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78 AZERBAIJAN CHEMICAL JOURNAL № 4 2021 ISSN 2522-1841 (Online)
ISSN 0005-2531 (Print)
UDC 541.49
DFT CALCULATIONS, HIRSHFELD ANALYSIS, ANTIMICROBIAL, ANTIFUNGAL PROPERTIES OF THE Cu(II) POLYMERIC COMPLEX WITH THIOSEMICARBAZONE OF GLYOXYLIC ACID
M.T.Huseynova
A.Guliyev Institute of Chemistry of Additives, NAS of Azerbaijan
Received 07.06.2021 Accepted 11.08.2021
The complex Cu(II) with thiosemicarbazone of glyoxylic acid was evaluated for biological activity against various microorganisms such as antibacterial Pseudomonas aeruginosa and Mycobacterium phlei and antifungal Aspergillus niger, Penicillium Chrysogenium, Cladosporium resinae. Some of the assayed compounds showed interesting activity against microbes and fungicides. Meat-paste agar (MPA) was used for growing bacterial crops, and wort-agar (CA) was used for mushrooms. These studies showed that the ligand does not show an antibacterial effect but shows an antifungal effect, and the copper complex with this ligand shows both antibacterial and antifungal effects. The antimicrobial action of the complex is much higher than the ligand itself and this action increases with increasing concentration of the complex compound in solution. The complex characterized DFT calculations and Hirsfeld analysis. DFT/TD-DFT calculations were performed to theoretically determine the structural, spectroscopic and crystallographic properties of the synthesized complex. Hirshfeld analysis was performed to determine the interactions between molecular crystals and to display the details. The results have been compared with the corresponding theoretical results.
Keywords: thiosemicarbazones, antibacterial activity, antifungal activity, DFT calculations, Hirsfeld analysis.
Introduction
Thiosemicarbazones and metallic complexes have biological activity. Their pharmacological applications have been extensively studied. There are a number of reviews on many aspects of the chemistry of these compounds, such as preparative methods, stereochemistry, bond types in metal complexes, spectral characteristics, and crystal structures [1-5]. Many papers mention the pharmacological properties of these versatile compounds [6-8]. The biological properties of thiosemicarbazones are often associated with their coordination of metal ions. The geometry optimization, vibration frequencies, and energies of the [Cu(HGAT>H2O]- nH2O compound were calculated by the B3LYP/ LANL2DZ level of theory in the DFT method. Hirshfeld surface analysis was studied to show interactions between molecular crystals.
Material and Methods
Practical part
The antibacterial and antifungal efficacy of the samples was determined by the method
of the zonal diffusion according to GOST 9.085-78 using the following microorganisms: bacteria - Pseudomonas aeruginosa, Mycobac-terium phlei; mushrooms: Aspergillus niger, Penicillium Chrysogenium, Penicilliumchrose-genum, Cladosporiumresinae. For a preliminary assessment of the effectiveness of antimicrobial properties, the test compounds were tested in a solvent (DFT for complex compounds) and ethyl alcohol (for the ligand).
Theoretical Calculations. Gaussian 09 [9] was used for theoretical calculations, and GaussView 5.0 [10] was used for the visualization of calculated results. Geometry optimization of the complex was conducted with Becke-3-LeeYang-Parr's functional correlation (B3LYP) [11-13] of the 6-31G(d,p) basis set for the density functional theory method. The geometry optimization of the complex was chosen as a stable form with C1 symmetry. Maps of the Hirshfeld surface were generated based on the crystallographic information file using the Crystal Explorer17.5 program [14].
Results and Discussion
The effect of Cu(II) complex on antimicrobial activity. For a preliminary assessment of the effectiveness of the antimicrobial properties of the tested compounds were examined in various solvents (DMF for complex compound) and ethyl alcohol (for ligand). DMF solvent and ethyl alcohol were used as controls. Pyridine was also tested as a solvent, but it turned out that it has high antimicrobial activity and completely inhibits the growth of microorganisms. Therefore, it is impractical to use this solvent as a control. Meat-peptone agar (MPA) was used to grow bacterial cultures, and mash agar (CA) was used for fungi. Test compounds were added to the solvent and alcohol in a mass percentage of 1.0, 0.5, and 0.25. The tests were carried out as follows: in a Petri dish poured the nutrient medium in an amount of 20-25 ml and allow it to cool. The sowing of microorganisms was performed on the surface of the nutrient medium. Then, wells of 4-5 mm in depth were made on the surface of the medium using a sterile drill with a diameter of 10 mm, to which 0.3-0.5 ml of the tested samples with the indicated compounds were added. Next, Petri dishes were placed in a thermostat and kept for 2
Table 1. Antimicrobial screening data
days using bacteria and 3-4 days for fungi at 29 ± 20C. It is more, the more effective antimicrobial action. These antimicrobial screenings are presented in Table 1.
