Carboxylic Function Research Articles

Synthesis and Post-Processing of Chemically Homogeneous Nanothreads from 2,5-Furandicarboxylic Acid.

Compared with conventional, solution-phase approaches, solid-state reaction methods can provide unique access to novel synthetic targets. Nanothreads-one-dimensional diamondoid polymers formed through the compression of small molecules-represent a new class of materials produced via solid-state reactions, however, the formation of chemically homogeneous products with targeted functionalization represents a persistent challenge. Through careful consideration of molecular precursor stacking geometry and functionalization, we report here the scalable synthesis of chemically homogeneous, functionalized nanothreads through the solid-state polymerization of 2,5-furandicarboxylic acid. The resulting product possesses high-density, pendant carboxyl functionalization along both sides of the backbone, enabling new opportunities for the post-synthetic processing and chemical modification of nanothread materials applicable to a broad range of potential applications.

Synthesis and Post‐Processing of Chemically Homogeneous Nanothreads from 2,5‐Furandicarboxylic Acid**

AbstractCompared with conventional, solution‐phase approaches, solid‐state reaction methods can provide unique access to novel synthetic targets. Nanothreads—one‐dimensional diamondoid polymers formed through the compression of small molecules—represent a new class of materials produced via solid‐state reactions, however, the formation of chemically homogeneous products with targeted functionalization represents a persistent challenge. Through careful consideration of molecular precursor stacking geometry and functionalization, we report here the scalable synthesis of chemically homogeneous, functionalized nanothreads through the solid‐state polymerization of 2,5‐furandicarboxylic acid. The resulting product possesses high‐density, pendant carboxyl functionalization along both sides of the backbone, enabling new opportunities for the post‐synthetic processing and chemical modification of nanothread materials applicable to a broad range of potential applications.

Examination of aminophenol-containing compounds designed as antiproliferative agents and potential atypical retinoids

Retinoic acid (RA, 1), an oxidized form of vitamin A, binds to retinoic acid receptors (RAR) and retinoid X receptors (RXR) to regulate gene expression and has important functions such as cell proliferation and differentiation. Synthetic ligands regarding RAR and RXR have been devised for the treatment of various diseases, particularly promyelocytic leukemia, but their side effects have led to the development of new, less toxic therapeutic agents. Fenretinide (4-HPR, 2), an aminophenol derivative of RA, exhibits potent antiproliferative activity without binding to RAR/RXR, but its clinical trial was discontinued due to side effects of impaired dark adaptation. Assuming that the cyclohexene ring of 4-HPR is the cause of the side effects, methylaminophenol was discovered through structure–activity relationship research, and p-dodecylaminophenol (p-DDAP, 3), which has no side effects or toxicity and is effective against a wide range of cancers, was developed. Therefore, we thought that introducing the motif carboxylic acid found in retinoids, could potentially enhance the anti-proliferative effects. Introducing chain terminal carboxylic functionality into potent p-alkylaminophenols significantly attenuated antiproliferative potencies, while a similar structural modification of weakly potent p-acylaminophenols enhanced growth inhibitory potencies. However, conversion of the carboxylic acid moieties to their methyl esters completely abolished the cell growth inhibitory effects of both series. Insertion of a carboxylic acid moiety, which is important for binding to RA receptors, abolishes the action of p-alkylaminophenols, but enhances the action of p-acylaminophenols. This suggests that the amido functionality may be important for the growth inhibitory effects of the carboxylic acids.

Effect of Hydrothermal Cycling on CNT-Embedded Glass Fiber-Reinforced Polymer Composites: An Emphasis on the Role of Carboxyl Functionalization

Effect of Hydrothermal Cycling on CNT-Embedded Glass Fiber-Reinforced Polymer Composites: An Emphasis on the Role of Carboxyl Functionalization

(η5-Carb-oxy-cyclo-penta-dien-yl)(η7-cyclo-hepta-trien-yl)manganese(I) hexa-fluorido-phosphate.

The title compound, [Mn(C7H7)(C6H5O2)]PF6 or [(Cht)Mn(Cp'CO2H)]PF6, with Cht = cyclo-hepta-trienyl and Cp' = C5H4, is an air-stable, purple, heteroleptic, cationic sandwich complex with manganese in oxidation state +I and π-coordinating cyclo-hepta-trienyl and cyclo-penta-dienyl ligands. The latter ligand carries the carb-oxy-lic acid functionality. This 'tromancenium-8-carb-oxy-lic acid' with hexa-fluorido-phosphate as counter-ion represents a rare case of a cationic carb-oxy-lic acid. Structurally, this organometallic carb-oxy-lic acid displays the common motif of planar Osp 2⋯H-Osp 3/Osp 3-H⋯Osp 2 hydrogen-bonded carb-oxy-lic acid dimers with anti-oriented metallocenyl moieties, the cationic charge of which is balanced by octa-hedrally shaped hexa-fluorido-phosphate anions. Positional disorder is observed in the cyclo-hepta-trienyl ring and the PF6 - anion.

