Free Amine Research Articles

Kartogenin releasing decellularized umbilical cord Wharton's jelly scaffold promotes rotator cuff fibrocartilaginous interface regeneration

Fibrocartilaginous regeneration at the tendon-to-bone interface is a major challenge for rotator cuff tear repair. We fabricated a decellularized umbilical cord Wharton’s jelly (DUCWJ) scaffold by decellularization method and performed histological and proteomic analyses. We then synthesized a kartogenin-conjugated DUCWJ (DUCWJ-KGN) scaffold using an EDC/NHS catalyst. 1H NMR, Fluorescence staining, and FTIR confirmed that the carboxyl group of KGN was covalently coupled with the free amine groups in the Wharton’s jelly (WJ) matrix, and the in vitro release profiles of KGN from the DUCWJ-KGN scaffold showed sustained release for 6 weeks. Both the DUCWJ and DUCWJ-KGN scaffolds had excellent biocompatibility and biofunctionality, supporting cell attachment, migration, and proliferation, and DUCWJ-KGN scaffolds the KGN-loaded scaffold could induce higher chondrogenic markers expression. The DUCWJ-KGN scaffold could also promote fibrocartilaginous regeneration at the rotator cuff tendon-to-bone interface, which indicates that the DUCWJ-KGN scaffold is a promising enthesis to enhance fibrocartilaginous interface regeneration.

Reactivity of Diamines in Acyclic Diamino Carbene Gold Complexes.

Acyclic diamino carbenes (ADCs) are interesting alternatives to their more widely studied N-heterocyclic carbene counterparts, particularly due to their greater synthetic accessibility and properties such as increased sigma donation and structural flexibility. ADC gold complexes are typically obtained through the reaction of equimolar amounts of primary/secondary amines on gold-coordinated isocyanide ligands. As such, the reaction of diamine nucleophiles to isocyanide gold complexes was expected to lead to bis-ADC gold compounds with potential applications in catalysis or as novel precursors for gold nanomaterials. However, the reaction of primary diamines with two equivalents of isocyanide gold chlorides resulted in only one of the amine groups reacting with the isocyanide carbon. The resulting ADC gold complexes bearing free amines dimerized via coordination of the amine to the partner gold atom, resulting in cyclic, dimeric gold complexes. In contrast, when secondary diamines were used, both amines reacted with an isocyanide carbon, leading to the expected bis-ADC gold complexes. Density functional theory calculations were performed to elucidate the differences in the reactivities between primary and secondary diamines. It was found that the primary amines were associated with higher reaction barriers than the secondary amines and hence slower reaction rates, with the formation of the second carbenes in the bis-ADC compounds being inhibitingly slow. It was also found that diamines have a unique reactivity due to the second amine serving as an internal proton shuttle.

Heat-induced glycosylation with dextran to enhance solubility and interfacial properties of enzymatically hydrolyzed zein

In order to increase aqueous solubility and emulsification properties, zein partially hydrolyzed by trypsin was conjugated to dextran with molecular weight of 2.5 or 6 kDa by Maillard reaction in aqueous mixtures at 90 °C. Change in free amine content, gel electrophoresis bands, and infrared spectra confirmed conjugation of the hydrolysates after 1, 3, and 6 h of heating. Conjugation increased aqueous solubility of zein hydrolysates up to 30% and decreased surface hydrophobicity up to 53%. In comparison to hydrolysates, conjugation reduced air-water interfacial tension and increased foaming capacity, foam stability, emulsifying activity index, and emulsion stability index. Properties were most improved for hydrolysates conjugated with 2.5 kDa dextran after 3 h heating, although emulsion stabilization was comparable for conjugates prepared with 6 kDa dextran. Emulsion droplet size and adsorbed content both decreased with dextran and were further reduced for samples with greater conjugation, implying surface activity of conjugates was greater than unconjugated hydrolysates. • Enzyme-hydrolyzed zein was conjugated to dextran of two molecular weights. • Conjugation increased solubility, foaming, and emulsification properties. • Shorter dextran chain reacted by heating for 3–6 h were best stabilizers.