Hirshfeld Surface Analysis
Hirshfeld surfaces allow for the simulation of intermolecular interactions, with various colors and intensities indicating the relative strength of the interactions. In the dnorm map (region: -0.544 Á to 1.3074 Á), the vivid red spots are due to H-O/O-H interactions. The aromatic rings are described by the white areas on either side of the molecular structures in the Hirshfeld surface, which are footmarks of pi-pi interactions.
Curvedness maps are used to classify common packing types. On the Hirshfeld surface map, two-dimensional fingerprint plots measure the contributions of each type of non-covalent interaction. H-H/H-H non-covalent interactions have the largest contribution to the overall Hirshfeld surface on the 2D fingerprint plots, accounting for 27.4%. Non-covalent interactions between O and H (O-H/H-O), which account for 23.6 percent of the sum, are represented by two sharp peaks in Figure 1.
Compound DMF solvent
Biocide concentration microbial extermination zone
bacterium (Pseudomonas aeruginosa, Mycobacterium phlei) mushrooms (Aspergillus niger, Penicillum Chrysogenium)
Thiosemicarbazide of glyoxylic acid (H2GAT) 1 2.5-3.1 2.7-3.2
0.5 2.3-2.5 3.0-3.2
0.25 2.7-2.9 2.5-2.5
[Cu(HGAT)-H2O] •nH2O 1 3.5-3.7 3.5-4.1
0.5 2.6-2.8 1.6-2.0
0.25 2.3-2.5 1.6-2.0
DMF test sample - 2.3-2.5 2.2-2.4
Figure 1. Hirshfeld surface (A), extended structure with dnorm (B) and fingerprint (C) of the complex.
Density Functional Theory Calculations
The geometry optimization of the complex was performed at the B3LYP/6-31G (d,p) level of theory using the density functional theory calculation method via Crystallographic Information File (.cif). There is no difference between the crystal shape and calculated molecule shape, and the bond lengths and angles are compatible with each other. EHOMO and ELUMO values were calculated as
Table 2.
Conclusion
The results of antimicrobial activity show that the metal complexes exhibit antimicrobial properties, and it is important to note that they exhibit increased inhibitory activity compared to the parent ligand. It was also found that concentration plays an important role in increasing the degree of inhibition; as the concentration increases, the activity increases. Hirshfeld surface
-4.94 eV and -1.21 eV, respectively and the bandgap value (EGAp), which is the difference between these HOMO and LUMO, was determined as 3.73 eV. The higher the ionization potential and the electron affinity, the electronegativity will also increase in parallel. If the chemical hardness increases, the softness decreases, or the hardness decreases as the softness increases. All these calculated values and formulas are given in Table 2.
analysis revealed important interactions that cause molecular packing within the crystal structure. The narrow HOMO-LUMO band gap obtained by DFT calculations means that the compound is relatively stable, with the presence of water, the bandgap narrowed, and the reactivity of the system increased, which increases the enzyme activity of the complex.
Figure 2. Optimized geometry (A), HOMO (B) and LUMO (C) orbitals of the complex.
