Carboxymethyl Derivatives Research Articles

Preparation and degradability of novel cross-linked functional hydrogels from enzymatic synthesized α-1,3-glucan and its carboxymethyl derivative

Abstract In this research, we prepared novel hydrogels from enzymatically synthesized α-1,3-glucan and its carboxymethyl derivative by crosslinking with ethylene glycol diglycidyl ether. The resulting hydrogels were highly swellable and pH-sensitive with an enhanced highly developed structure and showed excellent protein/dye adsorption performances. Furthermore, the hydrogels had good biodegradability and could be degraded in soil extract solution. Herein, the prepared hydrogels have potential applications as a green and environmentally friendly adsorbent for the effective removal of organic dyes in printing and dyeing wastewater.

PROSPECTS FOR MODIFYING THE STRUCTURE OF CHITIN AND CHITOSAN OF HIGHER FUNGI TO EXPAND THE POTENTIAL OF THEIR APPLIED USE

The review is devoted to summarizing scientific data in the field of the chemical structure and properties of chitin and chitosan obtained from fungal biomass, and to analyzing directions for their modification for use in medicine and the food industry as substances with antibacterial, antiviral, wound-healing and anticoagulant activity. The features of chitin biosynthesis by fungi of the Basidiomycota, Ascomycota, Deuteromycota departments and chitosan biosynthesis by fungi of the Zygomycota department are covered. It has been shown that higher fungi contain chitin in their cell walls in the form of a chitin-glucan complex, while lower fungi (zygomycetes) contain chitin in the form of chitosan-glucan. Effective components of substrates that influence the production of polysaccharides by fungi have been identified - carbohydrates in the form of glucose, sucrose and maltose, organic forms of nitrogen in the form of yeast extract and corn flour, mineral components in the form of dihydrogen phosphate and dipotassium monohydrogen phosphate. Particular attention is paid to methods for isolating chitin and modifying it to chitosan with a detailed description of the physicochemical and biological properties of polymers. The review also presents the main reactions and methods for obtaining carboxymethyl and sulfo derivatives of chitin and chitosan. The biological properties and application of these groups of substances are described. In the carboxymethylation of chitin and chitosan, the choice of appropriate reaction conditions and reagents makes it possible to obtain carboxymethyl chitin, N-, O-, N,O-carboxymethylchitosan, or N,N-dicarboxymethylchitosan. The properties and applications of carboxymethyl derivatives of chitin and chitosan strongly depend on their structure, degree of substitution, and arrangement of amino or hydroxyl groups. The main reagents in the preparation of carboxymethyl derivatives are sodium monochloroacetate, monochloroacetic and glyoxalic acids. Carboxymethyl derivatives of chitin and chitosan are used as drug delivery systems, antimicrobial agents, in tissue engineering, as components of cosmetics and food products. Modification of chitosan with sulfate groups makes it possible to obtain chitosan 2-N-, 6-O-, 2-N-6-O- and 3-O-sulphates. The main sulfonating agents are oleum, pyridine and chlorosulfonic acid. Sulfonic derivatives of chitin and chitosan can be used as a basis for obtaining hemocompatible materials (with antithrombotic and antibacterial activities).

Synergistic studies of Cassia tora gum with xanthan and guar gum: Carboxymethyl synthesis of cassia gum-xanthan synergistic blend and characterization

The present study describes the study of synergistic behavior of the Cassia tora (CTG) gum with xanthan gum (XG) and comparison with CTG and guar gum (GG) at varying temperatures. A carboxymethyl derivative of CTG: XG blend, having synergistic activity was synthesized and the reaction conditions were optimized using Taguchi's L′9 statistical design. The effect of solvent medium on the degree of substitution (DS) and the gelling property was also studied. The results reveal that synergistic interaction was found in the CTG: XG mixture whereas CTG: GG blend did not show synergistic behavior. The CTG: XG blend shows a highly viscous solution having 8371.9 cps viscosity at ambient temperature and gel is obtained by heating the blending solution and thereafter lowering the temperature. In continuum, an optimized carboxymethyl derivative (DS 0.16) also exhibits gelling properties. The carboxymethyl derivative was characterized by 1H NMR, FTIR spectroscopy and FESEM analysis. The synergistic action of gums may be utilized in food, cosmetics and pharmaceutical applications.

