Formamide Research Articles

Halogen-bonding-mediated synthesis of amides and peptides

We report the first methods for halogen-bonding-mediated formation of amide and peptide bonds. The methods can be used to synthesize not only amides but also dipeptides, tripeptides and pentapeptides in good to excellent yields without racemization.

Amine protection by in situ formation of choline chloride-based deep eutectic solvents

Protection of amine groups by amide formation is still among the preferred strategies for multifunctional molecular synthesis despite its waste production, especially the enormous quantities of organic solvents used.

Three-step process for the synthesis of favipiravir

A three-step process has been developed for the synthesis of antiviral drug favipiravir (T-705) starting from a readily available ethylenediamine and diethyl 2-oxomalonate. The synthesis involves the formation of ethyl 3-hydroxypyrazine-2-carboxylate by direct condensation of ethylenediamine with diethyl 2-oxomalonate followed by amide formation and electrophilic fluorination. This approach not only consists of three steps but also ensures the usage of inexpensive and easily available starting materials. It is an alternative process that can replace bromination or nitration, POCl3 etc that are used in previous methods.

The fabrication of N-doped carbon dots by methionine and their utility in sensing Cu2+ in real water.

Copper ions (Cu2+) are ubiquitous in the ecosystem and cause serious environmental pollution, posing a threat to human health. Therefore, sensitive detection of Cu2+ is urgently needed. Herein, we employed a solvothermal method to prepare blue-emitting carbon dots (Met-CDs) using formamide (FA) and methionine (Met) as precursors, with a high quantum yield (QY) of 38%. Based on the good optical stability of Met-CDs and selective quenching by Cu2+, a sensitive probe using Met-CDs for the detection of Cu2+ in water was successfully designed. Within the linear range of 0.15-2 μM, the limit of detection (LOD) was determined to be as low as 47.7 nM, enabling the quantitative detection of Cu2+. Moreover, the recovery data of the spiked analysis of lake/river water samples were also satisfactory and verified the feasibility of the probe by the analysis of Cu2+ in natural conditions.

Supramolecular intermediates in thermo-mechanochemical direct amidations.

We present a solvent-free thermo-mechanochemical approach for the direct coupling of carboxylic acids and amines, which avoids activators and additives. Detailed analysis of the reactions by ex situ and in situ monitoring methods led to the observation, isolation, and characterisation of multicomponent crystalline intermediates that precede the formation of amides. We applied our methodology for the quantitative synthesis of the active pharmaceutical ingredient moclobemide.

Research Progress in Niacinamide in the Prevention and Treatment of Mouth and Systemic Diseases

Nicotinamide (NAM) is the amide form of niacin and one of the precursors of nicotinamide adenine dinucleotide (NAD +). NAM can be used as a dietary supplement or clinical therapeutic drug to replenish NAD + levels in the human body and participate in key bodily functions such as cellular metabolism and DNA repair. NAM has the advantage of low cost, wide availability, and sound biosafety. It also has multiple biological functions, including antibacterial effect, anti-inflammatory effect, and modulation of cellular immunity, producing significant ameliorative effects on skin and neurodegenerative diseases. However, most studies on NAM are still at the laboratory stage. Herein we reviewed the role and mechanism of NAM in the prevention and treatment of oral and systemic diseases, explored its potential as clinical therapeutic medication, provided some basis and references for the clinical application of nicotinamide in the prevention and treatment of various diseases, and discussed its prospects for future research and application.

