Synthesis and Biological Evaluation of Novel Zn(II) and Cd(II) Schiff Base Complexes as Antimicrobial, Antifungal, and Antioxidant Agents

Abstract

(E)-N,N-Dimethyl-2-((E-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide (DMPTHP) and their Zn(II) and Cd(II) complexes have been synthesized and characterized. Different tools of analysis such as elemental analyses, IR, mass spectra, and ¹H-NMR measurements were used to elucidate the structure of the synthesized compounds. According to these spectral results, the DMPTHP ligand behaved as a mononegatively charged tridentate anion. Modeling and docking studies were investigated and discussed. Novel Schiff base (DMPTHP) ligand protonation constants and their formation constants with Cd(II) and Zn(II) ions were measured in 50% DMSO solution at 15°C, 25°C, and 35°C at I = 0.1 mol·dm⁻³ NaNO₃. The solution speciation of different species was measured in accordance with pH. Calculation and discussion of the thermodynamic parameters were achieved. Both log K₁ and –ΔH₁, for M(II)-thiosemicarbazone complexes were found to be somewhat larger than log K₂ and –ΔH₂, demonstrating a shift in the dentate character of DMPTHP from tridentate in 1 : 1 chelates to bidentate in 1 : 2; M : L chelates and steric hindrance were generated by addition of the 2^nd molecule. The compounds prepared have significant activity as antioxidants, similar to ascorbic acid. It is hoped that the results will be beneficial to antimicrobial agent chemistry. The formed compounds acted as a potent antibacterial agent. Molecular docking studies were investigated and have proved that DMPTHP as antibacterial agents act on highly resistant strains of E. coli and also as an anticancer agent.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

Lately, there has been a very successful interaction between inorganic chemistry and biology. Schiff bases and their complexes in medicinal chemistry are an essential class of compounds [1, 2]. Schiff bases play a crucial role in coordination chemistry, since they form stable metal complexes [3–12].

The role of coordination compounds in detoxification of heavy metals is a complex subject that involves cooperation between numerous scientific branches. The primary contribution of chemistry to this subject is to produce both models of coordination and complex formation constants between chelating agents and metal ions, in a parliamentary procedure to compare the power of the formed complexes with their properties. Column 12 metal complexes are typically attractive in view of their marked differences in chemical and biological behaviors.

Zn is the human body’s second most abundant trace metal [13] and can catalyze over 300 enzymes, such as those responsible for the synthesis of DNA and RNA [14]. It is also physiologically essential for bone metabolism, collagen synthesis, the integrity of the immune system, anti-inflammatory actions, and defense versus free radicals [15]. Therefore, Zn(II) is better removed by novel methods away from classical coordination methods used in vivo.

Nevertheless, cadmium is a very toxic metal ion that poses both human and animal health hazards. Its toxicity is done by its easy localization inside the liver and then by the binding of metallothionein, which eventually forms a complex and is transmitted into the blood stream to be lodged in the kidney.

The cause of Cd toxicity is the negative effect on cell enzyme systems that are the consequences of metallic ion substitution (mainly Zn²⁺, Cu²⁺, and Ca²⁺) into metalloenzymes and its strong interaction with thiol groups [16]. Zinc (II) replacement with Cd(II) ion usually causes apoprotein catalysis to break down [17, 18]. Thus, substances that can form stable chelates with Cd may be produced in a significant research field as they can be used as detoxifying compounds. Referable to the broad scope of pharmacological properties of thiosemicarbazone ligands and their compounds, these compounds can also very well fit for this role. With this in mind and in the perpetuation of our studies in the subject area of bioactive compounds [19–22], it seems of great interest to synthesize and identify novel compounds involving both thiosemicarbazone and hydrazo moieties. In addition, our goal is comparison of M complexes strength with DMPTHP in quantitative terms in order to evaluate the capability of that ligand to extract Cd and also to explore the biological activities of the identified compounds.

