2.6.1 [Cr(H₂L)(H₂O)₂Cl₂]Cl·5H₂O

Yield 79%; m.p. > 300 °C; dark brown solid. Anal. Calc. for C₁₉H₃₁Cl₃FeCrNO₁₀ (%): C, 35.21; H, 4.79; N, 2.16; Fe, 8.65; Cr, 8.03. Found (%): C, 34.95; H, 4.15; N, 2.09; Fe, 8.33; Cr, 7.89. Λ_m (Ω⁻¹mol⁻¹cm²) = 65; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3404br, carbonyl (C⚌O) 1780w, azomethine (C⚌N) 1652sh, ν(COO)_asy 1429 s, ν(COO)_sym 1367 m, H₂O stretching of coordinated water 847 s and 800w, (M—O) 537w. UV–Vis (λ_max, nm): 267 (π–π* of ferrocene) and 323 (n–π* of COOH, C⚌N and OH groups).

2.6.2 [Mn(H₂L)(H₂O)₃Cl]Cl·5H₂O

Yield 85%; m.p. > 300 °C; dark brown solid. Anal. Calc. for C₁₉H₃₃Cl₂FeMnNO₁₁ (%): C, 36.02; H, 5.21; N, 2.21; Fe, 8.85; Mn, 8.69. Found (%): C, 35.97; H, 5.14; N, 2.07; Fe, 8.33; Mn, 8.54. Λ_m (Ω⁻¹ mol⁻¹ cm²) = 58; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3391br, carbonyl (C⚌O) 1770w, azomethine (C⚌N) 1652sh, ν(COO)_asy 1440 s, ν(COO)_sym 1384 m, H₂O stretching of coordinated water 900w and 821w, (M—O) 561w. UV–Vis (λ_max, nm): 268 (π–π*).

2.6.3 [Fe(H₂L)(H₂O)₂Cl₂]Cl·2H₂O

Yield 94%; m.p. > 300 °C; dark brown solid. Anal. Calc. for C₁₉H₂₅Cl₃Fe₂NO₇ (%): C, 38.16; H, 4.18; N, 2.34; Fe, 18.75. Found (%): C, 37.99; H, 4.06; N, 2.19; Fe, 18.44. Λ_m (Ω⁻¹mol⁻¹cm²) = 61; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3430br, carbonyl (C⚌O) 1773w, azomethine (C⚌N) 1648sh, ν(COO)_asy 1428 m, ν(COO)_sym 1369 m, H₂O stretching of coordinated water 853 s and 810w, (M—O) 541w. UV–Vis (λ_max, nm): 265 (π–π* of ferrocene) and 307 (n–π* of COOH, C⚌N and OH groups).

2.6.4 [Co(H₂L)(H₂O)₂Cl₂].3H₂O

Yield 88%; m.p. > 300 °C; dark brown solid. Anal. Calc. for C₁₉H₂₇Cl₂FeCoNO₈ (%): C, 39.11; H, 4.63; N, 2.40; Fe, 9.61; Co, 10.12. Found (%): C, 39.01; H, 4.25; N, 2.22; Fe, 9.26; Co, 9.96. Λ_m (Ω⁻¹mol⁻¹cm²) = 39; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3382br, carbonyl (C⚌O) disappear, azomethine (C⚌N) 1651sh, ν(COO)_asy 1435 m, ν(COO)_sym 1382 m, H₂O stretching of coordinated water 824 s and 800w, (M—O) 560w. UV–Vis (λ_max, nm): 267 (π–π*).

2.6.5 [Ni(H₂L)(H₂O)₃Cl]Cl·2H₂O

Yield 86%; m.p. > 300 °C; dark brown solid. Anal. Calc. for C₁₉H₂₇Cl₂FeNiNO₈ (%): C, 39.11; H, 4.63; N, 2.40; Fe, 9.61; Ni, 10.12. Found (%): C, 39.03; H, 4.46; N, 2.13; Fe, 9.32; Ni, 9.95. Λ_m (Ω⁻¹ mol⁻¹ cm²) = 60; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3412br, carbonyl (C⚌O) 1760w, azomethine (C⚌N) 1652sh, ν(COO)_asy 1429 m, ν(COO)_sym 1374 m, H₂O stretching of coordinated water 860 s and 800w, (M—O) 535w. UV–Vis (λ_max, nm): 267 (π–π* of ferrocene) and 326 (n–π* of COOH, C⚌N and OH groups).

