Synthesis and Characterization of Novel Transition Metal Complexes of Benzo-α-Pyranone Derivatives and Their Biological Activities

 

Sangeeta V. Chavan, Sudhir S. Sawant* and Ramesh S. Yamgar

Department of Chemistry, Patkar College of Arts and Science, Goregaon (W), Mumbai 400 062, India

*Corresponding Author E-mail: sawantsudhir@hotmail.com

ABSTRACT:

Some novel transition metal [Mn(II), Co(II), Ni(II), Cu(II), Pd(II)] complexes of multidentate Schiff base ligand obtained from semicarbazide and substituted α-benzopyronone have been prepared and characterized by physical, spectral and analytical data. The synthesized Schiff base act as tridentate ligand for the complexation reaction with Mn(II), Co(II), Ni(II), Cu(II) and Pd(II) ions. The new compounds, possessing the general formula [M(L)₂.H₂O] where [M= Mn(II), Co(II), Ni(II), Cu(II) and Pd(II)] show an octahedral geometry. In order to evaluate the effect of metal ions upon chelation, the Schiff base and their metal complexes have been screened for antimicrobial activity. The transition metal complexes have shown enhanced antimicrobial activities as compared to Schiff base.

 

 

 

INTRODUCTION:

Schiff bases form an important group of compounds in chemistry not only because of their useful physical and chemical properties and large number of reactions they undergo but also because of their wide use in industry and their interesting pharmacological activity. Schiff bases derived from substituted aromatic amines and aromatic aldehydes have a wide variety of applications in many fields, e.g. biological, inorganic and analytical chemistry^1-5.

 

Among the organic reagents actually used, Schiff bases possess excellent characteristics, structural similarities with natural biological substances, relatively simple preparation procedures and the synthetic flexibility that enables design of suitable structural properties^6,7. Many biologically important Schiff bases have been reported in the literature possessing, antibacterial^8,9,10, antifungal^11,12,13, antimicrobial^14,15,16, anticonvulsant¹⁷, antiHIV¹⁸, anti-inflammatory and antitumor activities.

 

EXPERIMENTAL:

Material and Methods:

All chemicals and solvents used were of AR grade. All metal(II) salts were used as chlorides. IR spectra were recorded on a Shimadzu and Perkin Elmer spectrum BX FTIR Spectrophotometer. UV-Visible spectra were obtained in DMF on a Perkin Elmer Lambda 25 UV-Visible Spectrophotometer. Conductance of the metal complexes was determined in DMF on a Pico Lab India Conductivity Meter. Magnetic measurements were made on solid complexes using Gouy balance method. The proton magnetic spectra were recorded on a Bruker AMX-500 Spectrometer.

 

Synthesis of 6-methyl-benzopyran-2-one-4 acetic acid:

6-methyl-benzopyran-2-one-4 acetic acid was prepared by the reported method¹⁹.

 

Concentrated H₂SO₄ (160 ml) was cooled to 0⁰ C in ice bath. Mixture of ethylacetoacetate (65 ml) and p-Cresol (55 ml) was added in concentrated H₂SO₄ under vigorous stirring at 0-5ºC over a period of 1-1.5 hrs. Stirring was continued at 5ºC for 2 hrs. Temperature of reaction mixture was then raised slowly to 30⁰C and allowed to stand for 24 hrs. The solution was then poured in ice bath and water. The product precipitated was filtered. The crude product was dissolved in NaHCO₃ solution and the solution was then clarified with activated charcoal and filtered. Filtrate was acidified with conc. HCl to give respective 6-methyl-benzopyran-2-one-4-acetic acid. The yield of the product was around 65%.

 

Synthesis of 6-methyl-4-formyl coumarin:

6-methyl-benzopyran-2-one-4 acetic acid (56.4 g) were dissolved in xylene (300 ml) at 60-70ºC. SeO₂ (25 g) was added to a clear warm solution. Mixture was refluxed for 8 hrs and then the reaction mass was filtered in hot condition to remove insoluble selenium. Filtrate on cooling to 10ºC using ice-salt mixture, gave fine crystalline product. The yield of the product was around 80%.