2. Experimental

2.1. Chemicals Used

All the chemicals used were of A.R. grade quality. Metallic ion solutions were formed by the dissolution of metal ion salts in deionized H₂O, and EDTA titrations were used to calculate their concentrations. NaOH solution was accurately standardized by the standard KH phthalate solution.

2.2. Synthesis

2.2.1. 1-(p-Tolylhydrazono)-propan-2-one (PTHP) Compound

We have synthesized 1-(p-tolylhydrazono)-propan-2-one (PTHP) compound using the reported method [23, 24].

2.2.2. Synthesis of (E)-N,N-Dimethyl-2-((E)-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide (DMPTHP) Thiosemicarbazone Compound

PTHP (from Sigma–Aldrich) (0.1760 g, 1 mmol) in 30 ml ethanol was combined with N,N-dimethylthiosemicarbazide (from Sigma–Aldrich) in ethanol solution (30 ml) (0.120 g, 1 mmol) and refluxed for 3-4 hours into a hot plate. The isolated precipitate was washed with Et₂O and dried overnight under silica gel.

Yield, 76%. Anal. Calc. for C₁₃H₁₉N₅S: C, 56.29; H, 6.90; N, 25.26; and S, 11.56. Found: C, 56.18; H, 6.94; N, 25.19; and S, 11.66%. IR (KBr, cm⁻¹): 3352 (N₂H), 1499, 1250, 1080, and 798 (bands I, II, III, and IV of thiomide, respectively), 1082 (N-N), 1615 (C=N), 1548 (C=C), 3434 (N5H), and 3012 (C-H). MS (m/z): 279 (M⁺ + 2, 4.87%), 278 (M⁺ + 1, 14.92%), 277 (M⁺, 100%), 247 (2.51%), 11.39 (s, 1H, NH), 10.77 (s, H, NH), 6.91–7.11 (m, 4H, -Ar), 7.36 (s, H, CH=N), 2.02 (s, 3H, -CH₃), and 2.23 (s, 6H, -CH₃). ¹³C-NMR (DMSO): 178.4. 178.2, 148.6, 142.4, 135, 130, 120, 112.8, 40.1, 38.2, and 21.4.

2.2.3. Synthesis of M(II) Complexes

In presence of triethylamine, ethanol solution (2 mmol, DMPTHP) was gradually added with stirring to the warm aqueous metal solution (2 mmol) and refluxed for 5 hours into a hot plate. The solid product was filtered out, washed with C₂H₅OH followed by Et₂O, and vacuum-dried over P₄O₁₀.

(1) Zn(II)-DMPTHP Complex. Yield, 65%. Anal. Calc. for C₁₃H₁₈N₅SZnCl: C, 41.39; H, 4.81; N, 18.57; Cl, 9.40; and S, 8.50. Found: C, 41.28; H, 4.72; N, 18.45; Cl, 9.35; and S, 7.49%. IR (KBr, cm⁻¹): 1496, 1247, 1075, and 770 (bands of thiomide, I, II, III, and IV, respectively), 1092 (N-N), 1582 (C=N), 1522 (C=C), 3418 (N5H), 276 (Zn-Cl), 440 (Zn-N), and 318 (Zn-S). MS (m/z): 377 (M⁺ + 2, 58%), 375 (M⁺, 100%), 11.61 (s, 1H, NH), 6.70–7.01 (m, 4H, -Ar), 7.11 (s, H, CH=N), 1.95 (s, 3H, -CH₃), and 2.08 (s, 6H, -CH₃).