Synthesis, characterization, antibacterial activities, molecular docking, and computational investigation of novel imine-linked covalent organic framework

In this study, a novel imine linkage covalent organic framework (COFs) was synthesized via condensation of terephthaldehyde with diethylenetriamine under solvothermal conditions to afford the corresponding COFTDETA which exhibited high thermal and chemical stability. The structure of COFTDETA was characterized by Ultraviolet–Visible spectral measurements (UV/V), Brunauer-Emmett-Teller (BET) surface area, scanning electron microscopy (SEM), Fourier transforms Infrared spectroscopy (FTIR), Thermogravimetric analyzer (TGA), Nuclear magnetic resonance (NMR) and X-ray diffraction (XRD. COFTDETA showed higher sensitivity as an antibacterial agent than tobramycin drug against different antibacterial species. The higher sensitivity is due to higher conjugation, presence of imine linkage (C = N), and free amine (NH). These experimental results were confirmed through molecular docking simulation with different kinds of proteins. Moreover, COFTDETA was optimized utilizing DFT/B3LYP/6–311(G) and HF basis set to elucidate their physical descriptor, determination of its HOMO-LUMO band gap, ESP, and (MEP) which were more correlated with biological results. Furthermore, the comparative study between experimental and theoretical results was closely related to DFT/B3LYP/6–311(G) basis set according to their 1HNMR, 13CNMR, and FT-IR.

Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs.

Advanced glycation end-products (AGEs) constitute a non-homogenous, chemically diverse group of compounds formed either exogeneously or endogeneously on the course of various pathways in the human body. In general, they are formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amine groups of nucleic acids, proteins, or lipids, followed by further rearrangements yielding stable, irreversible end-products. In the last decades, AGEs have aroused the interest of the scientific community due to the increasing evidence of their involvement in many pathophysiological processes and diseases, such as diabetes, cancer, cardiovascular, neurodegenerative diseases, and even infection with the SARS-CoV-2 virus. They are recognized by several cellular receptors and trigger many signaling pathways related to inflammation and oxidative stress. Despite many experimental research outcomes published recently, the complexity of their engagement in human physiology and pathophysiological states requires further elucidation. This review focuses on the receptors of AGEs, especially on the structural aspects of receptor–ligand interaction, and the diseases in which AGEs are involved. It also aims to present AGE classification in subgroups and to describe the basic processes leading to both exogeneous and endogeneous AGE formation.

Small-Molecular Adjuvants with Weak Membrane Perturbation Potentiate Antibiotics against Gram-Negative Superbugs.

Combination therapy with membrane-targeting compounds is at the forefront because the bacterial membrane is an attractive target considering its role in various multidrug-resistant elements. However, this strategy is crippled by the toxicity associated with these agents. The structural requirements for optimum membrane perturbation and minimum toxicity have not been explored for membrane-targeting antibiotic potentiators or adjuvants. Here, we report the structural influence of different chemical moieties on membrane perturbation, activity, toxicity, and potentiating ability in norspermidine derivatives. It has been shown in this report that weak membrane perturbation, achieved by the incorporation of cyclic hydrophobic moieties, is an effective strategy to design antibiotic adjuvants with negligible in vitro toxicity and activity but good potentiating ability. Aryl or adamantane functionalized derivatives were found to be better resorts as opposed to the acyclic analogues, exhibiting as high as 4096-fold potentiation of multiple classes of antibiotics toward critical Gram-negative superbugs. The mechanism of potentiation was nonspecific, consisting of weak outer-membrane permeabilization, membrane depolarization, and efflux inhibition. This unique concept of "weakly perturbing the membrane" by incorporating cyclic hydrophobic moieties in a chemical design with free amine groups serves as a breakthrough for nontoxic membrane-perturbing adjuvants and has the potential to revitalize the effect of obsolete antibiotics to treat complicated Gram-negative bacterial infections.

