Spectroscopic, DFT and biological studies on some complexes of Girard's T dithiocarbazate and its application in removal of some heavy metal ions by flotation technique

Accepted Manuscript Spectroscopic, DFT and biological studies on some complexes of Girard's T dithiocarbazate and its application in removal of some heavy metal ions by flotation technique

D.A. Abdel-Latif, Hany M. Youssef, Y.G. Abou El Reash PII: DOI: Reference:

S0167-7322(17)31622-7 doi: 10.1016/j.molliq.2017.06.018 MOLLIQ 7464

To appear in:

Journal of Molecular Liquids

Received date: Revised date: Accepted date:

15 April 2017 29 May 2017 4 June 2017

Please cite this article as: D.A. Abdel-Latif, Hany M. Youssef, Y.G. Abou El Reash , Spectroscopic, DFT and biological studies on some complexes of Girard's T dithiocarbazate and its application in removal of some heavy metal ions by flotation technique, Journal of Molecular Liquids (2017), doi: 10.1016/j.molliq.2017.06.018

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ACCEPTED MANUSCRIPT Spectroscopic, DFT and Biological studies on Some Complexes of Girard's T Dithiocarbazate and its application in Removal of Some Heavy Metal ions by Flotation Technique D.A. Abdel-Latifa,b,*, Hany M. Youssefb and Y.G. Abou El Reashb a

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Chemistry Department, Deanery of Academic Services, Taibah University, Yanbu Branch, Yanbu El-Bahr, Saudi Arabia b Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt

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Abstract

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A new metal complexes of Potassium 2-(Trimethylglycyl) hydrazine -1carbodithioate chloride [KHdGT] with Cu(II), Ni(II), Co(II), Mn(II), Zn(II), Cd(II) and U(VI)O2 were prepared and characterized using spectroscopic IR, UV-Vis., ESR, 1H NMR and TG analysis. The IR records proved that the ligand behaved as mononegative tridentate SSO with Co(II), binegative tetradentate SNNO with Cu(II), Zn(II), Cd(II) and U(VI)O2, mononegative SNNO in Ni(II) and Mn(II) complexes. Computational DFT were performed for [KHdGT] by (B3LYP) function together utilizing “6-311++G(d,p)” basis set while semiempirical method was utilized for its Co(II), Cu(II) and Zn(II) chelates to infer the entire geometry stabilization and ordinary-style examination for separated chelates. The electronic parameters, for example frontier molecular orbitals, dipole moments and infrared intensities were ascertained. In addition, the prepared chelate used for the separation of Cu(II), Cd(II), Ni(II) and Pb(II) ions from aqueous solution by the inexpensive, simple and rapid flotation technique. The cytotoxic, antioxidant and SOD-like activities were studied for KHdGT and its complexes.

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Keywords Girard's T Dithiocarbazate, Flotation, DFT, Cytotoxicity assay Corresponding author Corresponding author: Dr. Doaa A. Abdel-Latif (D.A. Abdel-Latif) Chemistry Department, Faculty of Science, Mansoura University, 35516, Mansoura, Egypt E-mail; [email protected] Tel: 00966532891940

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ACCEPTED MANUSCRIPT 1. Introduction: Since a long time, Girard's reagents have been used intensely in analytical and coordination chemistry for the preparation of water soluble sulfur compounds which is often used as efficient ligands [1-4]. Recently, there is a great interest for the complexes of these reagents concerning their biological,

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pharmacological and catalytic properties [4]. Moreover, the dithiocarbazates and their metal complexes are frequently used as antibacterial, anticancer and

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antifungal agents [5-7]. The solubility in H2O of Girard's T dithiocarbazates assists in the usage of these compounds in removal of toxic metal ions from

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aqueous solutions and contaminated water samples via simple ionic flotation

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method. Where, in developing countries, biosphere contamination is considered as a significant consequence for the evolution of human being. Lately, this

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contamination increased significantly with growing the needs of human being to meet certain requirements of their daily life [8]. Environmental pollution arises mainly from agriculture [9], industrial [10] and mining activities [11].

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Discharging toxic heavy metals contaminants in water bodies may effect

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tremendously on how the ecosystems work and cause serious health threats, where they are not biodegradable and accumulate in living tissues throughout

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the food sequence causing various disorders and diseases [12-14]. As toxicity with heavy metals can cause reduced or destruction central and mental nervous

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function, lower energy levels and damage to lung area, liver, kidneys, blood structure and other essential organs. Therefore; purification of wastewater using an efficient way has become a vital issue [15]. Ion flotation is considered as an easy, rapid and important separating technique recognized since 1960s, and can be used effectively for the recovery and elimination of ionic species from diluted aqueous solutions (cMe ≤1×10−4) [16]. Ion flotation is a process relating to the adsorbent of counter ions and a surfactant at an air/aqueous solution interface. It showed promising results for 2

ACCEPTED MANUSCRIPT the isolation of toxic metal ions from diluted aqueous solutions. Ion flotation is the best separation method when compared with other methods; it has the features of low costs, ease of procedure and shows actual promise in treatment of large scales of aqueous solutions when diluted [17]. In continuation of our previous work [3, 4], new dithiocarbazate ligand

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[KHdGT] "Potassium 2-(Trimethylglycyl) hydrazine-1-carbodithioate chloride", derived from Girard's T reagent and carbon disulfide was prepared and

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investigated. Its Cu(II), Ni(II), Co(II), Mn(II), Zn(II), Cd(II) and U(VI)O2 chelates, were also prepared and investigated. Synthesis, spectral studies,

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thermal analysis, magnetic properties as well as DFT studies and biological

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activities of these compounds are reported. Furthermore; the recent work record the effect of this basic ligand on the ion flotation of metal ions with oleic acid.

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2. Experimental: 2.1. Chemicals:

and used as received.