(2) Cd(II)-DMPTHP Complex. Yield, 66%. Anal. Calc. for C₁₃H₁₈N₅SCdCl: C, 36.81; H, 4.28; N, 16.51; Cl, 8.36; and S, 7.56. Found: C, 36.78; H, 4.22; N, 16.45; Cl, 8.28; and S, 7.49%. IR (KBr, cm⁻¹): 1499, 1243, 1079, and 768 (bands of thiomide, I, II, III, and IV, respectively), 1090 (N-N), 1586 (C=N), 1525 (C=C), 3418 (N5H), 252 (Cd-Cl), 411 (Cd-N), and 298 (Cd-S). MS (m/z): 425 (M⁺, 100%), 11.53 (s, 1H, NH), 6.68–7.05 (m, 4H, –Ar), 7.08 (s, H, CH=N), 1.96 (s, 3H, –CH₃), and 2.05 (s, 6H, –CH₃).

2.3. Instruments

All the ingredients used have been supplied by Aldrich. A CHNS automatic analyzer, Vario EII-Elementar, was used to conduct elemental microanalysis for C, H, N, and S. In a Perkins Elmer FTIR, spectrophotometer type 1650 with KBr disk and IR was registered. A Perkin Elmer FTIR, type 1650 spectrophotometer with the potassium bromide disc was used to monitor IR spectra. On a spectrophotometer of Shimazdu 3101 pc, electronic spectra are recorded. A Bruker ARX-300 instrument was applied to monitor the ¹H-NMR spectra using deuterated dimethylsulphoxide (d₆-DMSO) as solvent relative to TMS. Mass spectrometry analyses have been carried out using Shimadzu GCMS-QP1000EX. A Metrohm 848 Titrino supplied with a Dosimat unit (Switzerland-Herisau) has been utilized for potentiometric titrations. Inside the cell, a constant temperature was maintained through the circulating waterbath. Based on low solutions for the DMPTHP synthesized compound and the potential aqueous solution hydrolysis, all potentiometric measurements were performed in 50% water-DMSO mixture.

2.4. Potentiometric Titrations

Through potentiometric technique, using the method depicted above in the literature, the constant ligand protonation and formation of complexes were estimated [25]. The standard buffer solutions are used for accurately calibrating the glass electrode to NBS standards using KH phthalate and mixture of KH₂PO₄ + Na₂HPO₄ as buffer solutions [26]. The standard solution of 0.05 mol/dm³ NaOH, free of CO₂, is used to titrate all samples in the N₂ atmosphere. Sample solution was developed to avoid hydrolysis of the DMPTHP compound during titration by mixing equal volumes of DMSO and water. In addition, the ionic strength was kept constant during titration using a mixture of NaNO₃ as supporting electrolyte.

As known, the calculated formation constants using a potentiometric method have been carried out using a concentration of hydrogen ion expressed in molarity. Nevertheless, the concentration in a pH meter has been expressed in activity coefficient −log a_H+ (pH). Thus, this equation of Van Uitert and Hass (equation (1)) was used to convert the pH meter readings (B) to [H⁺] [27, 28].$$\begin{array}{}\text{(1)}& -\log 10{\text{H}}^{+}=B+\log 10U_H\text{,}\end{array}$$where log₁₀U_H is the solvent composition correction factor and the ionic strength read by B. $p{K}_w$ for titrated samples was estimated as previously described [29]. All measurements and procedures comply with literature requirements [30–32].

Titrating (40 cm³) (1.25 × 10⁻³ mol/dm³) DMPTHP thiosemicarbazone solution with standard sodium hydroxide solution estimated the protonation constants of the compound thiosemicarbazone. Metal (II) complex formation constants were determined by titration (40 cm³) of (MCl₂·nH₂O) (1.25 × 10⁻³ mol/dm³) + (DMPTHP) (1.25 × 10⁻³ mol/dm³/2.5 × 10⁻³ mol/dm³). The following equations have described the equilibrium constants from the titration data in which M, L, and H represent M(II), DMPTHP, and H⁺, respectively.$$\begin{array}{}\text{(2)}& p\text{M}+q\text{L}+r\text{H}\rightleftharpoons {\text{M}}_p{\text{L}}_q{\text{H}}_r\text{(3)}& {\beta }_{pqr}=\frac{{\text{M}}_p{\text{L}}_q{\text{H}}_r}{{\text{M}}^p{\text{L}}^q{\text{H}}^r}.\end{array}$$

2.5. Processing of Data

MINIQUAD-75 computer program has been applied to calculate ca. 100 readings for each titration [33]. Species distribution diagrams for the studied samples were given by the SPECIES program [34].

