Synthetic Approach Research Articles

Chemoproteomic Profiling of Signaling Metabolite Fructose-1,6-Bisphosphate Interacting Proteins in Living Cells.

Fructose-1,6-bisphosphate (FBP), a cellular endogenous sugar metabolite in the glycolytic pathway, has recently been reported to act as a signaling molecule to regulate various cellular events through the engagement of important proteins. Though tremendous progress has been made in identifying specific FBP-protein interactions, the comprehensive identification of FBP-interacting proteins and their regulatory mechanisms remains largely unexplored. Here, we describe a concise synthetic approach for the scalable preparation of a photoaffinity FBP probe that enables the quantitative chemoproteomic profiling of FBP-protein interactions based on photoaffinity labeling (PAL) directly in living cells. Using such a protocol, we captured known FBP targets including PKM2 and MDH2. Furthermore, among unknown FBP-interacting proteins, we identified a mitochondrial metabolic enzyme aldehyde dehydrogenase 2 (ALDH2), against which FBP showed inhibitory activity and resulted in cellular ROS upregulation accompanied by mitochondrial fragmentation. Our findings disclosed a new mode of glucose signaling mediating by the FBP-ALDH2-ROS axis.

Синтез производных класса 2-алкил-5-фенил-4,5,6,7- тетрагидро-[1,2,4]триазоло[1,5-a]пиримидин-7-ола

The problem of acid corrosion of steel is of significant importance, particularly in the context of the oil extraction industry, where acid treatment of wells and surrounding spaces is widely employed. This research article focuses on the synthesis and investigation of previously unstudied derivatives of the class of 2-alkyl-5-phenyl-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidin-7-ols – organic compounds potentially highly effective as inhibitors of acid corrosion of steel. The method for synthesizing the proposed compounds involves the condensation of 3-alkyl-5-amino-1H-1,2,4-triazoles with cinnamaldehyde. The structure of the synthesized compounds has been confirmed using 1H NMR and LCMS methods. The study has revealed that the developed synthesis conditions yield the target tetrahydrotriazolopyrimidinols with alkyl substituents containing up to three carbon atoms. However, an increase in the length of alkyl substituents intensifies side reactions, making the isolation of the target compounds challenging. The obtained research results are significant for the development of effective organic inhibitors of acid corrosion of steel of a new class. These findings can serve as a basis for further research in this area, contributing to the development of new methods for corrosion prevention and improving the resistance of materials used in the oil industry. Thus, this study not only describes a new synthetic approach to obtaining inhibitors of corrosion in the tetrahydrotriazolopyrimidinol class but also holds prospective practical value in the field of industrial technologies and materials science.

ETFC-01: a dual-labeled chelate-bridged tracer for SSTR2-positive tumors.

Integrating radioactive and optical imaging techniques can facilitate the prognosis and surgical guidance for cancer patients. Using a single dual-labeled tracer ensures consistency in both imaging modalities. However, developing such molecule is challenging due to the need to preserve the biochemical properties of the tracer while introducing bulky labeling moieties. In our study, we designed a trifunctional chelate that facilitates the coupling of the targeting vector and fluorescent dye at opposite sites to avoid undesired steric hindrance effects. The synthesis of the trifunctional chelate N3-Py-DOTAGA-(tBu)3 (7) involved a five-step synthetic route, followed by conjugation to the linear peptidyl-resin 8 through solid-phase synthesis. After deprotection and cyclization, the near-infrared fluorescent dye sulfo-Cy.5 was introduced using copper free click chemistry, resulting in eTFC-01. Subsequently, eTFC-01 was labeled with [111In]InCl3. In vitro assessments of eTFC-01 binding, uptake, and internalization were conducted in SSTR2-transfected U2OS cells. Ex-vivo biodistribution and fluorescence imaging were performed in H69-tumor bearing mice. eTFC-01 demonstrated a two-fold higher IC50 value for SSTR2 compared to the gold standard DOTA-TATE. Labeling of eTFC-01 with [111In]InCl3 gave a high radiochemical yield and purity. The uptake of [111In]In-eTFC-01 in U2OS.SSTR2 cells was two-fold lower than the uptake of [111In]In-DOTA-TATE, consistent with the binding affinity. Tumor uptake in H69-xenografted mice was lower for [111In]In-eTFC-01 at all-time points compared to [111In]In-DOTA-TATE. Prolonged blood circulation led to increased accumulation of [111In]In-eTFC-01 in highly vascularized tissues, such as lungs, skin, and heart. Fluorescence measurements in different organs correlated with the radioactive signal distribution. The successful synthesis and coupling of the trifunctional chelate to the peptide and fluorescent dye support the potential of this synthetic approach to generate dual labeled tracers. While promising in vitro, the in vivo results obtained with [111In]In-eTFC-01 suggest the need for adjustments to enhance tracer distribution.

