Bioinorganic

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BIOINORGANIC CHEMISTRY - AN INORGANIC PERSPECTIVE OF LIFE
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TOPICS COVERED
* Distribution of elements - Bulk & Trace metals ; non metals - biological functions
* Porphyrins
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* Oxygen transport
* Hemoglobin & Myoglobin (Updated)
* Hemerythrin
* Hemocyanin
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* Electron transport
* Cytochromes - Cytochrome C oxidase - Cytochrome P450
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* Iron sulfur proteins - Ferridoxins - Reiske protein

* Rubredoxin
* Photosystems
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* PSII - OEC
* PSI
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* Metalloenzymes
* Carboxy peptidase
* Carboxy anhydrase
* Liver alcohol dehydrogenase
* Superoxide dismutase
* Nitrogen fixation
* Copper proteins
* Siderophores
* Ionophores
* Ferritin, Apoferritin & Tranferrin
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* Application of metals in medicine
* Practice questions (level 1)
* Advanced questions (level 2)
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PRELUDE
Bioinorganic chemistry deals with the role of metals and non metals in biological systems. The inorganic elements,
other than carbon, especially the metals, are also vital to the functioning of bio-systems. Many biological processes
such as photosynthesis, respiration, metal ion transport, enzymatic actions etc., fall into the realm of bioinorganic
chemistry. It is highly advanced interdisciplinary science.
The two major components of bioinorganic chemistry are: i) the study of naturally occurring inorganic elements in
bio-systems and ii) introduction of these elements as probes or drugs into biological systems and studying inorganic
models that mimic the behavior of various metallo-proteins. It also investigates the nutritional aspects, toxicity,
therapeutic action, transport & storage of metals and non metals in plants and animals including micro organisms.
DISTRIBUTION OF ELEMENTS IN THE EARTH CRUST AND HUMAN BODY
The organisms uptake elements in different forms from the earth crust and the surrounding
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atmosphere. However, it is evident from the following table that there is rather a weak correlation
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between the distribution of various elements in the earth crust to that in the biological systems.
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Hence certain efficient and optimized systems and mechanisms are evolved for the uptake, utilization
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and storage of essential elements; all of which fall into the scope of Bioinorganic chemistry.
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Ea rth crust Huma n body
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Element % Element %
O 47 O 63
Si 28 C 25.5
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Al 7.9 H 9.5
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Fe 4.5 N 1.4
Ca 3.5 Ca 0.31
Na 2.5 P 0.22
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K 2.5 K 0.08
Mg 2.2 S 0.06
INORGANIC ELEMENTS AND THEIR BIOLOGICAL FUNCTIONS

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The inorganic elements, especially the metals play an important role in biological systems. Based
on the relative concentrations in the biological systems, the metals are divided into:
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Bulk metals - Na, K, Mg & Ca

Trace metals - Zn, Fe, Co, Ni, Cu, Mo, V etc., which are present in low concentration and are
used for biocatalysis.
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Find the summary of biological functions metals and non metals in the following tables.
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Bulk Metal Biological functions
* As electrolytes.
* Maintain the concentration gradient in living cells (osmotic balance).
Na+ & K +
* Helps in active and passive transport.
* Charge carriers.
* Present in chlorophyll and helps in photosynthesis.

* In energy production (ATP --->ADP);
Mg2+ * Activation of enzymes.
* Information carrier.
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* Present in endo and exo skeletons.
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* Charge carrier.
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* In muscle and nerve functions - cell signalling.
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* It acts as second messenger and sentinel at synapse.
Ca2+ * Present in teeth as Ca 5(PO4)3(OH) (hydroxylapatite).
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* CaCO3 is present in endo and exo skeletons.

* In activation of enzymes.
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* In blood coagulation.
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* Among the metals present in human body, the most abundant is Calcium.
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Trace Metal Biological functions
* Hydrolytic enzymes: carboxypeptidase

* Metal storage: e.g., metallothionein.
Zn2+
* zinc finger proteins (genetic transcription), stabilization of
proteins.
I/II * Electron transfer.

Cu
* Transport and storage of dioxygen.
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* Electron transfer.
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* Transport and storage of dioxygen.
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II/III * Fe3O 4 is used to store iron, and, as it is magnetic, is used by
Fe
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magnetotactic bacteria to sense the direction of the Earth s magnetic
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field.
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* Conversion of N2 to ammonia (nitrogen fixation).

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III
Co * Cobalamine ( e.g. Vitamin-B12 )
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II/III/IV
Mn * In photosynthesis, generation of dioxygen by splitting water. It is
part of OEC (Oxygen Evolving Complex) in PS-II system.
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I/II/III * Electron transfer.

Ni
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* Hydrogenase and hydrolases (urease).
MoIV/VI,
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VIV/V * Conversion of N2 to ammonia (nitrogen fixation).
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In terms of abundance in the human body, zinc is the most important trace element after iron. Zinc is present in
i) carbonic anhydrase, an enzyme, which converts CO2 to HCO3-.
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ii) zinc finger proteins which recognize specific DNA sequences and are involved in gene function.
iii) Liver Alcohol DeHydrogenase (LADH), which facilitate the inter conversion between alcohols and aldehydes
(or ketones).
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Non metal Biological functions
P5+ * Found in Hydroxylapatite, ATP, cell membrane and DNA.
Se(II) * Selenocysteine
F- * As fluorapatite, Ca5(PO4)3F in teeth.
Cl- * Most important free anion, besides HCO3-
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-
I * functioning of hormones of the thyroid; in radiation therapy.
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PORPHYRINS
Porphyrins are the substituted porphins which are heterocyclic macrocyclics containing 4 modified
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pyrrole rings interconnected at their alpha carbons via methine(=CH-) bridges.

The simplest porphin found in Hemoglobin is called porphyrin.
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The porphin in chlorophyll is called chlorin.

In vitamin B12, the two of the pyrrole rings are directly connected to each other. This type of
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porphin is called corrin.

Porphyrin is a highly conjugated system and deeply colored. It is aromatic containing 26 -electrons,
a Huckel number.
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N NH
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N NH N NH
NH N NH N N N
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Porphyrin Chlorin Corrin
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e.g. Heme e.g. Chlorophyll e.g. Vitamin B12
Note: Actually above rings are substituted at various places by different substituents.
HEMOGLOBIN AND MYOGLOBIN

Hemoglobin (denoted as Hb) and Myoglobin (Mb) are dioxygen (O2) binding metalloproteins
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containing an iron porphyrin system, heme. Both of them contain Fe(II) ion. Hemoglobin is present
in Red Blood Cells (RBC) and helps in transport of dioxygen from lungs to tissues. Whereas, myoglobin
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stores dioxygen and is present in muscles.
STRUCTURE
Hemoglobin contains four heme units each embedded in a globular protein sub-unit. There are
two types of protein sub-units i.e., a and ß. Myoglobin contains only one heme unit surrounded by a
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globular protein, containing seven -helical and six non helical segments, made up of 153 amino
acids .
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Note: Heme moieties are shown in green color in above diagram. Fe(II) ion is shown in red color.
Heme is a porphyrin ring system made up of four pyrrole rings with an Fe(II) ion coordinated to
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nitrogens of pyrrole rings.

Globin part prevents irreversible oxidation of Fe(II) ion by providing hydrophobic environment. It
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enhances the selectivity for O2 binding. In hemoglobin, the tetramer arrangement allows for co-
operativity by making it more efficient in binding to dioxygen.
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Hemoglobin and Myoglobin exist in two forms i.e.,
1) deoxy form: No oxygen is bound to iron.

