1 Introduction

Thiosemicarbazones are compounds which have increased importance over the decades as prospective medicine candidates. When coordinated to elements, they have evidenced as good antitumor, antimicrobial, antioxidant and antiprotozoal managers. Transition element created complexes that hold several advantages over other metal chelated because of their good acceptability and decreased toxicity in living organisms [1, 2]. Thiosemicarbazone compound is of diverse importance for the reason that of their useful for living and pharmacological activities. Thiosemicarbazone derivatives have found application in drug development for the treatment of central nervous system disorders, of bacterial infection, as well as analgesic and antiallergic agent. Thiosemicarbazones are potent intermediates for the synthesis of pharmaceutical and bioactive materials, and thus, they are used extensively in the field of medicinal chemistry. Moreover, thiosemicarbazones have found their way into almost every branch of chemistry; commercially, they are used as dyes, photographic films, plastic and in textile industry [3]. The biological activity of these compounds depends upon the starting materials and their reaction conditions, also related to molecular conformation in particular, which can also be significantly affected by the presence of intra- and intermolecular hydrogen bonding [4]. Thiosemicarbazones commonly perform such as chelating compound for metal ions, attachment through (C=S) and (C=N–) groups, although in several cases they behave as monodentate compound where they bind through (C=S) only [5]. A series of copper(II) complexes of 2-phenylamino acetyl-N-phenyl hydrazine carbothioamide (H2L) have been prepared and characterized by chemical and physical studies. The thermal behaviors of these chelates before and after γ- irradiation show that the complexes have induced more thermal stability after γ-irradiation. Solid state dc electrical conductivity for complexes was investigated before and after γ- irradiation [6, 7]. Recently, complexes of VO2+, Mn2+, Zn2+, Ru3+, Pd2+, Ag+ and Hg2+ have been prepared by reacting their metal salts with ligand (4-(4-chlorophenyl)-1-(2-(phenylamino) acetyl) thiosemicarbazone). Structure of synthesized metal complexes was confirmed by different analytical and spectral techniques (1H NMR, MS, FT-IR, UV–Vis, EPR and Powder X-ray diffraction), thermogravimetric studies as well as molecular modeling. X-ray diffraction pattern of Mn2+, Pd2+ and Ag+ complexes before and after irradiation is recorded. The TGA studies of unirradiated and irradiated complexes showed that irradiated complexes were more thermally stable than unirradiated. The compound and its metal complexes have been examined for their inhibitory outcome on the growth of microorganisms against gram positive and gram negative [8,9,10,11]. In this work, we described the synthesis, characterization, DFT, molecular docking as well as antibacterial activities of Cu(I), Cu(II), Zn(II) and Cd(II) of complexes of ligand N-phenyl-2-(p-tolylglycyl)hydrazine-1-carbothioamide (B).

2 Materials and Methods

2.1 Materials

All chemicals used in this study were analytically reagent grade, commercially available from Fulka, and used without previous purification as CuI (anhydrous), Cu(ClO4)2, ZnSO4, and CdCl2 compounds which represent the metal ions (anhydrous), complexation process. All solvents were used as it is without previous purifications.

2.2 Synthesis of Thiosemicarbazide Ligand (B)

The organic ligand N-phenyl-2-(p-tolylglycyl)hydrazine-1-carbothioamide (B) was prepared by mixing equimolar amount of desired hydrazide (0.01 mol) in 10 ml of absolute ethanol and the appropriate amount of phenyl isothiocyanate in 10 ml of absolute EtOH [6]. The reaction mixture was reflux for 6 h. After cooling, the resulting precipitate was filtered off, washed several times with ethanol and diethyl ether and dried in vacuum in the presence of P4O10.

2.3 Synthesis of Metal Complexes

The metal complexes were prepared by adding to hot absolute ethanol solution (~ 20 mL) MX2.nH2O where M = Cu(I) and Cu(II), Zn(II), Cd(II), and X = I−, ClO4−, SO4− and Cl−, n = 0–1 in appropriate molar ratio. The resulting mixture was magnetically stirred at 60 °C for 6–8 h. The formed precipitate was filtered off while hot; otherwise, the solution was left at 35 °C to evaporate some of solvent to promote crystallization. The crystals were collected by vacuum filtrations, washed several times with anhydrous diethyl ether and dried under vacuum in the presence of P4O10.

