Introduction

Schiff bases are one of the most prevalent ligands in coordination chemistry. Their metal complexes have a variety of biological, medicinal and analytical applications, in addition to their important roles in catalysis and organic syntheses [1–9]. Schiff bases with oxygen and nitrogen donor atoms operate as good chelating agents for both transition and non-transition metals [10–13]. Complexes with tetradentate N2O2 donor set Schiff base ligands have been used as models for metalloproteins, for example oxygen transport proteins [14]. There are a few reports of the synthesis and structural characterization of potentially tetradentate salicylaldimine Schiff base ligands with Zr(IV) [15–19]. Solari et al. used salophen (salicylaldiminatophenylenediamine) for the synthesis of eight-coordinate Zr(IV) complexes, giving both dodecahedral and square antiprismatic coordination geometries. A comparative study of antibacterial activities by Al-Resayes et al. [20] showed that the free Schiff base was inactive, while its complexes showed considerable antibacterial activity. Other studies have also revealed the antibacterial properties of Schiff base complexes [21]. However, to date, there are only limited reports on the biological activity of zirconium Schiff base complexes. In the current project, we synthesized two zirconium(IV) Schiff base complexes based on Schiff base ligands derived from 4,5-dimethyl-1,2-phenylenediamine and 2,2-dimethyl-1,3-propanediamine, as shown in Scheme 1. The complexes were characterized using FTIR, lH NMR and 13C{1H} NMR, elemental analyses and single-crystal X-ray diffraction. The in vitro biological activities of the complexes were evaluated against Staphylococcus aureus and Escherichia coli.

Scheme 1
scheme 1

Structural formulae of the complexes

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Experimental

Materials and methods

All chemicals were of reagent grade and used without further purification. 1H and 13C{1H} NMR spectra were recorded at ambient temperature with a BRUKER AVANCE 400 MHz spectrometer using CDCl3 as solvent. The chemical shift values (δ) are given in ppm. Infrared spectra were recorded using KBr disks on an FTIR Prestige21 spectrophotometer. C, H and N microanalyses were obtained with a LECO CHNS-932 elemental analyzer. X-ray data for the complexes were collected at 293(2) K on a Bruker Smart APEX CCD diffractometer (Mo K α  = 0.71073 Å). Full spheres of reciprocal lattice were scanned by 0.3° steps in omega with a crystal–to–detector distance of 5 cm. Cell refinement and data reduction were performed with the help of the SAINT program [22]. Corrections for absorption were made with the multi-scan method and SADABS program [22]. The structures were solved with direct methods using SHELXL-2014, and structure refinement on F 2 was carried out with the SHELXL-2014 program [23]. All non-hydrogen atoms were refined using anisotropic displacement parameters. All calculations were done with PLATON [24]. Four ethyl groups in the Zr(L)2 complex were disordered over two positions with a refined site occupancy ratio of 0.729(6)/0.271(6) and 0.623(6)/0.377(6).

Syntheses of H2L and H2L′

To a stirred MeOH (20 mL) solution of 3-ethoxy-salicylaldehyde (0.66 g, 4 mmol) was added a MeOH (20 mL) solution of 4,5-dimethyl-1,2-phenylenediamine (0.27 g, 2 mmol) or 2,2-dimethyl-1,3-propanediamine (0.21 g, 2 mmol). The reaction mixture was heated at reflux for 1 h, and upon cooling to room temperature, the resulting precipitate was collected by suction filtration and washed with cold MeOH (3 × 10 mL) to afford the desired Schiff base. The Schiff bases were spectroscopically pure and used as obtained for the synthesis of the corresponding zirconium complexes. The crystal structures of the free Schiff bases were reported previously [25, 26].

(3-ethoxysalicylidene)-4,5-dimethyl-1,2-phenylenediamine (H2L)

Bright orange solid. Yield: 0.81 g (93%); m.p.: 89° C. Anal. calcd. for C26H28N2O4 (%): C, 72.20; H, 6.53; N, 6.48. Found: C, 72.14; H, 6.61; N, 6.37. IR (KBr, cm−1): 1614 (C=N), 1575, 1463 (C=C), 1249 (C–O). 1H NMR (400 MHz, CDCl3, ppm): δ = 13.40 (s, 2 H, O–H), 8.63 (s, 2 H, HC=N), 7.03 (d, 3 J = 7.8 Hz, 2 Hc), 7.01 (s, 2 Hd), 6.98 (d, 3 J = 7.8 Hz, 2 Ha), 6.86 (d, 3 J = 7.8 Hz, 2 Hb), 4.16 (q, 3 J = 7.0 Hz, 4 H, –CH2–CH3), 2.35 (s, 6 H, CH3), 1.53(t, 3 J = 7.0 Hz, 6 H, CH3–CH2–).

