BINUCLEAR Fe(III), Co(II), Ni(II), Cu(II) AND ZN(II) COMPLEXES WITH SCHIFF BASE 4, 4-(1, 4-PHENYLENE BIS(AZAN-1-YL-1- YLIDENE)) BIS(METHAN-1-YL-1-1-YLIDENE)-1, 2-DIOL. SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION

BINUCLEAR Fe(III), Co(II), Ni(II), Cu(II) AND ZN(II) COMPLEXES WITH SCHIFF BASE 4, 4^-(1, 4-PHENYLENE BIS(AZAN-1-YL-1- YLIDENE)) BIS(METHAN-1-YL-1-1-YLIDENE)-1, 2-DIOL. SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION

Amr Nassar*, Ali Hassan, Yahiya Ahmed and Ahmed Elkmash

Chemistry Department, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, Egypt

ABSTRACT

Condensation reaction of 1, 4-phenylene diamine and Protochatechu aldehyde in 1:2 molar ratio resulted in the formation of new Schiff base ligand 4, 4^-(1,4-phenylene bis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-1-ylidene)-1, 2-diol; (H₄L) .From the direct reaction of the ligand (1) with Co(II), Ni(II) and Cu(II) chlorides and Fe(III) and Zn(II)nitrates in 2M:1L molar ratio, the five new neutral complexes were prepared. The characterization of the newly formed compounds was done by ¹HNMR, U.V-Vis and IR spectroscopy and elemental analysis. The data showed tetrahedral geometry for Co, Ni, Cu and Zn complexes (3, 4, 5 and 6 respectively) and octahedral geometry for Fe complex (2). The in-vitro antibacterial activity against G^+ve bacteria (B. subtillus and S. aureus), G ^-ve bacteria (E. coli and P. aeruginosa) and antifungal activity against (C. albicans and A. niger) of the metal complexes were studied and compared with that of free ligand. Also MIC of the compounds against test microorganisms were detected.

MIC of biological evaluation

INTRODUCTION: Some Schiff bases were tested for fungicidal activity, which is related to their chemical structure ¹, there metal complexes are important in biochemical process. For example, the transamination reactions are catalyzed by metals ions through the formation of intermediate Schiff bases containing vitamin B6 ².

In the area of bioinorganic chemistry interest in Schiff base complexes has centered on the role of such complexes in providing synthetic models for the metal containing sites in metallo-proteins and enzymes ³. Schiff base ligands are potential anticancer drugs ⁴ and the anticancer activity of these metal complexes are enhanced in comparison to their free ligands ⁵.                 

3, 4-dihydroxybenzaldehyde, (Protocatechuaaldehyde, PCA) derivatives were evaluated and showed inhibition

for bacteria growth ⁶, antioxidants ⁷, antitumor ⁸, anticorrosion ⁹ and reagent in simple, rapid  and highly sensitive analysis of Cr(VI) and (V) ¹⁰ .

In the present work, new Schiff base derived from condensation of  PCA and p-phenylene diamine and its complexes were prepared and investigated using the  elemental analysis and UV-Vis, IR, ¹H-NMR spectral analysis as well as TGA and  the biological activities including MIC were studied.

MATERIALS AND REAGENTS: The analytical reagent grade (AR) 3, 4-Dihydroxy benzaldehyde, 1, 4-phenylene diamine, CoCl₂.6H₂O, NiCl₂.6H₂O, CuCl₂. 2H₂O, Fe(NO₃)₃. 9H₂O, Zn(NO₃)₂.6H₂O are Merk or Aldrich was used and Organic solvents used (methanol, ethanol, diethyl ether and acetone) were HPLC or extra pure grades and were used without further purification.

Instruments: Percentages of C, H and N were determined in the Microanalytical Laboratory. IR spectra were recorded using KBr pellets on a Perkin-Elmer 1430 Spectrometer for the region (200-4000cm^-1). Electronic spectra were measured in UV- Vis range (195- 1100 nm) using a Perkin-Elmer lambda 35 UV/Vis. The¹H-NMR spectra were recorded on DEITAZ NMR 500 MHZ Spectrometer at the National Research Centre. The mass spectra were recorded on GC- MSA- QP 5050A Shimadzu. Magnetic susceptibility measurements were carried out at room temperature on a Sherwood Scientific Magnetic Balance. Antimicrobial activity experiments were carried out.

Synthesis of Schiff base ligand (H₄L) (1): The Schiff base ligand (H₄L, 1) was prepared by dropwise addition of hot ethanolic solution (25ml) 3,4-dihydroxy benzaldehyde(1.381 g, 0.005mole) to hot ethanolic solution of 1,4-phenylene diamine (0.5405g, 0.005mole), The reaction mixture was heated under reflux for 3 hr, evaporation of solvent at r.t. allowed to appear of fine dark orange crystals, filtered, washed with ethanol, acetone and diethyl ether and air dried. M.p.160˚C; M.wt.-348.0; Anal. Calc. for C₂₀H₁₆N₂O₄: C, 68.96; H,4.59; N, 8.0%, Found: C, 68.67; H,4.60; N, 7.75%; Main IR Peaks (KBr,Cm^-1): ν(OH)3380, ν(C=N)1592.