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Throughout the experiments, all chemicals and solvents used were pure

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Chemicals: Girard's (GT), carbon disulfide (CS2) (BDH), potassium hydroxide (HmbG), nickel(II) chloride hexahydrate, cobalt (II) chloride, manganese (II)

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chloride tetrahydrate , cadmium(II) chloride monohydrate, copper(II) chloride dehydrate, zinc(II) acetate dehydrate and uranyl acetate (all from Fluka). Oleic

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acid (HOL) (J.T. Baker Chemical Co.), SG. 0.895. For flotation experiments; stock solution of HOL (0.01 mol L-1) was prepared by mixing 3 mL of HOL in a liter of kerosene. Also; stock solutions (1×10-2 mol L-1) of [KHdGT]; Cu(II), Cd(II), Ni(II) and Pb(II) ions were prepared in deionized water. Solvents: absolute ethanol (99.8%, Aldrich). 2.2. Synthesis of Potassium 2-(Trimethylglycyl) hydrazine-1-carbodithioate chloride [KHdGT]:

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ACCEPTED MANUSCRIPT 0.42 g Potassium hydroxide was dissolved in 50 mL absolute ethanol, then 0.85 g GT was added followed by stirring the mixture at ambient temperature for 2 hours. To the previous mixture, 4 mL CS2 was added with stirring over a period of 6 hours. Finally, a white product of [KHdGT] was formed then filtered off and left in a desiccator to dry over anhydrous CaCl2 for

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48 hours (Scheme 1).

Scheme 1: The outline of the synthesis of the ligand.

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2.3. Preparation of metal complexes: All studied metal complexes were synthesized by mixing 0.4 g [KHdGT]

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(1.0 mmol) with 1.0 mmol of metal salts in 50 mL absolute ethyl alcohol then refluxing the mixture for 6-8 h. The resulted precipitates were isolated by filtration and washed carefully with ethyl alcohol followed by diethyl ether and desiccated over anhydrous silica gel for 72 h (Scheme 2).

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Scheme 2: The outline of the synthesis of the metal complexes.

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2.4. Instrumentation and Apparatus: The prepared ligand and complexes were analyzed using different spectroscopic instruments. A Perkin-Elmer FT-IR Spectrometer 2000 was used

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in recording the IR spectra over a wave number range 4000–370 cm-1 for all samples as KBr pellets. Perkin-Elmer analyzer (2400 Series II) was utilized for

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the elemental analysis (C, H and N %). A UVUNICAM 2001 spectrophotometer used to detect the electronic spectra in quartz cells with 10 mm pass length at ambient temperature. As well, 1H NMR analysis measured at room temperature and 400 MHz using a Jeol spectrometer (JNM LA 300 WB), 5 mm probe head in CDCl3 and chemical shifts are presented in ppm with reference to tetramethylsilane (TMS). Also; for Cu(II) complex; ESR spectrum was carried out using Bruker EMX Spectrometer in a 2 mm quartz capillary tube at 25°C. The analysis was run under 100 kHz modulation frequency, 6 Gauss modulation 5

ACCEPTED MANUSCRIPT amplitude, X-band (9.7 GHz) and microwave power 5.041 mW. A low-field signal was gotten after four scans, and the receiver gain increased by ten folds. Thermogravimetric (TG) analysis was performed under heating rate of 15°C/min on a DTG-50 Shimazu instrument. Magnetic susceptibility measured using a magnetic susceptibility balance (Sherwood Scientific) at 25°C. A

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Perkin-Elmer 2380 AAS was employed to determine the concentration of Cu(II), Cd(II), Ni(II) and Pb(II) in aqueous solutions. In floatation experiments,

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the cell has the following specifications (250mm length, 15 mm inner diameter)

meter 8519 used for all pH measurements.

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2.5. Quantum chemical computations

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and closed tightly from the top using a quick fit stopper. A Hanna digital pH

The fundamental goal for the theoretical studies is to decide the most stable geometry of the ligand and its metal chelates. Computational DFT were

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performed for [KHdGT] by (B3LYP) function together utilizing “6311++G(d,p)” basis set while semi-empirical method was utilized for its

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divalent Co, Cu and Zn chelates to infer the entire geometry stabilization and

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ordinary-style examination for separated chelates [18–20]. Lorentzian band forms with complete width at half maximum were utilized to sketch the

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calculated IR spectrum. The improved structure was utilized to register the minimal spin-permitted electronic vertical excitation energies utilizing (B3LYP)

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utilitarian with standard Pople basis set that incorporates diffuse functions on atoms (6-311 ++ G (d, p). The electronic properties, for example frontier molecular orbitals, dipole moments and infrared intensities were ascertained. DFT studies have been utilized to ascertain the dipole moment, mean polarizability and first static hyperpolarizability into account the constrained field ideology. The basic and spectroscopic portrayal of an unfaltering molecule was done utilizing Gaussian 09 program bundle on the private PC [21].

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2.6. Procedure for flotation An appropriate amount containing a definite quantity of Cu(II), Cd(II), Ni(II) and Pb(II) ions quantified for every single experiment, is mixed with the ligand. The pH of solution desired for each experiment was adjusted using HNO3

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and/or NaOH solutions. In all experiments; test solutions were prepared into the flotation cell then completed to a total volume of 10 ml with double distilled water.

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In order to insure complete complexation; the cell was shacked well for 2 min. Thereafter; 2 ml of HOL were added and the cell was closed tightly using a rubber

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stopper then inverted upside down for tine times by hand. To confirm a complete

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flotation for the studied metal ions, the cell was left for 5 min and the final concentration of metal ions in the mother solution was detected using AAS.

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The removal percentage (R %) of each M(II) was calculated using the following

(1)

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relation :

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Where; Ci and Cf in (mg/L) are the primary and the remained concentrations of M2+ in the test solution before and after the experiment, respectively.