Comparative studies on enantioseparation of New Psychoactive Substances using cyclodextrin-assisted capillary electrophoresis with UV detection

New psychoactive substances (NPS) count as psychoactive substances, which are slightly modified compared to illicit drugs regarding their chemical structure to circumvent law. Compared to classical drugs such as heroin, cocaine, or amphetamine, they show similar psychoactive effects, however, because of their novelty there is few knowledge about their side effects or toxicity. NPS are available as different chemical substance classes, among them chiral novel derivatives of amphetamine, cathinone, and ketamine. Since in most cases no clinical studies are available about the possibly different effects of the two enantiomers, there is a big demand for enantioseparation method development. Besides high-performance separation techniques such as gas chromatography or HPLC, capillary electrophoresis has turned out to be a powerful alternative for chiral separation development. The addition of chiral additives such as cyclodextrins to the background electrolyte often results in successful attempts. The present study compares the chiral separation power of different previously used non-charged ß-cyclodextrins, among them native ß-cyclodextrin as well as some of its derivatives such as acetyl-, and 2-hydroxypropyl-β-cyclodextrin, with the negatively charged derivatives carboxymethyl-, carboxyethyl- and succinyl-β-cyclodextrin by capillary zone electrophoresis. A total of 136 chiral NPS were investigated with these cyclodextrins, 122 of them were resolved in their enantiomers successfully by means of a simple electrolyte composition consisting of 10 mM aqueous sodium hydrogen phosphate buffer, pH 2.5 and 10 mM of the chiral selector. Furthermore, the presented method turned out to be useful to distinguish between positional isomers and examples for both enantiomer order and positional order for seized samples are given.

Synthesis of carboxymethyl Xanthan/ double-walled carbon nanotube hybrid hydrogel nanocomposite for transdermal release of drug

ABSTRACT The inclusion of double-walled carbon nanotubes in carboxymethyl xanthan-based hydrogels was developed in order to improve both mechanical and drug release (diclofenac) properties of these nanocomposites for potential application in the biomedical field. The synthesis of carboxymethyl xanthan was carried out by an esterification reaction between xanthan gum and monochloroacetic acid, and the grafting was confirmed by FTIR analysis. The obtained carboxymethyl derivatives exhibited higher hydrophilicity degrees of substitution compared to the native xanthan gum. The nanocomposites prepared using either raw or modified xanthan gum were characterized in terms of physical properties, and we evidenced both an increase in viscoelasticity by one order of magnitude and an improved distribution of the nanotubes within the hydrogel matrix in the case of the carboxymethyl xanthan. The trapping efficiency of diclofenac was improved by the addition of the nanotubes, reaching up to 74 wt %. While the nanotubes also allowed a slower release of the molecule. An in-vitro study was carried out to ensure that the CNTs grafted onto the modified CMX were not released during the diffusion of the active ingredient.

Efficient Prediction of InVitro Piroxicam Release and Diffusion From Topical Films Based on Biopolymers Using Deep Learning Models and Generative Adversarial Networks.

The purpose of this study was to simultaneously predict the drug release and skin permeation of Piroxicam (PX) topical films based on Chitosan (CTS), Xanthan gum (XG) and its Carboxymethyl derivatives (CMXs) as matrix systems. These films were prepared by the solvent casting method, using Tween 80 (T80) as a permeation enhancer. All of the prepared films were assessed for their physicochemical parameters, their invitro drug release and exvivo skin permeation studies. Moreover, deep learning models and machine learning models were applied to predict the drug release and permeation rates. The results indicated that all of the films exhibited good consistency and physicochemical properties. Furthermore, it was noticed that when T80 was used in the optimal formulation (F8) based on CTS-CMX3, a satisfactory drug release pattern was found where 99.97% of PX was released and an amount of 1.18mg/cm2 was permeated after 48h. Moreover, Generative Adversarial Network (GAN) efficiently enhanced the performance of deep learning models and DNN was chosen as the best predictive approach with MSE values equal to 0.00098 and 0.00182 for the drug release and permeation kinetics, respectively. DNN precisely predicted PX dissolution profiles with f2 values equal to 99.99 for all the formulations.

