Synthesis and Characterization of Metal Complexes of N-Isonicotinamido-Furfuraldimine and Investigation of Their Biological Activity

 

Md. Sajjad Hossain, Md. Masuqul Haque*

Department of Chemistry, University of Rajshahi, Rajshahi-6205, Bangladesh

*CorrespondingAuthorE-mail:masuqul2003@ru.ac.bd

New complexes of N-isonicotinamido-furfuraldimine (INH–FFL) with Cu (II), Co (II) and Ni (II) have been prepared and characterized by analytical and physico-chemical techniques, such as magnetic susceptibility, conductivity measurements, electronic and IR spectral studies. The infrared spectral studies revealed the bidentate nature of the Schiff base in the complexes. A square- planar geometry is suggested for all the complexes. The prepared complexes were evaluated for their antimicrobial activity showing moderate outcome.

 

 

INTRODUCTION:

Schiff bases play an important role in the field of inorganic chemistry as they easily form stable complexes with most transition metal ions in the periodic table. The development of the bioinorganic chemistry has increased the interest in Schiff base complexes since it has been recognized that many of these complexes may serve as the model for biologically important species [1- 3].

 

During the past two decades, considerable attention has been paid to the chemistry of the metal complexes of Schiff bases containing nitrogen and other donors [4-7]. In recent years considerable interest has been enlivened in the comparative donor properties of oxygen and nitrogen when both are present in the same molecule.

 

These may be attributed to their stability, biological activity [8-10] and potential applications in many other fields such as oxidation catalysis [11], electrochemistry [12] and analytical chemistry etc [13-14].

 

It is generally known that hydrazones have significant antimicrobial, anticonvulsant, analgesic, anti-inflammatory and anti-tumoral activities [15-20].The remarkable biological activity of acid hydrazides R–CO–NH–NH₂, their corresponding aroylhydrazones R–CO–NH–N=CH–R’, and the dependence of their activity on the mode of chelating with transition metal ions have been of significant importance [21- 24].

 

As a continuation of my interest in the coordination behavior of Schiff bases with isonicotinoylhydrazones[25], the synthesis and characterization of a series of Cu (II), Ni(II) and Co(II)  complexes with N-Isonicotinamido-furfuraldimine (INH–FFL) ligand (Lb) are reported along with their biological activity studies herein.

 

EXPERIMENTAL:

All used chemicals were purchased from Merck and Loba chemicals. All the melting points were determined on a digital melting point apparatus. Products were characterized by comparison of spectroscopic data (UV-Visible and FT-IR) and melting points with authentic samples.

 

The wavelength of absorbance was determined by UV-Visible spectrophotometer [JASCO 503] using a quartz cuvette and ethanol as the reference. The IR spectra were recorded on FT-IR spectrophotometer [JASCO, FT-IR/4100] Japan using dry KBr as the standard reference. The magnetic susceptibility of the complexes was measured at room temperature using a Gouy balance.

 

General Procedure for Synthesis of N-Isonicotinamido-Furfuraldimine Ligand (Lb)

Isoniazid (INH) (1.37 g, 10.0 mmol) was mixed with absolute ethanol (15 mL) and the mixture brought to the boil, producing slurry. Barely sufficient additional ethanol was then added to give a homogeneous solution at reflux. Furfuraldehyde (0.837 mL, 10 mmol) was added drop-wise over 5 minutes and washed with 5 mL of ethanol. The reaction mixture was refluxed for 4 hours then allowed to cool slowly and to stand overnight. Finally, it produces a white crystalline solid which was filtered off and dried.

 

Scheme 1: Synthesis of Schiff base ligand Lb

 

Experimental Procedure for Synthesis of Complexes:

To the warm methanolic solution (10 mL) of ligand Lb (2 mmol), 10 mL warm methanolic solutions (1 mmol) of nitrate salts of metal Cu(II), Ni(II) and Co(II)  was added and the resulting mixture was refluxed for about 3-4 hours. The obtained precipitates were filtered, washed with methanol and finally dried under vacuum on anhydrous CaCl₂.