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2.7. Biological activity:

2.7.1. Cytotoxicity assay:

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2.7.1.1. Cell line:

The biological activities of free ligand and its complexes were checked in cell growth inhibition experiments. The experiments were applied on human lung fibroblast cell line (WI-38) gotten from ATCC through VACSERA Company for vaccines and biological products, Cairo, Egypt. 2.7.1.2. Chemical reagents: All reagents used in the experiment were obtained from Sigma company, USA (RPMI-1640 medium, Dimethyl sulfoxide (DMSO), 5-fluorouracil and 7

ACCEPTED MANUSCRIPT MTT), but Fetal Bovine serum was obtained from GIBCO, UK. 5-fluorouracil is an anticancer drug and it was used as a standard to make comparison with obtained results. 2.7.1.3. MTT assay: KHdGT and its solid complexes were utilized to test the inhibition of cell

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growth on the cell line stated previously via MTT test [22, 23]. MTT method is a colorimetric test depends on using mitochondrial succinate dehydrogenase to

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change the color of tetrazolium bromide (MTT) from yellow to purple color indicating the formation of formazan derivative in viable cells. The experiment

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was done in a RPMI-1640 medium. Tested cells were cultured with 10% fetal bovine serum and then 100 units/ml penicillin and 100µg/ml streptomycin were

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added. Thereafter; a 96-well plate used to seed the cells at a density of 1.0x104

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cells/well under conditions of (5% CO2 at 37 C for 48 h), then treated with diverse concentrations of ligand and its solid complexes and incubated for 24 h [24]. After 24 h of treatment with prepared compounds, 20 µl of 5mg/ml MTT

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solution was added and kept in an incubator for 4 h. Finally, to each well 100 µl

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DMSO was added to dissolve the formed purple formazan. The absorbance (A) of all samples was measured at wavelength 570 nm using a plate reader (EXL

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800, USA).

(2)

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Where At and Au are the absorbance of treated samples and untreated sample, respectively.

2.7.2. Anti-oxidant activity test using ABTS process: The antioxidant activity test was done by adding 2 mL of (60 mM) ABTS solution (ABTS is a chemical compound used to observe the reaction kinetics of specific enzymes) for each investigated compound and 25 mg/mL (3 M) MnO2 solution at pH 7 adjusted using phosphate buffer (0.1 M). This mixture was centrifuged for 4 min then filtered. The absorbance (Acontrol) of the separated 8

ACCEPTED MANUSCRIPT green-blue solution (ABTS radical solution) was detected at λ 734 nm. Also, 50 ml (2 mM) solution of each tested compound was prepared with the addition of MeOH/phosphate buffer (1:1). The absorbance (Atest) values were determined and the decrease in intensity of color expressed as inhibition%. The following equation used to calculate the inhibition % for each sample [25]:

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(3)

In this test; the positive control sample is made of the standard anti-oxidant

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vitamin C (Ascorbic acid). In blank sample; MeOH/phosphate buffer (1:1) used

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instead of sample without adding ABTS. Also; MeOH/phosphate buffer (1:1) used in negative control sample instead of tested compounds.

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2.7.3. SOD-like activity test:

Bridges and Salin technique [26] was utilized to test the superoxide

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dismutase (SOD)-like activity. This method depends on the inhibition of nitrobluetetrazolium (NBT) reduction using SOD, by giving off the superoxide

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anion via the (xanthine/xanthine) oxidase. All test solutions were prepared by

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dissolving KHdGT and its complexes in dimethylsulphoxide (DMSO). The activity of horseradish superoxide dismutase (HR SOD) was detected to

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compare it with studied compounds. 3. Results and discussion:

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KHdGT and its complexes were isolated and the physical properties were verified. It was found that; they are stable in air can be dissolved easily in water, dimethyl formamide DMF and/or DMSO. Thermal analysis proved that all complexes decompose thermally above 300ᵒC. The results of elemental analyses, proposed chemical formula, melting points and colors of both ligand and complexes are listed in Table 1. Table 1 9

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3.1.

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H NMR and IR spectral studies:

The position of IR bands for both KHdGT ligand and its complexes are collected in Table 2 and some are demonstrated graphically in supplementary figure S1. The IR spectrum of KHdGT exhibits two bands centered at 3238 and

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3095 cm-1 assigned to ν(N2H) and ν(N1H) [27], respectively. The keto-enol form of KHdGT via CO group was assured by the existence of ν(OH) band at 3395

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cm-1. The split band at 1122 and 1138 cm-1 attributed to νas(CSS) [28]. The

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ν(C=O) marked by a sharp band appeared at 1702 cm-1. Also, ν(N-N) vibration

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appears at 1010 cm-1 [27] (Structure 1).

Table 2 Fig. S1

H NMR spectrum of KHdGT (Supplementary figure S2) exhibits two

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Structure (1)

signals at 10.42 and 9.60 ppm, which disappear after the addition of D2O. These

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two signals are assigned to the N1H and N2H protons, respectively. The signals at the range from 3.1 to 4.6 ppm are assigned to the aliphatic CH2 and CH3 groups.

Fig. S2 KHdGT coordinates in a mononegative tridentate manner via CSS and C=O groups in [Co2(HdGT)2Cl2] complex as shown in structure 2. This behavior is supposed by the blue shift of ν(C=O) and the great change in both 10

ACCEPTED MANUSCRIPT position and shape of the bands assigned to νas and νs thiocarboxylic group. The red shift of ν NH's groups confirmed their absence in complex formation. The appearance of a single band at 1125 cm-1 is another good evidence for SS

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chelation [29].

Structure (2)

[Cd2(dGT)Cl2(H2O)2],

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The type of chelation is a binegative tetradentate in [Cu2(dGT)Cl2(H2O)2], [Zn2(dGT)(OAc)2(H2O)2]

and

[(UO2)2(dGT)(OAc)2

(H2O)2] complexes. This mode of chelation occurred through the deprotonated

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enolic oxygen and the nitrogen of N2H group towards one metal ion. While the

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other metal ion coordinate with both sulfur atom of the SK group and the nitrogen of N1H group (Structure 3). The following evidences supported this

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mode of chelation: (i) the appearance of a splitted band at 1125 cm-1 assignable to νas(CSS), confirming the unidentate nature of this group [29], (ii) the

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appearance of new bands attributable to ν(C=N) and ν(C-O) coinciding with the disappearance of both ν(C=O) and ν(N1H) bands (iii) the shift of ν(N-N) to a higher wavenumber. The unidentate nature of acetate group in Zn(II) and U(VI)O2 complexes is confirmed by the difference (146 and 183 cm-1) between its νas(1490 and 1551 cm-1) and νs(1344 and 1368 cm-1) vibrations. New bands appeared at 490-550 cm-1 and 450-455 cm-1 are attributed to ν(M-O) [30] and ν(M-N) [31] vibrations, respectively.

