A review article

Presented By

Rofyda El-Sayed Al-Azab Mahmoud Nail

Fourth Level

Biochemistry Program

Department of Chemistry

Supervised By

Dr / Nasser Mohamed Hosny

Associate professor of Inorganic chemistry

Faculty of Science

Port Said University

2015-2016

In the name of Allah, the Most Gracious and the Most Merciful Alhamdulillah, all

praises to Allah for the strengths and His blessing in completing this research.

I would like to express my deepest gratitude and sincere appreciation to

Dr. Nasser Mohamed Hosny Associate Prof. of Inorganic chemistry, Faculty of

Science, Port - Said University for his encouragement, valuable advice and for his

constructive and sincere guidance that he kindly offered throughout the development

of the present work.

I would like to thank the head of Chemistry Department Dr. Ibrahim Mohiee ,

Faculty of Science, Port - Said University.

I wish to express my deep gratitude to Dr. Mostafa Aly Hussien lecturer of Inorganic

Chemistry Department for drawing the structure of the complex and Dr. Ahmed

Abdelaziz in Microbiology Department, Faculty of Science, Port - Said University.

Many thanks and appreciation to all the stuff members of Chemistry Department for

their support and encouragement in the four years of my study in Chemistry

Department.

Last but not least, Sincere thanks to my parents and my brother for their endless love,

prayers and encouragement.

Subject Page

1. Introduction……………………………………………1

1.1. Anthranilic acid .......................................... ...................2

1.1.1. Uses of anthranilic acid ....................................................3

1.2. Ascorbic acid ……………………………………………………….…......4

1.2.1. Uses of ascorbic acid……………………………………………….......5

1.3. Literature survey ……………………………………………………….6-30

2. Aim of the work .............................................…......31

Aim of the work …………………………………………………………..…………32

Abstract…………………………………………………………………………….......33

3. Experimental…………………………………………..34

3.1. Reagents and Instrument………..……………………………………35

3.1.1. Reagents………………………………………………………………………35

3.1.2. Instrument ……………………………………………………………........35

3.2. General synthesis of complex ………………………………..……36

3.3. Antimicrobial activities ……………………………………………….37

4. Results and Discussion…….……………………....38

4.1. Infrared spectrum of ascorbic acid……………………….…....39-40

4.2. Infrared spectrum of Anthranilic acid………………..…….……41

4.3. Infrared spectrum of Ni (II) complex……………………..……42-44

4.4. Antimicrobial activities………………………………………….…..45-46

5. References………………………………………….47-58

Figure No Figure Name Page No

Figure 1 Structure of Anthranilic acid 2

Figure 2 Structure of Ascorbic acid 4

Figure 3 Synthesis of the ligand 2-(1,3dioxosioindolin-2-yl)benzoic acid

8

Figure 4 General structure of complexes ( anthranilic acid and phthalic anhydride ligands with some metals)

8

Figure 5

Proposed structure of the complexes (anthranilic acid

and alanine ligands with some metals ) 11

Figure 6 Proposed structure of the complexes (anthranilic acid and alanine ligands with some metals )

12

Figure 7 Preparation of the complexes (anthranilic acid and tributylphosphine ligands with some metals )

14

Figure 8 Proposed structure of the complexes(anthranilic acid

and tributylphosphine ligands with some metals ) 15

Figure 9 Reaction showing formation of schiff base 16

Figure 10 Structure of complexes (anthranilic acid and

vanillin ligands with some metals)

16

Figure 11 Proposed structure of complexex(anthranilic acid and phenylalanine ligands with some metals)

18

Figure 12 Schematic representation of synthesis of the ligand

(H2L) (Schiff base) 20

Figure 13 Reaction scheme for the synthesis of schiff base 23

Figure 14 Reaction scheme for the synthesis of schiff base,

anthranilic acid, metal(II) complexes 24

Figure 15 Proposed structure of mixed ligand chelates, metal(II),

8-hydroxy quinoline, anthranilic acid, o-aminophenol 25

Figure 16 Synthetic procedure of the ligands derived from diketone with anthranilic acid and their Ni-complexes.

28

Figure 17 Synthetic procedure of the ligands derived from

monoketone with anthranilic acid and their Ni-complexes

28

Figure 18 Outcome of the molecular modeling study RhAA/CNF 29

Figure 19 Chemical structures of the metal complexes 12–16 containing Schiff base ligands derived from

anthranilic acid and aldoses.

30

Figure 20 Infrared spectrum of the ascorbic acid 39

Figure 21 Infrared spectrum of the anthranilic acid 41

Figure 22 Infrared spectrum of the Ni(II)complex 42

Figure 23 The suggestion structure of the Ni(II) complex 43

Figure 24 The 3D-geometrical structure of the Ni(II) complex 44

Figure 25 Pictures shows the antimicrobial activities of the Ni(II) complex

46

Table No Table Name Page No

Table 1 Spectral data (cm-1

) and band assignments of ascorbic acid

40

Table 2 Spectral data (cm-1

) and band assignments of anthranilic

acid41

Table 3 Spectral data (cm-1

) and band assignments of complex 42

Table 4 Showed the inhibition circle diameter in millimeter for

the bacteria after 24 hours incubation paid and 37oC for

complex

45

1. Introduction

1.1. Anthranilic acid

Anthranilic acid (or o-amino-benzoic acid) is an aromatic acid with

the formula C6H4 (NH2) (CO2H). The molecule consists of a substituted benzene ring,

hence is classed as aromatic, with two adjacent, or "ortho-" functional groups,

a carboxylic acid and an amine. The compound is consequently amphoteric. In

appearance, anthranilic acid is a white solid when pure, although commercial samples

may appear yellow. It is sometimes referred to as vitamin L1 and has a sweetish

taste. The anion [C6H4 (NH2) (CO2)] −

, obtained by the deprotonation of anthranilic

acid, is called anthranilate[1]

.

Structure

Figure (1)

1.1.1. Uses of antharanilic acid

Industrially, anthranilic acid is an intermediate in the production of azo

dyes and saccharin. It and its esters are used in preparing perfumes to imitate jasmine

and orange, pharmaceuticals (loop diuretics e.g. furosemide) and UV-absorber as well

as corrosion inhibitors for metals and mold inhibitors in soya sauce.

Anthranilic acid can be used in organic synthesis to generate benzyne.[2]

It is also a DEA List I Chemical because of its use in making the now-widely

outlawed euphoric sedative drug methaqualone(Quaalude, Mandrax).[3]

It has been suggested that anthranilate esters could be efficient insect repellents,

replacing DEET.

Fenamic acid is a derivative of anthranilic acid, [4]

which in turn is a nitrogen

isostere of salicylic acid, which is the active metabolism of aspirin.[4]

Several non-

steroidal anti-inflammatory drugs, including mefenamic acid, tolfenamic

acid, flufenamic acid, and meclofenamic acid are derived from fenamic acid or

anthranilic acid and are called "anthranilic acid derivatives" or "fenamates".[5]

Anthranilic acid is an intermediate in the synthesis of some pharmaceutical

drugs including clozapine, lobenzarit, and nifurquinazol.

1.2. Ascorbic acid

Ascorbic acid is a naturally occurring organic compound with

antioxidant properties. It is a white solid, but impure samples can appear yellowish.

It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form

("vitamer") of vitamin C. It was originally called L-hexuronic acid, but, when it was

found to have vitamin C activity in animals ("vitamin C" being defined as a vitamin

activity, not then a specific substance); the suggestion was made to rename it. The

new name, ascorbic acid, is derived from a-(meaning "no") and scorbutus (scurvy),

the disease caused by a deficiency of vitamin C. Because it is derived from glucose,

many non-human animals are able to produce it, but humans require it as part of their

nutrition. Other vertebrates which lack the ability to produce ascorbic acid include

some primates, guinea pigs, teleost fishes, bats, and some birds, all of which require

it as a dietary micronutrient (that is ,in vitamin form)[6]

.

Structure

Figure (2)

1.2.1. Uses of ascorbic acid

Ascorbic acid is used for:

Treating and preventing low levels of vitamin C. It may also be used for other

conditions as determined by your doctor.

Ascorbic acid is a vitamin. It works by supplementing vitamin C, which is used in

many functions in the body [7].

Do NOT use ascorbic acid if:

You are allergic to any ingredient in ascorbic acid Contact your doctor or health

care provider right away if any of these applies to you [7]

.

1.3. Literature Survey

Anthranilic acid and phthalic anhydrides have the ability make ligand

complexes with the metal ions, which were found to be important for various

applications. In the present study, the attempts were carried to form complexes of

anthranilic acid and phthalic anhydride ligand with Lead acetate (Pb(CH3 COO)2 ),

Cobalt chloride (CoCl2 . 6H2O), Cadmium sulfate (CdSO4 ·H2O), Copper chloride

(CuCl2 .2H2O), and Tin chloride of well-defined stoichiometry in the range of pH 6

and 8 in variable ratios. The IR spectra of complexes were interpreted and compared

with data in the literature. Furthermore the resultant complexes were evaluated for the

anti-bacterial potential [8]

.

