ASSIGNMENT CHM579 - GROUP 3 - Nur Shahirah
ASSIGNMENT CHM579 - GROUP 3 - Nur Shahirah
ASSIGNMENT CHM579 - GROUP 3 - Nur Shahirah
introduction - 4
literature - 4
conclusion - 2.4
format - 1.6
total = 16
CHM579
ADVANCED INORGANIC CHEMISTRY
TITLE:
“Application of Coordination Compounds in Daily Life”
Cu(II) thiosemicarbazone
PREPARED BY:
GROUP :
RAS2224A
PREPARED FOR:
DR. MOHAMMAD SAIFULDDIN BIN MOHD AZAMI
ACKNOWLEDGEMENT ⅱ
INTRODUCTION 1
c. Reports on problems 2
a. Complex compound 4
d. Example of similar complex compound can be used for the chosen case study. 19
CONCLUSION 21
REFERENCES 22
ⅰ
ACKNOWLEDGEMENT
First and foremost, we would like to thank our lecturer for this assignment Dr.
Mohammad Saifulddin Bin Mohd Azami for giving such helpful information to complete this
assignment. He expressed full support and provided us with the different teaching aids that were
required to complete this assignment. We are really grateful because we managed to complete
Last but not least, this report also will not be complete without the cooperation of our
group members. We also like to give appreciation to both our parents and family members who
have motivated us to work harder and give moral support to complete this assignment.
ⅱ
INTRODUCTION
coordination chemistry. These ligands have great versatility, manifested by the existence
of two forms (thione-thiol), and the ability to bind metal ions acting as monodentate or
ions such as copper, zinc, platinum and palladium. The coordination compounds find
wide application in different aspects of daily life. In this issue, we will discuss the
First of all, the objective of this report is to learn about the coordination
compound that we have chosen, which is the Copper (ii) complex of thiosemicarbazone.
written to study the characteristics of the ligand and its metal ion. The biological activity
of the Copper (ii) complex of thiosemicarbazone and its mechanism also need to be
highlighted in this report. Lastly, the objective is to list the advantage and disadvantage
of the complex compound and to give an example of the similar complex compound.
1
c. Reports on problems
Thiosemicarbazones that have been mostly characterized are sulphur and nitrogen
great interest because of their biological activity. Due to this, many compounds derived
from thiosemicarbazone have been the subject of most biological studies. Some of the
ferrocene or pyridine fragments has been published in the limited literature information
journal. Furthermore, nothing has been reported on the characterization of their copper
complexes. In several studies, the ligand and their copper complexes have been tested for
their biological activities against bacterial, fungal, tumor and viral infections. However
very little has been done on the test against malaria parasites. The test that was done by
Rodriquiz-Arguelles et al. (2005), against bacteria shows that the ligands do not have
biological activity, while their copper complexes have higher biological activity
from the complex compound and the selected ligand. Cu (II) thiosemicarbazone
complexes are antibacterial and antitumor agents. Cu (II) complexes exhibited excellent
anticancer and antimicrobial activity and greatly exceed the corresponding metal-free
ligands.
2
The task for this report involved reviewing the importance of the compound,
analyzing the chemistry description on the preparation and the characteristics of the
compound, studying the mechanism of biological activity of the complex compound, and
The scope of content included both modern and archival information. The report
focused on theoretical methodology. All the credibility of these information sources come
from various journals found from the internet. The sources were cited in the report and
Thiosemicarbazone (TSCs) belongs to the inorganic metal chelators class and has
can form complexes with various transition metals such as Copper and Nickel.
Thiosemicarbazone are well known for their broad spectrum of biological activity. The
coordination of TSCs to metal ions results in metal complexes with anticancer properties.
