ASCORBIС ACID DEGRADATION IN N, N-DIMETHYLFORMAMIDE SOLUTIONS

Objective: Investigate the mechanisms of L-ascorbic acid transforтmation and formation of coloured enamines in N, N-dimethyl-formamide solutions. Methods: An automatic polarimeter Atago POL-1/2 was used for polarimetric investigation. Electronic spectra were recorded by UV-spectrometer Cary 60 (Agilent). The statistical analysis was carried out using the OriginPro 9.1 packages. Results: The Biot’s law violation was found in below 0.1% solutions of L-ascorbic acid (AA) in N, N-dimethylformamide (DMF). During the day, the specific rotation   of 1% AA solution varied from+37 to-1.0. Gradually, the solution acquired the red colour, and its intensity depended on the AA concentration. Spectrophotometrically, it was shown that after 15 min AA was absent in the n·10-3% solutions. The decomposition followed the first-order kinetics (k1=1.83·10-2с-1). At the same time, new absorption bands appeared at 273, 390, 533 nm. Model solutions containing dimethylamine (DMA) had a similar spectrum, and the intensity of the absorption bands increased in proportion to the concentration of DMA. Conclusion: The results show that the first step in the decomposition of ascorbic acid AA in DMF follows first-order kinetics. Numerous decomposition products are optically active compounds and reverse the sign of the optical rotation of the solution. The water resulting from the decomposition of AA is involved in the hydrolysis of the solvent. The hydrolysis product, the secondary amine DMA, interacts with the carbonyl groups of the AA decomposition products to form coloured enamines. Magnesium (II) accelerates the formation of coloured products

PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITY OF THE NEW ANTIVIRAL SUBSTANCE

Objective: To develop a set of quality control procedures for the promising antiviral pharmaceutical substance L-histidyl-1-adamantylethylamine dihydrochloride monohydrate, a derivative of rimantadine. Methods: Substances and solvents: synthesized in laboratory L-histidyl-1-adamantylethylamine dihydrochloride monohydrate (H-His-Rim•2HCl•H2O), rimantadine hydrochloride (Rim•HCl), 99%, ethanol 96%, N, N-dimethylformamide (DMF) anhydrous, 99.8% and n-hexane anhydrous, 95%, deionized high-resistance water (18.2 MΩ•cm at 25 °C, Milli-Q system), silver nitrate. Infrared (IR) Spectroscopy–Cary 630 Fourier Transform IR Spectrometer, elemental analysis–elemental composition analyzer CHNS-O EuroEA3000, ultraviolet (UV) spectrometry–Cary-60 spectrophotometer, polarimetry–POL-1/2 polarimeter with an external Peltier module, granulometric analysis by optical microscopy (Altami BIO 2 microscope) and low-angle laser light scattering (LALLS)–Master Sizer 3600, measurement of potential for hydrogen–potentiometer PB-11, Spirotox method–the study of temperature dependences of Spirostomum ambiguum lifetime to characterize the biological activity of the studied compounds. Results: The substance H-His-Rim•2HCl•H2O is an amorphous yellowish powder, slightly soluble in water, soluble in ethanol, freely soluble in N, N-dimethylformamide, and practically insoluble in n-hexane. A study of the elemental composition has confirmed the authenticity of H-His-Rim•2HCl•H2O. Comparison of the spectral characteristics of H-His-Rim•2HCl•H2O and Rim•HCl by IR spectroscopy and UV spectrometry confirmed the authenticity of the substance. The racemic form of the substance Rim•HCl with an insignificant amount of impurity of the levorotatory enantiomer was proved polarimetrically: α =-0.0126±0.0003 (1% aqueous solution, 20±0.5 °С). The specific optical rotation of 1% aqueous solution H-His-Rim•2HCl•H2O . In 1% ethanol solution -10.32±0.12. Using the method of laser light diffraction for a substance H-His-Rim•2HCl•H2O, the dimensional spectra «fraction of particles, %-d, μm» were characterized, the maximum of which in hexane is in the region of 40–50 μm. Arrhenius’s kinetics on the Spirotox model established statistically significant differences in ligand-receptor interactions, which are characterized by values of observed apparent activation energy °bsEa, kJ/mol: 132.36±1.55 for H-His-Rim•2HCl•H2O and 176.15±0.48 for Rim•HCl. Conclusion: The developed set of methods for assessment of physical and chemical properties and biological activity of a new antiviral substance H-His-Rim•2HCl•H2O is the basis for establish of regulatory documentation