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7SYNTHESIS AND ANALYSIS OF COPPER(II) ION COORDINATION COMPOUND WITH KETOPROFEN AND
CARBAMIDE
'Rustamov Temur Rustam ogli, 2Azizjanov Khushnud Maxsudovich, 3Khudoyberganov
Oybek Ikromovich
'Doctoral Student, Khorezm Ma'mun Academy 2Urgench State University, department of Chemistry, candidate of chemical sciences, associate
professor
3PhD., Senior Scientific Researcher, Khorezm Ma'mun Academy https://doi.org/10.5281/zenodo.10730456
Abstract. Nowadays, great amount of interest in the development of methods for the synthesis of metallocomplex compounds of biologically active compounds available in the world with 3d metals and in determining their physicochemicalproperties is steadily increasing. These compounds are actual for their use as antibiotics and painkillers in pharmaceutics, as biologically active substances in medicine, and as antibacterial active substances that inhibit the growth of bacteria for microorganism cells [1]. The synthesis of the complex combination of 2-(3-benzoylphenyl) propionic acid (Ketoprofen) with Cu2+ from saturated monocarboxylic acid derivatives was studied. Factors affecting the synthesis of CuC34H34N4O8 complex compound under room conditions were shown. In particular, the dependence of the yield of the reaction product on time, the effect of temperature, and the dependence on concentration were studied in practice. Physico-chemical research of the synthesized complex compound was studied using IR-Fourier-spectroscopy, elemental analysis, mass spectrometry, TG-DSK and X-ray structural analysis methods, its chemical structure was determined, and it was proved that this new complex compound is thermally and chemically stable. [2].
Keywords: ketoprofen, copper sulfate, carbamide, complex compound, metal complex, X-ray structural analysis, elemental analysis, antimicrobial, single crystals, Hirschfeld surface analysis.
Introduction._The study of coordination compounds allows to explain their main chemical properties, to form complexes, to determine the nature of chemical bonds between ligands, to determine the mechanisms of processes involving coordination compounds and changes in the reactivity of coordinated ligands using modern physical and chemical research. The obtained information is important for purposefully finding and synthesizing new chemical substances with predetermined specific characteristics, composition and structure, as well as other important properties. This is especially necessary for substances with biologically active properties used in medicine [3]. A metal complex compound of bioactive ligand ketoprofen was synthesized together with laboratory staff. Ketoprofen has a pronounced analgesic effect, and is used as an anti-inflammatory and moderate antipyretic agent. Inflammation and fever appear due to the entry of various disease-causing bacteria into the human body from the external environment. Ketoprofen is one of the non-steroid substances used to eliminate this process, and in order to strengthen its effect, biometals such as Cu, Mn, Co, Zn, Mo, Fe were selected from 3d-metals and a metallocomplex compound was synthesized. When these new metallocomplex
compounds are poisoned by microbes, they bind to them and try to remove them from the body faster or completely lose their effect [4].
Aim of the research consists of developing a methodology for synthesizing a complex combination of Cu2+ ion with ketoprofen and studying the composition and structure of the synthesized complex using modern physico-chemical research methods.
Literature review. Synthesis of complex compounds of propionic acid, which is a representative of saturated carbonic acid, ketoprofen with biometals, their spatial structure, scientific research aimed at determining the relationship between "bioactivity-structure" and leading scientific centers and higher educational institutions of the world, including Delhi Institute of Pharmaceutical Sciences and Research (India), Institute of Inorganic Chemistry of Aachen University (Germany), Institute of General and Inorganic Chemistry, Moscow State University (Russia), University of Tokyo (Japan), Royal Institute of London (England), Institute of Engineering and Technology (China), Jagiellonian University (Poland), Institute of General and Inorganic Chemistry (Uzbekistan) [ 5]
As a result of research conducted in the world on the structure of complexes of ketoprofen with biometals and their biological activities, a number of scientific results were obtained, including the following: synthesis of chelated complexes of metals was carried out, their spatial structure and charge density were determined (Institute of Inorganic Chemistry of Aachen University, Germany); mixed-ligand coordination compounds involving carboxylates were synthesized (Institute of General and Inorganic Chemistry, Moscow State University, Russia); complexes based on biometals were synthesized, molecular and crystalline structures, as well as bioactivity were determined (Royal Institute of London, Great Britain);
Scientific researches by Weiqing Mao Li, Xiang Yaofeng Chen, Dahale N.D., Chawla K.L., Venugopal V., Aubert T., Ledneva A., Grasset F., Kimoto K., Naumov N., Molard Y., Saito N., Haneda H., Cordier S., Amela-Cortes M., Circu V., Lang E.S., Stieler R., de Oliveira G.M., Mammino L., Kabanda M.M., Gier H., Roth W., Shumm S., Gerhards M. and others were devoted to the synthesis of complex compounds of 3d metals and ketorolac in solutions and the study of physico-chemical research methods in the world [6,7].