2.6.6 [Cu(H₂L)(H₂O)₂Cl₂].2H₂O

Yield 90%; m.p. > 300 °C; grey solid. Anal. Calc. for C₁₉H₂₅Cl₂FeCuNO₇ (%): C, 40.04; H, 4.39; N, 2.46; Fe, 9.83; Cu, 11.15. Found (%): C, 39.78; H, 4.21; N, 2.34; Fe, 9.09; Cu, 11.02. Λ_m (Ω⁻¹ mol⁻¹ cm²) = 3; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3431br, carbonyl (C⚌O) disappear, azomethine (C⚌N) 1651sh, ν(COO)_asy 1430 m, ν(COO)_sym 1310 s, H₂O stretching of coordinated water 920w and 830w, (M—O) 520 s. UV–Vis (λ_max, nm): 277 (π–π*).

2.6.7 [Zn(H₂L)(H₂O)₂Cl₂].H₂O

Yield 78%; m.p. > 300 °C; dark brown solid. Anal. Calc. for C₁₉H₂₃Cl₂FeZnNO₆ (%): C, 41.23; H, 4.16; N, 2.53; Fe, 10.13; Zn, 11.75. Found (%): C, 41.11; H, 3.99; N, 2.14; Fe, 10.04; Zn, 11.23. Λ_m (Ω⁻¹ mol⁻¹ cm²) = 13; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3442br, carbonyl (C⚌O) disappear, azomethine (C⚌N) 1648sh, ν(COO)_asy 1436 m, ν(COO)_sym 1380w, H₂O stretching of coordinated water 920w and 850w, (M—O) 550w. UV–Vis (λ_max, nm): 269 (π–π*).

2.6.8 [Cd(H₂L)(H₂O)₂Cl₂].3H₂O

Yield 75%; m.p. > 300 °C; dark brown solid. Anal. Calc. for C₁₉H₂₇Cl₂FeCdNO₈ (%): C, 35.85; H, 4.25; N, 2.20; Fe, 8.81; Cd, 17.61. Found (%): C, 35.47; H, 4.11; N, 2.10; Fe, 8.64; Cd, 17.42. Λ_m (Ω⁻¹ mol⁻¹ cm²) = 6; FT-IR (ν, cm⁻¹): hydroxyl (OH) 3448br, carbonyl (C⚌O) disappear, azomethine (C⚌N) 1652sh, ν(COO)_asy 1447 s, ν(COO)_sym 1384s, H₂O stretching of coordinated water 910w and 824s, (M—O) 550w. ¹H NMR (300 MHz, DMSO-d₆, δ, ppm): 4.22–4.77 (m, 9H, ferrocene ring), 6.00–7.95 (m, 3H, benzene), 10.11 (s, 1H, carboxylic-OH), 8.85 (s, 1H, phenolic-OH), 1.25 (s, 3H, methyl group of ferrocene). UV–Vis (λ_max, nm): 262 (π–π*).

3.1.1 Geometrical optimization of the Schiff base ligand (H₂L)

Calculating theoretical parameters would help in characterizing the molecular structure of the prepared compounds. So, the structure of the Schiff base ligand was optimized by using DFT method (Gaber et al., 2018; Singh et al., 2012). The calculated bond lengths and bond angles for H₂L ligand were listed in Supplementary Table (1) and the optimized structure of the H₂L ligand was shown in Fig. 1. Furthermore, other quantum chemical parameters such as: energy of the highest occupied molecular orbital, E_HOMO, energy of the lowest unoccupied molecular orbital, E_LUMO, energy gap (ΔE), chemical potentials, Pi, electronegativity, χ, dipole moment, μ, softness, σ, hardness, η, and additional electronic charge, ΔN_max had been calculated according to different equations as shown in Supplementary Information 1 (SI-1) and then were listed in Table 2 (Pearson, 1989; Geerlings et al., 2003; Chattaraj and Giri, 2007).