 

Synthesis of Schiff base:

The Schiff base [(1E)-1-((6-methyl-2-oxo-2H-chromen-4-yl)methylene)-4-phenyl semicarbizide (mocmps)] was obtained by the reaction of 4-phenyl semicarbazide with 6-methyl –4-Formyl coumarin in (1:1) molar proportion in methanol in the presence of traces of concentrated hydrochloric acid. The reaction mixture was refluxed for 30 minutes. On cooling, the product was isolated which was recrystallized from alcohol. The yield of the product was around 70%. It is characterized by UV, IR, NMR and elemental analysis.

 

Fig. 1

 

Synthesis of Metal Complexes of Schiff base:

First the Schiff base (mocmps) was dissolved in a solution of sodium hydroxide in 1:2 molar proportions to obtain its di-sodium salt. Then equimolar quantities of divalent metal chloride and disodium salt solution of ligand were mixed and the reaction mixture was heated on waterbath for about one hour. It was then cooled when coloured solid separated out which was washed with water and dried in vacuum dessicator. This is the general method for the synthesis of metal complexes of ligand with divalent metal chlorides MCl₂.H₂O Where M= Mn(II),  Ni(II), Cu(II), Co(II), Pd(II).

 

RESULTS AND DISCUSSION:

Physical properties:

The Schiff base (Fig. 1) were prepared by refluxing an appropriate amount of 4-phenyl semicarbazide with 6-methyl –4-Formyl coumarin in (1:1) molar proportion in methanol in the presence of traces of concentrated hydrochloric acid. The Schiff bases were established with the help of Elemental analysis, IR, NMR, UV.

 

This Schiff base was then used for the complexation with Mn(II), Co(II), Ni(II), Cu(II) and Pd(II) ions. All of the synthesized metal complexes were air and moisture stable. These were prepared by the stoichiometric reaction of the corresponding metal salts (as chlorides) and the Schiff base in molar ratios M:L of 1:2. The complexes are intensely colored, which decomposes above 200ºC. They are insoluble in common organic solvents such as ethanol, methanol, chloroform or acetone, but soluble in DMSO and DMF. Molar conductance values of the soluble complexes in DMF showed low values (5.868-12.300 µS) indicating them to be non-electrolytic.

 

Table 1: Characterisation  Data of the Schiff base

Description	Observations
Colour	Off white
Melting Point	274 oC
IR	γN-H 3300 cm-1 nC=O (Lacton) 1725 cm-1  nC=O1680 cm-1  nC=C 1559 cm-1  nC=N 1610 cm-1 nC-O-C 1076 cm-1
Elemental Analysis	C (67.25%), H(4.70%), N(13.05%),O(14.92%
UV	267 nm, 328.2 nm
1H NMR	CDCl3 (500MHz) 2.42(s, 3H), 6.9(s,1H), 7.30-7.90( m, 8H), 8.8(s, 1H)

 

Infrared spectra:

IR spectra of the Schiff base showed the absence of bands at 1725 and 3300 cm^-1 due to carbonyl n(C=O) and n(NH₂) stretching vibrations and, instead, appearance of a strong new band at ~ 1610 cm^-1 assigned²⁰ to the azomethine, n(C=N) linkage. It suggested that amino and aldehyde moieties of the starting reagents are absent and have been converted into the azomethine moiety (Fig.1). The comparison of the IR spectra of the Schiff base and their metal complexes (Table 2 &3) indicated that the Schiff base was principally coordinated to the metal atom

a)      The band appearing at 1610 cm^-1 due to the azomethine was shifted to lower frequency by ~ 10-15 cm^-1 indicating²¹ participation of the azomethine nitrogen in the complexation.

b)      A band appearing at 3374-3449 cm^-1 in metal complexes which have significantly different characteristic of n_OH stretching vibration due to stretching modes of coordinated water molecule.

c)      Further conclusive evidence of the coordination of these Schiff base compounds with the metals, was shown by the appearance of weak low frequency new bands at 565-640 and 435-522 cm^-1. These were assigned²² to the metal-nitrogen (M-N) and metal-oxygen (M-O) respectively. These new bands were observed in the spectra of the metal complexes and not in the spectra of its Schiff base compounds thus confirming participation of these hetero groups (O or N) in the coordination.