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H NMR spectrum of [(UO2)2(dGT)(OAc)2(H2O)2] complex supports the

chelation through the enolized C=O group because of the absence of N1H

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signal.

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M = Cu(II) and Cd(II), X = Cl. M = Zn(II) and U(VI)O2, X = Ac.

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Structure 3

Moreover, KHdGT also behaved as mononegative tetradentate in

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[Ni(HdGT)Cl(H2O)]n and [Mn(HdGT)Cl(H2O)]n complexes (Structure 4). This type of chelation happened by the coordination through the carbonyl oxygen

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and the nitrogen of N2H group from one side and sulfur atom in SK group and the nitrogen atom of N1H group on the other, a combined with the displacement

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of potassium ion from the CSSK group. This behavior was assured by: (i) the presence of a splitted band near 1122 cm-1, indicating a monodentate sulfur

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chelation and (ii) the shift of the stretching vibrations of C=O and NH to a lower wavenumber with a shift of ν(N-N) to a higher wavenumber. Finally; the bands located at 536-545 cm-1 and 456-480 cm-1 are attributed to ν(M-O) [30] and ν(M-N) [31] vibrations, respectively. The polymeric structures are confirmed by molecular weight determination.

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M = Ni(II) and Mn(II).

Structure 4

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The existence of hydrated and coordinated water molecules in metal complexes proved by the bands appeared at 3450-3353, 1630-1600 and 980-950 cm-1 range in the spectra of these complexes due to OH stretching, H2O

3.2.

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deformation and rocking [32].

Magnetic and Electronic Spectral Studies:

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The calculated ligand field factors, magnetic moments and the detected band position in Nujol are listed in Table 3. The resulted spectra are represented

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graphically in supplementary figure S3. Table 3 Fig. S3

For Cu(II) complex, the electronic spectrum revealed a wide band at 14285 cm-1, due to the 2B1g → 2A1g transition present in a square planar geometry [33, 34]. While the band observed at 25000 cm-1 can be attributed to the charge transfer [35]. Additionally, the calculated magnetic moment is 2.05 B.M.; which compatible to the range of Cu(II) ion. 13

ACCEPTED MANUSCRIPT In case of the green [Co2(HdGT)2Cl2] complex, a sharp band appeared at 14663 cm-1 attributable to the 4A2(F) → 4T1(P) transition. Whereas; the weak band detected at 16260 cm-1 specified to the spin coupling, confirming the proposed tetrahedral geometry. The green color and the calculated magnetic moment value are an additional indication for the tetrahedral geometry [36]. In the electronic spectrum of octahedral Ni(II) complex; two main bands 3

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appeared at ca. 15015 and ca. 24510 cm-1 attributable to 3A2g

→

T1g(F) and 3A2g

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→ 3T1g(P) transitions, respectively. The calculated ligand field parameters and magnetic moment values are in agreement with Ni(II) octahedral geometry [33]. 6

A1g → 4T2g(G) and 6A1g → 4T1g(G)

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While in Mn(II) chelate; both

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transitions ascertained by the two bands appeared at 18960 and 17125 cm-1 respectively, confirming its octahedral geometry. Also, the magnetic moment (5.3 B.M.) is in accordance with that reported for high spin d5 system [37].

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In U(VI)O2 complex; the 1Σg+ → 2πu transition for dioxouranium(VI) was detected by the band appeared at 18587 cm-1 , while the band observed at 23364

Electron Spin Resonance of Cu(II) Complex:

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3.3.

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cm-1 may be ascribed to the n → π* charge transfer [27].

The ESR spectrum of [Cu2(dGT)Cl2(H2O)2] complex shown in (Fig. S4)

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was analyzed at room temperature. An axially symmetric g-tensor parameters were obtained (g|| = 2.42 and g = 2.07); in which g|| > g >2.0023 confirming

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the proposed square planar stereochemistry of Cu (II) complex with dx2-y2 ground-state feature [38]. The spin-Hamiltanion parameters are calculated. Gvalues are calculated in the axial symmetry using the following equation: (4) G is the exchange interaction factor and it was found to be 6.09. As reported previously by Hathaway [39]; if G > 4, it means that there is no copper-copper exchange interaction. 14

ACCEPTED MANUSCRIPT In the coordination sphere of Cu(II); the tetrahedral distortion increased as a result of decreasing A|| with raising g|| value [40]. The degree of distortion was determined by calculating the f-factor (g||/A||) which is an empirical index of tetrahedral distortion [41]. In case of square planar complexes; the f-factor values ranges from 105 to 135 depending on to the nature of the coordinated

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atoms, but in case of a tetrahedral structure; these values are higher [42]. Pertaining to the complex under research, the g||/A|| quotient is 134, which is

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typical for square planar

The molecular orbital coefficients (α2) are measure for the covalency

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ligand orbitals were calculated as follow:

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degree of the in-plane -bond formed between 3d-orbital of Cu(II) and the

(5)

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β2 (covalent in-plane π-bonding), was determined using the following

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equations [43-45]:

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Where E is the electronic transition energy  = -828 cm–1 for the free Cu(II) ion and.

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As stated before [46-49]; when α2 = 1, this indicate the formation of ionic bond. While if α2 = 0.5; this denotes a 100% covalent bonding with neglecting

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the small values of the overlap integral.