(3-ethoxysalicylidene)-2,2-dimethyl-1,3-propanediamine (H2L′)

Bright yellow solid. Yield: 0.69 g (87%); m.p.: 97° C. Anal. calcd. for C23H30N2O4 (%): C, 69.32; H, 7.59; N, 7.03. Found: C, 69.57; H, 7.66; N, 6.92. IR (KBr, cm−1): 1637 (C=N), 1570, 1458 (C=C), 1246 (C–O). 1H NMR (400 MHz, CDCl3, ppm): δ = 14.05 (s, 2 H, O–H), 8.35 (s, 2 H, HC=N), 6.96 (dd, 3 J = 7.8 Hz, 4 J = 1.2 Hz, 2 H, Hc), 6.91 (dd, 3 J = 7.8 Hz, 4 J = 1.2 Hz, 2 H, Ha), 6.82 (t, 3 J = 7.8 Hz, 2 H, Hb), 4.16 (q, 3 J = 7.0 Hz, 4 H, –CH2–CH3), 3.53 (s, 4 H, –CH2–N), 1.53 (t,, 3 J = 7.0 Hz, 6 H, CH3–CH2–), 1.13 (s, 6 H, CH3).

Syntheses of the complexes

Zr(L)2: [bis(3-ethoxysalicylidene)-4,5-dimethyl-1,2-phenylenediamine] zirconium(IV): A solution of Zr(acac)4 (0.49 g, 1 mmol) in methanol (10 ml) was added to a solution of bis(3-ethoxysalicylidene)-4,5-dimethyl-1,2-phenylenediamine (0.86 g, 2 mmol) in methanol (20 ml). The mixture was refluxed for 5 h, then filtered. The solvent was evaporated, and the orange precipitate was recrystallized from methanol to obtain the pure complex. Suitable crystals of the complex for crystal structure determination were obtained upon slow evaporation at room temperature from methanol solution within a week. The complex was characterized by 1H NMR, 13C{1H} NMR, IR, elemental analyses and single-crystal X-ray diffraction.

Anal. calcd. for C52H52N4O8Zr (%): C, 65.59; H, 5.50; N, 5.88. Found: C, 65.55; H, 5.55; N, 5.90. IR (KBr, cm−1): 1616, 1593 (C=N), 1548, 1452 (C=C), 1305 (C–O), 550 (Zr–O), 416 (Zr–N). 1H NMR (400 MHz, CDCl3, ppm): δ = 8.81 (s, 2 H, Hi′–C=N), 8.19 (s, 2 H, Hi–C=N), 7.61 (s, 2 H, Hd′), 6.96 (dd, 3 J = 8.6, 4 J = 2.9 Hz, 2 H, Hc′), 6.82 (dd, 3 J = 8.6, 4 J = 3.2 Hz, 2 H, Hc), 6.57 (t, 3 J = 7.7 Hz, 2 H, Hb′), 6.49 (d, 3 J = 6.6 Hz, 2 H, Ha′), 6.47 (t, 3 J = 7.7 Hz, 2 H, Hb), 6.42 (s, 2 H, Hd), 6.36 (d, 3 J = 7.0 Hz, 2 H, Ha), 3.86 (dq, 2 J = 13.9, 3 J = 6.9 Hz, 2 H, Hf′), 3.72 (dq, 2 J = 13.9, 3 J = 6.9 Hz, 2 H, Hf), 3.62 (dq, 2 J = 13.9, 3 J = 6.9 Hz, 2 H, He′), 3.49 (dq, 2 J = 13.9, 3 J = 6.9 Hz, 2 H, He), 2.42 (s, 6 H, –CH3(m′)), 2.17 (s, 6 H, –CH3(m)), 1.42 (t, 3 J = 6.9 Hz, 6 H, –CH3(o′)), 1.35 (t, 3 J = 6.9 Hz, 6 H, –CH3(o)).

13C{1H} NMR (100 MHz, CDCl3, ppm): δ = 160.54, 159.09, 157.77, 155.25, 150.74, 149.34, 143.60, 143.16, 135.33, 134.59, 124.59, 123.62, 122.72, 121.87, 118.38, 117.97, 115.58, 114.95, 114.27, 112.92, 62.92, 62.86, 20.19, 19.67, 15.01, 14.47.