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Fig. 1

The optimized structure of organometallic Schiff base ligand (H₂L).

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When the value of E_HOMO become higher, the molecule is better for donating electrons. This means that the ligand offering electrons to unoccupied d-orbital of the transition metal ions and this increase the possibility of complexation to occur. Also, the small band gap energy showed that the molecule became more reactive one. The ΔE value of the H₂L ligand was very small (3.98 e.V). Dipole moment is considered as very important role in increasing the biological activities of the prepared compounds. The decrease in this value as observed in the prepared ligand may be the reason for increasing of its activities against breast cancer (Sagdinc et al., 2009).

3.1.2 Molecular electrostatic potential map (MEP)

MEP of the synthesized ligand was observed in Fig. 2. The MEP gave important information about charge density distributions, electrophilic interactions and chemically reactive sites that present in the ligand (Sahin et al., 2017). The positive electrostatic potential surfaces were represented by blue color which referred to the lower electron density regions. The negative regions were represented by red color which corresponded to nucleophilic sites (Ekmekcioglu et al., 2015; Aktan et al., 2011). The MEP of the ligand showed red color which surrounded the carboxylic and phenolic groups. While the ferrocene and benzene rings were surrounded by blue-green color. This indicated that the more reactive sites which were electrophilic surfaces that coordinated to metal ions were phenolic and carboxylic groups (Babur et al., 2015).

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Fig. 2

Molecular electrostatic potential map of organometallic Schiff base ligand (H₂L), the electron density isosurface is 0.004 a.u.

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3.1.3 Vibrational properties

For confirming the successfully preparation of the ligand, experimentally vibrational analysis was compared with the theoretical data that had been performed based on the optimized structure of the ligand. The data observed with the quantum chemical methods such as DFT method had systematic errors. So, using scaling factor of 0.96 for LanL2DZ level can overcome these errors (Alturk et al., 2016). The experimental data showed that the ligand had five important characteristic bands which were appeared at 3406, 1733, 1650, 1451 and 1371 cm⁻¹ which corresponded to ν(OH), ν(C⚌O), ν(C⚌N)_azomethine, ν(COO^–)_asy and ν(COO^–)_sym, respectively. These bands were calculated theoretically and their value were at 3666, 1720, 1680, 1482 and 1389 cm⁻¹. These data confirmed that the experimental values were close to the theoretical data. So, the ligand was prepared with successful method (Mahmoud et al., 2017b; Ermis, 2018).

3.1.4 UV–Visible analysis

The nature of the electronic transitions presented in the UV–Vis spectrum of the Schiff base ligand had been studied by high accuracy and low computational cost of DFT method (Mahmoud et al., 2017c; Reed et al., 1988). The experimental and theoretical electronic spectra of the ligand were showed in Supplementary Fig. 3. Also, electronic transitions with maximum oscillator strength from DFT calculations were listed in Supplementary Table 3. The experimental absorption spectrum of the Schiff base ligand was recorded in 10⁻⁴ M DMF solution. This spectrum showed bands at 271 and 314 nm which related to π–π* transitions of the ferrocene and benzene rings and to the n–π* transition of COOH, OH and C⚌N groups, respectively (Kucuk et al., 2015).

The data from TD-DFT method showed also two electronic transitions at 277 and 312 nm. The band observed at 277 nm was contributed to transition from HOMO-4 to LUMO. The second band computed at 312 nm with an oscillator strength of f = 0.3211 was represented by the contribution of HOMO → LUMO + 3 or contribution of HOMO-2 → LUMO (Gokce et al., 2017; Bilge et al., 2009). These transitions were shown in Fig. 4.

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Fig. 4

Theoretical electronic absorption transitions for Schiff base ligand (H₂L) in DMF solvent.

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3.2.1 Elemental analysis

The transition metal complexes were also prepared and then collected in pure form with satisfied yields. Their melting points, colors and percent of carbon, hydrogen, nitrogen and metal contents were determined. The complexes agreed well with a 1:1 metal: ligand stoichiometric ratio. They were air stable solids at room temperature and had high melting point values > 300 °C. They were soluble in N,N-dimethylformamide (DMF) for H₂L ligand, Fe(III), Cu(II) and Cd(II) complexes while in 1:1 mixture of DMF:DMSO for Cr(III), Mn(II), Co(II), Ni(II) and Zn(II) complexes. Also, they were insoluble in water, ethanol and methanol solutions.

