Transformation Of Small Molecules Research Articles

Ring-Opening α,β-Difunctionalization of Cyclopropanols with Azides Enables 4-Keto-Functionalized 1,2,3-Triazole Synthesis.

Selective C-C bond cleavage and transformation of organic small molecules to create products of increased value are one of the central goals in organic chemistry. In this study, we have developed a novel TEMPO-mediated ring-opening α,β-difunctionalization of cyclopropyl alcohols with organic azides to prepare structurally important 4-keto-1,2,3-triazoles under metal- and additive-free conditions. This protocol not only provides a straightforward and efficient method for the synthesis of 4-keto-functionalized 1,2,3-triazoles in one pot but also accomplishes the goal of constructing α,β-double C-N bonds via the ring opening of cyclopropyl alcohols for the first time. Additionally, the application of the skeletons of drugs and natural products and the synthesis of Kv1.5 channel blocker 4u further demonstrate the synthetic potential and practicability of this strategy.

A Survey of Reaction Energetics for Diverse Small Molecule Activation: Where Do Molecular Electrocatalysts Go From Here?

AbstractThe invention of technologies that can activate, transform, and upgrade small molecules is a significant challenge. The starting point for many such technologies is molecular catalysts. Their well‐defined active sites, multitude of tools to characterize their reactions, and their synthetic flexibility makes such molecules logical starting points. However, it is increasingly clear that challenges exist in the applications of molecular catalysts at the scales needed to address modern chemical and energy demands. In this review, we discuss selected classes of molecular electrocatalysts and highlight their development and key features. Of special interest are proton‐coupled transformations of H2, O2, N2, CO2, and related small molecules. We also frame important thermodynamic features for different catalysts using new approaches and ask forward looking questions about their applications in practical systems.

A Review of Electrochemical Synthesis and Transformations of Small Organic Molecules: Sulfoximines, Isoxazolines, and Benzimidazoles

A Review of Electrochemical Synthesis and Transformations of Small Organic Molecules: Sulfoximines, Isoxazolines, and Benzimidazoles

Experimental and computational aspects of molecular frustrated Lewis pairs for CO2 hydrogenation: en route for heterogeneous systems?

Catalysis plays a crucial role in advancing sustainability. The unique reactivity of frustrated Lewis pairs (FLPs) is driving an ever-growing interest in the transition metal-free transformation of small molecules like CO2 into valuable products. In this area, there is a recent growing incentive to heterogenize molecular FLPs into porous solids, merging the benefits of homogeneous and heterogeneous catalysis - high activity, selectivity, and recyclability. Despite the progress, challenges remain in preventing deactivation, poisoning, and simplifying catalyst-product separation. This review explores the expanding field of FLPs in catalysis, covering existing molecular FLPs for CO2 hydrogenation and recent efforts to design heterogeneous porous systems from both experimental and theoretical perspectives. Section 2 discusses experimental examples of CO2 hydrogenation by molecular FLPs, starting with stoichiometric reactions and advancing to catalytic ones. It then examines attempts to immobilize FLPs in porous matrices, including siliceous solids, metal-organic frameworks (MOFs), covalent organic frameworks, and disordered polymers, highlighting current limitations and challenges. Section 3 then reviews computational studies on the mechanistic details of CO2 hydrogenation, focusing on H2 splitting and hydride/proton transfer steps, summarizing efforts to establish structure-activity relationships. It also covers the computational aspects on grafting FLPs inside MOFs. Finally, Section 4 summarizes the main design principles established so far, while addressing the complexities of translating computational approaches into the experimental realm, particularly in heterogeneous systems. This section underscores the need to strengthen the dialogue between theoretical and experimental approaches in this field.

Expansion of Auxiliary Activity Family 5 sequence space via biochemical characterization of six new copper radical oxidases.