Studies of the Removal of Pb2+ and Cd2+ from Aqueous Solutions using POCl3 Cross-linked Carboxymethyl Derivatives of Legume Starch

Studies of the Removal of Pb2+ and Cd2+ from Aqueous Solutions using POCl3 Cross-linked Carboxymethyl Derivatives of Legume Starch

Microstructure of biopolymer-modified aerial lime mortars

Cellulose-based viscosity-modifying admixtures are used on daily basis in a wide range of building materials, dominantly in pre-mixed mortar systems. Lately, alternative admixtures such as different “gums” have emerged. In building materials, the gums have similar viscosity-enhancingeffects as cellulose ethers with different efficiency. Various ways of production, as well as diverse working mechanisms of the biopolymers are to be considered while choosing the most suitable admixture for the intended use. Influence of alternative admixtures in several doses on the microstructure of lime mortars was studied in this paper. Mortars were prepared with the same workability and the air content in fresh mortar was determined, for it can have notable impact on microstructure of hardened mortar. Hydroxypropyl derivative of chitosan showed air entraining ability, while the carboxymethyl derivative reported slight decrease in amount of air entrained into the mixture. In the case of diutan gum, the most water-demanding admixture, the percentage of entrained air dropped with growing dose. Admixture addition increased the volume of pores in diameter lower than 0.1 μm, and in region of pores around 10 μm. Only the diutan gum affected the distribution of capillary pores, which are typical for lime mortars. Hygric properties were in correlation with air content values.

Dipteran Carboxymethyl Chitosan as an Inexhaustible Derivative with a Potential Antiproliferative Activity in Hepatocellular Carcinoma Cells.

Traditional folk therapies indicate that insects have diverse medicinal potentials. However, the therapeutic application of insect chitosan and its derivatives has not been explored. To investigate the application of chitosan and its derivatives, the carboxymethyl derivative of chitosan (CM-Ch) was extracted from two dipteran larvae species, Chrysomya albiceps and Sarcophaga aegyptiaca. The degree of deacetylation (DD) and CM-Ch functional groups were validated using Fourier-transform infrared (FTIR) spectroscopy analysis and proton nuclear magnetic resonance spectroscopy (1H NMR), respectively. The molecular weight was estimated using MALDI-TOF MS analysis. The effect of CM-Ch on the morphology and proliferation of human liver HepG2 cancer cells was assessed. IC50 of CM-Ch induced significant growth-inhibitory effects in HepG2 cells. CM-Ch treatment altered the morphology of HepG2 in a dose-dependent manner and induced apoptosis in a caspase-dependent manner. CM-Ch treatment showed no signs of toxicity, and no alterations in liver and kidney biochemical markers were observed in albino rats. A CM-Ch derivative from commercial crustacean chitosan was used to assess the efficacy of the insect-derived CM-Ch. The data presented here introduce insect CM-Ch as a promising, inexhaustible, safe derivative of chitosan with antitumor potential in liver cancer. This is the first report highlighting the anticancer activity of insect CM-Ch in hepatocellular carcinoma cells.

Thermo-responsive microfibrillar graft copolymer based on carboxymethylagarose and N-isopropylacrylamide

Carboxymethylation of agarose with ClCH2COOH in 2-propanol, formamide or dimethyl sulfoxide were evaluated in order to obtain water soluble derivatives. Higher yield (86%) and degree of substitution of carboxymethylation in primary alcoholic groups (0.70) were obtained using dimethyl sulfoxide. Carboxymethylagarose-g-PNIPAAm copolymers were synthesized by free radical graft copolymerization using Ce4+ and S2O82−/TEMED as initiators via conventional or microwave-assisted methods. Carboxymethyl derivatives and graft copolymers were characterized by FT-IR and NMR spectroscopies, elemental analysis, TGA and DSC and morphology analysis by SEM and AFM. High nitrogen content (9.7%) was found with Ce4+ by conventional method and the obtained analysis allowed to confirm the NIPAAm grafting on the carboxymethylagarose chain. Thermoresponsive materials have a low critical solution temperature between 32 and 34 °C. Thermal stability increased ca. 60% with PNIPAAm grafting. Surface analysis of copolymers reveals a microfibrillar type morphology with diameter of 4–6 μm. Synthesized glycoconjugates could find applications in bioactive compounds transport in biological systems.