2.4 Physical Measurements

Elemental analyses (C, H and N) were performed at Microanalytical unit, Cairo University. Metal and halide analyses were estimated using standard literature methods [12]. The Fourier Transform Infrared (FT-IR) measurements were performed (4000–400 cm−1) in KBr disks using Nenexeus-Nicolidite-640-MSA FT-IR, Thermo-Electronics Co. The UV–visible absorption spectra were measured in DMF solution using 4802 UV/vis double beam spectrophotometer. The 1H-NMR spectra have been recorded in DMSO-d6 as a solvent using Varian Gemini 200 NMR spectrophotometer and Varian-Oxford Mercury at 300 MHz, respectively. Mass spectra were acquired using the electron impact (EI) ionization technique at 70 eV on a Hewlett-Packard MS-5988 GC–MS instrument at the Microanalytical Center, National Research Centre, Egypt. Thermal analysis (TG/DTG) was obtained out by using a Shimadzu DTA/TG-50 Thermal Analyzer with heating rate of 10 °C/min in nitrogen atmosphere with a following rate 20 mL/min in the range of ambient temperature up to 800 °C using platinum crucibles. X-ray powder diffraction analyses of solid samples were measured using APD 2000 PROModel GNR-X-ray Diffractometer at (NRC, Tanta University, Egypt). X-ray diffractograms give computer control formally finished by PHILIPS®MPDX´PERT X-ray diffractometer ready with Cu radiation CuKα (λ = 1.540 56 Å). The X’pert diffractometer has the Bragg-Brentano geometry. The x-ray tube used was a copper tube operating at 40 kV and 30 mA. The scanning range (2θ) was 5–90° with step size of 0.050° and counting time of 2 s/step. Quartz was used as the standard material to accurate for the instrumental expansion. This identification of the complexes was done by a known method. From the fit identified Scherer formula, the average crystallite size (D) is D = (Kλ/β Cos θ) Where: λ is the X-ray wavelength in the nanometer, K is factor related to crystallite shape, and with a value about 0.9 and ß is the peak width at half maximum height. The value of ß in the 2θ axis of diffraction shape must be in radians. The θ is the Bragg angle and be able to in radians since the Cos θ compatible with the same number.

2.5 Computational Studies

The input files of ligand and its metal complexes were prepared with Gauss View 5.0.8. Gaussian 09 rev. A.02 [13] was used to make the all calculations by the DFT/B3LYP method. 6‐31G and LANL2DZ are the standard basis sets for the synthesized ligand and its metal complexes, respectively.

2.6 Irradiation Studies

For irradiation studies of solid samples of ligand and complexes were subjected to γ-irradiation [14] to a dose of 60 kGy using Indian 60 Co γ-ray cell type GE-4000 A (at room temperature at the Egyptian Atomic Energy Authority Nasr City, Egypt) at a dose rate of 2.2 kGy h−1. After removing the samples from the radiation field the FT-IR, absorption spectra, XRD and thermal analysis (TG/DTG) and biological activity of the irradiated samples were investigated by the same methods used for before irradiated compound.

2.7 Antibacterial Activity

The in vitro antibacterial activity studies were carried out at Genetic Engineering and Biotechnology Research Institute, Department of Environmental Biotechnology at Sadat City University, Egypt, by using Broth Dilution Method [15] with some alterations, to investigate the inhibitory effect of some synthesized complexes before (B1–B4) and after (A1–A4) irradiation on the sensitive organisms Streptococcus pyogenes as for Gram-positive bacteria and Escherichia coli as Gram-negative bacteria. Nutrient broth medium and Brain Heart Infusion (BHI) medium were used as cultivation media for Escherichia coli and Streptococcus pyogenes, respectively. The test compounds in measured quantities were dissolved in DMSO which has no inhibition activity to get two different concentrations (1, 5 and 10 mg/mL) of compounds. The strains selected for the study were prepared in nutrient broth and (BHI) broth medium with shaking and autoclaved for 20 min 15 pounds of pressure and at 121 °C before inoculation. The bacteria were then cultured for 24 h at 37 °C in an incubator. One ml of the standard bacterial culture was used as inoculation volume. For growth studies, culture of microbial cells was inoculated and grown aerobically in nutrient broth and BHI broth for control and along with various concentrations of the test compounds in individual flasks. Growth was calculated turbidometrically at 650 nm using conventional Spectrophotometer, in which turbidity produced is measured by taking absorbance and compared with turbidity produced by control. The growth rate of different bacteria in the absence as well as in the presence of test compounds was performed for each concentration. Absorption measurements were accomplished by spectrophotometer after 24 and 48 h of incubation to determine the number of viable cells per milliliter of sample and were used to the calculated the % inhibition.

2.8 Molecular Docking

All docking steps were done by MOE 2008 (Molecular Operating Environment) software [16] to simulate the binding model of these compounds into topoisomerase II DNA gyrase enzymes (2XCT). The protein crystal structure was obtained from the Protein Data Bank (PDB).