Germinated sorghum (Sorghum bicolor L.) and seedlings show expressive contents of putrescine

Free bioactive amines were quantified during germination of tannin and tannin-free sorghum seeds (8 genotypes) and seedlings (2 genotypes). Among the ten amines investigated, three (putrescine, spermidine and spermine) were found. Tannin-free sorghum seeds had higher levels of spermidine, spermine, putrescine and total amines (1.28, 1.27, 0.35, 2.91 mg/100 g dwb, respectively), compared to tannin sorghum (0.91, 1.13, 0.06, 2.09 mg/100 g dwb, respectively). Throughout germination, in all seedling parts, putrescine was prevalent followed by spermidine. Spermine was only detected in the 7th germination day in the cotyledon and radicle of tannin sorghum. In the cotyledon, putrescine levels increased (24- and 30- fold for tannin and tannin-free sorghum, respectively). Spermine decreased, but it increased reaching initial levels (∼1 mg/100 g dwb) in two tannin-free genotypes. Spermidine changes were not significant. Germinated sorghum was characterized by high putrescine and low spermidine levels, with higher levels for tannin-free (29.55 mg/100 g putrescine; 2.79 mg/100 g spermidine) compared to tannin (24.41 mg/100 g putrescine, 1.40 mg/100 g spermidine) sorghums. Different from other seeds, germinated sorghum is rich in putrescine. By selecting the proper genotype one can modulate polyamine contents in germinated sorghum, thereby obtaining different profile of amines for specific food application.

Computational study of the transamination reaction in vinylogous acyls: Paving the way to design vitrimers with controlled exchange kinetics

AbstractOne of the key points in the design of vitrimers is controlling the associative exchange kinetics. One common chemistry used in vitrimers is based on the dynamic amine exchange reaction of vinylogous acyl compounds in presence of free amine. Understanding the reaction mechanism is essential to assist the optimization of the reaction conditions as well as the molecular structure of the reactant compounds in the pursuit of new materials. In this work, a computational study has been performed to explore different reaction mechanisms in neutral, acidic and in basic conditions or in the presence of Lewis acids, as well as the effect of chemical modifications in the exchange reaction. The results reveal that the formation of hydrogen bonds are a key feature and that the vinylogous urea improves the transamination compared to vinylogous urethane. The esteric hindrance of the amino group in the vinylogous compound also plays an important role. Finally, the nature of the free amine can improve the reactivity by equilibrating two contrary effects: the basicity favors the nucleophilic attack and the conjugated acidity favors the protonation. The findings of this theoretical work shed light in the design of new vitrimers with controlled exchange kinetics by chemical modifications.

Transamidation‐based vitrimers from renewable sources

AbstractVitrimers are polymeric materials that behave as thermosets at room temperature but, when heated, they exhibit a plastic flow similar to thermoplastics, enabling their reprocessability. A series of new bio‐based polyamide‐polyamine vitrimers are synthetized starting from tris(2‐aminoethyl)amine and epoxidized methyl oleate, a material that can be easily prepared from renewable resources obtainable both from natural products and waste. The incorporation of free amine groups in the network enables the transamidation exchange reaction with the crosslinking amide functions; this reaction, if appropriately catalyzed, donates a full reprocessability to the material. Boric acid, which is known to be a green, cheap and non‐toxic catalyst for transamidation reactions, is employed in this work. Once that the optimal condition for the transamidation reaction is found, different catalyst loadings are tested and the obtained materials are subjected to thermal and mechanical characterization. The obtained materials possess good thermal stability up to 300°C and a Tg value ranging between 7 and 21°C depending on the B(OH)3 content. Furthermore it is possible to observe how the introduction of boric acid in the materials reduces the Ea (inferred from stress‐relaxation experiments) of the transamidation reaction from 130 ± 8 KJ mol−1 to a mean value of 63 ± 4 KJ mol−1.

