The perdeuteration of the protein influences the hydrogen bond network and hydrophobic interactions. This is evident in the decreased thermal stability of deuterated MBP protein, in the conjugate, especially with high‐molecular‐mass polymers. [ABSTRACT FROM AUTHOR]

Recently deuteration has become a key technology for enhancing lifetime of OLED materials without affecting other performance parameters like efficiency and voltage. Over the past years, we intensively investigated the impact of the deuteration degree and pattern on the device performance. The focus of our investigation was triplet matrix materials (TMMs) in the emissive layer and the electron‐blocking layer (EBL). In this paper, we will discuss various aspects of the deuteration of OLED materials: from driving further performance improvements to scale‐up processes. [ABSTRACT FROM AUTHOR]

Herein, we report a mild and practical method for the deuteration of alkyl and aryl bromides by a thiyl radical catalyst and halogen-atom transfer (XAT) using disulfides and silanes under visible-light irradiation. In this study, various organic bromides such as 1°, 2°, and 3°-alkyl bromides and aryl bromides were converted to deuterated products in good to excellent yields and D-incorporation. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The deuteration of organic compounds has attracted more attentions in recent years for the potential applications in new drug discovery and synthetic chemistry. For this purpose, many efficient deuterium labeling methodologies have been developed, including hydrogen isotope exchange (HIE), reductive deuteration, and dehalogenative deuteration that allow for the synthesis of selectively deuterated compounds. In the last few years, great breakthroughs in selective isotope labeling have been achieved and the interest in new methodologies for the deuteration of organic molecules is rising. In this review, we summarized the recent developments in the selective deuteration of organic molecules since 2021. Several types of key processes in deuterium incorporation reactions, including H/D exchange, reductive deuteration and dehalogenative deuteration, are introduced and discussed. Key Scientists: In the 2000s, Derdau and Atzrodt's group have made great contributions to the directing group assisted noble‐metal catalyzed hydrogen isotope exchange of arenes and applications of labeled compounds. During the same period, Sajiki and co‐workers completed a series of deuteration reactions by heterogeneous platinum‐group metal catalysts. Since 2015, Gregory Pieters and co‐workers have developed ruthenium catalysts for selective hydrogen isotope exchange. In 2016, Chirik's group achieved hydrogen isotope exchange in the presence of a homogeneous iron complex. David MacMillan and coworkers have made breakthroughs in photocatalyzed HIE reactions for α‐amino C(sp3)–H bonds. From 2020, a series of nanoelectrodes were designed for selective dehalogenative deuterations and reductive deuteration of unactivated unsaturated bonds by Zhang's group. Recently, Beller's group developed several efficient strategies for isotopic labeling using heterogeneous earth‐abundant catalysts. Our review summarized the latest and important developments since 2021. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The deuteration of organic compounds has attracted more attentions in recent years for the potential applications in new drug discovery and synthetic chemistry. For this purpose, many efficient deuterium labeling methodologies have been developed, including hydrogen isotope exchange (HIE), reductive deuteration, and dehalogenative deuteration that allow for the synthesis of selectively deuterated compounds. In the last few years, great breakthroughs in selective isotope labeling have been achieved and the interest in new methodologies for the deuteration of organic molecules is rising. In this review, we summarized the recent developments in the selective deuteration of organic molecules since 2021. Several types of key processes in deuterium incorporation reactions, including H/D exchange, reductive deuteration and dehalogenative deuteration, are introduced and discussed. Key Scientists: In the 2000s, Derdau and Atzrodt's group have made great contributions to the directing group assisted noble‐metal catalyzed hydrogen isotope exchange of arenes and applications of labeled compounds. During the same period, Sajiki and co‐workers completed a series of deuteration reactions by heterogeneous platinum‐group metal catalysts. Since 2015, Gregory Pieters and co‐workers have developed ruthenium catalysts for selective hydrogen isotope exchange. In 2016, Chirik's group achieved hydrogen isotope exchange in the presence of a homogeneous iron complex. David MacMillan and coworkers have made breakthroughs in photocatalyzed HIE reactions for α‐amino C(sp3)–H bonds. From 2020, a series of nanoelectrodes were designed for selective dehalogenative deuterations and reductive deuteration of unactivated unsaturated bonds by Zhang's group. Recently, Beller's group developed several efficient strategies for isotopic labeling using heterogeneous earth‐abundant catalysts. Our review summarized the latest and important developments since 2021. [ABSTRACT FROM AUTHOR]

