metal coordination chemistry in the study … nternational j ournal of p harmaceutical b iological...
TRANSCRIPT
International Journal of Pharmaceutical
Biological and Chemical Sciences
e-ISSN: 2278-5191
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS)
| JUL-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45 www.ijpbcs.net or www.ijpbcs.com
Review Article
Pag
e36
METAL COORDINATION CHEMISTRY IN THE STUDY OF
BIOLOGICAL PATHWAY AND PROCESSES: A REVIEW
Jiayue Chen1, Keita Fukuzumi
2, Benny Ip
2, Florence
1, Abigail P. Cid
3
1Department of Biotechnology, Division of Applied Science, Osaka University,
1-1 Yamadaoka, Suita, Osaka Prefecture 565-0871, Japan 2Department of Applied Chemistry, Osaka University-1 Yamadaoka, Suita, Osaka Prefecture 565-0871, Japan
3International College, Osaka University, 1-30 Machikaneyama-cho,
Toyonaka, Osaka Prefecture, 560-0043, Japan
*Corresponding Author Email: [email protected]
1. INTRODUCTION
Coordination chemistry is a study of compounds formed
between metal ions and neutral or negatively charged
molecule called ligand, and this resulting compound is
called metal complex or coordination compound. The
coordination chemistry was pioneered by Nobel Prize
winner Alfred Werner (1866-1919), who created a
coordination theory of transition metal complexes [1].
Werner recognized the there are several forms of cobalt-
ammonia chloride. These compounds have different
physicalcharacteristics. The chemical formula is same,
but the arrangement of chloride ions that precipitate was
not always same, such as [Co (NH3)5Cl] Cl2 and [Co
(NH3)6] Cl3. Also these compounds are geometrically
different, having cis- and trans- conformations. Factors
such as metal ions involved, type of ligand, combination
of ligands, shape and bond angle all affect the character
of the coordination compound of coordination
compound. Bioinorganic chemistry, on the other hand,
is the interface of biology and inorganic chemistry which
emerged around 1962 in one of the Gordon Research
Conference "metals in biology" and was originally called
as "metals and metal binding in biology". Biological
system is a very diverse, sensitive and dynamic system
where varieties of metal ions are also found. Therefore it
is almost as expected to see coordination compound
involved in such a system. In this review, the topics
discussed are the basic ability of metal ions to coordinate
and then release ligands in some processes, and to
oxidize and reduce in other processes makes them ideal
for use in biological systems. Based on these features,
some important roles of metal complex in biological
pathways and life processes, and application for
Biomedical field are explored.
2. METAL COMPLEX AND BIOLOGICAL
LIGANDS
Biologically relevant ligands are categorized as
bioligands. Coordination complexes composed of metal
ion and bioligands have significant roles in biological
pathway. Metal ions act as Lewis acid, which able to
ABSTRACT:
Bioinorganic chemistry is the interface between biology and inorganic chemistry which is also referred to as metals and metal
binding in biology. The ability of metal ions to coordinate and then release ligands in some processes, and to oxidize and
reduce in other processes makes them ideal for use in biological systems. This review article highlights some important roles of
metal complex in biological pathways and life processes, application for biomedical field, and also potential biological
functions of metals that still left to be discovered and explored for development of new application in bioinorganic field.
KEYWORDS: Coordination Metals Complex; Metal; Biological Ligands; Enzyme; Photosynthesis; MRI agents
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e37
accept lone pairs of electron donated by ligands that act
as Lewis base. Often in biological system, rather than
small molecule ligands, we found biological ligands,
which form coordination complex that greatly affects the
biological pathway. The biological ligand for metal ions
is categorized into three classes: (A) Peptides with its
amino acid side chains, (B) macrocylic chelate ligands,
and (C) nucleobases (nucleic acids).