Carboxymethylated starch and cellulose derivatives-based film as human skin equivalent for adhesive properties testing

The films based on carboxymethyl derivatives of starch (CMS) and cellulose (CMC) were proposed as a novel human skin equivalent. The physicochemical properties (moisture absorption, solubility in water, mechanical properties) of CMS/CMC films were evaluated. Additionally, some properties were compared to the human skin ones (surface roughness, tribology). The system based on CMS/CMC 25/75 wt. % was selected for testing the adhesive properties of pressure-sensitive adhesives commonly used for medical purposes (acrylic, silicone and polyisobutylene). Similar tests were performed for human skin. The peel adhesion values for CMS/CMC film and human skin were similar for all adhesives types tested. Applying such a skin equivalent allows to evaluate the functional properties of medical pressure-sensitive adhesives without the ethical and economic issues.

High affinity antibody based on a rationally designed hapten and development of a chemiluminescence enzyme immunoassay for quantification of Alternariol in fruit Juice, maize and flour

Alternariol (AOH), a secondary metabolites of the genus Alternaria, is a genotoxic mycotoxin. Because the previous “Mannich antigen” for AOH readily underwent unstable induction, a new AOH hapten was designed for inducing a high-quality antibody against AOH using a conjugate of the AOH carboxymethyl derivative with a carrier protein as the immunogen. A competitive indirect chemiluminescence enzyme immunoassay (ciCLEIA) for AOH was optimized and showed good sensitivity (limit of detection 0.068 ng/mL), a linear range (0.11–1.23 ng/mL), and negligible cross-reactivity with analogues. Average rates of recovery from spiked samples (juice and cereal) were between 72.7% and 115.8%, with coefficients of variation <14.3%. Results from ciCLEIA correlated well with those of high-performance liquid chromatography coupled with tandem mass spectrometry, meaning the proposed method might be an effective screening tool for detection of AOH in food samples.

Differences in the complexation of sodium with methyl esterified carboxymethyl/methoxyacetyl-O-glucans in electrospray ionization-mass spectrometry

Methoxyacetates and (methoxycarbonyl)methyl ethers of alcohols are isomers where only the positions of CO and CH2 are interchanged. Therefore, methoxyacetates of methyl esterified carboxymethyl derivatives of glucans were expected to give equal response in electrospray ionization mass spectrometry which is a prerequisite for the quantitative analysis of substitution patterns in carboxymethyl celluloses (CMC). In order to find out why this is not the case, corresponding derivatives of 1,2-ethanediol and trans-1,2-cyclohexanediol, resembling the 2,3-diol feature of glucose, where studied in ESI–MS. At high total concentration (10−3M) in pure acetonitrile, the methoxyacetates of the model compounds were strongly discriminated. With dilution, the relative intensities (RI) of the isomeric analytes progressively dropped to achieve ∼2 at a total concentration of 10−10M. Similar retention in chromatography and surface activity and polarity parameters do not indicate to different surface chemistry of the constitutional isomers as predominant reason for this strong suppression. Quantum-chemical calculations (DFT) showed a difference of binding energies for Na+ between the two diol derivatives of about 50kJ/mol. While the CM-ethers can involve the more basic carbonyls into the tetra-coordinated sodium complex, this is sterically not possible for the methoxyacetates. At addition of 10% water RI drastically decreased probably due to change of conditional stability constants of the competing sodium complexes. Adjusting sodium molarities to 10−4M up to 10−2M caused typical salt effects, but will also influence the formation of sodium adducts. In case of mono- and substantially in di- and oligosaccharides, the number of conformations that can coordinate Na+ are more complex, and the discrepancy between the various substituent patterns decreases, but does not fully disappear.