Zr(L′)2: [bis(3-ethoxysalicylidene)-2,2-dimethyl-1,3-propanediamine] zirconium(IV): A solution of Zr(acac)4 (0.49 g, 1 mmol) in methanol (10 ml) was added to a solution of bis(3-ethoxysalicylidene)-2,2-dimethyl-1,3-propanediamine (0.80 g, 2 mmol) in methanol (20 ml). The mixture was refluxed for 5 h, then filtered. The solvent was evaporated, and the yellow precipitate was recrystallized from methanol to obtain the pure complex. Suitable crystals of the complex for crystal structure determination were obtained upon slow evaporation at room temperature from methanol solution within a week. The complex was characterized by 1H NMR, 13C{1H} NMR, IR, elemental analyses and single-crystal X-ray diffraction.

Anal. calcd. for C46H58N4O8Zr (%): C, 62.34; H, 6.60; N, 6.32. Found: C, 62.16; H, 6.72; N, 6.18. IR (KBr, cm−1): 1624, 1597 (C=N), 1556, 1467 (C=C), 1313 (C–O), 551 (Zr–O), 426 (Zr–N). 1H NMR (400 MHz, CDCl3, ppm): δ = 8.09 (s, 4 H, Hi–C=N), 6.64 (dd, 3 J = 7.6, 4 J = 1.6, 4 H, Hc), 6.38 (dd, 3 J = 7.6, 4 J = 1.6, 4 H, Ha), 6.33 (t, 3 J = 7.6, 4 H, Hb), 5.81 (d, 2 J = 10.8, 4 H, Hd′), 3.89 (q, J = 7.2, 8 H, –CH2(f)–), 2.92 (d, 2 J = 10.8, 4 H, Hd), 1.32 (s, 12 H, –CH3(e)), 1.27 (t, J = 7.2, 12 H, –CH3(g)).

13C{1H} NMR (100 MHz, CDCl3, ppm): δ = 165.49, 154.86, 148.76, 123.41, 122.26, 114.50, 113.71, 68.59, 63.14, 37.44, 25.82, 15.18.

Antibacterial activities

Antibacterial activities of the free Schiff bases and their zirconium(IV) complexes were assayed in vitro against the bacterial species E. coli ATCC 25922 (gram negative) and S. aureus ATCC 25923 (gram positive) by the disk diffusion method. The antibacterial tests used 64 μg/mL concentrations of the test compounds dissolved in DMSO. Bacteria culture Petri dishes treated with the test compounds were incubated for 24 h at 37 °C. The antibacterial activity was determined by evaluating the inhibition zone (mm), MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration). MIC is the lowest concentration of an antimicrobial compound that inhibits the noticeable growth of microorganisms at 37 °C after overnight incubation. The MIC values of the test compounds were assayed against bacterial strains through a broth dilution method, using test compound concentrations from 0.128 to 0.00025 mg/ml in DMSO.

Results and discussion

Syntheses and spectroscopic characterization

The Schiff bases were synthesized from 4,5-dimethyl-1,2-phenylenediamine and 2,2-dimethyl-1,3-propanediamine, respectively, in a Schiff base condensation reaction with 3-ethoxy-salicylaldehyde, in methanol. Reaction of Zr(acac)4 and H2L or H2L′, in refluxing methanol, afforded the neutral zirconium(IV) complexes. Both Schiff bases and the related complexes were obtained in high yields and are stable in the solid state and in solution. The complexes are insoluble in ethanol, methanol, n-hexane, acetone and acetonitrile but soluble in chloroform, dichloromethane, warm DMSO and DMF.

The stretching frequencies of the C=N and C–O bonds of the free Schiff bases and their corresponding Zr(IV) complexes are reported in Table 1. The strong bands around 1614 and 1637 cm−1 due to the azomethine group in the free Schiff bases are shifted to lower wavenumbers, appearing at 1593–1624 cm−1 in the spectra of the complexes. This indicates the involvement of azomethine nitrogen in coordination [27]. The C–O stretching bands of the free Schiff bases shift from 1246–1249 to 1305–1313 cm−1 upon coordination to Zr [28]. Medium sharp bands at 550, 551 cm−1 and 416, 426 cm−1 in the spectra of the complexes can be related to Zr–O and Zr–N bonds, respectively [29].

Table 1 IR spectral data of the Schiff bases and their corresponding Zr(IV) complexes
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The 1H and 13C{1H} NMR spectra of the complexes are shown in the supporting information (Figs. S1–S4). The 1H NMR spectra show the absence of a phenolic proton signal and downfield shift of the azomethine H, confirming coordination of the phenolic oxygen and azomethine nitrogen to the metal. The presence of two 1H NMR peaks for the azomethine protons in the Zr(L)2 complex is indicative of the magnetic non-equivalence of these protons. Similarly, on coordination of H2L to Zr, the CH2 protons become non-equivalent and a geminal coupling (2 J = 13.9 Hz) is observed. The 13C{1H} NMR spectra of the of zirconium(IV) complexes are in agreement with the 1H NMR data. Thus, Zr(L)2 and Zr(L′)2 (Figs. S2 and S4) show two and one resonances for the iminic carbon, respectively. According to the 13C{1H} NMR spectra, the Zr(L)2 and Zr(L′)2 complexes have 26 and 12 signals, respectively, indicating that the structures in solution are different. Hence, the complex of H2L is assigned a dodecahedral geometry, while H2L′ gives a square antiprism geometry.

X-Ray crystal structures

The solid-state structures of Zr(L)2 and Zr(L′)2 were determined by X-ray diffraction. The crystal data and refinement parameters are summarized in Table 2, and ORTEP plots of Zr(L)2 and Zr(L′)2 are shown in Fig. 1. Selected bond lengths and angles are summarized in Table 3. The metal in Zr(L)2 is eight-coordinate, such that the N2O2 planes of the two Schiff bases intersect perpendicularly [dihedral angle of 89.56(5)°] giving rise to a dodecahedral arrangement of the nitrogen and oxygen atoms (Fig. 2). The bond lengths and angles and the geometry around the Zr atom in Zr(L)2 are comparable to those of previously reported structures [15, 18, 19]. The asymmetric unit of Zr(L′)2 comprises two chemically equivalent but crystallographically independent molecules. The eight-coordination around zirconium in Zr(L′)2 is provided by the nitrogen and oxygen atoms of two Schiff base ligands. In each complex, the ligands coordinate in a bis-bidentate mode in which the N2O2 donor atoms of the different ligands occupy top and bottom coordination sites of Zr. The bond lengths and angles and the geometry around the Zr atom in Zr(L′)2 are comparable to those of a previously reported structure [17]. The resulting coordination polyhedron around zirconium can be described as a distorted square antiprism, with the N2O2 cores of the two ligands defining the bases (Fig. 2). The N2O2 cores are close to planarity (maximum displacements 0.0376(9), −0.044(1), −0.0484(9) and 0.0604(9) Å for N1/N3/O1/O5, N2/N4/O3/O7, N5/N8/O10/O14 and N6/N7O9/O13, respectively) and nearly parallel to each other (dihedral angle 0.79(4) and 0.36(6)° in the crystallography independent Zr1 and Zr2 complexes, respectively). An interesting feature of the crystal packing of Zr(L′)2 is the intermolecular C5–H5…O9B, O9B–H1W2…O3 and O9B–H2W2…O4 interactions which make two parallel infinite chains of the complexes running along the a-axis.

Table 2 Crystal data and refinement parameters for Zr(L) 2 and Zr(L′) 2
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Fig. 1
figure 1

ORTEP plots of Zr(L)2 (left) and Zr(L′)2 (right, only one complex with major component) with atom numbering and ellipsoids probability at 30%

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Table 3 Selected bond lengths (Å) and angles (°) of Zr(L) 2 and Zr(L′) 2
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Fig. 2
figure 2

The dodecahedral (left) and square antiprism (right) geometries of the ligands around Zr1 in Zr(L)2 and Zr(L′)2

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Antibacterial activities

The free Schiff bases and their Zr complexes were tested for their in vitro antibacterial activities. The minimum inhibitory concentrations (MIC) values are summarized in Table 4. As is frequently observed, the complexes exhibit higher antibacterial activities than the free ligands. Thus, the free ligands have low inhibitory effects on the growth of the test organisms. Zr(L)2 was the most effective compound against both bacteria, with MIC values of (0.001–0.004 mg/ml). The better performance of Zr(L)2 compared to Zr(L′)2 may be due to the lower polarity of the former, allowing for easier crossing of cell membranes. Comparison of the antibacterial properties of the present zirconium complexes with similar examples in the literature indicates that our new complexes are more potent. [30, 31].

Table 4 The inhibition diameter zone values (mm), MIC and MBC for ligands and its Zr complexes
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Conclusion

In this paper, the preparation and crystal structures of two eight-coordinate zirconium(IV) Schiff base complexes have been reported. In these complexes, the Zr(IV) centers adopt either dodecahedral or square antiprismatic geometries on the basis of steric hindrance and the flexibility of the diamine segment of the Schiff base ligand. The in vitro biological screening experiments showed higher activities for the complexes compared to the free Schiff bases.

Supplementary materials

CCDC 1525264 and 1525265 contain the supplementary crystallographic data for complexes. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.