A. Amino Acids as biological ligands
Approximately one-third of all functional proteins and
enzyme in our body requires metal ion as cofactor to
perform its specific role [1]. These proteins have metal
binding site in the 3D-structure which then the metals
are usually covalently bound to the polypeptide
backbone by endogenous ligand provided by amino acid
side residues, such as histidine, methionine, cysteine,
tyrosine, aspartate, and glutamate [2]. The typical
coordination numbers are 4 or 6; however it is often
found in certain enzyme that the coordination with
amino acid residues is not complete [3]. This incomplete
coordination is a fundamental structure for catalytic
activity of enzyme, as the open site remains available for
coordination with substrate. On the other hand, this open
site structure is not observed in protein that function in
electron transfer.
The metal complex formed at metal sites of the protein
has tremendous biological function [1].
Structural—configuration of protein in tertiary or
quaternary structure, such as
Storage—uptake, binding, and release of metal ion, for
example ferritins (store Fe (III) intracellularly) [4] and
metallothioneins.
Electron transfer—uptake, release, storage of electrons,
such as iron-sulfur protein, blue copper protein, and
cytochrome [5].
Dioxygen binding-metal-O2 coordination and
decoordination, such as myoglobin, hemoglobin [6],
hemerythrins[7], and hemocyanins.
Catalytic—substrate binding and activation, turnover,
such as hydrolytic enzyme (peptidase, phosphatase),
which generally employ Mg (II) or Zn (II) in their active
sites [8].
The specificity of metal ion in forming complex with
certain protein leads to the application of metal complex
protein in chromatography method, namely IMAC
(Immobilized Metal Ion Affinity Chromatography). By
utilizing the affinity of transition metal ions like Zn (II),
Cu(II), Ni(II), and Co(II) ions toward cysteine, histidine,
and tryptophan in aqueous solution, the metal ions are
immobilized to a support, such as agarose in order to
fractionate and purify proteins in solutions [9].
B. Macrocyclic Chelate Ligands
Macrocylic ligands are polydentate ligands containing
their donor atoms, either incorporated or attached to the
cyclic backbone [10]. Generally, macrocylic ligands
contain at least three donor atoms and the macrocylic
rings should contains at minimum of nine atoms.
Macrocylic ligand complexes are involved in number of
fundamental biological systems has long been
recognized. Macrocylic derivatives enhance the kinetic
and thermodynamic stabilities of important complexes as
the metal ions is held tightly in the cavity of macrocyles
such that the biological function is not impaired with
competitive binding with other metal ion or
demetallation reactions [11]. The selectivity of metal ion
according to the chelate ring size also introduce a
selectivity for metal ion in binding to certain macrocylic
chelate, which then crucial in ligand recognition. These
macrocylic chelate ligands is crucial in biological
pathway such as porphyrin ring (Figure 1A) of the iron-
containing heme proteins in oxygen transport of red
blood cell and chlorin complex (Figure 1B) of
magnesium in chlorophyll for photosynthesis of plant.
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e38
(A) (B)
Figure 1: The structure of (A) porphyrin ring part of hemeconnected to Fe and (B) chlorin ringpart of
chlorophyll a attached to Mg as macrocycles chelate ligands [11]
.
C. Nucleobases as biological ligands
Coordination chemistry has long been focused on the
role of metal ions in nucleic acid such as DNA
replication, transcription, translation, denaturation,
renaturation, RNA polymerization [12]. The cellular
regulation of DNA requires metallonuclease to catalyze
and repair DNA strand breaks. Nucleobases can exist in
different tautomeric forms and can be mono or
multidenate ligands. As the overall charge of nucleic
acid is negative, positive charged metal ions can bind
and affect hydrogen-bond interactions of base pairing in
DNA. The most important function of metal-nucleobase
complex can be seen in the chemotherapeutical of cancer
cell. The most recent founding is the inorganic construct
such as cisplatin and bimetallic rhodium acetate exert
antitumor activity by inner-sphere coordination to DNA
[13]. cis-diamminedichloroplatinum(II) or cisplatin is
widely used DNA-damaging agent in cancer therapy.
Cisplatin cross-links to DNA forming intra and inter-
strands abduct, thus further bend the DNA and damage
DNA and resulting cell-cycle arrest and apoptosis [14][15].