In this report, we have chosen Copper (ii) complexes as our complex compound. As we
growth which is good to kill the tumor cell. By doing this report, we can explore more
about this specific coordination compound that really gives benefits to our life which is
3
REVIEW OF LITERATURE REVIEW
a. Complex compound
The metal that we choose in this experiment is Cu(ii). since, addition of metal and
ligand form coordination compounds. So, the complex compound for this assignment is
Cu(ii) thiosemicarbazones. Every compound has their importance, the same goes to the
manifested by the existence of two forms (thione-thiol), and the ability to bind metal ions
which is Cu2+ in the neutral or anionic form, acting as monodentate or bidentate ligands.
after the Second World War while 2-formylpyridine thiosemicarbazone was the first
of the most extensively studied TSC for cancer chemotherapy. Although Triapine entered
a number of clinical trials, it was later abandoned due to severe side-effects and limited
chemotherapeutic agents, potentially useful for inhibiting the activities of cancer cells.
4
Copper(II) complexes possess a wide range of biological activity and are among the most
RNA-dependent DNA polymerases and the transforming ability of Rous sarcoma virus
active antimalarial agents. They possess strong antineoplastic activity against a number of
transplantable tumors, spontaneous murine tumors and human tumors. The mechanism of
their antitumor action is thought to involve either inhibition of the enzyme ribonucleotide
thiosemicarbazone.
5
As we know, the copper(II) complexes of thiosemicarbazone were prepared
water was added dropwise while stirring the solution of the ligand thiosemicarbazone in
acetone. The precipitate was separated by filtration using micro-filter paper, washed
several times with ethanol, followed by diethyl ether and dried on a vacuum pump. The
There are several methods, conventional and modern, available to explain the
structure of ligands and their coordination compounds. The complexes are characterized
one of the most important nitrogen sulfur donor ligands. Owing to the presence of the
bind to the metal ion either in the anionic thiolate form or in the neutral thione form. The
nitrogen content of the complexes was determined using kjeldahl method. Elemental
analysis (EA) served as a principal tool to distinguish complexes from their starting
material.
Next, there are several types of spectral which are infrared spectroscopy,
spectroscopy. Infrared spectra for copper(II) complexes shows that the functional group
6
values in the corresponding ligand. This indicates that the functional group is
a variety of ways. The most direct way is infra-red spectroscopy because vibrational
transitions typically require an amount of energy that corresponds to the infrared region
coordination chemistry by making use of the fact that interatomic bonds in ligands absorb
absorption of near ultraviolet and visible light by a sample. UV- vis spectroscopy is
usually applied to organic molecules and inorganic ions or complexes. The absorption of
UV or visible radiation corresponds to the excitation of outer electrons. There are three
types of electronic transition that can be considered for coordination compounds. The last
resonance ( 1HNMR and 13CNMR) spectroscopy. The 1H and 13C NMR spectral data of
the ligands and copper (II) complexes are listed in Table 4 and table 5.
Table 4 shows 1H NMR spectral data (ppm) of the ligands and copper (II) complexes.
7
8
b. Main biological activity
The main biological activity for Copper (ii) - TSCs complexes is antiproliferative.
Copper is an important part of human proteins and enzymes. A small amount of copper is
needed by many important enzymes to participate and activate. Higher proliferation rate
in enzymes make the tumor cell require more copper than normal cell.
Thiosemicarbazone derivatives and copper have significant antitumor activity. (Qi et al.,
2020, #). For many decades, TSCs have been investigated for anticancer activity and
which was led to further investigation of compound that was found to be an inhibitor of
was found to be related with carcinostatic activity and based on the journals, recently the
new one ,Cu complex of thiosemicarbazone NSC689534 inhibited tumor growth in vivo.
(Duncan & White, 2011, #). Three Cu (ii) thiosemicarbazone complexes (C1-C3) were
oxygen species (ROS) and cell cycle was studied according to (Qi et al., 2020, #)
9
Synthesis routes for C1-C3.
complexes 1–3 and of the corresponding pro-ligands (H2L1, H2L2 and H2L3) were
evaluated against a panel of human tumor cell lines derived from solid tumors. The
calculated from dose–survival curves), obtained after 72 hours exposure listed in table
below and cell lines representative of colon (HCT-15), lung (A549) and pancreatic
(BxPC3 and PSN-1) cancers, along with melanoma (A375), have been included
10
Mechanism of the biological activity of complex compound.