Bacterial and fungal copper radical oxidases (CROs) from Auxiliary Activity Family 5 (AA5) are implicated in morphogenesis and pathogenesis. The unique catalytic properties of CROs also make these enzymes attractive biocatalysts for the transformation of small molecules and biopolymers. Despite a recent increase in the number of characterized AA5 members, especially from subfamily 2 (AA5_2), the catalytic diversity of the family as a whole remains underexplored. In the present study, phylogenetic analysis guided the selection of six AA5_2 members from diverse fungi for recombinant expression in Komagataella pfaffii (syn. Pichia pastoris) and biochemical characterization in vitro. Five of the targets displayed predominant galactose 6-oxidase activity (EC 1.1.3.9), and one was a broad-specificity aryl alcohol oxidase (EC 1.1.3.7) with maximum activity on the platform chemical 5-hydroxymethyl furfural (EC 1.1.3.47). Sequence alignment comparing previously characterized AA5_2 members to those from this study indicated various amino acid substitutions at active site positions implicated in the modulation of specificity.IMPORTANCEEnzyme discovery and characterization underpin advances in microbial biology and the application of biocatalysts in industrial processes. On one hand, oxidative processes are central to fungal saprotrophy and pathogenesis. On the other hand, controlled oxidation of small molecules and (bio)polymers valorizes these compounds and introduces versatile functional groups for further modification. The biochemical characterization of six new copper radical oxidases further illuminates the catalytic diversity of these enzymes, which will inform future biological studies and biotechnological applications.

Approaches to Improving Selectivity During Photoelectrochemical Transformation of Small Molecules

Approaches to Improving Selectivity During Photoelectrochemical Transformation of Small Molecules

Third-order nonlinear optics and optical limiting of phenanthrenone derivatives

Organic nonlinear optical materials have attracted much attention due to their large nonlinear optical coefficients and ultrafast response speeds, as well as their potential applications in optical limiting (OL). Among them, nonlinear optical materials with phenanthrenone as the backbone are consistently understudied. We have successfully realized the transformation of organic small molecules in the nonlinear optical direction by replacing the carbonyl group on the structure of phenanthrenone with a malononitrile group. The nonlinear optical properties of CN-2 were investigated under different excitation conditions at 532 nm and the kinetic process of nonlinear optics was analyzed by transient absorption spectroscopy. In addition, we also investigated the OL properties of CN-2, and the OL experiments showed that CN-2 with a lower OL threshold has superior OL properties than C60.

Functional ladder-like heterojunctions of Mo2C layers inside carbon sheaths for efficient CO2 fixation

The development of two-dimensional heterogeneous catalysts with highly exposed active site areas for heterogeneous catalytic systems is highly promising for achieving the green transformation of small molecules. 2D transition metal carbides (TMCs) show great promise for catalysis and carbon capture but suffer from heavy aggregation and autooxidation. Mass transfer barrier is also a standard problem of lamellar TMCs caused by slight aggregation of layers. Here, we successfully developed a method to prepare “ladder-like” heterojunctions of Mo2C layers confined inside nitrogen-rich carbon sheaths (2D-Mo2C@NC) via an effective oxygen-diffusion etching strategy, acting as efficient catalysts for CO2 fixation. The enhanced electron enrichment of the as-integrated 2D-Mo2C subunits induced by the Schottky barrier could further keep the exposed Mo2C surface from possible autooxidation and aggregation confronted by conventional 2D TMCs. The experimental results and density functional theory (DFT) calculation further demonstrate that electron-rich Mo2C could boost the adsorption and activation of CO2 for universal carbonylation of various diamines, providing a turnover frequency value (TOF) of 10.2 h−1 to produce benzimidazolone, which is 5.2 times of that of the state-of-the-art catalyst in the literature under even critical conditions.

Formaldehyde-Mediated Hydride Liberation of Alkylamines for Intermolecular Reactions in Hexafluoroisopropanol.

The ability of alkylamines to spontaneously liberate hydride ions is typically restrained, except under specific intramolecular reaction settings. Herein, we demonstrate that this reactivity can be unlocked through simple treatment with formaldehyde in hexafluoroisopropanol (HFIP) solvent, thereby enabling various intermolecular hydride transfer reactions of alkylamines under mild conditions. Besides transformations of small molecules, these reactions enable unique late-stage modification of complex peptides. Mechanistic investigations uncover that the key to these intermolecular hydride transfer processes lies in the accommodating conformation of solvent-mediated macrocyclic transition states, where the aggregates of HFIP molecules act as dexterous proton shuttles. Importantly, negative hyperconjugation between the lone electron pair of nitrogen and the antibonding orbital of amine's α C-H bond plays a critical role in the C-H activation, promoting its hydride liberation.