The technology of obtaining complex compounds of various salts of metals with bioactive organic ligands was developed, the processes of formation of coordination compounds in solutions and solid phases were studied. The physicochemical properties of the synthesized compounds were analyzed. Despite the fact that there are many experimental materials on the study of complexes of metal salts with substances containing the carboxyl group and amino group, the synthesis of metallocomplexes of Cu2+ mixed with ketoprofen from these 3d-metal salts in solution has not been studied. In addition, there is no information about the structure of the coordination knot of compounds of this class [8].
Research Methodology. The synthesis process of the metal complex compound ketoprofen was carried out as follows: aqueous solutions of 0.25 g (0.001 mol) of CuSO^5H2O crystal hydrate salt and 0.508 g (0.002 mol) of ketoprofen were prepared. At the first stage, in order to increase the reactivity of ketoprofen, its sodium salt was obtained by reacting it with NaOH in a ratio of 1:1. At the second stage, ketoprofen sodium salt and CuSO4-5H2O crystalline hydrate salt were mixed in a ratio of 2:1. Then, at the last stage, 1ml of the 0.1N solution of carbamide solution obtained as an auxiliary ligand was added dropwise to the complex salt solution. Then it was thoroughly mixed in a MS-H280-Pro magnetic stirrer at a temperature of
60°C for 40 minutes [9]. Then, the solution of the synthesized complex compound is left to slowly evaporate at room temperature. After five days, the obtained precipitates were filtered, washed with ethyl alcohol, then evaporated to a dry residue in a rotary evaporator at 60°C and dried. As a result, dark-green crystals of the complex compound were formed. The synthesis reaction can be expressed as follows:
Scheme 1: The reaction to obtain the sodium salt of ketoprofen
+ Ni^SO- + 5 H20 Scheme 2: The reaction to obtain the copper salt of ketoprofen
Scheme 3: Reaction of coordination compound of copper (II) ion with ketoprofen and
carbamide
Analysis and results. The complex formed by ketoprofen with Cu(II) ion has a 6-coordinate, tetragonal (octahedral) geometric structure. The complex connection between Cu(II) ion and two molecules of ketoprofen was formed as a result of binding of metal ion to carboxyl-O and amide group, N,O-atoms of carbamide containing oxygen atoms. The carbonyl group of ketoprofen does not participate in complex formation, so the carbonyl group is still free in the ketoprofen complex [10]. Elemental analysis was conducted on the complex compound [Cu(HL)2(Kar)2] .
The amount of metal in the synthesized complex compounds was determined using the Novaa 300 apparatus of Analytik Jena (Germany), and the analysis of carbon, hydrogen, nitrogen and oxygen elements was determined using the EA 1108 apparatus of Carlo-Erba (Italy) (Table 1).
Table 1
The result of the elemental analysis of the complex formed by the Cu (II) ion with ketoprofen
The total formula of the synthesized complex compound Cu, % C, % H, % N, %
Obtained Calculated Obtained Calculated Obtained Obtained Calculated Obtained
CuC34H34N4Os 9,27 9,34 59,13 59,24 4,92 4,96 8,14 8,24
In order to better study the coordination number of the Cu atom and the geometric knot structure in this synthesized complex compound, IR-analysis of the synthesized complex compound was also carried out. In order to determine the binding properties of the coordination centers of the ligands to the central atom, the IR spectrum of the synthesized complex of 3 d-metal salts with the ketorolac ligand was obtained [11]. Valence vibrations of the carboxyl group were manifested in the 3310 cm-1 region, and for the CH-group, they were recorded in the 29803100 cm-1 region. When comparing the IR spectra of 3d metals, ketorolac and metal complexes with formate, acetate and carbamide, the absorption lines of the symmetric valence vibrations of the M-N bond and the =M-O= bond valence vibration in the ring undergo a sharp change, and the IR spectra of the complexes have a strong frequency compared to the ligand was observed to shift by ~20-40 cm-1 towards the field, and by ~30-40 cm-1 in the low-frequency field.
Figure 2. IR-spectrum of the coordination compound of Cu (II) with ketoprofen and
carbamide
In the spectra of the complexes, absorption lines were observed in the region of 412-452 cm-1 corresponding to M-N valence vibrations in the short wavelength range. Vibrations related to the -CH group of the benzene ring remained unchanged and appeared in the region of 29803100 cm"1. The carbonyl group in the complexes shifted to shorter wavelengths and was observed in the region of 3313-3264 cm1, which indicates that it is not involved in coordination. The X-ray structural analysis of the synthesized complex compound was also carried out and the
Table 2
Crystallographic data and parameters clarifying the structure of the Cu-complex compound.
