Canadian Journal of Applied Sciences


ISSN: 1925-7430
Short Key Title: Can J App Sci
DOI: http://dx.doi.org/10.21065/19257430
Start Year: 2011

SYNTHESIS, SPECTRAL CHARACTERIZATION OF SCHIFF BASE TRANSITION METAL COMPLEXES: ACHE INHIBITOR, ANTIOXIDANT AND ANTIMICROBIAL ACTIVITY STUDIES
K. H. Kumar Naik, B. Ashok, Avinash Prakashab, Nagaraja Naika
1. Department of Studies in Chemistry,University of Mysore, Manasagangotri,Mysore-06, India. 2. Department of studies in biotechnology,University of Mysore, Manasagangotri, Mysore-06, Karnataka, India.
Keywords: Schiff bases, Metal complexes, Enzymatic activity, DPPH Assay, Antimicrobial activity.
Abstract

In the present study, we synthesized Novel ligand and their metal complexes with 8-((2-(2,4-dinitrophenyl)hydrazono)methyl)-7-hydroxy-4-methyl-2H-chromen-2-one ligand. The colored complexes were prepared by the addition of chloride salts of Manganese(II), Cobalt(II), Nickel(II) and Copper(II) to a solution of ligand. In conclusion, the structures of the obtained complexes were characterized by FT-IR, elemental analysis, UV-spectral studies, conductmetric and magnetic susceptibility measurements. The synthesized metal complexes were investigated for biological activities. Enzymatic inhibition activity has been done by using acetylcholinesterase (AChE) enzyme, antioxidant activity by DPPH assay and also the antimicrobial studies. All tested metal complexes and ligand reveal effective biological activities.

Article Information

Identifiers and Pagination:
Year:2013
Volume:3
First Page:90
Last Page:107
Publisher Id:CanJAppSci (2013 ). 3. 90-107
Article History:
Received:June 11, 2013
Accepted:July 29, 2013
Collection year:2013
First Published:October 1, 2013

INTRODUCTION

In the recent years it has been the trend to synthesize the ligand molecules having definite frame work of donor atoms and co-ordinate them with different metal ions such of the complexes have been further explored for their catalytic and biological activities [1, 2]. For the last few years much attention has been casted on polyfunctional ligands, which can encapsulate the metal ions. Multi-metal complexes have acquired a position of significance in the area of bio-inorganic chemistry. Many enzymes and proteins involving multimetal systems have also been reported [3, 4]. Coumarin is structurally the least Complex member of large class of compounds known as benzopyrones. Coumarin constitute an important class of compounds with several type of pharmacological agents possessing anticancer, anti-HIV [5], anticoagulant, antithrombotic, antimicrobial [6], antiallergic, anti-inflammatory and spasmolytic [7]. It has been found that the binding of a metal to the coumarin moiety retains or even enhances its biological activity [8]. The enzyme acetylcholinesterase (AChE) hydrolyzes the neurotransmitter acetylcholine to acetate and choline at the cholinergic synapses [9], terminating nerve impulse transmission. It is known that AChE is effectively inhibited by organophosphate and carbamate pesticides, and also by metals [10].

Since the late 1980 a number of in-vitro and in-vivo studies have investigated the possible use of coumarins in the treatment of cancer [11]. The in-vitro effects of coumarins on the growth of cell carcinoma that derived cell lines show that coumarins and 7-hydroxy coumarin were potent cytotoxic and cytostatic agents [12]. The synthesis and biological importance of Co(II), Ni(II) and Cu(II) metal complexes of triazole Schiff bases have effective biological important [13] and also the lanthanide complexes of 4-methyl-7-hydroxycoumarin shows effective pharmacological activity [14]. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and for spasmolytic activity [15].

A survey of the literature aroused our interest in synthesizing and elucidating the structures of transition metal complexes with following new coumarin ONO donor Schiff base and also their biological importance in various fields.

MATERIALS AND METHODS

The chemicals used for synthesizing the precursors, Schiff base and metal complexes were of reagent grade. Organic solvents used included absolute ethylalcohol, diethylether, formamide (DMF). Reagent grade organic solvents were purified and dried by recommended procedures [16]. Hydrochloric and nitric acids (E-Merck) were used. De-ionized water collected from all glass equipments were usually used in all preparations and also for biological applications.

