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A novel photoredox‐neutral 1,2,5‐trifunctionalization of α‐hydroxyhexenoates is disclosed. The radical cascade proceeds via heteroaryl migration‐enabled alkene fluoroalkylheteroarylation and radical‐polar crossover deuteration, leading to functionalized α‐deuterated lactic acid derivatives. The reaction features mild photochemical conditions and provides an efficient approach for the synthesis of valuable deuterated molecules. [ABSTRACT FROM AUTHOR]

The analog of the diterpene precursor geranylgeranyl diphosphate with a double bond shifted from C14=C15 to C15=C16 (named iso‐GGPP III) has been synthesized and enzymatically converted with six bacterial diterpene synthases; this allowed the isolation of nine unnatural diterpenes. For some of the enzyme‐substrate combinations, the different reactivity implemented in the substrate analog iso‐GGPP III opened reaction pathways that are not observed with natural GGPP, resulting in the formation of diterpenes with novel skeletons. A stereoselective deuteration strategy was used to assign the absolute configurations of the isolated diterpenes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This research investigates the impact of deuteration on the operational lifetime of blue organic light‐emitting diodes (OLEDs). Our study focuses on the kinetic isotope effect (KIE) and how it enhances device lifetime. Specifically, we examine the effects of deuteration on OLEDs with emitters based on common polycyclic aromatic hydrocarbons by deuterating anthracene‐based host materials. Our findings show that the deuterated analogues with incremental deuterium substitutions exhibit similar electroluminescence (EL) performances but progressively prolonged device lifetimes as a function of deuteration, indicating a cumulative enhancement effect. We observed a twofold increase in device lifetime with partial deuterium substitutions, while highly deuterated hosts realized up to a fourfold improvement. Furthermore, we found that device degradation is initiated from the interface of the hole transport layer (HTL) and emitting layer (ETL), and deuteration can mitigate the degraded reactions in the devices, thereby improving operational stability. These results provide insight into how deuteration can increase the operational lifetime of OLEDs, which has important implications for developing more efficient and durable OLED materials. [ABSTRACT FROM AUTHOR]

Amide I spectroscopy probes the backbone C=O stretch vibrations of peptides and proteins. Amide I spectra are often collected in deuterated water (D2O) since this provides a cleaner background in the amide I frequency range; such data are often referred to as amide I′ spectra since deuteration induces changes in the mode structure, including a roughly ∼10 cm−1 redshift. For biological samples, however, deuteration is often not possible. As amide I frequency maps are increasingly applied to quantitative protein structural analysis, this raises the interesting challenge of drawing direct connections between amide I and amide I′ data. We here analyze amide I and amide I′ peak frequencies for a series of dipeptides and related compounds. Changes in protonation state induce large electrostatic shifts in the peak frequencies, allowing us to amass a sizable library of data points for direct amide I/amide I′ comparison. While we find an excellent linear correlation between amide I and amide I′ peak frequencies, the deuteration-induced shift is smaller for more red-shifted vibrations, indicating different electrostatic tuning rates in the two solvents. H2O/D2O shifts were negligible for proline-containing dipeptides that lack exchangeable amide hydrogens, indicating that the intrinsic properties of the solvent do not strongly influence the H/D shift. These findings indicate that the distinct tuning rates observed for the two vibrations arise from modifications to the intrinsic properties of the amide bond and provide (at least for solvated dipeptides) a simple, linear "map" for translating between amide I and amide I′ frequencies. [ABSTRACT FROM AUTHOR]

The design of bright short-wave infrared fluorophores remains a grand challenge. Here we investigate the impact of deuteration on the properties in a series of heptamethine dyes, the absorption of which spans near-infrared and SWIR regions. We demonstrate that it is a generally applicable strategy that leads to enhanced quantum yields of fluorescence, longer-lived singlet excited states and suppressed rates of non-radiative deactivation processes. [ABSTRACT FROM AUTHOR]

Amide-proton detected magic-angle spinning NMR of deuterated proteins has become a main technique in NMR-based structural biology. In standard deuteration protocols that rely on D2O-based culture media, non-exchangeable amide sites remain deuterated, making these sites unobservable. Here we demonstrate that proteins produced with H2O-based culture medium doped with deuterated cell lysate allow to overcome this 'reprotonation bottleneck', while retaining a high level of deuteration (ca. 80 %) and narrow line widths. We quantified coherence life times of several proteins prepared with this labelling pattern over a range of MAS frequencies (40–100 kHz). We demonstrate that under commonly used conditions (50–60 kHz MAS), amide 1H line widths with our labelling approach are comparable to those of perdeuterated proteins and better than those of protonated samples at 100 kHz. For three proteins in the 33–50 kDa size range many previously unobserved amides become visible. We report how to prepare the deuterated cell lysate for our approach from fractions of perdeuterated cultures which are usually discarded, and show that such media can be used identically to commercial media. The residual protonation of Hα sites allows for well-resolved Hα-detected spectra and Hα resonance assignment, exemplified by the de novo assignment of 168 Hα sites in a 39 kDa protein. The approach based on this H2O/cell-lysate deuteration and MAS frequencies compatible with 1.3 or 1.9 mm rotors presents a strong sensitivity benefit over 0.7 mm/100 kHz MAS experiments. [ABSTRACT FROM AUTHOR]

