Synthesis and Characterization of Mixed Ligand Complexes from Curcumin and New Schiff Base Derived from Isatin for Some Metallic Ions and Evaluation Biological Activities

 

Shaimaa Ahmad Hassan*

College of Remote Sensing and Geophysics, Al Karkh University of Science, Baghdad, Iraq.

 

ABSTRACT:

This study describes the synthesis of new Schiff base ligand (L') derived from isatin with 2- amino-6-methylbenzothaizole, also prepared mixed ligand complexes from curcumin (HL) and Schiff base (L') with metal ions, give formula: [M(L)(L') Cl] where: M = [Mn, Co, Ni, Cu, Zn, Cd], With (M: HL: L') [1:1:1] in ethanol as a solvent. The Schiff base (L') and all complexes were characterized by spectroscopic measurements (IR, 1H,13C-NMR, UV-Vis, A.A., LC-mas), magnetic susceptibility, elemental microanalysis, molar conductivity, chloride content, and melting point. Based on the results obtained an octahedral geometrical formula was suggested for all prepared complexes. The evolution of biological activity for ligands and their complexes was valued for two kinds of bacteria: (Escherichia coli, Staphylococcus aureus) and only one type for each of the mildew Candida Albicans. The results showed that the biological activity of the complexes against the bacteria and mildew are best than the ligands.

 

 

 

INTRODUCTION:

One of the most notable ligands used in coordination chemistry is the Schiff bases.Because of transition elements' ability to coordinate and form complexes with different structures and multiple uses¹, much attention has been paid to the study of transition elements complexes, special that complexes containing Schiff bases derived from Isatin. The chemists interested in the research field emphasized the magnificence of the Schiff bases when participating in the ions of transitional elements in their interactions^2,3. A large number of studies have been devoted to medical applications of complexes with Schiff rules originating from isatins^4-7, many of Schiff bases and their complexes derived from Isatin considered antifungal, antibacterial^8,9.

 

One of the chemical compositions of curcumin is {1,7 bis (4-hydroxy-3-methoxyphenyl) -1,6Heptadiene-3,5-dion}, this curcumin contains a highly conjugated ß-ketone di-anion could be a powerful natural chelating agent with its safety evaluated even if taken in high doses in humans ^10,11. Curcumin and its minerals have attracted a lot of attention over the past years, as one of its beneficial requirements in the treatment of its antioxidant activity in the laboratory and Alzheimer's disease. Furthermore, several mineral compounds from curcumin have been synthesized, differentiated, and evaluated for different biological activities^12.

 

Several techniques have been used to increase the bioavailability of curcumin, which includes the use of fatty curcumin, curcumin made from various auxiliary oils, curcumin phosphorous complexes, curcumin nanoparticles, unloading of the pharmaceutical precursor curcumin with inhibitors of glycol metabolism, and binding of curcumin with polyethylene. The combination of synthetic curcumin analogs and the use of the regulatory analogs of curcumin plays a major role in increasing the bioavailability^13,14. This work demonstrates the preparation and characterization of a new derivative of (Schiff Base L') for reactions of 2- amino-6 methyl benzothiazole and isatin and its mixed complexes for some metal ions.

 

EXPERIMENTAL:

(Isatin, 2-Amino-6-methylbenzothaizole, Curcumin), MnCl₂.4H₂O, CoCl₂.6H₂O, Ni Cl₂.6H₂O, CuCl₂.2H₂O, ZiCl₂, CdCl₂, Hydrobromic acide (HBr 48%), Ethanol, NaOH, and DMSO, all these chemicals were provided from Aldrich company.

 

Instruments:

Infrared spectra of compounds recorded by using (KBr discs) (Shimadzu FT-IR) at range (4000-400cm^-1) while the electronic spectra of compounds recorded by using double-bem (UV-Vis spectrophotometer) type (UV 160A (Shimadzu)) at rang (200-1100 nm, the (proton nuclear magnetic resonance and Carbon ¹³-nuclear magnetic resonance) using an ultrashield (400 MHz Switzerland). Electrical conductivity measured by using (conductivity meter, model 4070) at (25ºC) for (10^-3 mole. L^-1) solution of the samples(complexes) in DMSO.

 

In addition, was used (Shimadzu Atomic Absorption / Flame) atomic absorption spectrometry (A.A-160) to characterize the atomic absorption for complexes, while Magnetic Susceptibility of complexes measured by using Magnetic Susceptibility Balance Mode (MSB_MKI).  Electro thermal (Stuart melting point apparatus) was used the melting points for the compounds. The LC-mass spectra measured by using (LC-MS QP50A: Shimadzu).

