Abstract and Figures

Metal ions play many critical functions in humans. Deficiency of some metal ions can lead to disease like pernicious anemia resulting from iron deficiency, growth retardation arising from insufficient dietary zinc, and heart disease in infants owing to copper deficiency. Cancer is one of the most fatal diseases, with which millions of people die in unbearable pain every year all over the world. Almost everybody shows extreme fear of cancers and mostly turn pale once mentioning cancers. At the same time, antibiotic resistance has been growing at an alarming rate and consequently the activity of antibiotics against Gram-negative and Gram-positive bacteria has dropped dramatically day by day. In this sense there is a strong need to synthesis new substances that not only have good spectrum of activity, but having new mechanisms of action. Inorganic compounds particularly metal complexes have played an important role in the development of new metal based drugs. A significantly rising interest in the design of metal complexes as drugs and diagnostic agents is currently observed in the area of scientific inquiry, specifically termed medicinal inorganic chemistry. In this review our main focused on research proceed by Md. Kudrat-E-Zahan and et al. over the past few years.
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International Journal of Chemistry Studies
17
International Journal of Chemistry Studies
ISSN: 2581-348X; Impact Factor: RJIF 5.44
Received: 04-11-2019; Accepted: 06-12-2019
www.chemistryjournal.in
Volume 4; Issue 1; January 2020; Page No. 17-24
Recent advances on microbial activity of metal complexes: A short review
Md Saddam Hossain1, Md Abdul Mannan2, Md Kudrat-E-Zahan3*
1 Department of Chemistry, Begum Rokeya University, Rangpur, Bangladesh
2-3 Department of Chemistry, Rajshahi University, Rajshahi, Bangladesh
Abstract
Metal ions play many critical functions in humans. Deficiency of some metal ions can lead to disease like pernicious anemia
resulting from iron deficiency, growth retardation arising from insufficient dietary zinc, and heart disease in infants owing to
copper deficiency. Cancer is one of the most fatal diseases, with which millions of people die in unbearable pain every year all
over the world. Almost everybody shows extreme fear of cancers and mostly turn pale once mentioning cancers. At the same
time, antibiotic resistance has been growing at an alarming rate and consequently the activity of antibiotics against Gram-
negative and Gram-positive bacteria has dropped dramatically day by day. In this sense there is a strong need to synthesis new
substances that not only have good spectrum of activity, but having new mechanisms of action. Inorganic compounds
particularly metal complexes have played an important role in the development of new metal based drugs. A significantly
rising interest in the design of metal complexes as drugs and diagnostic agents is currently observed in the area of scientific
inquiry, specifically termed medicinal inorganic chemistry. In this review our main focused on research proceed by Md.
Kudrat-E-Zahan and et al. over the past few years.
Keywords: Metal complexes, Schiff base, mixed ligand complexes, antibacterial activity, cytotoxicity etc
Introduction
Metal complexes appear to provide a rich platform for the
design of novel chemotherapeutic drugs. We can choose the
metal itself and its oxidation state, the numbers and types of
coordinated ligands and the coordination geometry of the
complexes. The ligands can not only control the reactivity
of the metal, but also play critical role in determining the
nature of secondary coordination sphere interactions
involves in the recognition of biological target sites such as
DNA, enzymes and protein receptors. Also the ligands
themselves can sometimes undergo biologically-important
redox reactions or other modifications (e.g hydrolysis) in
vivo mediated by the metal. These variables provide
enormous potential diversity for the design of metallo-drugs
[1-3]. The introduction of metal ions or metal ion binding
components into a biological system for the treatment of
diseases is one of the main subdivisions in the field of
bioinorganic chemistry [4]. A characteristic of metals is that
they easily lose electrons to form positively charged ions
which tend to be soluble in biological fluids. It is in this
cationic form that metals play their role in biology. Metal
ions are electron deficient, whereas most biological
molecules such as proteins and DNA are electron rich. The
attraction of these opposing charges leads to a general
tendency for metal ions to bind and interact with biological
molecules [5-7]. This same principle applies to the affinity of
metal ions for many small molecules and ions crucial to life,
such as oxygen. Given this wide scope for the interaction of
metals in biology, it is not surprising that natural evolution
has incorporated many metals into essential biological
functions. Metals perform a wide variety of tasks such as
carrying oxygen throughout the body and shuttling
electrons. Hemoglobin, an iron-containing protein that binds
to oxygen by which it carries this vital molecule to body
Tissues. Similarly, calcium-containing minerals are the
basis of bones, the structural framework of the human body.
