rofyda el-sayed al-azab mahmoud nail...a review article presented by rofyda el-sayed al-azab mahmoud...
TRANSCRIPT
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.
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
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.
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