The compounds containing the complex ion or complex molecule in which

central metal atom or ion is surrounded by a number of oppositely charged ions or

molecules are known as co-ordination compounds [9]

, complex compound or simply

complex. Coordination basically refers to the "coordinate covalent bonds" (dipolar

bonds) between the ligands and the central atom in 1914, when first coordination

complex, hexol was resolved by Werner [10]

.

Among the ligands, anthranilic acid (C6H4(NH2)COOH) is one of the best

compound used by Carl Julius Fritzche (1808-1871) in the laboratory in St. Peterburg

by degrading ancient dye indigo [11]

. It is a white solid amino acid in pure form

whereas commercially available in yellow form. Its molecule consists of a benzene

ring with two adjacent functional groups, a carboxylic acid and an amine [11]

. Several

investigators worked on the synthesis of anthranilic acid dyes in the various

conditions which have shown significant biological activity especially against

bacteria S. aureus and E. coli and [12]

. The mixed ligand complexes of Co (II), Ni (II),

Cu (II) and Zn (II) with anthranillic acid and tributylphosphine have shown profound

activity against Staphylococcus, Klebsiella SPP. and Bacillas [13]

. Furthermore, the

rhodium complexes with (N-phenyl) anthranillic acid ligands are used as catalysts for

the hydrogenation [14]

.Several other mixed ligands complexes with anthranilic acid

were reported to have antifungal and antibacterial potential [15]

.

Phthalic anhydride (C6H4(CO)2O) is colorless solid and an important industrial

chemical, especially for the large-scale production of plasticizers for plastics [16]

.The

phthallic anhydride ring opening reaction by alcohols when carried out in presence of

different metal salts, results in the formation of metal carboxylate complexes [17]

.The

phathalate esters are also produced via phthallic anhydride ring opening reaction used

for chiral separation of optically active alcohols and amines [18]

, however in the

presence of amino acids such as glycine, the reactions of phthalic anhydrides help in

preparing N-phthaloylglycinato complexes of transition metals [19]

. The metal

complexes of amino acids with phthalic anhydride revealed higher antimicrobial

activity P. aerugenosa, E. coli, S. aureus and C. albicans than their respective ligands

[20].

This research studied synthesized the complexes of anthranilic acid and pthalic

anhydride ligands with cadmium (Cd), copper (Cu), of cobalt (Co), lead (Pb) and Tin

(Sn), however special emphasis has been given to the first ever complexes of Co and

lead Pb. For the structural elucidation of these complexes IR spectral analysis was

used.

The antibacterial potential of the complexes was assessed against Bacillus

subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Methicillin- Resistant

Staphylococcus Aureus (MRSA) [8]

.

Figure (3)

Figure (4): General structure of complexes

Rawate; synthesized mixed ligand complexes of zinc, cadmium and copper with

phthalic, succinic and anthranilic acid. The complexes have been characterized on the

basis of analytical data, thermogravimetric studies, IR and NMR. IR spectral studies

suggest that bidentate chelating behavior of succinic and phthalic and anthranilic acid

in its complexes [21]

.

The formation of mixed ligand complexes in solution with aspartic acid or

glutamic acid as a primary ligand has been potentiometrically studied [22]

. Some mixed

ligand complexes formed with glycine, nitrilotriacetic acid or histidine as primary

ligand and adenine, guanine, uracil, thymine or hippuric acid as secondary ligand have

also been studied [23-24]

. Some mixed ligand copper complexes of hippuric acid and

nitriloacetic acid have been studied [25]

. This paper described the synthesis, spectral

and thermal studies of mixed ligand complexes of Zn2+

, Cd2+

and Cu2+

with succinic,

phthalic and anthranilic acid.

Antharanilic acid form coordination complexes with many metals. the structure

of complexes with gallium and aluminum , [26]

, lithium , sodium and potassium[27]

,

magnesium [28]

, thallium [29]

, rubidium and cesium [30]

have all been determined by x-

ray crystallography . The ability of chelates with copper and cadmium has also been

investigated [31]

.

The new mixed ligand complex of Fe (III) with N,N-dimethyle-1,4-

phenylenediamine and anthranilic acid on aqueous media have been reported [32]

.

The complexes of cinnamaldehyde anthranilic acid have been investigated. The

dissociation constant and the stability constants of its complexes with Mn+2

, Cu+2

, Ni+2

, Co+2

, La+3

, Ce+3

, Uo2+2

and have Th+4

in monomeric and polymeric forms also

carried out by potentiometric studies [33]

.

Arylidene-anthranilic acid Schiff base complexes with Th+4

, Uo+2

, La+3

, Ce+3

and Zr+4

have been reported [34]

, also investigated the molecular structure effect of

these compounds on their tendency towards complex formation .

The complexes of rhodium with N-phenyl anthranilic acid and anthranilic acid

have investigated [35]

. The lanthanide complexes with N-phenyl anthranilic acid also

have been reported [36]

, also reported thermal decomposition process and mechanism

of those complexes. The mixed ligand metal complexes of o-bezoyl benzoic acid and

anthranilic acid have been reported [37]

.

Al-Noor et al; presented the synthesis and study of some new mixed-ligands

complexes containing anthranilic acid and amino acid L-alanine (Ala) with some

metals. The resulting products were found to be solid crystalline complexes which

have been characterized by using (FT-IR,UV-Vis) spectra , melting point, molar

conductivity , chloride ion content were also determin by (mohr method) and

determination the percentage of the metal in the complexes by (AAS).The proposed

structure of the complexes was suggested using program , Chem Office 3D(2004) .

The general formula have been given for the prepared complexes :

[M (A) (Ala)]. nH2O n= 0,2

AH = Anthranilic acid = C7H7NO2 AlaH = alanine = C3H7NO2

Anthranilate ion = C7H6NO2- Ala- = Alaninate ion = C3H6NO2

-

M(II): Mn(II) ,Fe(II),Co(II) , Ni(II) , Cu(II) , Zn(II) and Cd(II)[38]

.

The characterization and quantitative investigation of the binding properties of

amino acids towards transition metal ions plays an important role in our understanding

of metal~protein interactions [39]

. There are many reports on the metal anthranilate

complexes along with the structure of many of these compounds. Some transition

metal anthranilates have capability for aren't hydrogenation [40-41].

During the recent

years, there has been significant interest in the coordination chemistry , the

structural properties and the reactivity of metal complexes of amino acids [42-43]

.Metal

amino acid complexes have long been of interest as models for metal–ligand systems

and interaction which may occur in nature[44-45]

.In this paper we reported the

synthesis, spectroscopic and structural of complexes of M+2

ions using amino acid

alanine as a primary ligand and anthranilic acid - as asecondary ligand.

Figure (5): The proposed structure of the complexes,[M (A) (Ala)]. Fe (II) = Co

(II), Ni (II), Zn (II), Cd (II), M (II)

Figure (6): The proposed structure of the complexes

[M (A) (Ala)]. 2H2O M (II) = Cu (II), Mn (II)

Mixed ligand complexes of bivalent metal ions, viz;Co(II), Ni(II), Cu(II)and

Zn(II) of the composition [M(A)2((PBu3)2] in (1:2:2) (M:A:(PBu3).

Molar ratio, (where A-Anthranilate ion, (PBu3) = tributylphosphine. M=Co (II), Ni

(II), Cu (II) and Zn (II).

The prepared complexes were characterized using flame atomic absorption,

by FT-IR, UV/visible spectra methods as well as magnetic susceptibility and

conductivity measurements. The metal complexes were tested in vitro against three

types of pathogenic bacteria microorganisms: (Staphylococcus, Klebsiella SPP. and

Bacillas) to assess their antimicrobial properties, Results. The study shows that all

complexes have octahedral geometry; in addition, it has high activity against tested

bacteria.

Based on the reported results, it may be concluded that. The results showed that

the deprotonated ligand (anthranilc acid ) to anthranilate ion (A) by using (KOH)

coordinated to metal ions as bi dentate ligand through the oxygen atom of the

carboxylate group (−COO−), and the nitrogen atom of the amine group (-NH2), where

the Tributylphosphine coordinated as a monodentate through the phosphor atom[46]

.

Anthranilic acid (or o-amino-benzoic acid) is an organic compound with the

molecular formula C7H7NO2. The molecule consists of a benzene ring, hence is

classed as aromatic, with two adjacent, or "ortho-"functional groups, a carboxylic

acid and an amine. Thermodynamic and electrical functions of aminophenol and

anthranilic acid complexes with Mn(II), Fe(II),Co(II), Ni(II) and Cu(II) were

determined. Ga(III), Ho(III), and Ce(III), were calculated with the help of stability

constant values at different temperatures. It was found that the complexing processes

have an exothermic nature. The studied complexes behave like semiconductors [47]

.

