Aminolysis Reaction Research Articles

Bactericidal materials prepared via conjugation of responsive polymers to cysteine

Hybrid bioconjugates based on poly(N-isopropylacrylamide)(PNIPAM)/poly(acrylic acid) (PAA) and cysteine (Cys) (PNIPAM-Cys/PAA-Cys) were synthesized via combination of reversible addition–fragmentation chain-transfer (RAFT) polymerization and 2,2,6,6-tetra methylpiperidin-1-yl)oxyl (TEMPO) initiated thiol-ene reaction. In order to use cysteine for the preparation of these hybrids materials, functionalization of cysteine with 1,4-bis(acryloyloxy)butane was carried out using TEMPO initiated thiol-ene reaction in an aqueous medium under ambient reaction conditions. The synthesized Cys-Ene was characterized by 1H and 13C NMR spectroscopy and Zeta potential measurement. Thiol-functionalized responsive polymers, for example, PNIPAM-SH and PAA-SH were synthesized by RAFT polymerization followed by an aminolysis reaction. The resulting thiol terminated polymers were functionalized with Cys-Ene again using TEMPO initiated thiol-ene reaction in an aqueous medium under ambient reaction conditions to yield responsive hybrid bioconjugates. The synthesized hybrid materials were characterized by 1H NMR spectroscopy, UV-visible spectroscopy, dynamic light scattering and Zeta potential analysis. In addition, the antibacterial activity of hybrid materials based on cysteine was evaluated and the minimum inhibitory concentrations (MICs) were found to be 70 and 100 μg/mL against E. coli and R. erythropolis respectively. The results suggest that the constructed hybrid bioconjugates because of its efficacy towards a broad range of bacteria could potentially be useful in several biomedical applications.

Elucidating the Surface Functionality of Biomimetic RGD Peptides Immobilized on Nano-P(3HB-co-4HB) for H9c2 Myoblast Cell Proliferation.

Biomaterial scaffolds play crucial role to promote cell proliferation and foster the regeneration of new tissues. The progress in material science has paved the way for the generation of ingenious biomaterials. However, these biomaterials require further optimization to be effectively used in existing clinical treatments. It is crucial to develop biomaterials which mimics structure that can be actively involved in delivering signals to cells for the formation of the regenerated tissue. In this research we nanoengineered a functional scaffold to support the proliferation of myoblast cells. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] copolymer is chosen as scaffold material owing to its desirable mechanical and physical properties combined with good biocompatibility, thus eliciting appropriate host tissue responses. In this study P(3HB-co-4HB) copolymer was biosynthesized using Cupriavidus malaysiensis USMAA1020 transformant harboring additional PHA synthase gene, and the viability of a novel P(3HB-co-4HB) electrospun nanofiber scaffold, surface functionalized with RGD peptides, was explored. In order to immobilize RGD peptides molecules onto the P(3HB-co-4HB) nanofibers surface, an aminolysis reaction was performed. The nanoengineered scaffolds were characterized using SEM, organic elemental analysis (CHN analysis), FTIR, surface wettability and their in vitro degradation behavior was evaluated. The cell culture study using H9c2 myoblast cells was conducted to assess the in vitro cellular response of the engineered scaffold. Our results demonstrated that nano-P(3HB-co-4HB)-RGD scaffold possessed an average fiber diameter distribution between 200 and 300 nm, closely biomimicking, from a morphological point of view, the structural ECM components, thus acting as potential ECM analogs. This study indicates that the surface conjugation of biomimetic RGD peptide to the nano-P(3HB-co-4HB) fibers increased the surface wettability (15 ± 2°) and enhanced H9c2 myoblast cells attachment and proliferation. In summary, the study reveals that nano-P(3HB-co-4HB)-RGD scaffold can be considered a promising candidate to be further explored as cardiac construct for building cardiac construct.