3.2.2 Molar conductivity measurements

The molar conductivity of 10⁻³ Mol L⁻¹ solutions of all prepared complexes was measured at room temperature (25 °C). It was shown that Co(II), Cu(II), Zn(II) and Cd(II) complexes were located as non-electrolytes (Gull and Hashmi, 2015; Alothman et al., 2019). The data of these results assigned to the absence of any chloride anion in outer sphere of these complexes. While, Cr(III), Mn(II), Fe(III) and Ni(II) complexes behaved as electrolytes as the result of the presence of chloride anions in the outer sphere (Soliman and Mohamed, 2013; Mohamed et al., 2006).

3.2.3 IR spectra

In order to determine the mode of binding between the Schiff base and metal ions, IR spectra of all prepared complexes were compared with that of the Schiff base ligand. The IR spectrum of H₂L ligand showed band at 1650 cm⁻¹, this band attributed to azomethine group. In all metal complexes spectra, there were not any significant shifting in this band which confirming the non-participating of this azomethine group in the coordination (Firouzabadi and Firouzmandi, 2017). A broad band was appeared in the ligand spectrum at 3406 cm⁻¹. This band was shifted in all complexes to lower or higher frequencies in the range of 3382–3448 cm⁻¹ which confirming the participation of OH group in coordination with metal ions (Martins et al., 2017; Soliman and Mohamed, 2013). The carbonyl group, asymmetric and symmetric vibrations of carboxylic bands were exhibited in ligand at 1733, 1451 and 1371 cm⁻¹, respectively. These bands were shifted in all metal complexes to 1760–1780, 1428–1447 and 1310–1384 cm⁻¹, respectively (Ajlouni et al., 2016; Mahmoud et al., 2017d). The shift occurred in the carboxylate bands confirmed its participation in chelate formation with monodentate mode. Furthermore, two bands were assigned to the presence of coordinated water molecules in all metal complexes which appeared at 824–920 and 800–850 cm⁻¹ (Mahmoud et al., 2016). In lower frequencies of all metal complexes spectra, new band was found in the region of 520–561 cm⁻¹ which attributed to ν(M—O) (Halli et al., 2011). From the comparison between the spectrum of Schiff base and its metal complexes spectra, it was concluded that H₂L ligand behaved as bidentate ligand that can be coordinated to the metal ions through protonated phenolic-OH and protonated carboxylic-OH groups.

3.2.4 ¹H NMR spectra

The ¹H NMR spectra of H₂L ligand and its Cd(II) complex were recorded in DMSO-d₆ (Singh et al., 2010). The spectrum of the ligand showed multiplet signals that appeared in the region of 4.22–4.77 ppm which corresponded to the ferrocene protons (Zhang et al., 2001). These signals were appeared in Cd(II) complex at the same range. The methyl protons was observed as singlet signal at 1.56 ppm in the ligand and at 1.25 ppm in its Cd(II) complex (Yadav and Singh, 2011). The multi-signals within the 6.00–7.13 ppm range were assigned to the aromatic protons of benzene ring in the ligand which were indicated in the Cd(II) complex at 600–7.95 ppm (Bal et al., 2014). The carboxylic proton of salicylic acid was observed at 10 ppm in Schiff base ligand. This signal was still appeared in the Cd(II) complex but shifted to higher value at 10.11 ppm. This data indicated that this proton didn′t remove from the carboxylic group upon coordination (Bal et al., 2014; Roman and Andree, 2001). Also in the ¹H NMR spectrum of ligand, singlet signal was appeared at 8.75 ppm that related to the phenolic proton (Alaghaz et al., 2014b). This signal was still present in the spectrum of the Cd(II) complex but shifted to higher value 8.85 ppm. This confirmed the participating of this phenolic proton in coordination. Finally, the ligand behaved as neutral bidentate ligand as confirmed from the IR spectra (Fig. 5).

