and Synthesis, Characterization and Crystal Structures of Zinc(II) and Cobalt(III) Complexes Derived from Tridentate NNO- and NON- Schiff Bases with Antibacterial Activities

Two new polynuclear zinc complexes [Zn 2 Br 2 (L 1 ) 2 ] ( 1 ) and [Zn( μ 1,5 -dca)L 2 ] n ( 2 ), and two new mononuclear cobalt(III) complexes [CoL 1 N 3 (Brsal)] ( 3 ) and [CoL 2 (HL 2 )] ( 4 ), where L 1 = 5-bromo-2-(((2-dimethylamino)ethyl)imino)methyl) phenolate, L 2 = 5-bromo-2-(((2-hydroxyethyl)imino)methyl)phenolate, dca = dicyanoamide, Brsal = 5-bromo-2-formyl-phenolate, have been synthesized and characterized. The complexes were characterized by elemental analyses, IR, UV-Vis spectra, molar conductivity, and single crystal X-ray diffraction. X-ray analysis indicates that the Zn atoms in complex 1 are in distorted square pyramidal coordination, the Zn atoms in complex 2 are in distorted trigonal bipyramidal coordination, and the Co atoms in complexes 3 and 4 are in octahedral coordination. The molecules of the complexes are stacked through π···π interactions and hydrogen bonds. The complexes were assayed for antibacterial activities against three Gram-positive bacterial strains ( B. subtilis , S. aureus , and St. faecalis ) and three Gram-negative bacterial strains ( E. coli , P. aeruginosa , and E. cloacae ) by MTT method. Qian: Synthesis, Characterization and Crystal Structures ...


Introduction
Schiff bases are an important class of organic compounds and a great number of Schiff base compounds have been prepared due to their facile synthesis. These compounds have received considerable attention in pharmaceutical fields because of their excellent biological activities. 1 Moreover, Schiff bases are a kind of significant ligands in coordination chemistry, which can form versatile structures with interesting biological, magnetic, catalytic and photoluminescent properties. 2 In recent years, much efforts have been paid on zinc and cobalt complexes with Schiff base ligands due to their indispensable application in biological area such as antimicrobial agents. 3 We have reported some manganese and zinc complexes with antibacterial activities. 4 In continuation of our work on the exploration of new antibacterial agents, we report herein the synthesis, characterization including single crystal X-ray structures of two new zinc(II) and two new cobalt(III) complexes, [Zn-2 Br 2 (L 1 ) 2 ] (1), [Zn(μ 1,5 -dca)L 2 ] n (2), [CoL 1 N 3 (Brsal)] (3) and [CoL 2 (HL 2 )] (4), where L 1 = 5-bromo-2-(((2-dimethylamino)ethyl)imino)methyl)phenolate, L 2 = 5-bromo-2-(((2-hydroxyethyl)imino)methyl)phenolate, dca = dicyanoamide, Brsal = 5-bromo-2-formylphenolate. The antibacterial activity against three Gram-positive bacterial strains (B. subtilis, S. aureus, and St. faecalis) and three Gram-negative bacterial strains (E. coli, P. aeruginosa, and E. cloacae) by MTT method was studied. N,diamine and 2-aminoethanol were purchased from Sigma-Aldrich. All other reagents and solvents were purchased from commercial sources and used as received. FT-IR spectra were recorded as KBr pellets on Bruker Tensor-27. Elemental (C, H, and N) analyses were performed on a Perkin-Elmer 2400 II analyzer. Electronic spectra were obtained with Lambda 35 spectrophotometer. Single crystal X-ray diffraction was carried out with a Bruker Apex II CCD diffractometer. Molar conductivity of the complexes in methanol was measured with a DDS-11A molar conductivity meter.

1. Materials and Physical Methods
Caution! Azide complexes of metal ions are potentially explosive. Only a small amount of material should be prepared, and they should be handled with caution.

6. X-Ray Structure Determination
Intensity data of the complexes were collected at 298(2) K on a Bruker Apex II CCD diffractometer using graphite-monochromated MoK a radiation (λ = 0.71073 Å). For data processing and absorption correction the packages SAINT and SADABS were used. 5 Structures of the complexes were solved by direct and Fourier methods and refined by full-matrix least-squares based on F 2 using SHELXL. 6 The non-hydrogen atoms were refined anisotropically. The H atoms of the hydroxyl groups of complexes 2 and 4 were located from difference Fourier maps and refined with O-H distances restrained to 0.85(1) Å. The remaining hydrogen atoms have been placed at geometrical positions with fixed thermal parameters. Crystallographic data of the complexes are summarized in Tables 1a and 1b. Selected bond lengths and angles are listed in Table 2.

7. Antibacterial Activity
Antibacterial activity of the complexes was tested against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. coli, and E. cloacae using MTT medium. The minimum inhibitory concentrations (MICs) of the compounds were determined by a colorimetric method using MTT dye. 7 A stock solution of the compounds (50 μg mL -1 ) in DMSO was prepared and quantities of the compounds were incorporated in specified quantity of sterilized liquid medium. A specified quantity of the medium containing the compounds was poured into micro-titration plates. Suspension of the microorganism was prepared to contain approximately 10 5 cfu mL -1 and applied to micro-titration plates with serially diluted compounds in DMSO to be tested, and incubated at 37ºC for 24 h for bacteria. After the MICs were visually determined on each micro-titration plate, 50 μL of phosphate buffered saline (PBS 0.01 mol L -1 , pH 7.4: Na 2 HPO 4 · 12H 2 O 2.9 g, KH 2 PO 4 0.2 g, NaCl 8.0 g, KCl 0.2 g, distilled water 1000 mL) containing 2 mg mL -1 of MTT was added to each well. Incubation was continued at room temperature for 4-5 h. The content of each well was removed, and 100 μL of isopropanol containing 5% 1 mol L -1 HCl was added to extract the dye. After 12 h of incubation at room temperature, the optical density (OD) was measured with a microplate reader at 570 nm.

