Schiff's Base Ligands and Their Transition Metal

May 2014 –July 2014, Vol. 4, No. 3; 1946-1964.

E- ISSN: 2249 –1929

Journal of Chemical, Biological and Physical Sciences An International Peer Review E-3 Journal of Sciences Available online atwww.jcbsc.org

Section A: Chemical Sciences CODEN ( USA): JCBPAT

Research Article

Schiff’s Base Ligands and Their Transition Metal Complexes as Antimicrobial Agents Pallavi Goel, Dinesh Kumar, Sulekh Chandra 1 2

Department of chemistry, SRM University, Modinagar, Ghaziabad, 201204, India

Department of Chemistry, Banasthali Vidyapith, Banasthali, Rajasthan-304022, India 3

Department of Chemistry, Zakir Hussain Delhi College, New Delhi-110002, India Received: 08 July 2014; Revised: 17 July 2014; Accepted: 24 July 2014

Abstract: Schiff’s base ligands and their transition metal complexes comprise miscellaneous therapeutically potent applications in the field of medicinal chemistry and synthetic applications in the field of the organic and inorganic chemistry. This review includes synthesis of Schiff’s base ligands and their transition metal complexes (Mn (II), Cu(II), Ni(II) and Co(II) metal ions) and an appropriate balance between the broad spectrum pharmacological profile. This study overview, collecting the most significant strategies adopted in last few years to design promising antimicrobial transition metal complexes of schiff’s bases which would be a help to the working scientists or researchers in the biological field and is expected to hopefully produce analogues with better biological profiles and with the minimal requirement to maintain the activity. Keyword:Schiff’s baseligands, metal complexes, Biological activity, medicinal chemistry

1946 J. Chem. Bio. Phy. Sci. Sec. A, May 2014 – July 2014; Vol.4, No.3; 1946-1964

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INTRODUCTION One of the great researchers named Hugo Schiff in the year 1864 invented Schiff’s bases. Schiff’s bases are synthesized when condensation reaction take place between primary amine and carbonyl group (aldehyde or ketone). Basically, a Schiff’s base (Figure 1) is a carbon-nitrogen double bond (-CH=N-, azomethine or imine group) containing compound in which the carbonyl group (C=O) of an aldehyde or ketone has been replaced by primary amine. The azomethine group of Schiff’s base play an important role for showing excellent biological activities 1 .