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Fig. 5

a ¹H NMR spectrum of Schiff base ligand (H₂L). b ¹H NMR spectrum of [Cd(H₂L)(H₂O)₂Cl₂].3H₂O complex.

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3.2.5 UV–Visible spectra of the Schiff base ligand and its metal complexes

The electronic absorption spectra of the prepared organometallic Schiff base and its metal complexes were measured in the range of 200–700 nm at room temperature.

The absorption spectrum of organometallic Schiff base ligand showed two bands at 271 and 314 nm. The first band was related to π-π* transitions of the benzene and ferrocene rings. The second band was observed at λ_max = 314 nm that may be related to the n–π* transition of the COOH, OH and C⚌N groups (Soliman and Mohamed, 2013; Kianfar et al., 2013). In all metal complexes, the band that appeared at 271 in the ligand was shifted to the range of 262–277 nm. While the other band that related to n–π* transition was shifted to 307–326 nm. These shifting gave good indication for coordination of carboxylic group to the metal ions (Liu et al., 2007; Mahalakshmi and Rajavel, 2010).

3.2.6 Thermal analysis of Schiff base ligand and its metal complexes

Thermal analysis is considered as a very useful, effective and important technique that can be used to determine the thermal stability of materials and confirm their molecular structures. So, the thermal stability of organometallic Schiff base (H₂L) and its transition metal complexes were investigated using differential thermogravimetric (DTG) and thermogravimetric technique (TG) analyses. These analyses were investigated at heating rate of 10 °C/min in nitrogen atmosphere over the range from room temperature to 1000 °C. The data then were listed in Table 4.

The organometallic Schiff base ligand (H₂L) with the molecular formula (C₁₉H₁₇NO₃Fe) was thermally decomposed in five decomposition steps. The first and second steps with estimated mass loss of 19.74% (calculated mass loss = 19.84%) within the temperature range 70–405 °C may be correspond to the loss of C₃H₆NO molecule. The DTG curve gave maximum peaks temperature at 201 and 376 °C. The other three decomposition steps with estimated mass loss of 43.33% (calculated mass loss = 43.80%) within the temperature range 405–1000 °C may be correspond to the loss of C₁₁H₁₁O molecule. The DTG curve gave maximum peaks temperature at 424, 617 and 735 °C. At the end of decomposition FeO contaminated with carbon remained as residues. The overall weight loss amounted to 63.07% (calculated mass loss = 63.64%).

The [Cr(H₂L)(H₂O)₂Cl₂]Cl·5H₂O complex was thermally decomposed in three steps. The first step with estimated mass loss of 13.22% (calculated mass loss = 13.90%) within the temperature range of 40–125 °C corresponded to loss of five water molecules of hydration. The DTG curve gave maximum peak temperature at 78 °C. The second step corresponded to estimated mass loss of 20.83% (calculated mass loss = 20.54%) within the temperature range 125–455 °C and represented the loss of Cl₂ gas, 2H₂O and C₂H₂ molecules. The final step with estimated mass loss of 35.72% (calculated mass loss = 35.29%) within the temperature range 455–1000 °C corresponded to loss of C₁₃H₁₅NO_0.5Cl molecule. The DTG curve gave maximum peak temperature at 847 °C, leaving FeO and ½ Cr₂O₃ contaminated with carbon as residues. The overall weight loss amounted to 69.77% (calculated mass loss = 69.73%).

The [Mn(H₂L)(H₂O)₃Cl]Cl·5H₂O complex upon heating lost 5H₂O molecules in the first step of decomposition within the temperature range 40–145 °C at maximum peak temperature 77 °C, with a mass loss = 13.73% (calculated mass loss = 14.22%). The second step of decomposition occurred at maximum peak temperature at 310 °C, correspond to loss of Cl₂ gas and 3H₂O molecules with a mass loss = 20.18% (calculated mass loss = 19.75%), in the temperature range of 145–520 °C. The final step started the decomposition at 520 °C and ended at 1000 °C with maximum peak temperature at 660 °C and may be correspond to the loss of C₁₄H₁₇NO molecule with mass loss of 33.92% (calculated mass loss = 33.97%), leaving FeO and MnO oxides contaminated with carbon as residues of decomposition. The overall weight loss amounted to 67.83% (calculated mass loss = 67.94%).