Hydrolysis versus aminolysis of a potential nerve agent tabun: a computational reaction mechanism study

The mechanism for the hydrolysis and aminolysis reactions of potential nerve agent tabun have been investigated both at DFT/M062X level and at ab initio MP2 level of theory. Effect of solvent water has also been incorporated using Minnesota SMD model. Based on leaving groups, there are three probable dissociation pathways of tabun: (1) elimination of HCN, (2) elimination of dimethyl amine and (3) elimination of ethanol. Each of the pathways follows a stepwise neutral route through two transition states. From the mechanism, it has been established that the HCN removal pathway is most favorable than the other two due to greater leaving tendency of the cyanide group. The reaction possesses two four-membered transition state in each path, i.e., for the addition of ammonia/water and for the release of leaving groups. As the four-membered cyclic TSs are not so favorable, the investigated reactions were found quite a bit high energetic. The first addition step of the H2O or NH3 is found as the rate-determining step. The reactivity of ammonia toward tabun has been found highly favorable (by ~ 7.6 kcal mol−1) than the water. This can be easily explained using the fact that the nucleophilicity of NH3 is higher than the H2O. Further, we have seen that water can be a very effective catalyst in the aminolysis reaction as it reduces the barrier of activation of the RDS by ~ 10 kcal mol−1. Self-catalyzed hydrolysis of water has also been performed, and it decreases the activation of ~ 11 kcal mol−1 than the uncatalyzed pathways. The significant reduction of energy of activation takes place due to the formation of six-membered transition states that makes much easier hydrogen transfer compared to the four-membered transition state formed in case of uncatalyzed aminolysis reactions.

The syntheses of pyrazole amine substituted cyclotriphosphazenes: Spectroscopic and crystallographic characterizations

The aminolysis reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (1a) and di-spirodioxy cyclotriphosphazene derivative N3P3Cl2[OCH2(CF2)2CH2O]2 (1b) with 1-benzyl-1H-pyrazol-3-amine (2) were investigated. Two new pyrazole amine substituted cyclotriphosphazene derivatives (3a, b) were obtained. Both compounds (3a, b) have been characterized by elemental analysis, MALDI-TOF mass spectrometry, 1H, and 31P NMR spectroscopy. The molecular and crystal structures of 3a and 3b were confirmed by single crystal X-Ray crystallography. Hirshfeld surface analyses of the crystal structures of 3a and 3b were investigated to determine the remarkable interactions between the molecules and the packing nature of the molecules in the crystals.

Molecular Organization of Reagents in the Kinetics and Catalysis of Liquid-Phase Reactions: XIII. Cyclic Transition States Involving Solvent Molecules in the Mechanism of Aminolysis of Cyclocarbonates in an Alcohol Medium

Trends in the influence of a proton-donor solvent on the reaction of aminolysis of ethylene carbonate, which proceeds through concerted and stepwise mechanisms, are studied. The study is based on kinetic data of model reactions in alcohol solutions and results of DFT quantum chemical calculations of reaction paths that involve hydrogen-bonded transition states and intermediates containing different numbers of solvent molecules in the proton-transfer and stabilization cycles. The calculated data on the activation energies of the reaction, which includes cycles of different sizes, indicate that the stepwise mechanism is preferable compared to the concerted one when the reaction proceeds in methanol. The activation barrier of the stepwise path of the reaction is lower by 2.9 kcal/mol than that for the concerted path. Only the proton-transfer cycle is essential for the progress of the reaction, and the presence of a stabilization cycle does not lead to a decrease in the activation barrier.

Synthesis and Biological Activity of Benzamides Substituted with Pyridine-Linked 1,2,4-Oxadiazole.

To find pesticidal lead compounds with high activity, a series of novel benzamides substituted with pyridine-linked 1,2,4-oxadiazole were designed by bioisosterism, and synthesized easily via esterification, cyanation, cyclization and aminolysis reactions. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. The preliminary bioassay showed that most compounds had good larvicidal activities against mosquito larvae at 10 mg/L, especially compound 7a, with a larvicidal activity as high as 100%, and even at 1 mg/L was still 40%; at 50 mg/L, all the target compounds showed good fungicidal activities against the eight tested fungi. Moreover, compound 7h exhibited better inhibitory activity (90.5%) than fluxapyroxad (63.6%) against Botrytis cinereal. Therefore, this type of compound can be further studied.

Thermally Reversible Polymeric Networks from Vegetable Oils.