We report a straightforward H/D exchange method for the synthesis of α-deuterated primary amines from a diverse set of primary amines with high levels of deuteration and chemo- and site selectivity and preparative utility. This cost-effective strategy enables the direct conversion of primary amines to α-deuterated counterparts using D2O as the deuterium source under mild reaction conditions without requiring additional functionality manipulation and with minimal byproduct production. [ABSTRACT FROM AUTHOR]

Amide-proton-detected magic-angle-spinning NMR of deuterated proteins has become a main technique in NMR-based structural biology. In standard deuteration protocols that rely on D 2 O-based culture media, non-exchangeable amide sites remain deuterated, making these sites unobservable. Here we demonstrate that proteins produced with a H 2 O-based culture medium doped with deuterated cell lysate allow scientists to overcome this "reprotonation bottleneck" while retaining a high level of deuteration (ca. 80 %) and narrow linewidths. We quantified coherence lifetimes of several proteins prepared with this labeling pattern over a range of magic-angle-spinning (MAS) frequencies (40–100 kHz). We demonstrate that under commonly used conditions (50–60 kHz MAS), the amide 1 H linewidths with our labeling approach are comparable to those of perdeuterated proteins and better than those of protonated samples at 100 kHz. For three proteins in the 33–50 kDa size range, many previously unobserved amides become visible. We report how to prepare the deuterated cell lysate for our approach from fractions of perdeuterated cultures which are usually discarded, and we show that such media can be used identically to commercial media. The residual protonation of H α sites allows for well-resolved H α -detected spectra and H α resonance assignment, exemplified by the de novo assignment of 168 H α sites in a 39 kDa protein. The approach based on this H 2 O/cell-lysate deuteration and MAS frequencies compatible with 1.3 or 1.9 mm rotors presents a strong sensitivity benefit over 0.7 mm 100 kHz MAS experiments. [ABSTRACT FROM AUTHOR]

α‐Aminophosphonic acids have a remarkably broad bioactivity spectrum. They can function as highly efficient transition state mimics for a variety of hydrolytic and angiotensin‐converting enzymes, which makes them interesting target structures for synthetic chemists. In particular, the phosphonic acid analogs to α‐aminocarboxylic acids (PaAAs) are potent enzyme inhibitors, but many of them are only available by chiral or enzymatic resolution; sometimes only one enantiomer is accessible, and several have never been prepared in enantiopure form at all. Today, a variety of methods to access enantiopure α‐aminophosphonic acids is known but none of the reported approaches can be generally applied for the synthesis of PaAAs. Here we show that the phosphonic acid analogs of many (proteinogenic) α‐amino acids become accessible by the catalytic, stereoselective asymmetric transfer hydrogenation (ATH) of α‐oxo‐phosphonates. The highly enantioenriched (enantiomeric excess (ee) ≥ 98 %) α‐hydroxyphosphonates obtained are important pharmaceutical building blocks in themselves and could be easily converted to α‐aminophosphonic acids in most studied cases. Even stereoselectively deuterated analogs became easily accessible from the same α‐oxo‐phosphonates using deuterated formic acid (DCO2H). [ABSTRACT FROM AUTHOR]

In this work, we developed a phosphine‐catalyzed C‐methoxylation process of para‐quinone methides (p‐QMs). By employing a metal‐free phosphine catalyst [P(4‐MeC6H4)3] together with methanol and deuterated methanol (d4, d1, and d3) as C1 sources, a series of methoxylated diarylmethanes and the corresponding deuterated products were obtained without additional solvent under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Precise deuterium incorporation of bioactive molecules is highly desirable in order to improve ADME properties and monitor pharmacokinetics. Organic electrochemistry offers a powerful tool for molecular editing using electrons as traceless reagents. We herein present an electrochemical deuteration that can specifically modify the α-position of amides via an H/D exchange reaction under mild neutral conditions. This protocol provides an efficient tool for the rapid synthesis of α-deuterated amides in moderate to high yields with excellent levels of deuteration. In addition, the late-stage modification of drug molecules has been well demonstrated. Furthermore, the reduction of amides provides an efficient route to β-bisdeuterated amines, which are difficult to access by the existing methods. We envision that this on-demand deuterium incorporation will provide unique opportunities in biological research and therapeutics. [ABSTRACT FROM AUTHOR]

In chloroform solution, the reaction of bis(tert-butylamino)dimethylsilane ((tBuNH)2SiMe2) and an α-amino acid (α-amino isobutyric acid, H2Aib; D-phenylglycine, H2Phg; L-valine, H2Val) in the presence of N-methylimidazole (NMI) gave rise to the formation of the pentacoordinate silicon complexes (Aib)SiMe2-NMI, (Phg)SiMe2-NMI and (Val)SiMe2-NMI, respectively. Therein, the amino acid building block was a di-anionic bidentate chelator at the silicon atom. In solution, the complexes were involved in rapid coordination–dissociation equilibria between the pentacoordinate Si complex (e.g., (Aib)SiMe2-NMI) and its constituents NMI and a five-membered silaheterocycle (e.g., (Aib)SiMe2), as shown by 29Si NMR spectroscopy. The energetics of the Lewis acid-base adduct formation and the competing solvation of the NMI molecule by chloroform were assessed with the aid of computational methods. In CDCl3 solution, deuteration of the silaheterocycle NH group proceeded rapidly, with more than 50% conversion within two days. Upon cooling to −44 °C, the chloroform solvates of the adducts (Aib)SiMe2-NMI and (Phg)SiMe2-NMI crystallized from their parent solutions and allowed for their single-crystal X-ray diffraction analyses. In both cases, the Si atom was situated in a distorted trigonal bipyramidal coordination sphere with equatorial Si–C bonds and an equatorial Si–N bond (the one of the silaheterocycle). The axial positions were occupied by a carboxylate O atom of the silaheterocycle and the NMI ligand's donor-N-atom. [ABSTRACT FROM AUTHOR]