3 Results and Discussion

3.1 Elemental Analysis and Molar Conductance

The analytical and physical data of the prepared ligand and metal complexes are collected in Table 1. The chemical composition and stoichiometry of the prepared metal complexes were confirmed by the results of analytical and spectral tools. The obtained data showed satisfactory agreement with the proposed molecular formulae. These data also indicated that the metal complexes have 1:1 (metal/ligand) (B1 and B4) or 1:2 stoichiometry for complexes (B2 and B3).

Table 1 Elemental analyses and physical properties of ligand(B) and its metal complexes
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The complexes are found to be air stable for a long time, insoluble in different organic solvents such as (ethanol, methanol, carbon tetrachloride, chloroform, dichloromethane and acetone) but soluble to great extent in DMF and DMSO. Conductivity measurements in non-aqueous solution have frequently been used in structural studies of the prepared metal complexes within the limits of their solubility. The molar conductance values of 10–3 M solution of the complexes in DMF that are listed in Table 1 show that copper complexes (B1 and B2) are non-electrolytes [17, 18]. However, complexes (B3, B4) show molar conductivity values of 72 and 65 Ω−1 cm2 mol−1 indicating 1:2 and 1:1 electrolyte, respectively [19, 20].

3.2 Nuclear Magnetic Resonance Spectroscopy

Comparison of the proton nuclear magnetic resonance of N-phenyl-2-(p-tolylglycyl)hydrazine-1-carbothioamide (B) ligand before and after γ- irradiation (B and A) recorded in DMSO-d6 solution is shown in Figure S1. The 1H NMR spectrum of the ligand before γ—irradiation(B) in DMSO-d6 exhibited a chemical shift (δ/ppm), before and after γ- irradiation, the N(4)H signal appears at 9.44 ppm and the N(2)H signal appears at 9.51, 10.05 ppm indicating the involvement of these hydrogen through intra-molecular hydrogen bonding with the carbonyl oxygen, the peak of N(1)H appeared at 9.62 ppm for ligand after gamma irradiation. The singlet signal appears at 2.14, 3.9, 3.7 ppm attributed to the protons of methyl CH3, singlet signal appears at 3.7 ppm attributed to the protons of CH2, the multiplet signal appears at 5.85–7.1, 6.5–7.4 ppm attributed to the aryl protons. The intensity of the bands after irradiation is higher than before irradiation, and some bands disappear upon irradiation [21]. Also, 1H NMR spectra of [Zn(H2L)2]SO4 before and after γ-irradiation (B3,A3) displayed signals at 2.14(s, 6H, 2CH3), 3.76(s,4H,2CH2), 5.59(s,2H,2NH), 6.32–7.43(m, 18H, Ar–H), 9.55(s,1H, NH) and10.51(s, H, NH) as shown in Fig. 1 and. While [Cd(H2L)Cl] Cl before and after γ-irradiation (B4, A4) complexes displayed signals at 2.16(s, H, CH3), 3.77(s,2H,2CH2), 5.56(s, H, NH), 6.51–7.52(m, 9H, Ar–H), 9.44 (s,1H, NH), 9.61 (s,1H, NH) and 10.05(s, H, NH) as shown in Figure S2.

Fig. 1
figure 1

1H NMR spectra of complexes B3 before and after irradiation A3 in DMSO-d6 solution

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The effect of γ-irradiation on the chemical shift of [Zn(H2L)2]SO4 and [Cd(H2L)Cl]Cl after γ-irradiation is insignificant.

3.3 Mass Spectroscopy

Mass spectrum confirms the structure of the ligand as indicated by the molecular ion peak (M+) corresponding to its molecular weight Figure S3. MS of B, the observed peak at m/z = 313 corresponding to (C16H18N4OS, atomic mass m/z = 314 molecular ion peak). The spectrum also shows important fragment ions in the range m/z = 51 for [C4H4–H]+, 77 for [C6H5]+, 107 for [C7H8N]+ base peak, 120 for [C7H6NO]+, 135 for [C8H7S]+and 280 for [C14H13N3SO-H]+

Also, the mass spectrum of complex (B3) confirms its proposed formula by showing a molecular ion peak at m/z 807.4 amu corresponding to [Zn(H2L)2(H2O)SO4] (B3) Figure S4 which coincide with its formula weight (calculated m/z = 807.4 amu). The other fragments of the complex give the peak with various intensities at different m/z values like at Calc/Found: 77[C6H5], 91[C6H4NH], 120[C9H8NH], 255[C13H13N5O], 535[C24H24N8O2], 715[C30H29N8O4S2], 783[C30H38N8O7S2Zn], 807.4/806 [C32H38N8O7S2 Zn].

