Amido Group Research Articles

Base Modifications of Nucleosides via the Use of Peptide-Coupling Agents, and Beyond.

Several naturally occurring purine and pyrimidine nucleosides contain an amide linkage as part of the heterocyclic aglycone. Enolization of the amide and conversion to leaving groups at the amide carbon atom permits base modification by addition-elimination types of processes. Although a number of methods have been developed over the years for accomplishing such conversions, the present Personal Account describes efforts from the Lakshman laboratories. Facile activation of the amido groups in nucleobases can be achieved with peptide-coupling agents. Subsequent reaction with nucleophiles then accomplishes the base modifications. In many cases, the activation and displacement steps can be done as two-step, one-pot processes, whereas in other cases, discrete storable activated nucleosides can be isolated for subsequent displacement reactions. Using such an approach a wide range of nucleoside base modifications is readily achievable. In many instances, mechanistic investigations have been conducted so as to understand the activation process.

Synthesis, insecticidal activity, and mode of action of novel imidazopyridine mesoionic derivatives containing an amido group

In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. The bioassay results demonstrated that most of the target compounds had moderate-to-good insecticidal activity against Sogatella furcifera, and some exhibited good-to-excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S.furcifera and A.craccivora, with LC50 values of 10.5 and 2.09 μg mL-1 , respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system-related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real-time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the α4 and β1 subunits of this receptor. The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode-of-action of imidazopyridine mesoionic derivatives. © 2022 Society of Chemical Industry.

Hydroaminoalkylation of alkenes using transition metals complexes grafted on silica SBA15 as catalysts

The gas-phase hydroaminoalkylation reaction of propene catalyzed by group 4 (M = Ti, Zr and Hf) metal amido complexes [(≡Si–O-)(M(-NMe2)3] was investigated by using PBE0-D3/SVP//TZVP level of theory. The geometrical analysis traced the formation of the metallaaziridines and the azametallacyclopentanes as key intermediates in these reactions. The metallaaziridines were simulated through the activation of α-C-H bonds of the amido groups; while the azametallacyclopentanes were configured by slotting the propene double bond onto the M − C bonds of the metallaaziridines. The latter reaction was considered the rate-determining step. Thermochemical calculations showed that the order of catalytic activity is: Ti ≥ Zr > Hf; while the preference of the azametallacyclopentanes is: Hf > Zr ≥ Ti.

Migrative Carbofluorination of Saturated Amides Enabled by Pd-Based Dyotropic Rearrangement

Directly editing an all-carbon quaternary carbon itself of nonstrained acyclic molecules remains underexploited despite the recent advances in the fields of both C-H and C-C bond activation. Herein, we report a palladium-catalyzed migrative carbofluorination of saturated amides enabled by the activation of both the C(sp3)-H and the Cquaternary-Cσ bonds. In this transformation, the α-quaternary carbon of Weinreb amides is converted to α-tertiary fluoride with concurrent migration of an aryl or an amido group from the α- to β-carbon. DFT calculations indicate that the dyotropic rearrangement proceeds through an unusual anti-selective [2.1.0] bicyclic transition state. The reaction, compatible with a broad range of functional groups, is stereospecific and is applicable to the synthesis of enantioenriched products.

Catalytic addition reactions of amines, thiols, and diphenyl‐phosphine oxides to heterocumulenes using a bridging Sulfonylimido titanium(IV) complex

AbstractWe present here an efficient method for hydroelementation reactions such as hydroamination, hydrothiolation, and hydrophosphorylation of the heterocumulenes carbodiimides, aryl isocyanates, and isothiocyanates with anilines or thiophenols using a p‐tolylsulfonylimide‐supported dinuclear titanium complex. All the reactions were achieved in excellent yield under mild conditions and within a short reaction time. The products were isolated and fully characterized by spectroscopic techniques. We also propose a mechanism involving the proton abstraction (of the E−H of anilines or thiophenols) in the first step. In the reaction mechanism, the amido groups of the binuclear TiIV complex act as the leaving group whereas the sulfonylimide linkage remains unaffected.

Diverse Effects of Amino Acids on Monascus Pigments Biosynthesis in Monascus purpureus.