Carbon, hydrogen, nitrogen and oxygen were estimated by using Elemental Analyzer Carlo Erba EA1108 analyzer. The IR spectra of the Schiff bases and their few metal complexes were recorded on a HITACHI-270 IR spectrophotometer in the 4000–250 cm-1 region in a KBr disc. The electronic spectra of the complexes were recorded in HPLC-grade DMSO solvent on a VARIAN CARY 50-BIO UV spectrophotometer in the region 200–1100 nm. The electrochemistry of all the complexes was recorded on a CHI1110A-electrochemical analyzer (made in the USA) in DMSO containing 0.05M n-Bu4NClO4 as the supporting electrolyte. Molar conductivity measurements were recorded on an ELICO-CM-82 T Conductivity Bridge with a cell having a cell constant of 0.51 and the magnetic moment was carried out by using Faraday balance.

Synthesis of the ligand

Synthesis of  7-Hydroxy-4-Methylcoumarin[1].

A mixture of resorcinol (0.2 mol) and ethylacetoacetate (0.2 mol) is cooled to 0-5 oC and conc. sulphuric acid (25 mL) is added gradually with constant shaking [17]. The reaction mixture is then kept in a refrigerator for 24 h. and poured into crushed ice with stirring. The separated solid is filtered, washed with water and recrystallized from ethanol as cream colored needles. Yield: 82%; MP: 185 oC.     

Synthesis of 8-Formyl-7-Hydroxy-4-Methylcoumarin[2].

 8-formyl-7-hydroxy-4- methylcoumarin is synthesized as described in the literature [17]. 7-hydroxy-4-methylcoumarin (0.03 mol) and hexzmethylenetetramine(HMTA) (0.07 mol) in 50 mL glacial acetic acid was heated for 4-5 h. on water bath. To this, 75 mL of 20% HCl was added and the heating was continued for another 20 minutes. Then, the solution is cooled to room temperature and extracted with ether. The ether layer was evaporated and the remaining liquid portion was poured into crushed ice which resulted in the pale yellow colored solid. The product formed is filtered, dried and was recrystallized from hot ethanol. Yield: 16.36%; MP: 176-177oC.

Synthesis of Schiff base ligand[3].

The Schiff base has been synthesized by refluxing the reaction mixture of hot ethanolic solution (30 mL) of 2,4,dinitrophenyl hydrazine (0.01mol) and hot ethanolic solution (30 mL) of 8-formyl-7-hydroxy-4-methylcoumarin (0.01mol) for 4-5 h. with the addition of 2-3 drops of conc. hydrochloric acid [18]. Resulting mixture of Schiff base was filtered, washed with cold EtOH and recrystallized from EtOH.

For C37H35N8O16

Anal. Calc. %. C. 53.03, H. 3.10, N. 14.21, O.29.01.

Found %. C.53.09, H. 3.12, N.14.25. O. 29.07.

IR data (KBr; ?, cm–1): 2910-2920 br, 2310-2320 s, 1720-1725 s, 1475-1485 s, 1150-1155 v s,

Scheme;                                           


Synthesis of metal complexes. An alcoholic solution of Schiff base (2 m mol) was refluxed with (1 mmol) of metal chlorides in ethanol on water bath for 2-3 h [19]. Then, to the reaction mixture (2 m mol) of sodium acetate was added and reflux was continued for 3h. The separated complex was filtered, washed thoroughly with water, ethanol and ether. Finally the complexes were dried in vacuum over fused CaCl2.

Synthesis of [Mn(C37H35N8O16)(H2O)2] (1a). Yield: 61%. M.P: 182-185 oC, Anal. Calcd for: [Mn(C37H35N8O16)(H2O)2], Mn, 6.98; C, 49.02; H, 3.84; N, 12.21; O, 28.12. The new bands in the region of ~685-695 cm-1 and ~445-455 cm-1 in the metal complexes are assigned to stretching frequencies of ?(M-N) and ?(M-O) bonds respectively.