A literature review on pharmacological aspects, docking studies, and synthetic approaches of quinazoline and quinazolinone derivatives.

Quinazoline and quinazolinone derivatives piqued medicinal chemistry interest in developing novel drug candidates owing to their pharmacological potential. They are important chemicals for the synthesis of a variety of physiologically significant and pharmacologically useful molecules. Quinazoline and quinazolinone derivatives have anticancer, anti-inflammatory, antidiabetic, anticonvulsant, antiviral, and antimicrobial potential. The increased understanding of quinazoline and quinazolinone derivatives in biological activities provides opportunities for new medicinal products. The present review focuses on novel advances in the synthesis of these important scaffolds and other medicinal aspects involving drug design, structure-activity relationship, and action mechanisms of quinazoline and quinazolinone derivatives to help in the development of new quinazoline and quinazolinone derivatives.

Aspergillus Oryzae Mediated α‐Fe2O3 Nanoparticles for Photocatalytic Remediation of Basic Fuschin Dye and Antimicrobial Activities

AbstractGreen synthetic approach for the synthesis of Iron oxide (α‐Fe2O3) nanoparticles were successfully carried out using Aspergillus oryzae culture mediated biogenic route. The synthesized nanoparticle was confirmed by structural and optical characterization with the help of hematite phase. The α‐Fe2O3 nanoparticles show antimicrobial activity against bacterial strains Staphylococcus aureus, Pseudomonas aeruginosa and fungal strain Candida albicans. Under visible light, the α‐Fe2O3 nanoparticles demonstrate remarkable antibacterial action, confirming their superior efficacy for photocatalytic remediation. The present study discloses that the α‐Fe2O3 nanoparticles are efficient photocatalysts for 96 % degradation of basic fuchsin dye and highly active antimicrobial agent.

Insights into the photocatalytic and supercapacitor performance of V2O5 nanorods synthesized by green synthetic approach using Epipremnum aureum leaves extract

Insights into the photocatalytic and supercapacitor performance of V2O5 nanorods synthesized by green synthetic approach using Epipremnum aureum leaves extract

Atom Exchange Radical Cyclization: A Sustainable Synthetic Approach towards New Functionalized Targets

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel atom exchange radical cyclization (AERC) procedure. This method integrates the established atom transfer radical cyclization (ATRC) with halogen exchange in solution. The technique operates under mild conditions and requires small amounts of metallic copper, serving as both a supplemental activator and reducing agent.

Digital Twin-Enabled Response Function Analysis: A Synthetic Approach to Ship's Propulsion System Assessment

Analyzing the behavior of vessels in actual sea conditions is crucial for conceptual system design, safety and energy efficiency considerations. However, the essential seakeeping problem is reduced to the analysis of wave-hull interactions often neglecting consideration of the propulsion. But in the meantime, the synthetic consideration of wave–propulsion interactions is a key for safety and energy efficiency. Furthermore, safety evaluation of a ship's design with reduced propulsion power in adverse seas is vital for risk management. Response functions are commonly used to estimate propulsion system responses in incoming seaways. This paper proposes a synthetic approach using digital twin technology for rapid response function estimation. It introduces a companion linearized state-space model linked with the digital twin, enabling immediate retrieval of coefficients for response function analysis at the desired operating point. This integrated methodology provides a comprehensive representation of ship propulsion behavior in wave environments, offering a comprehensive framework for system performance assessment.

Pyrazolidinone-Aided Ru(II)-Catalyzed Regioselective C-H Annulation with Allenes.

Regioselective annulation of allenes via C-H activation represents an elegant synthetic approach toward the construction of valuable scaffolds. Considering the importance of allenes, herein we developed an unprecedented Ru(II)-catalyzed highly regioselective redox-neutral C-H activation/(4 + 1)-annulation of 1-arylpyrazolidinones employing allenyl acetates to access pyrazolo[1,2-a]indazol-1-one derivatives. Additionally, allenyl cyclic carbonates, which were never tested in C-H activation, were utilized to construct a similar class of heterocycles having a pendent alcohol functionality. Notably, double C-H functionalization was achieved by a simple modification of reaction conditions. The synthetic significance of this methodology is underscored by late-stage modification of natural products, broad substrate scope, gram-scale synthesis, and postfunctionalizations.

