Supramolecular complex of monoammonium salt of glycirrizinic acid with norsulfazol

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SUPRAMOLECULAR COMPLEX OF MONOAMMONIUM SALT OF GLYCIRRIZINIC ACID WITH NORSULFAZOL
77
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: [e-mail]
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 inter-
molecular 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 be-
longs 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 applica-
tions 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 

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Section 11. Chemistry
78
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 com-
plex compounds of GA or its monoammonium salt 
(MASGA) with various drugs. There was a decrease 
in dose, thereby undesirable effects, as well as im-
proved solubility of drugs. The ability of GA to affect 
the properties of drugs in the pharmacological litera-
ture 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 re-
duce the undesirable effects of the biologically active 
substance [3; 11; 13].
Sulfanilamide drugs are widely used in medi-
cine, 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, dys-
entery and other infectious diseases. The effective-
ness of this drug against streptococcus, gonococcus, 
staphylococcus and Escherichia coli was noted [14].
In previous works, we obtained molecular com-
plexes 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 in-
termolecular 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 de-
scribed 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 ΔА on 
the ratio of the components of the isomolar series at λ = 259 nm: 
c(Nor-Na) = 10
–4
M, c(MASGA) = 10
–4
M (pH 7.2, 25
o
C)

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SUPRAMOLECULAR COMPLEX OF MONOAMMONIUM SALT OF GLYCIRRIZINIC ACID WITH NORSULFAZOL
79
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 ap-
pear 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 com-
plex of the complex at 
λ = 259 nm was calculated 
using the following formula.
K
A A
c A
A
=
−
∆ ∆
∆
∆
0
1
0
1
(
)
where c is the total concentration equal to 10
–4
M, 
Δ
А
0
is the change in optical density corresponding to 
the complex in the complete absence of dissociation, 
Δ
A
1
is the change in optical density corresponding 
to the value on the actual curve.
c = 0.0001, ΔA
0
= 1.67, Δ
A
1
= 1.4;
K = 8.6 • 10
5
J/mol
Figure 2. UV absorption spectrum of an isomolar series of solutions 
of MASGA and Norsulfazole sodium (pH 7.2; 25
o
C)
The change in Gibbs energy ∆
G for the complex-
ation process is calculated by the formula:
Δ
G = –2.3 RTlgK
Δ
G = – 2.3 • 8.314 • 298 • 8.6 • 10
5
= – 23166.9 =
=–2.32 • 10
4
kJ/mol
The value of ∆
G 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