The article is devoted to the synthesis of new starch derivatives containing 2-aminoethyl sulfate. The study examined the influence of various parameters on the process of modification of polysaccharides, including reaction time, pH of the medium, temperature and concentration of reagents. Optimal reaction conditions were determined. The structure of the resulting product was analyzed using spectroscopy methods, including infrared spectroscopy. Additionally, the nitrogen content in the macromolecule was determined in order to assess the degree of modification, since nitrogen is often introduced into the molecule through amino groups, changing its properties and functionality. The influence of the amount of nitrogen on the formation of azomethine bonds and their distribution in the macromolecule was studied. It has been established that an increase in the number of sulfate groups in a macromolecule leads to an increase in its acidity, which can be an important factor when considering its biological activity. The results obtained represent an important contribution to the understanding of polysaccharide modification processes and their application in various fields of science and industry.

The presence of reactive aldehyde groups in the elementary units of dialdehyde polysaccharides enables to enter easily into a condensation reaction with reagents containing primary amino groups in the structure. This naturally expands the possibilities of obtaining new derivatives of polysaccharides with physiologically active properties. In this study, we synthesized azomethine derivatives of cellulose and pectin differing in the degree of substitution and the content of the nucleophilic reagent in the composition of the reaction products through chemical interaction of guanidine with macromolecules of dialdehyde polysaccharides. Therefore, regularities of the reaction of nucleophilic substitution of aldehyde groups of oxidized polysaccharides with guanidine were revealed. It was found that the interaction of guanidine amino groups with oxidized pectin in contrast to dialdehyde cellulose occurs through the formation of azomethine and ionic bonds. Moreover, the possibility of obtaining guanidine-containing derivatives of cellulose and pectin with different structural characteristics by varying the molar ratio of the nucleophile and the oxidation state of the starting polysaccharides was proved. The composition and structure of the reaction products were studied by physicochemical methods of analysis. The stability and rate of cleavage of guanidine groups from the macromolecules of dialdehyde cellulose and dialdehyde pectin were studied by hydrolysis of the synthesized samples in acidic and alkaline media.

Pectin polysaccharides, due to the presence of reactive carboxyl functional groups in the structure, have a high complexing ability. This expands the scope of their practical application for the development of new biologically active substances. In this work, we propose the preparation of complex compounds based on sodium pectate and guanidine hydrochloride. By varying the molar amount of guanidine in relation to the acid groups of the polysaccharide matrix, samples were obtained that differ in the degree of substitution, the content of the amino derivative of the compound, and the inherent viscosity. The optimal ratio of the starting compounds was determined, at which the limiting amount of guanidine is bound to -COO- groups of pectin macromolecules. The structure of the resulting complexes was studied by FTIR spectroscopy. It has been established that the interaction of guanidine with polysaccharide carboxyls is accompanied by a change in the intensity of the absorption bands corresponding to the ionized acid group. Also, the binding of guanidine to the polysaccharide matrix through ionic bonds has been proven by carrying out the hydrolytic cleavage of the complex compound in an acidic medium. It is shown that with an increase in the hydrolysis time from 3 to 24 h, a gradual decrease in the initial degree of substitution of the complex compound is observed. The antimicrobial properties of polymer complexes with different characteristics against Staphylococcus aureus and Escherichia coli were studied.

Chemical modification of starch and cellulose was carried out using the periodate oxidation reaction.The structure of oxidized polysaccharides with different aldehyde group contents was studied by titrimetric analysis, X-ray diffraction analysis, and electron microscopy.According to the X-ray diffraction analysis data, amorphization of the structure of polysaccharides occurs in the process of periodate oxidation.Electron microscopy substantiated that as aldehyde groups grow in the macromolecular chain of starch and cellulose, there is a significant change in the morphology of polysaccharides.

