Amide Function Research Articles

Rhodium‐Catalyzed Additive‐Free C−H Ethoxycarbonylation of (Hetero)Arenes with Diethyl Dicarbonate as a CO Surrogate

AbstractA rhodium‐catalyzed C(sp2)‐H ethoxycarbonylation of indoles and arylpyridines using diethyl dicarbonate was developed. The catalytic process features an additive‐free ethoxycarbonylation reaction, in which only ethanol and CO2 are produced as byproducts, providing a CO‐free and operationally simple protocol. The introduced ethoxycarbonyl group is easily transformed into other ester and amide functionalities in a single step. Moreover, the reaction can be successfully applied on gram scale, and allows for the efficient synthesis of indole‐2‐carboxylic acid esters and isophthalates.

Topology-guided synthesis and construction of amide-functionalized rare-earth metal–organic frameworks

Topology is playing an important role for the reticular chemistry of metal–organic frameworks (MOFs). We herein report two isostructural rare-earth amide-functionalized MOFs by virtue of topology-guided strategy and solvothermal reactions. Both MOFs display the desired (3,8,12)-c pek topological network and encompass dual cage-like and channel pore geometry replete with amide functionality. Low-pressure gas adsorption measurements show that both materials exhibit relatively high surface areas and pore volumes. Moreover, both materials selectively adsorb propylene over ethylene in a wide range of composition as revealed by high C3H6/C2H4 uptake rations and IAST selectivity.

Uniting Amide Synthesis and Activation by PIII/PV-Catalyzed Serial Condensation: Three-Component Assembly of 2-Amidopyridines.

An organophosphorus (PIII/PV redox) catalyzed method for the three-component condensation of amines, carboxylic acids, and pyridine N-oxides to generate 2-amidopyridines via serial dehydration is reported. Whereas amide synthesis and functionalization usually occur under divergent reaction conditions, here a phosphetane catalyst (together with a mild bromenium oxidant and terminal hydrosilane reductant) is shown to drive both steps chemoselectively in an auto-tandem catalytic cascade. The ability to both prepare and functionalize amides under the action of a single organocatalytic reactive intermediate enables new possibilities for the efficient and modular preparation of medicinal targets.

Imidazolium based gemini amphiphiles derived from L-valine. Structural elements and surfactant properties

Imidazolium amphiphiles often display excellent surfactants properties, while amide functionalities and chirality can implement self-assembly. The introduction of these functionalities in imidazolium gemini amphiphiles is expected to allow tuning their aggregation, achieving a higher emulsifying capacity of interest for practical applications. l-valine-derived gemini surfactants have been prepared and their aggregation investigated using NMR, UV-CD, fluorescence, LS or microscopy. The imidazolium gemini amphiphiles synthetized, presented excellent surfactant properties. The aromatic substitution pattern defines additional geometric constrains facilitating a fine tune of their properties, displaying the para-substituted compound best properties. This can be associated to facilitating the required conformational organization of polar and apolar fragments, while reducing coulombic repulsions between imizadolium rings. Two critical aggregation concentrations (CACs) were observed by fluorescence in aqueous media, with the formation of well-defined vesicles in the second step. Dynamic equilibria between aggregates of different sizes seem to be present. These gemini surfactants revealed of interest as emulsifiers for oil/water systems and for controlled fragrance delivery using (R)-limonene as a benchmark volatile compound.

Inheritance of physico-chemical properties and ROS generation by carbon quantum dots derived from pyrolytically carbonized bacterial sources.

Bacteria are frequently used in industrial processes and nutrient supplementation to restore a healthy human microflora, but use of live bacteria is often troublesome. Here, we hypothesize that bacterially-derived carbon-quantum-dots obtained through pyrolytic carbonization inherit physico-chemical properties from probiotic and pathogenic source-bacteria. Carbon-quantum-dots carbonized at reaction-temperatures below 200 ​°C had negligible quantum-yields, while temperatures above 220 ​°C yielded poor water-suspendability. Fourier-transform infrared-spectroscopy demonstrated preservation of amide absorption bands in carbon-quantum-dots derived at intermediate temperatures. X-ray photoelectron-spectroscopy indicated that the at%N in carbon-quantum-dots increased with increasing amounts of protein in source-bacterial surfaces. Carbonization transformed hydrocarbon-like bacterial surface compounds into heterocyclic aromatic-carbon structures, evidenced by a broad infrared absorption band (920-900 ​cm−1) and the presence of carbon in C–C functionalities of carbon-quantum-dots. The chemical composition of bacterially-derived carbon-quantum-dots could be explained by the degradation temperatures of main bacterial cell surface compounds. All carbon-quantum-dots generated reactive-oxygen-species, most notably those derived from probiotic lactobacilli, carrying a high amount of surface protein. Concluding, amide functionalities in carbon-quantum-dots are inherited from surface proteins of source-bacteria, controlling reactive-oxygen-species generation. This paves the way for applications of bacterially-derived carbon-quantum-dots in which reactive-oxygen-species generation is essential, instead of hard-to-use live bacteria, such as in food supplementation or probiotic-assisted antibiotic therapy.