Low cross-link density thermally reversible networks were successfully synthesized from jatropha and sunflower oils. The oils were epoxidized and subsequently reacted with furfurylamine to attach furan groups onto the triglycerides, preferably at the epoxide sites rather than at the ester ones. Under the same reaction conditions, the modified jatropha oil retained the triglyceride structure more efficiently than its sunflower-based counterpart, i.e., the ester aminolysis reaction was less relevant for the jatropha oil. These furan-modified oils were then reacted with mixtures of aliphatic and aromatic bismaleimides, viz. 1,12-bismaleimido dodecane and 1,1′-(methylenedi-4,1-phenylene)bismaleimide, resulting in a series of polymers with Tg ranging between 3.6 and 19.8 °C. Changes in the chemical structure and mechanical properties during recurrent thermal cycles suggested that the Diels–Alder and retro-Diels–Alder reactions occurred. However, the reversibility was reduced over the thermal cycles due to several possible causes. There are indications that the maleimide groups were homopolymerized and the Diels–Alder adducts were aromatized, leading to irreversibly cross-linked polymers. Two of the polymers were successfully applied as adhesives without modifications. This result demonstrates one of the potential applications of these polymers.

Synthesis of novel 2,5-substituted p-aminophenols and 2,5-substituted p-quinones in a one-pot reaction between α-alkoxyvinyl(ethoxy)carbene complexes, amines and alkynes

The synthesis of novel p-aminophenols 19a-o and p-quinones 21a-i was carried out by an aminolysis reaction/[3 + 2+1] cycloaddition cascade process of α-alkoxyvinyl (ethoxy) Fischer carbene complexes of group 6 metals (M = Cr, Mo, W), primary and secondary amines and terminal alkynes. The multicomponent reaction of carbenes 1a-c with morpholine (6a) and piperidine (6c), respectively, and terminal alkynes 17a-d only afforded the 4-aminophenols 19a-o in moderated yields. The products bore the terminal alkyne substituent at the ortho position of the hydroxyl group. These one-pot reactions showed highly regio- and chemoselectivity, favoring the benzannulation products. When carbene complexes 1a-c were reacted with primary amines 10a-c and alkynes 17a-c under the same conditions, the cascade process led to the formation of p-quinones 21a-21i, in moderate yields. The regiochemistry of the compounds was established by NOE experiments, and the structures of morpholinocarbene 7a, p-aminophenols 19b, 19d and p-quinone 21b were confirmed by single-crystal X-ray diffraction.

Influence of steric effects on the kinetics of cyclic-carbonate vegetable oils aminolysis

Polyurethane polymer is more and more famous because of its versatile properties. The current production process requires the use of isocyanate, which is a hazardous chemical. An alternative eco-friendly route of production is the aminolysis reaction between a cyclic-carbonate, from carbonated vegetable oil, and a diamine. Nevertheless, the kinetics of this reaction system is slow, which might be due to steric hindrance. In order to predict and evaluate this steric hindrance, different amines were tested for the aminolysis of carbonated methyl oleate. Four amines were used: n-butylamine, methylbutylamine, ethylbutylamine and dibutylamine. Kinetic models for the aminolysis with each amine were developed. A relationship between structure and reactivity of each substituent was found through the concept of Linear Free Energy Relationships.

The effect of carbon nanotubes on the curing processes of epoxy-amine compositions

The effects of the concentration and functionalization of carbon nanotubes on the degree of conversion of epoxy groups in epoxy-amine compositions based on ED-20 epoxy oligomer and the PEPA curing agent are studied. It has been shown that increasing the concentration of functionalized carbon nanotubes (CNT) from 0 to 0.5 % increases the degree of conversion of the epoxy groups during curing at a room temperature. Further increase in concentration CNT of up to 1 % does not effect on the reaction kinetics. For native CNT not established such a relationship. Explains such a pronounced effect on the f-CNT aminolysis reaction kinetics and ultimate degree of conversion of epoxy groups, apparently, the catalytic effect of oxygen-containing groups (hydroxyl, carboxyl, and others) grafted to the surface of CNTs and their direct involvement in the reaction. By optical microscopy showed that the size of the agglomerates of nanotubes were substantially higher in the native systems than in the system with the functionalized nanotubes. These results may be important for the development of creation of epoxy composites modified by nanoparticles.

