Low Pressure Carbonylation of Benzyl Carbonates and Carbamates for Applications in 13C Isotope Labeling and Catalytic CO2 Reduction

Herein, we report a methodology to access isotopically labeled esters and amides from carbonates and carbamates employing an oxygen deletion strategy. This methodology utilizes a decarboxylative carbonylation approach for isotope labeling with near stoichiometric, ex situ generated ¹²C, or ¹³C carbon monoxide. This reaction is characterized by its broad scope, functional group tolerance, and high yields, which is showcased with the synthesis of structurally complex molecules. A complementary method that operates by the catalytic in situ generation of CO via the reduction of CO₂ liberated during decarboxylation has also been developed as a proof-of-concept approach that CO₂-derived compounds can be converted to CO-containing frameworks. Mechanistic studies provide insight into the catalytic steps which highlight the impact of ligand choice to overcome challenges associated with low-pressure carbonylation methodologies, along with rational for the development of future methodologies.     

Modern Strategies for Carbon Isotope Exchange

In contrast to stable and natural abundant carbon-12, the synthesis of organic molecules with carbon (radio)isotopes must be conceived and optimized in order to navigate through the hurdles of radiochemical requirements, such as high costs of the starting materials, harsh conditions and radioactive waste generation. In addition, it must initiate from the small cohort of available C-labeled building blocks. For long time, multi-step approaches have represented the sole available patterns. On the other side, the development of chemical reactions based on the reversible cleavage of C−C bonds might offer new opportunities and reshape retrosynthetic analysis in radiosynthesis. This review aims to provide a short survey on the recently emerged carbon isotope exchange technologies that provide effective opportunity for late-stage labeling. At present, such strategies have relied on the use of primary and easily accessible radiolabeled C1-building blocks, such as carbon dioxide, carbon monoxide and cyanides, while the activation principles have been based on thermal, photocatalytic, metal-catalyzed and biocatalytic processes.     

Cu‐Catalyzed Alkylative Carboxylation of Ynamides with Dialkylzinc Reagents and Carbon Dioxide

Alkylative carboxylation of ynamides with CO₂ and dialkylzinc reagents using a N‐heterocyclic carbene (NHC)–copper catalyst has been developed. A variety of ynamides, both cyclic and acyclic, undergo this transformation under mild conditions to afford the corresponding α,β‐unsaturated carboxylic acids, which contain the α,β‐dehydroamino acid skeleton. The present alkylative carboxylation formally consists of Cu‐catalyzed carbozincation of ynamides with dialkylzinc reagents with the subsequent nucleophilic carboxylation of the resulting alkenylzinc species with CO₂. Dialkylzinc reagents bearing a β‐hydrogen atom such as Et₂Zn and Bu₂Zn still afford the alkylated products despite the potential for β‐hydride elimination. This protocol would be a desirable method for the synthesis of highly substituted α,β‐ dehydroamino acid derivatives due to its high regio‐ and stereoselectivity, simple one‐pot procedure, and its use of CO₂ as a starting material.     

特定化合物碳同位素分析系统中的氧化反应装置的研制

通过对比实验,研制了特定化合物碳同位素在线分析系统中连接气相色谱与同位素比质谱的核心部分——氧化反应装置,包括加热系统、氧化反应系统及接口系统,并以特定化合物的碳同位素分析为例,选用天然气工作标准样品,在600～950℃之间选择8个温度点进行了氧化反应实验,表明其碳同位素测定值(δ13C1,δ13C2,δ13C3)随反应温度升高而逐渐趋于稳定,符合氧化反应过程的一般规律.通过对不同碳数(1≤n≤31)烃类样品(工作标准、国际参考标准、天然气及原油样品)的测试,显示碳同位素值(δ13Calkane)的测试精度优于±(0.2～0.5)‰,满足研究需求,并有效降低了分析成本,具有良好的应用及推广价值.     

A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides

A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that ¹³C-labeled Ni^II-acyl complexes, formed from a ¹³CO insertion step with Ni^II-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of ¹³C-SilaCOgen or ¹³C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired ¹³C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the Ni^II-acyl complexes and the disulfide providing a reactive Ni^III-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of ¹³C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.     

Fluorogenic and Cell-Permeable Rhodamine Dyes for High-Contrast Live-Cell Protein Labeling in Bioimaging and Biosensing

The advancement of fluorescence microscopy techniques has opened up new opportunities for visualizing proteins and unraveling their functions in living biological systems. Small-molecule organic dyes, which possess exceptional photophysical properties, small size, and high photostability, serve as powerful fluorescent reporters in protein imaging. However, achieving high-contrast live-cell labeling of target proteins with conventional organic dyes remains a considerable challenge in bioimaging and biosensing due to their inadequate cell permeability and high background signal. Over the past decade, a novel generation of fluorogenic and cell-permeable dyes has been developed, which have substantially improved live-cell protein labeling by fine-tuning the reversible equilibrium between a cell-permeable, nonfluorescent spirocyclic state (unbound) and a fluorescent zwitterion (protein-bound) of rhodamines. In this review, we present the mechanism and design strategies of these fluorogenic and cell-permeable rhodamines, as well as their applications in bioimaging and biosensing.     