We developed an electrocatalytic reduction of (hetero)aryl halides under mild conditions using a proton exchange membrane (PEM) reactor. This approach allows substituting the halogeno groups on the aryl rings to protons by water and electron. Taking advantage of this transformation, deuterodehalogenation of (hetero)aryl halides, which forms mono‐deuterated (hetero)aryls, was demonstrated using heavy water as a deuterium source. The current efficiency and deuterium ratio could be increased by the conditions optimized by machine‐learning method, Bayesian optimization. [ABSTRACT FROM AUTHOR]

Mining of a terpene synthase from Streptomyces subrutilus resulted in the identification of the hexacyclic sesterterpene subrutilane, besides eight pentacyclic side products. Subrutilane represents the first case of a saturated sesterterpene hydrocarbon. Its structure, including the absolute configuration, was unambiguously determined through X‐ray crystallographic analysis and stereoselective deuteration. The cyclisation mechanism to subrutilane and its side products was investigated in all detail by isotopic labelling experiments and DFT calculations. The subrutilane synthase (SrS) also converted (2Z)‐GFPP into one major product. Additional compounds were obtained from the substrate analogues (7R)‐6,7‐dihydro‐GFPP and (2Z,7R)‐6,7‐dihydro‐GFPP with blocked reactivity at the C6−C7 bond. Interestingly, the early steps of the cyclisation cascade with (2Z)‐GFPP and the saturated substrate analogues were analogous to those of GFPP, but then deviations from the natural cyclisation mode occur. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of pharmaceutical drugs can be improved by replacing C−H bonds with the more stable C−D bonds at the α‐position to heteroatoms, which is a typical metabolic site for cytochrome P450 enzymes. However, the application of deuterated synthons is limited. Herein, we established a novel concept for preparing deuterated reagents for the successful synthesis of complex drug skeletons with deuterium atoms at the α‐position to heteroatoms. (dn‐Alkyl)diphenylsulfonium salts prepared from the corresponding nondeuterated forms using inexpensive and abundant D2O as the deuterium source with a base, were used as electrophilic alkylating reagents. Additionally, these deuterated sulfonium salts were efficiently transformed into dn‐alkyl halides and a dn‐alkyl azide as coupling reagents and a dn‐alkyl amine as a nucleophile. Furthermore, liver microsomal metabolism studies revealed deuterium kinetic isotope effects (KIE) in 7‐(d2‐ethoxy)flavone. The present concept for the synthesis of deuterated reagents and the first demonstration of a KIE in a d2‐ethoxy group will contribute to drug discovery research based on deuterium chemistry. [ABSTRACT FROM AUTHOR]

Deuterium labelling of organic compounds is an important process in chemistry. We report the first example of photocatalytic dehalogenative deuteration of both arylhalides and alkylhalides (40 substrates) over a metal–organic framework, MFM‐300(Cr), using CD3CN as the deuterium source at room temperature. MFM‐300(Cr) catalyses high deuterium incorporation and shows excellent tolerance to various functional groups. Synchrotron X‐ray powder diffraction reveals the activation of halogenated substrates via confined binding within MFM‐300(Cr). In situ electron paramagnetic resonance spectroscopy confirms the formation of carbon‐based radicals as intermediates and reveals the reaction pathway. This protocol removes the use of precious‐metal catalysts from state‐of‐the‐art processes based upon direct hydrogen isotope exchange and shows high photocatalytic stability, thus enabling multiple catalytic cycles. [ABSTRACT FROM AUTHOR]

Bulky tri‐isopropyl silyl (TIPS) substituents and deuterium atoms in the ligand design have been shown to enhance the site‐selective oxidation of aliphatic C−H bonds and the epoxidation of C=C bonds in non‐heme iron oxidation catalysis. In this work, a series of non‐heme iron complexes were developed by combining TIPS groups and deuterium atoms in the ligand. These bulky deuterated complexes show a significant increase in catalytic performance compared to their counterparts containing only TIPS groups or deuterium atoms. A broad range of substrates was oxidized with excellent yields, particularly, using [Fe(OTf)2((S,S)‐TIPSBPBP‐D4)] (1‐TIPS‐D4) (0.1 mol % to 1 mol %) via a fast or slow oxidant addition protocol, resulting in an overall improvement in catalytic performance. Notably, in the oxidation of the complex substrate trans‐androsterone acetate, the use of a slow addition protocol and a lower catalyst loading of 1‐TIPS‐D4 resulted in significant increases in reaction efficiency. In addition, kinetic and catalytic studies showed that deuteration does not affect the catalytic activity and the secondary C−H site‐selectivity but increases the catalysts' lifetime resulting in higher conversion/yield. Accordingly, the yield of selectively oxidized secondary C−H products also increases with the overall yield by using the bulky deuterated iron complexes as catalysts. These catalytic improvements of the bulky deuterated complexes exemplify the enhanced design of ligands for homogeneous oxidation catalysis. [ABSTRACT FROM AUTHOR]