The [Fe(H₂L)(H₂O)₂Cl₂]Cl·2H₂O complex showed four decomposition steps within the range 30–1000 °C. The first decomposition step was accompanied by loss of 2H₂O molecules of hydration in the temperature range of 30–105 °C with an estimated mass loss of 6.13% (calculated mass loss = 6.03%). The DTG curve gave maximum peak temperature at 69 °C (the maximum peak temperature). The second step of decomposition correspond to loss of C₂H₂, 2H₂O molecules and Cl₂ gas at 105–380 °C with an estimated mass loss of 22.96% (calculated mass loss = 22.26%) with maximum peak temperature at 144 °C. The final two decomposition steps within the range 380–1000 °C were assigned to loss of C₁₂H₁₅NO_0.5Cl molecule with a mass loss of 35.16% (calculated mass loss = 36.23%). Ferric and ferrous oxides contaminated with carbon were remained as residues. The overall weight loss amounted to 64.25% (calculated mass loss = 64.52%).

In the thermograph of [Co(H₂L)(H₂O)₂Cl₂].3H₂O complex, the first and second steps of decomposition correspond to mass loss of 27.02% (calculated mass loss = 26.85%) within the temperature range of 30–390 °C with maximum peaks temperature at 75 and 340 °C, represented the loss of 5H₂O, HCl and C₂H₆ molecules. The third step started the decomposition at 390 °C and ended at 610 °C with maximum peak temperature at 590 °C and may be accounted to the loss of C₃H₄O molecule with mass loss of 9.72% (calculated mass loss = 9.61%). The final step of the decomposition started at 610 °C and ended at 1000 °C with maximum peak temperature at 727 °C and may be accounted to the loss of C₁₀H₆NCl molecule with mass loss of 30.15% (calculated mass loss = 30.10%), leaving behind FeO and CoO oxides contaminated with carbon as residues of decomposition. The overall weight loss amounted to 66.89% (calculated mass loss = 66.56%).

In the thermograph of [Ni(H₂L)(H₂O)₃Cl]Cl·2H₂O complex, the first and second steps of decomposition displayed a gradual mass loss of 33.23% (calculated mass loss = 33.37%) within the temperature range of 40–520 °C which may be correspond to the loss of five molecules of water of hydration, HCl and C₄H₄O molecules. The DTG curve gave maximum peaks temperature at 89 and 340 °C. The final step represented a mass loss of 33.22% (calculated mass loss = 33.19%) which correspond to loss of C₁₁H₁₂NCl molecule within temperature range 520–1000 °C. The maximum peak temperature was at 843 °C. Finally, FeO and NiO contaminated with carbon remained as residues. The overall weight loss amounted to 66.45% (calculated mass loss = 66.56%).

The [Cu(H₂L)(H₂O)₂Cl₂].2H₂O complex gave decomposition pattern that started from 30 °C to 1000 °C with three steps. The first step within the temperature range of 30–130 °C with maximum peak temperature at 85 °C which represented the loss of two water molecules of hydration with a found mass loss of 6.43% (calculated mass loss = 6.32%). The second step which represented the loss of Cl₂ gas and 2H₂O molecules with a mass loss of 18.90% (calculated mass loss = 18.79%) within the temperature range 130–345 °C and maximum peak temperature at 313 °C. The final step was represented the loss of C₁₅H₁₇NO molecule with a mass loss of 39.97% (calculated mass loss = 39.86%) within the temperature range 345–1000 °C and maximum peak temperature at 600 °C. At the end of the thermogram, FeO and CuO contaminated with carbon remained as residues. The overall weight loss amounted to 65.30% (calculated mass loss = 64.97%).

In the thermograph of [Zn(H₂L)(H₂O)₂Cl₂].H₂O complex, the first and second decomposition steps displayed a gradual mass loss of 39.97% (calculated mass loss = 39.60%) within the temperature range of 40–635 °C which may be correspond to the loss of three molecules of water, Cl₂ gas and C₆H₆O molecule. The DTG curve gave peaks at 83 and 281 °C (the maximum peaks temperature). The third decomposition step indicated a mass loss of 21.67% (calculated mass loss = 21.88%) which correspond to loss of C₈H₁₁N molecule within temperature range 635–1000 °C. The maximum peak temperature was at 580 °C. Finally FeO + ZnO contaminated with carbon remained as residues. The overall weight loss amounted to 61.64% (calculated mass loss = 61.48%).

The [Cd(H₂L)(H₂O)₂Cl₂].3H₂O complex lost upon heating 5H₂O molecules in the first and second steps of decomposition within the temperature range of 30–325 °C, at maximum peaks temperature at 86 and 220 °C with estimated mass loss of 13.96% (calculated mass loss = 14.15%). The third and fourth steps accounted for the loss of HCl and C₃H₄NO molecules within the temperature range of 325–615 °C, at maximum peaks temperature at 432 and 588 °C, with estimated mass loss of 16.82% (calculated mass loss = 16.75%). The final step correspond to loss of C₁₆H₁₂Cl molecule within temperature range 615–1000 °C at maximum peak temperature at 699 °C, with estimated mass loss of 37.61% (calculated mass loss = 37.66%), leaving FeO and CdO as residues of decomposition. The overall weight loss amounted to 68.39% (calculated mass loss = 68.56%).

The prepared ferrocenyl ligand had iron atom. During the synthesis of its complexes with different transition metal ions, they contain two metal atoms. Due to that, these prepared complexes were very stable and their M.P. > 300 °C. So, the residues were a mixture of ferrous oxide and transition metal oxide which became contaminated with some carbon atoms.

3.2.7 Structural interpretation

The structure of transition metal complexes were characterized and confirmed by different spectroscopic techniques. Also, TG and DTG thermal studies were investigated. Finally, the structure of all prepared metal complexes was shown in Fig. 6.

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Fig. 6

The structure of organometallic Schiff base metal complexes.

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3.2.8 Antimicrobial activities

The main goal of the preparation of any antimicrobial compound is to help in inhibiting the causal microbe on the patients without any side effects. So, organometallic Schiff base (H₂L) and its Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes were investigated for antibacterial and antifungal activities against two strain of Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), two strain of Gram-negative bacteria (Escherichia coli and Salmonella typhimurium) and two pathogenic fungus (Aspergillus fumigatus and Candida albicans). The biological data were shown in Fig. 7.

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Fig. 7

Biological activity of organometallic Schiff base ligand (H₂L) and its metal complexes.

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The data of the biological activities of the Schiff base ligand and its metal complexes against four different bacterial and two fungal species showed that the ligand and Cr(III), Mn(II), Fe(III), Ni(II), Cu(II) and Cd(II) complexes had no activity against all species. While Co(II) and Zn(II) complexes had very high bacterial activity against all bacterial species. And also, they had fungicidal activity against Aspergillus fumigatus specie with inhibition zone diameter 20 and 12 mm for Co(II) and Zn(II) complexes, respectively.

Also the activities of these compounds against Gram-positive and Gram-negative bacteria were confirmed by calculating the activity index according to the following relation (Thangadurai and Natarajan. 2001; Mahmoud et al., 2017e; Chohan et al., 2004). $$\text{Activity index}(\text{A})=[\text{Inhibition Zone of compound}(\text{mm})/\text{Inhibition Zone of standard drug}(\text{mm})]\times 100$$ From the data, it was observed that the ligand and all complexes had no activity index against all species except Co(II) and Zn(II) had very high activity index value (Mahmoud et al., 2017e).

The higher value of biological activities of some metal complexes may be attributed to their high penetrating ability to the bacteria and fungi cell wall (El-Gammal, 2010; Karekal and Mruthyunjayaswamy, 2013).

3.2.9 Anticancer activities

The in vitro cytotoxic activities of the prepared organometallic Schiff base and its metal complexes were screened against cell line of breast cancer (MCF-7). Firstly, cytotoxic activities of these compounds were calculated at single concentration 100 μg/mL against MCF-7 cell line. It was found that H₂L ligand, Cu(II) and Cd(II) complexes had inhibition ratio value 70, 74 and 78%, respectively, while other metal complexes were <60%. Secondary, the compounds with inhibition ratio value equal or higher than 70% were investigated against four concentrations (0, 12.5, 25 and 50 μg/mL) and the median inhibitory concentration (IC₅₀) values of these compounds were calculated. These activities were then showed in Fig. 8. From these results, it was showed that the Cu(II) complex had the lowest IC₅₀ value = 47.3 μg/mL which can be considered as very active compound that may be used in future as very effective antibreastic drug (Mohamed et al., 2015).