3.4 FT-IR Spectra

3.4.1 FT- IR Spectra of the Ligand Before and After γ-Irradiation

Gamma irradiation can change the properties and morphology of matter and that exhibit in physical techniques as FT-IR, and the following comparison between the functional groups of the ligand before and after irradiation (B and A) is presented in Fig. 2 and Table 2. It has been found that the functional groups of the ligand before γ-irradiation and after presented at 3384,3336 cm−1; 3263,3185 cm−1; 3150,3126 cm−1; 1672,1689 cm−1 and 749,750 cm−1 are attributed to the stretching frequencies of υ(N4–H), υ(N2–H) and υ(N1–H), υ(C=O) and υ(C=S), respectively. After γ-irradiation, the bands corresponding to υ(C=O) slightly shift to higher frequencies as compared with before γ-irradiation [6]. After γ-irradiation, the peaks are sharper than before γ-irradiation, where we notice a change in frequency and intensity of peak we also note this change also in complexes.

Fig. 2
figure 2

IR spectra of the ligand (B) before irradiation and after irradiation (A)

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Table 2 Infrared spectral bands (cm−1) for ligand and its metal complexes before and after irradiation
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Where: B = before γ-irradiation, A = after γ-irradiation.

3.4.2 FT-IR Spectra of Copper Complexes Before and After γ-Irradiation

The FT-IR spectra of the Cu(I), Cu(II) complexes before and after γ-irradiation (B1, B2 and A1, A2) show significant changes compared to the spectrum of their free ligand Figs. 3 and S5. The most important diagnostic spectral bands are summarized in Table 2. The IR spectra of copper complexes (B1 and B2) show strong bands at 3431, 3437; 3293, 3295; 1597, 1595 and 740, 754 cm−1 for before irradiation and at 3434, 3433; 3295; 3297; 1597; 1595 and 745,756 cm−1 for (A1 and A2) after irradiation which assigned to the stretching frequencies of υ(N4–H), υ(N2–H), υ(C=O) and υ(C=S), respectively. The IR spectra of copper complexes before irradiation show that υ(C=O) and υ(N2–H) shift to lower frequency upon complexation as compared of free ligand, indicating the coordination of the ligand in keto-form and the ligand behaves as neutral bidentate or tridentate, coordination take place via (C=O) and N(2)H ( B2) and (C=S) (B1).

Fig. 3
figure 3

IR spectra of copper(II) complexes before irradiation (B2) and after irradiation (A2)

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The IR spectra of Cu(I), Cu(II) complexes before and after γ- irradiation display new bands at 603, 614 and 529,545 cm−1 assigned to υ(Cu–O) and υ(Cu–N), respectively [22, 23]. New bands appear at 1109, 1113 cm−1 assigned to υ(ClO4). IR spectra of the complexes (A1 and A2) showed that the intensity of the IR bands became sharper than after γ- irradiation [24].

3.4.3 FT-IR Spectra of Zinc(II) Complexes Before and After γ-Irradiation

The IR spectra of Zn(II) complexes Figure S6 show strong bands at 3420, 3170, 3164, 1593, 1619 and 738, 743 cm−1 before irradiation and after γ-irradiation which attributed to the stretching frequencies of υ(N4–H) υ(N1–H), υ(N2–H), υ(C=O) and υ(C=S) wagging vibrations, respectively. In the IR spectra of Zn(II) complex before and after γ- irradiation, it is seen that the band corresponding to υ(C=O) was shifted to lower frequency upon complexation and the ligand behaves as neutral bi/tridentate and coordination takes place via (C=O), (N2–H) and (C=S). High intensity of the function groups bands was observed after γ-irradiation. The new bands appeared at 614,618 and 512 cm−1 are assigned to υ(Zn–O) and υ(Zn–N), respectively [25]. New bands at 1027, 1025 cm−1 display υ(SO4) for complexes (B3 and A3).

3.4.4 FT-IR Spectra of Cd(II) Complexes Before and After γ-Irradiation

The FT-IR spectra of Cd(II) complexes Fig. 4 show strong bands at 3426, 3433; 3268, 3269; 3179; (1675,1613, 1617) and 735 cm−1 for before irradiation and after γ-irradiation which attributed to the stretching frequencies of υ(N4–H) υ(N2–H), υ(N1–H) and υ(C=S) wagging vibrations, respectively. The IR spectra of Cd(II) complexes before and after γ- irradiation showed that the band corresponding to υ(C=O) is shifted to higher frequency upon complex formation and the ligand behave as neutral tridentate and coordination take place via (C=O), (N2–H) and (C=S). The new bands appeared at 591, 533 and 532 cm−1 assigned to υ(Cd–O) and υ(Cd–N), respectively [26].