However, one of the major downside of cisplatin and its
derivatives is having damaging side effects to healthy
cells. Better understanding of biological pathway
involved in cisplatin toxicity will bring a development of
new cisplatin therapeutic strategy since up to this day,
only few papers have been published on the cisplatin-
induced apoptosis pathway [14]. Recent advances in the
field of chemotherapy include the development of
targeted anticancer agents, compounds that are directed
towards a specific biomarker of cancer, with hope to
reduce the side effect. This greater selectivity is obtained
by tailored several transition metal complex towards
biomolecules associated with cancer [16]. The rhodium
metalloisertors is one of the notably success compounds,
which can specifically bind to nucleic acid base
mismatched in DNA [16]. There are also some research
showing the replacement of cisplatin such as trans,trans-
[{PtCl2(NH3)}2(piperazine)][17] and [PtCl2(hpip)][18],
which are potential antitumor agents. The further
research on this field will bring enormous potential
towards a better cancer therapy.
3. METAL COMPLEX AFFECTS ENZYME
ACTIVITES
Coordination compounds can also affect some enzyme
activities. We know that small molecules are able to
selectively inhibiting a particular enzyme, which are
usually organic compounds. Controlling enzyme activity
by coordination compounds plays an important role in
discovering new inorganic drug candidates [19].
Furthermore, the advantage that metal-binding
compounds and metal complexes can provide such kind
of unique properties contributing to enzyme inhibition
that are not found in conventional in conventional
organic molecules [20]. The mechanisms that how they
control the enzyme activity varies from different
complexes. Some compounds directly bind to the active
side of the enzyme and blocking access of the substrate
to the enzyme. In contrast to those binding directly to
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e39
active site, some complexes bind to the non active site of
substrate or enzyme, changing their conformation in
order to prevent the correct binding of substrate to
enzyme. Other enzyme itself contains coordination
structure and functions the catalysis. There are many
other kinds of mechanisms as well but in this article we
mainly talk about the following examples.
A. Enzyme inhibition by binding to an active site of
the enzyme.
Porphyrins are typical enzyme inhibitor, which inhibit
the activity of acetylcholinesterase (AChE)[21][22].
Tetraphenylporphyrin (Figure 2) can form different kind
of metal complex with different functions by changing
the coordination center (e.g. Fe, Zn, Cu, Co, etc.). A
common example, which can be found in the structure of
myoglobin and hemoglobin in our body, is the
tetraphenylporphyrin complex with Fe as coordination
center. Monosulfonatetetraphenylporphyrin (TPPS1) is
able to forms a 1:1 complex with electric eel AChE,
changing its conformation and thus inhibit the enzyme
activity [23]. White and Harmon (2002) have observed
changes by measuring the absorbance of both TPPS1 and
AChE [23]. They reported that TPPS1 is an effective
reversible competitive inhibitor of AChE, which means
that TPPS1 competes directly with the normal substrate
for an enzymatic binding site of AChE. Therefore the
coordination compound acts as a competitive inhibitor
that binding the active site of AChE in order to reduce
the concentration of free enzyme available for substrate
binding.
B. Metal complexes can promote nucleophilic
catalysis by water ionization.[24]
The metal complexes are able to cause water ionization
through the metal ion in coordination center. The metal
ion provides charge that enables it to bind with water
molecules, making the water molecule more acidic than
free one. Thus, OH- ion can exist in environment with
pH below neutral. Then it promotes the nucleophilic
catalysis.One typical example is the catalytic mechanism
of carbonic anhydrase. Carbonic anhydrase is an enzyme
catalyzes the reaction as shown below.
Typical example of this reaction is metal complex
structure with Zn2+ ion as coordination center (Figure 3).
The water molecule first binds to the fourth liganding
position of Zn2+ ion, resulting in water ionization. The
Zn2+bound OH- becomes a potent nucleophile, which can
attack the CO2, converting it into HCO3- (Figure 4). At
last the catalytic site is regenerated back to the initial
state and ready to catalyze another CO2.
Figure 3.The ribbon model of carbonic anhydrase.
Taken from
http://guweb2.gonzaga.edu/faculty/cronk/biochem/C
-index.cfm?definition=carbonic_anhydrase.