Synthesis and Chemical Constitution of Diphenoxyphosphoryl Derivatives and Phosphonium Salts as Coupling Reagents for Peptide Segment Condensation

The reactions of diphenoxyphosphoryl chloride ((PhO) 2 P(O)Cl) and different chlorophosphonium salts ([R 3 PCl]X, R = (CH 3 ) 2 N, pyrrolidine, X = PF 6 m , BF 4 m ), respectively, with 7-aza-1-hydroxybenzotriazole (HOAt), 1-hydroxybenzotriazole (HOBt), hydroximinomalonitrile (HOxDCO), and ethyl hydroximinocyanoacetate (HOxO) are described. The structures of the new compounds, which are useful coupling reagents for epimerization-free peptide segment condensation, are discussed on the basis of their 1 H, 13 C, 31 P NMR, and IR spectra. The reactions of (PhO) 2 P(O)Cl lead to mixtures of O - and N -phosphorylated isomers of varying ratios. Contrary, reactions of chlorophosphonium salts yield exclusively one isomer.     

羧基化碳纳米管嵌入石墨修饰电极对多巴胺和抗坏血酸的电催化

采用涂层和嵌入修饰法 ,将羧基化多层碳纳米管制成两种修饰电极。以多巴胺 (DA)和抗坏血酸(AA)为模型化合物 ,研究了两种修饰电极对DA和AA共存时的电催化作用。结果表明 :嵌入的方式比涂层的方式显示了更多的优点。嵌入修饰电极不仅使峰电流增加 ,并且使两者共存时的氧化峰位分离达 16 0mV ,同时 ,该电极对DA的响应灵敏于AA ,这有利于在大量的AA存在下实现对DA的测定。在 1× 10 - 3 mol/L的AA的存在下 ,还原电流的一阶导数与DA浓度在 5× 10 - 7～ 1× 10 - 4 mol/L范围内呈良好的线性关系 ;检测下限达 1× 10 - 7mol L。     

Regioselective Alkylative Carboxylation of Allenamides with Carbon Dioxide and Dialkylzinc Reagents Catalyzed by an N‐Heterocyclic Carbene–Copper Complex

The alkylative carboxylation of allenamide catalyzed by an N‐heterocyclic carbene (NHC)–copper(I) complex [(IPr)CuCl] with CO₂ and dialkylzinc reagents was investigated. The reaction of allenamides with dialkylzinc reagents (1.5 equiv) and CO₂ (1 atm.) proceeded smoothly in the presence of a catalytic quantity of [(IPr)CuCl] to afford (Z)‐α,β‐dehydro‐β‐amino acid esters in good yields. The reaction is regioselective, with the alkyl group introduced onto the less hindered γ‐carbon, and the carboxyl group introduced onto the β‐carbon atom of the allenamides. The first step of the reaction was alkylative zincation of the allenamides to give an alkenylzinc intermediate followed by nucleophilic addition to CO₂. A variety of cyclic and acyclic allenamides were found to be applicable to this transformation. Dialkylzinc reagents bearing β‐hydrogen atoms, such as Et₂Zn or Bu₂Zn, also gave the corresponding alkylative carboxylation products without β‐hydride elimination. The present methodology provides an easy route to alkyl‐substituted α,β‐dehydro‐β‐amino acid ester derivatives under mild reaction conditions with high regio‐ and stereoselectivtiy.     

Hydrothermal Syntheses,Crystal Structures and Properties of Two Novel 3‐D Lanthanide(III) Coordination Polymers Constructed with Mixed Heterocyclic Carboxylic Acid

The hydrothermal reactions of Ln₂O₃ (Ln = Nd and Eu) with pyridine‐2,5‐dicarboxylic acid (H₂pydc) resulted in the formation of two isomorphic three‐dimensional (3D) polymeric Ln^III complexes, [Ln(pydc)(nic)·H₂O]_n (Ln = Nd( 1 ) and Eu( 2 )), in which nic (nicotinate; also named as pyridine‐2‐carboxylic acid) might have been formed from the pydc ligands through the C–C bond cleavage and CO₂ molecules releasing. Pydc ligands bridge lanthanide centers to form the three‐dimensional framework featuring hexagonal channels along the axis a which are occupied by bridging nic anions and mono‐coordinated water molecules. From the topological point of view, two three‐dimensional nets are binodal with six‐ and three‐connected nodes, which display a distorted rutile (4.6²)₂(4²·6¹⁰·8³) topology. Magnetic measurements (2‐300 K) reveal that all polymers possess weak antiferromagnetic property. A strong fluorescence emission spectrum of compound 2 was observed.     