Also; β2 parameters indicate the

covalence degree of in-plane -bonding, whereas β2 value decreases the covalence degree of bonding increase. According to the resulted α2 and 2 values which are 0.98 and 0.92; inplane -bonding and in-plane π-bonding are appreciably ionic. The value of β2 is lower than that of α2 indicating that; in-plane -bonding is less covalent than

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ACCEPTED MANUSCRIPT in-plane -bonding. These data agree well with previously reported values [4649]. Fig. S4 3.4.

Thermal studies: TG analysis was carried out to ensure the suggested formulae and

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structure of prepared ligand and its complexes. The analysis was done under conditions of nitrogen flow within a temperature range from 25 up to 800ºC.

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The resulted data presented in figure S5 support the proposed structures

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strongly. According to the obtained curves; all coordinated water molecules lost in one step within the temperature range of 195 to 306ºC. While; at temperature

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range from 195 to 747οC; the complexes decomposed to oxides or sulfides and very unstable and unspecified intermediate products were formed [50]. There is

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a good agreement between both found weight losses accompanying each step of decomposition and the calculated weight loss (Table 4).

Fig. S5

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3.5. Molecular modeling

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Table 4

3.5.1. IR

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Frequency estimation was done to earn the spectroscopic mark of [KHdGT]. There are little contrasts amongst hypothetical and exploratory

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vibrational wavenumbers as appeared in Fig. 1. The main reason for this difference is that the calculations were done for uncoordinated [KHdGT] in vacuum, yet the examinations were accomplished for solid [KHdGT]. Particularly, torsion, in- and out- of plane modes are hard to allocate as a result of interpreting with the ring modes furthermore with the derivative. In any case, there are some clear frequencies helpful to describe in the obtained chart. The correlation graphic portrayed concordance between the hypothetical and

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ACCEPTED MANUSCRIPT experimental wavenumbers (Fig. 2). There is linear relationship between the hypothetical and experimental wavenumbers as depicted by the next equation: vcal =1.00522 vexp – 36.06936 with correlation coefficients (R2 = 0.9994). Figs. 1, 2 3.5.2. Chemical reactivity

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3.5.2.1. Global reactivity descriptors It is important to assure the energies of frontier molecular orbitals

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(FMOs) because they are an essential criterion in quantum estimations (Figs 36). These orbitals includes both HOMO “Highest Occupied Molecular Orbitals”

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and LUMO “Lowest Unoccupied Molecular Orbital” The former orbitals

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behaves as an electron donor, while the later one acts as electron receiver. i. The EHOMO and ELUMO are practically negative indicating the stability of the isolated complexes [51-54].

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ii. Gutmann’s variation principle, ‘‘the bond strength increases as the neighboring bonds get to be weaker’’ which proved by Linert et al. [55].

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This explanation concurs with the results; since the increase of the EHOMO is

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accompanied with an elongation (weakness) of M-L bonds. This promotes a fortifying “shortness” of the distances beside the M-L sites.

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iii. KHdGT is characterized by small energy showing that charge move fluently in it. This factor affects the biological behavior of KHdGT [51 - 55]. DFT

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strategy gives an idea about the substance reactivity and site selectivity of the frameworks. EHOMO, ELUMO,

which clarifies the inevitable charge

exchange collaboration inside the studied material, electronegativity (χ), hardness (η), potential (µ), electrophilicity (ω), softness (S) and the softness (ϭ) [55, 56] are recorded in Table 5. The significance of η and ϭ is to evaluate both the reactivity and stability [57]. χ = -1/2 (ELUMO + EHOMO)

(7)

η =1/2 (ELUMO - EHOMO)

(8) 17

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(9)

ω = µ2/2 η

(10)

S =1/2 η

(11)

Table 5

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3.5.3. Geometry optimization using DFT study For the discussion of optimized molecular geometry; the following points can

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dedicated:

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1. The optimized C-N bond length shorten is due to its coordination in all complexes.

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2. O-C ketone-type group in the Cu(II) and Zn(II) complexes get enolized and leads to absence of double bond character. Also, the optimized C-O

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bond length elongated due to its coordination in these two complexes. While, the coordination of carbonyl group in Co(II) complex results in shortening of its length.

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3. In Zn(II) and Cu(II) complexes; C-O bond distance is longer because of M-O bond formation which results in a weaker C-O bond. 4. In KHdGT ligand; the bond angles around the coordination sites reduced

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or increased slightly upon coordination. 5. The coordination of N atom in Co(II), Cu(II) and Zn(II) complexes

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produces elongation in N-N. 6. The HOMO level of the ligand is largely localized on the O, N and S atoms (Fig. 8) showing that these atoms are the favored destinations for nucleophilic reaction at the central metal ion. Figs. 3-6 3.6. Floatation studies: 3.6.1. Effect of pH 18

ACCEPTED MANUSCRIPT The activity of KHdGT as a chelating agent in the separation of toxic metal ions from aqueous solutions have been tested using the simple and fast flotation technique under various parameters (pH, effect of different metal ion concentrations, effect of different concentrations of KHdGT and varying the concentration of HOL). In flotation technique; pH has been always considered as

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an essential parameter affecting the flotation process. Where; pH is controlling the ionization degree of metal ions, surfactants and chelating compounds. Moreover;

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the speciation of heavy metal ions in aqueous solution depends on pH, since various insoluble hydrolysis products are formed due to the change in pH [58]. The

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effect of variable pH on the floatability of 2×10-4 mol L-1 of Cu(II), Cd(II), Ni(II)

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and Pb(II) ions under conditions of KHdGT (4×10-4 mol L-1) and 1×10-3 mol L-1 HOL have been tested and the obtained results are plotted in Fig. 7. It can be seen

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that, (~100%) floatability of Cu(II), Cd(II), Ni(II) and Pb(II) was reached in the pH ranges (5-9). This confirm that; KHdGT ligand can be utilized for the separation of Cu(II), Cd(II), Ni(II) and Pb(II) from weakly acidic, neutral and

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slightly alkaline medium. Hence, pH 7 was adjusted in all further experiments for

