SYNTHESIS AND CRYSTAL STRUCTURE OF THE COMPLEX COMPOUND OF Co(II) ION WITH PARACETAMOL AND THREONINE

ABSTRACT

This article discusses the synthesis of a complex compound [Co(L₁)₂(Tre)₂(NO₃)₂], (L1-paracetamol, Tre-threonine amino acid) and its crystal structure. Additionally, the study focused on the dependence of the reaction on time, temperature, and reagent concentration. The complex compound was analyzed using various methods, including IR-Fourier-spectroscopy, elemental analysis, TG-DSK, and X-ray structural analysis. According to the analysis of the Cambridge Crystallographic Database (CCDC-2023), 142 metal complexes of paracetamol (acetaminophen, para-hydroxyacetanilide) and 326 metal complexes of threonine (2-amino-3-hydroxybutanoic acid) were obtained until 2023, and their structures were determined. In contrast to the works of these scientists, a complex compound [Co(L₁)₂(Tre)₂(NO₃)₂] of cobalt and amino acids consisting of paracetamol was synthesized, and monocrystals were grown for the first time. X-ray diffraction analysis was carried out on an XtaLAB Synergy diffractometer (Rigaki, Japan), installed in the public access center of the Institute of Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan.

АННОТАЦИЯ

В данной статье рассматривается синтез комплексного соединения [Co(L₁)₂(Tre)₂(NO₃)₂] (L₁-парацетамол, Tre-аминокислота треонин) и его кристаллическая структура. Кроме того, в исследовании основное внимание уделялось зависимости течения реакции от времени, температуры и концентрации реагента. Комплексное соединение анализировали различными методами, включая ИК-Фурье-спектроскопию, элементный анализ, ТГ-ДСК и рентгеноструктурный анализ. По данным анализа Кембриджской кристаллографической базы данных (CCDC-2023) до 2023 года получено 142 металлокомплексов парацетамола (ацетаминофен, парагидроксиацетанилид) и 326 металлокомплексов треонина (2-амино-3-гидроксибутановая кислота) и определены их структуры[1,2]. В отличие от работ этих ученых, было синтезировано комплексное соединение [Co(L₁)₂(Tre)₂(NO₃)₂] кобальта и аминокислот, состоящее из парацетамола, и впервые выращены монокристаллы и рентгеноструктурный анализ проведен на дифрактометре XtaLAB Synergy (Rigaki, Япония), установленном в общественном центре доступа Института биоорганической химии АН РУз.

Keywords: Coordination compound, paracetamol, threonine, elemental analysis, X-ray structural analysis, single crystal, coordination, reaction product, cobalt(II) nitrate, aqueous solution, hydrogen bond, stability constant, dimethylformamide (DMFA).

Ключевые слова: Координационное соединение, парацетамол, треонин, элементный анализ, рентгеноструктурный анализ, монокристалл, координация, продукт реакции, нитрат кобальта(II), водный раствор, водородная связь, константа устойчивости, диметилформамид (ДМФА).

Actuality of the research/The relevance of research: In recent years, the results of research on the coordination compounds synthesis with 3D metals and their application have attracted interest due to their application in agriculture, medicine, pharmaceuticals, agro-chemistry and various other fields. First-row transition metal ions possess a smaller size, which makes them easily coordinated with nitrogen and oxygen atoms. Their coordination numbers are mostly 4 or 6, which results in simple geometrical structures. Complex compounds of transition metals with mixed ligands play a significant role in various aspects of life, particularly in biological processes [3]. Based on these thoughts, a metal-complex compound of paracetamol with a mixed ligand was synthesized, and its crystal structure was studied. Cobalt(II) complexes have been extensively researched due to the formation of various coordination forms with ligands that exhibit specific biological activity against various bacterial and fungal strains. Paracetamol itself has weak anti-inflammatory and analgesic properties. Complex compounds formed by paracetamol with 3D metals (Cr, Mn, Fe, Co, Ni, Cu, Zn, Ag) have been widely discussed by many scientists, and it has been studied that the anti-inflammatory properties of paracetamol are stronger compared to paracetamol. In this work, a coordination compound [Co(L₁)₂(Tre)₂(NO₃)₂] consisting of a ternary system was synthesized and the structure of the grown monocrystal was analyzed.