Aligning Metal Coordination Sites in Metal–Organic Framework-Enabled Metallaphotoredox Catalysis

Construction of catalytic metal centers, the key modules in artificial photosynthetic systems, lies at the heart to explore unpaved reactivity patterns powered by light. Here, we disclose that the amino (-NH2) and carboxylic (-COO) functionalities, aligned in various visible-light-harvesting metal-organic frameworks (MOFs) (NH2-UiO-66, (NH2)2-UiO-67, and NH2-MIL-125), provide N/O-ligated Ni featuring different configurations and valence states. Of note, these Ni centers, in situ formed or preimplanted, demonstrated coordination units' spatial arrangement-dependent activity in cross-coupling of aryl halides and various nucleophiles. Our work provides a novel approach to construct and to regulate metal center(s) by MOFs' skeleton defined coordination environments, highlighting exclusive potential in exploring the reactivity pattern of the hosted metals.

Functionalized Thiophene-Based Aptasensors for the Electrochemical Detection of Mucin-1

Mucin-1 (MUC1) is a glycoprotein found in epithelial tissues; its function is to protect the body by blocking pathogens from reaching the cells. Overexpression and elevated serum levels of this protein are observed in breast cancer, lung cancer, stomach cancer, ovarian cancer, and many other types of malignancies. Current methods used to detect cancer are expensive and therefore not readily accessible; some methods are also invasive. The ability to detect MUC1 could allow for early detection of cancer, leading to more successful outcomes. This research focuses on the development of a robust biosensor platform based on aptamer-functionalized electroactive polymers (EAPs) that can be used for the detection of cancer. To achieve this, indium tin oxide slide surfaces were modified to enable the electrochemical growth of an electroactive copolymer of 3,4-ethylenedioxythiophene (EDOT) and 2,2-(3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine-3,3-diyl)diacetic acid (ProDOT(COOH)2), with the carboxylic acid functionalities added to introduce bonding sites for a MUC1-specific aptamer. Three copolymer ratios were investigated to maximize the performance. The aptamer was then attached to the EAPs to create aptasensors that could be used for the electrochemical detection of a MUC1 polypeptide. The limits of detection of the biosensors and their stabilities were evaluated. The MUC1 aptasensor showed stability for at least 6 days, depending on the ratio of the copolymer, when stored in 0.1 M phosphate-buffered saline. The 1:2 EDOT/ProDOT(COOH)2 copolymer was found to be the most stable over time and to offer one of the smallest limits of detection, making it the most favorable ratio for aptasensor optimization. Specifically, the 1:2 EDOT/ProDOT(COOH)2 biosensor provided a limit of detection of 369 fg/mL (418 fM) and a linear range of 625 fg/mL to 6.25 ng/mL (709 fM to 7.09 nM) with the MUC1 peptide APDTRPAPG. The sensor also showed selectivity when tested with competing agents including IgG and cell media. The performance of the aptasensor demonstrated its potential as a highly sensitive and selective biosensor for MUC1 detection.

Fast and Cost-Efficient 17 O-Isotopic Labeling of Carboxylic Groups in Biomolecules: From Free Amino Acids to Peptide Chains.

17 O NMR spectroscopy is a powerful technique, which can provide unique information regarding the structure and reactivity of biomolecules. However, the low natural abundance of 17 O (0.04 %) generally requires working with enriched samples, which are not easily accessible. Here, we present simple, fast and cost-efficient 17 O-enrichment strategies for amino acids and peptides by using mechanochemistry. First, five unprotected amino acids were enriched under ambient conditions, consuming only microliter amounts of costly labeled water, and producing pure molecules with enrichment levels up to ∼40 %, yields ∼60-85 %, and no loss of optical purity. Subsequently, 17 O-enriched Fmoc/tBu-protected amino acids were produced on a 1 g/day scale with high enrichment levels. Lastly, a site-selective 17 O-labeling of carboxylic functions in peptide side-chains was achieved for RGD and GRGDS peptides, with ∼28 % enrichment level. For all molecules, 17 O ssNMR spectra were recorded at 14.1 T in reasonable times, making this an important step forward for future NMR studies of biomolecules.