Metals such as copper, zinc, iron and manganese are
incorporated into catalytic proteins, the metalloenzymes,
which facilitate a multitude of chemical reactions needed for
life. Metal complexes are already in clinical use, and
encourage further studies for new metallo drugs such as
metal mediated antibiotics, antibacterials, antivirals,
antiparasitics, anti-HIV [8, 9], anti-diabetes, radio-sensitizing
agents and anticancer compounds [9-13]. Transition metal
complexes offer two distinct advantages as DNA-binding
agents [14, 15].
Metal Complexes as Biologically Active
Antibiotics are substances which, even at low
concentrations, inhibit the growth and reproduction of
bacteria and fungi. The treatment of infectious diseases
would be inconceivable today without antibiotics. M.S.
Islam and et al [16] were synthesized Pd(II), Pt(IV), Rh(III)
and Fe(III) mixed ligand complexes with diphenic acid and
heterocyclic amines.The ligand and metal complexes have
been screed for antibacterial activities aganist various gram
positive and gram negative bacterial species. M. Akter
Farooque and et al. [17]. M. Alim-Al-Bari and et al [18] were
synthesized four ferrocene derivatives and their metal
complexes. The ligands and metal complexes were also
screened against various bacterial species also showed
cytotoxicity against brine shrimp. The antimicrobial and
cytotoxic activities of two new chromium based
coordination complexes [Cr (Pht)2 (Cystine)2] indicated C1
and [Cr(Suc)2(Phenylamine)2] indicated C2, were
investigated against Gram-positive and Gram-negative
bacteria, fungi, and brine shrimp nauplii by M. Abdul Alim-
Al-Bari and et al [19]. Mixed ligand metal complexes of Mn
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(II), Co (II), Ni (II), Cu (II) and Zn (II) with ferrocene
dicarboxylates have been synthesized and characterized by
M. Abdul Alim-Al-Bari and et al. [20]. Antimicrobial activity
of the complexes have been examined against eight Gram
positive and Gram negative pathogenic bacteria and four
pathogenic fungi by disc diffusion method and compared
with that of standard antibiotics (Kanamycin for
antibacterial activity and Fluconazole for antifungal
activity). These complexes have been found to be moderate
to strong antimicrobial activity against the tested microbes.
Brine shrimp eggs were hatched in artificial sea water and
exposed to the complexes. The mixed ligand complexes of
Co(II) with amino acids and heterocyclic amines (fig-1)
have been synthesized and characterized by Md. Kudrat-E-
Zahan and et al. [21]. The antibceteril activity of the ligand
and metal complexes have been screened aganist various
gram positive and gram negative bacterial species.
Fig 1: Structure of the complex [Co (II)(Gly)2 (Py) 2]
The synthesis of Cr(III) / Fe(III) metal complexes with
amino acids and heterocyclic amines has been carried out by
Md. Kudrat-E-Zahan and et al. [22]. Antibacterial activity
of the complexes has been examined against six (gram
positive and gram negative) pathogenic bacteria by disc
diffusion method and compared with that of standard
antibiotic (Kanamycin). The Fe(III) complexes (fig-2) was
found to have strong antibacterial activity against the tested
bacteria than Cr(III) complex (fig-3).
Fig 2: Structure of complex [Fe (III) (Gly)2(8-HQ)]
Fig 3: Structure of complex [Cr (III)(Ala)2(Py)2]
Mixed ligand complexes of Zn(II) with anthranilic acid and
slicylic acid have been synthesized by Md. Kudrat-E-Zahan
and et al. [23]. Antimicrobial activity of the prepared
complexes were measured as resistance to antimicrobial
agents is emerging in a wide variety of nosocomial and
community-acquired pathogens.
Fig 4: Structure of Complex [Zn (NH2. C6H4. COO) (C7H4O3)]
The Cd(II) Ni(II) Co(II) and Zr(IV) metal complexes
containing a novel ligand naming bis(indoline-2-
one)diethylenetriamine have been synthesized by Md.