 

Antimicrobial Activity:

The ligand (Lb) and its metal complexes were screened for in vitro antimicrobial activity in DMSO against gram-negative Escherichia coli (E. coli) and gram-positive Bacillus Cereus (B. cereus) strains by Kirby Bauer’s disc diffusion technique. 

 

A uniform suspension of test organism of 24 hours old culture was prepared in a test tube containing the sterile saline solution. Sterile nutrient agar was then added in each of the Petri dishes. The dishes were related to ensuring the uniform mixing of the microorganism in the agar medium which was then allowed to solidify.

 

Sterile Whatmann filter paper discs were dipped in the solution of each compound and placed on the labelled plates. The DMSO was used as a control of the solvent.

 

Kanamycin was used as a standard compound for comparison. Plates were kept in the refrigerator for half an hour for diffusion and incubated at 37°C for 24 hours.

 

The diameter of the zone of inhibition around each disc was measured by scale and results were recorded in terms of mm. The observed data of antimicrobial activity of all the compounds and the standard drugs are given in Table 4.

 

RESULTS AND DISCUSSION:

In the present study, it was observed that the reaction under refluxed at 80°C had significantly improved the yield of the product. By the reaction of Cu (II), Ni(II)  and Co(II) nitrate with ligand Lb, complexes of the type [M(Lb)₂] were obtained. All the complexes have a different color, stable at room temperature, insoluble in common polar solvent but soluble in DMSO and DMF, do not have the sharp melting point but decompose above 250°C.

The measurement of molar conductivities at 10^-3 M concentration carried out in DMSO at room temperature. The molar conductivity values show that the nitrate complexes were 1:2 electrolytes [26].

The analytical and physical data (color, melting point, molar conductivity and magnetic moment) of the complexes are given in Table 1. For the Cu (II) and Co(II) complexes, the magnetic moments were 1.85 and 2.20 BM respectively indicating paramagnetic nature. These values correspond to the square planar geometry for both complexes [27-28]. For the Ni (II) complex the value for the magnetic moments is 0.21 BM indicates the diamagnetic complex of Ni (II) with square-planar geometry [27- 29].

 

Table 1: Analytical and Physical Properties Data of Lb and Its Complexes

Symbol of Compounds	Complexes	M.P or De (Decomposition Temp) / ºC	Color	Yield (%)	Solubility	Molar conductance ohm-1 cm2mol-1	µeff in B.M
					DMSO and DMF
Ligand (Lb)	C11H9N3O2	214	White	92	(+) ve	6
Co-Lb	Co(C11H9N3O2)2	280 (De)	Red	83	(+) ve	151	2.20
Ni-Lb	Ni(C11H9N3O2)2	295 (De)	Yellow	85	(+) ve	153	Dia
Cu- Lb	Cu(C11H9N3O2)2	275 (De)	Dark Brown	87	(+) ve	155	1.85

 

 

IR Spectral Studies:

The IR spectrum of ligand (Table 2) exhibited characteristic bands at 1650.62 cm^-1 and 1600.80 cm^-1 assigned to ѵ(C=O) and ѵ(C=N) respectively (Figure 1.1) [30].

 

The band at 1650.62 cm^-1, attributable to the ν(C=O) stretching vibration of the Schiff base ligand is shifted to another region ranging 1604–1622 cm^-1 in the complexes of Cu, Ni, and Co indicating coordination of the carbonyl oxygen to the metal ions (Figure 1.2, 1.3 and 1.4). The presence of bands at 554– 592 cm^-1 in the IR spectra of complexes is due to M–O stretching vibrations [26, 31].

 

The azomethine band at 1600.80 cm^-1 of Schiff base was shifted to lower frequencies ranging 1567–1579 cm^-1 in the spectra of all the complexes, confirming the participation of the azomethine nitrogen atom in the coordination of the metal ions. In the IR spectra of these complexes, the new bands which appear in the 404–444 cm^-1 region are assigned to the ν(M–N) vibration [26, 27, 31]. The strong sharp band observed at 1384 cm^-1 in the complexes can be assigned to uncoordinated nitrate ion [26].