The conduction takes place according to hopping mechanism. There have many

reports on the metal-anthranilic complexes. Some transition metal anthranilic

capability for aren't hydrogenation [48-49]

.The new substituted anthranillic acid

derivatives as potentanti-inflammatory agents, the structure of these compounds have

been established by IR, 1HNMR spectroscopic and elemental analysis [50]

. There are

many reports on the metal-anthranilate complexes along with the structure of many of

these compounds . Some transition metal anthranilate have capability for aren't

hydrogenation [51-52]

.

Tributylphosphine is the organophosphorus compound with the formula

P (C4H9)3= (C12H27P). Abbreviated or PBu3, it is a tertiary phosphine. It is an oily

liquid at room temperature, with a nauseating odor [53]. Tributylphosphine most

commonly encountered as a ligand in transition metal complexes and is also a

common ligand for the preparation of complexes of transition metals in low oxidation

states [54]

.

A series of square-planar nickel (II) hexamethylenedithio- carbamate

complexes with heterogeneous co-ordinationspheres of composition [NiX(hmidtc)Y].

nCHCl3[X = Cl, Br, I or NCS; hmi = C6H12, dtc = S2CN−; Y = PPh3 or PBu3, n=0, 1]

have been synthesized and characterized by elemental analyses, IR and UV– v.is.

Spectroscopy, magneto chemical and conductivity measurements, and by thermal

analysis. X-ray structures of [NiCl(hmidtc)(PPh3)]k·CHCl3 and [NiBr(hmidtc)(PPh3)]·

CHCl3 have been determined[55]

.

The presented paper reported the synthesized and characterization of new Co

(II), Ni(II), Cu(II) and Zn(II) complexes with mixed anthranilic acids acid and

tributylphosphine.

Figure (7): Preparation of the Complexes [M (A) 2(PBu3)2]

Figure (8) : The proposed structure and3D-geometrical structure of the complexes

[M(A)2(PBu3)2] , M =Co(II),Ni(II),Cu(II) and Zn(II)

Suresh and Prakash; studied new chelates of schiffs base derived from vanillin

and anthranilic acid with d-block elements such as Cr +3

, Mn +2

, Co +2

, Ni +2

, Cu +2

,

Zn +2

and Cd +2

have been synthesized and investigated. Their structures were

determined on the basis of the elemental analysis, infrared spectroscopy, electronic

spectroscopy, thermo gravimetric analyses and electron spin resonance spectroscopy.

Molar conductivity measured revealed the 1:1 electrolytic nature for Cr +3

complexes

and non-electrolytic for Mn +2

, Co +2

, Ni +2

, Cu +2

, Zn +2

and Cd +2

. On the basis of

the studies, the coordination sites were proven to come through the nitrogen atom of

azomethine and the hydroxyl group of the carboxyl group of anthranilic acid [56]

.

Complexes of schiffs bases are of great importance due to their biological,

pharmaceutical, clinical and analytical applications [57-58]

,whereas Cr +3

chelates of

schiffs base derived from vanillin and anthranilic acid have been reported in the

presence of pyridine as one of the ligand in a octahedral complex[59]

. A thorough

knowledge of the coordination chemistry of schiffs base derived from vanillin and

anthranilic acid with metals such as Mn +2

, Co +2

, Ni +2

, Cu +2

, Zn +2

and Cd +2

will be

of much interest in elucidating the structure, reactivity and microbiological study of

the complexes.

Figure (9): Reaction showing formation of schiffs base ligand

Figure (10): Structure of Mn +2

, Co +2

, Ni +2

, Cu +2

, Zn +2

and Cd +2

complexes

This paper presented the synthesis and study of some new mixed-ligand

complexes containing anthranilic acid and amino acid phenylalanine (phe) with some

metals.

The resulting products were found to be solid crystalline complexes which have

been characterized by using (FT-IR, UV-Vis) spectra, melting point, elemental

analysis (C.H.N) , molar conductivity .

The proposed structure of the complexes using program, chem office

3D (2000).

The general formula has been given for the prepared complexes:

[M(A-H)(phe-H)] M(II) : Hg(II), Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) .

A = Anthranilic acid = C7H7NO2 Phe = phenylalanine = C9H11NO2 [60].

Anthranilic acid is known to specific precursor of the alkolides skimmianine

and acordine [61]

.

There have been many reports on the metal-anthranilate complexes along with

the structure of many of these compounds. Some transition metal anthranilates have

capability for hydrogenation [62-63]

.

The new n-substituted anthranilic acid derivatives as potent anti-inflammatory

agents, the structure of these compounds have been established by IR, 1H-NMR.

Spectroscopic data and elemental analysis [64]

.

During the recent years, there has been significant interest in the coordination

chemistry, the structural properties and the reactivity of metal complexes of amino

acids.[65-66]

, several amino acids nucleophilic side chains that coordinate to transition-

metal ions, there ions may be intrinsic parts of the proteins and may be required the

protein's structure or function [67-68]

.

Figure (11): The proposed structure of the complexes

Al.Noor; studied new symmetrical Schiff base ligand (H2L) is prepared via

condensation of hydrazine hydrate and4-hydroxy-3-methoxybenzaldehyde in ethanol

solution at room temperature is reported. Polydentate mixed ligand complexes were

obtained from 1:1:1 molar ratio reactions with metal ions and H2L, NA on reaction

with MCl2.nH2O salt yields complexes corresponding to the formulas [M (L) (NA) 2].

All the complexes are air stable and soluble in water and common organic

except benzene .All complexes are soluble in dimethyl formamide (DMF) and

dimethyl sulfoxide (DMSO) solvent. Comparison of the IR spectra of ligands (H2L) and

(NA) and there metal complexes confirm that Schiff base behave as a dibasic

tetradentate ligand towards the central metal ion with an ONNO donor sequence

and nicotinamid. Behave as unidentate.

The ligands and their metal complexes were screened for their antimicrobial

activity against four bacteria (gram +ve) and (gram -ve) [69].

Metal ions play a vital role in a vast number of widely different biological

processes. The interaction of these ions with biologically active ligands, for example

in drugs, is a subject of considerable interest. Some of the biologically active

compounds act via chelation [70], but for most of them little is known about how

metal binding influences their activity. Therefore we have been interested in

studying the complexing ability of biologically active ligands. The Schiff base

compounds constitute an important class of ligands which have been extensively

studied in coordination chemistry. The nature of the effect of one ligand and its

transmission to another ligand through the central metal ion is very important in

coordination chemistry [71]. Antipyrine Schiff base derivatives can serve as

antiparasitic agents and their complexes with platinum (II) and cobalt (II) ions have

been shown to act as antitumour substances [72].

Nicotinamide is known as a component of the vitamin B complex as well as a

component of thecoenzyme, nicotinamide adenine dinucleotide (NAD). These are

more important for transfer of hydrogen in the cell breath. The presence of pyridine

ring in numerous naturally abundant compounds, adducts of nicotinamide are also

scientific interest. Therefore, the structure of nicotinamide has been the subject of

many studies [73-74].

In the area of bioinorganic chemistry the interest in the Schiff base complexes

lies in that they provide synthetic models for the metal-containing sites in

metalloproteins/enzymes and also contributed enormously to the development of

medicinal chemistry, radio immunotherapy, cancer diagnosis and treatment of tumor

[75-76]. In addition, some of the complexes containing N and O donor atoms are

effective as stereo specific catalysts for oxidation [77] eduction, hydrolysis, biocidal

activity and other transformations of organic and inorganic chemistry [78].

Figure (12): Schematic representation of synthesis of the ligand (H2L)

Abd El Wahed et al, study thermodynamic and electrical functions of

aminophenol and anthranilic acid complexes with Mn(II), Fe(II), Co(II), Ni(II) and

Cu(II) were determined. ∆Go, ∆H

o and ∆S

o were calculated with the help of stability

constant values at different temperatures. It was found that the complexing processes

have an exothermic nature. The studied complexes behave like semiconductors. The

conduction takes place according to hopping mechanism. To show the composition of

complexes conductometric and photometric titrations, IR spectra, thermal analysis and

X-ray diffraction techniques were employed [79]

.

In recent years the investigations on organic semiconductors have been much

intensified [80-81]

. Aminophenol and aminobenzoic acid have aroused interest owing to

their utility as starting materials for many azodyes [82]

, corrosion inhibitors [83],

bactericides [84]

and anti-inflammatory agent [85]

. From the complexing point of view,

many have taken interest in studying aminophenol and aminobenzoic acid as potential

ligands [86-87]

.In this course interest in the area of physical properties of organic

complexes, the present work aims to study the thermodynamic and electrical

properties of aminophenol and o-amino-benzoic acid (anthranilic acid) complexes

with Mn(II), Fe(II), Co(II), Ni(II) and Cu(II). Several techniques such as

conductometric and photometric titrations, IR spectra, thermal analysis and X-ray

diffraction were used to characterize the composition of complexes.