Kudrat-E-Zahan and et al. [24]. Antimicrobial activity of the
prepared complexes was measured as resistance to
antimicrobial agents is emerging in a wide variety of
nosocomial and community-acquired pathogens. Cadmium
complex is proven to have a higher antibacterial activity
than the other metal complexes.
Fig 5: Synthesis of Cd(II) Schiff base complex. Where, M =
Cd(II), Pd(II), Hg(II) and Zr(IV)
Md. Kudrat-E-Zahan and et al. [25] were synthesized Cd(II),
Pd(II), Hg(II) and Zr(IV) complexes of bis(indoline-2-one)
triethyelenetetramine which was made from isatin and
triethylenetetramine. The ligand and the metal complexes
were screened against various pathogenic bacterial species.
The antimicrobial results indicate that the cadmium complex
exhibit more activity than the palladium (II), mercury and
zirconium (II) complexes. Transition metal complexes of Cu
(II), Ni(II), Co(II) and Fe(III) Containing Bidentate Schiff
International Journal of Chemistry Studies http://www.chemistryjournal.in
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base, derived from the condensation of salicyladehyde and
2-aminophenol were synthesized and characterized by Md.
Akter Farooque and et al. [26]. Mixed Ligand complexes of
Ni(II) with amino acids and heterocyclic amines (fig.6) have
been has been produced by Md. Kudrat-E-Zahan and et al.
[27]. Antibacterial activity of the complexes has been
examined against six (gram positive and gram negative)
pathogenic bacteria by disc diffusion method and compared
with that of standard antibiotic (Kanamycin). The
complexes have been found to have moderate to strong
antibacterial activity against the tested bacteria.
Fig 6: Structure of the complex [Ni(II)(Gly)2(8-HQ)]
Md. Kudrat-E-Zahan and et al.[28] were synthesized Ag(I),
Cr(III), Fe(III) and Sb(III) complexes of bis(indoline-2-one)
triethyelenetetramine which was made from isatin and
triethylenetetramine. The ligand and metal complexes were
screened for antibacterial activity aganist various bacterial
species. Copper(II) complexes containing two Schi base
ligands derived from 2-hydroxybenzaldehyde with 2-
aminophenol and 3- aminophenol have been synthesized
and characterized by Md. Kudrat-E-Zahan and et al [29]
Bacteria, fungus, Entamoeba histolytica, and antineoplastic
activities of the synthesized complexes have been
determined by monitoring the parameters cell growth
inhibition, survival time of tumour mice, time-body relation,
causing of intraperitoneal cells and macrophages, alkaline
phosphatase activity, hematological eect, and biopsy of
tumour. Md. Kudrat-E-Zahan and et al. [30] were synthesized
four new metal complexes of Co (III) with glutamic acid
and heterocyclic amines. The antibacterial activity of metal
complexes were tested against various bacterial species. The
complexes showed strong to mode-rate activity against both
the gram positive and gram negative bacteria indicating the
higher zone of inhibition. Four new mixed ligand complexes
of Ni(II) containing amino acids and heterocyclic amines
have been prepared and characterized by Md. Kudrat-E-
Zahan and et al. [31]. The antibacterial activity of ligand and
metal complexes have been tested against various bacterial
species. Transition metal complexes of Co(II), Cu(II), Ni(II)
and Zn(II) Containing Bidentate Schiff base, derived from
the condensation of ethylenediamine and 4-anisaldehyde
have been prepared and characterized by IR, UV-Vis., and
some physical measurements. IR spectral studies show the
binding sites of the Schiff base ligand with the metal ion.
Molar conductance data and magnetic susceptibility
measurements give evidence for monomeric and electrolytic
nature of the complexes. Structural studies show that all the
complexes are tetrahedral. The mixed ligand complexes of
Fe (III) with tartaric acid/succinic acid and heterocyclic
amines have been synthesized and charaxterized by Md.
Kudrat-E-Zahan and et al. [32]. New mixed ligand peroxo
complexes of U(VI) and Mo(VI) with amino acids and
heterocyclic amines have been synthesized and
characterized by M. Saidul Islam and et al. [33]. Cytotoxic
activities of the complexes have been examined against
brine shrimp nauplii. U(VI) complexes were found to be
more toxic to brine shrimp than Mo(VI) complexes.