Surface modification of polyethylenterephthalate film with primary amines using gamma radiation and aminolysis reaction for cell adhesion studies

The success of biomaterials depends on several factors that determine their proper interaction with the biological environment. Their physical and chemical properties, such as the rigidity of the substrate and the topography and chemistry of the surface, have an important influence on cellular behavior. This work describes the modification of the surface of polyethylenterephthalate (PET) films with primary amino groups, as well as cell adhesion tests on these surfaces. Herein, gamma radiation was used to graft acryloyl chloride (AC) by an oxidative preirradiation method to obtain PET-g-AC with a grafting percent of 4.8 ± 0.07%. After grafting ethylenediamine (ED) was reacted with PET-g-AC via an aminolysis reaction to generate PET-g-EAAm where NH2 terminal groups are present on the polymer surface. The films were characterized by contact angle, FT-IR, TGA, SEM and AFM. The presence of NH2 groups on modified PET films’ surfaces was confirmed by XPS, and the amount (20.3 + 0.7 pmol mm-2) was calculated using a colorimetric method; this quantity was determined to be sufficient to carry out cell culture assays, demonstrating that PET-g-EAAm films with primary amines are biocompatible with epithelial and mesenchymal cells lines, which play a very important role in the development and design of new materials for biomedical applications.

Design of a maleimide monomer to achieve precise sequence control and functionalization for an alternating copolymer with vinylphenol

We designed an N-phenylmaleimide derivative bearing an activated NHS ester (NHS-PhMI) for radical copolymerization with tert-butoxystyrene (tBOS) to achieve both precise alternating sequence control and functionalization. Essential to the monomer design is the electron-deficient carbon-carbon double bond for precise alternating propagation as well as the facile substitution reaction for the activated ester pendant. The precision of alternating sequences was evaluated by MALDI-TOF-MS analysis in comparison with a series of copolymers. Some amine compounds were quantitatively incorporated onto the maleimide side chain through the aminolysis reaction, whereas the tBOS units were transformed into vinylphenol counterparts via deprotection under acidic conditions. The resultant vinylphenol-based alternating copolymers showed unique solubilities and thermal properties depending on the substituent of the maleimide units. Design of an N-phenyl maleimide derivative bearing an activated NHS ester for radical copolymerization with tert-butoxystyrene to achieve both precise alternating sequence control and functionalization.

New Efficient Eco-Friendly Supported Catalysts for the Synthesis of Amides with Antioxidant and Anti-Inflammatory Properties.

A new environmentally friendly approach for the synthesis of idrocilamide (1), a marketed myorelaxant and anti-inflammatory agent, is reported herein. The synthetic strategy involves a solvent-free aminolysis reaction catalyzed by zinc-containing species (ZnCl2 , montmorillonite K10 (MK10) impregnated with ZnCl2 or eco-catalysts). The latter have been prepared from the aerial parts of Lolium perenne L. plants grown on contaminated soils from northern France without and with thermal activation at 120 °C and supported on MK10 (Ecocat1 and Ecocat2, respectively). The best aminolysis catalysts in the current study (ZnCl2 and Ecocat2) were selected for additional aminolyses. Compared to ZnCl2 , Ecocat2 had the advantage of being reusable over five test runs and constituted a sustainable catalyst allowing a green route to idrocilamide. Synthesized derivatives 1-4, 6 and 9 were first evaluated for their effect on reactive oxygen species (ROS) generation from macrophages and displayed antioxidant properties by preventing ROS production. Next, the analysis of the effect of molecules 1-4, 6 and 9 on macrophage migration between epithelial cells to human opportunistic fungus Candida albicans indicated that molecules 2-4, 6 and 9 exert anti-inflammatory properties via reducing macrophage migration while the parent idrocilamide (1) did not show any significant effect. This work opens the way for the discovery of new analogues of idrocilamide with improved properties.