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the flotation-separation of all investigated metal ions. Fig. 7

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3.6.2. Effect of different metal ion concentrations It is important to detect the highest concentration of studied metal ions that

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can be separated from aqueous solutions using KHdGT via flotation method. In this experiment; various concentrations of Cu(II), Cd(II), Ni(II) and Pb(II) ions were floated using KHdGT (4×10-4 mol L-1) and HOL (1×10-3 mol L-1) at pH 7. The results obtained and drawn in Fig. 8 show that the ratio of (M:L) is 1:1 exhibit the maximum flotation efficiency (~100%). On the other hand; at higher metal ion concentration the flotation begins to decrease. This may be assigned to the lack of enough amount of ligand to bind all the studied metal ions [59]. 19

ACCEPTED MANUSCRIPT Fig. 8 3.6.3. Effect of ligand concentration To investigate the collecting ability of ligand towards studied metal ions; the concentration of ligand varied from (1- 5×10-4 mol L-1) and used to separate 4×10-4 mol L-1 of M(II) using HOL (1×10-3 mol L-1) at pH 7. The data shown in Fig. 9

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clarify that, the floatability of metal ions increases gradually and reached the maximum value (~100%) at M:L ratio of (1:1). This can be explained based on the

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presence of enough concentration of KHdGT to bind all exciting metal ions.

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Moreover; when the concentration of KHdGT raised over 1:1 ratio; no change noticed on the flotation process. Thus the separation of Cu(II), Cd(II), Ni(II) and

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Pb(II) ions from aqueous solutions carried out using 4×10-4 mol.L-1 of ligand throughout the experiments.

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Fig. 9

3.6.4. Effect of surfactant concentration

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Different concentrations of HOL were tested to float 2×10-4 mol L-1 of

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studied metal ions using 4×10-4 mol L-1 of KHdGT at pH 7. The results represented in Fig. 10 show that; Cu(II), Cd(II), Ni(II) and Pb(II) floated completely at the

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lower concentration of HOL ( 1×10-3 mol L-1), below this concentration the floatability reduced significantly. The decrease in floatability can be assigned to

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the absence of sufficient amount of surfactant needed to achieve a complete flotation for studied metal ions. The incomplete flotation of Cu(II), Cd(II), Ni(II) and Pb(II) ions at higher surfactant concentration is owing to forming a stable, hydrated envelope of surfactant on the surface of air bubbles. Therefore, the hydrophobicity of the formed complex was not suitable for flotation procedure [59, 60]. Thus, 1×10-3 mol L-1 of HOL was used in all experiments. Fig. 10 20

ACCEPTED MANUSCRIPT Briefly; according to the obtained results presented in section 3.6, KHdGT can be used efficiently in the separation of toxic metal ions from aqueous solution using flotation technique. Therefore; it can be used easily and effectively for the separation of toxic metal ions from water and various

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biological samples.

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3.7. Biological studies:

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3.7.1. Cytotoxicity assay:

KHdGT and its complexes are used to hinder the growth of cancer cells

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against Human lung fibroblast cell line (WI-38). In this study, the concentration of compounds that causes 50% of cell death (IC50) is determined. The

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cytotoxicity check of free KHdGT, its metal complexes as well as Fluorouracil (5-FU) was estimated under the same experimental conditions for comparison

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purposes and the data present in (Table 6). It is obviously observed that

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chelation of KHdGT with metal ions has a clear influence on the cytotoxicity. By comparing the cytotoxicity results it is indicated that; Ni(II) complex show higher IC50 value than the ligand alone. While, Cu(II), Co(II) and U(VI)O2 Table 6

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complexes show much lower IC50 value for WI-38.

3.7.2. Anti-oxidant activity screening: Anti-oxidant activity screening using ABTS method is given in table 7. The KHdGT ligand, its Ni(II) and U(VI)O2 complexes showed an elevated antioxidant activity. Table 7 3.7.3. SOD like activity: 21

ACCEPTED MANUSCRIPT As shown in table 8, free KHdGT shows a high SOD-like activity; where the inhibition percent is 78.0%. Cu(II), Co(II) and U(VI)O2 complexes exhibit low SOD-like activity in comparison to Ni(II) complex which exhibits a strong SOD-like activity with inhibition percent of 80.8%. It is well known that; SOD include three common classes vary in their metal cofactors. The CuZnSOD

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enzyme is periplasmic, while both MnSOD and FeSOD enzymes are cytoplasmic. Additionally, a new class of nickel-containing SODs has been

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recently detected in Streptomyces griseus and S. coelicolor [61]. The highest SOD-like activity of the ligand and its Ni(II) complex proved that they are

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effective antioxidants that can preserve the cells from the harmful influence of

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super oxide radicals.

Table 8

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Conclusions

This study includes the preparation of [KHdGT] and its metal complexes. The isolated ligand and its metal complexes are characterized using IR, UV-Vis., H NMR and ESR spectra. In addition TG analysis assured the proposed formulae.

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1

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The ligand coordinates in a mononegative tridentae, binegative tetradentate and mononegative tetradentate manners. Theoretical studies were performed to decide

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the most stable geometry of the ligand and its metal chelates. Also; [KHdGT] proved to be an effective organic chelate for the separation of about 100% of

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Cu(II), Cd(II), Ni(II) and Pb(II) ions from aqueous solution by applying the simple flotation method. This technique is a clean technology to treat water and wastewater; where KHdGT is safe for water media and have some biological significance. The ligand and some complexes exhibit high cytotoxic, antioxidant and SOD-like activities.

22

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Fig 1: Comparison of experimental and theoretical IR spectra of [KHdGT].

Fig 2: The linear regression between the experimental and theoretical frequencies characteristic for [KHdGT].

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ELUMO= -1.06eV

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(excited state)

EHOMO= -4.40 eV

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(ground state)

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Fig. 3: 3D plots frontier orbital energies using DFT method for [KHdGT].

