TUNGAL SCHOOL OF BASIC & APPLIED SCIENCES, JAMKHANDI

B.Sc Sem-IV
INORGANIC CHEMISTRY
UNIT-2
BIOINORGANIC CHEMISTRY

Syllabus:
Essential and trace elements in biological process, metalloporphyrins with respect to haemoglobin and
chlorophyll (structure and function), biological role of Na, K, Fe and Zn.

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.

Essential & Trace Elements in Biological Process:

Classification of elements according to their action in the biological system.

1) Essential elements:
• C, H, N, O - Bulk elements.
• Na, K, Mg, Ca, S, P, Cl, Fe -Macronutrients (relatively large amounts).
• Mn, Co, Ni, Cu, Zn, V, Cr, Mo, Se, F, I, Al, Pb, Sn, Si – Micronutrients (trace elements).

2) Non-essential elements: Al, Sr, Ba, Sn etc.

3) Toxic elements: Cd, Pb, Hg etc.

Essential elements are absolutely essential or necessary for life processes. Trace elements
are also necessary for life processes. Non-essential elements are not essential. If they are absent
other elements may serve the same function. Toxic elements disturb the natural functions of the
biological system.

Indeed, the human body is made up of 99.9% of just 11 elements, 4 of which (hydrogen,
oxygen, carbon and nitrogen) account for 99% of the total (62.8%, 25.4%, 9.4% and 1.4%
respectively).

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Significance of Biologically Important Elements:

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.
* Present in endo and exo skeletons.
* Charge carrier.
* In muscle and nerve functions - cell signaling.
* It acts as second messenger and sentinel at synapse.
Ca2+ * Present in teeth as Ca5(PO4)3(OH) (hydroxylapatite).
* CaCO3 is present in endo and exo skeletons.
* In activation of enzymes.
* In blood coagulation.
* Hydrolytic enzymes: carboxypeptidase
Zn2+ * Metal storage: e.g., metallothionein.
* zinc finger proteins (genetic transcription), stabilization of proteins.
* Electron transfer.
CuI/II * Transport and storage of dioxygen.
* Electron transfer.
* Transport and storage of dioxygen.
FeII/III * Fe3O4 is used to store iron, and, as it is magnetic, is used by
magnetotactic bacteria to sense the direction of the Earth s magnetic field.
* Conversion of N2 to ammonia (nitrogen fixation).
CoIII * Cobalamine ( e.g. Vitamin-B12 )
* Electron transfer.
MnII/III/IV * In photosynthesis, generation of dioxygen by splitting water. It is part of
OEC (Oxygen Evolving Complex) in PS-II system.
* Electron transfer.
NiI/II/III * Hydrogenase and hydrolases (urease).
* Electron transfer.
MoIV/VI, VIV/V * Conversion of N2 to ammonia (nitrogen fixation).

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Note: Not only metals, but some non metals are also found in biological systems. The biological
functions of some of non metals are given below.

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-
I- * functioning of hormones of the thyroid; in radiation therapy.

Applications of metals in medicine:

The importance of bioinorganic chemistry can be realized from the following
applications of metals and their compounds in medical field.

* cisplatin (containing platinum) and budotitane (containing Titanium) are used in treatment of
cancer.
* Iron in the form of ferrous sulfate or ferrous gluconate is 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.
* 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. Its half life is 6 hrs only and emits gamma rays.
* Silver sulfadiazine is used to treat and prevent bacterial or fungal infections of the skin.
* Selenium sulfide used to treat seborrheic dermatitis and Tinea versicolor.
* MoS42- (tetrathiomolybdate) is used as anti copper agent in Wilsons disease (excess of copper
accumulation in liver - a genetic disorder). It is also used as an antitumor agent.

Metalloporphyrins:
Metalloporphyrin is a compound, such as heme, consisting of a porphyrin combined with
a metal such as iron, copper, silver, zinc, or magnesium.

Examples: Haemoglobin. Chlorophyll etc.

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• Porphyrins are a group of organic compounds, many naturally occurring one of the best-known
porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin.
They typically have very intense absorption bands in the visible region and may be deeply
colored; the name “porphyrin" comes from Greek word for purple.