Development of smart hydrogels of etherified gum ghatti for sustained oral delivery of ropinirole hydrochloride

Gum Ghatti (GG) is a water soluble complex polysaccharide obtained from Anogeissus latifolia. Due to its non toxic and excellent emulsifying characteristics, it was widely used in different pharmaceutical preparations. Currently another facet was explored for its utility as release retardant polymer in oral controlled drug delivery system. As GG solely was incapable of forming microspheres therefore modification of GG to Sodium carboxymethyl (NaCMGG) derivative was done by carboxymethylation process and its gel forming capacity was explored by the use of trivalent cation (Aluminium chloride) which results into complete microbead system in a complete aqueous environment for controlled delivery of Ropinirole Hydrochloride (RHCl). Rheological property of NaCMGG showed pseudoplastic shear thinning behavior. Spherical shape of bead was observed under scanning electron microscope. Depending upon the formulation variables, Drug entrapment efficiency (DEE) varies from 47.66±3.51 % to 71.4±2.65%., and 80 to 90% drug was released in 6h in pH 6.8 phosphate buffer. Drug release was governed by both fickian diffusion and polymer relaxation simultaneously. Compatible environment for drug entrapment was established by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). Thus the modified derivative NaCMGG could be a promising polymer in biomedical application.

Development and characterization of seed gums from Tamarindus indica and Cassia fistula as disintegrating agent for fast disintegrating Thai cordial tablet

Crude seed gum and their carboxymethyl derivatives from Tamarindus indica and Cassia fistula seeds were developed and characterized to apply as the pharmaceutical disintegrant in fast disintegrating Thai cordial tablet. The chemical structure of crude gum was chemically modified via carboxymethylation. Degree of substitution (DS) of carboxymethylated gums was determined. Carboxymethylated gums with minimum and maximum DS values were chosen for further application. IR absorption spectra of gum samples were observed to verify their chemical structure changes. In physical properties, the intrinsic viscosity and swelling property of all gum samples were evaluated. The results showed that carboxymethylated gums had higher intrinsic viscosity than those of crude gum. Moreover, they could swell and be soluble in cold water better than those of crude gums. In conclusion, the modified gums from both plants could provide higher hardness and be better used than that crude gums for fast disintegrating Thai cordial tablet. However, this is a preliminary assessment to expressing pharmaceutical application possibility of these gums as disintegrants, diluents and drug release controlling agents.

Immunoregulatory effect assessment of a novel melanin and its carboxymethyl derivative

A novel melanin with low molecular weight (LIM205, 522Da) was isolated from the fermentation broth of Lachnum sp. and its carboxymethyl derivative (CLIM205) was prepared. The immunoregulatory effects of LIM205 and CLIM205 in immuno-compromised mice induced by cyclophosphamide were investigated. The results demonstrated that both LIM205 and CLIM205 could significantly increase the thymus and spleen indices, specific and nonspecific (including carbon clearance ability) immunity, humoral and cellular immunity of mice. Treatment with LIM205 and CLIM205 could increase activities of SOD, GSH-PX, CAT and decrease content of MDA in the mice. Furthermore, for all animal tests, the immunoregulatory activities of CLIM205 were more prominent than that of LIM205. In conclusion, our findings suggested that the natural products LIM205, as well as its carboxymethyl derivative CLIM205, had significant immunoregulatory activities, which might be a promising source of immunoregulator in healthcare field.