Amino-functionalized polymethylmethacrylate-co-polyethyleneimine (PMMA-co-PEI) as a template to fabricate nano-silica

Polymer template method is a general and facile to fabricate nano-structural matters. Some amphiphilic polymers or co-polymers were used as templates to synthesize nano-silica. In this contribution, polymethacrylate (PMMA) employed was a commercial hydrophobic acrylate polymer and grafted with a strong hydrophilic polyethyleneimine (PEI, a densely amino-groups polymer) via aminolysis reaction, which was monitored and identified by means of FT-IR. The aminolysis reaction was optimized and the suitable reaction time was 12 h at 110 °C. The obtained copolymer, PMMA-co-PEI was applied as a template to prepare nano-silica spheres that was characterized by a scanning electron microscope (SEM). When the dosage was 1 wt% of purified PMMA-co-PEI, the resultant nano-silica had uniform particle size, and average diameter of 311 nm. When the dosage of PMMA-co-PEI was increased to 2 wt% or 4 wt%, the resultant particles became bigger and inclined to aggregate. Nano-silica afforded by this template method will be a promising material in application of catalysis, energy, biology and chromatographic analysis and the copolymer of PMMA-co-PEI will be a template for producing metal oxide nano-spheres.

Computational study on the polymerization reaction of d-aminopeptidase for the synthesis of d-peptides.

Almost all natural proteins are composed exclusively of l-amino acids, and this chirality influences their properties, functions, and selectivity. Proteases can recognize proteins composed of l-amino acids but display lower selectivity for their stereoisomers, d-amino acids. Taking this as an advantage, d-amino acids can be used to develop polypeptides or biobased materials with higher biostability. Chemoenzymatic peptide synthesis is a technique that uses proteases as biocatalysts to synthesize polypeptides, and d-stereospecific proteases can be used to synthesize polypeptides incorporating d-amino acids. However, engineered proteases with modified catalytic activities are required to allow the incorporation of d-amino acids with increased efficiency. To understand the stereospecificity presented by proteases and their involvement in polymerization reactions, we studied d-aminopeptidase. This enzyme displays the ability to efficiently synthesize poly d-alanine-based peptides under mild conditions. To elucidate the mechanisms involved in the unique specificity of d-aminopeptidase, we performed quantum mechanics/molecular mechanics simulations of its polymerization reaction and determined the energy barriers presented by the chiral substrates. The enzyme faces higher activation barriers for the acylation and aminolysis reactions with the l-stereoisomer than with the d-substrate (10.7 and 17.7 kcal mol−1 higher, respectively). The simulation results suggest that changes in the interaction of the substrate with Asn155 influence the stereospecificity of the polymerization reaction.

Enhanced breakdown strength and suppressed dielectric loss of polymer nanocomposites with BaTiO3fillers modified by fluoropolymer

The introduction of ceramic fillers into a polymer matrix is an effective way to obtain dielectric nanocomposites with high energy storage density. However, the inorganic fillers are difficult to disperse evenly into the polymer matrix because of the poor compatibility, which stems from the large surface energy difference and the mismatch in dielectric constant between the fillers and polymer matrix. Polymer nanocomposites with high dielectric constant while maintaining high breakdown strength have great potential to achieve high energy storage density. In this work, poly(dodecafluoroheptyl methacrylate) terminated with a thiol end group (PDFMA-SH) was synthesized via a two-step process including Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization and subsequent aminolysis reaction. The polymer was then grafted into the surface of BaTiO3 (BT) nanoparticles by a “thiol–ene” click reaction to reduce the surface energy of BT nanoparticles. A novel nanocomposite consisted of the core–shell structured PDFMA@BT hybrid nanoparticles and poly(vinylidene fluoride–chlorotrifluoroethylene) (P(VDF–CTFE)) matrix was prepared. The influence of the fluoropolymer shell on the dispersion of fillers, the compatibility between the fillers and polymer matrix, dielectric properties and breakdown strength were investigated systematically. The results indicate that the strong interfacial adhesion between the hybrid nanoparticles and P(VDF–CTFE) matrix makes the fillers uniformly dispersed in the polymer matrix. Meanwhile, the excellent compatibility between the two components is favorable for enhancing the breakdown strength and suppressing dielectric loss, providing a condition to prepare dielectric materials with high energy storage density.

Tuning the Density of Zwitterionic Polymer Brushes on PET Fabrics by Aminolysis: Effect on Antifouling Performances.