Cu-complex compound
Formula CUC34H34N4OS Crystal size, [mm] 0.18x0.15x0.12
Molecular mass 690 T, °K 312
Syngonia monoclinic 9,°grad. 2,6; 52,4
Spatial group P2i/n Interval h,k,l 999;-99 ; 999:99 ; 999:-99
a, Ä 31.26 (9) Reflex 10281
b, Ä 32.36 (9) Refractive index 7137
c, Ä 32.54 (13) Rint 1672
a, ß, y, deg 90(7);90(7);90(6) F2>2o (F2) criterion 0.71073
V, Ä3 30549.523 Parameter 3682
Z 4 Eligibility Criteria (F) 322
Dx, g cm-3 0.165 R1, wR2(I>2o (I)) 1.04
^(CuKa), mm-1 0.027
Table 3
Bond lengths and bond angles of a complex compound
Bond d, Â Angle ro, degree
Cu(1)-O(1) 2.2739 O(1)-Cu(1)-O(2) 91.20
Cu(1)-O(2) 2.2726 O(1)-Cu(1)-O(3) 178.34
Cu(1)-O(3) 2.2712 O(1)-Cu(1)-O(4) 89.26
Cu(1)-O(4) 2.2575 O(2)-Cu(1)-O(3) 89.91
O(2)-C(1) 1.3585 O(2)-Cu(1)-O(4) 176.52
O(3)-C(2) 1.2011 O(3)-Cu(1)-O(4) 89.70
O(4)-C(3) 1.3622 Cu(1)-O(2)-C(1) 124.36
O(5)-C(1) 1.2236 Cu(1)-O(3)-C(2) 123.39
O(6)-C(3) 1.2221 Cu(1)-O(4)-C(3) 116.88
N(1)-C(2) 1.3365 H(1)-O(1)-H(2) 105.00
O(1)-H(1) 0.9900 Cu(1)-O(1)-H(1) 105.00
O(1)-H(2) 0.9900 Cu(1)-O(1)-H(2) 106.00
N(2)-C(6) 1.4299 C(6)-N(2)-C(9) 121.61
N(2)-C(9) 1.2879 O(2)-C(1)-O(5) 118.67
N(1)-H(3) 1.0300 O(2)-C(1)-C(5) 122.12
Table 4
Hydrogen bonds in the crystal structure (A )
Bond D-H--A Distance, Ä Angle D-H-A, grad. Atomic coordinates, A
D-H H-A D--A
[CuC34H34N4O8]
O(5)--H(5)...O(1) 1.11 2.34 3.241 138 1-x,-1/2+y,3/2-z
O(6)--H(6)...O(2) 1.12 2.39 3.444 159 1-x,1/2+y,3/2-z
O(2)--H(2B)...O(3) 0.78 1.83 2.664 142 1-x,-1/2+y,3/2-z
O(3)--H(3C)...O(4) 0.86 1.85 2.724 156 1-x,1/2+y,3/2-z
O(3)--H(3D)...O(1) 0.92 1.96 2.736 138 x,3/2-y,1/2+z
Also, differential thermal analysis was conducted in order to determine the thermal stability c endo- am crystalliza observed. decompos 700oC.In breaking <
ied compounds, evaporation of processes were lat the thermal -ange of 100°C-lich indicate the
Figure 4. Derivatogram of a similar complex compound
A number of endothermic and exothermic effects were observed in the DTA curve of the [Cu(HL)2 (Kar)2] complex. Above 1000C, the endothermic effect refers to the decomposition of water of crystallization. As a result of the increase in temperature, the decomposition of the complex compound increases intensively. As a result, hydrazine begins to break down into components such as nitrogen oxides and carbon dioxide. Copper (II) oxide is formed as a thermolysis product. Based on the analysis of the research results, the thermal stability of the synthesized complex compounds is expressed by the nature of the central ion and the acid residue, as well as the absence of water molecules in the complex compounds. It was concluded that the complex compound synthesized on the basis of ketoprofen is [Cu(HL)2(Kar)2] [13].
Conclusion. The complex [Cu(HL)2(Kar)2] is a mixed-ligand complex of Cu(II), ketoprofen, and carbamide with a 2:1 composition. The complex molecule contains O(5)--H(5)...O(1) and O(6)--H(6)...O(2) groups that can participate as donors in hydrogen bonds. The fact that the synthesized ketoprofen complex is important for temporary pain relief and anti-inflammatory use in all living organisms was shown by studying using physico-chemical research methods [14]. The solubility of the newly synthesized ketoprofen complex is 25 times higher than that of ketoprofen itself. It was determined by analyzing the Hirshfeld surface using the Crystall Explorer 17.5 program. According to it, the percentage of OH/HO interactions in the structure is higher than 36% on average and the share of HH interactions was less than 26% [8]. Therefore, this result increased the solubility of the obtained compound [15].
Figure 5. Hirschfeld surface analysis.
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