Fig. 4
figure 4

IR spectra of Cadmium complexes before irradiation (B4) and after irradiation (A4)

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3.5 UV-Vis Spectra and Magnetic Moment Properties

The electronic spectral data of the ligand (B) and Cu(I), Cu(II), Zn(II) and Cd(II) complexes in DMF solution within the range 200–800 nm are tabulated in Table 3 and depicted in Figures S7–S10. The electronic spectrum of the ligand exhibits bands at 314, 292 and 279 nm, respectively.

Table 3 The electronic absorption spectral data in DMF solution of ligand and its magnetic moment and its metal complexes before and after irradiation value
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3.5.1 The Electronic Absorption Spectra of Copper Complexes Before and After γ- Irradiation

The electronic spectra of Cu(I) complexes Figure S5 before and after irradiation (B1 and A1) displayed bands at 300 and 409 nm, respectively. Cu(I) ions have the d10 configuration, and therefore, the Cu(I) complexes should not exhibit any d–d transition and have tetrahedral geometry [27].

While the electronic absorption spectra of Cu(II) (B2 and A2) Figure S8 before and after irradiation exhibited bands at 308, 398 and 653 nm in DMF refer to L → M charge transfer and d → d transitions, respectively, in an octahedral geometry [28]. Diamagnetic behavior of complex (B1) and the magnetic suitability value of complexes (B2, A2) 1.8 B.M. are an indicative of tetrahedral and octahedral geometry [27, 29].

3.5.2 Zinc(II) Complexes Before and After γ-Irradiation

The electronic absorption spectra of Zn(II) complexes Figure S9 before and after γ-irradiation displayed bands at 300, 282; 448 and nm in DMF solution, octahedral structure of Zn(II) complex is suggested which is diamagnetic in nature [30].

3.5.3 Cadmium(II) Complexes Before and After γ-Irradiation

The electronic absorption spectra of Cd(II) complexes Figure S10 before and after γ-irradiation displayed three bands at 284, 390, 610 nm; 282,385 and 608 nm in DMF solution attributed to charge transfer transition which assigned to tetrahedral geometry around Cd(II) ion [31, 32]. The Cd(II) complexes are diamagnetic because of d10 electronic configuration of Cd(II) ion [33].

3.6 X-ray Diffraction Patterns

XRD analysis was performed to confirm the crystal phase of compound. Samples (B1, B2, A2 and B3, A3) for before and after irradiation as shown in Figures S11–S13 and Table 4. The XRD patterns of the synthesized compounds were carried out in order to give an insight about the lattice dynamics of the compounds. The X-ray diffraction was recorded by using (CuKα) radiation (1.5406 Å). The intensity were collected over a 2θ range of 5–90°. The average grain size of the samples was estimated using the diffraction intensity peak. The mean grain size (D) of the particles was determined from the XRD line broadening measurement using the Scherrer equation [18, 34, 35]: D = 0.89λ/β (Cosθ).

Table 4 XRD data of Cu(I), Cu( II) and Zn(II) complexes before (B1, B2, B3) and after irradiation(A2,A3)
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An observable peak sharpness in the diffraction pattern indicates that the Cu(I), Cu(II) and Zn(II) complexes before and after irradiation Figures S11–S13 and Table 4 are in the nanometer range. The diameter of particles is found in nanorange scale as follows: Cu(I) complex before (B1) 4.83 nm; Cu(II)complexes before and after irradiation (B2 and A2) 3.6, 5.79 nm; Zn(II) complexes before and after irradiation (B3 and A3) 5.97, 3.84 nm. The nanoparticles sized complexes may serve strongly in different application fields in between the biological one [36, 37]. Figures S11–S13 show that in Cu(I), Cu(II) and Zn(II) complexes new peaks appear and some peaks displaced to longer interplanar spacing. The major factors tending to influence the intensity of powder patterns are structure factor, polarization factor, atomic scattering factor, multiplicities and preferred orientations. Upon irradiation, the position of atoms in the lattice changes and consequently, the scattering power also changes, leading to changes in intensity which displays high resistance [38]. It should be noted that the Zn(II) complex (A3) after irradiation showed increase in the crystalline size than B3 before irradiation.

3.7 Thermal Behavior of Ligand and Metal Complexes Before and After γ-Irradiation

The thermal behavior of the ligand and Cu(I), Cu(II), Zn(II) and Cd(II) complexes before and after γ-irradiation was investigated by thermogravimetric technique in temperature range 25–800 °C. The thermal behavior data of the ligand and Cu(I,II), Zn(II) and Cd(II) complexes (B1–B4 and A1–A4) before and after γ-irradiation are tabulated in Table 5 and depicted in Figs. 5 and S14 and S15.