In this work, we studied the synthesis of a complex combination of Co(II) ion with paracetamol and threonine.

The amount of metal in the synthesized compound was determined on a Novaa 300 atomic absorption spectrometer manufactured by Analytik Jena (Germany), carbon, hydrogen and nitrogen were determined on an EA 1108 apparatus from Carlo-Erba (Italy) (Table 1). X-ray diffraction analysis was carried out at 293 K in an automatic Xcalibur ROxford Diffraction diffractometer (Cu Karadiation, k = 1.54184 Å, xscan mode, graphite monochromator).

Method of synthesis of coordination compound. An aqueous solution of 0.01 mol cobalt(II) nitrate salt was prepared. Then 0.02 mol paracetamol alcohol solution was added to it. The resulting mixture was heated for 1.5 hours with a reflux condenser connected[4]. After that, threonine was added to this mixture, it was again rotated on a magnetic stirrer, thoroughly mixed and heated. The solution was filtered and evaporated under vacuum to a dry residue. The resulting residue was redissolved in 20 ml of dimethylformamide, evaporated until 10 ml of solution remained, and stored at room temperature for 48 hours[5].

Product yield 72%, t_mt = 256-262ºC. The results of the elemental analysis of this synthesized complex compound with a new composition were studied [6].

Table 1.

Elemental analysis of the coordination compound of cobalt(II) nitrate with paracetamol and threonine

Results and discussion. As a result of studying the resulting monocrystal using X-ray diffraction analysis, the following structure was obtained (Fig. 1).

Figure 1. Structure of the coordination compound[Co(L₁)₂(Tre)₂(NO₃)₂]

Monocrystals of the synthesized complex compound were grown, and the relevant parameters were determined using the X-ray structural analysis method in the XtaLAB Synergy (Rigaki, Japan) diffractometer. The Cif file of this compound was obtained, and information about its structure and some details was obtained through the Mercury software[7,8,9]. As can be seen from the above picture, cobalt, considered the central atom, is connected with the oxygen of the carbonyl group of paracetamol and the oxygen of the carboxyl group of threonine using donor-acceptor bonds. Due to this, it can be seen that cobalt exhibits 6 valency in this coordination compound.

Table 2.

Parameters clarifying crystallographic data and the structure of the complex of Co(II) ion with paracetamol and threonine

The parameters of the unit cell of the crystal are as follows: spatial group I1, a=24.658 Å, b=24.658(13) Å, c=18.526(3)Å, α=60.22^o, β=60.26°, γ=68.18^o, V=1060.15ų, Z=2. Complex [Co(L₁)₂(Tre)₂(NO₃)₂] is mononuclear, formed by paracetamol, nitrate residue and threonine molecules of the Co²⁺ ion, and has a neutral nature. It can be seen that the distance between the Co(1)−O(1), Co(1)−O(2), Co(1)−O(3), Co(1)−O(4) and O(1)-N(1), O(2)-N(2) bonds in the complex is equal to 1.8614 Å, 1.8442 Å, 1.8099 Å, 1.8112 Å and 1.3386 Å, 1.3409Å, respectively. Angular sizes of O(1)-Co(1)-O(2), O(1)-Co(1)-O(3), O(1)-Co(1)-O(4), O(1)-Co(1)-O(5) and O(1)-Co(1)-O(6), O(2)-Co(1)-O(3) are equal to  93.65⁰, 77.91⁰, 79.52⁰, 93.07⁰ and 175.64⁰, 97.2⁰, respectively. The difference in the distance between the oxygen atom of paracetamol in the compound and the central cobalt atom is explained by the Yan-Tellar effect [10]. The central atom in the complex compound coordinates with the oxygen atom of the carbonyl group of two ligands paracetamol and the oxygen atoms of 2 nitrate residues, as well as with the donor oxygen atom of the carboxyl group of threonine amino acid. In this, paracetamol molecules participated as monodentate ligands through oxygen atoms and two nitrate residues through oxygen atoms. The central cobalt atom has a coordination number of 6 and is hybridized in the sp³d² state. According to the analysis results, the complex compound is stable due to the formation of a two-dimensional layer parallel to the bc plane due to the residue of nitrate, paracetamol and N(3)---H(4)…O(2), O(12)-H(13)…O(13), N(4)--H(15)…O(2) type hydrogen bonds (Table 5).