The mechanism starts with synthesizing the three ligands and three cu(ii)
complexes. Then, the structure of cu(ii) complexes was determined. All Cu(ii) complexes
were crystallized from methanol solution and their structure were identified by
If ligands are similar in structure, the copper (ii) complexes differ in structure.
The C1 complex contains neutral thiosemicarbazone ligand and has square pyramidal
geometry while the other complexes contain anionic deprotonated ligand and crystallized
thiosemicarbazone has significant activity against tumors such as liver and lung cancer.
The antiproliferative properties of the complex compound on two malignant cancer cell
11
(human lung cancer cell line, A549 and human colon cancer cell line ,Caco-2) were
enhance the antitumor activity. The results after 48 hour of incubation shows that Cu(ii)
complex was higher than the corresponding ligands and C1 was similar to C3 and the
ligands, and the antitumor activity of the ligands is enhanced by coordination with
copper.
Next, to prevent the malignant proliferation of tumor cells, the cell cycle arrest
played the role and followed by cell apoptosis assay or the programmed cell death which
refer to the orderly death of the cell. Apoptosis is usually suppressed in tumor cells,
12
The intervention of some exogenous drug will cause excessive production of
reactive oxygen species (ROS) in cells that leads to apoptosis. Compared with the
control, the intracellular ROS of the three drug-treated cells were significantly increased,
and C3 had the strongest ability to promote the production of ROS. Excessive
intracellular ROS can inhibit G1, S, and G2 phase proliferation and combined with the
above-mentioned cell cycle analysis, it can be found that G2/M phase block is related to
13
c. Advantage and disadvantage of the complex compound of case study
potential that are more efficient than cis-platin, a platinum-based anticancer drugs.
clinically used drug cisplatin because of its flexible Cu(I/II) redox behavior. It has been
found to be a more potent, clinically effective and less toxic antiproliferative agent. Some
studies showed that influx and efflux of platinum-based antitumor agents are also
transport system (Ma et al., 2014). Copper(II) can significantly propagate reactive oxygen
species (ROS) which further affects the development of cancer as well as the potential
manifestation of cytotoxicity. Copper was found to bind DNA with high affinity,
moreover higher than other divalent cations, thus promoting DNA oxidation. The binding
of copper ions to specific sites can modify the conformational structure of proteins,
of biological activity. In particular, their antitumor activity is often associated with metal
14
chelating ability, which controls the bioavailability of these metals. Moreover,
ligand-metal complexes are potential sources of free radicals. TSC complexation can also
affect important cellular processes such as cell cycle inhibition and the deactivation of the
reductase inhibitor that is the treatment of various tumors, including non-small-cell lung
cancer and renal carcinoma. In particular, this refers to a function of cancer cells (Ma et
al., 2014).
alone or in combination with other drugs. One small group of copper complexes exerts an
topology. DNA topoisomerases have been molecular targets for anticancer agents.
Topoisomerases regulate DNA winding and play essential functions in DNA replication
different molecular mechanisms, analyzed herein. They allow genesis of DNA breaks
after the formation of a ternary complex, or act in a catalytic mode, often display DNA
intercalative properties and ROS production, and sometimes display dual effects. These
amplified actions have repercussions on the cell cycle checkpoints and death effectors.