Solid-phase amination of Geotrichum candidum lipase: ionic immobilization, stabilization and fish oil hydrolysis for the production of Omega-3 polyunsaturated fatty acids

In this paper, solid-phase chemical amination was applied to enrich the surface of Geotrichum candidum lipase (GCL) with amino groups. The aminated enzyme was slightly thermostabilized and showed a different activity profile at different pH in relation to the non-aminated enzyme. Furthermore, the chemical modification allowed the enzyme to be rapid and easily immobilized on carboxymethyl and sulfopropyl agarose-based supports. The cationically exchanged derivatives presented higher thermostability and higher stability at alkaline pH than the soluble aminated enzyme. In addition, the carboxymethyl derivative was 5.4-, 8.7- and 9.1- and the sulfopropyl derivative was 6.6-, 11.7- and 10.7-fold more stable than the free aminated enzyme in methanol, propanol and cyclohexane, respectively. The ionic derivatives were applied for fish oil hydrolysis in organic aqueous medium at 37 °C. After 72 h of reaction, Omega-3 production corresponded to 354 and 482 μM using the carboxymethyl and sulfopropyl derivatives, respectively. These derivatives resulted, respectively, in 2.4- and 3.2-fold increased fish oil hydrolysis when compared to the soluble aminated lipase. After the reaction, carboxymethyl derivative presented 6.65 U per gram of support and sulfopropyl derivative showed 7.85 U per gram of support, making them attractive for industrial application.

Production of omega-3 polyunsaturated fatty acids through hydrolysis of fish oil by Candida rugosa lipase immobilized and stabilized on different supports

This paper describes the fish oil hydrolysis performed to obtain Omega-3 fatty acids using Candida rugosa lipase (CRL) immobilized and stabilized on different supports. The enzyme was successfully immobilized, presenting higher thermal stability than the free enzyme. Besides, the cationic derivatives were more stable than the others derivatives and free enzyme in methanol, propanol and cyclohexane. Reactions of fish oil hydrolysis were carried out in organic aqueous medium using 10 U of biocatalyst per gram of oil, at 37 °C. After 96 h, the CRL immobilized on cyanogen bromide agarose rendered the lower fish oil hydrolysis, producing 218 μM of Omega-3, which was 1.1-fold more than the hydrolysis catalyzed by free enzyme, while the ionic derivatives rendered the highest fish oil hydrolysis producing 582 and 577 μM of Omega-3 using the carboxymethyl and sulfopropyl derivatives, respectively. The carboxymethyl and the sulfopropyl derivatives resulted in a 2.9-fold increase in the hydrolysis of fish oil, making these derivatives attractive for industrial applications.

Carboxymethylated polysaccharide-based films as carriers for acrylic pressure-sensitive adhesives

A novel application of a biodegradable polysaccharide-based film as a pressure-sensitive acrylic adhesive carrier has been reported. For film preparation carboxymethyl derivatives of starch (CMS) and cellulose (CMC) have been used. Based on physicochemical tests results (solubility in water, moisture absorption, mechanical properties) the most promising CMS/CMC 50/50wt% film was selected as a carrier for an acrylic pressure-sensitive adhesive tape. Prepared double-sided self-adhesive tapes were characterized by good tack 5N/2.5cm, peel adhesion 12N/2.5cm and shear strength 90N/6.25cm2 at 20°C. Such acrylic self-adhesive tapes could find application in the paper industry.

Extraction and derivatization of Leucaena leucocephala (Lam.) galactomannan: Optimization and characterization

Water soluble gums also known as hydrocolloids are increasingly finding applications in the pharmaceutical and food industry due to their versatile functional properties. They possess considerable use in food and pharmaceutical industries as emulsifying, thickening and gelling agents. In the present investigation a heteropolysaccharide galactomannan was extracted from Leucaena leucocephala (Lam.) seeds by an aqueous method, characterized for its compositional analysis (mannose: galactose ratio), physicochemical and functional properties (solubility), and mechanical properties. The extracted gum was derivatized to form its carboxymethyl derivative and the method of its derivatization was optimized by varying the reaction parameters. The native and derivatized gum was characterized by FTIR, XRD, DSC, NMR, SEM and elemental analysis, etc. The yield of Leucaena leucocephala galactomannan (LLG) was found to be 20% (w/w). The optimized parameters for carboxymethylation reaction (degree of substitution 0.805) were found to be 6.0g NaOH, 10.0g MCA, at 60°C for 4h. The physicochemical and functional characteristics of native and derivatized gum suggest its potential role in food and pharmaceutical industries.