INTRODUCTION:

The co-ordination chemistry of organic transition metal complexes of Schiff base ligand with donor groups like N, O gained importance for more than two decades because of their uses as models of biological systems^(1-3), including antibacterial⁽⁴⁾, antifungal⁽⁵⁾, antitumour⁽⁶⁾, and anti-inflammatory activities⁽⁷⁾. Now a day’s chemist are very much focused on the Schiff base derived from heterocyclic ring with carbonyl compounds as it important special centre of attraction in many areas like biological clinical, analytical and pharmacological field etc^(8-10). 0Among them 4-aminoantipyrine based heterocyclic had a great importance as it is abundant in nature and have wide pharmacological activities⁽¹¹⁾.

EXPERIMENTAL:

Mebendazol (MBZ), 4-Aminoantipyrine, vanadyl(II) sulfate mono hydrate, manganis(II) chloridetetrahydrate, cobalt(II) chloridehexahydrate, nickel(II) chloridehexahydrate, cupper(II) chloridedehydrate, cadmium(II) chloride, zinc(II) chloride and mercury(II) chloride, DMSO, methanol and ethanol were provide from Aldrich company. Melting points for prepared complexes were measured by electro thermal (Stuart melting point apparatus). Infrared spectra were performed using a Shimadzu (FT–IR)–8400S, The electronic spectra of the compounds were recorded by using double-beam (U.V-Vis) spectrophotometer type U.V 160A (Shimadzu), Elemental micro analysis recorder by using Euro Vector, model EA 3000 single V.3.Osinglein, The Chloride contents were determined using (686-Titro processor-665. Dosimat Matron Swiss), Electrical conductivity measurements of the complexes were recorder at (25ºC) for (10^-3 mole.L^-1) solution of the samples in DMSO by using (conductivity meter, model 4070), Magnetic measurements of the metal complexes were performed on a Magnetic Susceptibility Balance Mode (MSB _MKI), ¹HNMR, acquired using a Brucker-400 MHz and 200 MHz for ¹³C-NMR, thermogravimetriv analysis(TGA) was carried out using STA PT-1000 Linseis company /Germany.

Synthesis of Schiff base ligand (L):

A solution of (4-aminoantipyrine) [0.2g, 1mmole] in (10ml ethanol) was added to a solution of (mebndazole) [0.29g, 1 mmole] in (10ml ethanol) and 3drops of HBr 48%. The mixture was refluxed for (30 hrs.) with stirring. The orang colored solid mass formed during refluxing was cooled to room temperature, filtered and washed by ethanol and recrystallized by (methanol ) to get a pure sample.Yield 78%, M.P.: 237-240^oC, M.wt : 480.30 gm/mol (C₂₇H₂₄N₆O₃). see scheme (1)

Scheme 1. Synthesis role of new Schiff base (L).

Synthesis of Schiff base complexes:

Synthesis of [(VO)(L)₂SO₄].H₂O:

A solution of (0.181g, 1mmole) of Vanadyl(II) Sulfate monohydrate dissolved in (10mL) of ethanol was added drop wise to a solution of [L] (0.960g, 2mmole) dissolved in (15mL) methanol. The reaction mixture was allowed to reflux for (3hrs.). A green precipitate was formed, which filtered off, washed several times with absolute ethanol and dried. Yield (79%) of the title complex, m.p. (151 – 153ºC).

Synthesis of other complexes:

Each of a hot EtOH solution (10 mL) of (0.197, 0.237, 0.237, 0.170, 0.136, 0.183, 0.271g,1mmole) of Mn(II), Co(II), Ni(II), Cu(II), Cd(II), Zn(II) and Hg(II) resoectyvely and hot methanol solution (15 mL) of (L) (0.960g g, 2mmole) were mixed in round flask with constant stirring,the mixture refluxed for an 3hrs. at (70°C), A colored complexes was precipitated, filtered and washed several times with cool ethanol.

RESULTS AND DISCUSSION:

Characterization of ligand (L):

The I.R. spectrum for (L):

Fig.(2), which exhibits the strong band at (1645)cm^-1indicates stretching frequency of carbonyl group u(C=O) of 4-AAP ring. On the other hand a new band at (1635) cm¹related to stretching frequency of imine (C=N)⁽¹²⁾. The band at (1357) cm^-1 where assigned to u(C-N) and a band at (1597) can be refer to u(C=N) stretching of MBZ.The stretching frequency of u(N-N)of five member ring appeared at (1082).The appearance of iminic band and the disappearance of carbonyl(C=O) band of MBZ in the ligand spectrum and disappearance of amino group (NH₂) band in the ligand, confirms the formation of Schiff base ligand⁽¹³⁾.