Nanoscale Cu2ZnSnSxSe(4−x) (CZTS/Se) for Sustainable Solutions in Renewable Energy, Sensing, and Nanomedicine

The importance and breadth of applications of the family of quaternary chalcogenides with the formula Cu2ZnSnSxSe(4−x) (CZTS/Se) where x = 0–4 are steadily expanding due to the tunable optoelectronic properties of these compounds and the Earth abundance of the elements in their composition. These p-type semiconductors are viewed as a viable alternative to Si, gallium arsenide, CdTe, and CIGS solar cells due to their cost effectiveness, Earth’s crust abundance, and non-toxic elements. Additionally, CZTS/Se compounds have demonstrated notable capabilities beyond solar cells, such as photoelectrochemical CO2 reduction, solar water splitting, solar seawater desalination, hydrogen production, and use as an antibacterial agent. Various routes have been explored for synthesizing pure CZTS/Se nanomaterials and significant efforts have been dedicated to reducing the occurrence of secondary phases. This review focuses on synthetic approaches for CZTS/Se nanomaterials, with emphasis on controlling the size and morphology of the nanoparticles and their recent application in solar energy harvesting and beyond, highlighting challenges in achieving the desired purity required in all these applications.

Synthesis and characterization of La-doped SnO2 nanoparticles with different shape: A comprehensive study on morphology, structure, and photocatalytic efficiency for eco-friendly wastewater treatment

New controllable synthetic approach to obtain of La-doped SnO2 nanoparticles based on the combination of co-precipitation method with post synthetical hydrothermal treatment has been developed. Nanoparticles with various shape (3 nm spheres and 5 nm cubes) and structural parameters, i.e. different amount of oxygen vacancies and defects, and different dopant concentrations of 11 mol% and 33 mol% were fully characterized using XRD, FTIR, XPS and Raman spectroscopy, TEM, SSA evaluation, optical absorption spectra study, luminescence spectroscopy, including quantum chemical calculations.It was shown that hydrothermal treatment (240 °C during 6 h) promotes nanoparticle growth via the mechanism of oriented attachment. Original computational approach based on the calculation of interaction energies between ions and crystal facets was engaged to study the growth process.The presence of intrinsic photoluminescence (406, 414, 438, 460, 500 and 676 nm) for all obtained samples was established, determined by a complex set of different parameters for sub-10 nm nanoparticles.Photocatalytic efficiency of 95 % on the example of methylene blue under commercially available LED lamp described via quantum chemical modelling and tested on the example of a colorless antibiotic solution. A clear dependance of the morphological and structural parameters on the photocatalytic properties has been obtained and studied in detail.Novel concept based on a combination of chemical and computational method, for effective visible-light driven photocatalyst synthesis with potential antibacterial properties for complex eco-friendly wastewater treatment was proposed.

Co-Ti Bimetallic Complex-Induced Phase Modulation of Co@Black TiO2 for Catalytic Hydrogenation of Cinnamaldehyde.

Transition-metal-doped black titania, primarily in the anatase phase, shows promise for redox reactions, water splitting, hydrogen generation, and organic pollutant removal, but exploring other titania phases for broader catalytic applications is underexplored. This study introduces a synthetic approach using a Co-Ti bimetallic complex bridged by a 1,10-phenanthroline-5,6-dione ligand as a precursor for the synthesis of cobalt-doped black titania [Co@L2N@b-TiO2]. The synthesis involves precise control of pyrolysis conditions, yielding a distinct structure dominated by the rutile phase over anatase, with active cobalt encapsulated within a nitrogen-doped graphitic layer, primarily as Co0 rather than CoII and CoIII. The synthesized material is employed for the selective hydrogenation of cinnamaldehyde (CAL) to cinnamyl alcohol (COL) under industrially viable conditions. The efficiency and selectivity of Co@L2N@b-TiO2 was compared with other catalysts, including cobalt-doped rutile TiO2 (Co@r-TiO2), anatase TiO2 (Co@a-TiO2), and black titania (Co@b-TiO2) as well as materials pyrolyzed under different atmospheres and temperatures, materials with phenanthroline ligands, and materials lacking any ligands. The superior performance of Co@L2N@b-TiO2 is attributed to its high surface area, stable Co0 within the nitrogen-doped graphitic layer, and composition of rutile and anatase phases of TiO2 and Ti2O3 (referred to as RAT), along with the synergistic interaction between RAT and Co0. These factors significantly influence the efficiency and selectivity of COL over hydrocinnamaldehyde (HCAL) and hydrocinnamyl alcohol (HCOL), indicating potential for broader applications beyond catalysis, particularly in designing of black titania-based materials.