PS-BPB09-2: DEVELOPMENT OF LONG-ACTING HUMAN ADRENOMEDULLIN FC FUSION PROTEINS

Background: Human adrenomedullin (hAM) is a hypotensive peptide hormone with strong anti-inflammatory effects. AM consists of 52 amino acid residues with an amidated C-terminus and a ring structure formed by intramolecular disulfide bonds. Both of these structures are necessary for binding to receptors and to exert their biological functions. AM has also shown therapeutic effects in various animal disease models, including inflammatory bowel disease, ischemic heart disease, sepsis and stroke. However, the short half-life of native AM in the blood required continuous administration for treatment. To solve this, we have developed four human IgG1 and IgG4 Fc fusion proteins containing full-length human AM or AM(6–52). Methods: Recombinant Fc-AM derivatives were generated using mammalian cells. After that, we tested the biological activities of Fc-fusion AMs (Fc-AMs) to stimulate the intracellular accumulation of cAMP in HEK-293 cells stably expressing the AM1 receptor. Next, we compared IgG1-AM (6–52) and IgG4-AM (6–52) concentrations in the peripheral blood and tissues of rats after subcutaneous injection. In addition, the antihypertensive effect of Fc-AM was examined on spontaneously hypertensive rats (SHRs) which were given high salt diets. Results: We have developed four Fc-AMs, which are long-acting AM derivatives in mammalian cells. Fc-AMs produced in mammalian cells do not require refolding or amidation. Indeed, Fc-AMs could be measured by mAM assay, which recognizes the amidated form, indicating that Fc-AMs produced in mammalian cells were amidated. Fc-AMs, generated in a mammalian cell production system can therefore easily be produced in large amounts with few purification steps. The Fc-AMs stimulated intracellular cAMP production in cultured cells stably expressing the AM type I receptor in vitro. Fc-AM (6–52) induced higher cAMP levels for the receptor than Fc-AM. The pharmacokinetic study was performed using N-terminal deficient AM derivatives, which have strong receptor binding ability. Sufficient concentrations of IgG1-AM (6–52) and IgG4-AM (6–52) were observed in blood 14 days after a single subcutaneous administration. Tissue transfer to the kidney and small intestine was observed after administration of IgG1-AM (6–52) or IgG4-AM (6–52) to rats. In addition, the single subcutaneous administration of IgG4-AM (6–52) suppressed the increase in blood pressure in SHRs which were loaded with high salt diets. Conclusion: Fc-AM produced from mammalian cells is easily prepared and seems to be an effective new therapeutic agent for hypertension.

Effects of various nitrogen fertilizers and the Extrasol biopreparation on the quality of garden strawberry (Fragaria×ananassa Duch.) at fertigation with drip irrigation on soddy podzolic soils

Current approaches to land use and agricultural production are increasingly aimed at achieving high productivity through the use of crop rotation, siderites, integrated plant protection, minimized soil cultivation, microbiological fertilizers, and biological preparations. Modern microbiological preparations enhance the uptake of nitrogen and ash elements by plants, improving the rhizosphere of plants and the quality of strawberry fruit. Aim. To establish the effect of Extrasol applied using drip irrigation and various forms of mineral nitrogen fertilizers on the chemical composition of leaves and fruit of garden strawberry.Materials and methods. Garden strawberry plants of the Rusich and Troitskaya cultivars were treated with Extrasol and mineral fertilizers. Experiments were carried out in 2017–2020 at open-ground plots of the Federal Horticultural Center for Breeding, Agrotechnology and Nursery (Moscow Oblast). The experimental plots were characterized by soddy podzolic soils of medium-loam granulometric composition. Plant samples were analyzed using conventional methods. The experimental scheme consisted in the application of various nitrogen fertilizers (ammonium nitrate, urea, and ammonium sulfate) either in combination (2 mL/L of the working solution) or without Extrasol. Conclusions. In strawberry cv. Rusich, the use of ammonium nitrate increased the calcium content in plant leaves and decreased its content in fruit, which negatively affected the crop quality. Mineral fertilizers applied in combination with Extrasol increased the nitrogen content in leaves and fruit. The combined use of the amide form of nitrogen (urea) and Extrasol adversely affected the level of nitrates in cv. Troitskaya fruit. The use of fertigation and Extrasol reduced the amount of soluble dry substances in strawberry fruit.