The electronic spectrum date of (L):

showed two high absorption peaks, the first at (263)nm (38023)cm^–1 resulted from electronic transition π→π*, the other peak appeared at (319) nm (31348)cm^-1resulted from electronic transition π→π*⁽¹⁴⁾ ¹H-NMR spectrum for the ligand L: In solution, it is clear that an intramolecular hydrogen bonding between the hydrogen of the N-H groups and the oxygen of the carbonyl group occurred. This phenomenon has been confirmed by the NMR spectra.¹HNMR spectrum for (L), in DMSO-d⁶ displayed The broaden hump signal at (δ_H =11.72-12.34ppm,2H) is due to the alter hydrogen bonding process occurred between the protons of the (N-H) groupsand the ion pairs of oxygen atoms of carbonyl group .The broadness of these signals could be related to hydrogen bonding (N–H…..O)⁽¹⁵⁾. The resonances at chemical shift (δ_H = 7.49 - 7.73ppm) (Ar–H) are assignable to protons of aromatic ring. The appearances of these protons as a multi are due to mutual coupling. Signal at chemical shift (δ_H =3.78 ppm) returns to protons group (CO₂CH₃)⁽¹⁶⁾. The sharp singlet signals at (δ_H = 3.18 and 2.49 ppm) equivalent to six protons (6H, S) is attributed to the protons of methyl group. The spectrum displayed chemical shifts at (δ_H = 2.56 ppm and 3.39 ppm) referred to the DMSO solvent, and the presence of water molecules in the solvent respectively. The ¹³CNMR spectrum of (L) in DMSO-d6solvent shows chemical shift at range (δ= 114.05-138.38 ppm) assigned to aromatic carbon atoms.The chemical shifts at (δ=167.55 ppm) attributed to the carbonyl carbon atom (C₁₈). The chemical shift at (δ=160.39 ppm) attributed to the imine carbon atom (C₂)⁽¹³⁰⁾. The chemical shift at (δ=154.33 ppm) attributed to the carbonyl carbon atom (C₁₀). The chemical shift at (δ=150.37ppm) attributed to the (C₁₉), while the chemical shift at (δ=149.37ppm) attributed to the (C₃).The chemical shift at (δ=110.78ppm) attributed to the (C₁₇). The chemical shift at (δ= 52.62 ppm) assigned to methoxy group carbon atom (C₁). The chemical shifts at (δ=33.05 ppm and 14.29 ppm) assigned to methyl group carbon atoms (C₂₁,₂₀) respectively⁽¹⁷^). The mass spectrum of (L) is depicted in Fig.(3). The molecular ion peak for the ligand is observed at m/z = 480.4 (M)⁺ for C₂₇H₁₉N₅O₃S; requires = 480.52. The other peaks detected at m/z = 450.1-77.1 correspond to [C₂₆H₂₂N₆O₂]⁺- [C₆H₅]⁺. The Suggested mass fragmentation of (L) is shown in scheme (2).

Scheme (2): Suggested mass fragmentation of Schiff base (L).

Physical, micro analytical and molar conductance data:

The molar conductance of metal complexes are measured using 10^-3M DMSO solvent.

Characterization of complexes: [VO(L)₂SO₄]. H₂O:

IR (KBr cm ^-1): 3402 (ν N-Hgroup), 1653 (ν C=O), 1629(ν C=Nimin), 540 (n M – N), 486 (n M-O). UV/visible (DMSO, nm): 266 (Intra-ligand), 315 (Intra-ligand), 360 (LMC.T(, 423(²B₂g→²A₁g), 681 (²B₂g→²B₁g), 809 (2B2g→ 2Eg)., meff (B.M): 1.85

_{Thermal analyses of [Mn(L)2(H2O)Cl]Cl.H2O:}

The thermogram for [Mn(L)₂(H₂O)Cl]Cl.H₂O is placed in Fig.(4). In the TGA curve, peak detected at 252.48ºC is related to the loss of (H₂O, Cl,Cl, H₂O, 2CH₄, N_2, H₂) portions, (det. = 3.308mg, 15.036 %; calc. = 3.311mg). The second step at 378.28ºC that indicated the loss of (CO, C₃H₅) fragment, (obs. = 1.358mg, 6.173%; calc. = 1.351 mg). The third step at 595.58ºC is related to the loss of (C₁₃H₁₁N_2, H₂) segments, (obs. = 3.864mg, 17.566 %; calc. = 3.865mg). The final residue of the compound that observed above 598.0ºC is assigned to the (MnC₃₅H₂₀N₈O₅), (det. = 13.469, 61.223 %; calc. = 13.470mg). The DSC analysis curve verified peaks at 96.4, 135.4, and 200.7, 595.5ºC refer to an endothermic decomposition process. Peaks observed at 268.2, 447.1 and 400.5ºC were related to exothermic decomposition processes. The exothermic and endothermic peaks may indicate combustion of the organic ligand in an argon atmosphere. The last endothermic peak may signify the metal-ligand bond breaking ^[18,19].

