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2-(2-(2-Hydroxybenzyliden) Hydrazinyl)-2-Oxo-N-(Pyridine-2-Yl) Acetamide Complexes: Synthesis, Characterization and Biological Studies | OMICS International
ISSN: 2150-3494
Chemical Sciences Journal
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2-(2-(2-Hydroxybenzyliden) Hydrazinyl)-2-Oxo-N-(Pyridine-2-Yl) Acetamide Complexes: Synthesis, Characterization and Biological Studies

Yasmeen Gaber Abou El-Reash, Rania Zaky* and Mahmoud Abbas Yaseen

Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt

*Corresponding Author:
Rania Zaky
Department of Chemistry
Faculty of Science, Mansoura University
Mansoura, Egypt
Tel: +20502383781
E-mail: [email protected]

Received date: November 01, 2016; Accepted date: December 05, 2016; Published date: December 08, 2016

Citation: El-Reash YGA, Zaky R, Yaseen MA (2016) 2-(2-(2-Hydroxybenzyliden) Hydrazinyl)-2-Oxo-N-(Pyridine-2-Yl) Acetamide Complexes: Synthesis, Characterization and Biological Studies. Chem Sci J 7:145. doi: 10.4172/2150-3494.1000145

Copyright: © 2016 El-Reash YGA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

2-(2-(2-hydroxybenzyliden) hydrazinyl)-2-oxo-N-(pyridine-2-yl) acetamide complexes of Ni(II) and Co(II) prepared. The proposed structures proved based on elemental, DFT, and spectral analysis. The DNA binding affinity and MIC activity against Gram-positive, Gram-negative bacteria, pathogenic C. albicans and A. flavus fungal strain tested.

Keywords

Hydrazones; DFT; DND; Potentiometry

Introduction

Hydrazones are versatile ligands and possessing an azomethine -NHN=CH- proton groups. They can be described by the following general structure R2C = NNR2. Hydrazone ligands and their metal complexes were attracted many authors because of their varied applications in biological, pharmaceutical, analytical, catalytic [1-5] and industrial fields. Hydrazones and their coordination compounds play important roles in treatment of different diseases. Hydrazones considered as an significant class of compounds with wide importance due to their various biological applications such as anticonvulsant, analgesic, anti-inflammatory, antidepressant, antimalarial, antiplatelet, antimycobacterial, antimicrobial, antiviral, anticancer, antidiabetic, vasodilator, anti-HIV, anthelmintic, and trypanocidal activities [6-14]. This work targets the synthesize and characterization Co(II) and Ni(II) complexes of 2-(2-(2-hydroxybenzyliden) hydrazinyl)-2-oxo-N- (pyridine-2-yl) acetamid (H2L). The geometry and modes of chelation of complexes were discussed based on the resulted (DFT) quantum calculations, the magnetic moment, the different spectroscopic methods (1H and 13C-NMR, UV-visible, IR, EI-mass). Moreover, the thermal decomposition steps were studied and both the kinetics and thermodynamic factors were determined using Coats-Redfern and Horowitz-Metzger models. In addition, potentiometric titrations were done in 50% DMSO-water mixture at various temperatures (298, 308 and 318 K) respectively. Moreover, their Minimum inhibitory concentration (MIC) and DNA-binding affinity assay were tested.

Experimental Methods

Instrumentation

(C, H and N) percent presented in the prepared ligand (H2L) and complexes were detected using a Perkin–Elmer 2400 series II analyzer, while chloride and metal contents determined using standard methods reported previously [15]. A thermogravimetric analyzer (TGA-50H) from Shimadzu, Japan, used for both thermogravimetric (TGA) and differential thermal analysis (DTA) measurements with a heating rate of 10°C/min on at temperature range (20-800°C) and nitrogen flow rate of 15 ml/min. A Sherwood Magnetic Balance was utilized to measure the magnetic susceptibility of solid complexes. A Mattson 5000 FTIR spectrophotometer was used to analyze the prepared ligand and complexes under range of (4000-400 cm-1) in KBr discs. While; the electronic spectra of complexes (in DMSO solution) was recorded using a Perkin Elmer Lamda 25 UV/Vis Spectrophotometer. 1H, 13C-NMR measurements were done on Mercury and Gemini 400 MHZ spectrometer at room temperature in d6-DMSO. pH meter HANNA -8519, Italy used in all pH- metric measurements.

Synthesis

Preparation of ligand (H2L)

Preparation of ethyl 2-oxo-2-(pyridin-2-ylamino) acetate: Ethyl 2-oxo-2-(pyridin-2-ylamino) acetate were prepared by adding of diethyl oxalate (1 mmol) dissolved in xylene to 2-amino pyridine (1 mmol) dissolved in xylene with stirring followed by reflux with stirring for 3 hr. Let the resulted product to cool then filtered off, washed by ether and at the end dried over anhydrous calcium chloride in a vacuum desiccator. The product is yellow color powder with m.p. (180°C).