Tricyclic Fused Lactams by Mukaiyama Cyclisation of Phthalimides and Evaluation of their Biological Activity.

We report that phthalimides may be cyclized using a Mukaiyama-type aldol coupling to give variously substituted fused lactam (1,2,3,9b-tetrahydro-5H-pyrrolo[2,1-a]isoindol-5-one) systems. This novel process shows a high level of regioselectivity for o-substituted phthalimides, dictated by steric and electronic factors, but not for m-substituted phthalimides. The initial aldol adduct is prone to elimination, giving 2,3-dihydro-5H-pyrrolo[2,1-a]isoindol-5-ones, and the initial cyclisation can be conducted in such a way that aldol cyclisation-elimination is achievable in a one-pot approach. The 2,3-dihydro-5H-pyrrolo[2,1-a]isoindol-5-ones possess cross conjugation and steric effects which significantly influence the reactivity of several functional groups, but conditions suitable for epoxidation, ester hydrolysis and amide formation, and reduction, which provide for ring manipulation, were identified. Many of the derived lactam systems, and especially the eliminated systems, show low solubility, which compromises biological activity, although in some cases, antibacterial and cytotoxic activity was found, and this new class of small molecule provides a useful skeleton for further elaboration and study.

The AP2/ERF transcription factor ORA59 regulates ethylene-induced phytoalexin synthesis through modulation of an acyltransferase gene expression.

The gaseous ethylene (ET) and the oxylipin-derived jasmonic acid (JA) in plants jointly regulate an arsenal of pathogen responsive genes involved in defending against necrotrophic pathogens. The APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) transcription factor ORA59 is a major positive regulator of the ET/JA-mediated defense pathway in Arabidopsis thaliana. The Arabidopsis agmatine coumaroyltransferase (AtACT) catalyzes the formation of hydroxycinnamic acid amides (HCAAs) which are effective toxic antimicrobial substances known as phytoalexins and play an important role in plant defense response. However, induction and regulation of AtACT gene expression and HCAAs synthesis in plants remain less understood. Through gene coexpression network analysis, we identified a list of GCC-box cis-element containing genes that were coexpressed with ORA59 under diverse biotic stress conditions and might be potential downstream targets of this AP2/ERF-domain transcription factor. Particularly, ORA59 directly binds to AtACT gene promoter via the GCC-boxes and activates AtACT gene expression. The ET precursor 1-aminocyclopropane-1-carboxylic acid (ACC)-treatment significantly induces AtACT gene expression. Both ORA59 and members of the class II TGA transcription factors are indispensable for ACC-induced AtACT expression. Interestingly, the expression of AtACT is also subject to the signaling crosstalk of the salicylic acid- and ET/JA-mediated defense response pathways. In addition, we found that genes of the phenylpropanoid metabolism pathway were specifically induced by Botrytis cinerea. Taking together, these evidence suggest that the ET/JA signaling pathway activate the expression of AtACT to increase antimicrobial HCAAs production through the transcription factor ORA59 in response to the infection of necrotrophic plant pathogens.

Evaluation of different fiber impurities on hydrothermal liquefaction of mixed textile waste

There is a need for more sustainable recycling technologies for mixed textile waste, including the two main fibers poly(ethylene terephthalate) (PET) and cotton but also containing other fiber types. Hydrothermal liquefaction has been shown to be a promising technology to recycle textile waste containing cotton and PET into bio-oil and terephthalic acid (TPA). However, the practically accumulated composition of textile waste is more complex and features more than two fibers. In the present study we investigated the effect of eight different fabrics individually in ternary mixtures with a fixed ratio of cotton and PET and in a complex mixture reflecting the global fiber production. It was found that between 3 and 12 wt% bio-oil and 17–77 wt% TPA can be obtained depending on composition and temperature. Fibers with a high nitrogen content, such as suede, acrylic and nylon, significantly decreased the TPA yields due to the formation of terephthalic amides.