Porphyrin

Functions & Structure of Haemoglobin:

Functions:
Haemoglobin is a protein in red blood cells that transports oxygen from the lungs to the
peripheral tissues of the body. It is responsible for the red color of red blood cells. Haemoglobin
tightly binds oxygen from the lungs, carries it from the lungs to the peripheral tissues of the
body, after unloading oxygen at the peripheral tissues, it binds carbon dioxides and returns it to
the lungs to be exhaled. It is composed of two protein subunits: alpha and beta. Haemoglobin
requires both subunits in order to function properly. Disorders can result from abnormalties in
either subunits. Abnormal-hemoglobin structure or function can result in a variety disorders
including sickel cell and thalassemia. It is remarkable that O2 does not oxidize hemoglobin,
considering the redox potentials for the reduction of O2 and oxidation of Fe2+.
The reversible binding of O2 in hemoglobin is due to the unique features of the porphyrin
ring system and the hydrophobic blocking of the large protein (globin). A porphyrin ring system
with coordinated iron (heme group).

Structure :
Hemoglobin contains four polypeptide subunits: two alpha chains and two beta chains,
each with 141 and 146 amino acids respectively. The "globin" in hemoglobin refers to the
individual protein subunits. Each subunit is comprised of mainly alpha helices with no beta
strands. Each subunit folds into eight alpha helical segments which forms a pocket that holds the
heme.
A heme molecule is a cyclic molecule that consists of nitrogen, carbon and hydrogen
atoms with a Fe2+ ion located in the center. Within the molecule, four nitrogen molecules hold

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the iron in the center. The iron ion also bonds with a histidine side chain from one of the subunits
that form the pocket. The Iron lon bonds to histidine 87 in the alpha chain and histidine 92 in the
beta chain. The histidine 87 and histidine 92 are both part of the F helix in each subunit. The
molar mass of hemoglobin is about 64,500 g/mol.

Hemoglobin Molecule Heme group

Functions & Structure of Chlorophyll:

Functions:
Chlorophyll is the molecule that absorbs sunlight and uses its energy to synthesize
carbohydrates from CO2 and water. This process is known as photosynthesis and is the basis for
sustaining the life processes of all plants. Since animals and humans obtain their food supply by
eating plants, photosynthesis can be said to be the source of our life also.
The overall chemical reaction involved in photosynthesis is:
6CO2 + 6H2O (+ light energy) → C6H12O6 + 6O2
Chlorophyll is a green pigment found in cyanobacteria and the chloroplasts of algae and
plants. Chlorophyll is vital for photosynthesis, which allows plants to absorb energy from light.
Its name is derived from the Greek words chloros (‘green’) and phyllon (‘leaf’). Chlorophyll
absorbs light most strongly in the blue portion of the electromagnetic spectrum, followed by the
red portion.

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Structure :
In the photosynthetic systems, the active component is the green pigment, chlorophyll.
Chlorophyll is a macrocyclic complex of Mg(II). Chlorophyll consists of a macrocyclic
tetrapyrrole system belonging to the porphyrin family with some modifications to the porphyrin
ring. The macrocyclic ring in chlorophyll is referred to as chlorin ring. Chlorin ring differs from
phorphyrin ring in several aspects: (i) one double bond in a pyrrole ring (denoted by IV) is
reduced; porphyrins with the reduced tetrapyrrole ring systems are in general known as chlorins;
(ii) a clopentanone ring is fused to one pyrrole ring (denoted by III); (iii) both the acid side
chains are esterified (cf. in heme, the acid side chains remain free). One side chain (attached with
the cyclopentanone ring) is a methyl ester while the other chain (attached with the ring IV which
is partially reduced) is an ester of phytol (C20H39OH). This long chain alcohol is a tetraisoprenoid
alcohol. In fact, presence of this phytol chain makes chlorophyll highly hydrophobic and soluble
in nonpolar media. In ring II. R differs for chlorophyll-b (R – CHO) and chlorophyll-a (R –
CH3). The most abundant chlorophyll, chlorophyll was first synthesized by Woodward in 1960.

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Metal Ions in the Biological System (Biological role):

Concentration of metal ions in human being's system is controlled within very fine limits.
This control is generally exercised by certain biological complexing agents. The deficiency or
excess of metal ions causes disorder, which leads to various diseases.