Chemical and redox non-innocence in low-valent molybdenum β diketonate complexes: novel pathways for CO2 and CS2 activation.

The investigation of fundamental properties of low-valent molybdenum complexes bearing anionic ligands is crucial for elucidating the molybdenum's role in critical enzymatic systems involved in the transformation of small molecules, including the nitrogenase's iron molybdenum cofactor, FeMoco. The β-diketonate ligands in [Mo(acac)3] (acac = acetylacetonate), one of the earliest low-valent Mo complexes reported, provide a robust anionic platform to stabilize Mo in its +III oxidation state. This complex played a key role in demonstrating the potential of low-valent molybdenum for small molecule activation, serving as the starting material for the preparation of the first reported molybdenum dinitrogen complex. Surprisingly however, given this fact and the widespread use of β-diketonate ligands in coordination chemistry, only a very limited number of low-valent Mo β-diketonate complexes have been reported. To address this gap, we explored the redox behavior of homoleptic molybdenum tris-β-diketonate complexes, employing a tertiary butyl substituted diketonate ligand (dipivaloylmethanate, tBudiket) to isolate and fully characterize the corresponding Mo complexes across three consecutive oxidation states (+IV, +III, +II). We observed marked reactivity of the most reduced congener with heterocumulenes CE2 (E = O, S), yet with very distinct outcomes. Specifically, CO2 stoichiometrically carboxylates one of the β-diketonate ligands, while in the presence of excess CS2, catalytic reductive dimerization to tetrathiooxalate occurs. Through the isolation and characterization of reaction products and intermediates, we demonstrate that the observed reactivity results from the chemical non-innocence of the β-diketonate ligands, which facilitates the formation of a common ligand-bound intermediate, [Mo( tBudiket)2( tBudiket·CE2)]1- (E = O, S). The stability of this proposed intermediate dictates the specific reduction products observed, highlighting the relevance of the chemically non-innocent nature of β-diketonate ligands.

Cu site differentiation in tetracopper(i) sulfide clusters enables biomimetic N2O reduction.

Copper clusters feature prominently in both metalloenzymes and synthetic nanoclusters that mediate catalytic redox transformations of gaseous small molecules. Such reactions are critical to biological energy conversion and are expected to be crucial parts of renewable energy economies. However, the precise roles of individual metal atoms within clusters are difficult to elucidate, particularly for cluster systems that are dynamic under operating conditions. Here, we present a metal site-specific analysis of synthetic Cu4(μ4-S) clusters that mimic the Cu Z active site of the nitrous oxide reductase enzyme. Leveraging the ability to obtain structural snapshots of both inactive and active forms of the synthetic model system, we analyzed both states using resonant X-ray diffraction anomalous fine structure (DAFS), a technique that enables X-ray absorption profiles of individual metal sites within a cluster to be extracted independently. Using DAFS, we found that a change in cluster geometry between the inactive and active states is correlated to Cu site differentiation that is presumably required for efficient activation of N2O gas. More precisely, we hypothesize that the Cu δ+⋯Cu δ- pairs produced upon site differentiation are poised for N2O activation, as supported by computational modeling. These results provide an unprecedented level of detail on the roles of individual metal sites within the synthetic cluster system and how those roles interplay with cluster geometry to impact the reactivity function. We expect this fundamental knowledge to inform understanding of metal clusters in settings ranging from (bio)molecular to nanocluster to extended solid systems involved in energy conversion.

Photochemistry of 2-(2-formylphenyloxy)acetic acid derivatives: synthesis of hydroxychromanones and benzofuranones.

Photochemical transformations of small molecules, such as ortho-substituted benzaldehydes, in the absence of a photocatalyst are significantly underexplored and may reveal unexpected outcomes. In the present paper, we showed that 2-(2-formylphenoxy)acetic acid and its esters undergo photocyclization into chromanone and benzofuranone derivatives under 365 nm irradiation. The reaction occurs exclusively in dimethyl sulfoxide and can be used to efficiently obtain hydroxychromanones in good yields (27-91%). A detailed mechanistic study revealed the clue of the divergent phototransformation with various products.

