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Section 11. Chemistry
https://doi.org/10.29013/ESR-19-11.12-77-87
IsaevYusup, Cand. chemical Sciences, Head of the Department of Chemistry Andijan State University
Andijan, Uzbekistan E-mail: yusufjon_67@inbox.ru
Rustamov Sanzhar, postgraduate student, Andijan State University,
Andijan, Uzbekistan
Askarov Ibrohim, Doc. chemical of Sciences, Professor Andijan State University, Andijan, Uzbekistan
Ziyayev Khayrulla Lutfullaevich, Doc. chemical of Sciences, Senior Researcher, The Institute of Bioorganic Chemistry, Tashkent, Uzbekistan
SUPRAMOLECULAR COMPLEX OF MONOAMMONIUM SALT OF GLYCIRRIZINIC ACID WITH NORSULFAZOL
Abstract. This article presents the results of studying the composition and nature of the intermolecular interactions of the components of the complex compound of the monoammonium salt of glycyrrhizic acid with norsulfazole sodium using the isomolar series method. Also calculated is the change in Gibbs energy and the stability constant of the complex.
Keywords: Licorice, glycyrrhizic acid, monoammonium salt of glycyrrhizic acid, isomolar series method, sulfonamides.
From ancient times, plants are considered the main raw material base of medicines. One of the famous medicinal plants is licorice. This plant belongs to the genus Glycyrrhiza, a family of legume Fabaceace.
In the world flora there are more than ten types of licorice. The most widespread and practical applications are found by Glycyrrhiza glabra L., Glycyrrhiza uralensis Fich, Glycyrrhiza Korshinskyi Grig [1-5].
Naked licorice is the most popular among them, its roots contain the largest number of biologically active substances [6; 7]. Licorice preparations were included in the pharmacopeias of eastern countries long before our era. The results of treatment based on tinctures of licorice root in medieval medicine are summarized by the great scientist Avicenna [1; 8].
The main active ingredient of licorice root -glycyrrhizic acid (GA) has attracted the attention
of many researchers because of its high biological activity, as well as its ability to enhance the effects of other drugs in various medicinal compositions [9-10]. So, many researchers have obtained complex compounds of GA or its monoammonium salt (MASGA) with various drugs. There was a decrease in dose, thereby undesirable effects, as well as improved solubility of drugs. The ability of GA to affect the properties of drugs in the pharmacological literature is usually associated with complexation, while more often than not giving physico-chemical data on the nature of the interaction of a pharmacon with a complexing agent [11-12].
Molecular encapsulation of biologically active substances with complexing organic substances is being studied as one of the convenient and effective ways to improve solubility (bioavailability) and reduce the undesirable effects of the biologically active substance [3; 11; 13].
Sulfanilamide drugs are widely used in medicine, as chemotherapeutic drugs for the treatment and prevention of infectious diseases in humans and animals. One of these drugs is norsulfazole sodium, which is used for pneumonia, meningitis, sepsis, dysentery and other infectious diseases. The effectiveness of this drug against streptococcus, gonococcus, staphylococcus and Escherichia coli was noted [14].
In previous works, we obtained molecular complexes of the monoammonium salt of the glycyr-rhizin salt with sulfanilamide preparations such as phthalazole, urosulfan, sulfalene, sulfadimesin and studied their interferon-inducing activity [3; 10; 15]. In addition, molecular complexes of MASGA with other sulfonamides were obtained and the intermolecular interaction of the components of the complexes by spectral methods was studied. This work presents the results of a study of the molecular complex of MASGA with norsulfazole sodium by spectrophotometric and IR spectroscopic methods.
The molecular complex of MASGA with norsul-fazole-sodium was obtained by the previously described method. The composition of the complex was determined by the method of isomolar series. This method is recommended for determining the composition of metal complex compounds, and has been used recently to study the composition of molecular complexes [13; 16; 17]. The curve of the isomolar series is shown in (Fig. 2). The electronic absorption spectrum has an absorption maximum at 240 nm (Fig. 2). The composition of the complex was determined by the isomolar series method (Os-tromyslensky-Zhob method) [16-17]. The stability constant of the complex is calculated on the basis of the isomolar curve.