General procedures for the Preparation of   complexes: The solid complexes; (Fig. 10 and 11) were prepared by drop-wise addition of an ethanolic solution of metal salts to an ethanolic solution of the ligand in 2:1 molar ratio metal salt: ligand, the reaction mixture refluxed for 3hr., the obtained precipitate was filtered and washed with ethanol, acetone and diethyl ether and air dried.

The complex, Fe₂L(H₂O)₆(NO₃)₂.2H₂O;(2): Black solid. M.p. >300˚c; M.wt.723.68; Anal.Calc. for C₂₀H₂₈Fe₂N₄O₁₈: C,33.19; H,3.86; N,7.7; Fe,15.43%; Found: C,33.48;H,3.4;N,6.77;Fe,15.00;   Main IR Peaks   (KBr,Cm^-1): ν(C=N)1580.

The complex, Co₂L(H₂O)₄.5H₂O;(3): Dark brown solid. M.p. 290˚C; M.wt.-623.8; Anal. Calc for C₂₀H₃₀Co₂N₂O₁₃:  C,38.48; H,4.85; N, 4.48; Co,18.9%; Found:   C, 38.45; H,4.25; N, 4.95; Co,18.25%; Main IR Peaks (KBr, Cm^-1) : ν(C=N)1596

  The complex, Ni₂L(H₂O)₄.3H₂O;(4): Dark brown solid, M.p. >300 ˚c; M.wt.587.4; Anal.Calc. for C₂₀H₂₆Ni₂N₂O₁₁: C,40.82 ;H,4.4; N,4.70; Ni,19.95%; Found: C,40.56;H,4.06;N,4.75;Ni,19.1%; Main IR Peaks (KBr,Cm^-1) : ν(C=N)1592.

2.4.4. The complex, Cu₂L(H₂O)₄.5H₂O;(5)

Black solid. M.p. >300 ˚c;M.wt.649.0;Anal.Calc. for C₂₀H₃₀Cu₂N₂O₁₄: C,36.94 ;H,4.62; N,4.30; Cu,19.50%; Found: C,36.75;H,4.45;N,3.73;Cu,19.0%; Main IR Peaks (KBr,Cm^-1): ν(C=N)1612.

The complex, Zn₂L(H₂O)₄.3H₂O;(6): Brown solid. M.p. 190˚C; M.wt.- 608.8; Anal. Calc. for C₂₀H₂₆Zn₂N₂O₁₁: C, 39.94; H, 4.35; N, 4.60 Zn, 21.72%; Found:       C, 40.07; H, 4.75;N,4.15;Zn,21.0; Main IR Peaks  (KBr,Cm^-1)  :              ν(C=N)1593.

RESULTS AND DISCUSSION: The present Schiff base ligand H₄L; (Fig. 1) was prepared by refluxing in ethanol an equimolar mixture of PCA and 1, 4-phenylene diamine. The structure of formed Schiff base was established by IR, ¹H-NMR, mass and U.V-vis spectra as well as elemental analysis. All complexes were prepared by direct reaction between Schiff base ligand H₄L and corresponding salts. The obtained complexes are stable in air and have melting points above 150˚c .They are insoluble in organic solvents such as diethyl ether and acetone, but soluble in DMF and DMSO. The elemental analysis data of the Schiff base and complexes (Section 2) are in well agreement with the expected structure.

FIGURE 1:  PROPOSED STRUCTURE OF (H₄L)

 The  molar  conductance  values  of  the  synthesized  complexes were determined  using  10^-3 M concentration   in DMF as solvent, are  in  the  range of 0.83 -1.65 Ω^-1 cm² mol ^-1 These values  suggest non-electrolyte nature for these complexes ¹¹.

Characterization of ligand (H₄L): The infrared spectrum of the Schiff base ligand (H₄L) in the region 200-4000 cm^-1showed a medium absorption band at 1592 cm^-1 assigned to the C=N stretching vibrations, indicating the formation of the Schiff base linkage. Furthermore, the absence of C=O and –NH₂ stretching vibration in the spectra of the ligand related to aldehyde and amine, respectively, indicated the occurrence of Schiff base condensation ¹².

The spectrum showed that a broad medium intensity band occurred at 3380cm^-1 assigned to νOH and the phenolic νC-OH stretching vibration was observed at 1287 cm^-1. The two weak intensity bands at 3929 and 2840 cm^-1 corresponding to ν(C-H)ar. and ν(C-H)aliph stretching vibration. νPh-N gave medium intensity band at 1172 cm^-1.