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Fig. 8

Anticancer activity against breast cancer of the Schiff bases ligand (H₂L) and its metal complexes.

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3.2.10 Molecular modeling of organometallic Schiff base ligand (H₂L), Co(II) and Zn(II) complexes: Docking study

Docking studies is considered as very active method that can be used to establish the multi-receptor interaction of the prepared Schiff base ligand to design drug resistance against different effects that occur in our bodies (Chacko and Samanta, 2017; Rauf and Shah, 2017). So, the optimized structure of the Schiff base ligand, Co(II) and Zn(II) complexes were docked with different possible biological targets such as: the receptors of crystal structure of Staphylococcus aureus (PDB ID: 4K3V), crystal structure of Salmonella typhimurium (PDB ID: 2YLB) and crystal structure of deglycating enzyme fructosamine oxidase from Aspergillus fumigatus (PDB ID: 3DJD). These bacterial and fungal species may cause some infections in skin and bone. Also, cause inflammation of sinuses and lungs. Three-dimensional structures of docking studies of all compounds were shown in Fig. 9. Furthermore, their binding energies with the three receptors were calculated and then were listed in Table 5.

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Fig. 9

3D structure of the interaction between Schiff base ligand (H₂L) with receptors of (a) 4K3V, (d) 2YLB and (g) 3DJD, 3D plot of the interaction between Co(II) complex with receptors of (b) 4K3V, (e) 2YLB and (h) 3DJD and 3D plot of the interaction between Zn(II) complex with receptors of (c) 4K3V, (f) 2YLB and (i) 3DJD.

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Fig. 9

3D structure of the interaction between Schiff base ligand (H₂L) with receptors of (a) 4K3V, (d) 2YLB and (g) 3DJD, 3D plot of the interaction between Co(II) complex with receptors of (b) 4K3V, (e) 2YLB and (h) 3DJD and 3D plot of the interaction between Zn(II) complex with receptors of (c) 4K3V, (f) 2YLB and (i) 3DJD.

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Firstly, the ligand and its Co(II) and Zn(II) complexes were studied against receptor of Gram positive bacteria such as Staphylococcus aureus (PDB ID: 4K3V) (Gribenko et al., 2013). The result showed that there was possible interaction (H-donor) between the ligand and this receptor. This interaction was increased in the Co(II) and Zn(II) complexes as H-donor and ionic bonds. The minimum binding energies for ligand, Co(II) and Zn(II) complexes were −6.5, −29.7 and −25.5 kcal mol⁻¹, respectively.

Secondary, these compounds were also investigated by molecular docking against Gram negative bacteria such as Salmonella typhimurium (PDB ID: 2YLB) (Sauer and Weichenrieder, 2011). The results indicated that the two complexes had stronger binding interaction with the receptor than the prepared ligand. The main interaction force of the ligand was H-acceptor while for complexes were H-donor and ionic bonds. The minimum binding energies for ligand, Co(II) and Zn(II) complexes were −2.0, –23.0 and −14.5 kcal mol⁻¹, respectively.

Finally, the three compounds were studied against receptor of deglycating enzyme fructosamine oxidase from Aspergillus fumigatus (PDB ID: 3DJD) (Collard et al., 2008). From the results, it was indicated that the main interaction force of the ligand was H-donor and H-acceptor, while in complexes some binding interaction also appeared beside the main interaction in the ligand such as ionic, cation-π and π-H. The minimum binding energies for ligand, Co(II) and Zn(II) complexes against this receptor were −6.1, −43.0 and −42.0 kcal mol⁻¹, respectively. So, Co(II) complex showed the best binding bonds and the lowest binding energies with the different receptors. From all of this data it was confirmed that the coordination with transition metal ions increase the activities against different bacteria and fungi and so decrease the binding energy.