Transition metal complexes of Co(II), Cu(II), Ni(II) and
Zn(II) Containing Bidentate Schiff base, derived from the
condensation of ethylenediamine/o-aminophenol and
cinnamaldehyde were synthesized and characterized by Md.
Kudrat-E-Zahan and et al. [34]. The complexes have been
found to have moderate antimicrobial activity against the
tested bacteria. Mixed ligand complexes of Cobalt(II) with
phthalic acid and heterocyclic amines have been prepared
and characterized by M. Saidul Islam and et al. [35].
Antibacterial activity of the complexes were tested against
various bacteraial species. Mixed ligand complexes of
Co(II), Ni(II) and Cu(II) containing Phthalimide and
heterocyclic amines have been synthesized and
characterized by Md. Kudrat-E-Zahan and et al. [37].
transition metal complexes of Mn(II), Fe(III) Co(II), Ni(II),
Cu(II), and Sb(III) containing the bidentate Schiff base
derived from condensation of S-methyldithiocarbazate and
cinnamaldehyde were synthesized by Md. Kudrat-E-Zahan
[38]. The metal complexes have been screened against
various pathogenic bacterial species. A novel bidentate
Schiff base containing NS donor sequences was synthesized
by condensing Smethyldithiocarbazate (SMDTC) with p-
anisaldehyde. A series of complexes of the ligand with
Cu(II), Ni(II), Zn(II), Pb(II), Co(II), Mn(II) and U(VI) were
studied and characterized by various physico-chemical
methods. Antimicrobial activity of the prepared complexes
was tested as resistance to antimicrobial agents in a wide
variety of nosocomial and community-acquired pathogens.
The highest antimicrobial activity was detected for the
complex of Co(II) against candida species.
Fig 7: Octahedral structure of metal complexes containig SBDTC
derived ligand.
A series of transition metal complexes of Cu(II), Ni(III)
Zn(II), Cd(II), Co(II), Sb(III) and Fe(III) Containing
Bidentate Schiff base, [NI-(4-chloro-benzylidene)-
hydrazecarbodithioicacid methyl ester] derived from the
condensation of S-methyldithiocarbazate and P-
chlorobenzaldehyde were synthesized and characterized by
Abdul Alim and et al. [40]. Transition metal complexes of
Co(II), Cu(II) and Mn(II) Containing Bidentate Schiff base,
derived from the condensation of ethylenediamine and
International Journal of Chemistry Studies http://www.chemistryjournal.in
20
Cinnamaldehyde were synthesized and characterized by Md.
Kudrat-E-Zahan and et al. [41]. Binuclear Cr(III) metal ion
complex was synthesized using diphenylacetic acid as
primary ligand and 2-methyl pyridine (2-picoline) as
secondary ligand. The synthesized compounds were tested
against various pathogenic bacterial species. The complex
showed moderate antibacterial activity with no antifungal
activity [42]. Mixed-ligand complexes of Ni(II) and Zn(II)
with Diphenylacetic acid and heterocyclic amines bases
have been synthesized by Mst. Tasmina Khatun and et al.
[43]. The synthesized complexes were tested against various
pathogenic bacterial species. Metal complexes of Cr(III) and
Sn(II) containing Schiff base ligand [4-{(pyridin-2-
ylimino)methyl}phenol] derived from condensation of 2-
amino pyridine with 4-hydroxybenzaldehyde was prepared
by Md. Saddam Hossain and et al. [44]. The synthesized
schiff base and their metal complexes have been screened
for antibacterial activity against various pathogenic bacterial
species. The Schiff base and its metal complexes have been
found to have moderate to strong antibacterial activity.