Carboxyl Function Group Introduced to Polyimide Binders for Silicon Anode Materials

Silicon has been considered as one of the most promising candidate anode material for Li-ion batteries due to its high theoretical specific capacity. Nevertheless, its low cycling performance due to the huge volume change during cycling hinders the commercial application of silicon anodes. Binders play a crucial role in Li-ion batteries and can effectively relieve the volumetric expansion stress of silicon anodes. Herein, we developed a polyimide binder with an introduced carboxyl group (PI-COOH). The introduced −COOH group can effectively bond with the oxide layer on the silicon surface through forming improved interface stability and then reducing the damage of the solid electrolyte interface film during cycling. Combined with the excellent intrinsic mechanical and thermodynamic properties of polyimide, the as-prepared PI-COOH binder significantly improved the cycling stability and rate performance of silicon anode.

Carboxyl Functionalization of N-MWCNTs with Stone-Wales Defects and Possibility of HIF-1α Wave-Diffusive Delivery.

Nitrogen-doped multi-walled carbon nanotubes (N-MWCNTs) are widely used for drug delivery. One of the main challenges is to clarify their interaction with hypoxia-inducible factor 1 alpha (HIF-1α), the lack of which leads to oncological and cardiovascular diseases. In the presented study, N-MWCNTs were synthesized by catalytic chemical vapor deposition and irradiated with argon ions. Their chemical state, local structure, interfaces, Stone-Wales defects, and doping with nitrogen were analyzed by high resolution transmission electron microscopy (HRTEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. Using experimental data, supercells of functionalized N-MWCNTs with an oxygen content of 2.7, 4 and 6 at. % in carboxyl groups were built by quantum chemical methods. Our analysis by the self-consistent charge density functional tight-binding (SCC DFTB) method shows that a key role in the functionalization of CNTs with carboxyl groups belongs to Stone-Wales defects. The results of research in the decoration of CNTs with HIF-1α demonstrate the possibility of wave-diffusion drug delivery. The nature of hybridization and relaxation determines the mechanism of oxygen regulation with HIF-1α molecules, namely, by OH-(OH-C) and OH-(O=C) chemical bonds. The concentration dependence of drug release in the diffusion mode suggests that the best pattern for drug delivery is provided by the tube with a carboxylic oxygen content of 6 at. %.

Colloidal synthesis of the mixed ionic-electronic conducting NaSbS2 nanocrystals.

Solution-based synthesis of mixed ionic and electronic conductors (MIECs) has enabled the development of novel inorganic materials with implications for a wide range of energy storage applications. However, many technologically relevant MIECs contain toxic elements (Pb) or are prepared by using traditional high-temperature solid-state synthesis. Here, we provide a simple, low-temperature and size-tunable (50-90 nm) colloidal hot injection approach for the synthesis of NaSbS2 based MIECs using widely available and non-toxic precursors. Key synthetic parameters (cationic precursor, reaction temperature, and ligand) are examined to regulate the shape and size of the NaSbS2 nanocrystals (NCs). FTIR studies revealed that ligands with carboxylate functionality are coordinated to the surface of the synthesized NaSbS2 NCs. The synthesized NaSbS2 nanocrystals have electronic and ionic conductivities of 3.31 × 10-10 (e-) and 1.9 × 10-5 (Na+) S cm-1 respectively, which are competitive with the ionic and electrical conductivities of perovskite materials generated by solid-state reactions. This research gives a mechanistic understanding and post-synthetic evaluation of parameters influencing the formation of sodium antimony chalcogenides materials.

Revisiting carboxylic group functionalization of silica sol-gel materials.

The carboxylic chemical group is a ubiquitous moiety present in amino acids, a ligand for transition metals, a colloidal stabilizer, and a weak acidic ion-exchanger in polymeric resins and given this property, it is attractive for responsive materials or nanopore-based gating applications. As the number of uses increases, subtle requirements are imposed on this molecular group when anchored to various platforms for the functioning of an integrated chemical system. In this context, silica stands as an inert and multipurpose platform that enables the anchoring of multiple chemical entities combined through several orthogonal synthesis methods on the interface. Surface chemical modification relies on the use of organoalkoxysilanes that must meet the demand of tuned chemical properties; this, in turn, urges for innovative approaches for having an improved, but simple, organic toolbox. Starting from commonly available molecular precursors, several approaches have emerged: hydrosilylation, click thiol-ene additions, the use of carbodiimides or the reaction between cyclic anhydrides and anchored amines. In this review, we analyze the importance of the COOH groups in the area of materials science and the commercial availability of COOH-based silanes and present new approaches for obtaining COOH-based organoalkoxide precursors. Undoubtedly, this will attract widespread interest for the ultimate design of highly integrated chemical platforms.