2.6. Molecular Modeling Studies

In the Materials Studio package [35], DFT calculations were carried using DMOL³ software [36–38]. Different calculations were carried out using double numerical base and functional polarization sets (DNP) [39] for DFT semicore pseudopods. The numerical RPBE functional is dependent on the generalized gradient approximation as the best correlation function [40, 41].

2.7. Molecular Docking

Docking is used to predict compound conformation and orientation in the binding pocket of the receptor. In this study, the molecular interaction of compound and its poses were studied against the three-dimensional structure of PDB ID: 1NEK in E. Coli and PDB ID: 3HB5 in breast cancer to get information correlated to their correct binding orientation and to realize the interaction nature between them. Crystal structure of the protein receptor 1NEK in E. Coli and 3HB5 in breast cancer were downloaded from the RCSB Protein Data Bank [42]. Docking of the compounds in the active site of the protein receptors is performed by MOE software [43]. Energy minimizations were performed with an RMSD (root of mean square deviation) gradient of 0.05 kcal·mol⁻¹·Å⁻¹ using the GBVI/WSADG force field, and the partial charges were calculated.

2.8. Biological Activity

2.8.1. In Vitro Antibacterial Activity

The ability thiosemicarbazone compounds to suppress the bacterial growth were checked by the disc diffusion method [44]. Aerobic Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative aerobic bacteria, Escherichia coli and Neisseria gonorrhoeae, are among the bacterial strains that were used in this study in addition to two fungal strains including Aspergillus flavus and Candida albicans. Novel synthesized compounds were prepared in DMSO. 100 μl of each of the synthesized thiosemicarbazone compounds was inserted into discs (0.8 cm), and then, they were allowed to dry. The discs were completely saturated with the synthesized compounds. The discs were then placed at least 25 mm from the edge into the upper layer of the medium. The disks were then gently placed on the same plate’s surface. At 37°C for 72 hours, the plate was then incubated, and the clear area of inhibition was examined. The inhibition zone (an area where there is no growth around the disc’s) was eventually determined by the ruler millimeter.

2.8.2. In Vitro Antioxidant Activity

Free radical scavenging action of the synthesized DMPTHP thiosemicarbazone compound was analyzed by 1,1-diphenyl-2-picrylhydrazyl assay [45] using ascorbic acid as a reference standard material. Using Thermo Scientific Evolution 201 UV-Visible Spectrometer, the absorbance of the sample, blank, and control were measured in the dark at 517 nm. The experimental test was performed three times. Antioxidant activity percentage was measured as follows:$$\begin{array}{}\text{(4)}& \text{Antioxidant\hspace{0.17em}activity\hspace{0.17em}percentage}=100-\frac{{\text{Abs}}_{\text{sample}}-{\text{Abs}}_{\text{blank}}\times 100}{{\text{Abs}}_{\text{control}}}.\end{array}$$

3. Results and Discussion

3.1. Characterization of DMPTHP Thiosemicarbazone Compounds

Condensation of the 1-(p-tolylhydrazono)-propan-2-one compound with N,N-dimethylthiosemicarbazide readily gives rise to the corresponding DMPTHP thiosemicarbazone compound. The isolated compounds are air stable and insoluble in H₂O, yet easily soluble in solvents such as DMF or DMSO. Cd-DMPTHP and Zn-DMPTHP complexes have a higher m.p. than the parent DMPTHP ligand. Different analytical tools were employed to identify the structure of prepared thiosemicarbazone compounds. The results from the basic analysis are well in line with the calculated results for the proposed formula.