The recently reported electrochemical, organo‐mediator enabled deuteration of styrenes, a reaction referred to as “electrochemical deuterium atom transfer”, differs mechanistically from reported direct electrochemical hydrogenations/deuterations only by a mediated, homogeneous SET to the substrates. By comparing direct vs. mediated processes in general and for styrene reduction, we display that Qiu's work does not change the concept of this chemistry. Experiments with mediators and the direct reduction of examples from the reported scope show that even electron‐rich substrates can be reduced when our direct protocol, published six months before Qiu's work, is applied. [ABSTRACT FROM AUTHOR]

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Abstract Constrained by a limited understanding of the structure and luminescence mechanisms of carbon dots (CDs), achieving precise enhancement of their photoluminescence (PL) performance without altering the emission wavelength and color remains a challenge. In this work, a deuterated CD is first achieved by simply replacing the reaction solvent from H2O to D2O. The substitution of D atoms for H atoms is not limited on the surface but also within the internal structure of CDs. Deuteration affects the formation of the π‐conjugated network structure by altering the content of sp2 carbon and sp3 carbon, ultimately inducing a reconstruction for energy level structure of CDs. Both the intrinsic state and surface state emission, including quantum yield, emission intensity and lifetime, are significantly enhanced after deuteration. It benefits from the reduction in non‐radiative transitions, since the lowered vibrational frequencies of D atoms and optimized local energy level distribution in CDs structure. The deuterated CDs are applied in the fabrication of white‐light‐emitting diodes to show their application potential. This work provides a highly versatile route for improving and controlling photoluminescence performance of CDs and has opportunities to guide the development of CDs for practical applications.

Abstract DGet! is an open-source analysis package written in Python for calculating the degree of deuterium enrichment in isotopically labelled molecules using mass spectrometric data. The nuclear properties of deuterium make it a valuable tracer in metabolic studies and an excellent contrast agent in nuclear spectroscopies. Determination of molecular deuteration levels is typically performed using mass spectrometry, however software options to perform these calculations are scarce. The in-house scripts and spreadsheets currently used rarely account for isotopic interferences from 13C or multi-isotopic elements that impact deuteration calculations. DGet! removes isotopic interferences using de-convolution and both the isotopological makeup and overall deuteration level can be accurately recovered. The software is available as command line and web applications that take a molecular formula and mass spectrometry data and output a graphical representation of the degree of deuteration as well as the distribution of partially deuterated analogues. These applications are designed to be easy to use and enable superior characterisation of deuterated molecules for users of all levels of expertise, without the limitations of techniques currently used by the majority of deuteration laboratories and researchers. Graphical Abstract

The combination of three types of catalysts in one pot, including borate, palladium, and lipase, enabled a one-pot β-specific methylene C(sp3)-H deuteration reaction of aliphatic acids using D2O. In the context of the widely used 8-aminoquinoline (8-AQ) directed C-H activation, this represented the first example of catalytic formation and cleavage of the directing group under mild conditions. Compared with previous deuteration methods, high chemo- and regioselectivity, high yields, and high deuterated rate were obtained without using environmentally unfriendly reagents such as strong acids, strong bases, or condensation reagents. The protocol was also amenable to the synthesis of a,a,β,β-tetradeuterated acids and various deuterated drug molecules. [ABSTRACT FROM AUTHOR]

DGet! is an open-source analysis package written in Python for calculating the degree of deuterium enrichment in isotopically labelled molecules using mass spectrometric data. The nuclear properties of deuterium make it a valuable tracer in metabolic studies and an excellent contrast agent in nuclear spectroscopies. Determination of molecular deuteration levels is typically performed using mass spectrometry, however software options to perform these calculations are scarce. The in-house scripts and spreadsheets currently used rarely account for isotopic interferences from 13C or multi-isotopic elements that impact deuteration calculations. DGet! removes isotopic interferences using de-convolution and both the isotopological makeup and overall deuteration level can be accurately recovered. The software is available as command line and web applications that take a molecular formula and mass spectrometry data and output a graphical representation of the degree of deuteration as well as the distribution of partially deuterated analogues. These applications are designed to be easy to use and enable superior characterisation of deuterated molecules for users of all levels of expertise, without the limitations of techniques currently used by the majority of deuteration laboratories and researchers. [ABSTRACT FROM AUTHOR]