Closing a Calix[6]arene-Based Funnel Zn2+ Complex at Its Large Rim Entrance: Consequences on Metal Ion Affinity and Host-Guest Properties.

A molecular capsule based on a calix[6]arene core closed at the small rim by a three-point coordinated metal ion and at the large rim by a three-point covalent capping is described. It is derived from a trisimidazole funnel complex capped by a trenamide unit that prevents in/out exchange of guest molecules through the large rim. A detailed comparative study with three different calixarenes provides a unique opportunity for (i) comparing the binding ability of two different coordination sites in well three-dimensional (3D)-structured macrocyclic receptors and (ii) evaluating the impact of a covalent closing of one rim of a funnel receptor while the other rim is closed by weaker coordination bonds. Indeed, this study allowed for highlighting various interesting new features. It is first shown that the trenamide site can bind a metal ion such as Zn2+ by itself. This involves a 1:1 coordination of the metal ion to the three carbonyl groups of the amide functions, which undergo trans-to-cis isomerization and are partially embedded in the calix core. When the trisimidazole core is present, the Zn2+ ion preferentially binds at the small rim, thus closing the cavity. Guest ligand exchange must then occur through a decoordination/recoordination process of the metal ion. The modification and rigidification of the calixarene conformation induced by the large rim capping strengthen the metal ion coordination at the small rim. This also leads to a selective metallo-receptor that readily binds EtNH2 under conditions where PrNH2 is not recognized at all. The increased rigidity of the receptor, however, weakens the host-guest interactions, precluding important induced-fit behaviors that are at work in the parent, large rim opened, funnel complex.

Surface Modification of a Graphite Felt Cathode with Amide-Coupling Enhances the Electron Uptake of Rhodobacter sphaeroides

Microbial electrosynthesis (MES) is a promising technology platform for the production of chemicals and fuels from CO2 and external conducting materials (i.e., electrodes). In this system, electroactive microorganisms, called electrotrophs, serve as biocatalysts for cathodic reaction. While several CO2-fixing microorganisms can reduce CO2 to a variety of organic compounds by utilizing electricity as reducing energy, direct extracellular electron uptake is indispensable to achieve highly energy-efficient reaction. In the work reported here, Rhodobacter sphaeroides, a CO2-fixing chemoautotroph and a potential electroactive bacterium, was adopted to perform a cathodic CO2 reduction reaction via MES. To promote direct electron uptake, the graphite felt cathode was modified with a combination of chitosan and carbodiimide compound. Robust biofilm formation promoted by amide functionality between R. sphaeroides and a graphite felt cathode showed significantly higher faradaic efficiency (98.0%) for coulomb to biomass and succinic acid production than those of the bare (34%) and chitosan-modified graphite cathode (77.8%), respectively. The results suggest that cathode modification using a chitosan/carbodiimide composite may facilitate electron utilization by improving direct contact between an electrode and R. sphaeroides.

Electron transfer study on newly synthesized Ti(IV)/Zr(IV) complexes of amide and oxime functionality: A pulse radiolytic and theoretical revelation

Complexes of the general formula Cp 2 Ti(IV)L, Cp 2 Zr(IV)L, Cp 2 Ti(IV)L 1 and Cp 2 Zr(IV)L 1 have been synthesized with N, N’-bis(2-pyridyl)pyridine-2,6-dicarboxamide(H 2 L) and 9, 10-phenanthrenequinone dioxime (H 2 L 1 ). The complexes have been characterized by different spectral techniques and their reduction reactions were carried out with hydrated electron as reducing radical, mechanism has been explored pulse radiolytically. Theoretical calculations have been performed to understand the effect of chelation and electron transfer processes in complexes.

Switching Lysophosphatidylserine G Protein-Coupled Receptor Agonists to Antagonists by Acylation of the Hydrophilic Serine Amine.