Despite widespread use of the deuterium isotope effect, selective deuterium labeling of chemical molecules remains a major challenge. Herein, a facile and general electrochemically driven, organic mediator enabled deuteration of styrenes with deuterium oxide (D2O) as the economical deuterium source was reported. Importantly, this transformation could be suitable for various electron rich styrenes mediated by triphenylphosphine (TPP). The reaction proceeded under mild conditions without transition‐metal catalysts, affording the desired products in good yields with excellent D‐incorporation (D‐inc, up to >99 %). Mechanistic investigations by means of isotope labeling experiments and cyclic voltammetry tests provided sufficient support for this transformation. Notably, this method proved to be a powerful tool for late‐stage deuteration of biorelevant compounds. [ABSTRACT FROM AUTHOR]

Utilized for gaining structural insights, small-angle neutron and X-ray scattering techniques (SANS and SAXS, respectively) enable an examination of biomolecules, including photosynthetic pigment-protein complexes, in solution at physiological temperatures. These methods can be seen as instrumental bridges between the high-resolution structural information achieved by crystallography or cryo-electron microscopy and functional explorations conducted in a solution state. The review starts with a comprehensive overview about the fundamental principles and applications of SANS and SAXS, with a particular focus on the recent advancements permitting to enhance the efficiency of these techniques in photosynthesis research. Among the recent developments discussed are: (i) the advent of novel modeling tools whereby a direct connection between SANS and SAXS data and high-resolution structures is created; (ii) the employment of selective deuteration, which is utilized to enhance spatial selectivity and contrast matching; (iii) the potential symbioses with molecular dynamics simulations; and (iv) the amalgamations with functional studies that are conducted to unearth structure-function relationships. Finally, reference is made to time-resolved SANS/SAXS experiments, which enable the monitoring of large-scale structural transformations of proteins in a real-time framework. [ABSTRACT FROM AUTHOR]

The deuteration of energetic materials contributes to high signal-to-noise ratios (SNRs) in neutron diffraction, thus allowing the structures of energetic materials to be effectively investigated. This study developed the synthesis methods of deuterated energetic materials through chemical synthesis or newly developed one-pot H/D exchange. Using these methods, it synthesized nine deuterated energetic materials in a concise and low-cost manner: deuterated 1,3,5-triamino-2,4,6-trinitrobenzene (TATB-d6, 1), 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX-d8, 2), 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX-d6, 3), dihydroxylammonium 5,5′-bis(tetrazole-1-oate) (TKX-50-d8, 4), nitroguanidine (NQ-d4, 5), 1,1-diamino-2,2-dinitroethylene (FOX-7-d4, 6), 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105-d4, 7), trinitrotoluene (TNT-d3, 8), and 3-nitro-1,2,4-triazol-5-one (NTO-d2, 9). Furthermore, the single crystals of HMX-d8 (2) and RDX-d6 (3) were obtained, and the α-, β-, γ-, and δ-polymorphs of HMX-d8 (2) were prepared accordingly. The deuterated energetic materials were characterized and analyzed using infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetry (TG), X-ray diffraction (XRD), and neutron diffraction. Besides, this study determined the decomposition activation energy (Ea), pre-exponential factor (A), decomposition rate constant (k), and critical explosion temperature (Tb) of TATB-d6 (1), HMX-d8 (2), and RDX-d6 (3) via DSC experiments at different heating rates. The NMR and neutron diffraction data show that these deuterated energetic materials have high deuteration rates of more than 95%. The DSC and TG analyses indicate that the deuterated energetic materials exhibit slightly higher decomposition temperatures than their nondeuterated counterparts. Furthermore, neutron diffraction shows that the deuterated energetic materials feature high SNRs.

Deuterium labelling techniques have shown widespread applications in organic synthesis, analytic chemistry, life science and material science. The design of practical deuteration reactions which is environmentally friendly is highly desired for pharmaceutical development and industrial processes while remaining underexplored. We herein report a convenient, transition metal-free strategy for reductive deuteration of ketone derivatives to α-deuterated alcohols by employing a conjugated aryl amine-based organophotocatalyst, a dipropyl disulfide co-catalyst and an inorganic reductant. Upon irradiation with visible light and under an air atmosphere, a variety of diaryl ketones, heteroaryl ketones, cyclic ketones, α-ketoesters, benzil derivatives, aliphatic ketones and drug-like molecules were converted into corresponding α-deuterated aryl alcohols in good to excellent yields and with high deuterium incorporation (up to 99% D-incorporation). Only low toxic side-products, such as sodium salts and carbon dioxide, were generated. Consequently, the synthetic utility of this method is highlighted by the preparation of several D-labeled drug-like molecules, including orphenadrine, carbinoxamine and modafinil.

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.

Mn-catalysed C–H activation has emerged as a useful sustainable methodology for the formation of new C–C bonds. To date most of the protocols are described in organic solvents. Water as solvent, on the other hand, would be highly advantageous, but is often incompatible with organometallic chemistry. Herein, we describe the C–H activation of indoles using an unmodified, commercially available manganese catalyst in water. Two types of valuable allyl groups can be added and a good substrate scope is described. Substitution at the C-3 group is tolerated, allowing access to medicinally important frameworks, and the reaction works on a gram scale. Finally, harnessing the tolerance of water as the reaction medium, D2O can be used as an inexpensive source of deuterium for the C-2 labelling of indoles.