The calculated parameters of the complex with DFT method
HOMO Energy (Ehomo) 'o j Hi i ë w o S £ Energy Gap (EGap) Dipole Moment (D) Ionization Potential (IP) Electron Affinity (EA) Electronegativity (x) Chemical Hardness (n) Global Softness (o) Electrophilicity index (œ)
(1) -4.94 -1.21 3.73 9.28 4.94 1.21 3.08 1.87 0.41 10.08
EgAP = EHOMO-ELUMO ip EHOMO ea eLUMO X (IP + EA)/2
n = (IP - EA)/2 c = 1/2n œ = ^/2n
The dipole moment unit is Debye (D). HOMO and LUMO energy, Energy gap, Electron affinity, Ionization potential, Chemical hardness, Electronegativity, and Electrophilicity index unit are eV. The global softness unit is eV-1._
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QLiOKSAL TURSUSUNUN TiOSEMiKARBAZONUNUN Cu(II) POLiMER KOMPLEKSiNiN DFT HESABLAMALARI, HiRSFELD ANALiZi, ANTiMiKROB, ANTiFUNQAL XÜSUSiYYOTLORi
M.T.Hüseynova
Qlioksal turçusunun tiosemikarbazonunun Cu(II) polimer kompleksinin, antibakterial Pseudomonas aeruginosa va Mycobacterium phlei va göbalak aleyhina Aspergillus niger, Pénicillium Chrysogenium, Cladosporium resinae kimi müxtalif mikroorqanizmlara qarçi bioloji aktivliya göra qiymatlandirilmiçdir. Test edilmiç birlaçmalardan bazilari mikroblara va funqisidlara qarçi maraqli tasir gôstarmiçdir. Bakteriyalari yetiçdirmak ûçûn at suyu aqardan, göbalaklar ûçûn isa aqardan istifada edilmiçdir. Bu tadqiqatlar zamani ligandin antibakterial tasir göstarmadiyini, lakin göbalaklara qarçi tasir göstardiyini eyni zamanda mis polimer kompleksinin ham antibakterial, ham da antifungal tasir göstardiyi malum olmuçdur. Kompleksin antimikrob tasiri ligandin tasirindan xeyli yüksakdir va bu tasir mahlulda kompleks birlaçmanin konsentrasiyasinin artmasi ila artir. Kompleks DFT hesablamalari va Hirsfeld analizi ila xarakteriza olun-muçdur. Sintez edilmiç kompleksin struktur, spektroskopik va kristalloqrafik xüsusiyyatlarinin nazari tayin edilmasi ûçûn DFT / TD-DFT hesablamalari apanlmiçdir. Hirsfeld analizi vasitasila molekulyar kristallar ila ekran detallari arasindaki qarçiliqli alaqa mûayyanlaçdirilmiçdir. Alinan naticalar müvafiq nazari naticalarla mûqayisa edilmiçdir.
Açar sözlar: thiosemicarbazon, bakteriya aleyhina, göbalak aleyhina tasir, DFT hesablamalari, Hirsfeld analizi.
РАСЧЕТЫ DFT, АНАЛИЗ ХИРСФЕЛЬДА, АНТИМИКРОБНЫЕ, ПРОТИВОГРИБКОВЫЕ СВОЙСТВА ПОЛИМЕРНОГО КОМПЛЕКСА Cu(II) С ТИОСЕМИКАРБАЗОНОМ ГЛИОКСИЛОВОЙ КИСЛОТЫ
М.Т.Гусейнова
Комплекс Cu(II) с тиосемикарбазоном глиоксиловой кислоты оценивали на биологическую активность в отношении различных микроорганизмов, таких как антибактериальные Pseudomonas aeruginosa и Mycobacterium phlei и противогрибковые Aspergillus niger, Pénicillium Chrysogenium, Cladosporium resinae. Некоторые из анализируемых соединений показали интересную активность в отношении микробов и фунгицидов. Мясопептонный агар (МПА) использовался для выращивания бактериальных культур, а сусло-агар (СА) - для грибов. Эти исследования показали, что лиганд не проявляет антибактериального эффекта, но проявляет противогрибковый эффект, а комплекс меди с этим лигандом проявляет как антибактериальный, так и противогрибковый эффекты. Антимикробное действие комплекса значительно выше, чем у самого лиганда, и это действие усиливается с увеличением концентрации комплексного соединения в растворе. Комплекс характеризовался вычислениями DFT и анализом Хирсфельда. Для теоретического определения структурных, спектроскопических и кристаллографических свойств синтезированного комплекса были проведены расчеты DFT/TD-DFT. Анализ Хирсфельда был проведен для определения взаимодействий между молекулярными кристаллами и отображения деталей. Полученные результаты были сопоставлены с соответствующими теоретическими результатами.
Ключевые слова: тиосемикарбазоны, антибактериальная активность, противогрибковая активность, расчеты DFT, анализ Хирсфельда.