We report herein the development of palladium‐catalyzed deacylative deuteration of arylketone oxime ethers. This protocol features excellent functional group tolerance, heterocyclic compatibility, and high deuterium incorporation levels. Regioselective deuteration of some biologically important drugs and natural products are showcased via Friedel–Crafts acylation and subsequent deacylative deuteration. Vicinal meta‐C−H bond functionalization (including fluorination, arylation, and alkylation) and para‐C−H bond deuteration of electro‐rich arenes are realized by using the ketone as both directing group and leaving group, which is distinct from aryl halide in conventional dehalogenative deuteration. [ABSTRACT FROM AUTHOR]

The introduction of added '3‐dimensionality' through late‐stage functionalisation of extended (hetero)aromatic systems is a powerful synthetic approach. The abundance of starting materials and cross‐coupling methodologies to access the precursors allows for highly diverse products. Subsequent selective partial reduction can alter the core structure in a manner of interest to medicinal chemists. Herein, we describe the precise, partial reduction of multicyclic heteroaromatic systems using a simple heterogeneous catalyst. The approach can be extended to introduce deuterium (again at late‐stage). Excellent yields can be obtained using simple reaction conditions. [ABSTRACT FROM AUTHOR]

Herein, we report cobalt‐catalyzed hydrogenation and deuteration reactions of bicyclic alkenes using H2O and D2O as the sole hydrogen and deuterium sources, respectively, employing Zn or Mn as a metal reductant. Lewis‐acid co‐catalysts were found to promote the reaction whilst simultaneously catalyzing transesterification processes. Use of 1 atm of H2 allows for catalytic loading of the metal reductant. In all cases, the reaction operated with high functional‐group tolerance and produced reduced products in high yield. [ABSTRACT FROM AUTHOR]

With perdeuteration, solid-state NMR spectroscopy of large proteins suffers from incomplete amide-proton back-exchange. Using a 72 kDa micro-crystalline protein, we show that deuteration exclusively via deuterated amino acids, well-established in solution to suppress sidechain protonation without proton back-exchange obstacles, provides spectral resolution comparable to perdeuterated preparations at intermediate spinning frequencies. [ABSTRACT FROM AUTHOR]

Insight into effect of deuterium isotopes on organic near‐IR (NIR) emitters was explored by the use of self‐assembled Pt(II) complexes H‐3‐f and HPh‐3‐f, and their deuterated analogues D‐3‐f and DPh‐3‐f, respectively (Scheme 2). In vacuum deposited thin film, albeit having nearly identical emission spectral feature maximized at ~810 nm, H‐3‐f and D‐3‐f exhibit remarkable difference in photoluminescence quantum yield (PLQY) of 29 % and 50 %, respectively. Distinction in PLQY is also observed for HPh‐3‐f (800 nm, 50 %) and DPh‐3‐f (798 nm, 67 %). We then elucidated the theoretical differences in the impact on near‐infrared (NIR) luminescence between Pt(II) complexes and organic small molecules upon deuteration. The results establish a general guideline for the deuteration on NIR emission efficiency. From a perspective of practical application, NIR OLEDs based on D‐3‐f and DPh‐3‐f emitters attain EQEmax of 15.5 % (radiance 31,287 mW Sr−1 m−2) and 16.6 % (radiance of 32,279 mW Sr−1 m−2) at 764 nm and 796 nm, respectively, both of which set new records for NIR OLEDs of >750 nm. [ABSTRACT FROM AUTHOR]