 

All of these IR data confirm a bidentate ligand coordinated in Cu, Ni, and Co metal complex through its O and N atoms respectively.

 

Table 2: Key Infrared Bands (cm^-1) of Complexes and Ligand Lb

Symbol of Compounds	Compounds	n (C=O)	n (C=N)	V (M-O)	n (M-N)
Ligand (Lb)	C11H9N3O2	1650.62	1600.80
Co-Lb	Co(C11H9N3O2)2	1621.27	1578.71	591.72	443.55
Ni-Lb	Ni(C11H9N3O2)2	1604.85	1571.30	565.04	404.62
Cu- Lb	Cu(C11H9N3O2)2	1613.96	1567.14	554.20	416.42

 

 

Figure 1.1: IR Spectrum of Lb

 

 

Figure 1.2: IR Spectrum of Cu-Lb

 

 

Figure 1.3: IR Spectrum of Ni-Lb

 

Figure 1.4: IR Spectrum of Co-Lb

 

UV- Visible Spectra:

The UV-Vis spectra of the obtained ligand (Lb) exhibits two bands at 273 and 337 nm, which are assigned to π-π* and n-π* transitions, respectively.

 

All the complexes showed the charge transfer transitions which can be assigned to charge transfer from the ligand to metal (LMCT) and vice versa. For complexes, absorption bands at the range of 365– 371 nm may be associated with L M charge transfer and vice versa (M L) [27- 28].

 

In the UV-region, the complexes showed absorption band at 264–268 nm (Figure 1.5) which may be assigned to transition. The spectra of all the complexes exhibiting bands assigned to  and ML charge transfer, the metals normally prefer square- planar geometry [27- 29]. All observations were summarized in the Table 3.

 

Table 3: UV- Visible Spectrum the Ligand (Lb) and its Complexes

Symbol of Compound	Compound	λ in nm	Assignment
Ligand (Lb)	C11H9N3O2	273 337	π-π* n-π*
Cu- Lb	Cu(C11H9N3O2)2	268 371	π-π* C.T
Ni-Lb	Ni(C11H9N3O2)2	267 370	π-π* C.T
Co-Lb	Co(C11H9N3O2)2	264 365	π-π* C.T

 

 

Figure 1.5: UV- Visible Spectrum of the Lb and its Complexes

 

From the electronic and physical properties (i.e. FT-IR, UV-Vis, Magnetic Susceptibility, Melting Points and Molar Conductance), the following structure can be proposed for our obtained complexes.

 

 

Figure 2: The proposed structure for MLb complexes (M²⁺ = Co, Ni and Cu)

Antimicrobial Screening Result:

The Schiff-base ligand, Lb and its metal complexes reported here were evaluated for antibacterial activity against Escherichia coli and Bacillus cereus. The values of zone inhibition were measured in millimeter. The data of antibacterial activities of ligand and complexes are given in Table 4.

 

The inhibitory zone data reveals that the ligand, as well as its metal complexes, shows good to moderate antibacterial activity. The biological activity of Schiff base ligand arises from the presence of imine group which imports in elucidating the mechanism of transformation reaction in biological systems. However, its metal complexes showed remarkable antibacterial activity as a result of chelation of metal with organic ligand synergistically increasing its effect [26, 30-32]. The DMSO control did not show any antimicrobial activity against the tested bacterial strains.

 

Table 4: Antibacterial Screening Results of Ligand Lb and its Complexes

Antibacterial Zone of Inhibition (in mm)
Compounds	Gram Negative	Gram Positive
	Escherichia coli	Bacillus cereus
Kanamycin	32	35
Ligand (Lb)	5	5
Cu- Lb	11	11
Ni-Lb	7	6
Co-Lb	14	15

 

CONCLUSIONS:

On the premise of results got after characterization and antibacterial activity studies it is obvious that all the synthesized metal complexes demonstrated square planar geometry and enhanced antibacterial properties against selected microbes. It has been observed that all metal complexes show more antibacterial activity than ligand. Although with respect to standard, all the tested compounds were found to be moderately active.