Figure 1: Formation of Schiff’s base ligand Where R = alkyl group or aryl group Although medicinal and biological chemistry was almost exclusively based on organic compound Schiff’s base ligand and its transition metal complexes, during the past decades. Transition metal complexes of Schiff’s base ligand had gain a growing interest in pharmacological field for the use as antimicrobial agents and show good biological activities against pathogenic microorganisms 2-6 . It had been observed with several experimental results that the metal complexes had more considerable antimicrobial activity than their parent ligands 7-9 . The currently available antimicrobial drugs provide the emerging microbial resistance which not only drives the search for novel prokaryotic targets but also new molecules which inhibit the activity of drugs. It may also represent an interesting task toward designing new antimicrobial drugs. Metal complexes of Schiff’s base ligands also showed good anticancer activity10-11 . Many of the anticancer drugs are multipurpose ligands12 , some of which demonstrate increased anticancer activity when used in the form of their metal complexes13 . It had been suggested that certain forms of cancer are caused by virus.The interaction between the metal ion and the ligand with cancer-associated viruses might signify an important way for designing new anticancer agents 14, 15 . There is also a possibility of inorganic metal complexes which provides the platforms for the development of selective and potent pharmaceutical agents16-17 . A lot of research has been suggested as per literature survey for the utilization of transition metal complexes of Schiff’s base ligands as drugs to cure numerous diseases like carcinomas 18 , infection control, diabetes, anti-inflammatory19, lymphomas, and neurological disorders. Transition metals show evidence of different oxidation states and can work together with a number of negatively charged molecules. This activity of metal ions had been responsible 1947 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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for the development of metal based drugs which possess potential medicinal and pharmacological applications20 . Schiff’s bases containing heterocyclic scaffolds had been known to possess a broad range of biological and medicinal activities for a long time 21 . In recent years, they are gaining significant interest in the area of drug research22-24 and development related to their broad bioactivities such as antibacterial, antifungal25 anti-inflammatory, antioxidant26 , antiviral and anticancer activities 27 . The chemistry involved in the formation of Schiff’s base complexes had been very well developed on account of the extensive diversity of feasible structure for the ligands and their complexes, depending upon the presence of donor atoms. A lot of Schiff’s bases and their transition metal complexes had been far and wide synthesized due to their pharmaceutical and industrial applications 28 . Recently, a number of researchers are expressing keen interest and are working in the field of functionalizing metal complexes with biomolecules and nanomaterials for therapeutic applications. The different routes have been used for attachment of metal complexes to different types of biomolecules and nanomaterials. The nano-functionalized metal complexes of Schiff’s base ligands have been acted towards targeted delivery and are used to demonstrate the broad range of opportunities and challenges of this promising approach29-30 . Manganese and its compounds are widely used in analytical chemistry, metallurgical processes, paint and pigments industry and alloy industry, particularly in stainless steels. Schiff base complexes of manganese (II) have an excellent catalytic property31 . After viewing the number of applications, it is highly demandable and advantageous to synthesize and characterize Mn(II) complexes of Schiff’s base ligands, which contain donor atoms (N, O, S). The transition metal complexes Mn(II), Co(II), Ni(II) and Zn(II) of 3-methoxysalicylaldehyde-2-aminobenzhydrazone had been exhibited higher antimicrobial activity than the free Schiff’s base ligand32 . Metal complexes of Mn(II) with a Schiff’s base ligand, which was derived from 3-Ethoxy Salicylaldehyde and 2-(2-amino-phenyl)1-H-Benzimidazol(2-[(Z)-{(2-(1H-benzimidazole-2yl)phenyl] imino} methyl]-6-ethoxy phenol) were synthesized. The synthesizedcomplexes were characterized by elemental analysis, magnetic moment measurements, conductivity measurements, IR, UV-VIS, 1H NMR, mass spectra and ESR spectral studies. Antimicrobial activity of the ligand and its Mn(II) complexes were studied against two gram negative bacteria: E.Coli, P.flourescenceand two gram positive bacteria: B.subitilis, S.aureus. The resulting data showed that the metal complexes were more active than the free Schiff’s base ligand33 . Complexes of Mn(II) had been synthesized with macrocyclic Schiff’s base ligand 2,3,9,10-tetraketo1,4,8,11-tetraazacycoletradecane(Figure 2). The ligand was derived by the condensation of diethyloxalate and 1,3-diamino propane and characterized by elemental analysis, mass, IR and 1H-NMR spectral studies. The structures of the complexes were confirmed by elemental analysis, molar conductance, magnetic susceptibility measurements, IR, electronic and electron paramagnetic resonance spectral studies. The molar conductance measurements of Mn(II) complexes in DMF correspond to nonelectrolyte nature. On the basis of spectral studies an octahedral geometry had been assigned. In vitro the ligand and its metal complexes were evaluated against some fungi species i.e., F.odum, A.niger and R.bataticola34 .

1948 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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O

NH Cl

Mn NH

O

O

HN Cl HN

O

Figure 2: Mn(II) complex of 2,3,9,10-tetraketo-1,4,8,11-tetraazacycoletradecane

Mn(II) complex of 5-aminosalicylicacid (Figure 3) had been synthesized and characterized by elemental analyses, magnetic measurements, 1 H NMR, FT-IR, electronic and thermal studies. On the basis of the above studies, the geometry of the metal complexes has been suggested. The synthesized ligand and its Mn(II) complexes had been examined in vitro against C.albicans and A.fumigatus fungi and P.aeruginosa, B.subtilis, E.coli, and S.aureus bacteria in order to check their antimicrobial activity. The experimental results signify that the metal complexes had more activity than the free ligand 5- aminosalicylicacid35. O

