SYNTHESIS OF POLYMERIC NITROGEN DONATIONS BASED ON INULIN DERIVATIVES
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330 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz SYNTHESIS OF POLYMERIC NITROGEN DONATIONS BASED ON INULIN DERIVATIVES 1Abduhomidova F.O. 2Khusenov A.Sh. 2Rakhmanberdiev G. 2Ibragimova K.S. 1Karshi State Technical University, Karshi city, Republic of Uzbekistan 2Tashkent Institute of Chemical Technology, Tashkent city, Republic of Uzbekistan e-mail: [email protected] https://doi.org/10.5281/zenodo.17337056 Relevance: Nitric oxide (NO) donors are widely used in the treatment of cardiovascular diseases, pulmonary hypertension, and are also actively studied in the treatment of neurodegenerative pathologies. Such drugs as Nitroglycerin, Molsidomine and Nicorandil are capable of releasing nitric oxide. In the context of the growing number of chronic diseases and an aging population, there is a growing need for effective and safe means regulating the bioavailability of NO. In addition, the improvement of synthesis methods makes it possible to obtain nitrogen donors with a given structure that ensures controlled release of NO under physiological conditions of the body. For these reasons, the development of new methods for the synthesis of nitrogen donors with controlled release and high biocompatibility is becoming a particularly interesting task. Purpose of the study: Synthesis of new nitrogen donors by targeted chemical modification of inulin esters. Materials and methods: For synthesize nitrogen donors, sodium salt of carboxymethylinulin (CMI) was initially synthesized by alkylation of the polysaccharide in the presence of monochloroacetic acid. For this, inulin was dispersed in ethanol for 2 hours, then a 15% alkali solution was added and stirred for 1 hour. The reaction was carried out with Na-MCUA (sodium salt of monochloroacetic acid) at a molar ratio of inulin:Na-MCUA=1:4, a temperature of 70°C for 1.5 hours. Purification was carried out by extraction with 96% ethanol, then the samples were dried at 50-60°C. A KMI sample with a substitution degree of 34 mol.%, dried to a constant weight, was esterified under homogeneous conditions with a nitrating mixture of the following composition: HNO3÷H3PO4÷P2O5, wt.% = 20:75:5 at room temperature for 30 minutes. Then the nitrating mixture was poured into a tenfold volume of ice-cold distilled water, the resulting white precipitate of inulin nitroester was separated on a Schott glass filter and washed in distilled water until the washing waters were neutral, dried in a vacuum oven and analyzed. Results: The FTIR spectra of the synthesized compounds showed absorption bands with maxima in the region of 1650 cm-1 (N=O), 838 cm-1 (N-O), 1280 cm-1 (symmetric stretching vibrations of N=O bonds), 1745 cm-1 (C=O). Elemental analysis showed that the weight nitrogen content in the sample was 9.7% and its substitution degree for -NO2 groups was 1.50 mol%. The obtained data indicate the efficiency of nitration with preservation of the main structure of the polysaccharide. The substitution degree indicates a partial but controlled introduction of nitro groups, which is important for subsequent regulation of their release. The rate of nitro group splitting at pH 7.4 was studied. Thus, it was found that nitro groups included in the polymer chain have a prolonged release in a weakly alkaline medium. Within 3, 6, 12 and 24 hours, the rate of nitrogen oxide release is 12, 37, 60 and 85%, respectively. These data prove that nitro groups contained in the inulin structure are unstable in a weakly alkaline medium and begin to split off within 24 hours.
331 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz Conclusions: The obtained nitro derivatives of inulin are characterized by a controlled level of substitution and the ability to prolonged release of nitrogen oxides in a weakly alkaline medium. This confirms their potential as nitrogen donors with controlled release kinetics.