Introduction. Up to the present time, there are practically no studies on the relationship between the structural characteristics and biological activity of antimicrobial polymers synthesized by the chemical addition of guanidine groups to polysaccharide macromolecules. Therefore, there is a need to carry out the chemical modification of guanidine with natural polymers, in particular polyaldehyde pectin, and to conduct comparative studies of the antimicrobial activity of the obtained samples with different physicochemical characteristics.Aim. To conduct the synthesis of guanidine-containing pectin derivatives. In addition, to determine the influence of structural variations in the obtained samples on exhibiting antimicrobial properties.Materials and methods. The synthesis of guanidine-containing pectin derivatives consisted of the following stages: periodate oxidation of the polysaccharide, modification of guanidine using polyaldehyde pectin, and chemical reduction of azomethine bonds. The amount of guanidine in the obtained samples was calculated by acidimetric titration, the nitrogen content (N, %) was determined using a Eura EA (Italy) elemental analyzer. The рКα values of the synthesized compounds were found by the back titration method. Absorption spectra were analyzed on a "UV 1280" spectrophotometer (Shimadzu, Japan) in the range λ = 180–400 nm. IR spectra were recorded on a Vector-22 spectrometer in the wavelength range of 400–4000 cm-1 in KBr tablets (3 mg sample / 300 mg KBr). The molecular weight characteristics of the synthesized derivatives were determined by high-performance gel permeation chromatography on an Agilent 1260 Infiniti liquid chromatograph. The acute toxicity of guanidine-containing pectin derivatives was calculated by the Prozorovsky method. Comparative assessment of antimicrobial activity was conducted by agar diffusion method.Results and discussion. By varying the oxidation level of polyaldehyde pectin, synthesized compounds differ in the degree of substitution, guanidine content, molecular weight, and pKα value. It was found that the levels of the antibacterial and antifungal activity of the studied samples depend on the degree of substitution and the nature of the counterion. The antimicrobial effect increases with an increase in the quantitative content of guanidine groups in the macromolecular chain of pectin. Moreover, it was found that the change of low molecular weight Cl–, NO3– , F–, I– counterions by carboxylate anions leads to a sharp decrease in antimicrobial properties. Upon oral injection of the synthesized compounds to mice, it was found that all samples belong to the category of practically non-toxic substances (V-class).Conclusion. Comparative analysis of guanidine-containing pectin derivatives with different characteristics showed that the severity of the antimicrobial action of the synthesized compounds against bacteria and fungi of the genus Candida depends on the quantitative content of cationic groups and the nature of the counterion.

Results of an investigation of the wound-healing activity and toxicity parameters of a gel based on guanidine-containing pectin derivatives are presented. It is established that the developed 0.5% pectin guanidine gel exhibits a high rate of wound healing that reaches 82% on the 7(th) day of treatment. The gel belongs to class VI of relatively harmless compounds, with an LD50 value of >3000 mg/kg for cutaneous application to rats. There were no signs of skin irritation in the form of redness, peeling, or changes in the fur cover in local shaven and adjacent regions in rats. Chronic toxicity studies showed that daily skin application of the pectin guanidine gel for 30 d did not produce any toxic effects on the quantitative composition and morphology of peripheral blood in experimental animals.

The article presents data on the synthesis and antimicrobial properties of guanidine-containing carboxymethylcellulose derivatives with different physical and chemical characteristics. The regularities of the reaction of nucleophilic substitution of the aldehyde groups of modified Na-carboxymethylcellulose (Na-CMC) by guanidine under different conditions have been studied. It has been found that the maximal replacement of reactive electrophilic groups by nucleophilic reagent depends on the pH value of the medium, molar ratio of guanidine, and the degree of oxidation of cellulose ester. The azomethine derivatives with different content of nitrogen-containing fragments in the polymer chain have been synthesized by varying the reaction conditions and the number of aldehyde groups in oxidized Na-CMC. Chemical reduction of labile azomethine bonds has led to water-soluble derivatives that contain strong amino-bound guanidine groups. The study shows and substantiates the influence of structural parameters (degree of substitution, quantitative guanidine content, p K α values, and nature of counterions) of macromolecular systems on antibacterial and antifungal properties. The developed approach to the synthesis opens up prospects for the creation of antimicrobial derivatives with regulated physical and chemical characteristics and specified biologically active properties.