Figure 2.Tetraphenyl porphyrin metal complex
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e40
4. ROLE OF METAL COMPLEX IN LIFE
PROCESSES
Many enzymes and proteins have metal ions embedded
in them that play key roles in catalysis. In bio-inorganic
chemistry, the development of ―small inorganic
coordination complexes‖ is vital in macroscopic view of
―wide life processes‖ as it provides the process with
structural and functional support. Several of well-known
life processes, in which metal complex holds a crucial
role, include but is not limited to, artificial
photosynthesis, metalloproteins and metalloenzymes.
Photosynthesis consists of the processes of light
harvesting, charge-separation, water reduction and
oxidation, and CO2 fixation. In the core of each
photosynthetic system is the reaction center. Artificial
reaction centers have been modeled on the Marcus
theory of electron transfer [25]. For instance, the
application of emizco, ethyl 4-methyl-5-
imidazolecarboxylate, the metal salts
CoC12.6H2O, CoBr2, Co(NO3)2.6H2O and their metal
coordination compounds [Co(emizco)2C12],
[Co(emizco)2Br2].H2O,
[Co(emizco)2(H2O)2](NO3)2.2H2O in the characterization
of CO2+ coordination on photosynthesis was performed
[26]. The results showed that the emizco coordination
compounds inhibit photosynthetic electron flow and
ATP-Synthesis [26]. These were typical of Hill reaction
inhibitors. Another model of an artificial reaction core
utilized a mononuclear ruthenium complex to show
multiple proton-coupled electron transfer toward multi-
electron transfer reactions [27]. In the context, a new
Ruthenium (II) complex, [Ru(trpy) (H2bim)(OH2)]
(PF6)2 was developed to demonstrate the four-step
proton-coupled electron transfer (PCET) shown in
Figure 5.
Figure 4.The mechanism of carbonic anhydrase catalyzed reaction. Imi = imidazole, quoted from Voet & Voet
(2013) [24]
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e41
Figure 5.A schematic view of the four-step PCET reaction ofRu(trpy)(H2bim)(OH2)](PF6)2 to give the four-
electron oxidized species, [RuIV
(trpy)(bim)(O))]2+
.(H2bim = 2,2’-biimidazole and trpy = 2,2’:6’,2”-terpyridine)
modified from Kobayashi et al. (2012) [27]
Bio-inorganic chemistry is a growing interdisciplinary
study in the fields of nanomaterial science and
biotechnology. Intricate enzymatic reactions such as
protein assembly employ the use of coordination metals.
Protein assemblies are often used as molecular scaffolds
[28]. In metal homeostasis, the formation of specific
protein-metal complexes are used to effect uptake and
efflux to name a few. Metal transporters move metal ions
across the impermeable cell membrane in directional
fashion. These protein complexes, metallochaperones,
traffic metals within a cellular compartment by readying
such complexes for transfer via appropriate acceptor
proteins. Metallochaperones have been identified for
copper [29]
, nickel [30]
, and iron-sulfur protein [31]
biogenesis. In light of recent research, it has also been
suggested that the periplasmicZn(II) binding protein,
YodA, has characteristics consistent with zinc
chaperones in E. coli. [32]
The acquisition of essential metal ions is of the
importance to bacterial systems. This requires the intake
of metal ions into the cytosol, genes are expressed to
encode for plasma membrane-bound transporters.
However, this system is of a negative feedback
inhibition. When the cytosolic concentration of metal
complexes becomes too high, the aforementioned genes
are repressed. Simultaneously, the effects of metal
complexes have to be mitigated. This occurs under the
forms of sequestration by intracellular chelators, such as
Cys-rich metallothioneins [33], ferritin-like
bacterioferritins, DPS complexes [34], or efflux of metal
complexes/ions from the cytosol [35].
5. METAL-RESPONSIVE MRI AGENTS
As one of the application of metal complex in medical
field, MRI has been widely used for investigation of the
anatomy and function of body in different condition.