Three human G protein-coupled receptors (GPCRs)-GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3-are activated specifically by lysophosphatidylserine (LysoPS), an endogenous hydrolysis product of a cell membrane component, phosphatidylserine (PS). LysoPS consists of l-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages. We previously generated potent and selective GPCR agonists by modification of the three modules and the ester linkage. Here, we show that a novel modification of the hydrophilic serine moiety, that is, N-acylations of the serine amine, converted a GPR174 agonist to potent GPR174 antagonists. Structural exploration of the amide functionality provided access to a range of activities from agonist to partial agonist to antagonist. The present study would provide a new strategy for the development of lysophospholipid receptor antagonists.

Brønsted Acid Mediated Nucleophilic Functionalization of Amides through Stable Amide C−N Bond Cleavage; One‐Step Synthesis of 2‐Substituted Benzothiazoles

AbstractWe have developed a Brønsted acid mediated synthetic method to directly cleave stable amide C−N bonds by a variety of alcohol and amine nucleophiles. Reverse reactivity was observed and alcoholysis of amides by activated primary and secondary benzylic, and propargylic alcohols have been achieved instead of the expected nucleophilic substitution of alcohols. As an application, 2‐substituted benzothiazole derivatives have been synthesized in one pot employing 2‐aminothiophenol as nucleophile.

New Insight into the Fluorescence Quenching of Nitrogen-Containing Carbonaceous Quantum Dots-From Surface Chemistry to Biomedical Applications.

Carbon-based quantum dots are widely suggested as fluorescent carriers of drugs, genes or other bioactive molecules. In this work, we thoroughly examine the easy-to-obtain, biocompatible, nitrogen-containing carbonaceous quantum dots (N-CQDs) with stable fluorescent properties that are resistant to wide-range pH changes. Moreover, we explain the mechanism of fluorescence quenching at extreme pH conditions. Our in vitro results indicate that N-CQDs penetrate the cell membrane; however, fluorescence intensity measured inside the cells was lower than expected from carbonaceous dots extracellular concentration decrease. We studied the mechanism of quenching and identified reduced form of β-nicotinamide adenine dinucleotide (NADH) as one of the intracellular quenchers. We proved it experimentally that the elucidated redox process triggers the efficient reduction of amide functionalities to non-fluorescent amines on carbonaceous dots surface. We determined the 5 nm–wide reactive redox zone around the N-CQD surface. The better understanding of fluorescence quenching will help to accurately quantify and dose the internalized carbonaceous quantum dots for biomedical applications.

PGRP-LB: An Inside View into the Mechanism of the Amidase Reaction.

Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play pivotal functions in insect immunity. Non-catalytic PGRPs are involved in the activation of immune pathways by binding to the peptidoglycan (PGN), whereas amidase PGRPs are capable of cleaving the PGN into non-immunogenic compounds. Drosophila PGRP-LB belongs to the amidase PGRPs and downregulates the immune deficiency (IMD) pathway by cleaving meso-2,6-diaminopimelic (meso-DAP or DAP)-type PGN. While the recognition process is well analyzed for the non-catalytic PGRPs, little is known about the enzymatic mechanism for the amidase PGRPs, despite their essential function in immune homeostasis. Here, we analyzed the specific activity of different isoforms of Drosophila PGRP-LB towards various PGN substrates to understand their specificity and role in Drosophila immunity. We show that these isoforms have similar activity towards the different compounds. To analyze the mechanism of the amidase activity, we performed site directed mutagenesis and solved the X-ray structures of wild-type Drosophila PGRP-LB and its mutants, with one of these structures presenting a protein complexed with the tracheal cytotoxin (TCT), a muropeptide derived from the PGN. Only the Y78F mutation abolished the PGN cleavage while other mutations reduced the activity solely. Together, our findings suggest the dynamic role of the residue Y78 in the amidase mechanism by nucleophilic attack through a water molecule to the carbonyl group of the amide function destabilized by Zn2+.

NSSN-Type Group 4 Metal Complexes in the Ring-Opening Polymerization of l-Lactide.