Here, we synthesize zwitterionic polymer brushes on polyester fabrics by atom transfer radical polymerization (ATRP) after a prefunctionalization step involving an aminolysis reaction with ethylenediamine. Aminolysis is an easy method to achieve homogeneous distributions of functional groups on polyester fibers (PET) fabrics. Varying the polymerization time and the prefunctionalization conditions of the reaction, it is possible to tune the amount of water retained over the surface and study its effect on protein adhesion. This study revealed that the polymerization time plays a major role in preventing protein adhesion on the PET surface.

Synthesis and characterization of novel multi-hydroxy polyaspartamide derivative and its crosslinked hydrogels

In this study, a new type of multihydroxy synthetic polymer and its crosslinked gels were prepared. Poly(N-2,3-dihydroxypropyl aspartamide) (PDHPA), a poly(amino acid) composed of a peptide backbone and pendent 1,2-dihydroxy functional groups, was synthesized from polysuccinimide, the precursor polymer, by aminolysis reaction using 3-amino-1,2-propanediol. This polyaspartamide derivative exhibited several valuable properties including biodegradability, high water solubility, excellent biocompatibility, and good adhesion. Because of its unique chemical structure, PDHPA could serve as a useful platform for combination with other materials and preparation of dynamically reversible and self-healing crosslinked hydrogels. PDHPA was reacted with boric acid (H3BO3) to produce a transparent, dynamically reversible, and self-healing hydrogel, whose viscoelastic behavior depended on the chemical composition, water content, and pH condition. Moreover, PDHPA and the crosslinked gel exhibited relatively strong adhesion toward various types of substrates including glass, paper, metal, and plastic. Another hydrogel was prepared using PDHPA and glutaraldehyde in the presence of an acid catalyst; this hydrogel exhibited relatively high gel strength and swelling ratios in the range of 2–5. This new class of hydrophilic water-soluble polymer and its crosslinked gels with excellent hydrolytic degradability, adhesive property, non-cytotoxicity, and biocompatibility have application potential in various biomedical fields.

Design, Preparation, and Characterization of Novel Calix[4]arene Bioactive Carrier for Antitumor Drug Delivery.

An amphiphilic and bioactive calix[4]arene derivative 8 (CA) is designed and successfully synthesized from tert-butyl calix[4] arene 1 by sequential inverse F-C alkylation, nitration, O-alkylation, esterification, aminolysis, reduction, and acylation reaction. The blank micelles of FA-CA and doxorubicin (DOX) loaded micelles FA-CA-DOX are prepared subsequently undergoing self-assembly and dialysis of CA and DSPE-PEG2000-FA. The drug release kinetics curve of the encapsulated-DOX micelle demonstrates a rapid release under mild conditions, indicating the good pH-responsive ability. Furthermore, the cytotoxicity of DOX-loaded micelle respect to the blank micelle against seven different human carcinoma (A549, HeLa, HepG2, HCT116, MCF-7, MDA-MB231, and SW480) cells has been also investigated. The results confirm the more significant inhibitory effect of DOX-loaded micelle than those of DOX and the blank micelles. The CDI calculations show a synergistic effect between blank micelles and DOX in inducing tumor cell death. In conclusion, FA-CA micelles reported in this work was a promising drug delivery vehicle for tumor targeting therapy.

An isophorone-fused near-infrared fluorescent probe with a large Stokes shift for imaging endogenous nitroxyl in living cells and zebrafish.

Nitroxyl (HNO) plays an important role in multiple physiological and pathological processes, but the detailed generation mechanism of the endogenous HNO still remained to explore and perfect further. There is an urgent need to develop an excellent fluorescent probe for selective recognition and sensitive detection of HNO in biological systems. Near-infrared (NIR) fluorescent probes with a large Stokes shift are an ideal tool for bioimaging applications. Here, we have developed a NIR fluorescent probe with a large Stokes shift, namely, NIR-HNO, to monitor HNO in cells and zebrafish. NIR-HNO consists of an isophorone-fused NIR fluorescence reporter and a diphenylphosphinobenzoyl HNO-responsive unit. Based on an aza-ylide intramolecular ester aminolysis reaction, NIR-HNO showed a rapid selective NIR fluorescent turn-on response for HNO, high sensitivity (detection limit was 39.6 nM), and large Stokes shift (265 nm). The biological imaging results indicate that NIR-HNO is a good candidate for imaging of endogenous HNO in living systems.