Table 5 Thermal analysis data of ligand and Cu(I), Cu(II), Zn(II) and Cd(II) complexes before and after irradiation
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Fig. 5
figure 5

TGA/ DTG curves of complexes before irradiation (B1), after irradiation (A1)

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3.7.1 The Ligand Before and After γ –Irradiation

The TG curves of the ligand before and after γ-irradiation show that it is thermally stable till 140 °C, and 125 °C, respectively. Also, the TG curves show three decomposition steps in the temperature range 140–550 °C;125–510 °C with total weight loss of Calc.100% (Found 100%) before and after γ-irradiation, respectively.

3.7.2 Copper Complexes

The TG thermograms of complexes (B1 and A1) display three steps of decomposition as shown in Table 5 and Fig. 5. The first step of decomposition appeared within the temperature range 134–255 and 147–293 °C with mass loss of 21% (calc. 21.2%) and 28.7% (calc. 28.3%) for complex (B1) and complex (A1), respectively, corresponding to loss of (CH3C6H5NH) and (HI + NH). The second step appeared at 258–410 and 294–385 °C with mass loss of 19.0% (calc. 18.2%) and 11.0% (calc. 10.1%) for complexes (B1 and A1), respectively, corresponding to further decompositions of organic ligand. The third TG decomposition step appeared within the temperature ranges 410–753 °C and 385–701 °C with mass loss of 36.0% (calc. 36.5%) and 35.0% (calc.34.1%), respectively, corresponding to complete decomposition of the organic ligand. The final remained product appeared above 735 °C with remain mass of 24.0% (calc. 22.9%) for complex (B1) and above 701 °C with mass remain of 25.3% (calc. 25.3%) for complex(A1) represent the formation of (CuO + 3C) and (CuO + 4C) as a final product [39].

The TGA curve of complexes (B2 and A2) displays successive steps of decomposition as shown in Table 5. The decomposition starts within the temperature range 420–620 and 440–790 °C with mass loss of 82.0% (calc. 83%) and 84.4% (calc. 84.6%) for complex (B2) and complex (A2), respectively. The final thermo-product appeared at 620 °C with mass loss 18.0% (calc. 17%) for complex (B2) and at 790 °C with mass loss 15.6% (calc. 15.7%) for complex(A2) represents the formation of (CuO + 7C) and (CuO + 6 C) as a final product [39].

3.7.3 Zinc (II) Complex

The TG thermograms of complexes (B3, A3) Figure S14 showed several steps of decomposition. The first step of decomposition appeared at 180–332 and 170–354 °C with mass loss 39% (calc. 39.3%) and 50% (calc. 50.3%) for complexes B3 and A3 which corresponded to decomposition of organic ligand. The second step of decomposition appeared at 332–749 and 354–705 °C with mass loss 39% (calc. 38.8%) and 50% (Calc.50%)), respectively, for complexes (B3, A3) which attributed to complete decomposition of organic ligand. The remaining weight for complex (B3) appeared above 704 °C and above 660 °C with mass remain of 22.1% (calc. 21%) and 21% (calc. 21.7%) corresponding to the formation of ZnO as final products in addition to 7C residue [39].

3.7.4 Cadmium (II) Complexes

The TG thermograms of complexes (B4, A4) Figure S15 display successive decomposition steps within the temperature range 134–789 and 139–718 °C with mass loss 88.2% (calc. 88.5%), respectively, for complexes (B4, A4), are assigned to the material decomposition. The final weight residue appeared at above 789 and 718 °C corresponded to Cd and CdO for complexes (B4, A4) as thermo-finial products in addition to carbon residue for complex (A4) [24, 40] (Fig. 6).

Fig. 6
figure 6

The suggested chemical structures of the ligand and its metal complexes

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From the above assignment, the suggested chemical structure of the ligand and Cu(I),Cu(II), Zn(II) and Cd(II) complexes(B1–B4) is shown in Fig. 5