OH2 O

O NH 2

Mn

H2 N O

O

OH2

.xH2O O

Figure 3: Mn(II) complex of 5-aminosalicylicacid Complexes of Mn(II) with curcumin ligand (Figure 4) had been synthesized and examined by elemental analysis, molar conductance, magnetic susceptibility, 1 H-NMR, Infra-red, Raman, UV-Visible, EPR spectroscopy, thermal analysis and X-ray diffraction analysis. The synthesized and its complexes were screened for their antibacterial activitiy against E.coli, P.aeruginosa,S.aureus and B.subtilis bacteria and fungicidal activity against C.albicans and A.flavus 36 . Tetradentate macrocyclic ligand [1,2,5,6tetraoxo-3,4,7,8tetraaza-(1,2,3,4,5,6,7,8)tetrabenzene] (Figure 5) and its transition metal complex of Mn(II) had been synthesized and analyzed by different spectral studies like elemental analysis, molar conductance, NMR, mass, FT-IR, electronic and EPR. The spectral studies FT-IR, electronic and EPR confirmed octahedral geometry for the metal complex. The LD 50 values of the ligand and its metal complex had been screened. The antimicrobial activities also examined against


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different bacteria and plant fungi. The result was showing that macrocyclic ligand was potentially more active towards tested microbial species than metal complex37 . CH3 O HO

OH

O CH3

O

H 2O

O

OH2

Mn O

O

CH 3 O

HO

OH O H3 C

Figure 4: Mn (II) complex of curcumin

O

O N H

X

HN

M NH O

X

H N O

Figure 5: Mn(II) complex of 1,2,5,6tetraoxo-3,4,7,8tetraaza-(1,2,3,4,5,6,7,8)tetrabenzene Transition metal complexes of Mn(II) with 2-acetyl thiophene thiosemicarbazone having general composition [MnL2 X2 ] (Figure 6) had been synthesized. The ligand and its metal complexes had also been characterized by elemental analysis, molar conductance, magnetic susceptibility, NMR, mass, IR, UV, and EPR. The spectral studies of the ligand and complex confirms the bidentate nature of the ligand and forms hexacoordinated Mn(II) complexes with octahedral geometry. The thermal studies shows that Mn(II) complexes were more stable as compared to parent ligand. The mycological activities of the complex had been examined against the plant pathogenic fungi i.e. R.bataticola, Fusariumodum, and M.phaseolina38 .


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X S

N HN

NH2

M NH

H2N

S

N

X

S C H3C

Figure 6: Mn(II) complex of 2-acetyl thiophene thiosemicarbazone Cobalt has corrosion resistant property and because of this property, it is used in electroplating to protect objects and give them an attractive finish. It is also widely used in alloy industries 39 . Cobalt compounds had been used as dyeing material to color porcelain, glass, pottery, tile and enamel. Cobalt complex with corrinoid ligands is also important biologically as cobalmins which is an essential part of vitamin B 12 40 . The human body contains 5 mg of cobalamines. The deficiency of cobalmins causes the disease malicious anaemia. Naturally occurring cobalt complexes involve the corrin ring system i.e.vitamin B12 41 . After knowing all important applications, there is need to synthesis the Co complexes of Schiff’s base ligand which may be used as biological agents. Co(II) complexes with 1-phenyl-2,3-dimethyl-4(2-iminomethylbenzylidene)-pyrozol-5-(α-imino)-indole3-propionic acid (Figure 7) of general composition ML2 had been synthesized. The synthesized complex was characterized by different spectral studies like elemental analysis, molar conductance, magnetic susceptibility data, 1 H-NMR, IR, UV-Visible, FAB-Mass and EPR. The antimicrobial activities of Schiff’s base ligand and its metal complex were also examined against the different agents of microorganisms. The experimental results show that the metal complexes were more active than the free ligand42 . O

R Ph

Me

O

N

N

Me N

Me

N

Co N

Me

N Me

N

N

O

Me

Ph R

O

Figure 7: Co(II) complex of 1-phenyl-2,3-dimethyl-4(2-iminomethylbenzylidene)pyrozol-5-(α-imino)-indole-3-propionic acid


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Transition metal complex of Co(II) with benzil bis(carbohydarzone) (Figure 8) was synthesized and studied structurally and pharmaceutically. The synthesized complex was characterized and analyzed by different spectral studies like elemental analysis like elemental analyses, molar conductance, and magnetic susceptibility, NMR, IR, UV-Visible, ESI mass and EPR. The biological activities of the complex was examined against A.niger,A.brassicae and F.oxysporum fungi, which concluded that metal free ligand had better growth inhibition power and this efficiency was positively affected by the Co(II) complex43 .