NIR-II organic small molecule probe for labeling lymph nodes and guiding tumor imaging

Organic small molecule fluorescent groups have injected new material support into the field of medical imaging due to their unique luminescence mechanism and easy tuning of structure. The great potential of NIR-II window imaging forces us to continuously optimize the structure of organic fluorophores to design better fluorescent molecules for fluorescence imaging-guided surgery. An ideal organic small molecule fluorescent group: it can penetrate into the inside of the organism, clearly present the internal structure and the edge contour of different tissues, so as to perfectly achieve internal imaging and accurately guide external surgery. In vivo, fluorescent groups do not damage normal tissues and organs. However, problems such as low quantum yield and poor biocompatibility greatly limit the clinical transformation of NIR-II fluorescent small molecules. To avoid the shortcomings of NIR-II fluorescent probes as much as possible and better realize image-guided surgery, in this experiment, the biplane donor unit was incorporated into the twisted D-π-A-π-D structure to expand the conjugated structure of the fluorescent group, which not only realized NIR-II emission, but also had high quantum yield and biosafety.

Application of Photo-inactive Ru(edta) Complexes in Photocatalytic Small Molecules Transformation over Semiconductor Surface - A Perspective

Abstract: Photocatalytic transformation of small substrate molecules to useful products through an environmentally benign and economically viable pathway is a challenging area of research of continual importance. This review focuses on our perception of the application of ruthenium(III) complexes comprising ‘edta’ ligand (edta4- = ethylenediaminetetraacetate) as a ‘redox mediator’ or ‘relay’ in photocatalytic electron transfer reaction pertaining to the conversion of small substrate molecules viz. hydrazine to ammonia, bicarbonate to formate, dioxygen to hydrogen peroxide. In this article, the prospect of [RuIII(edta)(H2O)]- and [RuIII(edta)(pz)]- to act as ‘redox mediator’ or ‘molecular catalysts’ in photocatalytic transformations of aforesaid small molecules are assessed systematically.

Ultrasonic Transformation of Antibiotic Molecules into a Selective Chemotherapeutic Nanodrug.

Ultrasound-based engineering of carrier-free nanodrugs by supramolecular self-assembly has recently emerged as an innovative and environmentally friendly synthetic approach. By applying high-frequency sound waves (490 kHz) in aqueous solutions, the transformation of small chemotherapeutic and antibiotic drug molecules into carrier-free nanodrugs with anticancer and antimicrobial activities was recently achieved. The transformation of the antibiotic drug molecules, i.e., doxycycline, into stable nanodrugs (~130 nm) with selective anticancer activity was achieved without requiring organic solvents, chemical agents, or surfactants. The obtained nanodrug exhibited reactive oxygen species (ROS)-mediated cytotoxicity on human breast cancer (MDA-MB 231 cells) but a negligible antiproliferative effect on healthy fibroblast cells. Imaging by super-resolution microscopy (STORM) provided insights into the intracellular trafficking and endosomal escape of the nanodrugs. Overall, these findings suggest that small antibiotic drugs can be transformed into chemotherapeutic nanodrugs with high selectivity against cancer cells.

Hydrothermal carbonization of waste furniture for clean blast furnace fuel production: Physicochemical, gasification characteristics and conversion mechanism investigation

This study aimed to investigate the physical and chemical characteristics of hydrochar derived from waste furniture through hydrothermal carbonization (HTC) and evaluate its suitability as a fuel for blast furnace injection, the formation mechanism of biomass conversion to hydrochar was also systematically investigated. The optimal HTC conditions were determined as 260 °C, liquid–solid mass ratio of 2:1. The resulting hydrochar exhibited a high calorific value of 27.78 MJ/kg, a specific surface area (St) of 3.01 m2/g, and K and Na concentrations of 203 mg/kg and 416 mg/kg, respectively. The apparent activation energy (E) for gasification was measured as 154.54 kJ/mol, indicating its potential as a clean injection fuel for blast furnaces. During HTC, cellulose, hemicellulose, and lignin underwent hydrolysis, decarboxylation, polymerization, and aromatization processes, resulting in the transformation of water-soluble small molecules into polymerized hydrochar and water-insoluble large molecules into polyaromatic hydrochar. This study provides insights into the possibility of replacing fossil fuels in the blast furnace iron-making process.