Взаимодействием диальдегид-производного полигалактуроновой кислоты последовательно с гидразидом изоникотиновой кислоты и этамбутолом получен конъюгат, содержащий гидразид изоникотиновой кислоты, присоединенный посредством азометиновой связи (20 ± 2 моль %), и этамбутол, присоединенный ионной связью (25 ± 2 моль %). В условиях in vitro на клинических штаммах M. tuberculosis и H37Rv, а также в условиях in vivo на штаммах Humanis и Bovis полученный конъюгат показал выраженную противотуберкулезную активность. При введении конъюгата крысам терапевтическая концентрация активных веществ (изониазида и этамбутола) в крови сохранялась дольше, чем их низкомолекулярных аналогов, что указывает на возможность пролонгирования их противотуберкулезной активности.

Aconjugate containing isonicotinic acid hydrazide linked with a hydrazone bond (20 ± 2 mol%) and ionically bonded ethambutol (25 ± 2 mol%) was prepared by reacting a dialdehyde derivative of poly(galacturonic acid) successively with isonicotinic acid hydrazide and ethambutol. The obtained conjugate showed pronounced antituberculosis activity in vitro on clinical strains of M. tuberculosis and H37Rv and in vivo on Humanis and Bovis strains. The therapeutic concentrations of the active substances (isoniazid and ethambutol) in blood after administration of the conjugate to rats persisted longer than those of their low-molecular-mass analogs, thereby exhibiting a prolonged antituberculosis effect.

The article presents data on the synthesis and antimicrobial properties of guanidine-containing carboxymethylcellulose derivatives with different physical and chemical characteristics. The regularities of the reaction of nucleophilic substitution of aldehyde groups of modified Na-carboxymethylcellulose (Na-CMC) by guanidine under different conditions are studied. Based on the results obtained, it was found that the limit replacement of reactive electrophilic groups with nucleophilic reagent depends on the pH value of the medium, molar ratio of guanidine and the degree of oxidation of cellulose ester. By varying the reaction conditions and the number of aldehyde groups in the oxidized Na-CMC composition, the azometin derivatives differing in the content of nitrogen-containing fragments in the polymer chain were obtained. Chemical restoration of labile azomethine bonds was performed and water-soluble derivatives containing strong amino-bound guanidine groups were synthesized. The study shows and substantiates the influence of structural indices (degree of substitution, quantitative guanidine content, pKα values and nature of counterion) of macromolecular systems on antibacterial and antifungal properties. The developed approach of synthesis opens prospects for creation of antimicrobial derivatives with regulated physical and chemical characteristics and set biologically active properties.

Preparation of new derivatives of polysaccharides showing biological activity, precisely, antimicrobial properties remains quite a priority task not only in chemistry of high molecular mass compounds but also in pharmaceutics and medicine, since some antimicrobial compounds obtained on the basis of natural polymers are superior to synthetic low molecular mass antimicrobial compounds on some criteria. New water soluble pectin derivatives containing sulphamic groups in their structure were obtained in this paper by the interaction of sulphamic acid with polysaccharide aldehyde groups. The structure and composition of the resulting compounds were studied by IR spectroscopy, elemental (nitrogen, sulphur) and X-ray crystal analyses. Sulphamic pectin derivatives with various contents of sulphamic groups were obtained by changing the concentration of sulphamic acid in relation to dialdehyde pectin derivatives. The optimum ratio of reactive components that is CHO/NH2SO3H = 1.0 : 2.5 and the reaction time of 45 min were found. Study results of antimicrobial action of the synthesized sulphamic pectin derivatives were presented. Biological activity of the resulting compounds was studied by the disk diffusion method in relation to Gram positive and Gram negative bacteria. Direct dependence of antimicrobial activity of the studied drugs on the quantitative content of sulphamic groups in pectin was found. It was determined that sulphamic pectin derivatives with a degree of substitution of 35.0 showed antimicrobial activity in relation to Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus vulgaris, Streptococcus faecalis, Streptococcus pyogenes, Streptococcus faecalis, Pseudomonas aeruginosa with a concentration of 50 Mg/mL. Antimicrobial action begins to decrease with the decrease in the number of sulphamic groups. Study results of acute toxicity of sulphamic pectin derivatives were presented. According to the results, they can be referred to class V almost nontoxic substances.