Flavin based supramolecular gel displaying multi-stimuli triggered sol-gel transition.

Herein, we report the design and synthesis of an amphiphilic flavin analogue as a robust low molecular weight gelator involving minimal structural modification. Four flavin analogues were evaluated for their gelation capabilities and the flavin analogue with antipodal positioning of the carboxyl and octyl functionalities was found to be the most efficient gelator with the minimum gelation concentration being as low as 0.03 M. A wide range of solvents were used for gelation studies suggesting its widespread applicability. Morphological, photophysical and rheological characterization studies were performed to fully characterize the nature of the gel. Interestingly, reversible multiple stimuli responsive sol-gel transition was observed with changing pH and redox activity, while metal screening showed specific transition in the presence of ferric ions. The gel was able to differentiate between ferric and ferrous species with well-defined sol-gel transition. The current results potentially offer a redox-active flavin-based material as a low molecular weight gelator for the development of next-generation materials.

Recent advances in catalytic decarboxylative transformations of carboxylic acid groups attached to a non-aromatic sp2 or sp carbon.

Chemists learn the most important transformations of the carboxylic acid functionality (COOH) from as early as the first semester of their studies. Carboxylic acids are not only safe to store and handle, but also broadly accessible with great structural diversity either from commercial sources or by means of a large variety of well-known synthesis routes. Consequently, carboxylic acids have long been recognized as a highly adaptable starting material in organic synthesis. A large body of reactions of carboxylic acids are based on catalytic decarboxylative conversions, in which the COOH group of carboxylic acids is catalytically replaced without trace by extrusion of CO2 chemo- and regioselectively. Within the last two decades, the area of catalytic decarboxylative transformations has expanded significantly by utilizing various classes of carboxylic acids as the substrate, including (hetero)aromatic acids, alkyl acids, α-keto acids, α,β-unsaturated acids and alkynoic acids. A literature survey reveals that compared to aromatic acids, the number of original research papers on decarboxylative reactions of α-keto acids, α,β-unsaturated acids and alkynoic acids has been rising every year lately, particularly within past five to six years. The prime aim of the current review is to give an overview of the decarboxylative transformations of α-keto acids, α,β-unsaturated acids and alkynoic acids that have been developed since 2017. The article focuses on the decarboxylative functionalizations that occur in the presence or absence of transition metal catalysts and/or under photoredox catalysis.

Tetrazole and acylsulfonamide bioisosteric replacements of the carboxylic acid in a dual MCL-1/BCL-xL inhibitor are tolerated.

Overexpression of the anti-apoptotic protein MCL-1 is associated with a plethora of human cancers, and it reduces the sensitivity of cancer cells to approved chemotherapies. Accordingly, the discovery of MCL-1 inhibitors is an active area of interest. Many inhibitors of the anti-apoptotic MCL-1 protein bear a crucial carboxylic acid that may engage Arg263 in the BH3-binding groove. We previously described the salicylic acid-based dual MCL-1/BCL-xL inhibitor 17cd, which is currently undergoing lead optimization. As part of that process, we wished to investigate bioisosteric replacement of 17cd's key carboxylic acid. Herein we describe the synthesis of a variety of analogues of a simpler analogue of 17cd presenting carboxylic acid surrogates. The acylsulfonamide and tetrazole motifs, which exhibit comparable pKas to the carboxylic acid function, displayed similar, or better, binding affinities to MCL-1 and BCL-xL as the corresponding carboxylic acid-containing lead. Our best compound was acylsulfonamide 7d with a Ki of 800 nM against MCL-1 and 1.82 mM against BCL-xL, and demonstrated an improved effect on the viability of the HL60 acute myeloid leukemia cell line relative to the parent carboxylic acid-containing dual inhibitor from which it was derived.

Development of an α'-hydroxy enone for the aminocatalytic asymmetric formal conjugate addition of aldehydes to acrylates, vinyl ketones and acrolein.

Aminocatalytic asymmetric conjugate addition of aldehydes to Michael acceptors is a well established C-C bond forming methodology. However, various acrylic-type acceptors, including acrylic acid derivatives and acrolein, remain reluctant. Here we demonstrate that the internal H-bonding self-activation in α'-hydroxy enones allows them to react smoothly with enolizable aldehydes using commercially available aminocatalysts to afford adducts in good yields and high enantioselectivity. Straightforward conversion of the ketol moiety of these adducts into aldehyde, ketone and carboxylic acid functionalities offers an indirect, unified entry to products derived from acrolein, alkyl-vinyl ketones and acrylates, respectively.