Olalekan et al; studied Schiff base (SB) was synthesized by the condensation

reaction of 2-aminobenzoic acid and p-hydroxybenzaldehyde. The reaction of the

Schiff base with metal ions in an alkaline aqueous medium yielded the metal (II)

complexes of the hydrolysed Schiff base product, identified as metal (II) complexes of

2-aminobenzoic acid. These compounds were characterized by physical and

spectroscopic techniques.

The elemental analysis indicated the ligand to metal ratio as 2:1 in the

complexes with general molecular formula M(L)2 (L = 2-aminobenzoic acid; M = Mn,

Co, Ni, Cu and Cd). IR data showed the ligand coordinated to the metal ion through

the carboxylate oxygen and the amine nitrogen. Room temperature magnetic

susceptibility and solid reflectance data suggested the complexes have four-coordinate

geometry. The conductance measurements showed the complexes are nonelectrolytes

and are covalent compounds in DMSO. The compounds were screened for in-vitro

antimicrobial activity against chosen strains of bacteria and fungi [88]

.

2-aminobenzoic acid is very useful in synthesis of heterocyclic systems and

other molecules. It serves as an excellent biochemical precursor to aromatic amino

acids and it also forms an important part of several alkaloids [89]

.The acid and its

derivatives are useful in various applications such as sunscreen production [90]

,

perfumery [91],

and monitoring of glycosylation of proteins [92].

Anti-convulsant [93],

and anti-inflammatory activity [89],

of 2-aminobenzoic acid

and its derivatives have been reported. Some transition metal anthranilates have

demonstrated ability for hydrogenation [94].

Hugo Schiff first reported the synthesis of Schiff bases [95]

, containing imine

group formed by a condensation reaction between primary amines and aldehydes.

Schiff bases are more stable and non-polymerizing when an aryl group (minimum

requirement) is attached to the nitrogen or to the carbon of the imine group [96]

.The

reaction can proceed in alkaline, acidic or neutral medium. This reaction is reversible

under suitable conditions and is termed hydrolysis.

This research work reported the preparation of metal complexes by heating to

reflux the mixture of a Schiff base with respective metal ions in an aqueous alkaline

medium. Hydrolysis of the Schiff base was facilitated under these conditions. The

resulting complexes were characterized and their antimicrobial potential was

investigated [88]

.

Figure (13): Reaction Scheme for the Synthesis of Schiff Base

Figure (14): Reaction Scheme for the Synthesis of Metal (II) Complexes

(M = Mn, x= 4; M= Co and Ni, x= 6; M=Cu, x= 2; M= Cd, x= 2.5)

The series of mixed ligand chelates of Co(II), Ni(II) and Cu(II) ions with some

ligands, such as 8-hydroxyquinoline [L1], anthranilic acid [L2] and o-aminophenol

[L3] acting as bidentate ligands have been prepared and characterized by various

physico-chemical analyses, such as elemental analysis, infrared spectra, molar

conductance measurements and electron paramagnetic resonance. Elemental analysis

data show the formation of 1: 1: 1 [M: L: L´] chelates.

The molar conductance measurements of the chelates exhibit the non-

electrolytic nature of the chelates. Infrared spectra display that the coordination

occurs via oxygen and nitrogen atoms. Electron paramagnetic resonance spectra show

the presence of paramagnetic phenomena and supported the geometrical structures of

the chelates that the presence of square-planar, tetrahedral or octahedral geometries

[97].

Figure (15): Proposed structures of metal chelates

Chacko and Parameswaran; studied the thermal decomposition of cobalt (II),

nickel (II), copper (II) and zinc (II) complexes of the Schiff base vanillidene

anthranilic acid was studied by TG. The chelates show somewhat similar TG plots

when heated in an atmosphere of air. Thermoanalytical data (TG and DTG) of these

chelates are presented in this communication. Interpretation and mathematical analysis

of these data and evaluation of order of reaction, the energy and entropy of activation

based on the differential method employing the Freeman-Carroll equation, the integral

method using Coats-Redfern equation and the approximation method using the

Horowitz-Metzger equation are also given. On the basis of experimental findings in

the present course of studies, it is concluded that the relative thermal stability of

vanillidene anthranilic acid chelates can be aligned as Co (II) ≅Ni (II)>Zn (II)>Cu (II)

[98].

Rhodium chloride hydrate RhCl3 · 3H2O reacts with anthranilic acid

(HA; C6H4 (COOH)NH2) in boiling dimethylformamide (DMF) yielding

dicarbonylanthranilatorhodium(I) [Rh(CO)2(A)], (1). In the reaction of (1) with an

excess of triphenylphosphine in DMF one carbonyl ligand is substituted by phosphine

and carbonyltriphenylphosphineanthranilatorhodium(I) [Rh(CO)(PPh3)A], (2) is

formed [99]

.

Rabiul Hasan et al;The nickel(II) complexes of the dibasic tridentate Schiff

bases viz. Sal-AnthraH2, HNP-AnthraH2, HAP-AnthraH2, HPP-AnthraH2, Acac-

AnthraH2, Etac-AnthraH2, and Bzac-AnthraH2, have been synthesized and

characterized by IR, 1H NMR, mass and electronic spectra, and magnetic and

conductance studies. On the basis of analytical data, four-coordinate geometry was

proposed for the prepared nickel (II) complexes. The complexes have been found to

possess 1:1 stoichiometry. The bio-efficacy of the prepared complexes has been

examined against the growth of bacteria and fungi in vitroto evaluate their

antimicrobial potential [100]

.

The chemistry of Schiff bases is an important area of research with increasing

interest due to their simple synthesis, versatility, and the diverse range of application

for their metal complexes, e.g., in the treatment of cancer, as antibactericidal agents,

as antiviral agents, as fungicidal agents and for other biological properties [101]

. Schiff

bases have been studied as a class of ligands [102]

, [103]

and [104]

and are known to

coordinate with metal ions through the azomethine nitrogen atom. The synthesis of

transition metal complexes with Schiff base ligands is studied due to sensitivity,

selectivity and synthetic flexibility towards metal atoms [105]

. Schiff bases are used as

catalysts in medicine, such as in antibiotics and anti-inflammatory agents, and in

industry as an anticorrosive [106]

and [107]

. They are also used as analytical reagents for

spectrophotometric metal analysis [108]

. Metal complexes of Schiff base ligands have

recently been used as precursors in the preparation of nanostructures of the respective

metal oxides [109]

, [110]

and [111]

.

Nickel is usually dipositive in its compounds, but it can also exist in the oxidation

states 0, 1+, 3+, and 4+. In addition to the simple nickel compounds or salts, nickel

forms a variety of coordination compounds. Currently, the bioinorganic chemistry of

nickel is a topic of increasing interest because the study of the interactions of Ni(II)

with Schiff bases offers an opportunity to understand various properties of Ni(II)

complexes. The preparation of nickel (II) complexes with Schiff base 2-((1H-

benzo[d]imidazol-4-ylimino) methyl) phenol [112]

and 3-hydroxyquinoxaline-2-

carboxalidene-4-aminoantipyrine [113]

has been reported. Complexes with nickel(II)

and Schiff bases derived from Bis(1-amidino-O-methylurea) Ni(II) chloride and

salicylaldehyde [114]

were prepared. Complexes of nickel(II) with N,N′-disalicylidene-

3,4-diaminotoluene (H2L1), N,N′-bis(3,5-di-tertbutylsalicylidene)-1,3 diaminopropane

(H2L2), tetrathiafulvalene-N,N′-phenylene bis (salicylideneimine) (H2L3), o-

hydroxybenzaldehyde, o-hydroxyacetophenone ethylene diamine (H2L4) and 1-

phenylbutane-1,3-dionemono-Smethylisothio-semicarbazone with 5-phenylazo-o-

hydroxybenzaldehyde (H2L5) have been synthesized [115]

. Three copper(II) and three

nickel(II) dinuclear oxalate-bridged compounds, that is, [(Cu(antrasal))2ox],

[(Cu(antrathio))2ox], [(Cu(antrafur))2ox], [(Ni(antrasal))2ox], [(Ni(antrathio))2ox] and

[(Ni(antrafur))2ox], were prepared [116]

.

Synthesis, characterization and biological activity of transition metal complexes of a

Schiff base derived from benzoin [117]

and 3-ethoxy salicylaldehyde [118]

with 2-amino

benzoic acid have been detailed. The Ni(II) Schiff base complex derived from

salicylaldehyde and o-amino benzoic acid has been prepared and

characterized[104]

and [119]

. Spectroscopic and potentiometric investigations of

copper(II) complexes with Schiff bases derived from 2-amino benzoic acid and

salicylaldehyde have been performed [120]

. The M(II) (Cu, Ni, Fe, Zn and Mn)

complexes with Schiff base derived from 2-amino benzoic acid and salicylaldehyde

were studied [121]

and [122]

.