 

REFERENCES:

1.      Ainscough EW, Brodie AM, Ranford JD, Waters JM. Hexafluorosilicate coordination to the antitumour copper(II) salicylaldehyde benzoylhydrazone (H2L) system: single-crystal X-ray structure of [{Cu(HL)H2O}2SiF6]·2H2O.InorgaChimica Acta236(1): 1995; 83

2.      Koh LL, Kon OL, Loh KW).Complexes of salicylaldehyde acylhydrazones: cytotoxicity, QSAR and crystal structure of the sterically hindered t-butyl dimer. J InorgaBiochem72(3): 1998,155

3.      Ainscough EW, Brodie AM, Denny WA, Finlay GJ, Gothe SA, Ranford JD. Cytotoxicity of salicylaldehyde benzoylhydrazone analogs and their transition metal complexes: quantitative structure-activity relationships.J InorgaBiochem77(3): 1999;125

4.      Djebbar SS, Benali BO, Deloume. Synthesis, characterization and electrochemical behaviour of some copper(II) complexes with linear and tripodal tetradentate ligands derived from Schiff bases. Polyhedron 16:1997; 2175

5.      Bhattacharyya P, Parr J, Ross AT. First synthesis of a unique dilead Schiff base complex. J Chem Soc Dalton:1998; 3149

6.      He L, Gou SH, Shi QF. The formation of a Schiff base intermediate: a nickel(II) complex of an asymmetric tripodal ligand. J Chem Crystallography 29: 1999;207

7.      Wu JC, Tang N, Liu WS, Tan MY, Chan ASC. Intramolecular hydrogen bond self-template synthesis of some new Robson-type Macrocyclic Ligands. Chin Chem Letters12:2001; 757

8.      Al-allaf TA, Sheet AZ. Platinum group metal Schiff base complexes-I. Platinum complexes. Polyhedron 14: 1995;239

9.      Highfield JA, Mehta LK, ParrickJ, Wardman P. Synthesis, hydroxyl radical production and cytotoxicity of analogues of bleomycin. Bioorg Med Chem8: 2000;1065

10.    Das A, Trousdale MD, Ren S, Lien E. Inhibition of herpes simplex virus type 1 and adenovirus type 5 by heterocyclic Schiff bases of aminohydroxyguanidine tosylate¹. J Antiviral Res 44: 1999;201

11.    Djebbar SS, Benali BO., DeloumejP. Synthesis, characterization, electrochemical behaviour and catalytic activity of manganese(II) complexes with linear and tripodal tetradentate ligands derived from Schiff bases Transit. Metal Chem 23:1998; 443

12.    Hamada YJ. The development of chelate metal complexes as an organic electroluminescent material. IEEE Trans Electron Devices 44:1997; 1208

13.    Patel PR, Thaker BT, Zele S. Preparation and characterisation of some lanthanide complexes involving a heterocyclic β – diketone. Indian J Chem 38:1999; 563

14.    Bhavna TM, Pralhad G. J Mol Catalysis 2:1992; 109

15.    Rollas S, Küçükgüzel SG. Biological Activities of Hydrazone Derivatives. Molecules12:2007; 1910

16.    Ainscough EW, Brodie AM, Denny WA, Finlay GJ, Gothe SA, Ranford JD. Cytotoxicity of salicylaldehyde benzoylhydrazone analogs and their transition metal complexes: quantitative structure–activity relationships. J InorgBiochem 77:1999; 125

17.    Bottari BR, Maccari, Monforte F, Ottana F, Rotondo E, Vigorita MG. Isoniazid-related copper(II) and nickel(II) complexes with antimycobacterial in vitro activity. Bioorg Med Chem Letters10:2000; 657