Alkene Difunctionalization Directed by Free Amines: Diamine Synthesis via Nickel-Catalyzed 1,2-Carboamination

Alkene Difunctionalization Directed by Free Amines: Diamine Synthesis via Nickel-Catalyzed 1,2-Carboamination

Elucidating the structure and cytochrome P450-mediated mechanism for novel metabolites of GDC-0575 in rats

1. GDC-0575 is an ATP-competitive small-molecule inhibitor of ChK1 that is being developed by Genentech for the treatment of various human malignancies. 2. In a radiolabeled mass balance study of GDC-0575 in rats, two novel metabolites, named M12 (-71 Da,) and M17 (+288 Da), were detected as abundant circulating metabolites. 3. Subsequent mass spectrometry and nuclear magnetic resonance analysis showed that M12 was a cyclized metabolite of GDC-0575, whereas M17 was its heterodimer to the parent. We further determined that M12 was mainly generated by cytochrome P450 (Cyp) 2d2. 4. We proposed the potential mechanism was initiated by the oxidation on the pyrrole ring and subsequent cyclisation of the free primary amine onto C-3 of the pyrrole ring. This was followed by expulsion of cyclopropylcarboxamide and a loss of water to form intermediate I, which can be further oxidised to form M12, or dimerise with another molecule of GDC-0575 as nucleophile to form M17. 5. To verify this hypothesis, we attempted to trap the intermediate I with glutathione (GSH) trapping assay and the GSH conjugate on the pyrrole ring was identified. This suggests the oxidation on the pyrrole led to reactive metabolite formation and supported this proposed mechanism.

Site orientation, accessibility, and surface hydrophobicity control on AFC polymer to increase hexavalent chromium removal performance

• Three versions of polymer, each version in acid salt and free base form. • Different versions have different surface properties due to the orientation of the functional group. • Hydrophilic salt forms showed a 20-fold increase in removal than the hydrophobic counterpart. • Salt forms remove 95%-98%, chromate concentrations 10–100 mg/L, dose 4 g/L. Aniline formaldehyde condensate (AFC) is a polymer with an amine functional group. It can exist in either an acid salt or free amine form. AFC Polymers in salt form, Poly-1s, and Poly-2s, were synthesized by switching the ratio between isopropanol to an aqueous solution in the reaction medium from 3:1 to 1:3. Another Poly-3s was prepared in a reduced volume using an intermediate solvent ratio. All three were hydrophilic with a contact angle of 0°. Treatment with a base produced the corresponding polymers in a free base form. Elemental analysis, FTIR, and MALDI mass analyses confirmed the formulation of the salt form and free base form without significant changes in the chemical identity of the polymers. Contact angle measurements showed that Poly-1b (from Poly-1s) was superhydrophobic (contact angle 154°), whereas Poly-2b (from Poly-2s) was hydrophilic (contact angle 0°). The reversal in hydrophobicity between Poly-1b and Poly-2b indicated a significant change in the orientation of the amine group. FESEM imaging and surface area measurements from the BET isotherm reflected the differences between them. In chromate removal experiments, all three salt forms showed 80%-93% chromate removal (initial chromate concentration 10–100 mg/L, adsorbent dose 1 g/L, pH 4). The adsorption capacity of salt forms, between 131 and 149 mg/g (dose 0.5 g/L, removal 66%-75%), is the highest reported for AFC. In contrast, the uptake of hydrophobic Poly-1b at 3.87 mg/g (dose 4 g/L, C i 100 mg/L) was the lowest found for AFC. This work demonstrates that the relationship between surface property and site accessibility profoundly impacts chromate binding property.

Zwitterionic microgel based anti(-bio)fouling smart membranes for tunable water filtration and molecular separation