 

Synthesis of Schiff base:

Isatin solution (0.147g, 1mmole) in (10 mL) ethanol was added to 2- Amino-6-methylbenzothaizole solution (0.164g, 1mmole) in (20mL) ethanol, then was add three drops of Hydrobromic acide 48% to the mixture. The mixture was refluxed for 7hrs. with stirring. The reaction mixture's color changed to pale orange then this mixture was cooled at room temperature. Precipitate pale orange powder, this precipitate was filtered and washed by Ethanol, Scheme (1). Yield (90%), (M.P.:189-191)ºC, M.wt: 293gm/mole (C₁₆H₁₁N₃OS) .

 

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

Synthesis of Mixed -ligand complexes:

In round (200mL) (0.198g, 1mmole) of MnCl₂.4H₂O dissolve in (20mL) ethanol and it is slightly heated to complete the dissolution process after that added gradually (0.368g,1mmole) of Curcumin dissolved in (20mL) ethanol) with (0.4g, 1mmol) of NaOH dissolved in distilled water to form sodium curcminate and (0.239g, 1mmole) of Schiff base (L') dissolved in (30mL) ethanol then the mixture was refluxed with stirring for 4 hours. A brown precipitate formed. The other complexes were prepared with the addition of metal chloride   of ions salts, Co (II) , Ni (II), Cu (II) , Zn(II)  Cd(II) in the same way . See Scheme (2). Table (1) includes some of the physical properties of the prepared compounds.

 

Scheme (2): Role of complexes synthesis.

 

Table (1): Some of the physical properties of the prepared compounds.

No	Empirical formula	Color	Yield	M.Wt	Elemental microanalysis, (Calc. %)
			%	g/mol.
					C	H	N	S	Metal	Cl
	C16H11N3OS	pale orange	90	293	65.23	3.34	13. 99	10.61	--------	------
					-65.52	-3.75	-14.33	-10.92
1	MnC37H30N3O7ClS	Blackish green	86	750	58.91	3.76	4.71	4.31	7.02	4.45
					-59.2	-4	-4.91	-4.62	7.33	-4.73
2	CoC37H30N3O7ClS	Dark brown	91	754	58.51 (58.88)	3.59	5.22	4.01	7.5	4.49
						-3.97	-5.57	-4.24	-7.82	-4.7
3	NiC37H30N3O7ClS	Brown	89	754	58.49	3.68	5.27	3.98	7.49	4.51
					-58.88	-3.97	-5.57	-4.24	-7.82	-4.7
4	CuC37H30N3O7ClS	Dark brown	82	759	58.19	3.66	5.31	3.99	8.19	4.32
					-58.49	-3.95	-5.53	-4.21	-8.43	-4.67
5	ZnC37H30N3O7ClS	Reddish brown	89	761	58.01	3.65	5.33	3.97	8.28	4.49
					-58.34	-3.94	-5.51	-4.2	-8.54	-4.66
6	CdC37H30N3O7ClS	Brown	84	808	54.66	3.4	4.82	3.67	13.51	4.12
					-54.95	-3.71	-5.19	-3.96	-13.86	-4.39

 

RESULTS AND DISCUSSION:

¹H and ¹³C-NMR Spectra:

The ¹HNMR spectrum of Ligand (L^') in solvent (DMSO-d⁶) Figure (1), displayed the signals: single at δ (9.82) ppm due to (2H, (N-H)), while aromatic protons of benzene ring appeared (multiples) at range δ (7.01- 7.56) ppm, a signal at δ (2.48) ppm for (-CH₃)¹⁵. The ¹³C-NMRspectrum of Ligand (L^') in (DMSO) as solvent, the ¹³C-NMR data tabled in table (2).

 

Table (2):¹³C-NMR Spectral date of Schiff base(L').

Schiff base	Function groups	δ ppm
(L')	C9 for C-N group	197.82
	C7 for C=N group	165.21
	C8 For C=O group	158.72
	[Ar–C]	(107.00-155.81)
	DMSO	(38.76-39.12)
	C13For CH3 group	22.69

 

Figure (1):¹H-NMR spectrum date Schiff base (L^').

 

Mass Spectra of (L^'):

Ligand's (L^') mass spectrum, shows the original ion peak at (M/Z⁺=293) refer to (C₁₆H₁₁N₃OS) while the other fragments of ligand tabled in table (3).