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ELUMO= -33.72 eV

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(excited state)

EHOMO= -30.11 eV (ground state)

Fig. 4: 3D plots frontier orbital energies using DFT method for Cu(II) complex.

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ELUMO= -1.69 eV

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(excited state)

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EHOMO= -7.09 eV

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Fig. 5: 3D plots frontier orbital energies using DFT method for Co(II) complex.

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ELUMO= -1.69 eV

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(excited state)

EHOMO= -7.09 eV (ground state)

Fig. 6: 3D plots frontier orbital energies using DFT method for Zn(II) complex.

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Fig. 7: Effect of pH on the floatability of 2×10-4 mol L -1 of Cu(II), Cd(II), Ni(II) and Pb(II) ions using 4×10-4 mol L -1 of ligand and 1×10-3 mol L-1 HOL.

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Fig. 8: Floatability of different concentrations of Cu(II), Cd(II), Ni(II) and Pb(II) ions using 4×10-4 mol L -1 of ligand and 1×10-3 mol L-1 HOL at pH ~7.

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MA

NU

Fig. 9: Floatability of 2×10-4 mol L -1 Cu(II), Cd(II), Ni(II) and Pb(II) ions using different concentrations of ligand and 1×10-3 mol L-1 HOL at pH ~7.

Fig. 10: Floatability of 2×10-4 mol L -1 Cu(II), Cd(II), Ni(II) and Pb(II) ions using different concentrations of HOL and 2×10-4 mol L -1 of ligand pH ~7.

39

ACCEPTED MANUSCRIPT Table 1: Analytical and Physical Data of KHdGT and Its Metal Complexes. Compound

Yello wish white

C6H13N3OS2 KCl

KHdGT

18 4

Green

>3 00

[Ni(HdGT)Cl(H2O NiC6H14N3O2 )] S2Cl2

Brow n

>3 00

[Mn(HdGT)Cl(H2 O)]

White

SC

NU

MA Green

>3 00

Yello w

>3 00

[Zn2(dGT)(OAc)2( Zn2C10H22N3 H2O)2] O7S2Cl

White

>3 00

[(UO2)2(dGT)(OA U2C10H22N3O c)2(H2O)2] 11S2Cl

Reddi >3 sh 00 brown

D

[Cu2(dGT)Cl2(H2O Cu2C6H16N3 )2 ] O3S2Cl3

>3 00

PT E

MnC6H14N3 O2S2Cl2

AC

CE

[Cd2(dGT)Cl2(H2O Cd2C6H16N3 )2 ] O3S2Cl3

25.5 8 (26. 33) 21.3 8 (21. 53) 20.3 7 (20. 11) 20.5 9 (20. 34) 15.1 5 (14. 85) 12.5 7 (11. 88) 22.8 1 (23. 55) 12.8 3 (12. 06)

4.6 5 (4. 75) 3.9 0 (3. 60) 4.0 0 (4. 55) 4.0 3 (4. 47) 3.4 0 (3. 60) 2.8 1 (2. 44) 4.2 1 (4. 75) 2.3 7 (2. 87)

RI

Co2C12H26N6 O2S4Cl4

[Co2(HdGT)2Cl2]

C

٪ Calc. (Found) H N M

40

14.9 1 (14. 02) 12.4 7 (13. 05) 11.8 8 (11. 35) 12.0 0 (12. 34) 8.83 (8.1 2)

-

Cl 12.5 7 (12. 95) 21.0 4 (20. 23) 20.0 4 (19. 81) 20.2 6 (20. 08) 22.3 6 (23. 12) 18.5 5 (19. 21) 6.73 (6.1 3)

17.4 9 (16. 87) 16.6 0 (16. 13) 15.6 9 (15. 22) 26.7 2 (26. 22) 7.33 39.2 (7.1 1 2) (38. 46) 7.98 24.8 (7.4 4 4) (24. 12) 4.50 50.8 3.79 (4.7 7 (4.1 6) (49. 3) 97)

PT

M. Color P. ºC

Empirical formula

ACCEPTED MANUSCRIPT

Table 2: Most Important IR Spectral Bands of KHdGT and Its Metal Complexes. ν(C=

H)

O)

N)

[Co2(HdGT)2Cl2]

3200

3114

[Mn(HdGT)Cl(H2O)]

1628

-

-

PT E

[Cd2(dGT)Cl2(H2O)2]

)2 ]

CE

[Zn2(dGT)(OAc)2(H2O

H2O)2]

AC

[(UO2)2(dGT)(OAc)2(

-

-

1671

-

1619

-

-

-

1620

-

1613

-

1610

41

-O)

M-

M-

O)

N)

-

-

-

1687

-

ν(

-

D

[Cu2(dGT)Cl2(H2O)2]

3120

-

MA

[Ni(HdGT)Cl(H2O)]

1702

ν(

S)

-

101

1138

0

1125

100 533

-

9 1122, 1140

-

-N)

1122,

RI

3095

ν(C νas(CS ν(N

PT

ν(C=

SC

KHdGT

ν(N1

NU

Compound

1122, 1100

120

1120,

5

1165

120

1126,

0

1150

120

1124,

5

1165

122

1098,

0

1110

107 545 456 2 106 536 480 0 101 530 450 4 106 520 490 0 108 550 453 1 100 523 449 6

ACCEPTED MANUSCRIPT Table 3: Magnetic Moments, Electronic Bands and Ligand Field Parametrers of Metal Complexes of KHdGT. Ligand Field

Band Compound

Positio

Assignme

n

nt

Dq

B

β

(cm-1) 4

(B.M. )

T1g →

4

15015

3

24510

3

-

-

-

4.6

T1g(P)

NU

A2g → T1g(F)

935.

76

0.7

1.6

A2g →

5

4

3

1

-

-

-

-

2.05

-

-

-

-

5.3

-

-

-

-

Diam.