Magnetic Resonance Imaging (MRI) provides a three
dimensional images of biological structure with
relatively high resolution, in harmless method. Its
popularity among medical field results from nuclear
magnetic resonance of water proton in the body using
energy from an oscillating magnetic field. Therefore the
contrast in the image depends on the concentration of
water of the region and on the longitudinal (T1) and
transverse (T2) relaxation times of its protons[36].
Under magnetic field, water protons are all aligned
parallel to its external field. However when a
radiofrequency pulse (RF pulse) is sent, it inverts the
magnetization vector of water proton that was previously
aligned with the external magnetic field. The time it
takes for the spins to realign with the external field is
characterized by T1. This time can be significantly
reduced if the spins are in contact with a local
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e42
paramagnetic center because it has much stronger
magnetic field of its own compared with that of water
proton, so interacting with stronger magnetic field results
in stronger signal intensity. Coordination complexes that
leave open coordination sites for water molecules to
access the inner-sphere of paramagnetic metal ions
(particularly Gd3+ with 7 unpaired f electrons, but also
high-spin Fe3+ and Mn2+ with 5 d electrons) are therefore
excellent candidates as agents that enhance MR images
via a T1mechanism[20].
MRI agent for calcium
Gadolinium (Gd) is a paramagnetic metal. When used in
MRI, it may show certain tissue, abnormalities and
diseases more clearly visible on the image. However
gadolinium itself is toxic, so it is usually bonded to non-
metal ions. GOPTA-Gd is a MRI contrast agent
consisting of BAPTA (1, 2- bis (o-aminophenoxyl)-
ethane-N, N, N', N'- tetraacetic acid) Ca2+
chelating motif
onto which Gd (DOTA)(1,4,7,10-tetraazacyclododecane-
1,4,7,10-tetraacetic acid) macrocycles fused. After Ca2+
is bound to DOPTA-Gd, the molecule undergoes a
conformational change that opens up the hydrophilic
face of the tetraazacyclododecanemacrocycle[37]. In
short, Ca2+ opens up a space for water to directly
interfere with Gd3+ center, (Figure 6A to A’) therefore
increasing accessibility of water to Gd3+. The discovery
of this conformational change provided a template for
other Gd based molecule, such as EDTA (B), APTRA
(o-aminophenol-N, N, O-triacetate) (C) and EGTA (D).
Figure 6.A schematic view of the chelating reaction of GOPTA-Gd (A to A’). Structures of other Gd based MR
agents (B, C and D). Taken from Li et. al, 2002 [37]
Making of probe functioning in biological media
The probe that is functional in biological environment
was created according to the idea of GOPTA-Gd as
discussed in previous section. Previously, the DOTA-
based probes all suffer from a loss of relaxivity in
biological media, most likely due to anions in the
buffered aqueous solution displacing water from Gd3+ in
the Ca2+ added form [38]. However, the Ca2+ response of
the EGTA-based probe in a complex cell culture medium
designed to mimic the brain extracellular medium gave
about 10% change in relaxivity over the 0.8 – 1.2 mM
[Ca2+] range which is a similar condition to that of brain
[39]. One of the challenges in making such probes is to
limit its chemical selectivity to the target metal ion only.
Since biological median is polar, protic and high in ionic
strength, selectivity over various metal ions present is
very hard[6]. Also it is also desired to have high relaxivity
and modulations in relaxivity so that it minimizes the
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e43
amount of contrast agent needed, minimizing the
potential side effect [40]. But in above case, EGTA-based
probe was selective in Ca2+ and were not affected by
other ions such as Mg2+
. Also the relaxivity in biological
media was significantly better than that of DOTA based
one.
MRI agents for zinc and copper
While Ca2+ enhanced Gd-based probes are widely
investigated, probes that are sensitive to metal ions like
Zn2+ and Cu2+ has been also made by decreasing the
number of carboxylic acid arms to lower the affinity for
Ca2+ while retaining affinity for these d-block metals.In
2007, Major et al. discovered that binding of Zn2+
to Gd-
diaminoacetate3 (diaminoacetate3, diaminoacetate with
three methylenes) increases relaxivity[41] (Figure 7). In
2006, Queand Chang found CG1 (Copper-Gad1), that
shows increase in relaxivity in the presence of Cu2+[42].