C

X

N

NH

Co

NH

C HN NH 2

C

N

C

X O

O

NH NH 2

Figure 8: Co(II) complex of benzil bis(carbohydarzone), Where X = Cl- and NO3 Co(II) complexes of 1,10-phenanthroline (1,10-Phen) and 2-(1-(2-phenyl-hydrazono)-propan-2ylidene)hydrazine-carbothioamide had been synthesized. To study the synthesized complexes, different analytical techniques were used like elemental analyses, 1 H-NMR, FT-IR, solid reflectance, molar conductance and magnetic moment. The disc diffusion method were utilized to check the antimicro bial activities of metal complexes against different types of bacteria like E.coli, B.subtillis, P.aeuroginosa and S.aureus and different fungi like C.albicans, P.italicum, G.candidum and A.flavus. The results confirmed the good antimicrobial activities of Co(II) complexes as compared to free ligand 44 . Co(II) complexes with Schiff’s base ligand (Figure 9) were synthesized. The ligand had been prepared by the condensation of 1,4-phenylenediamine with 5,7-dihydroxy-6-formyl-2-methylbenzopyran-4-one or 6formyl-7-hydroxy-5-methoxy-2-methylbenzo-pyran-4-one.The newly synthesized Co(II) complexes were analyzed by different tools such as elemental analysis, magnetic susceptibility, molar conductance, UV VIS, FT-IR, , ESR and thermal analysis. Both the Co(II) complexes of the two Schiff base ligands had been checked for antibacterial activities by using disk diffusion method against S.capitis and E.coli whereas to check the antifungal activity A.flavus and C.albicans were utilized. The Result confirmed better antibacterial activities of the newly synthesized complexes 45 . Two novel Schiff’s base metal complexes of Co(II) (Figure 10) had been synthesized from 2-[(5-bromo2-hydroxybenzylidene)amino]pyridin-3-ol,{5-chloro-2-[(2-hydroxynaphthylidene)amino]phenyl}-phenyl -methanone. All the synthesized compounds were characterized by various elemental and spectral analysis i.e., FT-IR, FAB-mass, molar conductivity, electronic spectra, ESR, thermal, magnetic susceptibility, cyclic voltammetry, electrical conductivity and XRD analyses and also tested against some bacteria and fungi. The Schiff’s base ligand and their Co(II) complexes displayed a good activity against the Gram-positive bacteria; S.aureusand Gram-negative bacteria; E.coliand fungi A.niger and C.albicans. 1952 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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The results showed that the metal complexes displayed better antimicrobial activity as compared to the free ligand46 . X X H C

H C N

N

O O

Co

Co

O O

N

N C H

C H

X X

Figure 9: Co(II) complexes of 1,4-phenylenediamine with 6-formyl-7-hydroxy-5methoxy-2-methylbenzo-pyran-4-one Where X = -OH Br H

N

C

N

O

O Co OH2

OH2 OH2

Figure 10: Co(II) complexes of 2-[(5-bromo-2-hydroxybenzylidene)amino]pyridin-3-ol

The coordination complexes of Co(II) with the Schiff’s base ligands derived from isatin with 3-chloro-4floroaniline and 2-pyridinecarboxaldehyde with 4-aminoantipyrine (Figure 11)had been prepared. The prepared compounds had been characterized by elemental analysis, molar conductance, electronic spectra, FT-IR, FAB mass and magnetic susceptibility measurements. Both Schiff’s base ligands behaved as bidentate and tridentate and coordinated through oxygen and nitrogen donor atoms. Schiff’s base ligands and their metal complexes of Co(II) exhibited good activity against the bacteria species; S.aureus, E.coliand S.fecalisand fungi A.niger, T.polysporum, C.albicans and A.flavus. The results indicated that the metal complexes had higher antimicrobial properties as compared to the free Schiff’s base ligands47 . Schiff’s base ligand 1-ethyl-1, 2, 3, 5, tetrahydroimidazo-quinazolin-5-one semicarbazone and its Co(II) metal complexes (Figure 12) had been synthesized. The ligand and metal complexes were formulated on the basis of elemental analysis, mass, IR, UV-visible, molar conductivity and magnetic susceptibility measurements. In the light of above studies it is proposed that the ligand behaved a bidentate ligand and coordination takes place through nitrogen of azomethine group and carbonyl oxygen of semicarbazone 1953 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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moiety. Thecomplexes were proposed octahedral geometry. Synthesized ligand and metal complexes hadbeen screened for antimicrobial activity 48 .