Preparation of 2-hydrazinyl-2-oxo-N-(pyridin-2-yl) acetamide: 2-hydrazinyl-2-oxo-N-(pyridin-2-yl) acetamide were prepared by adding of hydrazine hydrate (1 mmol) dissolved in xylene to ethyl 2-oxo-2-(pyridin-2-ylamino) acetate (1 mmol) dissolved in xylene with stirring followed by reflux with stirring for 3 hr. Let the resulted product to cool then filtered off, washed by ether and at the end dried in a vacuum desiccator over anhydrous calcium chloride. The resulted ligand is a yellow color powder with m.p (195°C).

Preparation of ligand (H2L): 1:1 molar ratio of 2-hydrazinyl- 2-oxo-N-(pyridin-2-yl) acetamide and 2-hydroxybenzaldehyde (salicylaldehyde) were mixed in a hot ethanolic solution with few drops of glacial acetic acid. The mixture was refluxed for 4 h under magnetic stirring. The formed products were separated by filtration, and then recrystallized from ethanol absolute. Finally, the resulted ligand was dried for 36 h in a vacuum desiccator, then investigated by TLC, elemental analysis (C, H and N), and spectroscopic methods (IR, UVVis., 1H NMR, 13C NMR and EI-mass).

Preparation of solid complexes: All the complexes were prepared by refluxing 1 mmol of ligand under investigation with 1 mmol of the metal salt, NiCl2.6H2O, and CoCl2.6H2O in an ethanolic solution on a water bath for 2-3 h. The resulting solid complexes filtered off, washed several times with absolute ethanol and finally dried.

Molecular modelling

Cluster calculations were evaluated using DMOL3 program [16] in Materials Studio package [17]. This program designed for the calculations of density functional theory (DFT) over a large scale. Moreover, DFT method was applied to calculate the semi-core pseudopods (dspp) by using the double numerical basis sets plus polarization functional (DNP). Delley et al. revealed that the DNP basis sets are more precise than Gaussian basis sets of the same size [18,19]. Lately; the RPBE basis sets are the best exchange-correlation functional [20,21]. It utilized for the determination of both the exchange and correlation effects of electrons based on the generalized gradient approximation (GGA). The geometric design predicted without any symmetry restriction.

pH-metric study

Potentiometric titrations were done at 298, 308 and 318°K in a mixture of dioxane-water 50% (v/v). All resulted values were adjusted using Van Uitert and Hass relation [22]:

image

Where logU0H and log γ± are the correction factors for the solvent composition and ionic strength, respectively and B is the reading.

In the experiments; the following mixtures were titrated against standardized free carbonate NaOH solution (8.5 × 10-3 mol L-1) in 50% (v/v) DMSO-water at constant ionic strength (1 mol L-1 KCl solution) The solution mixtures (i-iii) were prepared as follows:

i) 1.25 ml HCl (1.12 × 10-2 M)+1.25 ml KCl (1 M)+12.5 ml DMSO+10 ml bidistilled H2O.

ii) 1.25 ml HCl (1.12 × 10-2 M)+1.25 ml KCl (1M)+2.5 ml (5 × 10-3 M) H2PET+10 ml DMSO+10 ml bidistilled H2O.

iii) 1.25 ml HCl (1.12 × 10-2 M)+1.25 ml KCl (1M)+2.5 ml (5 × 10-3 M) H2PET+10 ml DMSO+0.5 ml metal ion (Mn+) (5 × 10-3 M), [where Mn+ = Co(II)]+9.5 ml bidistilled H2O.

The total volume attuned to 25 ml by DMSO in each prepared mixture.

Biological activity

Minimum Inhibitory Concentration (MIC): The biological activities for the prepared ligand and its solid complexes were examined against diverse types of strains isolated from animal byproducts. These strains were suspected to be the main reason for food intoxication in human. Staphylococcus aureus, Bacillus subtilis are examples for gram positive bacteria and Escherichia coli, Pseudomonas aeuroginosa are gram negative bacetria. All samples were tested in a Muller Hinton agar medium (Oxoid). Also, the anti-fungal activity for these compounds against (Candida albicans and Aspergillus flavus) was checked in Sabouraud dextrose agar medium (Oxoid). Ampicillin as anti-bacterial and Colitrimazole Fluconazole as anti-fungal were used as standard materials.

MIC [23] of the respective compounds were measured by agar streak dilution method. All steps of the experiments were carried out as reported previously [24].

Colorimetric assay for compounds that bind DNA: A suspended solution of 20 mg of DNA methyl green was prepared in 100 ml of Tris- HCl (0.05 M), buffered at pH 7.5 and contains 7.5 mM MgSO4. This mixture was stirred for 24 h at 37°C. In an ependoff tubes, 10, 100, 1000 mg of test samples dissolved in ethanol were prepared, then solvent was removed under vacuum, and 200 μl of the DNA/methyl green solution were added to all tubes. All samples were incubated for 24 h in the dark at ambient temperature, and then the absorbance values for the samples were evaluated at 642.5-645 nm. Reading values were corrected per the initial absorbance of the untreated standard [25].

Results and Discussion

Infrared and 1H, 13C NMR, mass spectra of H2L and its metal complexes

The Infrared spectrum of H2L (Structure 1) shown seven peaks at 3345, 3320, 3266, 1708, 1672, 1607 and 785 cm-1 which attributed to υ(OH) [8,26], υ(NH)1, υ(NH)2, υ(CH2) [27] υ(C=O)1, υ(C=O)2 [6], υ(C=N) and δ(C=N), respectively. The 1H-NMR spectrum of H2L was recorded in DMSO (Figure 1). The ligand (H2L) display three signals at 12.62, 11.21 and 10.82 ppm can be attributed to the protons of (OH), (NH)1 and (NH)2, respectively which they are disappeared on adding of D2O (Figure 2). The various signals detected in the region of (6.71- 8.99) ppm are assigning to the present aromatic and pyridine ring protons. The sharp signal observed 3.46 ppm was assigned to protons of –N=CH–.

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Structure 1: (a) Optimized molecular structure of H2L, (b) HOMO and (c) LUMO.

chemical-sciences-journal-1HNMR-spectra-H2L-d6-DMSO

Figure 1: 1HNMR spectra of H2L in d6-DMSO.

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Figure 2: 1HNMR spectra of H2L in d6-DMSO with addition of D2O.

The13C NMR spectrum of H2L was recorded in DMSO (Figure 3). The signals for the (C=O)1, (C=O)2, and (C=N) were displayed at downfield position (158.6, 162.7), and (149.8), respectively [27,28].

chemical-sciences-journal-mass-spectrum-fragmentation

Figure 3: 13CNMR spectra of H2L d6-DMSO. The mass spectrum of H2L is given in Figure 4 shows the molecular ion peak for H2L at m/z=284.20 (4.05%) corresponding to (C14H12N4O3) [29]. The fragmentation path of H2L is given in Ref. [30,31].

In the IR spectra of Ni(II) and Co(II) complexes (Structures 2 and 3), H2L behaves as binegative tetradentate via (C=N)az, both (C-O) enolized with deprotonation and (OH)phenolic. This suggestion indicated by:

i) ν(C=N)az shifted to a lower wavenumber.

ii) ν(C=O) disappeared with simultaneous appearance of new bands attributed to ν(C=N)* and ν(C-O) [29-32].

iii) ν(OH) shifted to a higher wavenumber.

iv) New bands appeared at (513 and 541) and (454 and 459) cm-1 which attributable to (M-O) and (M-N) [26], respectively.

chemical-sciences-journal-Optimized-molecular-structure

Structure 2: Optimized molecular structure of [Co(L)(H2O)2].2H2O.

chemical-sciences-journal-Optimized-molecular-structure

Structure 3: Optimized molecular structure of [Ni(L)(H2O)2].2H2O.

Magnetic properties and electronic spectra

The functions for all the spectral bands for the prepared ligand and its complexes in DMSO and the magnetic moments are compiled (Table 1). The ligand (H2L) showed two main absorption bands at 32787 and 27473 cm-1 assigned to π-π* and one obivious band at 25510 cm-1 attributed to n-π* of both C=O and C=N groups [33,34].

Compound Band position,cm-1 Dq(cm-1) B (cm-1) β μeff(B.M)
H2L 32787, 27473, 25510 - - - -
[Co(L)(H2O)2].2H2O 28249, 23148, 17136, 14084 964 916 0.99 5.04
[Ni(L)(H2O)2].2H2O 31646, 27624, 26667, 17391 1067 762 0.73 3.30

Table 1: Electronic spectral data of H2L and its complexes.

For [Co(L)(H2O)2].2H2O complex, two bands were observed at 14084 and 17136 cm-1 assignable to 4T1g(F)→4A2g(F)(ν2) and 4T1g(F)→4T1g(P)(ν3) transitions respectively, which agree with the high spin octahedral Co(II) [35,36]. Moreover, the ligand field parameters, Dq, B and β (964, 916 and 0.99) can be considered as an evidence for the proposed geometry. As well, the value of the magnetic moments (μeff.=5.04 BM) was consistent with the proposed octahedral geometry.

Furthermore, in [Ni(L)(H2O)2].2H2O complex; two bands appeared at 17391 and 26667 cm-1 that are assignable to 3A2g(F)→3T1g (F)(ν2) and 3A2g(F)→3T2g (P)(ν3) transitions. These transitions are distinguishing for the octahedral Ni(II) complexes [37] and the calculated ligand field factors, Dq, B and β (1067, 762 and 0.73) and magnetic moments value (μeff.=3.3 BM) support the supposed geometry. The position of υ1(7902 cm-1) was calculated theoretically [28].

Thermogravimetric studies

The TG and DTA curves for the decomposition of Ni(II)-complex were depicted in Figures 4 and 5. The obtained results approved the proposed formulae. Where, the complex decomposed in three main steps. The primary step implied losing hydrated water molecules at 40- 76°C, followed by the losing coordinated water at 76-200°C. Then, the deligation began at a temperature range of 200-800°C and at the end metal oxide was formed.

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Figure 4: Mass spectrum of H2L

chemical-sciences-journal-Thermal-analysis-curves"

Figure 5: Thermal analysis curves (TGA, DTG) of [Ni(L)(H2O)2].2H2O complex.

Kinetic data: The kinetic parameters were calculated by using nonisothermal methods of decomposition steps. The rate of degradation (dα/dt) is a linear function of rate constant (k) and function of conversion (α) and can be expressed as follow [a]:

dα / dt =K(T) f (α) (1)

k can be calculated by the Arrhenius equation:

K = Ae(−E/RT) (2)

Where R is the gas constant, E is the activation energy and A is the pre-exponential factor.

By substituting Eq. (2) into Eq. (1):

dα / dt = A /Ø(e(−E/RT) ) f (α) (3)

When the temperature varied by a constant and controlled heating rate, Ф=dT/dt, the change in degree of conversion which is a function of temperature dependent also on time of heating. Therefore, Eq. (3) becomes:

dα / dt = A /Ø(e(−E/RT) ) f (α) (4)

By integrating Eq. (4):

(5)

Where g(α) is the integrated form of the conversion dependence function? The right-hand side integral of Eq. (5) known as temperature integral; has no closed form solution and can be evaluated by Coats- Redfern (CR) method (Figure 6) [38] and the approximation method of Horowitz-Metzger (HM) (Figure 7) [39].

chemical-sciences-journal-Coats-Redfern-plots

Figure 6: Coats-Redfern plots of [Ni(L)(H2O)2].2H2O complex.

chemical-sciences-journal-Horowitz-Metzger-plots

Figure 7: Horowitz- Metzger plots of [Ni(L)(H2O)2].2H2O complex.

From the obtained results:

i) All kinetic parameters (E, A, ΔH*, ΔS* and ΔG*) for all prepared solid complex were calculated by CR and HM method (Table 2). Both methods gave comparable values.

Compound Step Mid
Temp.(K)
Method Ea A ΔH* ΔS* ΔG*
KJ/mol (S-1) KJ/mol KJ/mol.K KJ/mol
[Ni(L)(H2O)2].2H2O 1st 334.08 HM 203.82 1.09×1030 201.04 0.32915 91.08
CR 200.87 3.85×1029 198.09 0.32053 91.01
2nd 457.82 HM 26.02 1.43 22.21 -0.24548 134.60
CR 17.82 2.18×10-01 14.01 -0.26112 133.56
3rd 599.12 HM 859.55 2.49×1073 854.57 1.15437 162.96
CR 848.81 2.91×1072 843.83 1.13652 162.92

Table 2: Kinetic Parameters evaluated by Horowitz-Metzger and Coats-Redfern equations for Ni(II) and Cu(II) complexes of H2L.

ii) For all complexes; decomposition stages fitted better when (n=1) suggesting a 1st-order decomposition process. Other n values (eq. 3 and 4) did not show better correlations.

iii) The value of ΔG increases for complexes because while going from one decomposition step to another; the rate of H2L removal will be lower [40,41]. This can be due to, the rigidity of remaining complex after the explosion of one or more H2L molecules.

iv) The values of the entropy (ΔS*) for the decomposition steps of complexes show that the activated fragments have more ordered (negative values) or disordered (positive values) structure than the undecomposed complexes and/or the decomposition reactions are slow [38].

v) The positive value of ΔH* means the endothermic nature of the decomposition processes.

Generally, the values of stability constants decrease with increasing the number of H2L atoms attached to the metal ion [42,43]. Therefore, an opposite effect may occur during the decomposition process. Hence, the rate of removal of the remaining H2L will be lower than that of the rate before the explosion of H2L.

Potentiometric studies

Proton-ligand system: Irving-Rossotti equation used to calculate the average number of protons associated with the ligand (nA) at different pH-values.

image

Where Y is the number of ionizable protons in the ligand atom, CL is the initial ligand concentration, V1 and V2 are the volumes of NaOH needed to reach the same pH value in titration against the free acid and in the ligand mixtures, respectively. Vo is the initial volume of the mixture (25 ml), and N° and E° are the concentration of the alkali and the free acid, respectively. The formation curves plotted between nA and pH for the proton-ligand systems (Figure 8). It is found that nA values extend between 0 and 2 indicating that the ligand has two dissociable hydrogen ions of NH1 and NH2 respectively. Also, the dissociation constants, pK1 and pK2 can be obtained directly from these curves by interpolation at nA=0.5 and 1.5, respectively. The values recorded in Table 3. Inspection of the table reveals that pK1>pK2 at the same temperature. In addition, the pK values decrease with increasing temperature indicating that acidity increases with increasing temperature.

chemical-sciences-journal-Proton-ligand-formation-curve

Figure 8: Proton-ligand formation curve of H2L at (a) 298 °K (b) 308 °K (c) 318 °K.

Ligand Association constants
298 °K 308 °K 318 °K
pK1 pK2 pK1 pK2 pK1 pK2
H2L 9.95 6.94 9.20 6.76 9.11 6.24

Table 3: The association constants of H2L in 50% (v/v) DMSO- water, 0.05 M KCl and at different temperature.

Metal-ligand system: In the present work, metal ions under study were titrated against NaOH solution. n and pL values were evaluated by Irving and Rossotti.

image

Where V3 is the volume of NaOH needed to adjust the pH in the complex solution, CoM is the initial metal ion concentration.

Furthermore, pL values can be determined for dibasic acid using the following equation:

image

The formation of both ML and ML2 type of complexes was confirmed by the value of (n) that was found to be ~ 2. The calculated stability constant values summarized in Table 4.

Cation Stability constants
298 °K 308 °K 318 °K
logK1 logK2 logK1 logK2 logK1 logK2
Co(II) 6.35 6.27 4.29 6.23 3.87

Table 4: The Stability Constants of Metal Ions-H2L Complexes in 50% (v/v) DMSO-water, 0.05 M KCl and at different temperature.

Distribution curves: The different protonated forms as H2L, HLand L2- were detected during the titration processes. The distribution curves of H2L displayed in Figure 9 at 298oK as a symbolic example. It is obvious that all protonated species have a wide protonation range between pH 5-13. While increasing the pH results in loosing protons of ligands and conversion to the other forms. The percentage of H2L, HL- and L2- forms are above 95% and the free ligand (L) formed at pH 9.8 and reached its maximum at pH 13.2.

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Figure 9: distribution curve of (a) H2L (b) Co(II)- H2L.

The formed Co(II) complexes formulated as (ML2, ML) were pH dependent. The distribution curves resulted from the calculations shown in Figure 9 at 298oK. Co(II) complexes are formed after pH 4.9, while the intermediate complexes are formed between pH 1.3-5.0.

The thermodynamic parameters: The corresponding thermodynamic parameters (standard free energy change, ΔG° and the standard entropy change, ΔS°) for dissociation and metal complex formation were calculated via the following equations:

ΔG°=-2.303 RT log KH=2.303 RT pKH

ΔG°=ΔH°-T ΔS°

The calculated thermodynamic functions are recorded in Tables 5 and 6 and Figures 10 and 11.

chemical-sciences-journal-Temperatures-dependence-pK-values

Figure 10: Temperatures dependence of pK values of (a) pK1 (b) pK2 of H2L at ionic strength 0.05 M KCl.

chemical-sciences-journal-Relation-between-logK1-Against

Figure 11: The Relation between logK1 Against 1/T of Co(II)- H2L.

ligand Free energy changes (ΔG) KJ mol-1 Enthalpy changes (ΔH) KJ mol-1 entropy changes (ΔS) K J mol-1
298°K 308°K 318°K
H2L 98.52 87.02 99.23 87.81 99.94 88.59 77.37 63.49 -7.10 ×10-2 -7.90 ×10-2

Table 5: Thermodynamic parameters of H2L in 50% (v/v) DMSO-water, 0.05 M KCl and at different temperature.

  
Cation Free energy changes (ΔG) KJ mol-1 Enthalpy changes (ΔH) KJ mol-1 Entropy changes (ΔS) K J mol-1
298°K 308°K 318°K
Co(II) -12.58 -13.40 -14.21 11.83 8.19×10-2

Table 6: Thermodynamic parameters of Co-H2L in 50% (v/v) DMSO-water, 0.05 M KCl and at different temperature.

Checking these, values show that:

a) For proton-ligand system:

i) The positive values of ΔG° indicate a non-spontaneous dissociation processes.

ii) The negative values of ΔS° are due to increasing the order because of solvation process. This may be explained as the number of bound of solvent molecules accompanying with the undissociated ligand being less than those accompanying the dissociated form.

iii) The positive values of ΔH° indicate the endothermic nature of the dissociation of ligand in aqueous solution. The process accompanied by heat absorption indicating the favorability of the process at higher temperatures.

b) For metal-ligand system:

i) The negative values of ΔG° indicate that the spontaneous nature of the chelation process.

ii) The positive values of ΔS° are owing to the decreasing the order due to solvation process.

iii) The positive values of ΔH° indicate that the chelation process is endothermic and accompanied by consuming of heat and the chelation process is favorable at higher temperatures.

Molecular modelling

The molecular structures of H2L and its complexes shown in Structures 1-3 an insight to the data in Tables 7-13 reveals the following remarks:

Bond Length(Å) Bond Length(Å) Bond Length(Å)
C(17)-O(21) 1.385 C(17)-C(18) 1.422 C(18)-C(12) 1.46
N(11)-C(12) 1.300 N(10)-N(11) 1.362 C(9)-O(14) 1.235
C(9)-N(10) 1.375 C(8)-O(13) 1.245 C(8)-C(9) 1.55
N(7)-C(8) 1.365        

Table 7: Selected bond lengths (Å) of H2L in using DFT-method from DMOL3 calculations.

Angle Degree (°) Angle Degree (°) Angle Degree (°)
C(17)-C(18)C-(12) 121.689 O(21)-C(17)-C(18) 124.341 C(18)-C(12)-N(11) 122.273
C(12)-N(11)-N(10) 115.857 N(11)-N(10)-C(9) 122.561 O(14)-C(9)-N(10) 127.066
O(14)-C(9)-C(8) 123.274 N(10)-C(9)-C(8) 109.661 O(13)-C(8)-C(9) 121.955
O(13)-C(8)-N(7) 127.169 C(9)-C(8)-N(7) 110.876    

Table 8: Selected bond angles (°) of H2L in using DFT-method from DMOL3 calculations.

Bond Length(Å) Bond Length(Å) Bond Length(Å)
O(21)-C(14) 1.402 O(24)-Co(22) 2.37 O(23)-Co(22) 2.218
O(21)-Co(22) 2.407 O(20)-Co(22) 2.304 O(19)-Co(22) 2.282
C(13)-C(14) 1.441 C(12)-C(13) 1.439 N(11)-Co(22) 2.099
N(11)-C(12) 1.363 N(10)-N(11) 1.36 C(9)-O(20) 1.324
C(9)-N(10) 1.419 C(8)-O(19) 1.319 C(8)-C(9) 1.534
N(7)-C(8) 1.335

Table 9: Selected bond lengths (Å) of [Co(L)(H2O)2].2H2O in using DFT-method from DMOL3 calculations.

Angle Degree (°) Angle Degree (°) Angle Degree (°)
O(24)-Co(22)-O(23) 87.047 O(24)-Co(22)-O(21) 86.13 O(24)-Co(22)-O(20) 90.619
O(24)-Co(22)-O(19) 164.27 O(24)-Co(22)-N(11) 93.498 O(23)-Co(22)-O(21) 104.428
O(23)-Co(22)-O(20) 102.689 O(23)-Co(22)-O(19) 85.986 O(23)-Co(22)-N(11) 177.459
O(21)-Co(22)-O(20) 152.47 O(21)-Co(22)-O(19) 109.269 O(21)-Co(22)-N(11) 78.09
O(20)-Co(22)-O(19) 77.207 O(20)-Co(22)-N(11) 74.831 O(19)-Co(22)-N(11) 92.875
C(14)-O(21)-Co(22) 120.74 Co(22)-O(20)-C(9) 85.952 Co(22)-O(19)-C(8) 104.486
O(21)-C(14)-C(13) 118.651 C(14)-C(13)-C(12) 125.807 C(13)-C(12)-N(11) 124.527
Co(22)-N(11)-C(12) 133.076 Co(22)-N(11)-N(10) 107.35 C(12)-N(11)-N(10) 119.493
N(11)-N(10)-C(9) 109.723 O(20)-C(9)-N(10) 117.763 O(20)-C(9)-C(8) 114.492
N(10)-C(9)-C(8) 114.546 O(19)-C(8)-C(9) 111.335 O(19)-C(8)-N(7) 127.654
C(9)-C(8)-N(7) 120.987        

Table 10: Selected bond angles (o) of [Co(L)(H2O)2].2H2O in using DFT-method from DMOL3 calculations.

Bond Length(Å) Bond Length(Å) Bond Length(Å)
C(14)-O(21) 1.518 O(24)-Ni(22) 2.125 O(23)-Ni(22) 2.125
O(21)-Ni(22) 2.12 O(20)-Ni(22) 2.127 O(19)-Ni(22) 2.144
C(13)-C(14) 1.558 C(12)-C(13) 1.548 N(11)-Ni(22) 2.097
N(11)-C(12) 1.505 N(10)-N(11) 1.463 C(9)-O(20) 1.531
C(9)-N(10) 1.516 C(8)-O(19) 1.515 C(8)-C(9) 1.524
N(7)-C(8) 1.511        

Table 11: Selected bond lengths (Å) of [Ni(L)(H2O)2].2H2O in using DFT-method from DMOL3 calculations.

.

Angle Degree (°) Angle Degree (°) Angle Degree (°)
O(24)-Ni(22)-O(23) 90.077 O(24)-Ni(22)-O(21) 90.093 O(24)-Ni(22)-O(20) 177.723
O(24)-Ni(22)-O(19) 90.57 O(24)-Ni(22)-N(11) 92.124 O(23)-Ni(22)-O(21) 90.329
O(23)-Ni(22)-O(20) 91.861 O(23)-Ni(22)-O(19) 89.951 O(23)-Ni(22)-N(11) 177.593
O(21)-Ni(22)-O(20) 91.09 O(21)-Ni(22)-O(19) 179.279 O(21)-Ni(22)-N(11) 88.693
O(20)-Ni(22)-O(19) 88.237 O(20)-Ni(22)-N(11) 85.959 O(19)-Ni(22)-N(11) 91.001
C(14)-O(21)-Ni(22) 115.507 Ni(22)-O(20)-C(9) 87.219 Ni(22)-O(19)-C(8) 98.182
O(21)-C(14)-C(13) 122.718 C(14)-C(13)-C(12) 122.851 C(13)-C(12)-N(11) 121.286
Ni(22)-N(11)-C(12) 123.787 Ni(22)-N(11)-N(10) 107.168 C(12)-N(11)-N(10) 124.018
N(11)-N(10)-C(9) 105.804 O(20)-C(9)-N(10) 116.187 O(20)-C(9)-C(8) 111.086
N(10)-C(9)-C(8) 111.993 O(19)-C(8)-C(9) 114.38 O(19)-C(8)-N(7) 123.676
C(9)-C(8)-N(7) 121.756        

Table 12:Selected bond angles (o) of [Ni(L)(H2O)2].2H2O in using DFT-method from DMOL3 calculations.

 
Compound EH (eV) EL (eV) (EH-EL) (eV) Χ (eV) μ(eV) η(eV) S (eV-1) ω(eV) Ϭ (eV)
H2L -5.356 -2.791 -2.565 4.074 -4.074 1.283 0.641 6.469 0.780
[Co(L)(H2O)2].2H2O -3.980 -2.492 -1.488 3.236 -3.236 0.744 0.372 7.037 1.344
[Ni(L)(H2O)2].2H2O -4.296 -2.210 -2.086 3.253 -3.253 1.043 0.522 5.073 0.959

Table 13: 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 H2L and its complexes.

i) The bond angles of the hydrazone moiety of H2L changed slightly upon coordination; the largest change affects in H2L are O(21)-C(17)-C(18), C(18)-C(12)-N(11), C(12)-N(11)-N(10), N(11)-N(10)-C(9), O(14)-C(9)-N(10), O(14)-C(9)-C(8), O(13)-C(8)-N(7) and C(9)-C(8)-N(7) angles. The bond angles in ligand are reduced or increased on complex formation because of bonding [44].

ii) The bond angles in metal complexes are quite near to an octahedral geometry predicting d2sp3 or sp3d2 hybridization in all complexes [38].

iii) All the active groups in taking part in coordination have bonds longer than that already exist in the ligand moiety like (C-O)enol, (C-O) phenolic, C=Nazomethine. This is referred to the formation of the M-N bond which makes the C-N bond weaker because of coordination via N atom of (C=N) [45].

iv) The bond lengths of C(9)-N(10) and C(8)-N(7) become slightly longer in complexes as the coordination takes place via N atoms of -C=N-C=N- group that is formed on deprotonation of OH group in all complexes [44].

v) The bond distance of (CO)enolic that participate in coordination becomes longer due to the formation of the M-O bond which makes the C-O bond weaker [46] while the phenolic (C-O) that participates in complexes will become longer on coordination.

vi) The bond angles of ligand moiety containing atoms of coordination will be changed in all complexes due to the formation of the N-M-O chelate ring [47].

vii) The arrangement of complexes based on M-O and M-N bond lengths indicates that; the M-N and M-O in CO(II) complex have greater strength than in Ni(II) complex.

viii) The low HOMO energy values indicate the weak electron donating ability of molecules. LUMO energy indicate the ability of molecules to receive electrons [44].

ix) The overlap happens between both HOMO and LUMO is an important factor in all reactions. This can be indicated from the large values of molecular orbital coefficients. So, the orbitals that have the highest molecular orbital coefficients in the ligand can be considered as the sites of coordination. In addition; the energy gap (EHOMO -ELUMO) is a significant stability index that supports the characterization of both kinetic stability and chemical reactivity for the studied molecules [48]. Where molecules with smaller gap are more polarized and known as soft molecule that are more reactive than hard ones because they offer electrons easily to the acceptor. In case of ligand (H2L); the energy gap is small also due to the groups that enter conjugation. This indicates that charge transfer easily, which influences the biological activity of the molecule [49].

x) DFT method illustrates both the chemical reactivity and site selectivity for all molecular systems. The energies of frontier molecular orbitals (EHOMO -ELUMO), band gap describes the ultimate charge transfer happens within molecules, chemical potential (μ), electronegativity (χ), global softness (S) global hardness (η) and global electrophilicity index (ω) [50,51] are listed in, the inverse value of the global hardness is designed as the softness ϭ as follows:

ϭ=1/η

Biological activity

Minimum Inhibitory Concentration (MIC): Ligand and their complexes were evaluated for their antibacterial activity against Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis) as an example of Gram-positive bacteria, Escherichia coli (E. coli) and Pseudomonas aeuroginosa (P. aeuroginosa) as examples of Gramnegative bacteria and against a pathogenic Candida albicans (C. albicans) and Aspergillus flavus (A. flavus) fungal strain. Antimicrobial and Antimycotic Activities in terms of MIC (μg/mL) in Table 14. The fungicide Colitrimazole and the bactericide Ampicillin were used as references to compare the potency of the tested compounds under the same conditions (Figure 12).

chemical-sciences-journal-Biological-Activities-terms-MIC

Figure 12: Biological Activities in terms of MIC (μg/mL) of H2L and its complexes.

Compound E. coli P. aeuroginosa S. aureus B. subtilis C. albicans A. flavus
H2L 187.5 125 93.7 62.5 7.8 5.8
Co (II)-complex NA NA 500 375 125 375
Ni (II)-complex 250 187.5 125 125 11.7 7.8
Ampicillin 125 187.5 187.5 93.7 ---- ----
Colitrimazole ---- ---- ---- ---- 5.8 3.9

Table 14: Antimicrobial and Antimycotic Activities in terms of MIC (μg/mL) of H2L and its complexes.

H2L is the most potent compared with reference compounds against all bacterial and fungal stain. On the other hand, Co(II) complex shows no activity against E. Coli. While, it has lowest activity towards P. Aeuroginosa, S. aureus, B. Subtilis, C. Albicans and A. flavus with MIC 500, 375, 125, 375 μg/ml, respectively. Ni(II) complex exhibited moderate activity against all bacterial and fungal stain.

The prepared compounds can be arranged according to its activities towards E. coli, C. albicans and A. flavus as follows:

DNA-binding affinity assay: It was noticed that; methyl green binds in a reversible manner with polymerized DNA [25], and prepared complexes are stable in neutral pH medium, though free methyl green declines. In this study, buffer used for displacement reactions and after incubation for 24 hours, complete loss of methyl green absorbance was noticed. The dislodging of methyl green from DNA by studied compounds and the ability to bind to DNA was measured colorimetric. Where; the displacement was detected by the decrease in absorbance at 630 nm [52].

The prepared compounds were exhibited high affinity to DNA as shown in Table 15 and represented graphically in Figure 13, which was confirmed by keeping the DNA-complex at the origin or by migrating for short distances. The most active compounds were, H2L and Ni(II)- complex with IC50 27.8 ± 1.7 and 31.6 ± 2.1 μg/ml, respectively. The obtained results agree with the antimicrobial and antifungal screening data. This suggests that; binding with DNA may be contributed to the biological activity of these compounds against bacterial and fungal infections.

chemical-sciences-journal-DNA-methyl-green-metal-complexes

Figure 13: DNA/methyl green IC50 μ/ml of H2L and its metal complexes.

Compound (IC50, μg/ml)
H2L 27.8 ± 1.7
Co (II)-complex 69.1 ± 3.8
Ni (II)-complex 31.6 ± 2.1

Table 14: DNA/methyl green IC50μg/ml of H2L and its metal complexes.

IC50values (mean ± SD, n=3-5 separate determinations), exemplify the concentrations needed for a 50% decrease in the initial absorbance the DNA/methyl green solution.

Conclusion

The hydrazone derived from the condensation 2-hydrazinyl- 2-oxo-N-(pyridin-2-yl) acetamide to 2-hydroxybenzaldehyde (salicylaldehyde) and its Co(II) and Ni(II) complexes were produced. IR spectra suggest that the H2L coordinates as binegative tetradentate via (C=N)az, both (C-O) enolized with deprotonation and (OH)phenolic. The proposed geometries of isolated complexes were proved using DFT. The pH-metrically at different temperatures in 50% DMSO-water mixture was applied to estimate the dissociation constant of the ligand and the stability constants of the Co(II) metal ions. H2L shown the highest DNA binding affinity and minimum inhibitory concentration (MIC) activity than complexes.

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