They are both interfered by non-target ion of Zn2+ and
Cu2+ but are not affected by the presence of Ca2+.
Figure 7.A schematic view of binding of Zn to Gd-DAA3. Adopted from Major et. al, 2007 [41]
Magnesium and Potassium detection
For the function of muscle and nerve cells, the body
must control its intracellular and extracellular K+
concentration. The activities such as muscle contraction
are relying on membrane potential which is caused by
uneven concentration of K+. In 2007, Hifumi et al.
introduced gadolinium complex KMR-K1 which has two
15-crown-5 ethers into a Gd–DTPA core[43]. It showed a
slight decrease in relaxivity when K+ is added and the
agent does not respond to Na+, Mg2+, or Ca2+. Even
though the relaxivity decreased, the difference in
relaxivity leads to visualization in MRI. This was an
important discovery since it was a first potassium ion
selective gadolinium complex. At the same time, KMR-
Mg, a Gd–DTPA-derivative modified with one charged
β -diketonewas also introduced. The compound also
showed reduced relaxivity when Mg2+ is present in
median, which made it a first magnesium ion selective
gadolinium complex. Due to the difference in relaxivity
when certain ion is present, MRI can detect the presence
of the target ion just by looking at the image.
6. CONCLUSIONS AND OUTLOOK
There are obvious and crucial role of coordination metal
complex in biological pathway and processes. The works
cited in this review brought us to ainsights on how metal
trafficking in organism affects the biological pathway
and the whole biological process. As we seek to
understand the role of coordination metal complex in
biology, there will be more research opportunities to
develop better strategies for intercepting and manipulate
biological pathway and processes. Moreover, innovative
research on the design, functionality, and reactivity of a
certain metal complex can enlighten new biological
applications for metal complex such as a new MRI agent
or a DNA-probing agent.
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e44
REFERENCE
[1] Holm, R.H.; Kennepohl, P.; Solomon, E.I. Structural and
Functional Aspect of Metal Sites in Biology, Chem. Rev.
1996, 96: 2239-2314.
[2] Harding, M.M. Geometry of metal-ligand interaction in
proteins. ActaCryst. 2001, 57(3): 401-411.
[3] Riordan, J.F. The role of metals in enzyme activity.Ann
Clin Lab Sci.1997, 7(2): 119-29.
[4] Harrison, P.M. The ferritins: molecular properties, iron
storage function and cellular regulation.
BiochimBiophysActa.1996, 1275(3): 161-203.
[5] Yue, H.; Khoshtariya, D.; Waldeck, D.H. On the Electron
Transfer Mechanism Between Cytochrome c and Metal
Electrodes: Evidence for dynamic control at Short
distances, J. Phys. Chem. B. 2006, 110(40): 19906-
19913.
[6] Buchler, J. W.; Hemoglobin—An Inspiration for
Research In Coordination Chemistry. Angew. Chem. Int.
Ed. Engl.1978, 17, pp 407–423.
[7] Kurtz, D. M., Jr. Molecular Structure/ Function
Relationships of Hemerythins. Advances in Comparative
and Environmental Physiology. Blood and Tissue O2
Carriers; Mangum, C. P., Ed.; Springer Verlag,
Heidelberg, 1992; Vol. 13, pp 151-171.
[8] Vahrenkamp, H. Transitions, Transition States,
Transition State Analogues: Zinc
PyrazolylborateChemisry Related to Zinc Enzymes. Acc.
Chem. Res. 1999, 32 (7), pp 589–596.
[9] Cheung, R.C.F.; Wong, J.H.; Ng, T.B. Immobilized
metal ion affinity chromatography: a review on its
applications. ApplMicrobiolBiotechnol. 2012, 96(6):
1411-1420.
[10] Lindoy, L.F. The Chemistry of Macrocylic Ligand
Complexes, Cambridge University Press, 1990
[11] Busch, D.H. Distinctive Coordination Chemistry and
Biological Significance of Complexes with macrocylic
ligands. Acc. Chem. Res.1978, 11(10), pp 392-400.