H

Cl

F

H

H3C

N N

N

C N

C

H3C

O

Co

N

O

N

Cl2

Cl.H2O

Co

O

Cl

C N

F

N Cl

H

Figure 11: Co(II) complexes of isatin with 3-chloro-4-floroaniline and 2pyridinecarboxaldehyde with 4-aminoantipyrine H

NH2

N N

C N

C2H 5

N

C

N

O

X

Co

O

N C

H 2N

N

X

C2H 5

N C

N

N H

Figure 12: Co(II) complexes of 1-ethyl, 1,2,3,5, tetrahydroimidazo-quinazolin 5-one semicarbazone Three azo group-containing Schiff base ligands, namely 1-{3-[(3-hydroxypropylimino) methyl]-4hydroxyphenylazo}-4-nitrobenzene, 1-{3-[(3-hydroxypropylimino)methyl]-4-hydroxyphenylazo}-2chloro-4-nitrobenzene and 1-{3-[(3-hydroxypropylimino) methyl]-4-hydroxyphenylazo}-4-chloro-3nitrobenzene were prepared. The ligands were characterized by elemental analysis, FT-IR spectroscopy, UV-Vis, 13 C-NMR, 1 H-NMR spectroscopy and thermogravimetric analysis. The synthesized metal complexes of Co(II) were synthesized and characterized by the physicochemical methods elemental analysis, FTIR spectroscopy, UV-Vis spectroscopy, magnetic moment measurements, and thermogravimetric analysis (TGA) and DSC. Schiff’s base ligands and their Co(II) complex were evaluated for their biological inhibition against tested microorganisms49 . A large number of Ni(II) complexes of biological nature, for example amino acids (glycine, α- alanine, βalanine, L-valine, serine, histidine etc), amino acid derivatives (peptides proteins and enzymes), carbohydrates had already been reported. Nickel is one of the most toxic transition metals showing the toxicity even in low doses to both ainimals and plants 50 . Issues of nasal and lung cancers have been reported from the nickel refining industry. Nickel is found to exist in both the crystalline and amorphous 1954 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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state, out of which crystalline nickel compounds are carcinogenic while amorphous ones are weak or noncarcinogenic51 . Considering such a large number of applications of Ni(II) complexes in biological systems, it is highly demandable to prepare and analyze the nickel(II) complexes with Schiff’s base ligands. Ni (II) complexes were synthesized by the condensation of metal salts with semicarbazone / thiosemicarbazone derived from p-dimethylaminobanzaldehyde. The general composition of the complex was [NiL2 ]X2 ,where X = Cl- , NO3 - The metal complexes were characterized by elemental analysis, magnetic susceptibility, molar conductance, IR and AAS studies. The Schiff bases and their metal complexes were tested for their antibacterial and antioxidant activities52 . A novel transition metal complexes of Ni(II) had been synthesized with three different Schiff’s base ligands (Figure 13).. The ligands were prepared by condensation reaction of 3-amino-1H-1,2,4-triazole with pyrrol-2-carboxaldehyde, 4-bromo-thiophene-2-carboxaldehyde, and 5-iodo-2-hydroxy benzaldehyde. To confirm the structure of all the complexes different techniques like analytical, physical and spectral methods were adopted. All the newly synthesized complexes were in vitro studied for antimicrobial activities. The antibacterial activities were checked against four different Gram-negative i.e., E.coli, S.sonnei, P.aeruginosa and S.typhi and two Gram-positive i.e., B.subtilis and S.aureus bacterial species. The agar-well diffusion method is employed to check antifungal activity against fungal species i.e., T.longifusus, C.albicans, A.flavus, M.canis, F.solani and C.glabrata. All the newly synthesized complexes showed good antibacterial activity against one or more bacterial species. The analyzed data revealed that the Ni(II) metal complexes showed higher activity than the parent ligands due to complexation53 .