Synthesis of [Co(C37H35N8O16)(H2O)2] (1b). Yield: 51%. M.P: 196-198 oC, Anal. Calcd for: [Co(C37H35N8O16)(H2O)2], Co, 6.81; C, 48.31; H, 3.21; N, 12.07; O, 28.06. In the low-frequency region, two bands were observed for complexes at ~671-674 and ~452-456 cm-1, which were attributed to ?(M-N) and ?(M-O), respectively.

Synthesis of [Ni(C37H35N8O16)(H2O)2] (1c). Yield: 53%. M.P: 205-208 oC, Anal. Calcd for: [Ni(C37H35N8O16)(H2O)2], Ni, 6.83; C, 48.61; H, 3.45; N, 11.86; O, 28.14. In the low-frequency region, two bands were observed for complexes at ~670-673 and ~448-452 cm-1, which were attributed to ?(M-N) and ?(M-O), respectively.

Synthesis of [Cu(C37H35N8O16)(H2O)2] (1d). Yield: 65%. M.P: 198-200 oC, Anal. Calcd for: [Cu(C37H35N8O16)(H2O)2], Cu, 7.01; C, 48.12; H, 3.58; N, 12.10; O, 27.89. In the low-frequency region, two bands were observed for complexes at ~664-670 cm-1 and ~460-465 cm-1, which were attributed to ?(M-N) and ?(M-O), respectively.

Figure-1; Proposed structure of metal complexes

BIOLOGICAL TESTING

Enzymatic Activity (Acetylcholinesterase activity (AChE))

 Acetylcholine esterase activity was assessed as described by and modified by Briefly, claw muscles were homogenised on ice in 20 mM phosphate buffer, pH 7.0, 0.1% Triton X-100 (1/3 volume/weight) using an Ultra-Turax homogenizer and centrifuged for 20 min at 10000g. The acetylcholine esterase activity of 100 lL supernatant in presence of 0.01 M dithionitrobenzoic acid (DTNB) as reagent and 2.8 mM acetylthiocholine iodide (AcSCh) as substrate was then measured at 412 nm using a microplate reader at a controlled temperature of 20 oC. No attempt was made to distinguish between AChE and pseudo-cholinesterase. The activity of the enzyme was expressed in nmol of substrate hydrolysed per minute per milligram of protein.

Antioxidant activity

DPPH assay-The evaluation of antioxidant activity of newly synthesized compounds was done by DPPH radical scavenging activity assay. Internal standard BHA and the synthesized compounds of different concentrations were prepared in distilled ethanol, 1 mL of each compound solutions having different concentrations (10 µM, 25 µM, 50 µm, 100 µM, 200 µM and 500 µM) were taken in different test tubes, 4 mL of 0.1 mM ethanol solution of DPPH was added and shaken vigorously. The tubes were then incubated in the dark room at RT for 20 min. A DPPH blank was prepared without compound, and ethanol was used for the baseline correction.  Changes (decrease) in the absorbance at 517 nm were measured using a UV-visible spectrophotometer and the remaining DPPH was calculated. The percent decrease in the absorbance was recorded for each concentration, and percent quenching of DPPH was calculated on the basis of the observed decreased in absorbance of the radical. The radical scavenging activity was expressed as the inhibition percentage and was calculated using the formula:                     

                        Radical scavenging activity (%) = [(Ao-A1)/Ao X 100]                                 

Where Ao is the absorbance of the control (blank, without compound) and A1 is the absorbance of the compound.

Antimicrobial activity

The in vitro biological screening effects of the investigated compounds were tested against the bacteria: Escherichia coli, Bacillus subtilis and Ralstonia solanacearum by the well-diffusion method, 24 using agar nutrient as the medium. The antifungal activities of the compounds were evaluated by the well-diffusion method against the fungi viz., Aspergillus niger, Aspergillus flavus and Rhizoctonia bataicola cultured on potato dextrose agar as medium. The stock solution (10-2 M) was prepared by dissolving the compounds in DMSO and the solutions were serially diluted to find MIC values. In a typical procedure, 25 a well was made on the agar medium inoculated with microorganisms. The well was filled with the test solution using a micropipette and the plate was incubated 24 h for bacteria and 72 h for fungi at 35°C. During this period, the test solution diffused and the growth of the inoculated microorganisms was affected. The inhibition zone was developed, at which the concentration was noted.