Abstract We developed an electrocatalytic reduction of (hetero)aryl halides under mild conditions using a proton exchange membrane (PEM) reactor. This approach allows substituting the halogeno groups on the aryl rings to protons by water and electron. Taking advantage of this transformation, deuterodehalogenation of (hetero)aryl halides, which forms mono‐deuterated (hetero)aryls, was demonstrated using heavy water as a deuterium source. The current efficiency and deuterium ratio could be increased by the conditions optimized by machine‐learning method, Bayesian optimization.

Although very effective in decreasing NMR relaxation of large proteins, homogeneous deuteration can be costly, and anyway unsuitable for recombinant production in metazoan systems. We sought to explore other deuteration schemes, which would be adapted to protein expression in mammalian cells. Here, we evaluate the benefits of the deuteration on alpha- and beta-positions of amino acids for a typical middle size protein domain, namely the model 40 kDa-large kinase p38α. We report the position-specific deuteration of free amino acids by using enzyme-assisted H/D exchange, executed by the cystathionine gamma-synthase and a newly designed high-performance mutant E325A. Then, we used cell-free expression in bacterial extracts to avoid any scrambling and back-protonation of the tested isotopically labelled amino acids (Ala, Leu, Lys, Ser, Asp, Glu, Gly). Our results show signal enhancements up to three in 1H-15N spectra when these α/β-deuterated amino acids are integrated. Because our approach relies on single 2Hα/β-15N-amino acid labeling, an additional three-fold increase in sensitivity is obtained by the possible use of moderate resolution SOFAST-HMQC instead of the classical HSQC or TROSY experiments. This allows recording residue-resolved solution 1H-15N NMR spectra of 100 μg of p38α in one hour with S/N∼10.

Synthetic model triacylglyceride oils are important compounds for applications in pharmaceutical and food chemistry. Herein, a practical and highly efficient methodology for the synthesis of saturated and unsaturated triacylglycerides utilizing saturated and unsaturated fatty acids activated by 1,1'‐carbonyldiimidazole (CDI) has been developed and applied in the synthesis of deuterated medium chain triglyceride (MCT) oil for studies of plant‐based and diary food emulsions. The deuterium labelled compounds were used to gain new insight into the mechanism of the reaction, which was confirmed by density‐functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

All aromatic C–H bonds of triphenylphosphine (PPh3) were efficiently replaced by C–D bonds using Ru/C and Ir/C co-catalysts in 2-PrOH and D2O, an inexpensive deuterium source. Furthermore, non-radioactive and safe deuterium-incorporated Mito-Q (drug candidate) was prepared from deuterated PPh3 and used for the live-cell Raman imaging to evaluate the mitochondrial uptake. [ABSTRACT FROM AUTHOR]

Site‐specifically deuterated organocatalysts were prepared and found to show improved reactivity over the non‐deuterated analogs. Two privileged C2‐symmetric chiral binaphthyl‐modified tetraalkylammonium salts were selected for this study. The stability of these phase‐transfer catalysts was generally improved by site‐specific deuteration, though the degree of improvement was structure dependent. In particular, a large secondary kinetic isotope effect was observed for the tetradeuterated phase‐transfer catalyst. The performance of these deuterated catalysts in the asymmetric catalytic alkylation of amino acid derivatives was better than that of non‐deuterated analogs at low catalyst loadings. The results suggest that catalyst deuteration is a promising strategy for enhancing the stability and performance of organocatalysts. [ABSTRACT FROM AUTHOR]

Hydrogenation reactions are staple transformations commonly used across scientific fields to synthesise pharmaceuticals, natural products, and various functional materials. However, the vast majority of these reactions require the use of a toxic and costly catalyst leading to unpractical, hazardous and often functionally limited conditions. Herein, we report a new, general, practical, efficient, mild and high‐yielding hydrogen‐free electrochemical method for the reduction of alkene, alkyne, nitro and azido groups. Finally, this method has been applied to deuterium labelling. [ABSTRACT FROM AUTHOR]

We have developed an electrochemical reaction for the synthesis of 3‐selenylchromones and deutero‐selenylated chalcones of alkynyl aryl ketones. This method is free from metal catalysts and oxidants, and is regulated by solvents. The reaction conditions are mild, and a wide range of substrates can be employed to produce selenylated chromones and deutero‐selenylated chalcones, displaying potential anti‐inflammatory activities. Furthermore, we have demonstrated the applicability of this approach for the late‐stage deutero‐selenylation of the drug molecule, metochalcone. [ABSTRACT FROM AUTHOR]

Phthalimidine finds wide pharmaceutical applications and its deuterated derivative is supposed to exhibit enhanced stability towards metabolism. In this work, an electrochemically reductive deuteration strategy from phthalimide to phthalimidine‐d2 was achieved with D2O as a deuterium source at the reagent level in common solvents. This approach showed broad compatibility with a variety of functional groups. Mechanistic investigations assisted by electrochemical analysis revealed a 4‐electron reduction pathway, and the coupled anodic oxygen evolution collectively maintains a neutral to mild basic conditions for the ongoing electrochemical reaction. [ABSTRACT FROM AUTHOR]