Temperature-dependent enthalpy parameters of the molecular interaction for urea and tetramethylurea as solutes in formamide, ethylene glycol and water

Enthalpies of dilution of urea (U) solutions in formamide (FA), ethylene glycol (EG) and water were measured calorimetrically in the temperature range between (288.15 and 318.15) K. Based on the results obtained, the enthalpy-homotactic coefficients of pairwise (h22) and triplet (h222) interactions between the solvated U molecules were computed and compared with the similar data for the respective solutions of tetramethylurea (TMU). An analysis was done of how temperature influences the solvophilic and solvophobic effects manifested in the h22 and h222 parameters for U and TMU in the studied organic solvents with a spatial H-bonding network.

Castor Plant (Ricinus communis L.) Leaf Extract as Potential Antibacterial Against The Growth of Mycobacterium Tuberculosis

Highlight : Patients experiencing failure of first-line drug and developing multidrug resistant tuberculosis (MDR-TB) has increased throughout 2011-2015. Castor plant leaf extract (Ricinus communis L.) has an antibacterial potential against the growth of Mycobacterium tuberculosis bacteria. Abstract: Mycobacterium tuberculosis is the cause of pulmonary tuberculosis that can reduce human health. In the therapy of the disease, patients can develop resistance to tuberculosis drugs. Based on the 2015 health profiles of Indonesia, 15,380 people were suspected to have multidrug-resistant tuberculosis (MDR-TB), while 1,860 people were confirmed patients with MDR-TB. There is a need for innovation to develop the latest treatments using natural ingredients, one of which is castor plant (Ricinus communis L.) that contains antibacterial compounds against Mycobacterium tuberculosis. This study aimed to understand the antimicrobial potential of castor plant (Ricinus communis L.) leaf extract against the growth of Mycobacterium tuberculosis. This scientific paper was a quantitative systematic review study. Literature in the form of journal articles and books were obtained through search engines, i.e. ebook database, Google Scholar, Cochrane, Wiley, and PubMed. The results of the literature source search were 19 journal articles and 4 ebooks, as well as 4 journal articles that were in accordance with the title of this literature review and discussed the effects of castor plants on the growth of Mycobacterium tuberculosis. The results of the analysis showed that castor plant (Ricinus communis L.) leaf extract has the potential in the antibacterial activity against the growth of Mycobacterium tuberculosis because it contains phytochemicals in the form of flavonoids, saponins, alkaloids, tannins, and fatty acid amides derived from ricinoleic acid as the main constituent of castor plants (Ricinus communis L.). There is antimicrobial potential for castor plant (Ricinus communis L.) leaf extract against the growth of Mycobacterium tuberculosis.

Aqueous sodium ion hybrid batteries with ultra-long cycle life at -50 ℃

• Nonflammable formamide is used as cosolvent to lower the freezing point of ASIBs electrolyte with a high ionic conductivity of 1.75 mS cm−1 at -50°C. • Theoretical calculations and spectroscopic methods reveal that formamide has sufficient active sites to coordinate with water molecules. • The assembled full ASIHBs displayes a super-stable cycling life of 8000 cycles under 4 C at -50°C. • Smart phone and LED bulbs can be power by AHSIBs at -50°C. Aqueous electrolytes are considered as appealing alternatives for commercial organic electrolytes due to their unique merits, such as inherent safety, low cost and environmental friendliness. Unfortunately, they normally cannot operate under extremely low temperature conditions because of the relatively high freezing point of common aqueous electrolytes. To expand their application spaces, the strong polar solvent formamide (FA) is firstly used as a cosolvent for the widely used 17 m NaClO 4 electrolyte (m: mol kg −1 ) in this work. The lowest freezing point of the optimized electrolyte has been significantly reduced below -50°C. Theoretical calculations and spectroscopic methods reveal that FA has sufficient active sites to coordinate with water molecules, cuts off their direct connections and prevents them from forming long-range order structures under subzero temperatures. When paired with the optimized low-temperature electrolyte, the aqueous sodium ion hybrid batteries (ASIHBs) based on active carbon cathode and organic polymer anode deliver a high capacity of ∼80 mAh g −1 at 1 C (1 C = 150 mA g −1 ) and 8000 cycles lifespan at 4 C under -50°C. Encouragingly, the pouch batteries can recharge smart phone for potential application. This electrolyte-modification strategy opens a new avenue to explore superior electrochemical performance for ultra-low temperature ASIHBs.