Figure 13: Ni(II) complexes of 3-amino-1H-1,2,4-triazole with pyrrol-2-carboxaldehyde (1), 4-bromo-thiophene-2-carboxaldehyde (2), and 5-iodo-2-hydroxy benzaldehyde (3) where M = Ni (II) 1955 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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Ni(II) complex with novel ligand N,N′-bis(4-chlorobenzylidene)benzene-1,2-diamine (Figure 14) having general formula [NiL(ox)]Cl2 (where ox = C2 O4 2 − ) had been synthesized. The ligand and its metal complexes were analyzed by micro-analytical data, magnetic moment, molar conductance, 1 H-NMR, UVVisible, FT-IR, 13 C-NMR and EPR spectroscopic studies. The ligand and metal complex were tested for their antimicrobial activity and their MIC values suggested that the complex had better activity as compared to novel ligand and standard antibacterial (ciprofloxacin) and antifungal drugs (fluconazole) 54 .

N

O

O Ni

N

Cl 2 O

O

Figure 14: Ni(II) complex of N,N′-bis(4-chlorobenzylidene)benzene-1,2-diamine A new Ni(II) complex had been synthesized with 3,4,8,9 tetraoxo-2,5,7,10 tetraaza-1,6dithio(3,4,8,9)dipyridinedodecane (Figure 15), having general composition [Ni(L)]X2 [where X = NO3 −, Cl−, SO4 2−, CH3 COO−]. The ligand was hexadentate in nature. The newly synthesized complexes of macrocyclic ligand were characterized by elemental method, molar conductance, electronic, EPR spectral, mass, NMR, FT-IR, molecular modeling and thermal studies. The antimicrobial inhibition and MIC values of the ligand and its metal complex had been screened against different species of bacteria and fungi. As per the experimental results, the metal complexes showed better antibacterial and antifungal as compared to parent ligand55 . S O C

N H

N H

Ni

N

C O

O

C

H N

X2

N

H N C

C

C O

S

Figure 15: Ni(II) complex of 3,4,8,9 tetraoxo-2,5,7,10 tetraaza-1,6dithio-(3,4,8,9)dipyridinedodecane


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Schiff’s base ligand, 4-hydroxy-3-(1-(arylimino)ethyl)chromen-2-oneand its Ni(II) complexes (Figure 16) were synthesized by condensation. The ligand and the complexes were characterized by IR, 1 H-NMR, 13 C-NMR and mass spectral analysis. In vitro biological screening effects of the synthesized compounds were tested by Agar cup method against the bacterial species S.aureus, E.coli, S.typhi and B.subtilis. The poison food method had been employed to check antifungal activities against the fungal species A.niger, P.chrysogenum, F.moneliforme and A.flavus. The experimental studies indicated that the Ni(II) complexes exhibit higher antimicrobial activity than the free ligand56 .