3.8 Structure Characterization with DFT Study

The geometric structures of H2L ligand and its metal complexes were optimized as shown in Fig. 7. Upon coordination of H2L to the metal atom, some bond lengths become slightly longer than in the free ligand accompanied with changes in angles that are clarified in Table 6 as (C5–O8), (N4–C5), (N7–C6) and (N3–C2). This finding is due to the formation of M–N & M–O bonds in all complexes that make the C–O [41, 42] and C–N bonds weaker [43]. It was observed from the energy values that the stability of ligand increases upon complexation with Zn (II) and Cu(II) ions in ratio (1–2) metal to ligand. The ionic complexes (Cd(II) & and Cu(I)) show higher energy values than the parent ligand. The polarity of ligand increased after complexation by its coordination to metal ions as it is evident from the magnitude of their dipole moments. The ionic complexes have higher polarity than the non-electrolytic complexes. The molecular properties are mentioned in Table 6 which can be calculated as follows: Hardness η = (I − A)/2, Softness (S) S = 1/2η, Chemical potential (μ), μ = − (I + A)/2 and Electronegativity (χ), χ = (I + A)/2η. From HOMO–LUMO gap (ΔE), one can detect whether the molecule is hard or soft. Larger ΔE corresponding to harder molecule and small one related to the softer molecule. The polarizability of the soft molecule is more than the hard one because it needs lower energy to excitation, thus softness (S) and hardness (η) are properties of molecule that measures the chemical reactivity. We found the ligand and Cu(I) complex were more harder than the remaining complexes. The generated molecular orbital energy diagrams HOMO and LUMO are presented in Fig. 8.

Fig. 7
figure 7

Optimized 3D structures of ligand a H2L(B), b [Cu(H2L)I](B1), c [Cu(H2L)2ClO4] (B2), d [Zn (H2L)2(H2O)]SO4(B3) and e [Cd(H2L)Cl]Cl (B4)

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Table 6 Ground state properties of H2LB ligand using B3LYP/6-31G(+ +)d,p and its metal complexes using B3LYP/LANL2DZ
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Fig. 8
figure 8

Frontier HOMO and LUMO molecular orbitals for ligand a B = H2L, b B1 = [Cu(H2L)I], c B2 = [Cu(H2L)2ClO4], d B3 = [Zn(H2L)2ClO4] and e B4 = [Cd(H2L)Cl]Cl complexes calculated at DFT level

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The formal charge of cadmium, zinc and copper was Cd2+, Zn2+, Cu2+, Cu+, but the calculated charges on [Cd(H2L)Cl]Cl, Cu(H2L)2(ClO4)2, Cu(H2L)I and [Zn(H2L)2(H2O)] SO4 were 0.856, 0.579, 0.413 and 0.884, respectively. It can be explained due to the charge transfer from the examined ligand to the central metal ions, i.e., L → M. So, the theoretical calculations confirm the results that obtained from the analysis tools which were discussed in the previous characterization part (Table 7).

Table 7 Some of the optimized bond lengths, Å and bond angles, degrees, for (H2L) and its metal complexes using B3LYP/6-311G(+ +)d,p
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3.9 Antibacterial Activity

The utilization of heavy metal compounds as a choice to treat bacterial borne diseases shows up as a novel and promising thought. A few reports affirm the antimicrobial capability of copper and zinc compounds on different microbes that cause nosocomial illness in people [44,45,46]. Our results showed an attempt to use metals complexes as an alternative choice in treatment of these diseases. In our study, we tested antibacterial activity of different copper, zinc and cadmium complexes as well as ligand (B, A) before and after irradiation on E.coli and Streptococcus pyogenes bacteria and data obtained showed a promising future in this branch of biotechnological application.

The synthesized ligand, Cu(I), Cu(II), Zn(II) and Cd(II) complexes (B and B1–B4) were separately exposed to gamma irradiation to test their improvement as active antibacterial drugs [47]. Results in Table S1 and Figs. 9, 10 showed antibacterial activity against the tested microbes. Generally, it was found that antibacterial activity of both the synthetic ligand and metal complexes before and after γ-irradiation (B, B1–B4 and A, A1–A4) was proportionally increased with increased concentration. All compounds were tested starting from zero time of bacterial growth curve to examine the effect of added concentrations throughout all the stages of growth. The tested compounds before and after γ-irradiation are found to have remarkable biological activity. In case of E.coli, that the corresponding Zn(II) and Cu(II) complexes showed much better antibacterial activity with respect to the individual ligand and complexes against the same microorganism under identical experimental conditions, the antibacterial activity of the tested compounds were found to follow the order: A3 > A2 > A1 > B3 > B1 > B2 > A > A4 > B4 > B for 1, 5 and 10 µg\ml for before and after irradiation. On the other hand, antibacterial activity was recorded when using the ligand and metal complexes with S. pyogenes follow the order: A3 > A2 > B3 > A1 > B2 > B1 > A > B > A4 > B4 for before and after irradiation with1 and 5 μg/ml concentration [23, 48]. Obtained data showed more antimicrobial activity to E.coli than S. pyogenes corresponding to the hypothesis of the complexity of the cell wall structure of Gram-positive bacteria and Gram-negative bacteria [49]. The lipid membrane facilitates the passage of any fat-soluble substance, and liposolubility is known to be an important factor in controlling antibacterial activity. The results are consistent with the hypothesis that copper complexes may initially cause instability of the outer membrane, destroying the cell membrane, leading to bacterial cell lysis.