A search through the literature studied that no work has been conducted on the

Ni-complexes of Schiff bases such as HNP-AnthrH2, HAP-Anthr H2, HPP-Anthr H2,

Acac-Anthr H2, Etac-Anthr H2, and Bzac-Anthr H2, rather than Sal-Anthr H2. This

paper reports the synthesis of the above tridentate ligands formed by the condensation

of monoketone (Sal, HNP, HAP, HPP) or diketone (Acac, Etac, Bzac) with 2-amino

benzoic acid or anthranilic acid. Complexes of nickel (II) ion with these Schiff bases

have been prepared and characterized. Some of the prepared complexes have been

tested for possible biological (antifungal and antibacterial) activities.

Figure (16) Figure (17)

The immobilisation of the rhodium-anthranilic acid complex onto fishbone

carbon nanofibres was executed via the following steps: (i) surface oxidation of the

fibres, (ii) conversion of the carboxyl groups into acid chloride groups, (iii)

attachment of anthranilic acid and (iv) complexation of rhodium by the attached

anthranilic acid. The immobilisation process was followed and the resulting surface

species were characterised by IR, XPS, XAFS spectroscopy, and molecular modelling.

Anthranilic acid bonds to the CNFs by an amide linkage with the carboxyl groups that

are present after surface oxidation of the fibres. The immobilised anthranilic acid co-

ordinates to rhodium via the nitrogen atom and the carboxyl group. The as-synthesised

Rh(III) complex itself is not active in the liquid-phase hydrogenation of cyclohexene.

After reduction with sodium borohydride in order to obtain a Rh(I) complex, small (d

= 1.5-2 nm) rhodium metal particles result, which are highly active. The results

indicate that different activation procedures for the immobilised Rh/anthranilic acid

system should be applied, such as reduction with a milder reduction agent or direct

complexation of the rhodium in the Rh (I) state [123]

.

Figure (18)

Anthranilic acid is a core precursor to a number of anti-inflammatory agents,

such as mefenamic acid.[123]

From 2013, Iqbal and co-workers evaluated the anti-

inflammatory and COX inhibitory activities of Mn(II) (12), Fe(II) (13), Co(II) (14),

Ni(II) (15) and Zn(II) (16) complexes containing Schiff base ligands derived from

anthranilic acid and aldoses (Fig. 19).[124]

The metal ions formed four-coordinate,

ML2-type complexes with the bidentate Schiff base ligands, with spectral and

magnetic data indicating a tetrahedral geometry for Mn(II) and Fe(II) complexes, and

a square-planar geometry for the Co(II), Ni(II) and Zn(II) complexes. Oral

administration of the Mn(II) and Zn(II) complexes reduced kaolin-induced paw edema

in rats, indicating that the complexes possessed anti-inflammatory activity.

Furthermore, all of the complexes displayed COX-2/COX-1 selectivity index values

of 0.34–0.52, which were similar to that of aspirin 7 (0.41). Unfortunately, the ligands

were found to be unstable and could not be isolated in the Free State. Additionally, the

stability of the complexes was not reported.

Figure (19)

2. Aim of the work

In this work we aimed to prepare nickel complex derived from

antharanilic acid and ascorbic acid mixed ligand and study the

antimicrobial activities of ligand and complex against the four types of

pathogenic bacteria (Staphylococcus, E-coli, Pseudomonas, and

Streptococcus).

Abstract

This paper presnts the synthesis and study of a new mixed-ligand complex

containing anthranilic acid C6H4 (NH2) (COOH) and ascorbic acid with NiCL2.6H2O

metal. The resulting products were found to be solid crystalline complex which have

been characterized by using (FT-IR) spectra.the proposed structure of complex using

program, Chem Draw Ultra 12+serial. The metal complex was tested in vitro against

four types of pathogenic bacteria microorganism: (Staphylococcus, E-coli,

Pseudomonas, and Streptococcus) to assess their antimicrobial properties. The results

showed that the deprotonted ligand (Anthranilic acid ) to anthranilate ion (A-)

coordinated to metal ion as bidentate ligand through the oxygen atom of the

carboxylate group (-COO-) and the nitrogen atom of the amine group (-NH2),Where

the Ascorbic acid coordinated as monodentate through the oxygen atom of both the

hydroxyl group(OH) and the keton (C=O).

3. Experimental

3.1. Reagents and Instruments

3.1.1. Reagents

The metal ion Ni (II) was used in the form of Nickel chloride

hexahydrate (NiCl2.6H2O).

Antharanilic acid C6H4 (NH2) (CO2H) and Ascorbic acid (C6H8O6).

3.1.2. Instrument

FTIR spectra were recorded as KBr discs using type A FTIR 4100

spectrometer.

3.2. General synthesis of complex

Dissolved 1.37 gm. of anthranilic acid and 1.76 gm. of ascorbic acid in 100 ml

of distilled water and complete the dissolving by slightly heating of the solution, 2.37

gm. of (NiCl2.6H2O) dissolved in small amount of distilled water 5 ml. The metal

solution was added drop by drop to the ligand solution until a faint green precipitate

was formed , let it come down then filtrate the solution ,discard the mother liquor

and let the precipitate in air to dry .

3.3. Antimicrobial activities

Antimicrobial activities of the ligands and their complex have been carried out

against four types of pathogenic bacteria. Two types of them were gram (-Ve) as,

Pseudomonas and Escerichia coli. Other types were gram (+Ve) as, streptococcus

and staphylococcus. Using nutrient agar, the test solution prepared (complex solution)

by dimethylformamide (DMF), cut filter paper as discs have the same size as 5 mm

diameter and 1mm thickness then soaked these discs in the test solution .These discs

of filter paper placed on plates which already seeded by nutrient agar medium, each

plate has two discs one for test solution (complex solution) and the second for DMF

(control) then incubated at 37°C for 24 hours. The diameters (mm) of the inhibition

zone around each disc were measured after 24 hours.

4. Results and Discussion

4.1. Infrared spectrum of ascorbic acid

Figure (20)

Table (1): Spectral data (cm-1

) and band assignments of ascorbic acid [126]

.

IR

Assignments

3412s - 3317s - 3221 s OH stretching

3032 sbr-2916 m CH stretching

1753 s C=O stretching

1668 vs C=C ring stretching

1500 m CH bending

1431 w CH bending , CH2 scissoring

1321 s CH bending (wagging)

1273 s C-O-C stretching

1220 s, 1197 s C-C(=O)-O stretching

1139 vs ,1116 vs C-O-C stretching

1070 m C-O-C stretching and C-O-H bending

1026 vvs C-O-H bending

985 s C-H and O-H bending

868 w,821 m C-C ring stretching

758 s, 721 w OH out or plane deformation

684 w, 628 s, 567 m OH out of plane deformation / C-C ring stretching

447 s C-O in plane deformation

4.2. Infrared spectrum of anthranilic acid

Figure (21)

Table (2): Spectral data (cm-1

) and band assignments of anthranilic acid [127]

.

IR

Assignments

3240 sh (NH2)

1679 s as(COO)

1486 s s (COO)

1140 cm-1

(C-C)

2586 cm-1

(C-H)

3390 cm-1

(OH)

1321 -1371 cm-1

(C-O)

1616 cm-1

δ (NH2)bending

4.3. Infrared spectrum of Ni(II)complex

Figure (22)

Table (3): Spectral data (cm-1

) and band assignments of complex.

compounds

(NH2)

δ(NH2)

s(COO-)

as(COO-)

(OH)

(C-O)

M-N

M-O

Anthranilic_ acid

3240

1616

1679

1486

3390

1321

__

__

Ascorbic_ acid

__

__

1753

1220 ,1197

3412 ,3317 ,3221

1273

__

__

Complex 3226.33

1592

1623 ,1640

1405 ,1238

3444.2,3

303.4

1330.64 ,1290

426.1

516.82 ,560 ,570

These bands assigned to NH2 and δ NH2 at 3240 and 1616 cm-1

, respectively have

ban shifted to 3226 and 1592 respectively. These shifts indicate that NH2 is an active

site of coordination. The bands at 1679 and 1486 cm-1 assigned to as and s (COO) of

anthranilic acid have been shifted to 1640 and 1405 cm-1

, respectively .This behavior

confirm the participate of (COO) anthranilic acid in bonding after deprotonation .The

bands at 1753 and 1220 cm-1

have been shifted to 1640 and 1238 cm-1

, respectively

indicating the participate of (COO) ascorbic acid in bonding. The disappearance of the

band assigned to (OH) group of ascorbic acid confirms the participate of (OH) after

deprotonation.