H 2O

O O

O

Ar

CH3

N Ni

O

O

N H3C

Ar

H 2O

O

Figure 16: Ni(II) complex of 4-hydroxy-3-(1-(arylimino)ethyl)chromen-2-one Copper with chelating ligands forms coordination compounds. Copper(II) exists as [Cu(H2 O)6]2+ in aqueous solution. Cu(II) complex exhibits the fastest water exchange rate for any transition metal aqua complex. In recent years, a lot of research had been carried out to study the applications of copper containing coordination complexes in various fields like medicinal, bioinorganic chemistry, catalyst, analytical chemistry and many other industries 57-58 . Copper metal complexes with three different ligands i.e.,4-phenyl-2,6-di(thiazole-2-yl)pyridine,4-(anthracen-9-yl)-2,6-di(thiazole-2-yl)pyridine,4-(benzofuran-2-yl)-2,6-di(thiazole-2-yl) had been prepared and analyzed. On the basis of elemental analysis and spectral studies, the metal complexes had general composition [Cu(L)Cl2 ]. The synthesized metal complexes also screened for their biological activity. The metal complexes displayed good activity against tested microorganism59 . A number of water soluble copper(II) metal complexes of the general composition [Cu(L)Cl] and [Cu(L’)Cl2 ] had been synthesized, where L is 2-(2-(1H-benzimidazol-2yl)ethyliminomethyl)phenol and 2-(2-(1H-benzimidazol-2-yl)-ethyliminomethyl)-4-methylphenol and L’ is(2-pyridin-2-yl-ethyl)pyridin-2-ylmethyleneamine,2-(1H-benzimidazol-2-yl)ethylpyridin-2-ylmethylene amine,2-(1H-benzimidazol-2-yl)ethyl(1H-imidazol-2-lmethylene)amine and 2-(1H-benz imidazol-2yl)ethyl-(4,4a-dihydroquinolin-2-ylmethylene)amine. All the synthesized complexes with ligands were characterized by different analytical and spectral techniques like elemental analysis, electronic absorption, mass, IR and EPR. All the complexes were found to have incredible cytotoxic properties against the HBL-100 human breast cancer cell line with potency more than that of the widely used drug cisplatin and hence they had the potential to act as promising anticancer drugs. Interestingly, they were nontoxic to normal cell lymphocytes isolated from human blood samples, revealing that they were selective in killing only the cancer cells60 . 1957 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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Schiff’s base ligands were synthesized by the condensation reaction between 4,6-diacetylresorcinol with 3-hydrazino-5,6-diphenyl-1,2,4-triazine and isatin monohydrazone, respectively. The structures of the ligands were elucidated by elemental analyses, IR, 1 H-NMR, electronic and mass spectra. Metal complex of copper(II) (Figure 17) with Schiff’s base ligands were also synthesized. The mixed metal complex was derived by reaction between synthesized ligands and Cu(II) ion in the presence of a secondary ligand [8hydroxyquinoline, 1,10-phenanthroline or benzoylacetone]. The newly synthesized mixed metal complexes had been characterized by various analytical and spectroscopic techniques such as elemental analysis, thermal analysis, molar conductivity, magnetic moment susceptibility, mass, IR, electronic and ESR. The ligands and metal complexes exhibited significant antimicrobial property61 .

CH3 Ph

H N

N

COCH 3

1.5 H2O

N

Cu

N Ph

OH 2 O

N O

OH

O C CH 3

Figure 17: Cu(II) complex of 4,6-diacetylresorcinol with 3-hydrazino-5,6-diphenyl1,2,4-triazine and isatin monohydrazone Schiff’s base ligand was synthesized by the condensation of 4-aminoantipyrine with furfural and amino acid. Cu(II) metal complex (Figure 18) of synthesized Schiff’s base ligand was also synthesized. Structural features of ligand and metal complex were obtained from the analytical and spectral techniques. The in vitro antibacterial and antifungal assay suggested that Cu(II) complex was good antimicrobial agents against tested pathogens 62 .

Figure 18: Cu(II) complex of 4-aminoantipyrine with furfural and amino acid 1958 J. Chem. Bio. Phy. Sci. Sec. A, May 2014-July 2014; Vol.4, No.3; 1946-1964.

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Schiff base ligands, derived from the condensation of 2-aminobenzenthiol with monoacetyl ferrocene in the molar ratio 1:1 or in the molar ratio 1:2 for diacetyl ferocine had been derived. The chelation of the ligands to metal ions took place through the sulphur atom of the thiol group and the nitrogen atoms of the azomethine group. The chemical structures of ligands were identified by elemental analysis, IR, UVvisible spectra, and 1 H-NMR spectra. Complexes were analysed by elemental analyses, IR, electronic spectra, 1H-NMR as well as the magnetic susceptibility and conductivity measurement. The metal complexes displayed different geometrical arrangements such as octahedral and square pyramidal coordination. Schiff’s base ligands and their metal complexes were tested against two pathogenic bacteria and fungi to study their biological activity. All the complexes exhibit antibacterial and antifungal activities against tested organisms 63 . Schiff’s base ligand containing 4-methoxy or 4-ethoxy thiosemicarbazone moieties and their transition metal complexes with Cu(II) (Figure 19) were synthesized and characterized using 1 H-NMR, 13C-NMR, HMQC, Mass, IR and UV-visible spectroscopy, elemental analysis, and magnetic susceptibility measurements. The antimicrobial activity was also examined. Synthesized ligand and its metal complexes exhibited good inhibition against certain bacteria and yeasts. Some of them were comparatively higher or equipotent to the standard antibiotic and antifungal drugs. Some compounds showed moderate antibacterial and antifungal activity 64 . O