New water-soluble derivatives of starch, pectin, and Na-CMC containing the sulfamic groups have been obtained by the reaction of sulfamic acid with dialdehyde polysaccharide derivatives. The structure and composition of the resulting compounds have been studied by IR spectroscopy, elemental (nitrogen and sulfur) analysis, and X-ray diffraction. The sulfamic derivatives of starch, pectin, and Na-CMC with a different content of the sulfamic groups have been obtained by varying the ratio of sulfamic acid to the dialdehyde polysaccharide derivatives. The optimal–СНО: NH2SO3H ratio was found to be 1: 2.5. The interaction rate of sulfamic acid with the dialdehyde derivatives of starch, pectin, and Na-CMC has been evaluated. The antibacterial and antifungal effects of sodium salts of the sulfamic starch, pectin, and Na-CMC derivatives against Gram-positive and Gram-negative bacteria and fungi have been studied at different concentrations (10, 25, 50 mg/mL) by the disk diffusion method. The synthesized compounds have not been found to exhibit antifungal activity against Candida albicans. Nevertheless, they have been shown to have the antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus vulgaris, Streptococcus faecalis, Streptococcus pyogenes, and Streptococcus faecalis at the concentration of 50 mg/mL. The concentration dependence of antibacterial action of sodium salts of the starch, pectin, and Na-CMC sulfamic derivatives has been demonstrated. The antibacterial activity of the drugs has been found to directly depend on the content of the sulfamic groups in polysaccharides. The results on the acute toxicity of the sulfamic polysaccharide derivatives have shown that these compounds can be attributed to low-toxicity substances of Class V.

Polymeric guanidine derivatives occupy a special place among antimicrobial compounds. Guanidines are well soluble in water, have a wide spectrum of antimicrobial action and durable effects, nontoxic, and also meet modern medical requirements. Due to the high reactivity of guanidine to interact with various functional groups, we manage to carry out a number of new chemical modifications that allow obtaining new biologically active low and high molecular mass compounds. The present paper presents preparation of water-soluble guanidine derivatives of pectin and carboxymethyl cellulose bound between each other with the amine bond. A process for the preparation of guanidine derivatives of pectin and carboxymethyl cellulose consists of the following stages: periodate oxidation of polysaccharides, the condensation reaction of guanidine with oxidized pectin and carboxymethyl cellulose, -C=N bond reduction. The structure and composition of the resulting compounds were studied by IR spectroscopy, X-ray structural and elemental analysis (by nitrogen content). It was determined that the maximum number of guanidine groups in the resulting products was contained during the interaction of dialdehyde derivatives of pectin and carboxymethyl cellulose with guanidine in a 1.0 : 2.3 molar ratio. Antimicrobial activity of resulting guanidine derivatives of pectin and carboxymethyl cellulose against Staphylococcus aurcus, Staphylococcus epidermidis, Klebsiella, Escherichia coli and Streptococcus faecalis was explored. It was found that bacteriostatic effect began to increase with an increase in the concentration of the obtained compounds. The paper gives acute toxicity studies results on guanidine derivatives of pectin and carboxymethyl cellulose, upon the results of which they can be referred to class IV slightly toxic substances.