 

NMR spectra:

The ¹H NMR spectra of the Schiff bases and of their complexes  was taken in DMSO-d₆. The proton magnetic resonance spectrum of Schiff base (mocmps) in DMSO solution showed azomethine proton at d 8.8 and  –NH protons of Schiff  base (mocmps) is seen to resonate at d 7.05 and methyl protons of  6-methyl-4-formyl coumarin at  d 2.42 in metal complex.

Because of the paramagnetic nature of some of the complexes the signals were not clearly resolved. An important feature of PMR spectra of metal complexes of Schiff base (mocmps) is the prominent absence of –NH proton signal which shows the deprotonation of –NH group in 4-phenyl semicarbazide. The methyl protons and aromatic protons of Schiff base of the divalent metal ion complexes did not show significant shift in d values.

 

Magnetic moments and UV-visible spectra:

The room temperature magnetic moment of the solid cobalt (II) complexes was found to be 3.84 B.M, indicative of three unpaired electrons per Co (II) ion in an octahedral environment. The Cu (II) complex showed μ_eff value 1.72 B.M indicative of one unpaired electron per Cu (II) ion suggesting this complex within the range consistent to spin-free distorted octahedral geometry. The Mn(II) complex shows high spin paramagnetic moment of 5.45 B.M. corresponding to the presence of five unpaired electrons in an octahedral environment. Similarly the Ni (II) complex showed μ_eff value of 2.73 B.M, corresponding to two unpaired electrons per Ni(II) ion for their ideal six-coordinated configuration. The Pd(II) complex was found diamagnetic.

 

The electronic spectra of the Co(II) chelates showed three bands observed at 13221, 15108 and 16667 cm^-1  which may be assigned to  ³A_2g(F) → ³T_2g (F) (ν₁), ³A_2g(F) → ³T_1g (F) (ν₂)  and ³A_2g(F) → ³T_1g (P) (ν₃), transitions respectively and suggestive of the octahedral geometry around the cobalt ions.

 

The Cu(II) complexes showed bands at  and 13,225; 15,199; 19,696  cm^-1 which indicates three transitions ²B_1g→ ²A_1g, ²B_1g→ ²B_2g and  ²B_1g→ ²E_g respectively, expected for an octahedral geometry of this complex due to the presence of unpaired electrons. The Ni(II) exhibited thee spin-allowed bands at 13221; 15108 and 16600 cm^-1respectively, to the transitions ⁴T_1g(F) → ⁴T_2g(F), ⁴T_1g(F) → ⁴A_2g(F) and ⁴T_1g(F) → ⁴T_1g(P) , expected for an octahedral geometry. The Mn(II) complex showed three d-d absorption bands at 13,224 16,263 and 19,223 cm^-1 corresponding to  ⁶A_1g→ ⁴T_1g (⁴G), ⁶A_1g→ ⁴T_2g (⁴G)  and ⁶A_1g→ ⁴E_1g, ⁶A_1g (⁴G) transitions and are consistent with suggested octahedral geometry around the metal ion. The electronic spectra of Pd(II) complexes showed three bands at 13,225; 14,861 and 15,800 cm^-1 which indicated three transitions ⁴T_1g(F) → ⁴T_2g(F), ⁴T_1g(F) → ⁴A_2g(F) and ⁴T_1g(F) → ⁴T_1g(P) respectively, expected for an octahedral geometry²³.

 

From the discussion of the results of various physico-chemical studies presented above, it may be concluded that the proposed geometry for the transition metal complexes with general formula ML₂.H₂O is octahedral for Co^(II),Ni^(II), Mn^(II) complexes and for  ML₂ is square planer for Cu^(II), Pd^(II) complexes and the bonding in the complexes can be represented as Fig-2.

 

 

Table-2 Physical and analytical data of the metal (II) chelates

Complex	Colour	M.P. °C (decomp)	Molar Conductance µS	B.M. (µeff)	Found (Calc) % C            H           N         O      M
Cu (mocmps)2.H2O	Green	230	12.300	1.72	59.87       4.15    11.62   15.52    8.89 (59.88) (4.16) (11.64)  (15.52) (8.80)
Mn (mocmps)2.H2O	Off white	260	6.484	5.45	60.57    4.20     11.77    15.70    7.70 (60.59)  (4.21)  (11.78)  (15.71) (7.71)
Ni (mocmps)2.H2O	Yellow	250	6.010	2.73	60.27    4.17      11.70    15.61    8.16 (60.28)  (4.18)  (11.72)   (15.63)  (8.19)
Co (mocmps)2.H2O	Blackish brown	255	5.868	3.84	60.25     4.16      11.71    15.62   8.21 (60.26)  (4.18)   (11.72)  (15.63) (8.22)
Pd (mocmps)2.H2O	Green	240	6.689	Diamagnetic	56.49    3.90      10.97     14.64    13.90 (56.51)  (3.92)  (10.99)   (14.65) (13.92)

 

Table 3: IR and UV-visible spectral data of the metal(II) chelates

Complex	IR (cm-1)	Intra-Ligand transitions Band in cm-1	d-d transitions Band in cm-1
Cu (mocmps)2.H2O	1597 (s, C=N), 1171 (s, C-O), 3447 (s, OH), 566 (ms, M-N), 506 (ms, M-O)	30030; 37579	13225; 15199; 19696
Mn(mocmps)2.H2O	1597 (s, C=N), 1172 (s, C-O), 3349 (s, OH), 565 (ms, M-N), 506 (ms, M-O)	29949; 37707	13224; 16263; 19223
Ni (mocmps)2.H2O	1597 (s, C=N), 1171 (s, C-O), 3348 (s, OH), 565 (ms, M-N), 506 (ms, M-O)	30021; 37721	13221; 15108; 16600
Co (mocmps)2.H2O	1597 (s, C=N), 1173 (s, C-O), 3324 (s, OH), 565 (ms, M-N), 505 (ms, M-O)	30039; 37721	13221; 15108; 16667
Pd (mocmps)2.H2O	1597 (s, C=N), 1174 (s, C-O), 3345 (s, OH), 565 (ms, M-N), 506 (ms, M-O)	30713; 37580	13225; 14861; 15800

S=sharp, ms=medium sharp

 

 

Figure 2

 

Proposed structure of the metal(II) complex

 

Antibacterial properties:

The title Schiff base and their metal chelates were evaluated for their antibacterial activity against the strains Staphylococcus aureus and Staphylococcus abony and antifungal activity against strain Candida albicance by the tube dilution technique.

 

The lowest concentration which showed no visible growth was taken as an end point known as minimum inhibitory concentration (MIC).

 

A comparison of the antimicrobial activity of the Schiff base and their metal complexes showed that the antimicrobial activity of the Schiff base was enhanced due to the complexation with metal ion. The results of the studies of minimum inhibitory concentration of the Schiff base and their metal complexes are summarized in Table 4.

 

Antimicrobial^a Activity (MIC, µg ml^-1) of Schiff base (mocmps) and its   Metal Complexes

Compound	1	2	3
Schiff base (mocmps)	<200	<200	<200
Co(mocmps)2.H2O	100	100	75
Cu(mocmps)2.H2O	100	100	100
Mn(mocmps)2.H2O	100	100	100
Ni(mocmps)2.H2O	50	100	75
Pd(mocmps)2.H2O	100	100	75

^a 1: S. aureus,  2: S. abony, 3: Candida albicance

 

CONCLUSION:

In the antibacterial screening against bacteria S. aureus and S. abony it was found that  the Schiff base showed  MIC values greater than 200 μg/ml, where as transition metal complexes of Schiff base showed MIC value 100 μg/ml except [Ni(mocmps)₂.H₂O] which was found to be 50 μg/ml.

 

Antifungal screening was done against organism such as Candida albicance, the Schiff base show MIC values 200 μg/ml. Metal complexes of transition metals of the Schiff base shoed that they have better activity against Candida albicance.

The results of the screening of the Schiff base and their metal complexes for antimicrobial activity indicate that the antimicrobial activity of the Schiff base was enhanced on complex formation with metal in all cases studied.

 

ACKNOWLEDGEMENTS:

The authors gratefully acknowledge to Mr. Devidas Jadhav for helping for NMR facility and Mrs. Sanjivani for screening antimicrobial activity. We are also grateful to the Management and Principal of Patkar-Varde College and Dr. A G Gadre, Head, Department of Chemistry for guidance, constant encouragement and support to carry out this research work.

 

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Received on 21.03.2011        Modified on 02.04.2011

Accepted on 13.04.2011        © AJRC All right reserved