2) oxy form: dioxygen is bound to iron.
In deoxy-hemoglobin, four of the coordinated sites of iron are occupied by nitrogens of porphyrin
ring. The fifth site is occupied by Histidine residue (called proximal histidine) of globin. The sixth
position is occupied by weakly bonded water molecule. Hence some authors tend to report Fe(II)
ion in deoxy form as pentacoordinated. Deoxy-hemoglobin is said to be in T-state (tense).
On the opposite side of the proximal histidine, there is one more histidine group (called distal
histidine) placed near the iron ion. It forces the binding of dioxygen in "end on bent" confirmation.
Note: The bent confirmation discourages the binding of CO to heme iron. Otherwise, CO may
have even more affinity with the iron ion. It is observed that CO binds to hemoglobin 200X stronger
than dioxygen but binds 20,000X stronger with unprotected heme.
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Hemoglobin coordinated to dioxygen is called oxy-hemoglobin. It is also referred to as R-state

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(relaxed). In oxy-hemoglobin the sixth coordinated position of iron is occupied by dioxygen in

"end on bent" geometry.
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Hemoglobin is sometimes called as dimer of dimers since it contains two alpha and two beta
subunits.
FUNCTIONING OF HEMOGLOBIN - A BIOINORGANIC PERSPECTIVE

In deoxy-Hemoglobin, the porphyring ring is dome shaped. The Fe(II) is in high spin state and is
paramagnetic. Its size is 0.78 Ao and is positioned above the plane of the porphyrin ring.
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However, in oxy-Hemoglobin, the size of iron ion is reduced to 0.61 Ao and can fit into the cavity
of planar porphyrin ring and hence moves into the cavity of porphyrin ring with concomitant dragging
of proximal histidine that triggers the conformational changes in other globin subunits and thus by
opening other heme sites. As a result, the binding capacity of other heme irons with dioxygen is
enhanced. This is best example for co-operativity through allostery.
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N N
N N
H H
H-bond
CH3
com O
O
ry.
H 3C CH3
N N H 3C
H 3C N N CH3
i st N
FeIII
N
m
II
Fe N N
e
- -
O OC-H 2 C-H 2 C CH 2 -CH 2 -COO H 3C CH3
ich -
O OC-H 2 C-H 2 C
N
CH 2 -CH 2 -COO
-
A
N
d N
H
N
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H
Oxy Hb
Deoxy Hb
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Planar porphyrin
Domed porphyrin
Fe ion moves into the ring
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High spin Fe(II) - out of ring
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Bent O2
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The nature of Fe in oxy-Hemoglobin or in oxy-Myoglobin is controversial.
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According to old Pauling model, there is a low spin Fe(II) ion that is bound to singlet O2 in oxy-
Hb. Both are diamagnetic.
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However, according to Weiss model, there is Fe(III) ion bound to superoxide radical anion (O2-).
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Though both are paramagnetic, a strong paramagnetic coupling between them ensues diamagnetic
behavior . This model is supported by the O-O stretching frequency at 1105 cm-1 in resonance raman
spectrum that is consistent with the fact that O2 is in superoxide form. This deems to be more
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accurate and modern explanation.
Why are all the oxygen carriers that contain iron and porphyrins are found inside the cells?
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The inside cell environment is reducing and sustains Fe(II), whereas outside the cell the O2
concentration is high and hence the probability of the oxidation of Fe(II) ions to Fe(III) increases.
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What prevents synthetic (simple) iron porphyrins from functioning as O2 carriers?

In the naturally occuring porphyrins, like Hemoglobin, there is a globular protein around the heme
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groups. It prevents the irreversible oxidation of Fe(II) to Fe(III) and solvolysis of Fe(II)-O2 complex
by providing hydrophobic environment around iron. It stops the formation of Fe-O2-Fe dimer.
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However in synthetic porphyrins, protein part is absent. As a result, Fe(II) is oxidized to Fe(III)
and Fe-porphyrins easily dimerize to Fe-O2-Fe and then Fe-O-Fe (a  -oxo dimer) and hence cannot
function as oxygen carriers.
The steps, involved in conversion of free heme in aqueous solutions to hematin, a  -oxo dimer,,
when exposed to dioxygen, are summarized below.
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2+ 2+
Fe + O2 Fe O Binding of dioxygen molecule
O
3+
2+ Fe O
Fe O
O
+ 2+ O Fe
3+ Formation of  peroxo complex
Fe
Fe
3+
O 4+ 4+ Formation of ferryl complexes in which
Fe O O Fe
O Fe
3+ iron is in +4 formal oxidation state
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3+
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4+ 2+ Fe O Hematin formation
Fe O + Fe
Fe
3+
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Note: This  -oxodiiron(III) moiety has a distinctive fingerprint that has made it easy to identify
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this motif in proteins regardless of the geometry, type and number of ligands.
Magnetic susceptibility = 1.5 to 2.0 Bohr magnetons, indicating one unpaired electron. It is due
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to strong antiferromagnetic coupling of iron centres through oxygen. (Actually the value should be
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more)
Asymmetric Fe-O stretching frequency at 730 - 880 cm-1
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What is the "Cooperative effect" in hemoglobin?

Coordination of one O2 leads to conformational changes in the protein chain leading to facilitated
coordination of O2 by the other 3 sub-units in hemoglobin.
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Explain why does carbon monoxide binds strongly to iron(II) porphyrin complexes but not
iron(III) porphyrins. Compare the infrared frequency of CO in this complex to that of free
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CO.
Ans:- The Fe(II)-CO bond is strong because there are strong d  -p  * backbonding interactions
which strengthen the Fe-C bond. This is much less important for Fe(III)-CO because of higher
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positive charge on the metal.

The IR frequency of free CO is higher than that of CO in a porphyrin complex because
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backbonding adds electron density to the  * antibonding orbital of the CO bond, decreasing its
strength.
HEMERYTHRIN
Hemerythrin is a iron containing NON HEME oligomeric protein which transports O2 in marine
invertebrates. It is a respiratory protein.
The monomer of hemerythrin is myohemerythrin, which is present in the muscles of marine
invertebrates and stores dioxygen. (hemerythrin contains 8 subunits) hem stry
Deoxy forms are colorless, whereas oxy forms are violet pink in color.
Active site: The oxygen binding site is a binuclear iron centre. Deoxyhemerythrin contains two
high-spin ferrous ions bridged by hydroxyl group
The iron ions are coordinated to the protein through the carboxylate side chains of one glutamate,
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one aspartate, and five histidine amino acid residues.
One iron is hexacoordinate and another is pentacoordinate.
Histidine Histidine Histidine
N N
N
N N Asp N
O O
2+ H 2+
Fe Fe
O
O O
N N
Asp N
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Histidine Histidine
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The pentacoordinated Fe(II) binds to triplet dioxygen(3O2) and oxidized to Fe(III). Then the
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hydrogen on hydroxy group is transferred onto peroxide group. Now the second Fe(II) is also
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oxidized to Fe(III). In this process, an oxo bridge is formed between iron ions. The O-OH group is
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associated with this oxo bridge by hydrogen bonding.

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O
2+ O
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Fe 3+
Fe
O=O H
O H O
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2+ 3+ H-bonded
Fe Fe
Deoxy form Oxy form
Colorless Violet-pink
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Unlike in hemoglobin, there is no cooperative effect observed in case of hemerythrin.

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Its affinity towards CO is less than with O2, unlike hemoglobin which has a very high affinity for
CO. Its low affinity for CO reflects the importance of hydrogen-bonding in the binding of O2. Since
CO cannot engage in hydrogen bonding, its affinity with Hemerythrin is very small.
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HEMOCYANIN
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Ans:- Hemocyanin is respiratory protein containing two copper centres at the active site. It is a
dioxygen carrier suspended in the hemolymph (blood) of most molluscs and arthropods. It contains
NO HEME.
The deoxy form contains Cu(I) ions and is colorless, whereas the oxy form contains Cu(II) and
is blue in color.
In the deoxy form, each Cu(I) is coordinated to three histidine residues. Side-on bridging
coordination occurs with dioxygen in its oxy form.
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Histidine Histidine Histidine Histidine
N N N N
N N N N
O2
O
N + + N N 2+ 2+ N
N Cu Cu N N Cu Cu N
O
Histidine N N Histidine Histidine N N Histidine
N N N N
Histidine Histidine Histidine Histidine
* Cu(II) has d9 configuration. The unpaired electrons in both Cu(II) ions couple by a bonding
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interaction through the bridging peroxy ligand. Hence oxyHc is diamagnetic.
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Spectroscopic evidences of above oxyHemocyanin (oxyHc) structure;
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1) Raman spectroscopy indicates symmetric binding and rules out mononuclear peroxo
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compound.
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2) OxyHc is EPR silent indicating the absence of unpaired electrons.
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CYTOCHROMES
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* Cytochromes are, membrane-bound hemoproteins that contain 4 heme groups as co-factors

and carry out electron transport. Most of them contain iron (either in Fe(II) or Fe(III) oxidation
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states) at their active site.