A new class of zirconium and hafnium complexes coordinated by linear dianonic tetradentate NSSN ligands is reported. The ligands feature two amide functions coupled with two thioether groups linked by a central flexible ethane bridge and two lateral rigid phenylene bridges and differ for the substituents on the aniline nitrogen atoms, i.e., isopropyl, cyclohexyl, or mesityl substituents: NSSN-iPr, NSSN-Cy, or NSSN-Mes. They were prepared by reacting 2-aminothiophenol with dibromoethane to afford the NSSN ligands without substituents on the aniline nitrogen atoms, which were subsequently alkylated through a reductive amination of acetone or cyclohexanone or palladium-catalyzed cross-coupling reaction with mesityl bromide. The corresponding zirconium and hafnium complexes 1-5 were obtained through a transamination reaction between the neutral ligands and Zr(NMe2)4 or Hf(NMe2)4 [(NSSN-iPr)Zr(NMe2)2 (1), (NSSN-Cy)Zr(NMe2)2 (2), (NSSN-Mes)Zr(NMe2)2 (3), (NSSN-iPr)Hf(NMe2)2 (4), and (NSSN-Cy)Hf(NMe2)2 (5)]. They were characterized in solution by NMR spectroscopy and in solid state by X-ray diffraction analysis (except for 3). All complexes present an octahedral coordination geometry with a fac-fac ligand wrapping and a cis relationship between the other two monodentate ligands. The catalytic performances of 1-5 in the ring-opening polymerization of cyclic esters were investigated. Complex 1 was the most active: its polymerization activity was superior to those generally displayed by zirconium complexes featuring OSSO ligands and compared well with those of the most active group 4 complexes operating in a toluene solution.

Reductive Functionalization of Amides in Synthesis and for Modification of Bioactive Compounds.

In this review, applications of the amide reductive functionalization methodology for the synthesis and modification of bioactive compounds are covered. A brief summary of the different protocols is presented in the introduction, followed by the synthetic application of these in late-stage functionalization, leading to known pharmaceuticals or to their derivatives, including bioisosteres, with potential higher activity as the main axis of the article. The synthetic approach to natural products based on amide reduction is also discussed; however, this is given in a condensed form focusing on recent or as yet unexplored applications due to a number of recently published excellent reviews covering this topic. The aim of this review is to illustrate the potential of reductive functionalization of amides as an elegant and useful tool in the synthesis of bioactive compounds and inspire further work in this field.

Advantages of Covalent Immobilization of Metal‐Salophen on Amino‐Functionalized Mesoporous Silica in Terms of Recycling and Catalytic Activity for CO2 Cycloaddition onto Epoxides

AbstractNiII and MnIII Schiff base complexes (Salophen‐Ni and Salophen‐MnCl) bearing a pending carboxylic group were prepared and characterized. Both complexes were grafted onto a mesoporous amino‐functionalized SBA‐15 silica, by formation of an amide function between the propylamine groups of the support and the carboxylic acid functions of the salophen ligand (corresponding respective to 1.30 wt.% of Ni and 1.06 wt.% of Mn). The co‐catalytic behaviour of the free and grafted complexes was then evaluated in the CO2 cycloaddition reaction onto styrene oxide, using tetra‐butylammonium bromide (n−Bu4NBr) as the main catalyst. In homogeneous conditions, the MnIII Schiff base complex and the NiII one, to a lesser extent, behave as efficient co‐catalysts for this reaction (styrene conversion of 100 % and 65 % respectively after 3 h at 120 °C, under 15 bars of CO2). Upon immobilization at the surface of the amino‐functionalized SBA‐15, we showed that the co‐catalytic activity of the less efficient one, i. e. Ni2+ salophen complex, could be enhanced (reaching a full conversion after 7 h), hence highlighting a potential synergistic effect between the unused amine functions of the support and the Ni2+ salophen co‐catalyst. Both salophen complexes were successfully re‐used in homogeneous conditions or after their immobilization without any appreciable loss of activity. This work is only a first step towards a completely heterogeneous catalytic system, in which the tetraalkylammonium halide catalyst and the metal‐salophen co‐catalyst will both be covalently anchored on the same support.

Supramolecular Polymerization of Triarylamine-Based Macrocycles into Electroactive Nanotubes

A S6-symmetric triarylamine-based macrocycle (i.e., hexaaza[16]paracyclophane), decorated with six lateral amide functions, is synthesized by a convergent and modular strategy. This macrocycle is shown to undergo supramolecular polymerization in o-dichlorobenzene, and its nanotubular structure is elucidated by a combination of spectroscopy and microscopy techniques, together with X-ray scattering and molecular modeling. Upon sequential oxidation, a spectroelectrochemical analysis of the supramolecular polymer suggests an extended electronic delocalization of charge carriers both within the macrocycles (through bond) and between the macrocycles along the stacking direction (through space).