RESULTS AND DISCUSSION

Chemistry. The synthetic strategies adopted for the synthesis of the intermediate and target compounds are depicted in the Scheme-1. A mixture of 8-formyl-7-hydroxy-4-methylcoumarin and 2,4-dinitrophenylhydrazine in 1:1 ratio in alcoholic medium containing 5-6 drops of concentrated HCl was refluxed for 3-4 h to form Schiff base [18]. The purity of the ligands was confirmed by elemental analyses, electronic spectra and IR spectral studies.

Physico-chemical techniques

         Electrical Conductivity.

^M     =            1000 x Cell Constant x Specific Conductance

                                        Molar Concentration                      

 

Conductivity measurements of the complexes in HPLC grade DMSO solutions were made to verify the ionic formulation of the complexes. The molar conductivity of a solution was obtained from a following relation. The measurements were made by using a systronics conductivity meter 304 conductivity bridge provided with a dip-type conductivity cell having platinised platinum electrodes. The cell constant was determined by measuring the resistance of aqueous KCl solutions, the specific conductivities of which were known accurately from literature [19]. The conductivity measurements of the complexes were carried out at 10-3 M is HPLC grade DMSO solvents.

The magnetic susceptibility measurements of the complexes were obtained at room temperature using Gouy balance. Pure Hg[Co(SCN)4] was synthesized and used as calibration standard [20]. The effective magnetic moment values of the complexes are in table-1. The complexes are paramagnetic in nature. The magnetic moment values of complexes are in the range 1.29-5.85 BM, which suggests that the complexes have high spin octahedral geometry [21, 22]. The Mn(II), Co(II), Ni(II) and Cu(II)   complexes are colored, stable and non-hygroscopic in nature. The complexes are insoluble in common organic solvents like chloroform, ethanol and methanol but soluble in DMF and DMSO. The elemental analyses shows that, the above complexes have 1:2 stoichiometry of the type ML2.2(H2O) where L stands for a singly deprotonated ligands . The molar conductance values are too low to account for any dissociation of the complexes in DMSO, indicating the non-electrolytic nature of the complexes in DMSO  shown in table-1.

 

Figure-1. Proposed structure for metal complex

Table-1; Molecular weight, melting point, Elemental analysis, yield, magnetic measurements

 

Compounds

 

Mol. Formula

 

Mol.wt

 

M.p. oC

 

Calc. (found) (%)

 

Yield(%)

 

µeff.(B.M.)

 

Mol.cond.(?cm2 mol-1)

M

C

H

N

O

L

C17H12N4O7

389.25

195-198

--

53.03(53.09)

3.10(3.12)

14.21(14.25)

29.01(29.07)

40

--

--

1a

[Mn(C37H35N8O16)(H2O)2]

901.86

182-185

6.98(7.03)

49.02(49.11)

3.84(3.92)

12.21(12.30)

28.12(28.18)

61

5.81

28

1b

[Co(C37H35N8O16) (H2O)2]

901.56

196-198

6.81 (7.04)

48.31(48.40)

3.21(3.45)

12.07(12.12)

28.06(28.11)

51

3.75

23

1c

[Ni(C37H35N8O16) (H2O)2]

898.41

205-208

6.83(7.01)

48.61(48.65)

3.45(3.51)

11.86(11.91)

28.14(28.20)

53

2.45

32

1d

[Cu(C37H35N8O16) (H2O)2]

905.26

198-200

7.01(7.09)

48.12(48.15)

3.58(3.61)

12.10(12.14)

27.89(27.94)

65

1.29

36

Table-2; The Important Infrared Frequencies (in cm-1) of Metal Complexes.