Figure (23) : The suggestion structure of Ni+2

complex

Figure (24)

4.4. Antimicrobiology activities

The zone inhibition of bacterial growth were measured in mm depending upon the

dimeter. The antibacterial activity results revealed that the ligands and its complex

show weak activity when compared to the control (DMF).

Table (4)

compound streptococcus Pseudomonas E.coli staphylococcus

Control(DMF) - Ve - Ve 12 mm 4 mm

Complex - Ve - Ve 5 mm 2 mm

From the previous results we can conclude that the mixed ligand complex does not

have any biological activity against Pseudomonas and Streptococcus respectively as

shown at figure (B), (D). Figure (A),(C) shows an inhibition zone of bacterial growth

but the inhibition zone around the control (DMF) is bigger than the inhibition zone

around the test (the mixed ligand complex dissolving in DMF) so we can conclude

that DMF probably inhibited the anti-toxicity of the mixed ligand complex.

Figure (25): Shows the antimicrobial activity of the complex

A B

C

D

5. References

[1]. https://en.wikipedia.org/wiki/Anthranilic_acid.

[2]. F. M. Logullo, A. H. Seitz, L. Friedman. "Benzenediazonium-2-carboxy- and

Biphenylene". Coll. 5 (1973)54.

[3]. S. A. Angelos, J. A. Meyers.”The isolation and identification of precursors and

reaction products in the clandestine manufacture of methaqualone and

mecloqualone". Journal of Forensic Sciences .30 (4) (1985)1022–1047.

[4]. D. Sriram, p. Yogeeswari. Medicinal Chemistry, 2nd Edition. Pearson Education

India, (2010) 235.

[5]. J. Deruiter. Auburn University course material. Principles of Drug Action 2,

1: Non-Steroidal Antiinflammatory Drugs (NSAIDS) fall (2002)1-26.

[6]. M. Y. Lachapelle and G. Drouin. "Inactivation dates of the human and guinea pig

vitamin C genes". Genetica, 139 (2) (2010)199–207.

[7]. http://www.drugs.com/cdi/ascorbic-acid.html.

[8]. S. Raza, Y. Iqbal, I. Hussian, M. Raza, S. U . A. Shah, et al. Biochem Anal

Biochem. Synthesis of Anthranilic Acid and Phthalic Anhydride Ligand and their

Metal Complexes. 143 (2013)2-4.

[9]. F. A. Cotton, C. A. Murillo, M. Bochmann, G. Wilkinson . Advanced Inorganic

Chemistry. (1999)Sixth edition 1355-1376

[10]. A. Werner. Zur Kenntnis des asymmetrischen Kobaltatoms X. Ber. deutsch.

Chem. Ges. 47(1914)1916-1979.

[11]. F. E. Sheibley . Carl Julius Fritzsche and the discovery of anthranilic acid, 1841.

J. Chem. (1943), Educ 20: 115-117.

[12]. W. O. Foye, T. C. Lemke, D. A. Williams. Principles of Medicinal

Chemistry,4th Ed, BT Waverly Pvt. Ltd., New Delh. (1995)247.

[13]. T. H. Al-Noor, K. F. Ali, A. J. Jarad, S. Kindeel. Synthesis, spectral and

antimicrobial activity of mixed ligand complexes of Co(II), Ni(II), Cu(II) and Zn(II)

with Anthranillic Acid and Tributylphosphine. Chem. Mater. Res 3(2013)126-133.

[14]. T. G. Ros, M. K. vander Lee, A. J. Van Dillen, J. W. Geu, D. C. Koningsberger

. Rhodium complexes with N-phenyl anthranilic acid ligands as catalysts for

hydrogenation. J. Mol. Catal. A-Chem .186 (2002)13-24.

[15]. B. B. Prasad, R. A. Sah. biomimicing approach to the mixed ligand complexes of

bivalent transition metal. Int. J. Appl. Sci. Biotechnol .1 (2013)16-20.

[16]. M. L. Peter, K. T. Friedrick, E. Walter, J. Rudolf, B. Naresh, et al. Phthalic Acid

and Derivatives in Ullmann's Encyclopedia of Industrial Chemistry, Weinheim:

Wiley-VCH (2007).

[17]. K. Deka, N. Barooah, R. J. Sarma, J. B. Baruah. Self assembled carboxylate

complexes of zinc, nickel and copper, J. Mol. Struct . 827(2007)44-49.

[18]. H. B. Mereyala, S. R. Koduru, and V. N. Cheemalpati. Resolution of 1-

arylalkylamines with 3-O-hydrogen phthalate glucofuranose derivatives: role of steric

bulk in a family of resolving agents. Tett. Asym .17 (2006)259-267.

[19]. N. Barooah, R. J. Sarma, A. S. Batsanov, J. B. Baruah. N-phthaloylglycinato

complexes of cobalt, nickel, copper and zinc, Polyhedron.25(2006)17-24.

[20]. A. C. Tella, S. O. Oguntoye, W. A. Osunniran , R. O. Arise. Coordination

compounds of N-phthaloylglycine and N-phthaloyltyrosine and their antimicrobial

activities. Elixir Appl. Chem.45 (2012)7620-7623.

[21]. G. D. rawate. Chemical Science Transactions. 3(4) (2014)1396-1399.

[22]. N. B. Nigam, P. C. Sinha and M. N. Srivastava. Indian J Chem.22A (1983)

218,24A (1985) (1893).

[23]. N. P. Singh, M. N. Srivastava and G. Kumar. Orient J Chem. 16(2000)223,

Tanz J Sci.16 (1990)111.

[24]. G. Kumar and M. N. Srivastava. Res J Chem. 9 (2005)43.

[25]. M. K. Singh, A. Das, R. Laskar and Paul, J Indian Chem Soc. 85(8) (2008)485-

490.

[26]. C. S.Branch, J. Lewinski, I. Justyniak, S. G. Bott, J. Lipkowski and A. R.

Barron. J.Chem..Soc., Dalton Trans. 8(2001)1253-1258.

[27]. F.Wiesbrock and H. Schmidbaur .J.Chem.Soc.,Dalton Trans .24(2002)4703-

4708.

[28].F.Wiesbrock, A.Schier and H. Z. Shmidbaur. Naturforsch.B:Chem.Sci.57(2)

(2002)251-254.

[29]. F. Wiesbrock and H. Schmidbaur. J.Am.Chem.Soc. 125(12) (2003), 3622-3630.

[30]. F. Wiesbrock and H. Schmidbaur. Inorg. Chem. 45(22) (2003)7283-7289.

[31].W. F. Harries and T. R. Sweet. J.Phys.Chem. 60(1956)509-510.

[32]. B. K. Aziz, D. I. Tofig, D. M. Salih and D. K. Mahmed. Asian Trans actions on

Science & Tech. 2(1)(2012)28-31.

[33]. A. Z. El-Sobati, A. A. El-Bindary, N. A.El-Deeb .Reactive & Functional

Polymers . 50(2002)131-138.

[34]. M.R.Mahmoud, M.A.Hamed, M.S.Kamel,and S.A.El-Gyar, Monatshefte Fur

Chemie . Vol.116(1985),p.1291-1304.

[35].J. G. Ros, M. K. Vander Lee, A. J. Van Dillen, J. W. Geus, D. C. Koningsberger,

J.molecular catalysis A:Chemical. 186(1) (2002)13-24.

[36].B. Yan, H. J. Zhang, G. L. Zhou and J. Z. Ni, Chem.Pap. 57(2)(2003)83-86.

[37]. G. Valli and M. Sankareswari. Int. J. Pharma. Research and Dev. 3

(11)(2011)205-212.

[38]. http://www.iasj.net/iasj?func=fulltext&aId=30015.

[39]. R. H. Prager and G. R. Skurray , Aust. J. chem . 21(1968)1037 .

[40]. A .F. Borowski and D. J. Cole-Hamilton, Polyhedron. 12(1993)1757.

[41]. T. Huey Lu, P. hattopadhyay , F.L , Liao and J. Mau Lo.J.Analytical sciences

.17(2001)905-906.

[42]. P. Gurcan , N.Sari , N.J. Inorg . Chem.38 (1999)2807-2817.

[43]. M.A. Al-Khuzaee, syntheses and characterization of some Lanthanides (III)

complexes with Antranilic acide and phenylalanine.M.Sc. Thesis, college of education

(Ibn Al-Haitham, university of Baghdad (2003).

[44]. S. L. Gao, Y. D. Hou, M. Ji, S. P. ChenandQ and Z. Shi, J. Thermo Chim.

Acta.35 (2000) 47.

[45]. M.R.Ermarcora; D.W.Ledman; R.O.Fox. Nat. struct. Biol., Vol.3 (1996), p. 59.

[46]. Taghreed, H. Al-Noor; Khalid, F. Ali; Amer J. Jarad and Aliea,S.kindeel.

Chemistry and Materials Research. Vol.3 No.3, (2013), p.126-133.