Figure 2. The bond length of the atoms in the coordination compound

Table 3.

Bond lengths of a complex compound

Table 4.

Bond angles of a complex compound

Figure 3. Hydrogen bonds in the complex compound containing [Co(L₁)₂(Tre)₂(NO₃)₂]

Table 5.

Hydrogen bonds in the crystal structure (A˚)

Conclusion. Coordination compounds of cobalt metal with single and mixed ligands were synthesized. The synthesis process was carried out in a solution medium, and a complex compound with a mixed ligand was obtained by taking the Co(II) ion with paracetamol and threonine in a 1:2 mol ratio. Single crystals of this complex compound were grown and X-ray structurally analyzed. The composition and structure of the synthesized compounds were determined. According to the results of the analysis, a coordination compound containing [Co(L₁)₂(Tre)₂(NO₃)₂] was obtained, and it was shown that the coordination number of cobalt is equal to 6 and the compound has an octahedral structure.

References:

1. Oxford Diffraction CrysAlis PRO CCD. Oxford Diffraction Ltd, Yarnton, England. -2009.
2. Sheldrick, G. M. Crystal structure refinement with SHELXL// Acta Cryst. 2015.–V. P. 71, PP. 3–8. doi:10.1107/S2053229614024218.
3. Dobrynina N.A. Biologicheskaya rol nekotorykh khimicheskhih elementov. // Khimia v 36 shkole. - 1991. - №2. PP. 6 – 14. [In Russian].
4. Saedi Z., Hoveizi E., Roushani M., Massahi S., Hadian M., Salehi K., Synthesis,  characterization, anticancer properties and theoretical study of asymmetrical Cd(II)N2-Schiff base complexes // J. Mol. Struct. 1176. -2019. – PP. 207-216.
5. Khudoyberganov O.I., Ruzmetov A.X., Ibragimov A.B., Ashurov J.M., Khasanov Sh.B., Ibragimov B.T. Synthesis, crystal structure and Hirshfeld surface analysis of the binuclear Cu(II) complex with 4-nitrobenzoic acid and triethanolamine. Chemical Data Collections.100802. doi: 10.1016/j.cdc.2021.100802.
6. Fadeeva V. P., Tikhova V. D., and Nikulicheva O. N. Elemental Analysis of Organic Compounds with the Use of Automated CHNS Analyzers // Journal of Analytical Chemistry, 2008, -V.63(11), - PP.1094–1106.
7. Savitskaya L.K. Rentgenostrukturniy analiz: uchebnoe posobie // Tomsk: SKK – 2006. – P. 274. [In Russian].
8. CrysAlisPro. Ver. 1.171.33.40, UK: Oxford Diffraction, 2007.
9. Sheldrick G.M. // SHELXS97, SHELXL97, Programs for Crystal Structures Solution and Refinement, University of Göttingen, Göttingen, Germany. 1997.
10. Macrae C.F, Bruno I.J, Chisholm J.A. et. al. Mercury CSD 2.0 – new features for the visualization and investigation of crystal structures // J. Appl. Cryst. -2008. – V.41. -PP. 466-470.