 

Compound

Coordinated

?(H2O)(cm-1)

Lactonyl

?(C=O) (cm-1)

?(C=N) (cm-1)

?(NH) (cm-1)

Phenolic

? (C-O) (cm-1)

? (M-N) (cm-1)

? (M-O) (cm-1)

Ligand(C37H35N8O16)

--

1720-1725

1475-1485

2910-2920

1150-1155

--

--

[Mn(C37H35N8O16)(H2O)2]

3420-3430

1732-1740

1516-1525

2926-2930

1080-1085

685-695

445-450

[Co(C37H35N8O16) (H2O)2]

3446-3450

1697-1700

1614-1624

2924-2931

875-880

671-674

452-456

[Ni(C37H35N8O16) (H2O)2]

3450-3455

1705-1710

1620-1625

2930-2935

995-1005

670-673

448-452

[Cu(C37H35N8O16) (H2O)2]

3425-3435

1702-1015

1595-1605

2932-2940

1050-1060

664-670

460-465

 

Table-3; Enzymatic Inhibition (%) of the Schiff base ligand and its metal complexes

Compounds No.

Complexes

% AchE. Inhibition

L

Ligand(C37H35N8O16)

64±0.25

1a

[Mn(C37H35N8O16)(H2O)2]

72±0.09

1b

[Co(C37H35N8O16) (H2O)2]

81±0.13

1c

[Ni(C37H35N8O16) (H2O)2]

53±0.14

1d

[Cu(C37H35N8O16) (H2O)2]

91±.56

 

Table-4; Antioxidant activity (IC50) of the Schiff base ligand and its metal complexes

Compound No.

Compounds

IC50 (µM)

L

Ligand (C37H35N8O16)

>310

1a

[Mn(C37H35N8O16)(H2O)2]

209±0.13

1b

[Co(C37H35N8O16) (H2O)2]

121±0.09

1c

[Ni(C37H35N8O16) (H2O)2]

224±0.53

1d

[Cu(C37H35N8O16) (H2O)2]

122±0.21

Standard

Ascorbic acid

63±0.05

 

 

Table-5; Antibacterial activity of the Schiff base ligand and its metal complexes (minimum inhibitory concentration × 10-2 M).

Compounds

E. coli

B. subtilis

R. solanacearum

Ligand(C37H35N8O16)

5.2

11.0

06.0

[Mn(C37H35N8O16)(H2O)2]

4.5

10.3

04.6

[Co(C37H35N8O16) (H2O)2]

4.1

08.0

05.0

[Ni(C37H35N8O16) (H2O)2]

4.6

10.0

07.3

[Cu(C37H35N8O16) (H2O)2]

3.8

10.2

06.2

chloramphenicol

6.0

07.0

04.0

 

Table-6; Antifungal activity of the Schiff base ligand and its metal complexes (minimum inhibitory concentration × 10-2 M).

Compounds

A. niger

A. flavus

R. bataicola

Ligand(C37H35N8O16)

6.0

5.4

5.1

[Mn(C37H35N8O16)(H2O)2]

3.1

3.5

4.5

[Co(C37H35N8O16) (H2O)2]

4.9

4.2

5.1

[Ni(C37H35N8O16) (H2O)2]

5.6

5.1

6.1

[Cu(C37H35N8O16) (H2O)2]

5.1

4.1

3.4

Nystatin

8.0

7.1

5.4

 

Figure-1; Proposed structure of metal complexes

 

Figure-2; Electronic Absorption Spectrum of Schiff base

Figure-3; Electronic Absorption Spectrum of Co(II) Complex

Figure-4;  Electronic Absorption Spectrum of Ni(II) Complex

 

Figure-5; IR Spectrum of Schiff Base

 

Figure-6; IR Spectrum of Co (II) Complex

 

Figure-7; IR Spectrum of Ni (II) Complex

 

 

Figure-8; Enzymatic Inhibition (%) activity of the Schiff base ligand and its metal complexes


Figure-9; Antioxidant activity of the Schiff base ligand and its metal complexes

 

Figure-10; Antibacterial activity of the Schiff base ligand and its metal complexes

 