H H3C O

N

H N

H N

H

N

O N

H H N

H N

CH3 N

O

Cu S

S N O

N H

O

Figure 19: Cu(II) complex of 4-methoxy thiosemicarbazone

Cu(II) complexes (Figure 20) had been synthesized with a Schiff’s base ligand (1,4,5,7,10,11,12,15 octaaza,5,11,16,18-tetraphenyl, 3,4,12,13-tetramethyl cyclooctadecane) (L) derived from Schiff base (obtained by the condensation of 4-aminoantipyrine and dibenzoylmethane) and ethylenediamine. The chemical structure of the ligand was investigated by using various techniques i.e., elemental analysis, IR, 1 H-NMR, Mass and molecular modeling where as the coordination mode and geometry of the complexes were confirmed by elemental analysis, molar conductivity, magnetic susceptibility, IR, electronic and EPR spectral studies. On the basis of studies, the general composition of the complex was [Cu(L)Cl2 ]. The complex was non-electrolyte in nature. The ligand and its metal complex had shown antifungal activity with their LD50 values determined by probit analysis against two economically important fungal plant pathogens i.e. M.phaseolina and F.solani65.


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C H3C

H2 C

CH2 Cl

N

C N

CH3

Cu H3C

N

Cl

N

N

N

CH3

(CH2)2

Figure 20: Cu(II) complex of 1,4,5,7,10,11,12,15 octaaza,5,11,16,18-tetraphenyl, 3,4,12,13-tetramethyl cyclooctadecane Tetraaza macrocyclic Cu(II) complexes (Figure 21) of composition [CuLX2 ] (where L = N4 donor macrocyclic ligands) and (X = Cl−, NO3 −) had been synthesized and characterized by elemental analysis, magnetic moments, IR, EPR, mass, electronic spectra and thermal studies. The biological activity of all the complexes against gram-positive and gram-negative bacteria was compared with the activity of existing standard antibacterial drugs like Linezolid and Cefaclor. Metal complexes were found to be most potent against both gram-positive as well as gram-negative bacteria due to the presence of thio group in the parent ligands66 . O

HN

NH Cl

N

N

Cu Cl

N NH

N HN

O

Figure 21: Cu(II) complex of Tetraaza macrocyclic ligand Cu(II) complex of Schiff’s base ligand had been synthesized, which was derived from o- hydroxy benzaldehyde and 2-amino pyridine. The ligand and the complex were characterized by elemental analysis, molar conductance, magnetic susceptibility, electronic spectra, IR and ESR spectroscopy. On the basis of electronic spectral analysis and magnetic susceptibility values, geometry of complex was proposed to be octahedral. The molar conductivity data of complex suggested non-electrolytic nature. The ligand and metal complexes had been screened for microbiological activity67.


Schiff’s …

Pallavi et al. H C

N N

O

Cu O

N N

C H

Figure 22: Cu(II) complex of o- hydroxy benzaldehyde with 2-amino pyridine According to the literature survey and researchers, it may be concluded that there is a great diversity to synthesize novel transition metal complexes based on the choice of ligands. In view of its med icinal use much concern is focused on Schiff base ligands due to the presence of donor atoms. So there is broad scope for undertaking a well-organized study of coordination complexes of transition metals with variety of Schiff’s base ligands. CONCLUSION The paper concludes that the Schiff’s base ligands and their transition metal complexes contribute diverse therapeutically potent applications along with less economical, harmless and environmental friendly. It reflects with careful investigation that a new strategy or new route can be developed to synthesize medicinally potent new drug molecules. Also these heterocycles plays important and great potentials in the field of the organic chemistry, inorganic chemistry as well as medicinal chemistry. These are considered as magic moieties which not only possess almost all types of biological activities but also have wide diversity in the biological profile which is the base to explore these Schiff’s base ligands and their transition metal complexes to their multiple potentials against several activities. ACKNOWLEDGMENTS Author is thankful to Dr. (Prof) Manoj Kumar Pandey, Director and Dr S. Viswanathan, Administrative Officer, SRM University, Modinagar for providing facilities and my Supervisor as well as co-supervisor who always encourages, guide me throughout this work. REFERENCES

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Corresponding author: Pallavi Goel; 1 Department of chemistry, SRM University, Modinagar, Ghaziabad, 201204, India

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