Synthesis of Novel Cavitand Host Molecules via Palladium-Catalyzed Aryloxy- and Azidocarbonylation

Novel, elongated, resorcine[4]arene-based cavitands were synthesized via various consecutive reaction steps, including homogeneous catalytic aryloxy- and azidocarbonylation processes. The effects of carbon monoxide pressure and temperature on the conversion were examined in aryloxycarbonylation. It was revealed that a reaction temperature of 100 °C is required to achieve complete conversion both with monodentate (PPh3) and bidentate (Xantphos) phosphines at different carbon monoxide pressures (1-40 bar). Using ten different phenols as O-nucleophiles, partial hydrolysis of the esters to the corresponding carboxylic acids took place-i.e., 58-90% chemoselectivities toward esters were obtained. Moreover, the influences of temperature, reaction time and the catalyst ratio on the selectivity and conversion were described in the case of azidocarbonylation reaction. The formation of the acyl azide with high chemoselevtivity can be achieved at room temperature only. The higher reaction temperatures (50 °C) and higher catalyst loadings favor the formation of the primary amide. The characterization of the target compounds (esters and acyl azides) was carried out by IR and 1H and 13C NMR. The discussion of the influences of various parameters is based on in situ NMR investigations.

Chitosan-Carboxymethylcellulose Hydrogels as Electrolytes for Zinc–Air Batteries: An Approach to the Transition towards Renewable Energy Storage Devices

Biopolymers are promising materials as electrolytes with high flexibility, good performance, cost effectiveness, high compatibility with solvents, and film-forming ability. Chitosan (CS) and carboxymethylcellulose (CMC) can form an intermolecular complex, giving rise to hydrogels capable of absorbing ionic solutions. Citric acid (CA) is an effective biological chemical crosslinker that assists the formation of amide and ester bonds between CMC and CS, resulting in a structure with high ionic conductivity and good structural integrity. In this study, a chemical crosslinking strategy is used to synthesize electrolyte hydrogels for zinc–air batteries. The effects of crosslinking are studied on the structural and electrochemical performance of the membranes. The results show an improvement in the ionic conductivity with respect to the homologous electrolyte hydrogel systems reported, with a maximum of 0.19 S∙cm−1 at 30 °C. In addition, the cyclic voltammetry studies showed a current intensity increase at higher CA content, reaching values of 360 mA∙cm−2. Structural characterization suggests a higher thermal stability and a decrease in the degree of crystallinity caused by the polymers’ crosslinking. Finally, these membranes were tested in Zn–air batteries, obtaining power densities of 85 mW∙cm−2. The proposed hydrogels show to be appropriate for energy zinc–air battery applications and present an alternative to support the sustainable energy transition.