[12] Marzilli, L.G.; Kistenmacher, T.J. Stereoselectivity in the
Binding of Transition-Metal Chelate Complexes to
Nucleic Acid Constituents: Bonding and Nonbonding
Effects, Acc. Chem. Res.1977, 10(4), pp 146-152.
[13] Boerner, L.J.K.; Zaleski, J.M. Metal complex—DNA
interactions: from transcription inhibition to
photoactivated cleavage. BiocatalBiotransform. 2005,
9(2), pp 135-144.
[14] Jordan, P.; Fonseca-Carmo, M. Molecular mechanism
involved in cisplatin cytotoxicity, CMLS, 2000, 57(8-9):
1229-1235.
[15] Cohen, S.M.; Lippard, S.J. Cisplatin: from DNA damage
to cancer chemotherapy, Prog Nucleic Acid Res Mol
Biol.2001, 67, pp 93–130.
[16] Weidmann, A.G.; Komor, A.C.; Barton, J.K. Targeted
Chemotherapy with Metal Complexes, Comments on
Inorganic Chemistry, 2014.
[17] Brabec, V.; Christofis, P.; Slámová, M.; Kostrhunová,
H.; Nováková, O.; Najajreh, Y.; Gibson, D.; Kaspárková,
J. DNA interactions of new cytotoxic
tetrafunctionaldinuclear platinum complex trans,trans-
[{PtCl2(NH3)}2(piperazine)], Biochem Pharmacol,
2007, 73(12):1887-900.
[18] Hambley, T.W.; Ling, E.C.; Munk, V.P.; Davies, M.S.
Steric control of stereoselective interactions between the
platinum(II) complex [PtCl2(1,4-diazacycloheptane)] and
DNA: comparison with cis-[PtCl2(NH3)2] and
[PtCl2(ethane-1,2-diamine)] using DNA binding and
molecular modeling studies, J BiolInorg Chem. 2001,
6(5-6):534-42.
[19] Louie, A.Y.; Meade, T.J.Metal complexes as enzyme
inhibitors, Chem Rev.1999, 99(9):2711-34.
[20] Haas, K.L.; Franz,K.J..Application of Metal
Coordination Chemistry to Explore and Manipulate Cell
Biology, Chem Rev. 2009, 109(10): 4921–4960.
[21] Lee, B.H.; Park, M.B.; Yu, B.S.Inhibition of electric eel
acetylcholinesterase by porphyrin compounds, Bioorg.
Med. Chem. Lett. 1998, 8, pp 1467-1470.
[22] Moon, S.C.; Shin, J.H.; Jeong, B.H.; Kim, H.S.; Yu,
B.S.; Lee, J.S.; Lee, B.S.; Namgoong, S.K.Synthesis of
tetrakis(multifluoro-4-pyridyl)porphin derivatives as
acetylcholinesterase inhibitors, Bioorg. Med. Chem. Lett.
2000, 10, pp 1435-1438.
[23] White, B.J.; Harmon, H.J. Interaction of
monosulfonatetetraphenylporphyrin, a competitive
inhibitor, with acetylcholinesterase, BiosensBioelectron.
2002, 17(6-7):463-469.
[24] Voet D; Voet J.G. Biochemistry, 4th edition John Wiley
and Sons, 2011
[25] Fukuzumi, S.; Kojima. T. J. Photo functional nano
materials composed of multipophyrins and carbon-based
-electron acceptors, Mater. Chem. 2008, 18, 1427
[26] Díaz, B.K.; Ayala, J.M.; Guzmán, C.E.; Blum, S.E.C.;
Prieto, R.I.; Hennsen, B.L.; Behrens, N.B.BioinorgChem
Appl. 2005; 3(1-2): 93–108.
[27] Kobayashi, M.; Masaoka, S.and Sakai K.Photoinduced
Hydrogen Evolution from Water by a Simple Platinum
(III) Terpydine Derivative: A Z-Scheme Photosynthesis,
Angew. Chem., Int. Ed. 2012; 51, 7431–7434.