Figure-11; Antifungal activity of the Schiff base ligand and its metal complexes

Electronic Absorption Spectral Studies. The UV-Visible spectra in the region 200-1100 nm were measured by systronics double beam spectrophotometer 2202 model  using calibrated quartz cells. Weighed samples were dissolved in appropriate solvents of HPLC grade at a concentration of 10-6 and 10-7 M. All the measurements were carried out at room temperature. The electronic absorption spectrum of the Schiff base is depicted in figure-2 exhibited two absorption bands around 340 nm and 420 nm respectively. The first band around 340 nm corresponds to ???* of the azomethine group and second band at 420 nm corresponds to n? ?* transitions.The typical electronic absorption spectrum of the Co(II) complex assented in figures-3. The electronic spectra of Co(II) complexes exhibit absorption bands in the region 8000-10000 cm-1 and 18000-20000 cm-1 corresponding to the transitions 4T1g (F) ? 4T2g (F) (?1) and 4T1g (F)?4T1g (P) (?3) respectively [23]. In the present investigation, brownish Co(II) complexes shows the absorption bands around 240 nm  and 384 nm corresponding to ?1 and ?3 transitions respectively. The ?2 band is not observed due to strong proximity to ?3 transition. These bands are characteristic of high spin octahedral Co(II) complexes. The spectrum is presented in the figure-3. The Ni(II) complex exhibited three bands at 246, 261 and 266 nm attributed to the 3A2g ?3T2g (?1), 3A2g ? 3T1g (F) (?2)  and 3A2g ? 3T1g (P) (?3) transitions respectively, which indicate octahedral geometry around Ni(II) ion and the spectra shown in figure-4. And also for Cu(II) and Mn(II) complexes results comparable with other reported complexes [24-26].The electronic spectra of Cu(II) complexes display two prominent bands: a low-intensity broad band around 16,243 cm-1 is assignable to 2Eg ? 2T2g transition and another high-intensity band at 26,366 cm-1 is due to ligand? metal charge transfer. On the basis of electronic spectra, the distorted octahedral geometry around the Cu(II) ion is suggested [27]. The Cu(II) complexes showed magnetic moment of 1.80–1.86 BM, which is slightly higher than the spin-only value (1.73 BM) expected for one unpaired electron, which offers the possibility of an octahedral geometry [28].

Infrared Spectral Studies. The Spectra of ligand and its metal complexes were obtained on a Shimadzu 8400-S, Japan, in the region 4000-350 cm-1. The typical infrared spectrum of the Schiff base has been reproduced in figure-5. The most important IR bands of Schiff base exhibited a broad band at 3489 cm-1­­­­, strong band at 1683 & 1622 cm-1 assigned to H-bonded -OH stretching, ?(C=O) lactonic carbonyl and azomethine ?(C=N) vibrations respectively [28].  A medium band around 975cm-1 is characterized for ? (O-C-O) vibrations. A broad band in the range 2924 cm-1 is ascribed to the stretching vibration of ?(NH) [28]. The medium intensity bands at 1050 and 1150 cm-1 are attributed to ?(N-N) and ?(C-O) vibrations, respectively [29].   The IR spectra of the metal complexes clearly indicate the bonding mode of Schiff base with the metal ions. The prominent infrared spectral data are presented in the table-2 and the some of  IR spectra of the representative Co(II), Ni(II) complexes are shown in figures-6 and figure-7 respectively.

In comparison with the spectra of the Schiff base,  the metal complexes exhibited the band of ?(C=N) in the region 1612 cm-1; showing the shift of band to lower wave numbers indicating that, the azomethine nitrogen is coordinated to the metal ion. The disappearance of the broad band due to H-bonded –OH stretching in the spectra of the metal complexes gives evidence for the formation (M-O) bonds via deprotonation. Further, the high intensity band due to phenolic ?(C-O) appeared as 1080 cm-1. The new bands in the region of 451 and 694 cm-1 in the metal complexes are assigned to stretching frequencies of (M-O) and (M-N) bonds respectively The unaltered position due to lactonyl ?(C=O) in all the metal complexes confirms its non involvement in coordination. Thus, the IR spectral data provide strong evidence for the complexation of the potentially bidentate Schiff base [30].

Enzymatic Activity (Acetylcholine esterase activity (AChE)). In present investigation, we studied the Ache enzyme inhibition activity percentage of our newly prepared ligand and metal complexes for the discovery of new acetylcholinesterase inhibitors. Various  structural studies revels that the specific positioning of the nitrogen atom and octahedral geometry of the metal complexes in relation to the aromatic ring will shows better inhibition activity [34] and it  is essential for the strong affinity between the antagonists and the receptor. Examined the overlap factor (HOMO) through an indirect approach receptor mapping [31]. According to his calculations, the metal complexes of 1a, 1b and 1d are very active compounds and the metal complexes of 1c and ligand shows moderate enzymatic inhibition activity the data shown in table- 3 and figure-8.

Antioxidant activity.

DPPH Radical Scavenging Activity. The antioxidant activity of ligand as well as metal complexes is presented in table-4 and figure-9. At the different concentration of 10, 25, 50, 100, 200 and 500 µM, few complexes showed a much stronger DPPH scavenging (>80%) than free Ascorbic acid (63%). The vitamin C showed 63% of DPPH scavenging property. The marked antioxidant activity of ligand [L] and metal complexes 1a and 1c in comparison to free Ascorbic acid, could be due to the coordination of metal after complexation of the system, increasing its capacity to stabilize unpaired electrons and Thereby, to scavenge free radicals. And remain complexes of 1b and 1d shows moderate activity of scavenging property [32].

Antimicrobial activity.

The minimum inhibitory concentration (MIC) values of the compounds against the respective strains are summarized in table-5, table-6, figure-10 and figure-11. The antimicrobial screening results of all the synthesized ligand and their metal complexes exhibited antimicrobial properties. It is important to note that the metal complexes exhibited a more inhibitory effect compared to their respective parent ligands. The enhanced activity of the complexes over the ligand can be explained on the basis of chelation theory [33]. It is known that chelation makes the ligand a more powerful and potent bactericidal agent, thus killing more of the bacteria than the ligand. The enhancement in the activity may be rationalized on the basis that ligands mainly possess an azomethine (C = N) bond. It has been suggested that ligands with hetero donor atoms (nitrogen and oxygen) inhibit enzyme activity, since the enzymes that require these groups for their activity appear to be especially more susceptible to deactivation by metal ions on coordination. It is observed that, in a complex, the positive charge of the metal ion is partially shared with the hetero donor atoms (nitrogen and oxygen) present in the ligand, and there may be p-electron delocalization over the whole chelating system [34]. Thus the increase in the lipophilic character of the metal chelates favors their permeation through the lipoid layer of the bacterial membranes and blocking of the metal binding sites in the enzymes of microorganisms. Other factors, namely solubility, conductivity and bond length between the metal ion and the ligand, also increase the activity. The increase in the activity of metal complexes against fungi is due to the formation of a hydrogen bond between the azomethine nitrogen atom and active centers of the cell constituents, resulting in interference with the normal cell process.

 

CONCLUSION

Based on these studies, the newly synthesized ligands and their complexes were characterized by various spectral studies and analytical data. The coordinating ability of the ligands was proved in complexation reactions with Mn(II), Co(II), Ni(II) and Cu(II) ions. In all the complexes ligand act as a tridentate chelate around the metallic ion with 2 compartments and provide ONO donating sites to each metal ion in both compartments. On the basis of different techniques, it is proposed that, the metal complexes have octahedral geometries and the Schiff base act as a versatile tridentate ligand. The bonding of ligand to metal ion was confirmed by the analytical  and spectral studies. All these observations put together lead us to propose the following structure for the Mn(II), Co(II), Ni(II) and Cu(II) complexes. The biological activity results show that all the complexes exhibited effective activity when compared to their respective ligand.

 

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Editor in Chief
Xianghui Qi (PhD)
Jiangsu University, Zhenjiang, China

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Dr. Xianghui Qi is working as Professor in the School of Food & Biological Engineering, Jiangsu University, China. His research interests: Biosynthesis of high value-added chemicals by microbes and engineered strains; Discovery of novel genes, enzymes and new strains; Rational & Irrational design of microbial enzymes; Isolation, identification and evolution of microbes; Metabolic engineering & Pathway engineering of functional microbes, and biotransformation; Metabolic regulation based on the research of microbial omics; Application of high value-added products including functional sugar alcohols by biosynthesis and biotransformation based on microbial engineered strains.

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