18.    Sridhar SK, Saravanan M, Ramesh A. Synthesis and antibacterial screening of hydrazones, Schiff and Mannich bases of isatin derivatives. Eur J Med Chem 36: 2001; 615

19.    Koçyiğit KB, Rollas S. Synthesis, characterization and evaluation of antituberculosis activity of some hydrazones. Farmaco 57:2002; 595

20.    Agarwal RK, Sharma D, Singh L, Agarwal H. Synthesis, Biological, Spectral, and Thermal Investigations of Cobalt(II) and Nickel(II) Complexes of N-Isonicotinamido-2′,4′-Dichlorobenzalaldimine. Bioinorg Chem Appl:1; 2006

21.    Singh NK, Singh N, Sodhi A, Shrivastava A. Synthesis, characterization and antitumour studies on N-salicyl-N′-thiobenzohydrazide and its copper(II) complex. Transition Met Chem 21: 1996; 556

22.    Singh NK, Singh N, Prasad GC, Sodhi A, Shrivastava A. Antitumor activity studies of newly synthesized N-salicyloyl-N′-(p-hydroxybenzthioyl)hydrazine and its Copper(II) complex both in vivo and in vitro. Bioorg Med Chem 5:1997; 245

23.    Agarwala BV, Hingorani S, Nagna Gowda GA. Synthetic and physicochemical studies of uranium complexes with semicarbazone and hydrazoneInorgChim Acta176:1990; 149

24.    Maurya RC, Verma R, Singh T. Synthesis, Magnetic, and Spectral Studies of Some Mono‐ and Binuclear Dioxomolybdenum(VI) Complexes with Chelating Hydrazones Derived from Acid Hydrazides and Furfural or Thiophene‐2‐aldehyde. Synth React Inorg Met Org Chem 33:2003; 309

25.    Mitu L, Raman N, Kriza A, Stanica N, Dianu M. Synthesis, characterization and antimicrobial activity of Cu (II), Ni (II), Co (II), Zn (II) complexes with isonicotinoylhydrazone-4-benzyloxybenzaldehyde. Asian J Chem 21: 2009; 5749

26.    Mariana LD, Angela K, Nicholae S, Adina MM. Transition metal M(II) complexes with isonicotinic acid 2-(9-anthrylmethylene)-hydrazide. J Serb Chem Soc. 2010:75(11):1515.

27.    Ikechukwu PE, Peter AA. Synthesis, Characterization and Biological Studies of Metal(II) Complexes of (3E)-3-[(2-{(E)-[1-(2,4-Dihydroxyphenyl) ethylidene]amino}ethyl)imino]-1-phenylbutan-1-one Schiff Base. Molecules 20: 2015; 9788

28.    Raman N, Dhaveethu JR., Sakthivel A. Synthesis, spectral characterization of Schiff base transition metal complexes: DNA cleavage and antimicrobial activity studies. J Chem Sci 119(4): 2007; 303

29.    Patricia RB, Richard MCW, Sue CC. Square-planar transitioin metal complexes with tetradentate thioiminato Schiff base ligands. Inorga Chem 13(2): 1974; 450

30.    Ganesh SK., Priyanka LA, Digambar DG, Dnyandeo MJ. Efficient ultrasound synthesis and biology screening of metal complexes of N-(4- methoxybenzylidene) Isonicitinohydrazone. W J Pharma Research5(2): 2016; 1153

31.    Abdul H, Ahmed A, Salima A, Ben G. Synthesis and Characterization of Some Transition Metals Complexes of Schif Base Derived From Benzidine and Acetylacetone.J Science and Its Appl2(1): 2008; 83

32.    Vogt RL, Dippoid L. Escherichia Coli O157:H7 Outbreak Associated with Consumption of Ground Beef, June–July 2002 Public Health Reports 120: 2005; 174

 

 

 

Received on 26.02.2019                    Modified on 28.03.2019

Accepted on 02.04.2019                   ©AJRC All right reserved