Amino acids could act as nitrogen sources, amido group donors, or bioactive molecules in fungi fermentation, and consequently, play important roles in Monascus pigments (MPs) biosynthesis. But the understanding of the effects of various amino acids on MPs biosynthesis is still incomprehensive. In this work, 20 free amino acids were added to the fermentation medium to evaluate their effects on MPs biosynthesis in Monascus purpureus RP2. Six amino acids, namely, histidine (HIS), lysine (LYS), tyrosine (TYR), phenylalanine (PHE), methionine (MET), and cysteine (CYS), were selected as the valuable ones as they exerted significant effects on the production yield and even on the biosynthesis metabolic curves of MPs. Moreover, the dose-dependent and synergistic effects of valuable amino acids on MPs biosynthesis were observed by tests of serial concentrations and different combinations. In addition, it revealed that HIS and MET were the prominent amino acids with dominant and universal influences on MPs biosynthesis. The analog compounds of HIS (amitrole) and MET [calcium 2-hydroxy-4-(methylthio)] were added to the fermentation medium, and the results further confirmed the extraordinary effects of HIS and MET and their analogs on MPs biosynthesis. Furthermore, the gene transcription profile indicated that a differential expression pattern was observed in the polyketide synthase (PKS) cluster responsible for MPs biosynthesis in response to HIS and MET, revealing that they could oppositely regulate MPs biosynthesis in different ways. These findings would benefit the understanding of MPs biosynthesis regulation mechanism in M. purpureus and contribute to the industrial production of MPs by fermentation.

Chemical approaches towards installation of rare functional groups in bacterial surface glycans.

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.

Bioinspired Di-Fe Complexes: Correlating Structure and Proton Transfer over Four Oxidation States.

Metalloproteins with active sites containing di-Fe cores exhibit diverse chemical reactivity that is linked to the precise transfer of protons and electrons which directly involve the di-Fe units. The redox conversions are commonly corroborated by spectroscopic methods, but the associated structural changes are often difficult to assess, particularly those related to proton movements. This report describes the development of di-Fe complexes in which the movements of protons and electrons are pinpointed during the stepwise oxidation of a di-FeII species to one with an FeIIIFeIV core. Complex formation was promoted using the phosphinic amido tripodal ligand [poat]3- (N,N',N″-[nitrilotris(ethane-2,1-diyl)]tris(P,P-diphenylphosphinic amido)) that provided dynamic coordination spheres that assisted in regulating both electron and proton transfer processes. Oxidation of an [FeII-(μ-OH)-FeIII] complex led to the corresponding di-FeIII species containing a hydroxido bridge that was not stable at room temperature and converted to a species containing an oxido bridging ligand and protonation of one phosphinic amido group to form [Hpoat]2-. Deprotonation led to a new species with an [FeIII-(μ-O)-FeIII] core that could be further oxidized to its FeIIIFeIV analogue. Reactions with phenols suggest homolytic cleavage of the O-H bond to give products that are consistent with the initial formation of a phenoxyl radical─spectroscopic studies indicated that the electron is transferred to the FeIV center, and the proton is initially transferred to the more sterically hindered oxido ligand but then relocates to [poat]3-. These findings offer new mechanistic insights related to the stability of and the reactions performed by di-Fe enzymes.

Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases.

We examined the ability of two human cytosolic transaminases, aspartate aminotransferase (GOT1) and alanine aminotransferase (GPT), to transform their preferred substrates whilst discriminating against similar metabolites. This offers an opportunity to survey our current understanding of enzyme selectivity and specificity in a biological context. Substrate selectivity can be quantitated based on the ratio of the kcat/KM values for two alternative substrates (the ‘discrimination index’). After assessing the advantages, implications and limits of this index, we analyzed the reactions of GOT1 and GPT with alternative substrates that are metabolically available and show limited structural differences with respect to the preferred substrates. The transaminases’ observed selectivities were remarkably high. In particular, GOT1 reacted ~106-fold less efficiently when the side-chain carboxylate of the ’physiological’ substrates (aspartate and glutamate) was replaced by an amido group (asparagine and glutamine). This represents a current empirical limit of discrimination associated with this chemical difference. The structural basis of GOT1 selectivity was addressed through substrate docking simulations, which highlighted the importance of electrostatic interactions and proper substrate positioning in the active site. We briefly discuss the biological implications of these results and the possibility of using kcat/KM values to derive a global measure of enzyme specificity.