The¹H-NMR spectrum of the Schiff base ligand (Fig. 2- a, b) showed signals lying at rang 8.9-9.7ppm were due to the resonance hydroxyl groups, the signals of OH groups lying at higher field side could be attribute to the contribution of the OH group intramolecular and intermolecular hydrogen bonds. Addition of D₂O to the pervious solution results disappearance of the signal due to proton exchange. The resonance of imine proton downfield shifted to (9.6 ppm) due to the strong shielding effect of the hydroxyl groups. Also the multiple signals lying in range 6.3-7.6 ppm were attributed to resonance of aromatic protons.

The electronic spectrum of the ligand in DMF displayed bands below 330nm which were attributed to intraligand π-π* and n-π* transitions of the benzene ring and azomethine group.

The mass spectrum of the free Schiff base ligand (Fig. 3) showed its molecular ion peak at m/e=348 which was coincidence with its formula weight.

FIGURE 3: THE MASS SPECTRUM FOR (H₄L)

Characterization of the complexes:

1. Infrared spectra: The infrared spectra (table 1) of the complexes provide some information about the bonding in the complexes. The band in the IR spectrum of the ligand at 1592 cm^-1 is found to be unaffected; this is characteristic feature for uncoordination through azomethine group ¹³. Also, the νM-N bands were not appearing, due to uncomplexation via azomethine group. Deprotonation of of all phenolic functions was confirmed by the lack of  phenolic O-H stretching bands at 3380 indicating the Participation with the metal ion as –O^- ,on the other hand very broad bands observed in the spectra of the complexes in the range (3390-3427) cm^-1considerable support the presence of water molecules in the complexes ¹⁴.

The band at 1287cm^-1 in the free ligand ascribed to the phenolic C-O stretching vibration, this band was shifted to lower frequencies (1185-1216cm^-1) due to O- metal coordination ¹⁵. The weak bands appeared in the far IR    spectra   between (555-583) cm^-1 were attributed to νM-O.

The infrared spectra of complexes (2) and (6) exhibited bands around 1543, 1289 and 1125 cm^-1 due to ν(N=O), ν_asym(NO₂) and  , ν_sym(NO₂), respectively which were corresponding to nature of coordinated monodentate nitrate group ¹⁶.

TABLE 1: THE IR SPECTRA DATA FOR COMPOUNDS (1-6)

*nitrate complexes

1. Electronic spectra: The electronic spectrum of Fe⁺³ complex (2)in DMF, exhibited two bands at 440 and 320 nm assignable to the spin allowed electronic absorption of T_2g(F)         5E_g transition in octahedral configuration and charge transfer ,respectively. The magnetic moment (5.60 B.M) infers the presence of octahedral geometry around the central Fe⁺³ ion ¹⁷. The electronic spectrum of Co(II) complex (3) in DMF showed the low intensity shoulders at 590 and 654 .the former bands is probably due to ⁴A₂(F)               ⁴T₁ (P)  and  ⁴A₂(F)           ⁴T₁(F) which indicating tetrahedral geometry of this complex ¹⁸.

The magnetic moment of 4.27 BM sustained this configuration. The spectrum of the Ni(II) complex (4) in DMF showed a very broad band at 600nm indicating the ³T₁           ³T₁(P) corresponding to the tetrahedral configuration of this complex. The magnetic moment (3.2 B.M) indicated the tetrahedral geometry of the ligand around Ni ⁺² ion ¹⁹. The spectrum of Cu(II) complex (5) in DMF gave abroad band at 517nm, hence, the copper complex appear to be in tetrahedral geometry. The µeff value (1.7 B.M) was corresponding to tetrahedral geometry arrangement of the ligands around the Cu⁺² ion ²⁰. The electronic absorption spectrum of Zn(II)complex (6) in DMF showed only charge transfer transition which can be assigned to charge transfer from the ligand to the metal and vice versa and no d-d transition are expected for d¹⁰ Zn(II) complexes ²¹.

1. The ¹H-NMR spectra: The ¹H-NMR spectrum of the zinc complex (Fig.4a) recorded in DMSO-d6 at room temperature. In the spectrum of the complex the phenolic protón signals observed at δ 8.9-9.7 ppm in the spectrum of the free ligand was found to be absent, confirming subsequent involvement of deprotonated hydroxyls in chelation to the metal ions. The strong broad signal appeared at δ 4.4 ppm which not found in the spectrum of the free ligand due to resonance of protons of coordinated water molecules.  Addition of D₂O to the previous solution showed the absence of the signal due to proton exchange (Fig. 4b).

1. Thermal analysis: The thermogravimetric analysis (TGA); Figuress 5-8, curves for complexes (2, 3, 4 and 5), respectively were obtained at a heating rate of 10⁰C/min and flowing nitrogen atmosphere over a temperature range of 20–1000C and recorded in table 2. The decomposition temperature and the weight losses of the complexes were calculated from TGA data.

FIG. 8: TG AND DTG OF COMPLEX (6)

TABLE 2: THERMAL GRAVIMETRIC ANALYSIS FOR COMPOUNDS (2, 3, 4 AND 6)