Tunable gating polymeric nanostructured membrane with excellent water permeability and precise molecular separation is highly advantageous for smart nanofiltration application. Polymeric nanostructures such as microgels with functionalizable cross-linkable moieties can be an excellent choice to construct membranes with a thin separation layer, functionality, and tunable transport properties. In the present work, we prepared switchable anti(bio)fouling membranes using zwitterionically functionalized antibacterial thermoresponsive aqueous core-shell microgels with a thin separation layer for controlled filtration and separation applications. The microgels were synthesized using a one-step graft copolymerization of poly(N-isopropylacrylamide) and polyethyleneimine (PEI) followed by zwitterionization of free amine groups of PEI chains with 1,3-propane sultone. Microgel synthesis and zwitterionization were confirmed by spectroscopic and elemntal analysis. The obtained microgels were thoroughly characterized to analyze their thermoresponsive behavior, morphology, charge, and antibacterial properties. After that, characterizations were performed to elucidate the surface properties, water permeation, rejection, and flux recovery of the microgel membranes prepared by suction filtration over a track-etched support. It was observed that zwitterionic membrane provides better hydrophilicity, lower bovine serum albumin (BSA) adsorption, and desirable antimicrobial activity. The pure water permeability was directly related to the microgel layer thickness, applied pressure, and temperature of the feed solution. The novel nanostructured membrane leads to an excellent water permeance with a high gating ratio, high flux recovery rate with low irreversible fouling, better rejection for various dyes, and foulant. Most importantly, the long-term performance of the membrane is appreciable as the microgel layer remains intact and provides excellent separation up to a longer period. Owing to easy preparation and well control over thickness, the zwitterionic microgel membranes constitute unique and interactive membranes for various pressure-driven separation and purification applications.

A new near-infrared fluorescent probe for sensing extreme acidity and bioimaging in lysosome

Since the intracellular pH plays an important role in the physiological and pathological processes, however, the probes that can be used for monitoring pH fluctuation under extreme acidic conditions are currently rare, so it is necessary to construct fluorescent probes for sensing pH less than 4. In this work, we developed a new near-infrared (NIR) fluorescent probe Cy-SNN for sensing pH fluctuation under extremely acidic conditions. For the preparation of this probe, benzothiozolium moiety was chosen as lysosomal targeting unit and NIR fluorophore, and barbituric acid moiety was fused in the polymethine chain of probe to introduce protonation center. Surprisingly, on the basis of the balance of quaternary ammonium salts and free amines, the pka value of Cy-SNN was calculated as low as 2.96, implying that Cy-SNN can be used in acidic conditions with pH < 4. Moreover, Cy-SNN exhibited highly selective response to H+ over diverse analytes in real-time with dependable reversibility. Importantly, Cy-SNN can be used to specifically target lysosome, providing potential tools for monitoring the function of lysosome in autophagy process.

Effects of ferulic acid on the oxidation stability and nitrozation of myofibrillar proteins under oxidative stress

This study investigated the effects of ferulic acid (FA) on the oxidative stability and nitrozation of porcine myofibrillar proteins (MPs) under oxidative stress. The addition of FA significantly (P < 0.05) inhibited the formation of carbonyl and dityrosine, and reduced the sulfhydryl and free amine content compared with the oxidized MPs. Moreover, FA intensified oxidation-initiated loss of surface hydrophobicity and α-helix conformation, and enhanced protein cross-linking. A progressive quenching of MP endogenous fluorescence intensity was observed with the increase of FA concentration, and the emission wavelength showed a slight red shift. Beside, the addition of FA significantly eliminated sodium nitrite and almost completely inhibited the formation of 3-nitrotyrosine (3-NT) and N-nitrosodimethylamine (NDMA) at 200 μmol/g. Principal component analysis indicated that there were positive correlations between protein oxidation variables (carbonyl, dityrosine and surface hydrophobicity) and nitrozation indexes (3-NT and NDMA), as well as between 3-NT and NDMA. These results suggest that FA could suppress the nitration via controlling MP's oxidation.

Ligand relay catalysis for cobalt-catalyzed sequential hydrosilylation and hydrohydrazidation of terminal alkynes

Sequential double hydrofunctionalizationalization of alkynes is a powerful method to construct useful vicinal compounds. Herein, we report a cobalt-catalyzed sequential hydrosilylation/hydrohydrazidation of alkynes to afford 1,2-N,Si compounds via ligand relay catalysis. A phenomenon of ligand relay is found that the tridentate anionic N-ligand (OPAQ) could capture the cobalt ion from bidentate neutral P-ligand (Xantphos) cobalt complex. This protocol uses three abundant chemical feedstocks, alkynes, silanes, and diazo compounds, and also features operationally simple, mild conditions, low catalyst loading (1 mol%), and excellent functional group tolerance. The 1,2-N,Si compounds can be easily further derivatized to afford various substituted silane derivatives via Si-H functionalization, alcohols via Fleming-Tamao oxidation, free amines and amides via N-N bond cleavage and protection. The asymmetric reaction could also be carried out to afford chiral products with up to 86% ee. The ligand relay has been supported by control experiments and absorption spectra.