Biological activity:

Microorganisms:

The Bauer method was used to test the effect of all prepared complexes and ligand against the Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) by agar-well diffusion method, The media were prepared by add 28g of nutrient agar in 1000mL of distilled water and disinfected in the autoclave to prevent contamination at 121°C for 30 min then spilled in petri dish,after rigidity the media, the bacterial was spread, each of the prepared complexes was dissolved in (DMSO) to give concentration of (0.01)mg/ml, and incubated the media at 37°C for 24 h and checked for the growth of inhibition zone as wells against fungu (Candida albicans),. The zone of inhibitions of the ligand (L) and its complexes against the growth of bacteria and fungu was given in Fig.(5)^[20,21]

RESULTS AND DISCUSSION:

CHEMISTRY.:

In IR spectra of prepared complexes The detected band at (1635) cm^-1 which was assigned to the stretching frequency of azomethine group u(N=C) of the free ligand, this band was shifted to lower frequency at range (1620-1629) cm^-1 in spectra of all prepared complexes, this shift to lower frequency may be due to involved nitrogen atom of azomethine group in coordination with metal ions and delocalization of metal electronic density to the ligand (p–system), (HOMO→LUMO), where:.

The band at (1645) cm^-1 stretching vibration which refers to uC=O for 4-AAP ring of free ligand, was shifted to higher frequency at range (1650-1660) cm^-1 in the spectra of all complexes, showing that the coordination between oxygen atom of this group (C=O) and metal ions was happened.

The IR spectra of all prepared complexes exhibited broad band at range (3446-3342) cm^-1, that may be attributed to u(O-H) of hydrated water molecules in molecular formula of complexes but the spectra of complexe (Mn) and (Co) revealed a broad band at (3475, and 3432)cm^-1 and new bands at (875 and 840) attributed to ν(OH) and δ(OH) which refer to coordinated H₂O molecule (aqua) with Mn(II) and Co(II). The new band in the IR spectrum of VO(II) complex at (995) cm^-1 was attributed to uV=O group. Also new other bands in the spectrum of VO(II) complex, at (960, 1033) cm^-1 and at (439, 644) cm^-1which refer to u(SO₄^-2) and d(SO₄^-2) respectively indicates that the SO₄^-2involved in the coordination with VO(II) ion as monodentate ligand⁽²²⁾. At the lower frequency region, the IR spectra of all prepared complexes showed new bands which are not present in the spectrum of the free ligand, these bands are located at (516– 559) cm^-1 and at (455–493) cm^-1which are attributed to u(M-N) and u(M-O) respectively⁽²³⁾.

These observation in the IR spectra of the ligand (L) and it's complexes indicate that the ligand coordinates with metal ions: Mn(II), Co(II), Ni(II),

Cu(II), Zn(II), Cd(II), and Hg(II) via oxygen atom of (C=O) group of 4-AAP ring.

The TGAdata of:

[Mn(L)₂(H₂O)Cl]Cl.H₂O,[Ni(L)₂Cl]Cl.H₂O,[Hg(L)₂Cl₂].H₂O has agreement with their molecular formula⁽²⁵⁾.

Fig. (1): suggested structure of complexes

CONCLUSIONS:

1-The Schiff base (L) and behave as bidentate ligand through one nitrogen atom of imine group and oxygen atom of C=O group of five member ring with the central metal ions: (VO(II), Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) forming complexes with general molecular formula: [M(L)₂H₂OCl].H₂O, [M(L)₂Cl₂].H₂O, [VO(L)₂SO₄].H₂O and [M(L)₂Cl].H₂O

2- The octahedral geometrical structure was suggested for all prepared complexes except the complexe [Ni(L)₂Cl].H₂O It showed the shape trigonal bipyramidal based on the characterization data using all previous techniques. 3-These prepared complexes have higher inhibition activity against bacterial and fungus that make it possible to use as drugs.

Fig.(5) Biological activity (E. coli) for the Land it's complexes.

Fig.(6) Electronic spectrum of [Mn(L)₂Cl₂].H₂O in 10^-3M.

CONCLUSION:

Based on date for all techniques we suggested that all the prepared complexes have octahedral geometry, the value of antibacterial activity of this prepared complexes showed higher inhibition activity compared to the free ligand and starting material.

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Received on 08.09.2018 Modified on 28.01.2019

Research J. Pharm. and Tech 2020; 13(6): 3001-3006.

DOI: 10.5958/0974-360X.2020.00531.4