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They are found in the mitochondrial inner membrane and endoplasmic reticulum of eukaryotes,
in the chloroplasts of plants, in photosynthetic microorganisms, and in bacteria.
* Cytochromes are classified based on heme type or heme iron coordination.
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1) Cytochrome-a contains heme-a

2) Cytochrome-b contains heme-b
3) Cytochrome-c contains heme-c
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* In cytochromes, the iron is hexacoordinated. The four coordination sites are occupied by four
nitrogens on pyrrole rings of heme group and remaining are occupied by usually Histidine, Cysteine
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residues.
* Depending upon the ligand, the redox potential of a given cytochrome can be tailored to meet
specific need in electron transfer schemes.
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The potentials are such that the electron flow is always from
cyt-b ----> cyt-c ----> cyt-a ----> O2
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* In the mitochondrial electron-transfer chain, cytochrome-c accepts an electron from cytochrome-
c1 and then transfersit to cytochrome c oxidase. Ultimately, the electron is used in the four-electron
reduction of O2
* Only cytochrome-a has the ability to bind to O2 and reduce it. The CN- ion can bind strongly to
the sixth coordination site and stabilize Fe(III) in cytochrome-a. This makes cyt-a to stop functioning
in electron transfer reactions.
Cytochrome C is a redox protein but myoglobin is an oxygen storage protein. Justify. hem
In cytochrome C, the iron the six coordination sites are permanently occupied. It has fixed two
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axial ligands along with 4 pyrrole nitrogens from porphyrin ring. Hence it cannot store or carry
dioxygen. It is an electron carrier.
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(S)Cys
N N
Fe
N N
(N)His
Coordination pattern in Cytochrome C
But in Myoglobin or in Hemoglobin, the sixth coordinated site is occupied by losely bound water
which can be replaced by dioxygen easily. Hence Mb and Hb can store and carry dioxygen respectively.
(sometimes the iron in deoxy hemoglobin is said to be pentacoordinated only i.e., sixth coordinated
site is vacant)
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OH2 O
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O
N N N
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Fe Fe
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N N N
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N
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(N)His (N)His
Coordination pattern in Mb and Hb

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CYTOCHROME-C OXIDASE
* Cytochrome-c oxidase (not cytochrome-c) is the major respiratory protein of animal and plant
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mitochondria. It catalyzes the oxidation of Fe(II) of cytochrome-c, and the reduction of dioxygen to
water by supplying four electrons. It contains two hemes (with two Fe3+) and three copper atoms,
arranged in three centers.
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CYTOCHROME P450
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* Cytochrome P450 oxidases constitute a super family of monooxygenase cytochromes.

* They are so named for the characteristic Soret peak at wavelengths near 450 nm when the
heme iron is reduced (with sodium dithionite - Na2S2O4) and complexed to carbon monoxide.
* These enzymes are primarily involved in steroidogenesis and detoxification.
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* They oxidise alkanes to alcohols.
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* Their reaction with dioxygen involve higher oxidation states of iron, such as Fe(IV).
* In all monooxygenases, only one oxygen atom in dioxygen is transferred to the substrate while
the other is converted into H2O.
E.g.1) R 3CH + O2 + 2e- + 2H+ 
P450
 R 3C-OH + H2O
2)
O P450 O
H OH
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H H
Camphor 5-Exo-hydroxy camphor
Mechanism:
* The active site has Fe centre which is switched between II, III and IV oxidation states.
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* In step-1, RH replaces H2O while the low spin Fe(III) is converted to high spin Fe(III).
* The substrate RH is bonded by hydrophobic interaction into the protein pocket close to the
active centre.
* Only one oxygen atom is retained on the active site (step-5). Another is converted into water.
* Overall two electrons are utilized in each catalytic cycle. These two electrons are provided by
NADH (=NAD+ + H+ + 2e-)
H H step-1 step-2
O RH
RH
N N N N e- N N
3+ RH 3+ 2+
Fe Fe Fe
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N N N N
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N N
S(Cys)
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S(Cys) S(Cys)
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low spin high spin
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O2 step-3
step-6 +H2O -ROH
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RH - RH -
RH O O
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O
O- O
N N N N
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+ -
N N +2H 3+ e 3+
4+ Fe Fe
Fe
-H2O N N N N
N N
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S(Cys) S(Cys)
S(Cys)
Compound-I with Fe(IV)
step-5 step-4
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IRON SULFUR PROTEINS

Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters and are best
known for their role in the oxidation-reduction reactions of mitochondrial electron transport.
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E.g., Ferredoxins, as well as NADH dehydrogenase, hydrogenases, nitrogenase etc.

* Additionally some Fe-S proteins regulate gene expression.
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* Fe-S proteins are vulnerable to attack by biogenic nitric oxide.
In most iron-sulfur proteins, the clusters function as electron-transfer groups.
FERREDOXINS
Ferredoxins are small proteins containing iron and sulfur atoms organized as iron-sulfur clusters.
containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. These biological
"capacitors" can accept or discharge electrons, the effect being change in the oxidation states (+2 or
+3) of the iron atoms. Thus ferredoxin acts as electron transfer agents in biological redox reactions. hem stry
The following diagram illustrates the redox scheme between low-potential and high-potential
(HiPIP) ferredoxins containing Fe4S4clusters. The formal oxidation numbers of the iron ions can be
[2Fe3+, 2Fe2+] or [1Fe3+, 3Fe2+] in low-potential ferredoxins. The oxidation numbers of the iron ions
in high-potential ferredoxins can be [3Fe3+, 1Fe2+] or [2Fe3+, 2Fe2+]
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S S S
S Fe S Fe S Fe
S 1- +e- S 2- +e- S 3-
Fe S Fe S Fe S
S Fe S S Fe S S Fe S
-e- -e-
S Fe S Fe S Fe
S S S
Following is Fe2S2 type of ferredoxin.

Cys Cys
S S
S
Fe Fe
S
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S S
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Cys Cys
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Note: High potential iron-sulfur proteins (HiPIPs) form a unique family of Fe4S4 ferredoxins that
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function in anaerobic electron transport chains.
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* Aconitase hydratase contains Fe4S4 cluster in active form and Fe3S4 cluster in inactive form.
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* Rubredoxin is considered as another iron-sulfur protein which does not contain inorganic sulfide.
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It is also an electron transport agent.

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Ferredoxin (Fd) is a sulfur-containing protein which undergoes redox reactions in a variety of

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microorganisms; Fdox+ + e- -------> Fdred , Eo = 0.439V at pH = 7.0. Will Fd generate hydrogen

gas from hydronium ions dissolved in water if the standard potential for the reduction 2H+ +
2e- ---------> H2 is -0.421 at pH=7.0.
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Show the redox reaction and explain your answer.

Ans:-L: 2H+(aq) + 2e- -----------> H2(g) ; Eo = -0.421V
R: Fdox+ + e- -----------> Fdred ; Eo = 0.439V
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Overall cell reaction

Fdox+ + H2(g) + -----------> Fdred + 2H+(aq)
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Ecell = ER - EL = 0.439 - (-0.421)V = 0.86V ------- which is > 0

This means that  rG < 0 (why? see the note). Hence reduction of Fdox+ is spontaneous and NOT
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the liberation of hydrogen. Therefore H2 gas is consumed, and not produced in this reaction.
Note: 1) The electrode with low reduction potential is written on the Left hand side and that with
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high potential is written on the Right hand side of the galvanic cell. Left hand side half cell is considered
as anode and oxidation occurs in this cell. Whereas, Right hand side half cell is the cathode where
reduction occurs.
2)  G = -nFE
In the following reaction ferredoxin-1 is the oxidised form of ferredoxin. State whether the
following reaction is true or false?
NO 2 - + ferredoxin-1 
nitrite reductase
 NH 3 + ferredoxin-2 hem stry
Ans:- False.
This is a reduction reaction. Hence only reduced form of ferredoxin can reduce NO2- to ammonia
as follows.
15
NO 2- + ferredoxin-2 
nitrite reductase
 NH 3 + ferredoxin-1
(reduced) (oxidised)
RIESKE PROTEIN
Rieske protein is an iron-sulfur protein (ISP) component of electron transfer chains like:
1) cytochrome bc1 complex (found in mitochondria).
2) the cytochrome b6f complex (found in photosynthetic systems).
It is a 2Fe-2S protein. It was first discovered and isolated by John S. Rieske.
The active centre is Fe2S2 cluster in which one iron is coordinated by two cysteine residues and the
other iron is coordinated by two histidine residues.
(Cys)S S N(His)
om
try n
Fe Fe
is ha
(Cys)S S N(His)
ch v by
.c
It is involved in electron transfer in respiration (in mitochondria) and photosynthesis (in
chloroplasts). d
di ya ed
em ar
.a it par
In mitochondria it accepts electron from Ubiquinol and transfers electron to heme iron in
cytochrome-c.
re
Whereas in Chloroplasts it accepts electron from Plastoquinol and transfers electron to heme iron
in cytochrome-f.
w .A P
RUBREDOXIN
d
Rubredoxin is a low molecular weight iron containing bacterial protein involved in electron transfer.
Sometimes rubredoxins are classified as iron-sulfur proteins. However, in contrast to iron-sulfur
proteins, rubredoxins do not contain inorganic sulfide.
Rubredoxin’s active site contains an iron ion (either in II or III oxidation state) which is coordinated
V
by the sulfurs of four cysteine residues forming an almost regular tetrahedron.