Mn(II), Fe(II), Co(II) and Sn(II) ions with tridentate N,O
containing Schiff base ligand 2-{(4-hydroxybenzylidene)
amino} phenol derived from condensation of 2-amino
phenol with 4-Hydroxy Benzaldehyde have been prepared
and characterized by Md. Kudrat-E-Zahan and et al. [45]. The
ligand and metal complexes were tested against various
gram positive and gram negative bacterial species. Mn(II),
Fe(II), Co(II) and Cd(II) complexes with Schiff base ligand
4-{(pyridin-2-ylimino)methyl}phenol derived from
condensation of 2-amino pyridine with 4-
hydroxybenzaldehyde was prepared. The ligand and metal
complexes were tested against various pathogenic bacterial
species [46]. Laila Arjuman Banu and et al. [47] were
synthesized Co(II), Cu(II) and Ni(II) complexes containing
Schiff bases and Heterocyclic amines.The synthesis metal
complexes were tested against various pathogenic bacterial
species. Md. Saddam Hossain and et al. [48] Metal
complexes of Cr(III), Co(II) and Cd(II) ions were
synthesized with a ONS containing Schiff base ligand, 2-
bis(2-oxoindolin-3-ylidene)hydrazinecarbothioamide which
was derived from the condensation reaction of
thiosemicarbazide and isatin. The ligand and complexes
were isolated from the reaction in the solid form and
characterized by IR, UV-Visible, Thermal analysis and
some physical measurements. Spectroscopic evidence
indicated that the Schiff base behaved as ONS coordinating
hexadentate chelating agent. Magnetic susceptibility data
coupled with electronic spectra suggested a distorted
octahedral structure of the complexes. The synthesized
ligand and metal complexes were tested for antibacterial
activitiy study against various pathogenic bacterial species.
Jasmin Ara Shampa and et al. [50] were synthesized Schiff
base ligand and its Cu (II) complex by the condensation
reaction of isatin with amino acids (cysteine / glycine /
leucine / alanine). The Schiff base Cu (II) complex was
subjected to antimicrobial studies screened by employing
the Disc Diffusion method. All the synthesized complexes
showed strong antibacterial activity. Metal complexes of
Cu(II) and Co(II) ions with two Schiff base ligands {2-((2-
hydroxybenzylidene) amino) phenol}and {2,2'-((1,2-
phenylenebis (azanylylidene)) bis (methanylylidene))
diphenol} was derived from the condensation reaction of
salicylaldehyde with 2-aminophenol and o-phenyldiamine
respectively. The Schiff base ligands and their complexes
were subjected to antimicrobial studies screened by using
the Disc Diffusion method. All the synthesized compounds
showed moderate to strong antibacterial activity. The
complexes showed more antibacterial activity than their
corresponding ligands [51]. Mst. Sadia Afrin Dalia and et al.
[52] were synthesized Zn(II), Mn(II) and Ni(II) ions with
tetradentate N, O coordinating Schiff base ligand [2-bis(2-
hydroxybenzylidene)}hydrazinecarboxamide],
(C15H13N3O3) were synthesized. The Schiff base ligand was
derived from the condensation of semicarbazide
hydrochloride and salicylaldehyde. Farhana Afsan and et al.
[53] were synthesized Zn(II), Ni(II) and Mn(II) complexes
containing Schiff base ligand derived from
thiosemicarbazide and salicyaldehyde. Co(II) complexes
containing Schiff bases derived from 4-hydroxy
benzaldehyde and 4-amino benzoic acid also prepared and
characterized. All the synthesized ligands and metal
complexes were tested against various bacterial species.
Three new Mo(VI) peroxo complexes
[MoO(O2)(Val)2(IQ)2], [MoO(O2)(Val)2(2-Apy)] and
K[MoO(O2)(Val)2(8-HQ)], where Val = Valine, 2-Apy = 2-
Aminopyridine, IQ = Isoquinoline, and 8-HQ= 8-
Hydroxyquinoline were reported by F. K. Camellia and et
al. [54]. Four complexes of Cu(II) ions containing Schiff base
ligands, L1(C20H14O4N4) [N,N`-Bis-(2-nitro-benzylidene)-
benzene-1,2-diamine] derived from condensation reaction of
o-phenylenediamine and 2-nitrobenzaldehyde,
L2(C8H8N3SCl)[2-(2-chlorobenzylidene)
hydrazinecarbothioamide] derived from condensation
reaction of thiosemicarbazide and ochlorobenzaldehyde and
L3(C9H11N3OS) [2-(4-methoxybenzylidene)-
hydrazinecarbothioamide, derived from the condensation
reaction of anisaldehyde and thiosemicarbazide respectively
by Kismat Ara Elachi and et al. [55]. All the ligands and
complexes were tested for antibacterial activity against
various bacterial species. Metal complex [Co (SB) (SCN)]
(where, SB = 2-[(6-Amino-hexylimino)-methyl] phenol)
have been reported by Md. Kudrat-E-Zahan and et al [56].