Catalyst-Free Site Selective Hydroxyalkylation of 5-Phenylthiophen-2-amine with α-Trifluoromethyl Ketones through Electrophilic Aromatic Substitution.

An original and effective approach for achieving trifluoromethyl hydroxyalkylation of 5-phenylthiophen-2-amine using α-trifluoromethyl ketones is described. In the last few years, reaction of Friedel-Crafts had been widely used to realize hydroxyalkylation on heterocycles such as indoles or thiophenes by means of Lewis acid as catalyst. Additionally, amine functions are rarely free when carbonyl reagents are used because of their tendency to form imines. This is the first time that a site-selective electrophilic aromatic substitution on C3 atom of an unprotected 5-phenylthiophen-2-amine moiety is reported. The liberty to allow reaction in neutral conditions between free amine is valuable in a synthesis pathway. The reaction proceeds smoothly using an atom-economical metal-and catalyst-free methodology in good to excellent yields. A mechanism similar to an electrophilic aromatic substitution has been proposed.

Possible inhibitory effect of microbial transglutaminase on the formation of biogenic amines during Trappist cheese ripening

ABSTRACT Trappist cheese (semi-hard, rennet-coagulated cheese with round eyes) was manufactured and matured for 4 weeks at 12 ± 1°C, 85% relative humidity (RH). The effect of microbial transglutaminase (MTGase) was followed by measuring the levels of free amino acids (FAAs) and biogenic amines (BAs) every 2 weeks during 4 weeks of cheese ripening. Results show that MTGase can decrease the cadaverine production by 30%, but only at the initial stage of ripening. Application of MTGase results in 49% less putrescine, 12% less tyramine production at the end of 4 weeks ripening time, and can decrease histamine levels by 8% after 2 weeks of ripening time in the examined semi-hard cheese type.

Dioxygen-promoted cobalt-catalyzed oxidative hydroamination using unactivated alkenes and free amines

Catalytic Markovnikov-selective hydroamination of unactivated alkenes, in particular by using secondary amines as nucleophiles and/or in an intermolecular setting, remains a challenge. Here we address this problem by developing a cobalt-hydride-catalyzed hydroamination reaction based on a bimetallic redox-triggered oxidative amination pathway. This system enables the use of dioxygen as a sustainable oxidant that is compatible with free amines, while suppressing the facile radical oxygenation that leads to classical Drago-Mukaiyama oxidation. We demonstrate intra- and intermolecular formal addition of secondary amines across unactivated alkenes as well as vinylarenes at ambient temperature. The scope of this method also encompasses alternative nitrogen nucleophiles, such as sulfonamides, amides, and carbamates. Stoichiometric reactions of well-defined organocobalt complexes provide direct evidence for the proposed key amination process.

Near-infrared fluorescent probe for sensing local microscopic extreme acidity and its application in mitochondria

In this paper, a novel near-infrared (NIR) fluorescent probe Cy-BNN for sensing local microscopic pH under extremely acidic conditions (pH < 4) was constructed and reported. For the preparation of Cy-BNN, a barbituric acid moiety was fused in the polymethine chain of the cyanine dye to introduce nitrogen atoms as protonation center. In different pH, the balance of quaternary ammonium salts and free amines of Cy-BNN was adjusted, and the pka value of Cy-BNN was calculated based on the Sigmoidal equation. Surprisingly, the pka value of Cy-BNN as low as 3.32, implying that Cy-BNN can be used for sensing extreme acidity. As expected, Cy-BNN exhibited highly selective response to H+ over diverse analytes, and can be used to monitoring the intracellular pH fluctuation under extremely acidic conditions. Importantly, Cy-BNN can be used to specifically target mitochondria, providing potential possibilities for monitoring mitochondria–lysosome interactions in live cells and mitophagy process.