w
Cys
Fe Active site of Rubredoxin

S Cys
w
Cys S S
ACi
Cys
Rubredoxins perform one-electron transfer processes. The central iron atom changes between the
+2 and +3 oxidation states. In both oxidation states, the metal remains high spin, which helps to
minimize structural changes.
The oxidized state is reddish (due to a ligand metal charge transfer), while the reduced state is
colourless (because the electron transition has an energy of the infrared level, which is imperceptible
for the human eye).
hem stry
16

PHOTOSYSTEMS
There are two photosystems, Photosystem-I and II, within the thylakoid membranes of the
chloroplast. The photosystem I (PSI) absorbs photons of a wavelength of 700 nm, whereas,
photosystem II (PSII) absorbs photons of a wavelength of 680 nm. The electrons flow from PSII
through cytochrome bf to PSI.
PSII uses light energy to oxidize two water molecules into one molecule of dioxygen.The 4
electrons removed from the water molecules are transferred by an electron transport chain to ultimately
om
reduce 2NADP+ to 2NADPH. The proton gradient generatedacross the thylakoid membrane during
try n
the electron transport drives the synthesis of ATP.
is ha
In PSII there is a a special pair of chlorphyll-a molecules, known as P680, with Mg2+ ions and an
ch v by
.c
oxygen evolving complex (OEC) consisting of four manganese and one calcium ions.
d
di ya ed
em ar
OXYGEN EVOLVING COMPLEX (OEC) OF PHOTOSYSTEM-II
.a it par
‘Mn’ is present in Oxygen Evolving Complex (OEC) of photosystem-II. It helps in generation of

dioxygen by oxidising water molecule.The OEC is a cluster compound containing four Mn ions
(probably two in Mn(II) and remaining two in Mn(IV) states). These help in electron tranfer reactions.
re
w .A P
(Glu)O N(His)
(His)N O Mn
Asp
d
(Glu)O H2O
Mn O
OH2
Mn Oxygen Evolving Complex
H2O Ca O
(OEC)
O Mn H2O O(Glu)
V
O
H2O
OH
w
Asp
Each time the P680 is excited and an electron is kicked out, the positively charged special pair
w
extracts an electron from the manganese center.

The intermediary electron transfer complex between PSII and PSI is cytochrome bf. In this electron
ACi
transfer complex electrons are passed one at a time from plastoquinol to plastocyanin (Pc) a copper
protein of the thylakoid lumen.
In PSI also there is a a special pair of chlorphyll-a molecules, known as P700 and a 4Fe-4S cluster.
Dioxygen’s reduction potential is +0.816 mV at pH = 7 and hence is a good oxidizing agent. Yet
it does not react with organic molecules under normal conditions. Explain.
hem
Dioxygen in the ground state exists in triplet state, whereas organic molecules are mostly instry
singlet state. Hence dioxygen is kinetically inert towards organics.
But it readily reacts with metals irreversibly. (That is why iron in hemoglobin is to be protected
in the hydrophobic environment of globin.)
METALLOENZYMES
17
CARBOXY PEPTIDASE
It is a hydrolase enzyme. It removes C-terminal aminoacid from a protein. This process is repeated
until all the amino acids are removed from C-end. Thus this enzyme helps in degradation of peptides
in biological systems.
The active site in carboxy peptidase contains tetrahedrally coordinated Zn2+. It is coordinated to
two histidine residues, one glutamate residue and one water molecule.
OH2
2+
Zn
His(N) O(Glu)
His(N)
Mechanism:
i) Zn2+ activates water molecule for nucleophilic attack
om
try n
ii) H2O is polarized by a nucleophile (base)
is ha
iii) polarization of carbonyl bond which is to be cleaved.
ch v by
.c
Do you know the Edman degradation (in the laboratory) is a method for removing the N - terminal
d
di ya ed
amino acid? If you don’t, just remember.

em ar
.a it par
CARBOXY ANHYDRASE
It catalyzes the conversion of carbondioxide to bicarbonate.
re
Carbonic anhydrase
w .A P
+ -
CO 2 + H2O H + HCO 3
The active site contains tetrahedrally coordinated Zn2+. It is coordinated to three histidine residues
d
and one water molecule.

OH 2
2+
Zn
V
His(N) (N)His
His(N)
w
Mechanism:
Step 1: Deprotonation of coordinated water molecule. This is crucial step. The zinc bound water
w
is more acidic than free H2O and loses proton easily.
ACi
Step 2: Thus formed zinc bound hydroxyl group carries out nucleophilic attack on CO2 to get
(His)3Zn-OCO2H complex. (IT IS A NUCLEOPHILIC ADDITION ON CO2)
Step 3: Displacement of -OCO2H by water molecule.
H+
2+ +
(His)3Zn -OH2 (His)3Zn -OH
-HCO 3
-
CO2 hem stry
H2O
+
(His)3Zn -OCO2H
18
LIVER ALCOHOL DEHYDROGENASE (LADH)
It catalyses the oxidation of primary and secondary alcohols to the corresponding aldehydes or
ketones by the transfer of a hydride anion to NAD+ with release of a proton.

OH O
LADH
R R
1 + NAD
+
R R
1 + NADH + +
H
H
The active site in carboxy anhydrase (carbonic anhydrase) contains tetrahedrally coordinated Zn2+.
It is coordinated to two cysteine residues, one histidine residue and one water molecule.
OH 2
2+
Zn
Cys(S) (N)His
Cys(S)
om
try n
is ha
ch v by
.c
SUPER OXIDE DISMUTASE (SOD)
d
Sequential additions of electrons to dioxygen during the action of oxygenase or oxidative
di ya ed
em ar
phosphorylation produce harmfull species like superoxide, hydrogen peroxide. These species can be
eliminated by super oxide dismutases (SODs) and catalases.
.a it par
SOD converts superoxide ion into oxygen and hydrogen peroxide. Catalases then convert hydrogen
peroxide to oxygen and water.
re
w .A P
- SOD
O2 O 2 + H2O 2
Catalase
d
H2O 2 O 2 + H2O
Eucaryotic SOD contains Cu-Zn active centre. The Cu and Zn atoms are connected through an
imidazole ring(of histidine).
V
His Asp
w
His
His Cu Zn
N N His
His
w
His
ACi
During catalysis, the Cu binds to superoxide and cycles between the +1 and +2 oxidation states.
Conversion of superoxide to oxygen occurs when the Cu is reduced from +2 to +1, and conversion
of superoxide to hydrogen peroxide occurs when Cu is oxidized from +1 to +2.
2+ - +
SOD-Cu + O2 SOD-Cu + O2
+ + - 2+
SOD-Cu + 2H + O2 SOD-Cu + H2O 2
Note: Prokaryotic SOD contain either iron or manganese instead of copper & zinc. Some
hem stry
prokaryotes also contain Nickel.
Why are d-metals such as Mn, Fe, Co, and Cu are present in redox enzymes in preference to
Zn, Ga, and Ca?
19
Ans:- Mn, Fe, Co, Cu occur naturally in redox enzymes because they can have at least two stable
oxidation states. Redox reactions involve the cyclic oxidation and reduction of the metal ion. The
other metals i.e., Zn, Ga, Ca, have only one stable oxidation state, and hence cannot be oxidized or
reduced at physiological potentials.
However Zn and Ca are also present in biological systems to carry out other functions.