Synthesis of N‐Substituted Pyrrole‐2,5‐dicarboxylic Acids from Pyrroles

AbstractPyrrole‐2,5‐dicarboxylic acid (PDCA) is a heterocyclic aromatic dicarboxylic acid that may emerge as a new monomer for polyester production. Compared to its structurally related and bio‐based furan‐2,5‐dicarboxylic acid (FDCA) that is already used for the production of polyethylene furanoate (PEF), PDCA shows excellent potential as its nitrogen can be targeted for further derivatization, thus enabling tuning of the properties of a PDCA containing polymer. In light of this, we recognized the need to explore efficient synthetic approaches for producing PDCAs in high yields. Here, we report a five‐step synthesis route for N‐substituted PDCAs starting from pyrrole, with total yields up to 42 %. The synthetic approach allowed the introduction of several different functional moieties to the pyrrole nitrogen, such as aliphatic saturated and unsaturated side‐chains, as well as benzylic groups.

Pyrazole Paradigms: Unveiling Synthetic Pathways and Unraveling Anti-Cancer Potential.

This review investigates the synthetic methods and anti-cancer activities of pyrazole compounds. Various synthetic approaches, including traditional organic synthesis and microwaveassisted synthesis, have been used to change the pyrazole core structure, resulting in new compounds with improved pharmacological properties. The paper also covers the mechanisms of action that underpin pyrazole derivatives' anti-cancer characteristics, focusing on interactions with major molecular targets implicated in cancer growth and proliferation. SAR insights help to rationally develop novel anti-cancer drugs. In conclusion, the review emphasizes the versatility of pyrazole derivatives as scaffolds for the discovery and development of new anti-cancer medicines. By understanding synthesis routes and unravelling anti-cancer potential, this study hopes to encourage new research endeavours focused on leveraging the therapeutic advantages of pyrazole paradigms in the fight against cancer.

Optogenetic therapeutic strategies for diabetes mellitus.

Diabetes mellitus (DM) is a common chronic disease affecting humans globally. It is characterized by abnormally elevated blood glucose levels due to the failure of insulin production or reduction of insulin sensitivity and functionality. Insulin and glucagon-like peptide (GLP)-1 replenishment or improvement of insulin resistance are the two major strategies to treat diabetes. Recently, optogenetics that uses genetically encoded light-sensitive proteins to precisely control cell functions has been regarded as a novel therapeutic strategy for diabetes. Here, we summarize the latest development of optogenetics and its integration with synthetic biology approaches to produce light-responsive cells for insulin/GLP-1 production, amelioration of insulin resistance and neuromodulation of insulin secretion. In addition, we introduce the development of cell encapsulation and delivery methods and smart bioelectronic devices for the in vivo application of optogenetics-based cell therapy in diabetes. The remaining challenges for optogenetics-based cell therapy in the clinical translational study are also discussed.

Do No Harm? Unintended Consequences of Pharmaceutical Price Regulation in India

The Drugs (Prices Control) Order of 2013 in India regulated the prices of certain essential and life-saving drugs to ensure their affordability and availability, expecting an increase in sales of those drugs. The authors study the effects of the regulation on sales volumes of each regulated drug using a synthetic control approach with sales data from a comparable country that did not experience a regulatory change. They assess the robustness of the results via multiple empirical approaches to triangulate the findings. Contrary to the order's objectives, they find that sales volumes declined for regulated drugs. Since the order placed restrictions on production levels and on drugs exiting the market, the lowered margins of regulated drugs could have pushed pharmaceutical firms to reduce their marketing expenditures on them. The authors provide evidence of such a reduction using detailing data from a large pharmaceutical firm. The findings illustrate that this shift in detailing adversely affected prescriptions from physicians without formal medical degrees who treat poor and disadvantaged people in India—patients that the order was intended to help the most. A survey the authors conducted shows that these physicians rely on detailing more than medically trained doctors. Taken together, the results provide insights into the strategic actions of firms when faced with regulations, and highlight their unintended consequences. The generalizable nature of the study's findings across a broad set of medications has implications for governmental agencies in terms of the need to account for the entire ecosystem when implementing such regulations.