[Display omitted] • A Ru-catalysed universal transfer hydrogenation, deuteration, and methylation of diverse functional compounds using MeOH. • General and convenient TH/TD strategy to large-scale synthesize of deuterated pharmaceuticals. • Kinetic and mechanistic investigations of Ru-catalyzed TH/TD protocols. Catalytic valorization of methanol in organic synthesis and energy technologies is interesting and important for both fundamental research and industrial applications. In particular, its utilization as hydrogen, deuterium and methyl sources for selective reduction and deuteration reactions as well as to access N -methylated products is highly desirable and can be considered as a potential methodology for the amplification of transfer hydrogenation and C1 chemistry. Here, we report homogeneous Ru-MACHO complex catalyzed transfer hydrogenation of different functionalized compounds such as ketones, aldehydes, alkynes, alkenes, imines, azobenzenes, and nitro compounds as well as deoxygenation of N -oxide derivatives employing methanol as an affordable hydrogen donor and solvent. This Ru-based strategy has been proven to be very convenient for the deuteration process to synthesize advanced deuterium-labelled compounds, including the gram-scale synthesis of deuterated pharmaceuticals such as d -Cloperastine, d -Buclizine, d -Diphendyarmine, d -Modafinil, and d -Adrafinil using CD 3 OD. In addition, the application of methanol as a C1 source for the preparation of N -methylated products is showcased. Finally, kinetic and mechanistic investigations for this Ru-catalyzed transfer hydrogenation and deuteration protocols have been performed. [ABSTRACT FROM AUTHOR]

Cellular membranes are complex systems that consist of hundreds of different lipid species. Their investigation often relies on simple bilayer models including few synthetic lipid species. Glycerophospholipids (GPLs) extracted from cells are a valuable resource to produce advanced models of biological membranes. Here, we present the optimisation of a method previously reported by our team for the extraction and purification of various GPL mixtures from Pichia pastoris. The implementation of an additional purification step by High Performance Liquid Chromatography-Evaporative Light Scattering Detector (HPLC-ELSD) enabled for a better separation of the GPL mixtures from the neutral lipid fraction that includes sterols, and also allowed for the GPLs to be purified according to their different polar headgroups. Pure GPL mixtures at significantly high yields were produced through this approach. For this study, we utilised phoshatidylcholine (PC), phosphatidylserine (PS) and phosphatidylglycerol (PG) mixtures. These exhibit a single composition of the polar head, i.e. , PC, PS or PG, but contain several molecular species consisting of acyl chains of varying length and unsaturation, which were determined by Gas Chromatography (GC). The lipid mixtures were produced both in their hydrogenous (H) and deuterated (D) versions and were used to form lipid bilayers both on solid substrates and as vesicles in solution. The supported lipid bilayers were characterised by quartz crystal microbalance with dissipation monitoring (QCM-D) and neutron reflectometry (NR), whereas the vesicles by small angle X-ray (SAXS) and neutron scattering (SANS). Our results show that despite differences in the acyl chain composition, the hydrogenous and deuterated extracts produced bilayers with very comparable structures, which makes them valuable to design experiments involving selective deuteration with techniques such as NMR, neutron scattering or infrared spectroscopy. [ABSTRACT FROM AUTHOR]

Context. Molecular lines are commonly detected towards protostellar sources. However, to get a better understanding of the chemistry of these sources we need unbiased molecular surveys over a wide frequency range for as many sources as possible to shed light on the origin of this chemistry, particularly any influence from the external environment. Aims. We present results from the PILS-Cygnus survey of ten intermediate- to high-mass protostellar sources in the nearby Cygnus-X complex, through high angular resolution interferometric observations over a wide frequency range. Methods. Using the Submillimeter Array (SMA), a spectral line survey of ten sources was performed in the frequency range 329–361 GHz, with an angular resolution of ~1″.5, or ~2000 AU at a source distance of 1.3 kpc from the Sun. Spectral modelling was performed to identify molecular emission and determine column densities and excitation temperatures for each source. Emission maps were made to study the morphology of emission. Finally, emission properties were compared across the sample. Results. We detect CH3OH towards nine of the ten sources, with CH3OCH3 and CH3OCHO towards three sources. We further detect CH3CN towards four sources. Towards five sources the chemistry is spatially differentiated, meaning that different species peak at different positions and are offset from the peak continuum emission. Low levels of deuteration are detected towards four sources in HDO emission, whereas deuterated complex organic molecule emission is detected towards one source (CH2DOH towards N63). The chemical properties of each source do not correlate with their position in the Cygnus-X complex, nor do the distance or direction to the nearest OB associations. However, the five sources located in the DR21 filament do appear to show less line emission compared to the five sources outside the filament. Conclusions. This work shows how important wide frequency coverage observations are combined with high angular resolution observations for studying the protostellar environment. Furthermore, based on the ten sources observed here, the external environment appears to only play a minor role in setting the chemical environment on these small scales (<2000 AU). [ABSTRACT FROM AUTHOR]