NITROGEN FIXATION
om
try n
Nitrogenase catalyses the reduction of dinitrogen to ammonia.
is ha
N 2 + 8e- + 8H + +16MgATP  NH 3 + H 2  16MgADP + Pi
ch v by
All the nitrogenases consists of two subunits
.c
i) M-cluster (FeMo cofactor) - containing Fe, S and Mo
d
di ya ed
ii) P-cluster - containing Fe and S

em ar
According to modern view, the M-cluster is involved in the reduction of dinitrogen to ammonia.
.a it par
The iron centres at the middle (shown in circles) are involved in binding of dinitrogen. (Note: These
irons are just having three bonds and with open configuration)
re
w .A P
S
S S O
Fe Fe
d
(Cys)S Fe Mo O O
S Fe S Fe S
N(His)
S Fe Fe S
S
V
M-cluster
w
The P-cluster contains cubane like [4Fe,4S] ferredoxins which are involved in the transfer of
electrons to M-cluster.
w
Note: The molybdenum, may be replaced by vanadium or iron in some organisms.
ACi
COPPER PROTEINS
In copper proteins, one or more copper ions are present as prosthetic groups. They are broadly
divided into three types as follows:
Type I :
* Contain single copper atom, coordinated in distorted trigonal planar geometry to two histidine
hem stry
and a cysteine residue. A loosely bound methionine residue is also present at axial distant position.
i.e. The geometry arond the Cu is distorted tetrahedral.
* These are called blue copper proteins or cupredoxins. They show beautiful intense blue color
due to LMCT (Ligand to Metal Charge Transfer) at 600 nm. Charge transfer occurs between Cys-S
to Cu(II). There is transfer of electron density from non bonding orbitals of sulfur atom of Cysteine
to the empty d-orbitals. LMCT are Laporte permitted and hence show intense absorption.
20
-4 -1
* Small hyperfine EPR coupling constant (5x10 cm ).
* They have relatively high reduction potentials (> 250 mV)
* Function as electron transfer agent.

* E.g. Plastocyanin ( helps in electron transfer in PSII to PSI)
Type II:
* Square planar geometry. Coordination through O or N. No coordination with S containing
ligands.
* His, Tyr and H2O are the ligands. There is no cysteine.
* There are non blue copper proteins. Only normal d-d transitions are possible. As they are Laporte
forbidden, the color is not intense.
* Normal hyperfine EPR coupling constant (18x10-4 cm-1) comparable to regular copper
coordination compounds.
* Catalyse redox reactions.
om
try n
* E.g. Galactoseoxidase and superoxide dismutase
is ha
Type III:
ch v by
.c
* Contain two copper centres, each of which are coordinated by three histidine residues.
d
* Intense blue color in oxidised form due to LMCT from O2- to Cu(II).
di ya ed
em ar
* No EPR signal due to strong antiferromagnetic coupling between metal ions through the bridging
.a it par
ligand. The spins are paired up due to covalent overlapping of metal ions through the bridging
ligand.
* E.g. Hemocyanin, Tyrosinase.
re
More examples:
w .A P
*Ceruloplasmin, which helps in absorption of iron, is a Cu protein containing 7 Cu centres

representing types I, II and III.
d
It is involved in the process of oxidizing Fe(II) to Fe(III) during the transfer of iron from
transferritin to ferrritin.
* Nitritereductase contains type II (substrate activation) and type I Cu centres (for e- transfer)
V
Others:
w
e.g. CuA (binuclear copper centre) and CuB in cytochrome-c oxidase.

Cuz centre found in nitrous-oxide reductase. It has 4 copper centres coordinated by 7
histidine residues and bridged by a sulfur atom.
w
SIDEROPHORES
ACi
Siderophores are the multidentate anionic ligands released by microbes under extreme iron
deficiency conditions. Under highly oxidising conditions, iron is oxidized to Fe3+ and forms insoluble
Fe(OH)3. Hence not available to microbes. But microbes release siderophores to absorb them. These
molecules chelate with Fe3+ and make insoluble Fe3+ into soluble form and thus help in absorption of
iron. Citrate is a simple siderophore.
Other e.g. Catecholates - like Enterobactin
Hydroxamate - like Mycobactin
Desferrichrome, Desferrioxamine B etc., hem stry
Siderophores can fully satisfy the octahedral geometry requirements of iron without significant
distortion and can bind flexibly.
Note: 1) Methanobactin is a siderophore for absorbing Cu metal.

2) In humans, iron is mobilized by transferrin.
21
IONOPHORES
An ionophore is a lipid soluble macrocyclic molecule, which transport ions (especially hard cations)
across the lipid bilayer of the cell membrane. Ionophores are involved in passive transport.
There are two types of ionophores as follows;
* Carrier ionophores which bind to a particular ion and facilitates its transport through the
lipid membrane. It shields the charge on ion from the surroundings and forms a lipophilic shell
around the ions.
* Channel forming ionophores, which form a hydrophilic pore (or channel) in a membrane,
allowing ions to pass through it.
Ionophores are ‘charge and size’ selective. They usually coordinate through O and N. Chelation
plays major role in stabilizing the complex. Selectivity depends on number of coordination bonds
and confirmation of ionophore.
These are used to used to increase the permeability of biological membranes to certain ions
om
try n
and also act as antibiotics.
Ionophores disrupt transmembrane ion concentration gradients, required for the proper
is ha
functioning and survival of microorganisms, and thus have antibiotic properties.
ch v by
.c
Examples of ionophores with the ions upon which they act.
Valinomycin (K+) d
di ya ed
em ar
Salinomycin (K+)
.a it par
Gramicidin A (H+, Na+, K+) ---- It is a transmembrane channel forming ionophore.

Nonactin (NH4+)
Ionomycin (Ca2+)
re
2,4-Dinitrophenol (H+)
w .A P
Monensin (H+, Na+) ----- used in cattle feed

* Crown ethers are the laboratory analogues of ionophores.
d
FERRITIN, APOFERRITIN AND TRANSFERRIN

Ferritin is a globular protein complex consisting of 24 protein subunits and is the main intracellular
V
iron storage protein in both prokaryotes and eukaryotes. It has the shape of a hollow sphere. Inside
the sphere, iron is stored in the Fe(III) oxidation state. It is incorporated in the mineral ferrihydrite,
w
[FeO(OH)]8[FeO(H2PO4)], which is attached to the inner wall of the sphere. Whenever required by
the body, iron is reduced and released as hydrated Fe(II).
Ferritin that is not combined with iron is called apoferritin.
w
Transferrin is a glycoprotein present in blood plasma that binds Fe(III) very tightly but reversibly.
Affinity to iron decreases with decrease in pH. It helps in transport of iron.
ACi
APPLICATIONS OF METALS IN MEDICINE
* cis platin and budotitane are used in treatment of cancer.
* Iron in the form of ferrous sulfate, ferrous gluconate are used in treatment of iron deficiency
anemia.
* Li+, in the form of Li2CO3, is used in the treatment of depression, hypertension.
* Sb(III) salts are used in eczema (inflammatory condition of skin).
* Bi(III) salts (as Bismuth subsalicylate ) are used in gastric ulcer.
* BaSO4 is used as contrast agent in radiography.
hem stry
* Gd3+ is used as contrast agent in NMR.
* 99mTc (in Cardiolyte) is used in radio diagnostics. 99mTc is a metastable isotope of Technetium, an
artificially made element. It’s half life is 6hrs only and emits gamma rays.
* Silver sulfadiazine is used to treat and prevent bacterial or fungal infections of the skin.
22
* Selenium sulfide used to treat seborrheic dermatitis and Tinea versicolor.
* MoS42- (tetrathiomolybdate) is used as “anti copper agent” in Wilson’s disease (excess of copper
accumulation in liver - a genetic disorder). It is also used as an antitumor agent.