Fig. 9
figure 9

Antibacterial activity for ligand (B, A) and copper, zinc and cadmium (B1, B2,B3, B4 and A1,A2,A3, A4) complexes before and after irradiation against S. pyogenes

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Fig. 10
figure 10

Antibacterial activity for ligand (B, A) and copper, zinc and cadmium (B1, B2,B3, B4 and A1,A2,A3, A4) complexes before and after irradiation E.coli

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Results also suggested that in case of 1 μg/ml, 5 and 10 µg/ml Zn(II) and Cu(II) and complexes have higher activity than other complexes. The chelation could facilitate the ability to cross the cell membrane of E. coli and can be explained by Tweedy’s chelation theory. Chelation/complexation could enhance the lipophilic nature of the central metal atom which in turn, favors its permeation through the lipoid layer of the membrane thus causing the metal complex to cross the bacterial membrane more effectively thus increasing the activity of the complexes. Besides from this many other factors such as solubility, dipole moment, conductivity influenced by metal ion may be possible reasons for remarkable antibacterial activities of these complexes [50]. Exposure to gamma irradiation remarkably enhanced the antibacterial activity for both the ligand and its complexes when it was used in case of E.coli. Additionally, it also has been observed that some moieties such as N(2)H linkage introduced into such compounds exhibit extensive biological that may be responsible for increase in hydrophobic character and liposolubility of the molecules in crossing the cell membrane of the microorganism and enhance biological utilization ratio and activity of complexes activity [51]. The antibacterial studies of the prepared compounds screened against both Gram-positive and Gram-negative bacteria proved that these compounds exhibit remarkable antibacterial activity and can be used in the future as therapeutic drugs for pathogenic bacterial diseases.

3.9.1 The molecular docking

To understand the interaction of all the synthesized molecules with topoisomerase II DNA gyrase enzymes, the crystal structure of topoisomerase II was downloaded from Protein Data Bank (PDB ID: 2XCT) and the molecular docking studies were performed using the Moe program. The protein ligand interaction plays a significant role in structural based drug designing. The different types of interactions are mentioned in Table 8 and seen in Fig. 11. The preferred compounds Cd(II), Cu(II) and Zn(II) complexes had a scoring values of − 5.02, − 9.41 and − 10.87, respectively. The Zn(II) complex showed the highest binding affinity and interaction with topoisomerase II DNA gyrase enzymes (2XCT) by using most types of protein binding interactions. The binding affinity of our compounds achieved higher or the same values numerous previous works against the same type of protein [52, 53]. The molecular docking of our work supported that the chelates are more active than their parent ligand against the same microorganism as mentioned also in many of our previous works [54].

Table 8 Comparison of binding affinity of metal complexes against topoisomerase II DNA gyrase enzymes (PDB Code: 2XCT)
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Fig. 11
figure 11

Binding pose of a B = H2L, b B1 = [Cu(H2L)I], c B2 = [Cu(H2L)2ClO4], d B3 = [Zn(H2L)2ClO4] and e B4 = [Cd(H2L)Cl]Cl complexes in the active pocket of topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT)

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4 Conclusions

New Cu(I), Cu(II), Zn(II) and Cd(II) complexes of N-phenyl-2-(p-tolylglycyl) hydrazine-1-carbothioamide (B) have been prepared and characterized by physical and analytical technique, and the effect of gamma irradiation on these compounds has been studied. The biological activities of unirradiated and irradiated compounds were investigated. And it turns out the following: the ligand behaves as neutral for tridentate, tetradentate coordinated to the ligand through the (C=O), N(2)H, (C=S) and coordination take place via two (C=O) and two N(2)H for complexes (B2 and B3), elemental analysis data indicated that the metal complexes have 1:1 (metal/ligand) (B1 and B4) or 1:2 stoichiometry for complexes (B2 and B3). X-ray diffraction patterns improve the crystallite size of the complexes by using gamma-irradiation. The proposed structures of complexes were geometrically optimized, also showed that the Cu(I), Cu(II), Zn(II) and Cd(II) complexes have four and six coordination geometries; this is also in a good agreement with the experimental results. In vitro antibacterial activity of Zn(II) after irradiation complex has higher activity than other complexes, which indicates the extent to which gamma radiation affects the morphology and properties of matter.