Chemoproteomic Approaches for Unraveling Prokaryotic Biology.

Bacteria are ubiquitous lifeforms with important roles in the environment, biotechnology, and human health. Many of the functions that bacteria perform are mediated by proteins and enzymes, which catalyze metabolic transformations of small molecules and modifications of proteins. To better understand these biological processes, chemical proteomic approaches, including activity-based protein profiling, have been developed to interrogate protein function and enzymatic activity in physiologically relevant contexts. Here, chemoproteomic strategies and technological advances for studying bacterial physiology, pathogenesis, and metabolism are discussed. The development of chemoproteomic approaches for characterizing protein function and enzymatic activity within bacteria remains an active area of research, and continued innovations are expected to provide breakthroughs in understanding bacterial biology.

Gas-phase reactions driven by polarized metal-metal bonding in atomic clusters.

Multimetallic catalysts exhibit great potential in the activation and catalytic transformation of small molecules. The polarized metal-metal bonds have been gradually recognized to account for the reactivity of multimetallic catalysts due to the synergistic effect of different metal centers. Gas-phase reactions on atomic clusters that compositionally resemble the active sites on related condensed-phase catalysts provide a widely accepted strategy to clarify the nature of polarized metal-metal bonds and the mechanistic details of elementary steps involved in the catalysis driven by this unique chemical bonding. This perspective review concerns the progress in the fundamental understanding of industrially and environmentally important reactions that are closely related to the polarized metal-metal bonds in clusters at a strictly molecular level. The following topics have been summarized and discussed: (1) catalytic CO oxidation with O2, H2O, and NO as oxidants (2) and the activation of other inert molecules (e.g., CH4, CO2, and N2) mediated with clusters featuring polarized metal-metal bonding. It turns out that the findings in the gas phase parallel the catalytic behaviors of condensed-phase catalysts and the knowledge can prove to be essential in inspiring future design of promising catalysts.

Structural Reconstruction of Catalysts in Electroreduction Reaction: Identifying, Understanding, and Manipulating.

Electroreduction transformation of small molecules (CO2 , N2 , and H2 O) into chemical feedstocks offers a promising approach to eliminate carbon emissions and harness renewable energy. Most cathodic catalysts often undergo structural transformation under operating electroreduction conditions. These structural reconstructions are reflected in changes in their catalytic activity. In-depth understanding of the change of active sites and influence parameters of reconstruction behaviors is an essential precondition for the design of highly efficient catalysts. Despite the previous achievements, comprehensive insight toward the structural evolution mechanism in cathodic catalysts, compared to anode ones, under reaction conditions is still lacking. Herein, an overview of structural reconstruction for cathodic catalysts in terms of fundamental mechanisms, reconstruction process, advanced characterizations, and influencing parameters is provided. On this basis, the typical strategies for manipulating the structural reconfiguration of catalysts are also explicitly discussed from the catalyst structure and working environment. By delivering the mechanism, strategies, insights, and techniques, this review will provide a comprehensive understanding of the structural reconstruction of cathodic catalysts in electroreduction reactions and future guidelines for their rational development.

Gastight rotating cylinder electrode: Toward decoupling mass transport and intrinsic kinetics in electrocatalysis

AbstractDecoupling and understanding the various mass, charge, and heat transport phenomena involved in the electrocatalytic transformation of small molecules (i.e., CO2, CO, H2, N2, NH3, O2, and CH4) is challenging but it can be readily achieved using dimensionless quantities (i.e., Reynolds, Sherwood, Schmidt, Damköhler, Nusselt, Prandtl, and Peclet Numbers) to simplify the characterization of systems with multiple interacting physical phenomena. Herein we report the development of a gastight rotating cylinder electrode cell with well‐defined mass transport characteristics that can be applied to experimentally decouple mass transfer effects from intrinsic kinetics in electrocatalytic systems. The gastight rotating cylinder electrode cell enables the dimensionless analysis of electrocatalytic systems and should enable the rigorous research and development of electrocatalytic technologies.