Enantioselective Catalytic C-H Amidations: An Highlight

The crucial role played by compounds bearing amide functions, not only in biological processes but also in several fields of chemistry, life polymers and material sciences, has brought about many significant discoveries and innovative approaches for their chemical synthesis. Indeed, a plethora of strategies has been developed to reach such moieties. Amides within chiral molecules are often associated with biological activity especially in life sciences and medicinal chemistry. In most of these cases, their synthesis requires extensive rethinking methodologies. In the very last years (2019–2020), enantioselective C-H functionalization has appeared as a straightforward alternative to reach chiral amides. Therein, an overview on these transformations within this timeframe is going to be given.

Synthesis, molecular modeling and biological evaluations of novel pyrrolidine derivatives as potential cyclooxygenase-2 (COX-2) inhibitors

Toward the development of selective cyclooxygenase-2 inhibitors, a series of pyrrolidine derivatives is described. All the compounds containing sulfonamide, ester, nitrile, acid, amide and urea functionalities were computationally screened, and binding affinity scores for all synthesized compounds with cyclooxygenase-1 and cyclooxygenase -2 were compared. The computational observations showed three top-ranked compounds (8b, 8d and 10a) having selectively more affinity for cyclooxygenase -2. These were selected for pharmacological evaluation using carrageenan-induced rat paw edema model. Compound 8b showed maximum activity (54.83%) which was closer to standard drug indometacin (57.48%). The safety parameter of the potent compound (8b) was assessed using aspirin induced gastric ulceration animal model.

Green synthesis, in vivo and in vitro pharmacological studies of Tamarindus indica based gold nanoparticles.

The current investigation aims to synthesize gold nanoparticles (AuNPs) from aqueous extract of Tamarindus indica and to evaluate the in vitro anti-bacterial and in vivo sedative and anelgescic activities of crude extract as well as synthesized AuNPs. Several methods have been reported to synthesize AuNPs; however, most of them were not ecofriendly. In the present study, the green synthesis of AuNPs has been carried out. Using the green synthesis method, AuNPs of T. indica were synthesized at room temperature (25°C) by mixing 5mL of HAuCl4 (1mM) with 1mL of T. indica seed extract solution. This extract solution was prepared by taking 5 gm dry seeds in 100mL of double deionized water with continuous stirring for up to 24h at 80°C. The stability of AuNPs was confirmed with the help of relevant experimental techniques including ultraviolet-visible (UV/Vis) showing maximum absorbance at 535-540nm, Fourier transform infrared showing a broad signal at 3464cm-1 which can be attributed to either amide or hydroxyl functionalities and atomic force microscopy analysis showed that the biomaterial surrounding AuNPs was agglomerated which proves the formation of discrete nanostructutres. These AuNPs have been evaluated for their antibacterial potential. The results revealed good antibacterial activity of the samples against. Klebsiella pneumonia, Bacillus subtilis and Staphylococcus epidermidis with 10-12mm zone of inhibition range. The AuNPs were also found stable at high temperature, over a range of pH and in 1mM salt solution. Moreover, the crude extract and respective AuNPs also exhibited interesting sedative and analgesic activities. Hence, we focused on phytochemicals-mediated synthesis of AuNPs considered as greatest attention in the treatment of anti-bacterial, analgesic, and sedative.

Multifunctional Isosteric Pyridine Analogs-Based 2-Aminothiazole: Design, Synthesis, and Potential Phosphodiesterase-5 Inhibitory Activity.

The elaboration of new small molecules that target phosphodiesterase enzymes (PDEs), especially those of type 5 (PDE5), is an interesting and emerging topic nowadays. A new series of heterocycle-based aminothiazoles were designed and synthesized from the key intermediate, 3-oxo-N-(thiazol-2-yl)butanamide (a PDE5 inhibitor that retains its amidic function), as an essential pharmacophoric moiety. The PDE5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thereby causing severe hypotension as a marked side effect. Hence, an in vivo testing of the target compounds was conducted to verify its relation with arterial blood pressure. Utilizing sildenafil as the reference drug, Compounds 5, 10a, and 11b achieved 100% inhibitions of PDE5 without significantly lowering the mean arterial blood pressures (115.95 ± 2.91, 110.3 ± 2.84, and 78.3 ± 2.57, respectively). The molecular docking study revealed that the tested compounds exhibited docking poses that were similar to that of sildenafil (exploiting the amide functionality that interacted with GLN:817:A). The molecular shape and electrostatic similarity revealed a comparable physically achievable electrostatic potential with the reference drug, sildenafil. Therefore, these concomitant results revealed that the tested compounds exerted sildenafil-like inhibitory effects (although without its known drawbacks) on blood circulation, thus suggesting that the tested compounds might represent a cornerstone of beneficial drug candidates for the safe treatment for erectile dysfunction.