3.2. IR Spectrum

The preliminary allocations of the major IR bands of DMPTHP and its M(II) complexes show the following characteristics:

(1) New band of ν (C=N) stretching vibration [46] at 1615 cm⁻¹ with disappearance of the ν (>C=O) confirming the condensation reaction and formation of the DMPTHP compound

(2) Presence of -NH-C=S linkage support thione  ↔  thiol tautomerism of thiosemicarbazone compounds [47], but ν (S-H) absorption band at 2500–2600 cm⁻¹ was absent with an appearance of ν (C=S) band at 798 cm⁻¹ indicating the presence of the DMPTHP compound in the solid state as a thione form

(3) For the DMPTHP thiosemicarbazone compound, vibrational bands with the wave numbers of 3012 cm⁻¹ (ν_C-H and Ar-H), 1615 cm⁻¹ (ν_C=N), 1548 cm⁻¹ (ν_C=C), and 1082 cm⁻¹ (ν_N-N) were detected

(4) In the DMPTHP thiosemicarbazone compound spectra, the bands observed in the range 1499, 1250, 1080, and 798 cm⁻¹ are attributed to the bands of thiomide I, II, III, and IV, consecutively [48]

(5) The far IR spectra of the Cd(II)-DMPTHP complex showed a band at 411 cm⁻¹ and 298 cm⁻¹ referring to the ν (Cd-N) and ν (Cd-S) vibrations, respectively [49], while the Zn(II)-DMPTHP spectrum displays a band at 440 cm⁻¹ and 318 cm⁻¹ corresponding to the ν (Zn-N) and ν (Zn-S) vibrations, respectively [50]. Such new nonligand bands due to M-N and M-S vibrations in DMPTHP complexes are in the predictable order of increasing energy, (M-N) > (M-S), as expected due to the greater dipole moment change in the M-N vibration, greater electronegativity of the N atom, and shorter M-N bond length than the M-S bond length.

(6) According to literature, the ranges from 160 cm⁻¹ to 300 cm⁻¹ are allocated to the M-Cl and M-Br vibration bonds where M is the metal [51, 52]. The ν (M-Cl) that appeared in our work between 252 cm⁻¹ and 276 cm⁻¹ are well in line with the literature values. According to these spectral results, the DMPTHP ligand is asserted to have lost the N2-H proton and bonded to Mⁿ⁺ as a mononegatively charged tridentate anion after deprotonation via the thiolate sulfur atom and the two azomethine N atoms.

3.3. NMR Spectrum

¹H-NMR spectra of DMPTHP in DMSO-d₆ show no resonance at approximately 4.0 ppm due to -SH proton [48], whereas the presence of a peak at 10.77 ppm (signal field of existence of the NH group next to C=S) suggests that they remain in the thione form even in a polar solvent like DMSO. Methine proton of the characteristic azomethine group (CH=N) for the DMPTHP compound was observed at δ = 7.36 ppm. Signals of the aromatic protons appear at 6.91–7.11 ppm. Methyl group was observed as a singlet signal at δ = 2.02–2.21. As common [53], the interaction with the d¹⁰ Cd(II) ion moves the complex ¹H-NMR signals downfield from those of free DMPTHP (Δδ = 0.0–0.2 ppm) as a result of coordination via the N-atom [54] (α 11.39 ppm in DMPTHP and 11.53 in the complex).

3.4. UV-Vis Spectrum

Electronic DMPTHP ligand spectrum shows two absorption bands. The first band at about 33020 cm⁻¹ was assigned to $\pi ⟶{\pi }^{\ast }$ and the second one at 26830 cm⁻¹ region is due to the $n⟶{\pi }^{\ast }$ transition. Always, $n⟶{\pi }^{\ast }$ transitions often take place at lower energy than $\pi ⟶{\pi }^{\ast }$ transitions [55].