CIS PLATIN
om
try n
is ha
ch v by
.c
d cis-Diamminedichloridoplatinum(II)
di ya ed
em ar
Note: chlorido is very recent IUPAC usage instead of chloro.
.a it par
* Pt (Z=78). Belongs to Nickel group. with e.c - [Xe] 4f14 5d8 6s2
* For Pt2+ -- [Xe] 4f14 5d8 .
re
* Hybridization of Pt2+ is dsp2 . It is a square planar and low spin complex with zero magnetic
w .A P
moment. The crystal field splitting of square planar complexes is shown below.
d
V
w
w
ACi
Action: Upon administration to the cancer patient, the chloride ligands are displaced by water
and thus aqua platinum complexes are formed in cells, which bind and cause crosslinking of DNA-
--- ultimately triggers apoptosis - programmed cell death.
More stuff - with brief explanation
* Vitamin B-12 contains Co(III). There is a corrin ring system in it. (Can you mention the difference between heme and corrin
ring systems?)
hem stry
* Be, Cd, Hg, Tl and Pb are toxic elements. These elements have strong complexing ability and an especially strong affinity for
sulfur. They may displace essential elements such as Ca and Fe, and may also disrupt protein structure by breaking S-S bridges.
Once attached to suitable ligands they are hard to displace.
Chelation therapy is used in treatment for heavy metal poisoning. It uses chelating ligands like EDTA that bind very
strongly with toxic elements in complexed form and remove them.
* Calmodulin (CALcium MODULated proteIN) is a calcium binding protein present in all eukaryotic cells. It can bind to and
regulate a multitude of different protein targets, thereby affecting many different cellular functions such as inflammation, metabolism,
apoptosis, muscle contraction, intracellular movement, short-term and long-term memory, nerve growth and the immune response.
23
Gadolinium salts as MRI agents
* A good MRI agent should have following charactersitics:

1) High magnetic moment;
2) Long electron-spin relaxation time;
3). Low toxicity;
* Gd3+ salts like [Gd(dtpa)(H2O)]2-(gadopentetate dimeglumine) and [Gd(dota)(H2O)]- (gadoterate
meglumine) fit this for the purpose.
PRACTICE QUESTIONS
Key & explanation to problems in this book are available at following link:
om
try n
is ha
ch v by
1) Complexes of which of the following metals are used in the treatment of rheumatoid arthritis:
.c
1. Gold
d
2. Ruthenium 3. Iron 4. Copper
di ya ed
em ar
2) In biological systems, the metal ion involved in the dioxygen transport besides Fe is
.a it par
a) Co b) Zn c) Mg d) Cu
re
3) In photosynthesis, the predominant metal present in the reaction centre of photosystem II is

w .A P
(a) Zn (b) Cu (c) Mn (d) Fe
4) Zn in carbonic anhydrase is coordinated by three histidine and one water molecule. T h e

d
reaction of CO2 with this enzyme is an example of

(a) electrophilic addition (b) electron transfer
(c) nucleophilic addition (d) electrophilic substitution.
V
5) The metals present in nitrogenase are

w
(a) Fe and Mg (b) Mo and K (c) Mo and Fe (d) Fe and K
6) The transition metal present in vitamin B12 is_______

w
7) The trivalent ion of lanthanoid element which is used as NMR contrasting agent is
ACi
1) Gadolinium 2) Technetium 3) Cerium 4) Lutetium
8) Match the following

1) Li+ A) Ulcer treatment
2) Bi3+ B) Eczema
3) Sb3+ C) Anemia
4) Fe2+ D) Depression
9) The enzyme which removes C-terminal amino acid from a peptide is

hem stry
1) Carbonic anhydrase 2) Carboxy peptidase 3) Zymase 4) All
10) Which of the following metal is stored by metallothionein in biological systems?

1) Fe 2) Cu 3) Zn 4) Co
24
11) The metals present in superoxide dismutase are: (CSIR NET DEC 2011)
a) Zn & Fe 2) Cu & Fe 3) Mo & Cu 4) Cu & Zn
12) In human body, by mass, the most abundant nonmetal is _____ and most abundant metal is
_____.
13) The copper containing non heme respiratory protein is

1) Cytochrome-c 2) Hemerythrin 3) Hemocyanin 4) Myoglobin
14) The oxidation state of iron stored in ferritin is

1) +2 2) +1 3) +3 4) 0
15) The enzyme which catalyzes the conversion of carbondioxide to bicarbonate is
om
try n
1) Carboxy peptidase 2) Superoxide dismutase
3) Carboxy anhydrase 4) Hydrogenase
is ha
ch v by
.c
16) The number of methine bridges present in porphyrin is _______ and in corrin is _____ .
d
di ya ed
em ar
17) The ionophore used in the cattle feed to improve the permeability of Na+ and H+ ions is
.a it par
1) Crown ethers 2) Monensin 3) Ionomycin 4) Nonactin

re
A) Silver sulfadiazine 1) Anti copper agent

w .A P
B) Selenium sulfide 2) Skin fungal infections

C) tetrathiomolybdate 3) Radiodiagnosis
d
D) Cardiolyte 4) Seborrheic dermatitis
19) The function of Na+ and K+ in biological systems is

1) To maintain osmotic balance in the cells 2) Help in active & passive transport
V
3) As charge carriers 4) All

w
20) Fluoride is present in the teeth in the form of

1) CaF2 2) Na3AlF6 3) Ca5(PO4)3F 4) CaF2.CaCO3
w
21) Which of the following is a channel forming ionophore?

1) Valinomycin 2) Salinomycin 3) Gramicidin 4) All
ACi
22) The porphin system in chlorophyll is called as
1) porphyrin 2) chlorin 3) corrin 4) heme
23) The metal present in both superoxide dismutase and hemocyanin is

a) Zn b) Fe c) Cu d) Ni
24) The metal ion present in urease is____ . hem stry

25) The ionophore valinomycin is highly selective for:
a) K+ b) Na+ c) Mg2+ d) Ca2+
26) The metal ions that have highest mobility in biological media are:
25
a) Mg(II) & Ca(II) b) Zn(II) & Fe(II) c) Na(I) & K(I) d) Ni(II) & Cu(II)
27) Cisplatin is:

a) diamagnetic b) paramagnetic c) ferromagnetic d) anti-ferromagnetic
28) Hemerythrin belongs to the group of:

a) non-heme iron protein b) heme-iron protein
c) binuclear copper protein d) non heme non iron protein
29) Which of the following is correct concerning the differences between hemoglobin and
myoglobin?
A) Hemoglobin is a monomeric protein and myoglobin is a tetrameric protein.
B) Hemoglobin exhibits a hyperbolic O2 saturation curve while myoglobin exhibits a sigmoid
shaped curve.
om
try n
C) Hemoglobin exhibits cooperative binding of O2 while myoglobin does not.
D) Hemoglobin exhibits a higher degree of O2 saturation at all physiologically relevant partial
is ha
pressures of O2 than does myoglobin.
ch v by
.c
d
30) The metal present in carbonic anhydrase is
di ya ed
em ar
(a) Cobalt (b) Nickel (c) Zinc (d) Magnesium.
.a it par
31) In biological systems, the metal ions involved in electron transport are
(a) Na+ and K+ (b) Zn2+ and Mg2+
re
(c) Ca2+ and Mg2+ (c) Cu2+ and Fe3+

w .A P
32) Which one of the following statements for hemoglobin is NOT correct?
d
(A) The binding with O2 is weaker in comparison with myoglobin.

(B) Iron is 5-coordinated.
(C) Iron is coplanar with the porphyrin ring in the absence of oxygen.
(D) The oxidation state of iron is +2.
V
33) When a reduced cytochrome transfers an electron from its Fe (II) to the bound O2,
w
(a) The bond order of O2 is reduced by one and  O2 decreases.