15
The following observations have been revealed for the anticancer potency of
anticancer activity. Next, replacement of the hydrogen atom at N(4) position of the
thiosemicarbazone by the electron releasing group increases its cytotoxicity. For example,
metabolism, and can be rapidly taken up by cells, all of which can affect their ability to
function as catalysts for CuAAC in living systems. The mechanisms by which copper
inhibits or kills overloaded cells are not known. In studies of eukaryotic cells treated with
excess copper, people detected elevated levels of DNA lesions, protein oxidation, lipid
peroxidation, and reactive oxygen species generation. In vitro studies showed that copper
is capable of generating hydroxyl radicals from H2O2 and thereby facilitates oxidative
Oxidative stress has more harmful properties than helpful ones. It can break down
cell tissue and cause a disadvantage which is DNA damage. This damage results in
16
in some cases. Often associated with these copper(II) complexes is their instability in the
ROS-induced DNA damage products are both mutagenic and cytotoxic. Hydrogen
peroxide (H2O2), which generates hydroxy radicals in the presence of transition metal
inflammatory cell respiratory burst. Because it is freely diffusible, H2O2 can potentially
reach the nucleus to interact with DNA. H2O2 causes strand breaks and base damage in
DNA by a mechanism that requires transition metal ions, such as iron or copper.
Mixtures of Cu(II) ions and an oxidant like H2O2, often with the presence of
reductant such as ascorbic acid, generate ROS. These ROS produce extensive strand
breaks in DNA. Strand breaks often occur near guanine residues, and it has been
DNA damage in aerobic aqueous solutions is believed to be induced in vitro and in vivo
A variety of copper complexes with different structural features have been shown
damage upon reductant/H2O2 activation. The interaction of the Cu complex with DNA
17
results in hyperchromism and shifts to longer wavelengths of the strongest transitions in
attacks the adjacent DNA, is responsible for the DNA oxidative damage. The λDNA
damage chemistry illustrates that the competence and selectivity of double-strand λDNA
damage by the copper complexes are dependent on their geometric structures and types
of ligands.
These observations suggest that the structure of the copper complexes not only
governs DNA recognition, but also determines the DNA damage chemistry. The
identification of molecular structure which can efficiently and specifically perform DNA
understanding the reactions of DNA binding transition metal complexes (Liu et al.,
18
d. Example of similar complex compound can be used for the chosen case study.
The similar complex compound that can be used for the chosen case study other
the interaction between these compounds and DNA has attracted great attention in
medicinal chemistry due to the potential use of these complexes as antineoplastic agents
(D. S. Kalinowski, Y. Yu, P. C. Sharpe, 2007). Next is, because of the pharmacological
diffraction studies revealed that, in the solid state, ligand 𝐻2L1 is present in the form of
thione, showing bond distances which reveal charge delocalisation between the atoms of
were performed. The results obtained from the electronic absorption spectra, viscosity
measurements, and oxidative cleavage reactions showed that complexes 1–4 can
efficiently interact with DNA strands. The antibacterial activity assays showed that the
complexes have concentration-dependent bactericidal activities, and the best results were
19
obtained for copper complexes 1 and 2 with MIC values of 3.9 μg·mL−1 for S. aureus
In short, these results are promising and contribute to ongoing studies on the
mechanisms of action of coordination complexes, and these results will inspire research
on the design of new and better metallodrugs containing this kind of ligands.
20
CONCLUSION
In the final analysis, we learned the fundamental role of metal ion copper(II) and the
recognition of its complexes as important bioactive compounds in vitro and in vivo aroused an
ever-increasing interest in these agents as potential drugs for therapeutic intervention in various
diseases as well as its application in daily life. We get to know that thiosemicarbazone is well
known for their broad spectrum of biological activity and has numerous forms that can be
synthesized for anticancer properties. As for the coordination compound chosen, Cu(ii)
activity in which it inhibits cell growth which is good to kill the tumor cell. In other word, we
can concluded that these coordination compound play an important role in our life especially the
fight against infectious diseases, one aspect of this field, has seen great advances via multiple
investigations have been performed to test new free organic or metal coordination compounds,
which can be precursors of more efficient and less toxic drugs by acting through different
biological mechanisms. The vast array of information available for their bioinorganic properties
and mode of action in several biological systems, combined with the new opportunities offered
by the flourishing technologies of medicinal chemistry, is creating an exciting scenario for the
development of a novel generation of highly active drugs with minimized side effects which
21
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