ЗАВИСИМОСТЬ БИОЭЛЕКТРИЧЕСКОГО ПОТЕНЦИАЛА В КОРНЕОБИТАЕМОЙ СРЕДЕ ОТ ФОРМЫ АЗОТА В ПИТАТЕЛЬНОМ РАСТВОРЕ

The influence of the nitrogen form (nitrate, amide, nitrate-ammonium) in the composition of the nutrient solution on the electrical characteristics of a bioelectrochemical system based on the electrogenic properties of lettuce was studied. The dynamics of the bioelectric potential (BEP) in the root environment-plants system, biometric and biochemical parameters of plant production using various nutrient solutions during the cultivation of lettuce by the panoponic method in intensive artificial lightculture have been registered. The average BEP value was 243 mV when using the nitrate form of nitrogen in the nutrient solution, 147 mV for the amide form and 178 mV for the nitrate-ammonium form. The maximum observed potential difference was characteristic of the variant containing nitrogen in the nitrate form, which probably indicates the potential-forming role of NO3-. An increase in the concentration of positive ions (Ca2+, K+, NH4+) on the lower electrode and negative (NO3-) on the upper one was noted, which corresponds to the polarity observed in the BES – the upper electrode is electronegative relative to the lower one. It is shown that the nutrient solution containing nitrogen in the nitrate form was the best in terms of size and stability of the studied options. The diffusion of ions in the root environment during the life of plants can become a new alternative source of electricity.

Conversion of a AuI Fluorido Complex into an N‐Fluoroamido Derivative: N−F versus Au−N Reactivity

AbstractThe AuI complex [Au{N(F)SO2Ph}(SPhos)] (SPhos=dicyclohexyl(2′,6′‐dimethoxy[1,1′‐biphenyl]‐2‐yl)phosphane) (2) bearing a fluoroamido ligand has been synthesized by reaction of the fluorido complex [Au(F)(SPhos)] (1) with NFSI (NFSI=N‐fluorobenzenesulfonimide). A reaction with CO resulted in an unprecedented insertion into the N−F bond at 2. With the carbene precursor N2CH(CO2Et) N−F bond cleavage gave the Au−F bond insertion product [Au{CHF(CO2C2H5)}(SPhos)] (7). The presence of CNtBu led to Au−N cleavage at 2 and concomitant amide formation to give the cationic complex [Au(CNtBu)(SPhos)][N(F)SO2Ph)] (5), which reacted further to give FtBu as well as the cyanido complex [Au(CN)(SPhos)] (6). These results led to the development of a process for the amination of electrophilic organic substrates by transfer of the fluoroamido group NF(SO2Ph)−.

Conversion of a AuI Fluorido Complex into an N-Fluoroamido Derivative: N-F versus Au-N Reactivity.

The AuI complex [Au{N(F)SO2 Ph}(SPhos)] (SPhos=dicyclohexyl(2',6'-dimethoxy[1,1'-biphenyl]-2-yl)phosphane) (2) bearing a fluoroamido ligand has been synthesized by reaction of the fluorido complex [Au(F)(SPhos)] (1) with NFSI (NFSI=N-fluorobenzenesulfonimide). A reaction with CO resulted in an unprecedented insertion into the N-F bond at 2. With the carbene precursor N2 CH(CO2 Et) N-F bond cleavage gave the Au-F bond insertion product [Au{CHF(CO2 C2 H5 )}(SPhos)] (7). The presence of CNtBu led to Au-N cleavage at 2 and concomitant amide formation to give the cationic complex [Au(CNtBu)(SPhos)][N(F)SO2 Ph)] (5), which reacted further to give FtBu as well as the cyanido complex [Au(CN)(SPhos)] (6). These results led to the development of a process for the amination of electrophilic organic substrates by transfer of the fluoroamido group NF(SO2 Ph)- .

472 Nicotinamide improves cutaneous field cancerization on an ex-vivo study

Cutaneous field cancerization (FC) is a tissue area chronically exposed to sun light, in which cells present altered cell cycle, proliferation, differentiation, and death despite their normal appearance. On normal sun-exposed skin the most mutated gene is p53 which regulates the expression of p21 which controls cell cycle progression and cellular differentiation. Treatment of cutaneous FC with safe and low-cost molecules could reduce the probability of skin cancer recurrence. Nicotinamide (NAM) is the amide form of vitamin B3, a water-soluble molecule assumed by daily diet.