[47]. M. G. Abd El Wahed, S. M. Metwally, M. M. El Gamel and S. M. Abd El

Haleem . (Thermodynamic and Electrical Properties of Aminophenol and Anthranilic

Acid Complexes with Some Transition Metals), Bull. Korean Chem. Soc. 22(7)(2001)

663- 668.

[48]. A. F Borowski and D. J. Cole-Hamilton .Structures and Properties of

Anthranilato and N-phenylanthranilato-rhodium (I) complexes containing

triphenylphosphine ligands Polyhedron. 12(1993)1757 -1763.

[49]. M. A. Al-Khuzaee. (Syntheses and characterization of some Lanthanides (III)

complexes with Antranilic acide and phenylalanine).M.Sc. thesis,college of

education(Ibn Al-Haitham, university of Baghdad. (2003).

[50]. S. Sharma, V. K. Srivastave and A. Kumar, Eur. J.Med .Chem. 37 (2005) 689-

697.

[51]. R.Roy, S. K. Panchanan and P. S. Roy. Transition Met. Chem.12 (1987)137-140.

[52]. T. H. Al- Noor, I.Dawood and I. K. Malih .International Journal for Sciences and

Technology .7(3) (2012)32-42

[53]. J. Svara, N. Weferling and T. Hofmann ."Phosphorus Compounds, Organic" in

Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, (2006).

[54]. M. M. Rahman, H. Y. Liu, A. Prock and W. P. Giering ."Steric and Electronic

Factors influencing Transition-Metal–Phosphorus (III) Bonding". Organometallics.

6(3) (1987)(3)650–58.

[55].M.Pavlíček,Z.Trávníček,R.Pastorek.Marek,Nickel(II)hexamethyleneimi

nedithiocarbamate complexes with triphenylphosphine or tributylphosphine

J.Transition Metal Chemistry. 28(3) (2003) 260-264.

[56]. M. S. Suresh 1 and V. Prakash 2 *. International Journal of the Physical

Sciences. 5(9) (2010)1443-1449,

[57]. H. Y. Shrivastava, S. N. Devaraj, B. U. Nair. “Synthesis and Physiochemical

Charasterisation of some Schiff base complexes”, J. Inorganic Biochem. (2004)98:

387.

[58].E. C. G. Ceniceros-Gomez Agueda , F. D. Rio-Portilla, O. Hansson, E. Castillo-

Blum Silvia. “Electron transfer between plastocyanin and benzimidazolic coordination

compounds in DMSO–H2O”, Inorganic Chim Acta. (2002)331: 59.

[59]. R. K. Dubey, U. K. Dubey, C. M. Mishra. “Synthesis and Physiochemical

Charasterisation of some Schiff base complexes of Cr (III) complexes”, Indian J.

Chem. 45A (2006)1638-1642.

[60]. S. M. H. Obed. AJPS. 4(1) (2007)32-37.

[61]. R.H. Prager and G. R. Skurray . Aust.J.chem. 21(1968)1037.

[62]. A.F. Borowski and D.J. Cole-Hamilton, Polyhedron. 12 (1993)1757.

[63]. T. HueyLu, P. hattopadhyay, F. L. Liaoand and J. MauLo. J.Analyticalsciences.

17(2001)905-906.

[64]. S. sharma, V. K. Srivastave, A. Kumar. EurJ.Med.chem. 37(8) (2005)689-697.

[65]. P. Gurcan, N. Sari, N. J. Inorg. chem. 38(12) (1999)2807-2817.

[66]. M. A. AlKhuzaee, syntheses and characterization of some Lanthanides (III)

complexes with Antrhranilic acide and phenylalanine.“M.Sc. Thesis, university of

Baghdad (2003).

[67]. L. Zhu, N. N. Kostic. Inorg. Chem.Acta .21 (1994)217.

[68]. M. R. Ermarcora, D. W. Ledman, R. O. Fox .Nat. struct.Biol. 3 (1996)59.

[69]. T. H. Al.Noor , F. H. Ghanim , I. Y. MajeedTaghreed H. Al.Noor , F.H, Ghanim

, I.Y.Majeed. Advances in Physics Theories and Applica. 17(2013) 23-33.

[70]. E .Silvia, C. Blum, N. B. Behrens. Coordination chemistry of some biologically

active ligands, Coordination Chemistry Reviews. 196 (2000) 3–30.

[71]. M. Mahmoud Mashaly, H. Zinab Abd-Elwahab and A. Abeer Faheim .

Preparation, Spectral Characterization and Antimicrobial Activities of Schiff Base

Complexes Derived from 4-Aminoantipyrine, Mixed Ligand Complexes with 2-

Aminopyridine, 8-Hydroxyquinoline and Oxalic Acid and their Pyrolytical Products ,

J. Chin. Chem. Soc. 51(5A) (2004) 901 -915.

[72]. Z. H. Abd El-Wahab, M. M. Mashaly, and A. A. Faheim. Synthesis and

Characterization of Cobalt(II),Cerium(III),andDioxouranium(VI) Complexesof 2,3-

Dimethyl-1-phenyl-4-salicylidene-3-pyrazolin-5-one Mixed Ligand Complexes,

Pyrolytic Products, and Biological Activities,J. Chem. Pap.59 (1) (2005)25-36.

[73]. H. Icbudak, Z. Heren1, D. Ali Kose and H. Necefoglu. Bis(Nicotinamide) and

Bis(N,N-Diethyl Nicotinamide) P-Hydroxybenzoate Complexes Of Ni(II), Cu(II) And

Zn(II)Spectrothermal Studies,Journal of Thermal Analysis and Calorimetry.76 (2004)

837–851.

[74]. C. J. Williams, H. Morris, J. Svorec, M. Valkov, M. Valko, J. Moncol, M.

Mazur, F. Valach and M. Melnik .A study of copper(II) carboxylato complexes with

the biological ligands nicotinamide and papaverine. J.Molec. Struct. 659 (2003) 53–

60.

[75]. H. B. Shawish, M. J. Maah and S. N. Abdul Halim, Synthesis and

characterization of mixed nickel thiosemicarbazone complexes, Malaysian Journal of

Fundamental & Applied Sciences. 8(3) (2012) 162-166.

[76]. L. Yet.Practical and Effective Catalyst Systems for the Regio- and

Stereoselective Catalytic Hydroamidation of Terminal Alkynes Chem. Rev.103 (2003)

4283.

[77].R. I. Kureshy, N. H. Khan, S. H. R. Abdi, Iyer, P.; S. T. Patel. Chiral Mn(III)

Schiff base complex catalyzed aerobic enantioselective epoxidation of prochiral non-

functionalized olefins. Polyhedron. 18 (12) (1999) 1773-1777.

[78]. G. Aysegul, Wheatley, D. Havva, T. Mehmet, D. Mustafa. Investigations into

the Inhibition of Luminol Chemiluminescence by some Novel Metal Complexes,

Current Analytical Chemistry.6 (2) (2010)144-153.

[79]. M. G. Abd El Wahed, S. M. Metwally, M. M. El Gamel and S. M. Abd El

Haleem. Bull. Korean Chem. Soc. 22(7)(2001)663-668.

[80].M. G. Abd El-Wahed, S. R. Selim, S. A. Seliman, M. M. ElGamel .Bol. Soc.

Quim. Peru. 64(1998)246.

[81]. M. G. Abd El-Wahed, S. M. Metwally, K. A. El Manakhly. Mater. Chem. Phys.

47(1997) 62.

[82]. R. Bartnik, W. Strzyzewski, W. Pol. J. Appl. Chem. 36(1992) 207.

[83]. H.Yokota .Boseikanri.38 (1994)127.

[84]. G. T. Musev, G. G. Alimamdov, Talibov A. G. sb. Tr.Akad. Nauk Az. SSR Inst.

Neftekkim. Protsessovim. Akad.Yu. G. Mamedalieva. 14 (1984) 145.

[85]. T. R. Sorenson. J. Med. Chem.19 (1976), p.135.

[86]. P. R.Shukla. Indian J. Chem.6 (1968)114.

[87]. M.K.Alyaviya, Tephyakova, Z. M. Zh. Neorgan. Khim. 10 (1995)2504.

[88]. T.E. Olalekan, Ph.D.1*and T.E. Bakare, M.Sc.2, The Pacific Journal of Science

and Technology.16 (1) (2015) 233-239.

[89]. T. Dileep, S. Haque, S. Misra,and R. Chandra. “Synthesis and Pharmacological

Screening of N–Substituted Anthranilic Acid Derivatives”. International Journal of

Drug Development & Research. 3 (2) (2011) 265 –271.

[90]. A. Beeby and A.E Jones. “The Phytophysical Properties of Methyl

Anthranilate”. Journal of Photochemical Photobiology. 64 (2001) 109-116.