(b) A metal bound superoxide is formed and  O2 decreases.
w
(c) A metal bound superoxide is formed and  O2 increases
ACi
(d) The bond order of O2 is reduced by one and  O2 increases

I II
P) Liver alcohol dehydrogenase 1) Cu at the active site
Q) cytochrome C oxidase 2) Fe and Cu at the active site
R) Hemocyanin 3) Zn at the active site
S) Myoglobin hem
4) Fe at the active site stry
5) Mo at the active site
6) Cu and Zn at the active site
(a) P-6, Q-2 R-1, S-4 (b) P- 3, Q-2, R-1, S-4

(c) P-3, Q-2, R-4, S-5 (d) P-5, Q -6, R-1,S-2
26
I II
P) Cytochrome C I) Zinc
Q) Calmodulin II) Potassium
R) Chlorophyll III) Magnesium
S) Alcohol dehydrogenase IV) Calcium
V) iron
(a) P - I Q - II R -III S - IV
(b) P - II Q - III R -IV S-I
(c) P - III Q- IV R-I S- II
(d) P-V Q- IV R - III S-I
om
try n
36) Which statement is the correct description of hemerythrin?
1) A heme protein with one Fe centre at the active site..
is ha
2) A metalloprotein containing two Fe centres at the active site.
ch v by
.c
3) A non-heme protein with one Fe centre at the active site.
d
4) A heme protein without Fe centre at the active site.
di ya ed
em ar
.a it par
37) Match the following:

P. Ferritin I. Electron transport
Q. Vitamin B12 II. Ionophore
re
R. Cytochromes III. Oxygen transport

w .A P
S. Valinomycin IV. nitrogen fixation

V. Organometallic enzyme
d
VI. Iron storage.
(a) P - VI Q - IV R-II S-I

(b) P - I Q - III R-VI S - IV
V
(c) P - III Q- V R - IV S- VI
(d) P-VI Q-V R-I S - II
w
38) The iron containing respiratory protein without heme is _____.

w
39) The Cu-siderophore used in absorption of Cu by bacteria is
ACi
1) Methanobactin 2) Enterobactin 3) Mycobactin 4) Desferrioxamine
40) Inactive form of Aconitase hydratase, which catalyzes the stereospecific isomerization of
citrate to isocitrate via cis-aconitase, contains
1) Fe4S4 cluster 2) Fe2S2 cluster 3) Fe3S4 cluster 4) Fe(S-Cys)4 cluster
41) Choose the incorrect statement about Types 1, 2 and 3 centres in copper proteins?
hem
a) Type 1 centre exhibits an intense LMCT band in the electronic spectrum.
b) Ceruloplasmin contains all Types of copper centres.
stry
c) Type 3 centre contains two Cu centres which are antiferromagnetically coupled.
d) Plastocyanin contains a Type 1 Cu centre.
e) Type 2 centre does not give rise to an EPR signal.
f) Hemocyanin contains Type 2 Cu centre.
27
42) Iron-sulfur proteins where one Fe atom is coordinated by two His residues are named:
A) Poison iron-sulfur proteins

B) Rieske iron-sulfur proteins
C) Warburg iron-sulfur proteins
D) Homo iron-sulfur proteins
E) Cytochrome C iron-sulfur proteins
43) Which statement correctly describes the function of cytochromes P-450?

1) Cytochrome P-450 acts as monooxygenases and catalyses the insertion of O into a C–H
bond.
2) Cytochrome P-450 couples to cytochrome-c in the mitochondrial electron-transfer chain.
3) Cytochrome P-450 act as dioxygenases.
4) Cytochrome P-450 contains high-spin Fe(III); this directly binds O2 and acts as an O2 carrier.
om
try n
44) Which statement about Fe–S proteins is INCORRECT?
is ha
1) A rubredoxin contains an FeS4 unit, each S coming from a Cysteine residue.
ch v by
.c
2) A [2Fe–2S] ferredoxin contains six S donors, two of which are S2– ligands.
d
3) A [4Fe–4S] ferredoxin contains a cubane core.
di ya ed
em ar
4) In a [4Fe–4S] ferredoxin, four redox couples that make use of the four Fe centres are
.a it par
accessible in Nature.
45) Nitrogenase contains:

re
A) an Fe-protein and an FeMo-protein that operate in conjunction with each other.

w .A P
B) an FeMo-protein in which the active site consists of a single [3FeMo-4S] cluster.

C) an FeMo-protein in which the P-cluster is in an irreversibly reduced state.
d
D) an Fe-only containing protein in which the P-cluster is the active site.
46) Enterobactin is used by microbes to chelate and absorb

1) soluble Fe(II) 2) insoluble Fe(III) 3) soluble Fe(III) 4) insoluble Fe(II)
V
47) The iron-sulfur protein which does not contain inorganic sulfides is________ .
w
48) The enzyme which contains cubane like ferredoxin is

1) Carbonic anhydrase 2) Urease 3) Zymase 4) Nitrogenase
w
49) Which of the following statement is not correct?
ACi
a) The sixth coordination position in T-state of hemoglobin is occupied by losely bound water
molecule.
b) The affinity of Hemoglobin with CO will be even more without the presence of distal histidine
residue.
c) In T-state of hemoglobin, the iron is in low spin and has bigger size (0.78 Ao).
d) In R-state of hemoglobin, the iron is in low spin state and has smaller size (0.61 Ao)
e) The porphyrin ring in T-state of hemoglobin is dome shaped.
hem
50) Biphosphoglycerate stabilizes the T-state of hemoglobin. As a consequence:
stry
1) Affinity of hemoglobin with dioxygen improves in lungs.
2) Affinity of hemoglobin with dioxygen decreases in lungs.
3) More dioxygen is released in the tissues where the pO2 is less.
28
4) Less dioxygen is released in the tissues where the pO2 is high.
51) The type of cytochrome with lower reduction potential is

1) Cytochrome a 2) Cytochrome b
3) Cytochrome b 4) All with same reduction potentials
52) In cytochrome-c oxidase, the number of iron centres is _____ and the numbe of copper
centres is ______ .
53) The metal found at the active site of Rieske protein is

a) Ni b) Fe c) Cu d) Zn
54) The 2Fe-2S protein found in mitochondria and in photosynthetic systems which involve in
tranfer of electrons is
om
try n
a) Ferredoxin b) Rubredoxin c) Rieske protein d) All
is ha
55) The respiratory non heme iron protein containing binuclear iron centre is
ch v by
.c
a) Hemerythrin b) Hemocyanin c) Cytochrome-c d) Hemoglobin
d
di ya ed
em ar
56) Choose the correct statement about copper proteins.
.a it par
a) EPR signal is abnormal in Type-II copper proteins.

b) Type-III copper proteins are intense blue in color due to MLCT.
c) Hemocyanin is a Type-II copper protein.
re
d) Plastocyanin is a Type-I copper protein.

w .A P
57) Type I and III copper proteins are intense blue in color due to
d
a) LMCT b) d-d transitions c) MLCT d) f-f transitions
58) EPR signal is absent for which of the following blue copper protein:
a) Superoxide dismutase b) Hemocyanin
V
c) Plastocyanin d) Nitrite reductase

w
59) The number of MgATP’s required in the reduction of N2 to ammonia is

a) 4 b) 12 c) 16 d) 6
w
60) The blue copper protein which helps in the transport of iron is
a) Ceruloplasmin b) Plastocyanin c) Tyrosinase d) Nitritereductase
ACi
61) The part of nitrogenase enzyme which is involved in transfer of electrons is
a) M-cluster b) Molybdenum c) P-cluster d) protein part
62) During the oxidations catalysed by cytochrome P450, one atom of dioxygen enters into the
organic substrate and the other atom of oxygen finds its way into
a) CO2 b) H2O2 c) H2O d) CO
63) Iron sulfur clusters in biological systems are involved in

hem stry
a) proton transfer b) atom transfer
c) group transfer d) electron transfer
64) Non-heme iron-sulfur proteins are involved in:

29
A) Electron transfer.
B) Proton transfer.
C) Both electron and proton transfer

D) Oxygen transfer.
65) The reduction of nitrogen to ammonia, carried out by the enzyme nitrogenase needs:
(CSIR DEC 2011)
a) 2 electrons b) 4 electrons c) 6 electrons d) 8 electrons
66) The changes (from A-D given below) which occur when O2 binds to hemerythrin are:
(CSIR JUNE 2012)
(A) One iron atoms is oxidized
(B) Both the iron atoms are oxidized
(C) O2 binds to one iron atom and is also hydrogen bonded.
om
try n
(D) O2 binds to both the iron atoms and is also hydrogen bonded.
Choose the correct option.
is ha
1) B and C 2) B and D 3) A and D 4) A and C
ch v by
.c
d
67) A metal ion that can replace manganese(II) ion in mangeno-proteins without changing its
di ya ed
em ar
function is: (CSIR NET DEC 2011)
.a it par
a) Fe(II) b) Zn(II) c) Mg(II) d) Cu(II)
68) Carboxypeptidase contains: (CSIR NET JUNE 2011)

re
1) Zn(II) and hydrolyses CO2.

w .A P
2) Zn(II) and hydrolyses peptide bonds.