β‐Ketoenamine‐Linked Covalent Organic Frameworks Synthesized via Gel‐to‐Gel Monomer Exchange Reaction: From Aerogel Monoliths to Electrodes for Supercapacitors

AbstractCovalent organic frameworks (COFs) possess intrinsic nanoscale pores, limiting mass transport and impacting their utility in many applications, such as catalysis, supercapacitors, and gas storage, demanding efficient diffusion throughout the material. Hierarchical porous structures, integrating larger macropores with inherent micro‐/meso‐pores, facilitate rapid mass transport. Recently, the fabrication of aerogel monoliths is reported exclusively from imine‐linked COFs, offering flexibility in aerogel composition. However, challenges in synthesizing robust β‐ketoenamine‐based COFs with comparable surface areas prompted innovative synthetic approaches. Leveraging the dynamic nature of COF bonds, in this work efficient monomer exchange from imine to partially β‐ketoenamine‐linked COFs within the gel phase is demonstrated. These aerogels can be transformed into electrodes using the compression technique. The new flexible electrodes‐based β‐ketoenamine‐linked COF composites with C super P exhibit superior durability and redox activity. Through supercapacitor assembly, the β‐ketoenamine‐linked COF electrodes outperform their imine‐based counterparts, showcasing enhanced capacitance (88 mF cm−2) and stability at high current densities (2.0 mA cm−2). These findings underscore the promise of β‐ketoenamine‐linked COFs for pseudocapacitor energy storage applications.

Polyglycerol Sebacate Elastomer: A Critical Overview of Synthetic Methods and Characterisation Techniques

Poly (glycerol sebacate) is a widely studied elastomeric copolymer obtained from the polycondensation of two bioresorbable monomers, glycerol and sebacic acid. Due to its biocompatibility and the possibility to tailor its biodegradability rate and mechanical properties, PGS has gained lots of interest in the last two decades, especially in the soft tissue engineering field. Different synthetic approaches have been proposed, ranging from classic thermal polyesterification and curing to microwave-assisted organic synthesis, UV crosslinking and enzymatic catalysis. Each technique, characterized by its advantages and disadvantages, can be tailored by controlling the crosslinking density, which depends on specific synthetic parameters. In this work, classic and alternative synthetic methods, as well as characterisation and tailoring techniques, are critically reviewed with the aim to provide a valuable tool for the reproducible and customized production of PGS for tissue engineering applications.

Electrochemical Asymmetric Radical Functionalization of Aldehydes Enabled by a Redox Shuttle

AbstractAminocatalysis is a well‐established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility is underscored by its seamless integration with various synthetic approaches. While the combination of aminocatalysis with metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, its synergy with electrochemical activation remains largely unexplored. Herein, we present the successful merger of electrochemistry and aminocatalysis to perform SOMO‐type transformations, expanding the toolkit for asymmetric electrochemical synthesis. The methodology harnesses electricity to drive the oxidation of catalytically generated enamines, which ultimately partake in enantioselective radical processes, leading to α‐alkylated aldehydes. Crucially, mechanistic studies highlight how this electrochemical strategy is enabled by the use of a redox shuttle, 4,4′‐dimethoxybiphenyl, to prevent catalyst degradation and furnishing the coveted compounds in good yield and high enantioselectivity.

Electrochemical Asymmetric Radical Functionalization of Aldehydes Enabled by a Redox Shuttle.

Aminocatalysis is a well-established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility is underscored by its seamless integration with various synthetic approaches. While the combination of aminocatalysis with metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, its synergy with electrochemical activation remains largely unexplored. Herein, we present the successful merger of electrochemistry and aminocatalysis to perform SOMO-type transformations, expanding the toolkit for asymmetric electrochemical synthesis. The methodology harnesses electricity to drive the oxidation of catalytically generated enamines, which ultimately partake in enantioselective radical processes, leading to α-alkylated aldehydes. Crucially, mechanistic studies highlight how this electrochemical strategy is enabled by the use of a redox shuttle, 4,4'-dimethoxybiphenyl, to prevent catalyst degradation and furnishing the coveted compounds in good yield and high enantioselectivity.