1) Biological Role of Na:

Sodium is the predominant extracellular cation in animals and man. An adult human has
about 105 g Na, about 24% is located in bone and about 65% in extracellular water. Sodium ion
equilibrium is maintained primarily by the kidney, the key organ in water and electrolyte
balance.
Sodium, potassium, and chlorine occur almost entirely in the fluids and soft tissues of the
body, sodium and chlorine being found mainly in the body fluids, and potassium occurring
mainly in the cells.
• They serve a vital function in controlling osmotic pressures and acid-base equilibrium.
They also play important roles in water metabolism.
• Sodium ions constituting 93% of the ions (bases) found in the blood stream. Although the
principal role of sodium in the animal is connected with the regulation of osmotic
pressure and the maintenance of acid-base balance, sodium also has an effect on muscle
irritability, and plays a specific role in the absorption of carbohydrate.
Sodium chloride (salt) is the predominant dietary source. Although excessive dietary Cl
appears to have no significant ill effect on health, there is much evidence that excessive Na
intake results in elevated blood pressure (hypertension) and that reduces Na intake or increased
K intake helps to reduce high blood pressure.

Role of Na+:
• Extracellular fluid.
• Osmotic balance ‘sodium pump’.
• Acid-base balance.
• Conformation of proteins & nucleic acids.
• Electrical impulse of nerve system.

2) Biological Role of K:
An adult human has approximately 140 g of K of which >90% is both intracellular and
exchangeable (K is the predominant cation in intracellular water) since muscle contains most of
body's intracellular water, it also contains most of the K. Since K is found in most animal and
vegetable foods, dietary deficiency is exceedingly rare except under unusual conditions (such as
diets very high in refined sugars, alcoholic individuals deriving most of their calories from low-
K alcoholic beverages in the states of starvation etc.).
• Potassium is the major cation of intracellular fluid, and regulates intracellular osmotic
pressure and acid-base balance.
• Like sodium, potassium has a stimulating effect on muscle irritability.

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• Potassium is also required for glycogen and protein synthesis, and the metabolic
breakdown of glucose.

Role of K+:
• Enzyme activator.
• Conformation of proteins & RNA (replication).
• Secretion of gastric acid.
• Transmembrane potentials.

3) Biological Role of Fe:

The average human adult has about 4-5 g Fe. Of this amount, about 60-70% is present in
haemoglobin in red blood cell, 3-5% is in muscle myoglobin, 15% is bound to the Fe storage
cellular protein, ferritin, 0.2% occurs as a component of critical respiratory enzymes and 0.004%
is bound to the serum transport protein uanslerin. Iron deficiency causes anemia because red
cells of blood containing less hemoglobin than in normal condition. Acute iron poisoning leads
to vomiting pallor, shock, circulatory collapse and coma. Chronic conditions are also known in
which Iron is deposited in tissues and organs of the body. This condition is known as siderosis.

The principal biological functions of Iron may be summarized as follows :

• Iron is an essential component of the respiratory pigments haemoglobin and myoglobin.
• Iron is an essential component of various enzyme systems including the cytochromes,
catalases, peroxidases, and the enzymes xanthine and aldehyde oxidase, and succinic
dehydrogenase.
• As a component of the respiratory pigments and enzymes concerned in tissue oxidation,
Iron is essential for oxygen and electron transport within the body.

Role of Fe:
• Electron-transfer.
• Redox proteins and enzymes.
• Oxygen carrying proteins.
• Nitrogen fixation.

4) Biological Role of Zn:

An adult has about 1.5-3.0 g Zn with the largest amounts being in liver and bone. There is
evidence that Zn-concentrations in blood and several tissues vary considerably in response to
many stimuli. Zinc appears to be critical in many functions. Human Zn deficiency in an inherited
form in infants is termed acrodermatitis enteropathica and is characterized by behavioral
disturbances, diarrhea, hair loss and severe peri-orificial skin rash, all of which respond with
remarkable promptness to Zn administration.

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The principal biological functions of zinc may be summarized as follows :

• Zinc is an essential component of more than 80 metalloenzymes, including carbonic
anhydrase (required for the transport of carbon dioxide by the blood and for the secretion
of HCl in the stomach), glutamic dehydrogenase, alkaline phosphatase, pyridine
nucleotide dehydrogenase, alcohol dehydrogenase, superoxide dismutase, pancreatic
carboxypeptidase, and tryptophan desmolase.
• Zinc serves as a cofactor in many enzyme systems, including arginase, enolase, several
peptidases, and oxalacetic decarboxylase.
• As an active component or cofactor for many important enzyme systems zinc plays a
vital role in lipid, protein, and carbohydrate metabolism; being particularly active in the
synthesis and metabolism of nucleic acids (RNA) and proteins.
• Although not proven, it has been suggested that zinc plays a role in the action of
hormones such as insulin, glucagon, corticotrophin, FSH and LH.
• Zinc is believed to play a positive role in wound healing.

Role of Zinc:
• Metalloenzymes.
• Structure promoters.
• Lewis acid.
• Not a redox catalyst.

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