Glycan Metabolic Fluorine Labeling for In Vivo Visualization of Tumor Cells and In Situ Assessment of Glycosylation Variations

The abnormality in the glycosylation of surface proteins is critical for the growth and metastasis of tumors and their capacity for immunosuppression and drug resistance. This anomaly offers an entry point for real-time analysis on glycosylation fluctuations. In this study, we report a strategy, glycan metabolic fluorine labeling (MEFLA), for selectively tagging glycans of tumor cells. As a proof of concept, we synthesized two fluorinated unnatural monosaccharides with distinctive ¹⁹F chemical shifts (Ac₄ManNTfe and Ac₄GalNTfa). These two probes could undergo selective uptake by tumor cells and subsequent incorporation into surface glycans. This approach enables efficient and specific ¹⁹F labeling of tumor cells, which permits in vivo tracking of tumor cells and in situ assessment of glycosylation changes by ¹⁹F MRI. The efficiency and specificity of our probes for labeling tumor cells were verified in vitro with A549 cells. The feasibility of our method was further validated with in vivo experiments on A549 tumor-bearing mice. Moreover, the capacity of our approach for assessing glycosylation changes of tumor cells was illustrated both in vitro and in vivo. Our studies provide a promising means for visualizing tumor cells in vivo and assessing their glycosylation variations in situ through targeted multiplexed ¹⁹F MRI.     

In situ Generated Iridium Nanoparticles as Hydride Donors in Photoredox-Catalyzed Hydrogen Isotope Exchange Reactions with Deuterium and Tritium Gas

We have studied the photoredox-catalyzed hydrogen isotope exchange (HIE) reaction with deuterium or tritium gas as isotope sources and in situ formed transition metal nanoparticles as hydrogen atom transfer pre-catalysts. By this means we have found synergistic reactivities applying two different HIE mechanisms, namely photoredox-catalyzed and CH-functionalization HIE leading to the synthesis of highly deuterated complex molecules. Finally, we adopted these findings successfully to tritium chemistry.     

Azulenesulfonium Salts: Accessible,Stable, and Versatile Reagents for Cross‐Coupling

Azulenesulfonium salts may be readily prepared from the corresponding azulenes by an S_EAr reaction. These azulene sulfonium salts are bench‐stable species that may be employed as pseudohalides for cross‐coupling. Specifically, their application in Suzuki–Miyaura reactions has been demonstrated with a diverse selection of coupling partners. These azulenesulfonium salts possess significant advantages in comparison with the corresponding azulenyl halides, which are known to be unstable and difficult to prepare in pure form.     

Azulenesulfonium Salts: Accessible,Stable, and Versatile Reagents for Cross‐Coupling

Azulenesulfonium salts may be readily prepared from the corresponding azulenes by an S_EAr reaction. These azulene sulfonium salts are bench‐stable species that may be employed as pseudohalides for cross‐coupling. Specifically, their application in Suzuki–Miyaura reactions has been demonstrated with a diverse selection of coupling partners. These azulenesulfonium salts possess significant advantages in comparison with the corresponding azulenyl halides, which are known to be unstable and difficult to prepare in pure form.     

Sensitive Electrochemical Prostate Specific Antigen Aptasensor: Effect of Carboxylic Acid Functionalized Carbon Nanotube and Glutaraldehyde Linker

The performance of carboxylic acid functionalized carbon nanotubes (CNTs_(COOH)), chitosan (Chit), carbon nanotubes‐chitosan (CNTs‐Chit and CNTs_(COOH)‐Chit) for immobilizing of amino‐functionalized ssDNA and fabrication of electrochemical prostate specific antigen (PSA) aptasensor were studied in detail using X‐ray diffraction spectroscopy (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT‐IR) and electrochemical impedance spectroscopy (EIS). The assemblies of capture probe are formed on the surface via two approaches: EDC/NHS chemistry and glutaraldehyde linker. Cyclic voltammetry (CV), differential pulse voltammetry (DPV) and EIS techniques were used to investigate the analytical performance of the PSA aptasensor. Under optimum conditions the sensitivity of 0.0026 µA/(ng/ml) and a limit of detection of 0.75 ng/ml (22 pM) were obtained for PSA detection. This protocol offers a new means for sensitive detection of PSA with some advantages in terms of simplicity, selectivity, ease of use and regenerability.     

Versatile Synthesis of Carbon Materials using Protic Ionic Liquids and Salts as Precursors

Carbon materials (CMs) hold immense potential for applications across a wide range of fields. However, current precursors often confront limitations such as low heteroatom content, poor solubility, or complicated preparation and post-treatment procedures. Our research has unveiled that protic ionic liquids and salts (PILs/PSs), generated from the neutralization of organic bases with protonic acids, can function as economical and versatile small-molecule carbon precursors. The resultant CMs display attractive features, including elevated carbon yield, heightened nitrogen content, improved graphitic structure, robust thermal stability against oxidation, and superior conductivity, even surpassing that of graphite. These properties can be elaborate modulated by varying the molecular structure of PILs/PSs. In this Personal Account, we summarize recent developments in PILs/PSs-derived CMs, with a particular focus on the correlations between precursor structure and the physicochemical properties of CMs. We aim to impart insights into the foreseeable controlled synthesis of advanced CMs.