Property and Structure Characterization of High Molecular Weight Polyacrylonitrile Polymers Initiated by 2,2'-Azobis (2-methyl propionamide) Dihydrochloride Using Aqueous Deposited Polymerization Technique

Powdery high molecular weight polyacrylonitrile (HMW-PAN) polymers were successfully synthesized by aqueous deposited polymerization (ADP) method with 2,2'-azobis (2-methyl propionamide) dihydrochloride (AIBA) as the initiator and itaconic acid (IA) as comonomer. The utilization of IA into the ADP system was conducive to relax the proceeding of thermo-oxidation process. Differential scanning calorimeter (DSC) curves of obtained PAN copolymers showed the doublet peaks character under air atmosphere, attributing to the exothermic cyclization and oxidative reactions during heat-treatment process. With the utilization of IA in the reaction system, crystallinity and grain sizes of the PAN polymers decreased. The stretching vibration of nitrile group (C≡N) at 2240cm-1 was the strongest peak in both Fourier transform infrared spectra (FTIR). And the stretching vibration and bending of CH2 were the stronger peaks in FTIR. Amido group (NH2), carbonyl group (C=O) and C-O single bond existed in FTIR of PAN homopolymer and copolymers, indicating occurrence of C≡N hydrolysis during polymerization process except carboxyl group (COOH) introduced by IA.

Novel Synthesized Cationic Gemini Surfactants Bearing Amido Group and Their Application in Nanotechonoly

Novel Synthesized Cationic Gemini Surfactants Bearing Amido Group and Their Application in Nanotechonoly

Improvement of the biodegradability of diatrizoate by electroreduction of its amido groups

The occurrence of iodine X-ray contrast media (ICM) in the environment is a global concern since they can be transformed into toxic compounds during water disinfection process. Among the different approaches that have been tested to degrade them, electroreduction offers the advantages to be selective, targeting in a cost-effective way the functional groups responsible for ICM biorecalcitrance and allowing the recovery of iodide ions. We have previously shown that total deiodination of diatrizoate, a highly biorecalcitrant ICM, did not lead to a significant enhancement of its biodegradability. In this work, the electroreduction of amido groups of diatrizoate was attempted to further improve its biodegradability. Electrolyses of diatrizoate and its deiodinated derivative, were investigated in neutral and acidic medium. A total deiodination of diatrizoate was rapidly achieved in both media along with a slower reduction of the amido groups, as shown by LC-MS/MS analysis of by-products. The biodegradability of the solutions was estimated by the evaluation of the BOD5/COD ratio. Results show that it was improved after the electroreduction performed in acidic medium. This result was confirmed by a biological treatment on activated sludge over a 21 days period, leading to mineralization yields of 46% and 68% for diatrizoate and 3,5-diacetamidobenzoic acid, respectively, after the electroreduction process.

Sulfonyl and Carbonyl Groups in MSTC Effectively Improve the Performance and Stability of Perovskite Solar Cells

Intrinsic defects are key factors that would affect the performance and stability of perovskite solar cells (PSCs). Herein, a sulfonamides additive, methyl 3‐sulfamoyl‐2‐thiophenecarboxylate (MSTC), is introduced into the PbI2 or FAI/MACl/MABr precursor solution, to prepare high‐quality PSCs with a two‐step method. After the addition of MSTC, all the devices show enhanced performance. With optimized MSTC incorporated into PSCs, the champion power conversion efficiency (PCE) of the PSCs is increased from 19.19% to 22.14%, and the stability is also improved. The MSTC‐FAI based device can still maintain 89% of its initial PCE compared to 68% of the control one after 15 days in ambient condition under relative humidity of 40–50% at room temperature in dark. Test results reveal that amido group in MSTC would coordinate with PbI2 or FAI through hydrogen bonding (NH···I), thus effectively enhancing the performance of devices. Nevertheless, the sulfonyl and carbonyl groups in MSTC would coordinate with the FAI precursor through chemical bond of COS and COC. And with the hydrogen bonding connection between MSTC and FAI, the inherent defects in the MSTC‐FAI based device are effectively suppressed, leading to the enhanced photovoltaic performance.

Fabrication and application of icephobic silicone coatings on epoxy substrate

In winter, when the trains run at high speed, snow that falls on the track is easily drawn onto the bottom of the train, and quickly forms ice. Such icing may cause serious safety issues. In this paper, the epoxy resin is used as a primary coat and a hydroxyl-terminated silicone oil (PDMS) was coated on it. Siloxane, with amido or epoxy terminal group, named KH 550 or KH 560, respectively, was used as a co-crosslinking agent of the epoxy and PDMS in order to ensure high adhesive strength between the two layers. The hydrophobic, icephobic and mechanical properties of the coatings were characterized by contact angle measurements, ice-adhesion tests and tensile tests, respectively. The results show that the contact angle of the PDMS coating crosslinked by the KH 550 reaches 114.1°, and it can still show good hydrophobic properties after being immersed in water for 10 days. The adhesive strength of the ice on the PDMS coating is only 2.5% of that of ice on the epoxy coating. The low surface energy and the low elastic modulus should be responsible for the excellent icephobic properties. Moreover, the bonding force between the PDMS coating and the epoxy primer is also excellent. When the KH 560 was used as the co-crosslinking agent, the hydrophobic and icephobic properties of the top PDMS coating were improved due to its week polarity compared with KH 550. This study will be helpful in resolving the problems associated with the running of high speed trains in winter or the electric power system which requires resistance to freezing rain.