Coaxial assembly of helical aromatic foldamers by metal coordination.

Deprotonation of acid-terminated helical aromatic foldamers with a mineral base in chlorinated solvents led to their dimerization through the coordination of a metal cation (Li+, Na+, K+, Ag+, or Hg2+) with the terminal carboxylate functions. This new ligation method was applied to oligomerize diacid-functionalized foldamers.

Effect of the Structure of Magnetic Nanocomposite Adsorbents on the Lysozyme Separation Efficiency.

In this study, we prepared various anionic magnetic adsorbents through the carboxyl functionalization of core/shell-structured Fe3O4/SiO2 (FS) particles by either succinic anhydride (FSC), low-molecular-weight (MW 1800) polyacrylic acid (PAA) (FSP1), or high-molecular-weight (MW 100,000) PAA (FSP2), and then, investigated the effect of the structure of adsorbents and operational parameters on their performance for the lysozyme separation. The type and size of functional molecules have significant effects on the surface concentration of functional carboxyl groups onto the adsorbent particles (increase in the order of FSP2 > FSP1 > FSC), and consequently on the adsorption efficiency (AE) (∼100, 98, and 62%, respectively) and adsorption capacity (AC) (∼1000, 980, and 621 mg·g-1, respectively) of the adsorbents. However, the loss of the antibacterial activity of separated lysozyme molecules due to the molecular conformational change increased in the order of FSP2 > FSP1 = FSC, as compared to the free lysozyme. The application of basic buffer solutions for the elution of adsorbed enzyme molecules resulted in more adverse effects on the enzyme activity. The obtained results recommend that FSP1 can be used as a suitable anionic adsorbent for the isolation of positively charged proteins, owing to its high adsorption capacity, excellent reusability, and structural stability, as well as the high purity, structural stability, and activity recovery of the isolated proteins.

Bovine serum albumin-derived poly-l-glutamic acid-functionalized graphene quantum dots embedded UiO-66-NH2 MOFs as a fluorescence ‘On-Off-On’ magic gate for para-aminohippuric acid sensing

Evaluating para-aminohippuric acid (PAH) is emerging as a promising biomarker for the diagnostics of renal disease and other kidney-related illnesses. The present study aims to develop novel bovine serum albumin-derived poly-l-glutamic acid (PLGA) functionalized graphene quantum dots (PLGA-fGQDs) embedded in UiO-66-NH2 metal–organic frameworks (PLGA-fGQDs@UiO-66-NH2 MOFs) for monitoring of PAH. Initially, GQDs were achieved from bovine serum albumin (green precursor) via the single-step hydrothermal method. Here, functionalization with PLGA offers a tremendous increment in optical properties of GQDs. Then, highly luminescent UiO-66-NH2 MOFs were achieved using zirconium tetrachloride (ZrCl4) and 2-Aminoterephthalic acid (2-ATA) as a metal ion source and organic linker. Here, surface modification of GQDs with PLGA offered high quantum yield (QY), and responsiveness. Also, luminous UiO-66-NH2 MOFs afford a wide surface area for decorating of PLGA-fGQDs. The addition of gallium ions (Ga3+) into the probe solution resulted in fluorescence quenching (Turn-Off) whereas the incorporation of PAH resulted in fluorescence recovery (Turn-On). It is because of interaction with carboxylic functionality of PAH to Ga3+ followed by Ga-PAH complex formation. Herein, the wide concentration range and lowest limit of detection (LOD) were found to be 10 ng/mL to 900 ng/mL and 15.88 ng/mL, respectively. The specificity and real-time analysis in artificial urine validated the real-time adoption of a sensor for PAH detection. As well, it demonstrated good intraday/interday precision, stability analysis, and repeatability. In near future, the bundled illuminating PLGA-fGQDs@UiO-66-NH2 MOFs nanoprobe will be an attractive preference for tracking PAH in clinical specimens.

Ni‐Ferrite an efficient catalyst for synthesis of 3‐aryl substituted isoxazole‐5‐carboxylic acids via one‐pot multicomponent reaction

AbstractHere, we have reported an efficient one‐pot, three‐component reaction between various aryl aldehydes, NH2OH.HCl, and propargyl alcohol using Ni‐Fe2O4 as a nanocatalyst. Reactions were performed in ethanol at room temperature to obtain various 3‐aryl substituted isoxazole‐5‐carboxylic acids. The advantage of this protocol is that it formed isoxazole derivatives with free carboxylic acid functionality in one pot, which could transform into various other functional groups. This approach has several merits, including a quick reaction time, a wide range of substrates, excellent product yields, and reusable catalysts.