3.5. Mass Spectrum

The proposed formulas can be further proven by mass spectroscopy. In addition to a number of peaks that are attributive to the different fragments of the DMPTHP compound, the electron mass impact spectrum of DMPTHP support the anticipated formulation by displaying a peak at 277, which corresponds to the compound moiety (C₁₃H₁₉N₅S). These data suggest that a ketone PTHP group is condensed with the N-dimethylthiosemicarbazide NH₂ group. The M(II) complex mass spectra have been studied. Comparing the molecular formula weights with m/z values confirm the suggested molecular formula for these complexes. Molecular ion peaks for Zn-DMPTHP and Cd-DMPTHP complexes were observed at m/z = 375 and 425, respectively. These data agree very well with the molecular formulation proposed for (Zn(DMPTHP)Cl) (1) and (Cd(DMPTHP)Cl) (2) complexes.

3.6. Conductivity Measurements and Magnetism

Conductivity measurements provide an insight into the degree of complexes ionization, i.e., the ionized complexes have a higher molar conductivity than nonionized ones. The molar conductance is calculated by this relationship:$$\begin{array}{}\text{(5)}& {\Lambda }_M=\frac{K}{C}\times 1000,\end{array}$$where C (mol/l) represents the concentration of the solution, and K is the specific conductivity. The obtained lower values (Λ_M = 8.9–10.2 Ω⁻¹·cm²·mol⁻¹) for conductivity measurements agree with the fact that nonelectrolytes have Λ_M < 50 Ω⁻¹·cm²·mol⁻¹ in DMSO solutions [56]. This observation was also confirmed by a chemical analysis in which the addition of the AgNO₃ solution does not precipitate Cl⁻ ion.

3.7. Molecular Modeling

The following parameters such as dipole moment, total energy, binding energy, HOMO, and LUMO energies have been measured and provided in Table 1 after geometric optimizations of the free DMPTHP compound structures and their M(II) complexes using DFT semicore pseudopod calculations using DMOL³ software [35–38] in the Materials Studio package.

Table 1

The calculated quantum chemical parameters of the DMPTHP ligand and M(II)-DMPTHP complexes.

Compound	EH	EL	ΔE	IE	EA	x	η	S	ΔNmax	ω	ω−	ω+
DMPTHP	−8.50	−2.19	6.31	8.50	2.19	5.35	3.16	0.32	−2.69	4.53	7.59	2.25
Zn-L	−4.61	−2.17	2.44	4.61	2.17	3.39	1.22	0.82	−3.78	4.71	6.56	3.17
Cd-L	−4.75	−1.98	2.77	4.75	1.98	3.37	1.39	0.72	−3.43	4.09	5.94	2.58

The DMPTHP compound’s molecular structure and zinc (II) complex along with the atom numbering scheme are shown in Figures 1 and 2.

[figure omitted; refer to PDF]

With the well-known relations (20) and (21), from the values of free energy change (ΔG) and enthalpy change (ΔH), one can deduce the entropy change (ΔS):$$\begin{array}{c}\text{(22)}& \Delta G^o=-2.303RT\log 10K,\Delta S^o=\frac{\Delta H^o-\Delta G^o}{T}.\end{array}$$

The main reasons for the protonation constant determination can be explained as follows:

(1) Protonation constants can be used in determination of the pH and ratio of the various forms of a substance

(2) A newly synthesized compound can also supply structural details. The suggested structure can be reliable where protonation constants are theoretically well calculated according to the experimental values.

(3) Because different types of substances have different UV spectrums, quantitative spectrophotometric analysis can be performed by choosing the appropriate pH value. To choose the pH values, the known protonation constants are required.