3.1

MA

3

-

SC

4

A2g

PT

T1g →

RI

4

16,260

[Ni(HdGT)Cl(H2O)]

ν2/ν 1

14,663 [Co2(HdGT)2Cl2]

μeff

Parameters

3

2

14285

2

D

17125

6

18960

4

CE

4

18587

O)2]

23364

1

A1g 

T1g(G)

6

[(UO2)2(dGT)(OAc)2(H2

A1g

CT

[Mn(HdGT)Cl(H2O)]

AC

B1g →

25000

PT E

[Cu2(dGT)Cl2(H2O)2]

T1g(P)

A1g 

T2g(G)

Σg+ → 2πu n → π*

42

ACCEPTED MANUSCRIPT

AC

CE

PT E

D

MA

NU

SC

RI

PT

Table 4: The Maximum Temperature, TmaxoC and Weight Loss Values of the Decomposition Steps for the Metal Complexes of KHdGT. % Weight Decom Loss T Compound positio oma Lost Species Fo C x C n un al d c. 22 First 22. 195 2H2O+Cl2 .4 step 83 8 262 25 [Cu2(dGT)Cl2( Second 25. 645 H2S+NH3+N2+HCl+3H2 .5 H2O)2] step 27 747 6 51 51. Residue CuO+CuS+6C .9 45 6 25 First 25. 279 H2O+Cl2 .4 step 94 0 33 [Mn(HdGT)Cl Second 500 34. 0.5N2+H2+2H2S+2NH3 .7 (H2O)] step 673 07 4 40 40. Residue MnO+6C .8 11 5 12 First 12. 306 2H2O+0.5CL2 .4 step 16 7 39 [Cd2(dGT)Cl2( Second 450 40. H2S+Cl2+N2+NH3+0.5H2+3C2H2 .9 H2O)2] step 661 53 5 47 47. Residue CdO+CdS .5 31 8 13 First 13. 220 0.67H2O+0.33CO2+0.33CS .2 step 30 [(UO2)2(dGT)( 6 OAc)2(H2O)2] 19 Second 357 H2S+0.33Cl2+3NH3+1.33CO+2.67 19. .0 step 515 H2+0.33H2O+0.33C2H2+0.33HCl 73 5 43

ACCEPTED MANUSCRIPT

Residue

67. 00

0.66U3O8+6C

67 .6 9

Table 5: Calculated EHOMO, ELUMO, energy band gap (EHOMO – ELUMO), dipole moment (DM)

PT

chemical potential (μ), electronegativity (χ), global hardness (η), global softness (σ), global

∆E (a.u.)

DM (D)

KHdGT

-0.16188

-0.05899

0.22087

19.3409

Cu-complex

-0.28694

-0.11014

0.39708

17.9028

Zn-complex

-0.29059

-0.06199

0.35258

Co-complex

-1.10689

-1.23943

7.3953

MA 2.34632

η (a.u.)

11.1475

σ (a.u.)-1

SC

ELUMO (a.u.)

µ (a.u.)

(a.u.)

 (a.u)

TE (a.u.)

0.051445

19.43824

-0.11044

0.110435

0.118533 -1272.42978

0.0884

11.31222

-0.19854

0.19854

0.222953

-0.037323

0.1143

8.748906

-0.17629

0.17629

0.135949

-0.320392

-0.06627

-15.0898

-1.17316

1.17316

NU

EHOMO (a.u.)

RI

electrophilicity index (ω) and total energy (TE) for KHdGT and its complexes.

-10.384068 -0.075169

PT E

D

Table 1: The calculated quantum chemical descriptors of the investigated ligand and its metal complexes.

CE

Table 6: Cytotoxic activity of KHdGT and its complexes against WI-38 cell line. In vitro Cytotoxicity IC50 (µg/ml)

AC

Compounds WI-38

5-Fluorouracil

5.3±0.64

KHdGT

71.8±4.38

[Ni(HdGT)Cl(H2O)]

82.3±4.89

[Cu2(dGT)Cl2(H2O)2]

10.5±1.25

[(UO2)2(dGT)(OAc)2(H2O)2]

50.9±3.60 44

ACCEPTED MANUSCRIPT 33.5±2.81

% inhibition

0.510 0.055 0.070

0% 89.2% 86.3%

SC

Absorbance of samples

NU

Compounds Control of ABTS L-Ascorbic acid KHdGT [Ni(HdGT)Cl(H2O)] [Cu2(dGT)Cl2(H2O)2]

RI

Table 7: Anti-oxidant assays by ABTS method.

PT

[Co2(HdGT)2Cl2]

0.064

87.4%

0.413

19.0%

AC

CE

PT E

D

MA

0.098 80.8% [(UO2)2(dGT)(OAc)2(H2O)2] 0.325 36.3% [Co2(HdGT)2Cl2] % Inhibition = (Acontrol - Atest /Acontrol)×100

Table 8: Superoxide (SOD)-like activity of the metal complex as antioxidative enzyme. Compounds Control of ABTS L-Ascorbic acid KHdGT [Ni(HdGT)Cl(H2O)] [Cu2(dGT)Cl2(H2O)2]

Δ through 5 min 0.442 0.089 0.097 0.085 0.427 45

% inhibition 0% 79.9% 78.0% 80.8% 3.4%

ACCEPTED MANUSCRIPT [(UO2)2(dGT)(OAc)2(H2O)2] 0.372 [Co2(HdGT)2Cl2] 0.395 % Inhibition = (Acontrol - Atest /Acontrol)×100

15.8% 10.6%

PT

Highlights

[KHdGT] was prepared and characterized.

RI

1- Potassium 2-(Trimethylglycyl) hydrazine -1-carbodithioate chloride

using spectroscopic and TG analysis.

SC

2- A new metal complexes of KHdGT were prepared and characterized

NU

3- Computational DFT were performed for [KHdGT] and its Co(II), Cu(II) and Zn(II) chelates.

MA

4- KHdGT was used for the separation of some metal ions from aqueous solution by flotation technique.

D

5- The cytotoxic, antioxidant and SOD-like activities were studied for

AC

CE

PT E

KHdGT and its complexes.

46