The D/H ratio in astrophysical environments has instigated the scientists for at least 50 years. The wide range of values in the interstellar medium (ISM) from 10e to 7 to 10e-1 have usually been claimed to be due to small zero-point energy differences between reactants and products involving D and H (mainly at low temperatures). Here, we present a new source of deuteration processes in the ISM clouds as a result of cosmic ray irradiation. As a study object, we consider a typical molecular clump under the presence of incoming cosmic rays simulated computationally. The calculations were performed employing the Monte Carlo toolkit GEANT4 code (considering hadronic physics) and considering mainly the proton and alpha component of the incoming cosmic rays from the ISM (the dominant ones for the production of secondary protons and deuterons). The results suggest an increasing D/H ratio as function of time in the central part of molecular clumps (<200 AU) with the largest deuteration in the central region of the cloud, and a bump in the D/H ratio around 2–10 AU (which becomes more pronounced for clouds with larger timescales; > 10 Myrs). The results also show that for timescales between 10 and 100 Myrs the central part of the cloud has D/H around 6-16e-3, a value compatible with the observed D/H in some interstellar clouds. This work adds a new piece to the D/H puzzle of the ISM and might also help to explain the D/H ratio measured in different objects inside the Solar system. [ABSTRACT FROM AUTHOR]

The limited exciton lifetime (τ, generally <1 ns) leads to short exciton diffusion length (LD) of organic semiconductors, which is the bottleneck issue impeding the further improvement of power conversion efficiencies (PCEs) for organic solar cells (OSCs). However, efficient strategies to prolong intrinsic τ are rare and vague. Herein, we propose a facile method to efficiently reduce vibrational frequency of molecular skeleton and suppress exciton‐vibration coupling to decrease non‐radiative decay rate and thus prolong τ via deuterating nonfullerene acceptors. The τ remarkably increases from 0.90 ns (non‐deuterated L8‐BO) to 1.35 ns (deuterated L8‐BO‐D), which is the record for organic photovoltaic materials. Besides, the inhibited molecular vibration improves molecular planarity of L8‐BO‐D for enhanced exciton diffusion coefficient. Consequently, the LD increases from 7.9 nm (L8‐BO) to 10.7 nm (L8‐BO‐D). The prolonged LD of L8‐BO‐D enables PM6 : L8‐BO‐D‐based bulk heterojunction OSCs to acquire higher PCEs of 18.5 % with more efficient exciton dissociation and weaker charge carrier recombination than PM6 : L8‐BO‐based counterparts. Moreover, benefiting from the prolonged LD, D18/L8‐BO‐D‐based pseudo‐planar heterojunction OSCs achieve an impressive PCE of 19.3 %, which is among the highest values. This work provides an efficient strategy to increase the τ and thus LD of organic semiconductors, boosting PCEs of OSCs. [ABSTRACT FROM AUTHOR]

In this work, we study deuterium fractionation in four starless cores in the low-mass star-forming region L1688 in the Ophiuchus molecular cloud. We study how the deuterium fraction (RD) changes with environment, compare deuteration of ions and neutrals, core centre and its envelope, and attempt to reproduce the observed results with a gas–grain chemical model. We chose high and low gas density tracers to study both core centre and the envelope. With the IRAM 30 m antenna, we mapped N2H+(1–0), N2D+(1–0), H13CO+ (1–0) and (2–1), DCO+(2–1), and p -NH2D(111–101) towards the chosen cores. The missing p -NH3 and N2H+(1–0) data were taken from the literature. To measure the molecular hydrogen column density, dust and gas temperature within the cores, we used the Herschel/SPIRE dust continuum emission data, the Green Bank Ammonia Survey data (NH3), and the COMPLETE survey data to estimate the upper limit on CO depletion. We present the deuterium fraction maps for three species towards four starless cores. Deuterium fraction of the core envelopes traced by DCO+/H13CO+ is one order of magnitude lower (∼0.08) than that of the core central parts traced by the nitrogen-bearing species (∼0.5). Deuterium fraction increases with the gas density as indicated by high deuterium fraction of high gas density tracers and low deuterium fraction of lower gas density tracers and by the decrease of RD with core radii, consistent with the predictions of the chemical model. Our model results show a good agreement with observations for RD (N2D+/N2H+) and R D (DCO+/HCO+) and underestimate the RD (NH2D/NH3). [ABSTRACT FROM AUTHOR]