Cationic Carbene Analogues: Donor-Free Phosphenium and Arsenium Ions.

Carbenes and their analogues have constantly enthralled chemists with their intriguing reactivity of ambiphilic character stemming from their electronic structures. Phosphenium and arsenium ions are fiercely reactive cationic species, the stabilization of which has been so far achieved in the condensed phase by dispersing the positive charge through electromeric conjugation with at least one electron‐rich substituent (frequently amido groups). Although observed in the gas phase, the isolation of dicoordinate phosphenium and arsenium ions lacking such stabilizing ligands has eluded chemists for decades. Herein we show that by judicious choice of aromatic substituents, dicoordinate, donor‐free, Lewis‐superacidic phosphenium and arsenium ions can be kinetically stabilized. They feature singlet electronic ground states possessing a vacant p‐orbital and an electron lone pair with predominantly s‐character.

Electrochemical Oxidation Dearomatization of Anisol Derivatives toward Spiropyrrolidines and Spirolactones

Spiro compounds are widely prevalent in biological activities and natural products. However, developing new strategies for their efficient synthesis and derivatization remains a challenge. Outstand...

Mechanism-Guided Development of Transition-Metal-Catalyzed C-N Bond-Forming Reactions Using Dioxazolones as the Versatile Amidating Source.

Catalytic reactions that construct carbon-nitrogen bonds are one of central themes in both synthetic and medicinal chemistry since the obtainable nitrogen-containing motifs are commonly encountered in natural products and have also seen a growing prominence as key structural features in marketed drugs and preclinical candidates. Pd-catalyzed cross-couplings, such as Buchwald-Hartwig amination, are at the forefront of such synthetic methods in practical settings. However, they require prefunctionalized substrates such as (hetero)aryl halides that must be prepared independently, often by multiple operations. One emerging way to circumvent these preparatory steps and directly convert ubiquitous C-H bonds into valuable C-N bonds is catalytic C-H amination, which allows synthetic chemists to devise shorter and more efficient retrosynthetic schemes. The past two decades have witnessed considerable progress in expanding the repertoire of this strategy, especially by identifying effective amino group precursors. In this context, dioxazolones have experienced a dramatic resurgence in recent years as a versatile nitrogen source in combination with transition-metal catalyst systems that facilitate decarboxylation to access key metal-acylnitrenoid intermediates. In addition to their high robustness and easy accessibility from abundant carboxylic acids, the unique reactivity of the transient intermediates in the amido group transfer has led to a fruitful journey for mild and efficient C-H amidation reactions.This Account summarizes our recent contributions to the development of C-N bond-forming reactions using dioxazolones as effective nitrenoid precursors, which are categorized into two subsets according to their mechanistic differences: inner- versus outer-sphere pathways. The first section describes how we could unveil the synthetic potential of dioxazolones in the realm of the inner-sphere C-H amidation, where we demonstrated that dioxazolones serve not only as manageable alternatives to acyl azides but also as highly efficient reagents to significantly reduce the catalyst loading and temperature. Taking advantage of the mild conditions in combination with group 9 Cp*M complexes (M = Rh, Ir, Co) or isoelectronic Ru species, we have dramatically expanded the accessible synthetic scope. Mechanistic investigations revealed that the putative metal-nitrenoid species is involved as a key intermediate during catalysis, which leads to facile C-N bond formation. On the basis of the mechanistic underpinning, we have succeeded in developing novel catalytic platforms that harness the intermediacy of metal-nitrenoids to explore C-H insertion chemistry via an outer-sphere pathway. Indeed, the tailored catalysts were capable of suppressing the competitive Curtius-type decomposition, thus granting access to versatile lactam products. We have further repurposed the catalytic systems upon modification of chelating ligands and also the identity of the transition metal to achieve three goals: (i) addressing selectivity issues to control the regio-, chemo-, and enantioselectivities, (ii) developing sustainable catalysis by first-low metals, and (iii) navigating chemical space for (di)functionalization of alkenes/alkynes. Together with our own research efforts, highlighted herein are some important relevant advances by other groups. We finally conclude with a brief overview with an eye toward further developments.

Optimizing Protein-Glutaminase Expression in Bacillus subtilis.

Protein-glutaminase (PG) is a promising protein deaminase. It only hydrolyzes the side chain amido groups of protein-bound to generate ammonia and protein-L-glutamic acid and does not catalyze any other undesirable changes in protein structures. Deamidation of proteins via PG can influence the solubility, emulsification, foaming, and gelation properties of proteins, which are important properties for some food proteins. Therefore, there is great potential for the application of PG in the food industry. PG is derived from Chryseobacterium proteolyticum (C. proteolyticum); however, wild strains are difficult to industrialize because of their low levels of enzyme production. In this article, we studied different strategies for PG expression in B. subtilis. Results showed that PG produced from C. proteolyticum could be successfully secreted in B. subtilis WB800N, and actively secreted in B. subtilis 168(BS168) or DB403 containing a pro-peptide (pro-PG). The secreted PG from B. subtilis WB800N was inactive unless digested by exogenous proteases, such as trypsin, alkaline protease, and neutral protease. However, active PG was secreted by the self-processing of BS168 and DB403. The specific activity of purified PG reached 20.9 U/mg. PG showed maximum activity at pH 5.5, 55°C and more than 80% of PG activity was retained within a range of pH 3.5-6.5. When Cbz-Gln-Gly was used as the substrate, PG activity was 31.1 ± 0.9μMmin-1mg-1. Mg2+, Ca2+, and Zn2+ stabilized and even activated PG activity. These strategies concerning PG expression in B. subtilis and the enzymatic properties of PG provide efficient alternatives for PG research and contribute to the industrial-scale production of PG.

Novel asymmetrical bis-surfactants with naphthalene and two amide groups: Synthesis, foamability and foam stability

A series of novel asymmetrical bis-surfactants (CnNCS, n = 10, 12, 14, 16), comprising a naphthalene group and a long chain hydrocarbon (as hydrophobic moieties), a quaternary ammonium group, one ether group and double amides (as hydrophilic moieties), and ethylidene as linkage groups, were designed, prepared, and characterized through proton and carbon nuclear magnetic resonance, Fourier-transform infrared, and electrospray ionization mass spectrometry analyses. The surface activity was studied by surface tension measurements. CnNCS exhibited low critical micelle concentrations (0.708–0.004 mmol L−1) and excellent surface tension reducing abilities. Moreover, the introduction of naphthyl and amido groups into C12NCS significantly enhanced the foamability and foam stability. This is attributed mainly to cooperative noncovalent interactions such as hydrophobic interactions of the long chain hydrocarbons, π-π stacking of the naphthyl groups, hydrogen-bonding of the amido groups of C12NCS itself and hydrogen bonding of C12NCS with water, and electrostatic interaction, which induced a decrease in the surface tension, leading to a compact and dense arrangement of the C12NCS molecules at the air–water interface to form a tight film. Both features enabled foam formation, slowed liquid drainage from the foam, and prevented the gas from diffusing through the monolayer, thus enhancing the foam stability. In addition, the long-acting emulsifying ability of C12NCS and good antibacterial activity of CnNCS were also demonstrated. Moreover, hydrogen-bonding of the amido groups and π-π stacking of the naphthyl groups of CnNCS were verified from the 1H NMR and fluorescence spectra, respectively. This work provides a feasible strategy for the synthesis of highly efficient foaming, emulsifying, and bacteriostatic agents.

Investigation of iron-ammine and amido complexes within a C3-symmetrical phosphinic amido tripodal ligand.

The primary and secondary coordination spheres can have large regulatory effects on the properties of metal complexes. To examine their influences on the properties of monomeric Fe complexes, the tripodal ligand containing phosphinic amido groups, N,N',N''-[nitrilotris(ethane-2,1-diyl)]tris(P,P-diphenylphosphinic amido) ([poat]3-), was used to prepare [FeII/IIIpoat]-/0 complexes. The FeII complex was four-coordinate with 4 N-atom donors comprising the primary coordination sphere. The FeIII complex was six-coordinate with two additional ligands coming from coordination of O-atom donors on two of the phosphinic amido groups in [poat]3-. In the crystalline phase, each complex was part of a cluster containing potassium ions in which KO[double bond, length as m-dash]P interactions served to connect two metal complexes. The [FeII/IIIpoat]-/0 complexes bound an NH3 molecule to form trigonal bipyramidal structures that also formed three intramolecular hydrogen bonds between the ammine ligand and the O[double bond, length as m-dash]P units of [poat]3-. The relatively negative one-electron redox potential of -1.21 V vs. [FeIII/IICp2]+/0 is attributed to the phosphinic amido group of the [poat]3- ligand. Attempts to form the FeIII-amido complex via deprotonation were not conclusive but isolation of [FeIIIpoat(NHtol)]- using the p-toluidine anion was successful, allowing for the full characterization of this complex.