 

Complex's [Ni (L) (L^') Cl] mass spectrum Fig (2), appeared molecular weight =754 for [NiC₃₇H₃₀N₃O₇ClS] ¹⁶. at (m/z⁺=754).).

 

Table (3):LC-Mass fragmentation  for (L^') .

Fragment	mass/charge (m/z)
[M]+[C16H11N3OS] +	293.2
[C15H8N3OS] +	278.3
[C9H6N3OS] +	204.2
[C8H5N2O] +	145.3
[C6H5] +.	77.2

 

Figure (2): Mass spectrum date for [Ni(L)(L^') Cl].

 

The FT-IR spectral:

In FT-IR spectrum of curcumin a band at (1627cm^-1) refer to ν(C=O) carbonyl group, in complexes this band was shifted to lower frequencies between (1621 -1616 cm^-1) that means occurring coordination between metal ion and carbonyl group (C=O)^17,18. The two inoleic bands at (1279) cm^-1 and (743) cm^-1 refer to u (C-O) and δ (C-O) respectively in free curcumin (HL), while in IR of    complexes this bands shifted to lower frequencies at (1270-1264) cm^-1 for u (C-O) and at (736-727) cm^-1 for δ (C-O). This displacement confirms that there is a coordination between the metal ion and the inoleic atom (O) in curcumin¹⁹, which means that curcumin, behaves like a bidentate ligand by (O) a ketone atom and an inoleic group.

 

The u (C=N imine) was interfered with u (C = N in plane) in free ligand (L^') this band appeared at (1615) cm^-1 while in complexes this band shifted to higher frequencies at (1621-1632), this displacement at the location of the two groups that indication of the harmony between the (C=N imine) and (C = N in plane) atoms of the (L^') base with the metal ion^20-22.

 

The absorption frequency band of group (C = O amide) of the ligand (L^') appeared at (1733) cm^-1 has been observed to change in the form, intensity and position in the spectra of all complexes at (1739-1743) that indicating their compatibility with the metal ions^23,24, Mn (II), Co (II), i (II), Cu (II), Zn (II), Cd (II). This means that (L') behaves like a tridentate ligand by (N) atoms in (C=N inplane) and (C=N imine) and from (O) atom in (C=O amide). The spectrum of complexes showed do not change in located of the ʋ (C-S-C) band at (706-708) cm^-1 when compared with its free ligand (L^'), indicating an incoordination of the S atom with the metal ion^25,26. As noted in the spectrum of complexes two new weak beams, the first range (525-559cm^-1) and the two at the range (422-469) cm^-1 were attributed to u (M-N) ʋ and (M-O) respectively^27,28. This supports the harmony between the metallic ion and the ligand (HL) and (L^') by atoms (O) and (N). The IR spectrum of [Ni (L) (L^') Cl] complex fig (3).

 

Figure (3): FT-IR spectrum of [Ni(L)(L^') Cl].

 

The (UV-Vis) spectral:

The electronic spectrum of the curcumin (HL) table (4), showed three electronic transitions peaks at (268, 334 and 434 λmax ) nm to π→ π*, π→ π* and n→π* respectively²⁹. The UV-Vis of ligand (L^') shows two electronic transitions peaks at (285 and 416 λmax) nm refer to (π→ π*) and (n – π*) respectively.

 

The UV-Vis for prepared complexes (1-6) displayed electronic transitions peaks, the first peak at range (266-273 λmax) nm (37593- 36630) cm^-1 , while the second peak at range (301-307 λmax)nm (33222-32573cm^-1)³⁰, a third peak at the range (345-351 λmax) nm (28985 -28490cm^-1) in the end ,the fourth peak (390-430 λmax) nm (25641-23255cm^-1), these peaks are induced by electronic intra-ligand transitions , and change in form, displacement and intensity are an indicator of consistency ³¹ . All UV-Vis data tabled in table (4) and figure (4) showed electronic spectrum of [Ni (L) (L') Cl].

 

Table (4): UV-Vis data, Molar Conductivity and Magnetic Sensitivity of ligands and complexes.