In this study, incorporation of one deuterium atom was achieved by H−D exchange of one of the two identical methylene protons in various dihalomethanes (halogen=Cl, Br, and I) through a rapid‐mixing microflow reaction of lithium diisopropylamide as a strong base and deuterated methanol as a deuteration reagent. Generation of highly unstable carbenoid intermediate and suppression of its decomposition were successfully controlled under high flow‐rate conditions. Monofunctionalization of diiodomethane afforded various building blocks composed of boryl, stannyl, and silyl groups. The monodeuterated diiodomethane, which served as a deuterated C1 source, was subsequently subjected to diverted functionalization methods to afford various products including biologically important molecules bearing isotope labelling at specific positions and homologation products with monodeuteration. [ABSTRACT FROM AUTHOR]

Annulations of unsaturated systems through C–H activation represent a powerful tool for producing multicyclic scaffolds. Having coordinating centers in both annulation partners (a dual coordination strategy) would afford remarkable selectivities in the outcomes. Along this concept, we report herein a Pd-catalyzed regioselective rollover cascade dual C–H annulation of o-arylphenols with alkynols for constructing phenanthrene scaffolds. Control, KIE and deuteration studies were conducted to determine the reaction mechanism, and downstream transformations and scaled-up reactions were carried out to assess the robustness of the transformation. [ABSTRACT FROM AUTHOR]

We present a novel and effective photocatalytic method for the methylation of β‐diketones with controllable degrees of deuterium incorporation via development of new methyl sources. By utilizing a methylamine‐water system as the methyl precursor and a cascade assembly strategy for deuteration degree control, we synthesized methylated compounds with varying degrees of deuterium incorporation, showcasing the versatility of this approach. We examined a range of β‐diketone substrates and synthesized key intermediates for drug and bioactive compounds with varying degrees of deuterium incorporation, ranging from 0 to 3. We also investigated and discussed the postulated reaction pathway. This work demonstrates the utility of readily available reagents, methylamines and water, as a new methyl source, and provides a simple and efficient strategy for the synthesis of degree‐controllable deuterium‐labelled compounds. [ABSTRACT FROM AUTHOR]

Cyclopentadienyliron dicarbonyl‐based complexes present opportunities for underexplored disconnections in synthesis. Access to challenging dihydropyrrolone products is achieved by propargylic C−H functionalization of alkynes for the formation of cyclic organoiron species. Excellent regioselectivity for unsymmetrical alkynes is observed in many cases. Notably, regioselectivity under these stoichiometric conditions diverges from those observed previously under catalysis, occurring at the more‐substituted terminus of the alkyne, allowing for methine functionalization and the formation of quaternary centers. Divergent demetallation of the intermediate organoiron complexes gives access to chemically diverse products which are amenable to further functionalization. [ABSTRACT FROM AUTHOR]

The direct electrophilic deuteration of the aromatic moiety in aromatic and aralkyl amines is reported. The acid‐catalyzed deuteration is facilitated by deuterated trifluoromethanesulfonic acid, [D]triflic acid, CF3SO3D, TfOD, which acts as both the reaction solvent and the source of the deuterium label. The mild conditions enable room temperature hydrogen/deuterium exchange for most of the para‐substituted aromatic amine derivatives studied. In addition, short reaction times and a high degree of aromatic deuteration are achieved and isolation of the product is simple. The optical activity of the chiral aralkyl amines studied was preserved. [ABSTRACT FROM AUTHOR]

Ambrox is a marine natural compound with a delicious ambergris-type scent widely used in fine perfumery. The increase in the long-term scent and shelf life of perfumes has become a paramount endeavor in the fragrance industry. To the best of our knowledge, the exchange of hydrogen by deuterium to decrease the volatility of the constituents of a perfume has not yet been investigated. In this article, we propose this new use of deuteration to synthesize deuterated ambrox in order to decrease its volatility and improve the long-term scent and extend the shelf-life of perfumes. [ABSTRACT FROM AUTHOR]

Catalytic methods for the direct introduction of hydrogen isotopes into organic molecules are essential to the development of improved pharmaceuticals and to the alteration of their absorption, distribution, metabolism, and excretion (ADME) properties. However, the development of homogeneous catalysts for selective incorporation of isotopes in the absence of directing groups under practical conditions remains a long-standing challenge. Here, we show that a phosphine-ligated, silver-carbonate complex catalyzes the site-selective deuteration of C-H bonds in five-membered aromatic heterocycles and active pharmaceutical ingredients that have been resistant to catalytic H/D exchange. The reactions occur with CH3OD as a low-cost source of the isotope. The silver catalysts react with five-membered heteroarenes lacking directing groups, tolerate a wide range of functional groups, and react in both polar and nonpolar solvents. Mechanistic experiments, including deuterium kinetic isotope effects, determination of kinetic orders, and identification of the catalyst resting state, support C-H bond cleavage from a phosphine-ligated, silver-carbonate intermediate as the rate-determining step of the catalytic cycle.

We investigate the structure of copper formate and deuterated copper formate clusters using infrared multiple photon dissociation in combination with quantum chemical calculations. Symmetric and asymmetric C–O stretching vibrations along with C–H/C–D stretching vibrations were characterized. Fermi interactions between the C–H stretch and likely a C–O combination band and/or the overtone of a C–H in-plane bending motion have been confirmed by deuteration. The spectra reveal a strong dependence on the monodentate or bidentate binding motif of the formate ligands. Many minima are energetically accessible on the potential energy surface through rotation of the monodentate formate ligands into several almost isoenergetic local minima. While the C–H/C–D stretching vibration is heavily influenced by the charge distribution in the cluster, the C–O vibrations are largely unaffected. The C–H stretch region is not very diagnostic due to a variety of possible Fermi resonances, which also depend on the charge distribution at the formate ligand. Deuteration yields unperturbed spectra in the C–D stretch region and reveals characteristic shifts of the C–D stretching mode for the different binding motifs, with a strong dependence of the band position on the oxidation state of the copper center. The observed bands are compared with formate adsorbed on copper surfaces from the literature. [ABSTRACT FROM AUTHOR]

Correction for 'Catalyst-free decarboxylative deuteration using tailored photoredox-active carboxylic acids' by Shuai Liu et al., Green Chem., 2024, https://doi.org/10.1039/D4GC01134A. [ABSTRACT FROM AUTHOR]

Erbium is widely considered as a promising tritium storage material due to its high capacity and stability. In this work, the influences of the grain size of original erbium and the deuteration conditions on the microstructure of erbium deuteride film were studied by SEM, FIB-TEM and XRD. The results indicate that the erbium films with small grains transformed into large grains after deuteration, whereas those with large grains changed to smaller grains. The lattice expansion after the loading of deuterium was measured, which confirmed that the films possess small grains present a weaker expansion (7.7%) than those with large grains (10.8%). All of the as-prepared erbium deuteride films exhibited a strong (111) preferred orientation and the film with smaller change of grain size during deuteration presents much stronger preferential growth. It is demonstrated that the deuteration temperature and pressure have a significant effect on the grain size of erbium deuteride films, which the higher deuteration temperature and pressure would induce a bigger change of grain size. In final, the underlying cause of the effect of grain size and deuteration conditions is discussed based on the thermodynamic and kinetics. The higher reaction rate under high deuteration temperature and pressure would prefer to increase the internal stress and the transformation of grain size. • Effects of grain size and deuteration condition on ErD 2 microstructure were studied. • The erbium films with small grains transformed into larger grains after deuteration. • Higher deuteration temperature and pressure induces a bigger change of grain size. • The volume expansion of Er films after deuteration ranges from 7.7% to 10.8%. • Reason of deuteration condition on ErD 2 microstructure is discussed by kinetics. [ABSTRACT FROM AUTHOR]

The employing visible light to drive organic transformations is the most promising choice to meet the needs for green synthesis, in which the reactions promoted by visible light may provide a more efficient and greener method. Currently, the most abundant methods for activation and functionalization of reaction substrates have relied on the direct single‐electron transfer (SET) between the excited photocatalyst and substrates, and these wonderful works were summarized and docoumented in many reviews. As a complement to the above reactions, the photoredox‐mediated atom transfer transformations (photocatalyst‐to‐HAT catalyst‐to‐substrates) to generate radical species are showing an explosively growing trend. In this review, we highlight recent significant developments in this rapidly growing area, mainly focusing on the photoinduced base‐to‐substrates charge transfer reactions. [ABSTRACT FROM AUTHOR]

The administration of low doses of D2O to living organisms was used for decades for the investigation of metabolic pathways and for the measurement of the turnover rate for specific compounds. Usually, the investigation of the deuterium uptake in lipids is performed by measuring the deuteration level of the palmitic acid residue using GC-MS instruments, and to our knowledge, the application of the modern untargeted LC-MS/MS lipidomics approaches was only reported a few times. Here, we investigated the deuterium uptake for >500 lipids for 13 organs and body liquids of mice (brain, lung, heart, liver, kidney, spleen, plasma, urine, etc.) after 4 days of 100% D2O administration. The maximum deuteration level was observed in the liver, plasma, and lung, while in the brain and heart, the deuteration level was lower. Using MS/MS, we demonstrated the incorporation of deuterium in palmitic and stearic fragments in lipids (PC, PE, TAG, PG, etc.) but not in the corresponding free forms. Our results were analyzed based on the metabolic pathways of lipids. [ABSTRACT FROM AUTHOR]

Other than triarylamines, which are protonated by strong acids both at their N‐atom and aromatic rings, pyrrole and its N‐substituted derivatives were exclusively protonated at the carbon atoms of their heteroaromatic rings. Whereas with the strong trifluoromethane sulfonic acid (TFS) stable pyrrolium salts were obtained, with the weaker trifluoroacetic acid (TFA) oligomers are formed. E.g. from the N‐(tert‐butyl)pyrrole a dimeric compound could be unambiguously identified and structural characterised by means of 1H NMR measurements. Treatment of N‐aryl substituted pyrroles with deuterated TFS revealed an H/D exchange not only at the pyrrole rings but also at their aryl moieties even. [ABSTRACT FROM AUTHOR]

The kinetic isotope effect (KIE) is beneficial to improve the performance of luminescent molecules and relevant light-emitting diodes. In this work, the influences of deuteration on the photophysical property and stability of luminescent radicals are investigated for the first time. Four deuterated radicals based on biphenylmethyl, triphenylmethyl, and deuterated carbazole were synthesized and sufficiently characterized. The deuterated radicals exhibited excellent redox stability, as well as improved thermal and photostability. The appropriate deuteration of relevant C-H bonds would effectively suppress the non-radiative process, resulting in the increase in photoluminescence quantum efficiency (PLQE). This research has demonstrated that the introduction of deuterium atoms could be an effective pathway to develop high-performance luminescent radicals. [ABSTRACT FROM AUTHOR]