[28] Ma, Z.;Jacobsen, F.E.; Giedrocl, D.P. Metal Transporters
and Metal Sensors: How Coordination Chemistry
Controls Bacterial Metal Homeostasis,Chem Rev.2009;
109(10): 4644–4681.
[29] Tottey, S.; Harvie, D.R.; Robinson, N.J. Understanding
How Cells Allocate Metals Using Metal Sensors and
Metallochaperons. Acc. Chem. Res. 2005(38):775
Abigail Cid* et al; METAL COORDINATION CHEMISTRY IN THE STUDY OF ……
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JULY-SEPT 2014 | VOLUME 3 | ISSUE 3 | 36-45| www.ijpbcs.net
Pag
e45
[30] Maier, R.J.; Benoit, S.L.; Seshadri, S. Nickel-binding and
accessory proteins facilitating Ni-enzyme maturation in
Helicobacter pylori, BioMetals. 2007, 20:655
[31] Bandyopadhyay, S.; Chandramouli, K.; Johnson,
M.K. Iron-Sulphur Cluster Biosynthesis, Biochem. Soc.
Trans. 2008, 36:1112.
[32] Graham, A.I.; Hunt, S.; Stokes, S.L.; Bramall, N.; Bunch,
J.; Cox, A.G.; McLeod, C.W.; Poole, R.K. Severe Zinc
Depletion of Escherichia coli, J. Biol. Chem 2009, 284:
18377-18389.
[33] Blindauer, C.A.; Harrison, M.D.; Robinson, A.K.;
Parkinson, J.A.; Bowness, P.W.; Sadler, P.J.; Robinson,
N.J. Multiple bacteria encode metallothioneins and
SmtA-like zinc fingers. Mol. Microbiol. 2002, 45, p
1421.
[34] Andrews, S.C.; Robinson, A.K.; Rodriguez-Quinones, F.
Bacterial Iron Homeostasis, FEMS Microbiol. Rev. 2003,
27:215.
[35] Giedroc, D.P.; Arunkumar, A.I. Metal sensor proteins:
nature’s metalloregulated allosteric switches, Dalton
Trans. 2007, 29, p 3107.
[36] Caravan P., Ellison J.J., McMurry T.J., Lauffer
R.B.Gadolinium (III) Chelates as MRI Contrast Agents:
Structure, Dynamics, and Applications,. Chem. Rev.
1999; 99:2293.
[37] Mechanistic studies of a calcium-dependent MRI contrast
agent, Li WH, Parigi G, Fragai M, Luchinat C, Meade
TJ, InorgChem, 2002 Jul 29;41(15):4018-24.
[38] Dhingra K, Maier ME, Beyerlein M, Angelovski G,
Logothetis NK. Synthesis and characterization of a smart
contrast agent sensitive to calcium. Chem. Commun.
2008;29:3444.
[39] Angelovski G, Fouskova P, Mamedov I, Canals S, Toth
E, Logothetis NK. Smart Magnetic Resonance Agents
that Sense Extracellular Calcium Fluctuations.
ChemBioChem.2008; 9: 1729
[40] Que E.L.; Chang C.J. Responsive magnetic resonance
imaging contrast agents as chemical sensors for metals in
biology and medicine, Chem. Soc. Rev., 2010,39, 51-60
[41] Major JL, Parigi G, Luchinat C, Meade TJ. The synthesis
and in vitro testing of a zinc-activated MRI contrast
agent.Proc. Natl. Acad. Sci. USA. 2007;104:13881.
[42] Que EL, Chang CJ. A Smart Magnetic Resonance
Contrast Agent for Selective Copper Sensing, J. Am.
Chem. Soc.2006; 128: 15942.
[43] Hifumi H, Tanimoto A, Citterio D, Komatsu H, Suzuki
K.Novel 15-crown-5 ether or beta-diketone incorporated
gadolinium complexes for the detection of potassium
ions or magnesium and calcium ions, Analyst. 2007 Nov;
132 (11):1153-60.
*Corresponding author address:
Email address: