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Journal of Transition Metal Complexes
Vol. 3 (2020), Article ID 246100, 15 pages
doi:10.32371/jtmc/246100
Research Article

Synthesis, Characterization and Biological Studies of Cu2+, Ni2+, Cd2+, and Pt4+ Complexes Derived from 3-(3H-1,2,4-Triazole-4-(5H)-Ylimino)Butane-2-One-Oxime (L)

Doaa E. El-Kholy and Mohsen M. Mostafa

Chemistry Department, Faculty of Science, Mansoura University, Egypt
Address correspondence to Mohsen M. Mostafa, [email protected]

Received 22 April 2020; Revised 22 May 2020; Accepted 26 May 2020; Published 2 July 2020

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How to Cite this Article

Doaa E. El-Kholy and Mohsen M. Mostafa, Synthesis, Characterization and Biological Studies of Cu2+, Ni2+, Cd2+, and Pt4+ Complexes Derived from 3-(3H-1,2,4-Triazole-4-(5H)-Ylimino)Butane-2-One-Oxime (L), Journal of Transition Metal Complexes, 3 (2020), art246100. doi:10.32371/jtmc/246100

Abstract

Novel Cu2+, Ni2+, Cd2+, and Pt4+ complexes derived from 3-(3H-1,2,4-triazole-4-(5H)-ylimino)butane-2-one-oxime (L) were synthesized and characterized. FTIR spectra propose that L acts in different methods (bi- tri- and/or tetradentate) depending on the metal used. Electronic spectra and magnetic measurements of the complexes suggest a structure that is tetrahedral for Ni2+, octahedral for Cd2+, while square-planar for Cu2+ and Pt4+ complexes. Density functional theory (DFT) parameters were applied for Cu2+, Ni2+, and Pt4+ complexes which prove the geometry of L towards the metal ions. Coats-Redfern and Horowitz-Metzger methods were used to calculate the kinetic and thermodynamic parameters of the isolated complexes. The cyclic-voltammogram curve of the Cu2+ complex was reported. The biological activity of L and its complexes were tested against three types of cancer cell lines, and against different bacterial strains.

Keywords

complexes of triazole derivatives; biological activity; electronic and magnetic studies

1. Introduction

1,2,4-Triazoles synthesized from the substitution reaction of N-atom of hydrazides or amide N-atom reaction are regarded as an example of cyclic-hydrazides. Recently, 1,2,4-triazoles acquired great importance as a ligand system attributed to the ability to behave as a mono, bior tridentate ligand. Noncovalent interactions such as dipole-dipole, hydrogen bonding lone-pair (N)-π, and π-stacking admit numerous varieties of 1,2,4-triazole with biological goals [1, 2]. The chemical importance of 1,2,4-triazole system is mainly due to its ability to bridge between different metal centers [3]. Biological activities such as anathematic [4,5], antiviral [6], antifungal [7], antimicrobial [8], hypnotic [9], pesticide [10,11], mastectomy cancer preventive [12,13], anticancer, anticonvulsant and anti-inflammatory [14,15,16,17,18,19,20,21,22,23], CNS depressant [24], antitumor [25], and antihypertensive activities are reported for 1,2,4-triazoles [26]. [Cu3LCl2(H2O)5]4Cl, [NiLCl(H2O)]Cl·1.5H2O, [Pt2LCl5(EtOH)0.5(H2O)0.5]3Cl, and [Cd3LCl6(H2O)7] were obtained and characterized. All the complexes were distinctive by different tools including chemical (C, H, M, Cl), spectral (IR, UV-Vis), TGA, and magnetic moments. The biological activity of the ligand 3-(3H-1,2,4-triazole-4-(5H)-ylimino)butane-2-one-oxime (L) and its complexes was tested.

2. Experimental

2.1. Materials and methods

The solvents and chemicals used herein were of AR quality, such as 2,3-Butanedione-monoxime (BDH; Poole, UK), hydrazine hydrate (Fisher Scientific; MA, USA), ethyl formate (Merck; NJ, USA), NiCl2·6H2O, CuCl2·2H2O, CdCl2, and H2PtCl6. The chemicals, solvents, and apparatus as well as the methods of analyses were used as reported earlier [27].

2.2. Preparation of L

L, (E)-N-[(3E)-3-[(4H-1,2,4-triazol-4-yl)imino]butan-2-ylidene]hydroxylamine was synthesized as discussed in our earlier work [28].

2.3. Preparation of complexes
2.3.1. Synthesis of Ni2+ complex

[NiLCl(H2O)]Cl·1.5H2O was obtained by adding the ligand (0.50 g; 3 mmol) in ethanol to an ethanolic solution of NiCl2·6H2O (0.72 g; 3 mmol). The green gel mixture at pH = 5.0 was formed and then the reactants were refluxed for 7 h. Finally, the complex was separated from the filtrate, continuously washed with ether, and finally dried in a dryer (yield: 60%). Elemental analyses: Anal. Found: for C6H14Cl2NiN5O2.5 (%): C, 21.2; H, 4.2; Ni, 18.1; Cl, 21.5. Calcd.: (%) C, 21.1; H, 4.1; Ni, 17.2; Cl, 20.7, m.p. 233 °C, Λm: 47 ohm−1 cm2 mol−1 and μeff: 4.03 BM.

2.3.2. Synthesis of Pt4+ complex

[Pt2LCl5(H2O)0.5(C2H5OH)0.5]3Cl was formed by adding the ligand (0.33 g; 2 mmol) dissolved in ethanol (15 mL) to a solution of H2PtCl6 (0.82 g; 2 mmol) in EtOH (10 mL). The pH of the mixture was found to be 3–4. Yellow precipitate was formed at once then the reactants were refluxed with stirring on a heater for 6 h. The resulting solid compound was separated by filtration, laved several times by diethyl ether, and then left to dehydrate in a vacuum dryer over P4O10 (yield: 60%). Elemental analyses: Anal. Found: for C7H13Cl8Pt2N5O2 (%): C, 9.5; H, 1.8; Pt, 45.3; Cl, 31.7. Calcd.: (%) C, 9.6; H, 1.5; Pt, 44.7; Cl, 32.5, m.p. > 300 °C, Λm: 96 ohm−1 cm2 mol−1 and μeff: diamagnetic.

2.3.3. Synthesis of Cd2+ complex

[Cd3LCl6(H2O)7] was synthesized by adding the ligand (0.33 g; 2 mmol) soluble in ethanol (15 mL) to CdCl2·H2O (0.40 g; 2 mmol) disbanded in EtOH (10 mL). The pH of the solution was found to be 6.0. A white precipitate was obtained and the reactant was refluxed with stirring on a heater for 7 h. The resulting solid product was separated by filtration, laved many times by diethyl ether, and then dried in a dryer over phosphorous pentaoxide (crop: 50%). Elemental analyses: Anal. Found: for C6H23Cl6Cd3N5O8 (%): C, 8.6; H, 1.9; Cd, 40.1; Cl, 24.9. Calcd.: (%) C, 8.5; H, 2.4; Cd, 40.0; Cl, 25.2, m.p. > 300 °C, Λm: 12 ohm−1 cm2 mol−1 and μeff: diamagnetic.

2.3.4. Preparation of Cu2+ complex

The Cu2+ complex with the general formula [Cu3LCl2(H2O)5]4Cl was synthesized by adding the ligand (0.167 g; 1 mmol) disbanded in 15 mL of EtOH to a solution of CuCl2·6H2O (0.48 g; 2 mmol) dissolved in 10 mL of EtOH. The reaction mixture was adjusted at pH in the range 3–4 and the reactants were then refluxed with stirring for 8 h. Pale green precipitate was formed and its yield equals about 60%. The resulting solid complex was obtained by filtration, washed continuously with diethyl ether, and then left to dry in a dryer over P4O10. Elemental analyses: Anal. Found: for C6H19Cl6Cu3N5O5 (%): C, 11.4; H, 2.1; Cu, 29.1; Cl, 32.9. Calcd.: (%) C, 10.9; H, 2.8; Cu, 28.8; Cl, 32.2, m.p. 220 °C, Λm: 124 ohm−1 cm2 mol−1 and μeff: 0.98 BM.

2.4. Molecular modeling

Cluster calculations using DMOL3 program were utilized to attain the structures without any symmetry modality in Materials Studio Package which is determined for achieving of large-scale density functional theory (DFT) calculations [29,30,31,32,33,34].

2.5. Biological studies
2.5.1. Cytotoxic activity

In vitro cytotoxicity of L and four complexes (Cu2+, Cd2+, Pt4+, and Ni2+) was applied against three cancer cell lines [prostate cancer (PC-3), breast cancer (MCF-7), and Hela cell lines] brought from a holding corporation for the products and injections (VACSERA) located in Egypt. The doxorubicin as a typical anticancer medication was used. MTT, DMSO, and RPMI-1640 medium were obtained from Sigma Aldrich (MO, USA) while the fetal bovine serum was obtained from GIBCO (UK). Colorimetric assay effects were recorded at 750 nm using a plate reader (EXL 800). The relative cell practically in rate was computed by using the equation (A570 of treated examples/A570 of uncured sample) × 100. The effect on mammary MCF-7 observed with ELISA and the percentage of safety was estimated using the equation [1-(ODT/ODC)] × 100%, where ODT is the average optical density of cells cured with the compounds and ODC is the average optical density of uncured cells [35,36].

2.5.2. Antibacterial and antifungal activity

In order to test the complexes against two classes of bacteria: Staphylococcus aurous (Gram-positive) and Escherichia coli (Gram-negative), and two kinds of fungi: Candida albicans and Aspergillus flavus, the disc diffusion method was utilized [37,38].

2.5.3. Antioxidant activity and screening assay for erythrocyte hemolysis

Samples of blood from the rats were withdrawn in heparinized tubes. Red blood cells (RBCs) were detached from plasma and the buffy coat was washed about three times with 10 volumes of 0.15 M saline solution. After the middle of the last launder, the erythrocytes were centrifuged at 2,500 rpm for 10 min to obtain a constantly packed cell preparation. In the measured coordination polymer system, erythrocyte hemolysis was permeated by peroxyl radicals [39,40]. The same volume of 10% suspension of erythrocytes in a phosphate-buffered saline (PBS; pH = 7.4) and 200 mM 2,2′-azobis(2-amidinopropane) dihydrochloride solution were added to each other in PBS containing samples to be examined at varied concentrations. The reactant was cradled gently and incubated at 37 °C for 2 h. After that, the mixture was emptied, diluted with eight volumes of PBS, and centrifuged for 10 min at 1,500 g. The supernatant absorption was recorded at 540 nm. Also, for achieving a complete hemolysis, the reactant was treated with 8 volumes of distilled water, and the supernatant after centrifugation was measured at 540 nm. L-ascorbic acid was wielded as a positive control.

2.5.4. Colorimetric assay for compounds that bind DNA

DNA methyl green (20 mg) was suspended in 100 mL of 0.05 M Tris-HCl buffers (pH 7.5) containing 7.5 mM MgSO4. The mixture was then stirred at 37 °C for one day. Test samples (10 mg, 100 mg, 1,000 mg) were dissolved in EtOH; after that the solvent was separated under vacuum and to each tube 200 μL of the DNA/methyl green solution was added. Samples were incubated in the dark at ambient temperature. After one day, the final absorbance of the samples was determined at 642.5–645 nm. Results were corrected for premier absorbance and normalized as the percentage of the untreated standard. The absorbance of the pure DNA (A260/280) is ∼ 1.8.

3. Results and discussion

3.1. Infrared spectra

The ligand spectrum in KBr exhibits bands at 3,216 sh, 3,125 s, 2,980 m, and 2,784 m cm−1 attributed to OH (free), OH (hydrogen-bonded), CH, and CH3, respectively, as shown in Table 1. Three bands attributed to the azomethine groups: (C=N) at 1,678 cm−1, (C=NOH) at 1,658 cm−1, and (C=N−N) at 1,597 cm−1, are relocated to a lower wavelength in the metal chelates indicating the involvement of these groups in bonding. The IR spectrum of [NiLCl(H2O)]Cl·1.5H2O shows five bands at 3,421 cm−1, 3,141 cm−1, 1,691 cm−1, 1,626 cm−1, and 1,575 cm−1 in which the first four bands are directed to low shifts while the latter band is shifted to higher wavenumbers (Figure 1). The first band at 3,421 cm−1 refers to the free hydroxyl group of the oxime molecule. Also, the band at 3,141 cm−1 refers to the coordinated OH group of H2O while the two bands at 1,691 cm−1 and 1,626 cm−1 are assigned to the coordinated azomethine groups ν [C=N(oxim) and C=N(aliph)] vibrations, respectively. Furthermore, the band noticed at 1,575 cm−1 refers to the uncoordinated (C=N)(cyclic) band [41]. So, the ligand behaves as a tetradentate ligand around the Ni2+ ion. The IR spectra of the Cd2+, Pt4+, and Cu2+ are recorded in Figures 2–4.

tab1
Table 1: The most important assignments of the ligand and its complexes.
fig1
Figure 1: IR spectra of [NiCl(H2O)]Cl·1.5H2O.
fig2
Figure 2: IR spectra of [Pt2LCl50.5H2O0.5EtOH].
fig3
Figure 3: IR spectra of [Cu3LCl2(H2O)5]4Cl.
fig4
Figure 4: IR spectra of [Cd3LCl6(H2O)7].
3.2. Electronic spectra and magnetic measurements

The geometries of metal ions in the complexes are assigned according to the positions and number of d-d transition peaks that appear in the electronic absorption spectra. The electronic spectra of the ligand and its complexes varied in DMSO. Three bands are observed in the spectrum of L. The first two bands at 45,871 cm−1 and 41,666 cm−1 are attributed to π → π∗ transitions. The third band at 38,759 cm−1 is assigned to n → π∗ transition. The visible spectrum of Ni2+ complex shows four bands at 20,964 cm−1, 17,605 cm−1, 14,792 cm−1, and 12,903 cm−1; the first band due to 3T1 → 1T2 and the second and third bands are assigned to 3T1 → 3T1(p), respectively. The fourth band is assigned to 3T1 → 3A2. The magnetic moment of the complex (4.03 BM) suggests a d8 tetrahedral structure around the nickel ion [42]. Cu complex showed new three bands at 17,543 cm−1, 11,641 cm−1, and 10,822 cm−1, where the first band is assigned dz2 → dX2−Y2 and the other two bands are attributed to dxz,dyz → dX2−Y2 and dxy → dX2−Y2, respectively. The μeff of the complex (0.98 Bohr Magneton) proposed a d9 square-planar structure around the Cu2+ ion [42]. The two bands (31,446 cm−1 and 26,881 cm−1) of the diamagnetic Pt4+ complex are assigned to n → π∗ and M → L transitions, respectively, and the results are recorded in Table 2.

tab2
Table 2: The electronic spectra and magnetic moments for L and its complexes.
3.3. Thermal analysis

The analysis of TGA plays an important role in studying the attributes of the metal complexes. The curves are consummated to make sure that the suggested formulae and the structures of the complexes under investigation are correct. A thermo-gravimetric analysis was performed in the range from 20 °C up to 800 °C. TGA results were utilized to appraise and calculate mass loss in addition to the results of the elemental analyses. The decomposition steps for [NiLCl(H2O)]Cl·1.5H2O are depicted in Figure 5. The first started from 30 °C to 120 °C gets along with the loss of one and half H2O molecules (Found: 8.4%, Calcd.: 7.9%). The second and third steps show losses in the 120 °C to 800 °C corresponding to the removal of H2O molecule and the fragments of C4H9N5OCl2 (Found: 68.2%, Calcd.: 67.8%). The residue corresponds to Ni+2C in the theoretical loss (24.1%), which is matching the experimental loss 23.4%. The TGA curves for the Ni2+, Cu2+, Cd2+, and Pt4+ complexes are shown in Figures 5–8. The results of thermal decomposition steps for the complexes are tabulated in Table 3.

fig5
Figure 5: TGA of [NiLCl(H2O)Cl]Cl·1.5H2O.
fig6
Figure 6: TGA of [Cu3LCl2(H2O)5]4Cl.
fig7
Figure 7: TGA of [Cd3LCl6(H2O)7].
fig8
Figure 8: TGA of [Pt2LCl5(H2O)0.5(EtOH)0.5]3Cl.
tab3
Table 3: The most thermal decomposition steps of the complexes.
3.4. Results of kinetic data together with the thermal degradation steps of complexes

The results of kinetic data of the isolated complexes (Ni2+, Pt4+, and Cu2+) as well as the thermodynamic parameters of activation were calculated by Eyring equation [43]. All the data are recorded in Table 4 by two isothermal methods such as Coats-Redfern (CR) [44] (Figures 9, 11, and 13) and Horowitz-Metzger (HM) [45] methods (Figures 10, 12, and 14).

tab4
Table 4: Kinetic parameters of Cu2+, Ni2+, and Pt4+ complexes evaluated by Horowitz-Metzger (HM) and Coats-Redfern (CR) methods.
fig9
Figure 9: 1st, 2nd, and 3rd thermal degradation steps of Ni2+ complex using CR method.
fig10
Figure 10: 1st, 2nd, and 3rd thermal degradation steps of Ni2+ complex using HM method.
fig11
Figure 11: 1st, 2nd, and 3rd thermal degradation steps of Pt4+ complex using CR method.
fig12
Figure 12: 1st, 2nd, and 3rd thermal degradation steps of Pt4+ complex using HM method.
fig13
Figure 13: 1st and 2nd thermal degradation steps of Cu2+ complex using CR method.
fig14
Figure 14: 1st and 2nd thermal degradation steps of Cu2+ complex using HM method.

The results in Table 4 pointed out to the following remarks:

 (i) The stages of decomposition illustrate that the best fit is when n = 1, while the other values for n did not fit the best correlation.

 (ii) ΔG* with positive values suggest that the decomposition steps are a nonspontaneous process since the free energy of the final residue is higher than the initial compound. ΔG* values increase since the value of TΔS* are higher than the value of ΔH* [46,47].

 (iii) All the decomposition stages are an endothermic process since the values of ΔH* have positive values.

 (iv) ΔS* of the decomposition steps have positive values suggesting that the disordered structure of the activated fragments is less than that of the undecomposed complex and consequently the decomposition reactions are slow [43].

3.5. Cyclic voltammetry (CV)

The redox properties of Cu2+ complex was studied by CV technique as shown in Figure 15. The measurements of Cu2+ complex (10−3 M) were officiated in a nonaqueous DMF solution containing the supporting electrolyte 0.1 M of [(n-Bu)4N]PF6 within the potential range from 0.8 V to −0.4 V at scan rate 100 mV/s. The Cu2+ complex exhibits quasi-reversible reduction waves at positive potentials for one electron transfer and at E1/2 = 0.227 V, ΔE =286 mV, where Epc = +0.084 V and Epa = +0.37 V (Cu2+/Cu+).

fig15
Figure 15: Cyclic-voltammetry of Cu(II) complex.
3.6. Molecular computational calculation using DFT

The structures of metal complexes together with the atom numbering are depicted in Figures 16–18. The following remarks are obtained from the results of bond angles and lengths.

 (i) The bond distance

  N(6)−C(21), N(2)−C(7), N(2)−N(6), N(22)−C(21), N(6)−C(4), C(20)−N(1), and N(3)−C(4)

  in the separated complex switched to be longer than that of L as a result of the formation of M−O and M−N bonds.

 (ii) Upon coordination the bond angles of L are amended to some degree; such

  N(2)−C(7)−C(20), N(2)−C(7)−C(12), C(20)−C(7)−C(12), C(21)−N(6)−N(2), C(21)−N(6)−C(4), and N(2)−N(6)−C(4)

  angles are decreased or increased on bonding as a result of bonding.

 (iii) The bond angles in Pt4+ and Cu2+ complexes afforded square-planar geometry, while Ni2+ complex shows tetrahedral geometry with sp3 geometry. Finally, Cd2+ complex illustrates octahedral geometry.

 (iv) We can predict an increase in the molecular weight and a decrease in the gas phase energy on the basis of the data in Table 5.

 (v) The energy of both HOMO (π-donor) and LUMO (π-acceptor) is important in quantum chemical monographs, since the orbital behaves as an electron donor and known as a HOMO while the orbital acts as an electron acceptor and nominated as a LUMO. These molecular orbitals are known as frontier molecular orbitals (FMOs).

fig16
Figure 16: Molecular modeling of (a) Ni2+ complex, (b) electron density, (c) HOMO, and (d) LUMO.
fig17
Figure 17: Molecular modeling of (a) Cu2+ complex, (b) electron density, (c) HOMO, and (d) LUMO.
fig18
Figure 18: Molecular modeling of (a) Pt4+ complex, (b) electron density, (c) HOMO, and (d) LUMO.
tab5
Table 5: Calculated EHOMO, ELUMO, energy band gap (EH-EL), chemical potential (μ), electronegativity (χ), global hardness (η), global softness (S), and global electrophilicity index (ω) for the new complexes.

Table 5 depicted the chemical reactivity and site selectivity of the molecular systems by the DFT method concept. The energies of (EHOMO+ELUMO) and energy band gap (EHOMO−ELUMO) which feigned the end charge-transfer interaction within the molecule, electronegativity (χ), chemical potential (μ), global hardness (η), global softness (S) and global electrophilicity index (ω) are recorded in Table 5 [48,49,50]. The characterizations of kinetic stability and chemical reactivity of compounds depend on the energy gap (EHOMO−ELUMO) which is considered the main stability index that facilities the description. Upon the group that enters in the conjugation, the low value of energy gap suggests the easier of charge-transfer which influences the biological activity of the compounds. It is well known that the soft ligand with small gap is more reactive and more polarized than the hard one due to the ease in donating electron to the acceptor. Table 6 illustrates some of energies the isolated complexes.

tab6
Table 6: Some of energetic properties for the new complexes using DFT method.
3.7. Mass spectra

The mass spectrum of [Cu3LCl2(H2O)5]4Cl (Figure 19) shows a peak at 660.91 [m/z] that coincides with the estimated value (660.61), which indicates that the formula of the compound is corrected. The fragmentation manner of the Cu2+ chelate (2:1) is depicted in Scheme 1. Also, the results of elemental analysis and thermal analyses are wielded to emphasize the suggested formula.

fig19
Figure 19: Mass spectra of [Cu3LCl2(H2O)5]4Cl.
sch1
Scheme 1: The fragmentation manner of [Cu3LCl2(H2O)5]4Cl.

The mass spectrum of [Pt2LCl5(H2O)0.5(EtOH)0.5]3Cl (Figure 20) exposes the molecular ion peak at 874.24 [m/z], which is in agreement with the theoretical value (873.0). This proposes that the suggested formula of this compound is approved with the experimental data. Scheme 2 explored the fragments of the Pt(IV) complex (1:1). The data of elemental and thermal analysis are also taken as an evidence for that assumption. The mass spectrum indicates the dissociation of Pt(IV) complex.

fig20
Figure 20: Mass spectra of [Pt2LCl5(H2O)0.5(EtOH)0.5]3Cl.
sch2
Scheme 2: The fragmentation manner of [Pt2LCl5(H2O)0.5(EtOH)0.5]3Cl.
3.8. Biological studies
3.8.1. Antitumor activity

The in vitro cytotoxicity of L and its complexes was scanted by MTT-based assays [35,36,51]. Through colorimetric technique, MTT assay is considered an adequate method to decide the cytotoxicity and for measuring cell growth. It is known that the yellow color of [MTT; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] changes to purple due to the formation of formazan via mitochondrial dehydrogenases of the cells [52]. The purple formazan which is insoluble becomes soluble on the addition of suitable solvent to form the colored solution. And hence the value of the absorbance at specific wavelength of the colored solution was purposed. In comparing the cured cells with the compounds and those obtained by unreacted control cells of the amount of purple formazan formed, we get the efficacy of the complexes in triggering death of cells concluded by the formation of a potion response curve and the results are shown in Table 7. The data obtained show that the estimating of L has availed chemotherapy since it exhibits a very strong activity towardsmammary gland breast (MCF-7) and human cervical epithelioid carcinoma (Hela) with IC50 values of 7.91 μg/mL and 6.83 μg/mL, respectively. Also, the ligand has a strong activity against prostate cell line (PC-3) with IC50 value of 12.13 μg/mL. Almost the same result is with the Ni(II) complex as it has a very strong activity towards (MCF-7) and (Hela) with IC50 values of 9.98 μg/mL and 8.14 μg/mL, while it exhibits a strong activism towards (PC-3) with IC50 values of 16.97 μg/mL. In addition to that the Cu(II) chelate has a strong IC50 value in (MCF-7) and (Hela) and a moderate activity against (PC-3) cell line. On the other hand, in (Hela) cell line, Cd2+ complex exhibits a moderate cytotoxicity effect, while the Pt4+ chelate has a weak IC50 in the same cancer cell line. The extent of the activities of ligand and its complexes lies between very strong and moderate to weak as shown in Figure 21.

tab7
Table 7: Cytotoxic activity of the ligand and some metal complexes against human tumor cells.
fig21
Figure 21: Cytotoxic activity of some compounds against human tumor cells.
3.8.2. DNA/methyl green colorimetric assay of the DNA-binding compounds

Green methyl dye reacts with DNA and produces a dyed DNA-methyl green in which the product of an addition reaction is reversible. This color remains unchanged in neutral pH, in which the free methyl green disappeared at this pH value. DNA-binding active compounds dislodge DNA from its methyl green complex. Upon alteration of DNA from methyl green by intercollators DNA, adding of water to the dye was allowed, which led to the development of the pale carbinol, then the absorbance declines as observed from the colorimetric curves. The offset was calculated by a spectrophotometric assay as a decrease in the absorbance at 630 nm. The results were announced as inhibition concentration 50% value (IC50) calculated by linear regression of data plotted on a semi-log scale and represented in Table 8. In this assay, doxorubicin was used as a control. Doxorubicin or Adriamycin, this drug belongs to a group of antitumor medications or the socalled antimetabolic drugs. It works to stop the growth of tumor cells by interfering with the DNA, which is the genetic material present in the cell. L displayed a very strong inhibitory activity and powerfully intercalate DNA at a decreased IC50 value in the range of 29.18 ± 1.6 μM. Approximately, the activity of tested chelates is arranged in the order Ni(II) > Cu(II) > Cd(II) > Pt(IV) comparing to Doxorubicin with IC50 values as shown in Table 8.

tab8
Table 8: DNA/methyl green colorimetric assay of the DNA-binding compounds.
3.8.3. Antioxidant activities

The ligand (L) and its metal complexes were examined for their antioxidant activity by the erythrocyte hemolysis. The results of the antioxidant activity with vitamin C are depicted in Table 9 and represented in Figure 22. The ligand showed a high antioxidant activity with respect to erythrocyte hemolysis. The activity of the tested complexes is arranged in the order Co(II) > Pd(II) > Fe(III) in comparison to vitamin C with respect to erythrocyte hemolysis.

tab9
Table 9: Antioxidant erythrocyte hemolysis assay for the ligand and isolated complexes.
fig22
Figure 22: Antioxidant activity through erythrocyte hemolysis.
3.8.4. Antibacterial and antifungal activity

In the antimicrobial activities, the ampicillin (a broad-field antibiotic) acts as a positive control for the antibacterial test while DMSO was utilized as a negative control and solvent. The diameter of inhibition zone of ampicillin towards E. coli is 25 mm and towards S. aurous is 21 mm. Table 10 depicts the results of the antibacterial test of the tested complexes towards Gram-negative (E. coli) and Gram-positive (S. aurous) bacterial strains. The Cd(II) complex shows the maximum antibacterial activity towards E. coli with 24 mm inhibition zone diameter. On the other hand, the complexes of Cu(II) and Ni(II) manifested a sensible antibacterial activity towards E. coli with 13 mm and 12 mm inhibition zone diameter, respectively. Pt(IV) complex exhibits the weakest antibacterial activity recording 5 mm inhibition zone diameter. The antibacterial behavior of the examined chelates against Gram-positive bacterial strain S. aurous is illustrated in Table 10. The Cd(II) complex (31 mm) > the reference antimicrobial ampicillin (21 mm) > Pt(IV) (16 mm) > Cu(II) (13 mm) = Ni(II) (13 mm).

tab10
Table 10: Antimicrobial activity of the isolated compounds.

Amphotericin B (antifungal agent) recorded the antifungal activities towards the fungal strains A. flavus and C. albicans of 17 mm and 21 mm, respectively. Only Cd(II) and Cu(II) compounds exhibit an antifungal effectiveness towards fungal strain C. albicans with 27 mm and 11 mm inhibition zone diameter, respectively. While Ni(II) and Pt(IV) chelates do not display any antifungal reactivity towards fungal strain C. albicans. Cd(II) complex shows a potent activity against fungal strain A. flavus and Ni(II) and Cu(II) compounds show moderate antifungal activities against fungal strain A. flavus. While Pt(II) complex does not show any antifungal activities against fungal strain A. flavus. It was perceived that the ligand has no effect against bacteria or fungi as represented in Table 10. The antimicrobial activities of L and its chelates are shown in Figure 23. The efficient and effective propagation of compounds via cell membrane or interaction with microorganism cell wall give rise to a high antibacterial activity, which is known as lipophilic characteristics (i.e., penetrating the lipid cell wall linked to the polarity of central metal ion and raised with the formation of chelation ring, sharing the positive charge on metal ion with the N-donor atom of L causing π-electron delocalization on the chelation ring, which is also corroborated by the works in [53,54,55]).

%Activity index = Zone of inhibition by test compound (diameter) Zone of inhibition by standard (diameter) × 100 .
fig23
Figure 23: Antibacterial and antifungal activities of L and its complexes.

4. Conclusion

A novel ligand, 3-(3H-1,2,4-triazole-4-(5H)-ylimino)butane-2-one-oxime (L), and its complexes were synthesized and characterized using chemical, spectral (FTIR, UV-Vis, mass), cyclic voltammetry, and magnetic measurements. Electronic spectra and magnetic measurements of the complexes suggest a structure that is tetrahedral for Ni2+, octahedral for Cd2+, while square-planar for Cu2+ and Pt4+ complexes. Also, DFT parameters were applied for Cu2+, Ni2+, and Pt4+ complexes which prove the geometry of L towards the metal ions. Kinetic and thermodynamic parameters of the isolated complexes were calculated by CR and HM methods. The biological activity of L and its complexes was tested against three types of cancer cell lines, and against different bacterial strains.

Acknowledgments

This article is based on a M.Sc. thesis entitled “Spectroscopic, cyclic voltammetry and biological studies of some complexes derived from dialkyl hydrazines and oximes of some metal ions” by Doaa E. El-Kholy in “2020” at “Mansoura University, Egypt”.

Conflict of interest

The authors declare that they have no conflict of interest.

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