1. Chemistry
Reaction of the newly formed Schiff base HL 1 with zinc bromide affords the dinuclear zinc complex 1, with cobalt chloride and sodium azide affords the mononuclear cobalt complex 3. Similarly, reaction of the newly formed Schiff base HL 2 with zinc nitrate and sodium dicyanoamide affords the polynuclear zinc complex 2, with cobalt nitrate affords the mononuclear cobalt complex 4. The poor conductivity of the complexes (20-45 Ω -1 cm 2 mol -1 ) indicated that the ligands are coordinated to the metal centers and are not dissociated in solution. 8

2. Infrared and Electronic Spectra
In the infrared spectra, the weak absorptions at 3635 cm -1 for 2 and 3427 cm -1 for 4 are assigned to the hydroxyl groups of the Schiff base ligands. The characteristic imine stretching of the complexes is observed at 1643-1647 cm -1 as strong signal. 9 In the spectrum of 2, appearance of intense bands at 2341, 2275 and 2195 cm -1 indicates the presence of dicyanoamide ligand. 10 In the spectrum of 3, appearance of intense band at 2027 cm -1 indicates the presence of azide ligand. 11 The Schiff base ligands coordination is substantiated by the phenolic C-O stretching bands at 1170-1200 cm -1 in the four complexes. 12 Coordination of the Schiff bases is further confirmed by the appearance of weak bands in the low wave numbers 400-600 cm -1 , corresponding to ν(M-N) and ν(M-O  (7) Co3-O10 1.912 (7) Co3-O11 1.861 (7) Co3-O12 1.941(6) Co3-N5 1.920 (8) Co3-N6 1.909 (7) Co4-O13 1.884 (7) Co4-O14 1.912 (8)   The electronic spectra of the complexes exhibit typical bands centered at 320-360 nm which can be assigned to ligand to metal charge transfer. 14 The bands at 220-250 nm and 260-280 nm are attributed to the π-π* and n-π* transitions. 15

4. Structure Description of Complex 2
Molecular structure of complex 2 is shown in Fig.  3. The [ZnL 2 ] units are linked by μ 1,5 -dca ligands, to form zigzag chain structure. The Zn atom is coordinated in distorted trigonal bipyramidal geometry as evidenced by the τ value of 0.65. 16 The basal plane of the trigonal bipyramidal coordination is defined by the imino N atom of the Schiff base ligand and two terminal N atoms from two dca ligands. The axial positions of the trigonal bipyramidal coordination are occupied by the phenolate O and hydroxyl O atoms of the Schiff base ligand. The Zn atom deviates from the basal plane by 0.195(2) Å. The trigonal bipyramidal geometry is distorted from ideal model, as evidenced by the bond angles. The angles in the basal plane are in the range of 108.2(3)-128.6(3)º. The bond angles among the axial and basal donor atoms are in the range of 76.8(3)-98.7(3)º. And, the two axial donor atoms form an angle of 167.5(2) º with the Zn atom. The distortion is mainly caused by the strain created by the five-membered chelate ring Zn1-N1-C8-C9-O2. The Zn-O and Zn-N bond lengths are comparable to those observed in dca coordinated Schiff base zinc complexes. 18 As shown in Fig. 4, the [CuL 2 ] units are bridged by μ 1,5 -dca ligands, to form zigzag chain along the a axis. The chains are further linked through O-H···O hydrogen bonds (Table 3)

5. Structure Description of Complex 3
Molecular structure of complex 3 is shown in Fig. 5. The Co atom is coordinated by one Schiff base ligand, one 5-bromo-2-formylphenolate ligand and one azide ligand, forming octahedral coordination. The equatorial plane of the octahedral coordination is defined by the phenolate O, imino N and amino N atoms of the Schiff base ligand, and the carbonyl O atom of the 5-bromo-2-formylphenolate ligand. The axial positions of the octahedral coordination are occupied by the phenolate O atom of the 5-bro-mo-2-formylphenolate ligand, and the azide N atom. The Co atom deviates from the equatorial plane by 0.003(2) Å. The octahedral geometry is distorted from ideal model, as evidenced by the bond angles. The cis and trans angles in the equatorial plane are in the ranges of 86.3(2)-95.0(2) º and 178.2(2)º, respectively. The bond angles among the axial and equatorial donor atoms are in the range of 87.0(2)-94.0(2)º. And, the two axial donor atoms form an angle of 175.5(2)º with the Co atom. The distortion is mainly caused by the strain created by the five-membered chelate ring Co1-N1-C8-C9-N2. The Co-O and Co-N bond lengths are comparable to those observed in azide coordinated Schiff base cobalt complexes. 19 As shown in Fig. 6, the molecules are linked through C-H···N hydrogen bonds (Table 3), to form one dimensional chains along the b axis. The chains are further linked by weak Br···N interactions along the c axis to form a two dimensional sheets parallel to the bc plane.

7. Antibacterial Activities
The two complexes and the free Schiff base were screened for antibacterial activities against three Gram-positive bacterial strains (B. subtilis, S. aureus, and St. faecalis) and three Gram-negative bacterial strains (E.

Acknowledgments
This project was supported by the Henan Province Universities and Colleges Funded Scheme (21A530010).

Conclusion
In summary, two new polynuclear zinc(II) complexes and two new mononuclear cobalt(III) complexes with tridentate Schiff base ligands have been synthesized. Single crystal structures of the complexes were confirmed by X-ray diffraction method and described. The antibacterial assay of the complexes indicates that the zinc complexes are prospective antibacterial agents for B. subtilis and St. faecalis.