[91]. M. S. Krishnan and G. D. Yadav . “An Eco-friendly Catalytic Route for the

Preparation of Perfumery Grade Methyl Anthranilate from Anthranilic Acid and

Methanol”. Organic Process Research and Development. (1998) 2-86.

[92]. V. Susindran, S. Athimoolam and S. Asath Bahadura. “Spectroscopic and

Thermal Studies of Anthranilic Acid (Vitamin l) with –Br and –Cl”. Journal of

Chemical and Pharmaceutical Research. 4(10) (2012)4628 –4636.

[93]. P. J. Mendu, Pragathi.C and Gyana.K. “Synthesis, Spectral Characterization,

Molecular Modeling and Biological Activity of First Row Transition Metal

Complexes with Schiff Base Ligand Derived from Chromone-3-Carbaldehyde and o-

Aminobenzoic Acid”. Journal of Chemical and Pharmaceutical Research. 3(4) (2011)

602 –613.

[94]. V. Susindran, S. Athimoolam and S. Asath Bahadura. “Spectroscopic and

Thermal Studies of Anthranilic Acid (Vitamin l) with –Br and –Cl”. Journal of

Chemical and Pharmaceutical Research.4 (10)(2012)4628 –4636.

[95]. H.Schiff. Justus Liebigs Ann. Chem.131(1864) 118–119.

[96]. R. D. Gillard, Wilkinson,G., and J. A. McCleverty. Comprehensive Coordination

Chemistry: The Synthesis, Reactions, Properties & Applications of Coordination

Compounds. Pergamon Press: New York, NY.2 (13.1) (1987)23-43.

[97]. M.M. El-Ajaily*, A.A. Maihub† and S.M. Filog.Asian Journal of chemistry. 18

(4) (2006) 2421-2426.

[98]. J.chacko and G.parameswaran. Journal of thermal analysis. 29 (1984) 3-11.

[99]. E.Kwaskowka ,Che`e` and J.J.Zio`lkowski .Transition Met .Chem .8 (1983)

103-105.

[100]. Md. Rabiul Hasan, Mohammad Amzad Hossain, Md. Abdus Salam,

Mohammad Nasir UddinJournal of Taibah University for Science. +Model JTUSCI-

262 (2016) 8.

[101]. S. Kumar, D.N. Dhar, P.N. Saxena, Applications of metal complexes of Schiff

bases – a review, J. Sci. Ind. Res. 68 (2009) 181–187.

[102]. D.A. Chowdhury, M.N. Uddin, F. Hoque, Dioxouranium(VI) complexes of

some bivalent tridentate Schiff-base ligands containing ONS donorset, Chiang MaiJ.

Sci. 37 (3) (2010) 443–450.

[103]. M.N. Uddin, D.A. Chowdhury, K. Hossain, Titanium(IV) complexes of

unsymmetrical Schiff bases derived from ethylenediamine and o-

hydroxyaldehyde/ketone and their anti-microbial evaluation, J. Chin. Chem. Soc. 59

(2012) 1520–1527.

[104]. F.M. Morad, M.M. El-Sjaily, S. Ben Gweirif, Preparation, physical

characterization and antibacterial activity of NI (II) Schiff base complex, J. Sci. Appl.

1 (1) (2007) 72–78.

[105]. A. Blagus, D. Cinci c,´ T. Frisˇci c,´ B. Kaitner, V. Stilinovic,´ Schiff bases

derived from hydroxyaryl aldehydes: molecular and crystal structure, tautomerism,

quinoid effect, coordination compounds, Maced. J. Chem. Chem. Eng. 29 (2) (2010)

117–138.

[106]. J. Liu, B. Wu, B. Zhang, Y. Liu, Synthesis and characterization of metal

complexes of Cu(II), Ni(II), Zn(II), Co(II), Mn(II) and Cd(II) with tetradentate Schiff

bases, Turk. J. Chem. 30 (2006) 41.

[107]. A. Budakoti, M. Abid, A. Azam, Synthesis and anti-amoebic activity of new 1-

N-substituted thiocarbamoyl-3,5-diphenylpyrazoline derivatives and their Pd(ll)

complexes, Eur. J. Med. Chem. 41 (I) (2006) 63.

[108]. M.J. Ahmed, D.A. Chowdhury, M.N. Uddin, K.J. Hassan, M.D.A. Chowdhury,

T. Jannat, 2-Hydroxyacetophenonebenzoylhydrazone – a novel spectrophotometric

reagent for the determination of traces of rear metals, Pak. J. Anal. Environ. Chem. 5

(2) (2004) 48–55.

[109]. S. Zinatloo-Ajabshir, M. Salavati-Niasari, M. Hamadanian, Praseodymium

oxide nanostructures: novel solvent-less preparation, characterization and

investigation of their optical and photocatalytic properties, RSC Adv. 5 (2015) 33792–

33800.

[110]. S. Mortazavi-Derazkola, S. Zinatloo-Ajabshir, M. SalavatiNiasari, Novel

simple solvent-less preparation, characterization and degradation of the cationic dye

over holmium oxide ceramic nanostructures, Ceram. Int. 41 (8) (2015) 9593–9601.

[111]. S. Mortazavi-Derazkola, S. Zinatloo-Ajabshir, M. SalavatiNiasari, Preparation

and characterization of Nd2O3 nanostructures via a new facile solvent-less route, J.

Mater. Sci. Mater. Electron. 26 (2015) 5658–5667.

[112]. N.K. Chaudhary, P. Mishra, Synthesis, characterization and molecular

modeling of Ni(II) & Cu(II) complexes with Schiff base derived from 1H-

benzo[d]imidazole-4-amine and 2-hydroxy benzaldehyde, Arch. Appl. Sci. Res. 5 (5)

(2013) 191–197.

[113]. V. Arun, N. Sridevi, P.P. Robinson, S. Manju, K.K.M. Yusuff, Ni(II) and

Ru(II) Schiff base complexes as catalystsfor the reduction of benzene, J. Mol. Catal.

A: Chem. 304 (2009) 191–198.

[114] .T.P. Devi, R.K.H. Singh, Complexes of nickel(II) with the Schiff bases derived

from condensation of salicylaldehyde and bisNi(amuh)2Cl2, RASAYAN ˇ J. Chem. 3

(2) (2010) 266–270.

[115]. A. Prakash, M.P. Gangwar, K.K. Singh, Synthesis, spectroscopy and biological

studies of nickel(II) complexes with tetradentate Schiff bases having N2O2 donor

group, Int. J. ChemTech Res. 3 (1) (2011) 222–229.

[116]. L.A. Saghatforoush, R. Khalilnezhad, S. Ershad, S. Ghammamy, M.

Hasanzadeh, Synthesis, characterization and electrochemical properties of -oxalato

copper (II) and nickel (II) complexes of anthranilic acid Schiff base ligands, Asian J.

Chem. 21 (8) (2009) 6326–6334.

[117]. H.N. Aliyu, A.S. Mohammed, Synthesis and characterization of iron(II) and

nickel(II) Schiff base complexes,Bayero J. PureAppl. Sci. 2 (1) (2009) 132–134.

[118]. K. Mounika, B. Anupama, J. Pragathi, C. Gyanakumari, Synthesis,

characterization and biological activity of a Schiff base derived from 3-ethoxy

salicylaldehyde and 2-amino benzoic acid and its transition metal complexes, J. Sci.

Res. 2 (3) (2010) 513–524.

[119] H.N. Aliyu, I. Ado, Studies of Mn (II) and Ni (II) complexes with Schiff base

derived from 2-amino benzoic acid and salicylaldehyde, Biokemistri. 23 (1) (2011) 9–

16.

[120]. H.N. Aliyu, I. Ado, Spectroscopic and potentiometric investigations of

copper(II) complexes with Schiff base derived from 2-amino benzoic acid and

salicylaldehyde, Biosci. Res. Commun. 21 (5) (2009) 215–220.

[121]. H.N. Aliyu, I. Ado, Studies of Mn(II) and Ni(II) complexes with Schiff base

derived from 2-amino benzoic acid and salicylaldehyde, Bayero J. Pure Appl. Sci. 3

(1) (2010) 245–249.

[122]. R. Johari, G. Kumar, D. Kumar, S. Singh, Synthesis and antibacterial activity

of M(II) Schiff base complex, J. Ind. Counc. Chem. 26 (1) (2009) 23–27.

[123]. http://dspace.library.uu.nl/bitstream/handle/1874/753/c5.pdf?sequence=5.

[124]. S. Sharma, V. K. Srivastava and A. Kumar, Eur. J. Med. Chem. 37(2002)689.

[125]. M. S. Iqbal, S. J. Khurshid and B. Muhammad, Med. Chem. Res.22 (2013)861.

[126].http://www.slideshare.net/saravanamoorthy/growth-and-spectroscopic-studies-

on-vitamin-c-crystal.

[127]. http://www.chemicalbook.com/Spectrum/118-92-3_IR3.gif.