Figure 1. The dependence of the change in optical density AA on the ratio of the components of the isomolar series at A = 259 nm: c(Nor-Na) = 10-4 M, c(MASGA) = 10-4 M (pH 7.2, 25 oC)
To study the nature of intermolecular bonds in the complex, the IR spectroscopic method was used. So, in the IR spectrum of the complex, two bands are observed at 3352 and 3255 cm-1. In the spectrum of the MASGA itself, vibrations characteristic of OH groups appear in the form of a single band at 3228 cm-1. In the IR spectrum of norsulfazole, the -NH- vibrations of the primary amino group appear as a broad band at 3184 cm-1. This band is not observed in the IR spectrum of the complex.
Thus, in an aqueous solution, an equilibrium is established between MASGK and norsulfazole: MASGA + Nor-Na ^ MASGA-Nor-Na
Based on the isomolar curve, the stability complex of the complex at A = 259 nm was calculated using the following formula.
ÀA0 AA1
K =
c (AA0 -AA1)
where c is the total concentration equal to 10-4 M, AAQ is the change in optical density corresponding to the complex in the complete absence of dissociation, AA1 is the change in optical density corresponding to the value on the actual curve.
c = 0.0001, AA0 = 1.67, AA1 = 1.4; K = 8.6. 105 J/mol
Figure 2. UV absorption spectrum of an isomolar series of solutions of MASGA and Norsulfazole sodium (pH 7.2; 25 oC)
The change in Gibbs energy AG for the complex-ation process is calculated by the formula:
AG = -2.3 RTlgK AG = - 2.3 . 8.314 . 298 . 8.6 . 105 = - 23166.9 = =-2.32 . 104 kJ/mol The value of AG confirms that the equilibrium in the process of complex formation is shifted towards the formation of a complex compound.
In the IR spectrum of the complex, the position of the absorption bands of the MASGA carbonyl groups at 1714 and 1656 cm-1, the C - S bond at 670
cm-1, and the C = N bond intensity of the thiazole ring at 1440 cm-1 change. These changes confirm the participation in the complexation of the carboxyl and hydroxyl groups of MASGA, as well as the primary amino group and thiazole nitrogen atom.
h9n-
O Na+ S- /
s- N" Л
O N
The results ofquantitative and qualitative composition of complex compounds are shown in (table 2).
Table 2.- Qualitative and quantitative determination of the composition of the complex compound MASGA: Norsulfazole-Na method by HPLC
Theoretically% Practically% Retention time min.
MASGA Norsulfazol-Na MASGA Norsulfazol-Na
91.7 8.3 90.8 8.2 7.509
From the data given in (table No. 2) it can be seen that the results obtained coincide with the theoretically calculated data, which were confirmed by the results of IR and UV spectroscopy.
Experimental part.
For experiments, MASGA of 92% purity (by HPLC) obtained by the known method [8] and the substance of norsulfazole sodium (2- (p-amino-benzenesulfamido) thiazole sodium) were used. IR spectra were recorded on an IRTracer-100 IR Fourier spectrometer (Shimadzu, Japan). UV spectra were recorded on a Shimadzu-1280 spectrophotometer in quartz cuvettes (l = 10 mm); aqueous solutions of MASGA and norsulfazole were used to prepare solutions of the isomolar series (pH 7.2; c = 10-4 M phosphate buffer). HPLC was performed on an Agilent 1200 autosampler and gradient pump.
IR spectrum of HC(v, cm1): 3228(OH, NH), 2927(CH), 1714(C = O), 1656(C11 = O; C = c), 1593(COO), 1039(C0C).
IR spectrum of norsulfazole (v, cm1): 3184 (NH), 1440(C = N), 1238(NH), 1122(CHAr), 677(C-S).
Quantitative determination of monoammonium salt of glycyrrhizic acid (MASGA) and norsulfazole-sodium by HPLC
To determine the content of MASGA and norsul-fazole-Na, the HPLC method using a diode-matrix detector with an autosampler was used. Chromatography conditions:
Mobile phase: acetonitrile - water - glacial acetic acid in a ratio of 35: 64.5: 0.5(by volume).
Detector: diode array (wavelength 254 nm);
Solvent system: acetate buffer: acetonitrile (65:35);
Column XDB -C18, 5 ym, 4.8 x 150 mm,
Flow - 1ml/min;
The regime is isocratic. Column temperature -30 oC.
Output
Thus, for the first time, a complex compound of the monoammonium salt of HA and norsulfazole sodium was obtained. In aqueous solutions at pH 7.2 it was found by the isomolar series method that the components of the complex were found to be in a 1:1 ratio. The stability constant of complex K and the change in Gibbs energy AG of the complexation process are calculated.
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