3) Mg(II) and hydrolyses CO2.
d
4) Mg(II) and hydrolyses peptide bonds.
69) In metallo enzymes, the metal centers are covalently linked through the side chains of the
amino acid residues. The correct set of aminoacids, which are involved in the primary coordination
V
spheres of metallo enzymes is: (CSIR NET DEC 2012)

1) Ala, Leu, His 2) Glu, His, Cys 3) Leu, Glu, Cys 4) Ala, His, Glu
w
70) Based on behaviour of metalloenzymes, consider the following statements.

A. In the enzymes, the zinc activates O2 to peroxide species.
w
B. In the enzymes, the zinc activates H2O and provides a zinc bound hydroxide.
C. In the oxidases, the iron activates O2 to break the bonding between two oxygens.
ACi
D. Zinc ion acts as nucleophile and attacks at the peptide carbonyl.
The set of correct statements are, (CSIR NET DEC 2012)
1) A & B 2) B & C 3) C & D 4) A & D
71) Fe2+ porphyrins fail to exhibit reversible oxygen transport and cannot differentiate CO from
hem
O2. However, the hemoglobin is free from both these pitfalls. Among the following, stry
A. Fe2+ porphyrins undergo -oxodimer formation and same is prevented in case of hemoglobin.
B. Fe-CO bond strength is much low in case of hemoglobin when compared to the Fe2+ porphyrins.
C. While Fe-CO is lineare, Fe-O2 is bent and is recognized by hemoglobin.
D. The interlinked four monomeric units in the hemoglobin are responsible to overcome the pitfalls.
30
The correct statements are, (CSIR NET DEC 2012)
1) A & B 2) A & C 3) C & D 4) B & D
72) The coordination geometry of copper(II) in the type I copper protein plastocyanin is:
(CSIR NET JUNE 2013)
1) square planar 2) tetrahedral
3) octahedral 4) distorted tetrahedral
73) The metal ions present in the active site of nitrogenase enzyme co-factor are:
1) Fe, Mo 2) Fe, W 3) Fe, Ni 4) Fe, Cu
74) For the metalloprotein hemerythrin, the statement that is NOT TRUE is:
om
try n
1) There are two iron centers per active site.
is ha
2) Both iron centers are hexacoordinated in the active state.
ch v by
.c
3) One iron is hexacoordinated while the other is pentacoordinated in the active site.
d
4) It is found in marine invertebrates.
di ya ed
em ar
.a it par
ADVANCED PROBLEMS
re
1) The elemental analysis of an electron transport protein suggests that it contains only metallic
w .A P
element - zinc. Therefore, we can conclude that:

a) Zinc(II) is a cofactor and helps in electron transport.
d
b) There must be another cofactor that helps in electron transport.

c) Zinc exists in two oxidation states in the protein i.e Zn(I) and Zn(II).
d) All of the above are possible.
V
2) Arthropods utilizes hemocyanins for dioxygen transport. It is found that an arthropod is suffering
from anemia. The possible treatment is to supplement its diet with:
w
a) iron b) copper c) nickel d) zinc
3) Catalase is a heme protein that catalyzes the decomposition of hydrogen peroxide. Cyanide
w
anion inhibits catalase but carbon monoxide does not. It implies that the oxidation state of Fe in the
active form of catalse is:
ACi
a) +1 b) +2 c) +3 d) 0
4) Which of the following ion can effectively replace Fe(II) in Rubredoxin?

a) Co(II) b) Zn(II) c) Co(III) d) Cr(III)
5) If the active form of Superoxide dismutase is represented by Cu2Zn2SOD, which of the following
derivative of it is not expected to show enzymatic activity?
a) Cu2Cu2SOD b) Cu2Fe2SOD c) Zn2Zn2SOD hem
d) Cu2Ni2SOD stry
6) Enterobactin, a siderophore, represented by ent6- can chelate with Fe3+ ion to form a complex
[Fe(ent)]3- for which the dissociation constant is 10-25 at neutral pH. The number of free ions present
per one litre in the 1M [Fe(ent)]3- solution at this pH is:
a) 1.9 x 1011 b) 6.02 x 1011 c) 6.02 x 1023 d) 1.9 x 1023
31
7) From isomeric shift values of Mossbauer spectrum, the average valence of iron in the iron-
molybdenum (MoFe6) co-factor of nitrogenase is found to be 2.66. The number of iron ions showing
+2 oxidation state in this co-factor is:
a) 2 b) 4 c) 3 d) 6
8) Nature has chosen Zn(II) ion at the active site of many hydrolytic enzymes because:
(a) Zn (II) is a poor Lewis acid.
(b) Zn (II) does not have chemically accessible redox states.
(c) Zn (II) forms both four and higher coordination complexes
(d) Zn (II) forms weak complexes with oxygen donor ligands.
9) Studies of Zn(II)-containing proteins often make use of Co(II)-for-Zn(II) substitution. Which
om
try n
statement is correct?
is ha
a) Tetrahedral coordination is one of several environments observed for both Co2+ and Zn2+.
ch v by
b) Tetrahedral Co2+ and Zn2+ are both diamagnetic.
.c
d
c) The ionic radius of Co2+ is significantly smaller than that of Zn2+.
di ya ed
d) The visible spectra of complexes of Co2+ are similar to those of related complexes of Zn2+.
em ar
.a it parre
Key & explanation to problems in this book are available at following link:
w .A P
d
V
w
w
ACi hem stry

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1

Prepared by V. Aditya vardhan adichemadi(at)gmail.com www.adichemistry.com

Updated on: 10th Dec, 2013

power in you to achieve this. More information at: www.brahmakumaris.com

* Iron sulfur proteins - Ferridoxins - Reiske protein

DISTRIBUTION OF ELEMENTS IN THE EARTH CRUST AND HUMAN BODY

INORGANIC ELEMENTS AND THEIR BIOLOGICAL FUNCTIONS

Bulk metals - Na, K, Mg & Ca

ACi hem stry

Bulk Metal Biological functions

* Present in chlorophyll and helps in photosynthesis.

* CaCO3 is present in endo and exo skeletons.

CSIR NET STUDY MATERIAL

FOR OTHER TOPICS, MODEL

Trace Metal Biological functions

* Hydrolytic enzymes: carboxypeptidase

I/II * Electron transfer.

* Conversion of N2 to ammonia (nitrogen fixation).

I/II/III * Electron transfer.

* Hydrogenase and hydrolases (urease).

Non metal Biological functions

P5+ * Found in Hydroxylapatite, ATP, cell membrane and DNA.

F- * As fluorapatite, Ca5(PO4)3F in teeth.

Cl- * Most important free anion, besides HCO3-

pyrrole rings interconnected at their alpha carbons via methine(=CH-) bridges.

The porphin in chlorophyll is called chlorin.

porphin is called corrin.

Porphyrin Chlorin Corrin

HEMOGLOBIN AND MYOGLOBIN

nitrogens of pyrrole rings.

Worryig is a waste of time. It does not change anything.

1) deoxy form: No oxygen is bound to iron.

Hemoglobin coordinated to dioxygen is called oxy-hemoglobin. It is also referred to as R-state

(relaxed). In oxy-hemoglobin the sixth coordinated position of iron is occupied by dioxygen in

FUNCTIONING OF HEMOGLOBIN - A BIOINORGANIC PERSPECTIVE

accurate and modern explanation.

What prevents synthetic (simple) iron porphyrins from functioning as O2 carriers?

Learn Rajayoga meditation to awaken your inner divine powers to

What is the "Cooperative effect" in hemoglobin?

positive charge on the metal.

Histidine Histidine Histidine

associated with this oxo bridge by hydrogen bonding.

Unlike in hemoglobin, there is no cooperative effect observed in case of hemerythrin.

Histidine Histidine Histidine Histidine

* Cytochromes are, membrane-bound hemoproteins that contain 4 heme groups as co-factors

states) at their active site.

1) Cytochrome-a contains heme-a

Coordination pattern in Cytochrome C

Coordination pattern in Mb and Hb

* Cytochrome P450 oxidases constitute a super family of monooxygenase cytochromes.

* They oxidise alkanes to alcohols.

IRON SULFUR PROTEINS

E.g., Ferredoxins, as well as NADH dehydrogenase, hydrogenases, nitrogenase etc.

Following is Fe2S2 type of ferredoxin.

It is also an electron transport agent.

Ferredoxin (Fd) is a sulfur-containing protein which undergoes redox reactions in a variety of

microorganisms; Fdox+ + e- -------> Fdred , Eo = 0.439V at pH = 7.0. Will Fd generate hydrogen