(4) Protonation constants are required for buffer solutions preparation at different pH values [48, 90]

(5) Therefore, the measurements of the stability constants for the complicated formation of bioactive ion compounds include protonation constants to be determined

  Additionally, their protonation constants are used for calculating the stability constants of the dynamic formation of bioactive compounds with metal ions [91]

(6) The equilibrium constants of certain compounds must be understood to measure the concentration of each ionized species at pH to understand their physiochemical behavior [92]. The protonation constants of the newly synthesized compounds were thus calculated by this study. Table 8 describes the thermodynamic functions measured and can be interpreted as follows:

(1) The corresponding thermodynamic processes for the protonation reactions are as follows:

(i) Neutralization reaction is an exothermic process

(ii) Ions desolvation is an endothermic process

(iii) Structure alteration and H-bonds alignment in free and protonated ligands

(2) When the temperature rises, the value of pK^H decreases and its acidity rises

(3) Negative ∆H^o for DMPTHP protonation means its interaction is followed by release of heat

(4) DMPTHP’s protonation reaction has a positive entropy, which could be due to increased disorder due to desolvation processes and breakdown of H-bonds

Table 7 includes the step-by-step stability constants of the complexes formed at various temperatures. Such values decrease and confirm that the complexation is preferred at low temperature. These results provide the following findings:

(1) Negative ∆G^o for complexation (Table 9), indicating the spontaneity of the coordination process

(2) The coordinating process is exothermic with −ve ∆H^o, i.e., the complexation reaction is preferred at low temperatures

(3) It is commonly found that ∆G^o and ∆H^o values for the 1 : 1 complexes are more negative than that of 1 : 2 complexes, indicating a change in this ligand’s dentate character from tridentate in 1 : 1 chelates to bidentate in 1 : 2. M : L chelates and steric hindrance are generated by addition of the 2^nd molecule.

(4) The electrostatic attraction in the 1 : 1 complex is greater than in the 1 : 2 complex due to the 1 : 1 complex being formed by the interaction between the dipositively charged metal ion and the mononegatively charged ligand anion. While the 1 : 2 complex is generated by the monopositively charged 1 : 1 complex and mononegatively charged ligand anion interactions.

(5) The ∆S^o values for all investigated complexes are positive due to the release of bound solvent molecules on coordination is greater than the decrease results from the coordination process itself.

4. Conclusion

The condensation reaction of 1-(p-tolylhydrazono)-propan-2-one (PTHP) with N,N-dimethylthiosemicarbazide in the molar ratio (1 : 1) provided the corresponding (E)-N,N-dimethyl-2-((E)-1-(2-(p-tolyl)hydrazono)-propan-2-ylidene)hydrazine-1-carbothioamide (DMPTHP) compound. The IR spectra showed that, after deprotonation via the two azomethine nitrogen atoms and the thiolate sulfur atom, the DMPTHP compound presents in the thione form in the solid state and coordinated to the metal(II) ion as a tridentate anion. M(II) complexes are nonelectrolytes with a distorted tetrahedral structure. The antibacterial and antimicrobial testing data show that a newly generated compound is a moderately to highly antimicrobial agent. Inverse correlation exists between dipole moment and synthesized compounds’ behavior against the studied bacterial and fungal organisms, as stated by SAR studies. The relationship between morphological and biological characteristics has been studied, which can assist in the production of more effective antibacterial agents. Potentiometric studies have shown that DMPTHP forms complexes 1 : 1 or 1 : 2 with ions Zn(II) and Cd(II). Comparison of Zn(II) and Cd(II) stability constants with DMPTHP shows that DMPTHP stability constants with Cd(II) are higher than Zn(II) constants. The log K₁ and −ΔH₁, for M(II) DMPTHP complexes are larger than log K₂ and −ΔH₂, demonstrating alteration of the DMPTHP dentate character from tridentate in 1 : 1 chelates to bidentate in 1 : 2; M : DMPTHP chelates and steric hindrance is generated by addition of 2^nd molecule. DMPTHP may be viewed from the biological perspective, as it constitutes a highly stable compound, as a possible antidote to Cd^{2 +} ion.

Acknowledgments

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; the authors, therefore, acknowledge with thanks the DSR technical and financial support.

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