Compounds	l (nm)	u– (cm–1)	emax (molar-1 cm-1)	Assignment	Suggested Structure	S. cm-1mole-1	𝞵eff (B.M)
[L']	285	35087	2444	π→π*	------	------	-------
	416	24038	521	n→π*
HL	268	37313	530	π→π*	------	-------	--------
	334	29940	538	π→π*
	434	23041	2065	n→π*
[ Mn(L)(L') Cl]	271	37037	1489	Intra-ligand	Oh	8.65	5.22
	306	32679	929	Intra-ligand
	350	28571	1010	Intra-ligand
	404	24752	1715	Intra-ligand
	429	23310	2220	Intra-ligand
	450	22222	2024	C.T+6A1g→4T2g(G)
	537	18657	12	6A1g→4T1g(G)
[ Co(L)(L') Cl]	270	37037	1160	Intra-ligand	Oh	9. 79	3.85
	306	32680	684	Intra-ligand
	346	28902	712	Intra-ligand
	405	24691	1634	Intra-ligand
	429	23310	1959	MLCT
	514	19455	163	4T1g(F)→4T1g(P)( u3)
	778	12853	23	4T1g(F)→4A2g(F)( u2)
	880	11363	12	4T1g(F)→4T2g(F)(u1)
[ Ni(L)(L') Cl]	271	36900	1671	Intra-ligand	Oh	11. 77	2.84
	301	33222	1666	Intra-ligand
	345	28985	1632	Intra-ligand
	429	23310	2342	Intra-ligand
	452	22124	2311	MLCT+3A2g(F)→3T1g(P)
	709	14104	69	3A2g(F)→3T2g(F)
[ Cu (L)(L') Cl]	273	36630	2010	Intra-ligand	Oh	4. 69	1.79
	307	32573	1601	Intra-ligand
	351	28490	1908	Intra-ligand
	390	25641	71537	Intra-ligand
	460	21739	737	MLCT
	801	12484	11	2Eg→2T2g
[ Zn(L)(L') Cl]	267	37453	1057	Intra-ligand	Oh	12.35	-
	304	32894	946	Intra-ligand
	349	28653	1108	Intra-ligand
	430	23255	1909	Intra-ligand
	450	22222	1723	MLCT
[ Cd(L)(L') Cl]	266	37593	1184	Intra-ligand	Oh	5.42	-
	306	32779	1160	Intra-ligand
	350	28571	1584	Intra-ligand
	428	23346	2189	Intra-ligand
	451	22172	2104	MLCT

 

Figure (4): Electronic spectrum of [Ni(L)(L^') Cl].

 

Molar Conductivity and Magnetic Sensitivity of complexes:

The conductance measure for complexes in (DMSO d⁶) in range (5.42 to 12.35) S. cm^-1. mole^-1 that indicated all complexes are non-electrolytic behavior ³² while the magnetic sensitivity of complexes at 303ºK in rang (1.79 to5.22) that mean all complexes suggest octahedral geometry. All data tabled in table (4).

 

Biological Effectiveness:

The studied of biological activity for Schiff base ligand (L^') and its complexes by using the method of inhibition of the two types of (G+, G-) bacterial that are [Esherichia Coli and Staphylococcus aureu) and one type fungi is Candida albicans]^33-36, the results tabled in the table (5)

 

Table (5): Biological activates of ligands and thier complexes.

No.	Compounds	Staphylococcus aureu (G+) (mm)	EsherichiaColi (G-) (mm)	Candida albicans
	Control	-	-	-
	(HL)	17	20	12
	(L')	21	28	11
1	[Mn(L)(L') Cl]	31	38	19
2	[Co(L) (L') Cl]	10	23	22
3	[Ni(L)(L') Cl]	15	22	28
4	[Cu(L)(L') Cl]	19	29	30
5	[Zn(L)(L') Cl]	14	27	20
6	[Cd(L)(L') Cl]	33	30	35

 

Figure (5): Biological activity (E. coli) for the L' and it's complexes.

 

CONCLUSION:

Ligands (HL and L¹) and their mixed complexes have been diagnosed by (UV-Vis, FT- IR, ¹H,¹³CNMR, LC-Mass, A.A, elemental microanalysis, magnetic susceptibility, chloride content and electrical conductivity.

 

Curcumin (HL) ligand is a bidentate ligand coordinated with metal ions M(II)=Mn, Co, Ni, Cu, and Cd by two Oxygen atoms (O) from ketonic and enolic group, while the Schiff base ligand (L') is a tridentate ligand by two (N) atoms one from the azomethine group (C = N) and another one from (C=N ring) and an oxygen atom (O) from the amide group, to form complexes that have the molecular formula [M (L)(L^') Cl]. All complexes appeared biological activity mor than ligands .

 

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Accepted on 19.08.2021           © RJPT All right reserved

Research J. Pharm.and Tech 2022; 15(4):1537-1542.