Several biomedical toxicological properties of the complex
has been determined by monitoring the parameters cell
growth inhibition, survival time of tumour mice, time body
relation, causing of intraperitoneal cells and macrophages,
alkaline phosphatase activity, haematological effect and
biopsy of tumour. The synthesized Schiff base Co(II)
complex was found to have anticancer and cytotoxic
function. Ni(II), Cu(II), and Zn(II) complexes with Schiff
base containing the nitrogen−sulfur donor chain [(CH3)2N
C6H4CH=NNHC(S)SCH2C6H5] was prepared by the
condensation of 4-(dimethylamino)benzaldehyde and S-
benzyldithiocarbazate was reported by Md. Abdul Latif and
et al.[57]. The biological activity testing results showed that
the complexes were more potent antibiotics than the free
ligand. The Cu(II) and Ni(II) complexes displayed high
antibacterial potency and Zn(II) was moderately active
against bacteria. A series of Schiff base complexes of U(VI)
and Zr(IV) containing heterocyclic amines has prepared and
reported by Laila Arjuman Banu and et al. [58]. The
complexes have been found to have moderate to strong
antimicrobial, antifungal and cytotoxic activity. Mixed
ligand complexes of Ni(II) and Cd(II) with phthalic
International Journal of Chemistry Studies http://www.chemistryjournal.in
21
acid/succinic acid and heterocyclic amines have been
synthesized and reported by Jeasmin Akter and et al. [59].
The synthesized metal complexes were tested in various
pathogenic bacterial species. Two new mixed ligand
complexes of transiton metals were synthesized from a
Schi base (L1) obtained by the condensaton reacton of
isoniazid and p- anisaldehyde as primary ligand and 2.2′-
bipyridine (L2) as secondary ligand. The biological actvites
of the new compounds were tested against Escherichia coli
(E. coli) and Bacillus cereus (B. cereus) showing the
enhance actvity of complexes against the species as
compared to the free ligand [60]. Two complexes of Cu(II)
and Ni(II) with the ligand N- (4-methoxybenzylidene)
isonicotinohydrazide, having the formula [M(La)2]2+ (M =
Cu(II) and Ni(II)) were synthesized. The ligand was
synthesized by the condensation of isonicotinic acid
hydrazide (isoniazid) with 4-methoxybenzaldehyde
(panisaldehyde). In vitro antibacterial activity against
human pathogens like gram negative Escherichia coli (E.
coli) and gram positive Bacillus cereus (B. cereus) strains
[61]. Ranjan K. Mohapatra and et al. [62] have studied the
recent advancement of urea and thiourea based metal
complexes.
Conclusions
In this work, the biological activity such as antibaceterial,
anftifungal, cytotoxicity and anticancer effects of a some
metal complexes containing schiff bases and various of
coordinating ligands have been reviewed. The application of
bioinorganic chemistry to medicine is a rapidly developing
field. Novel therapeutic and diagnostic metal complexes are
now having an impact on medical practice. Advances in
bioinorganic chemistry are important for improving the
design of compounds to reduce toxic side-effects and
understand their mechanisms of action. This review reveals
that the pharmacologically interesting metals could be a
suitable strategy to develop novel therapeutic tools for the
development of metal based drugs.
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Kudrat-E-Zahan, Ashik Mossadik, Choudhury Zakaria
Anwar Ul Islam. Synthesis, Characterization,
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Hossen, Saidul Islam, Kudrat-E-Zahan. Studies on
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Haque, Faruk Hossen, Akhter Farooque Kudrat-E-
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... Aswell, Schiff -base is a fascinating class of ligands that have played significant acting in the betterment of coordination chemistry. Schiff -bases and their complexes have a diversity of applications in the biological activity studies and industry [5][6][7][8][9][10] to they are used radiotracers in nuclear medicine and drugs [11]. Moreover, Schiff-bases are extremely momentous substances for inorganic chemists as these are generally used in medicinal inorganic chemistry because of their various biological, pharmacological, antitumor activities as well as their outstanding chelating ability [12]. ...
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