Inorganic Chemistry-5 (Bioinorganic Chemistry) BCH6T14

Syllabus topics (RTMNU)

• Definition and scope of bioinorganic chemistry
• Overview of the role of metal ions in biological systems
• Metal ions in biological processes, with emphasis on their biochemical significance
• Types of bioinorganic compounds (metalloenzymes, metalloproteins, etc.)
• Transport of metal ions (Fe, Mg, Zn and Cu) in organisms

Definition and Scope of Bioinorganic Chemistry

Definition: Bioinorganic chemistry is the branch of chemistry that studies the role of metal ions and other inorganic elements in living systems — their structure, function, transport, storage, toxicity and use in medicine.

Scope:

1. Function of metal ions in proteins and enzymes (oxygen transport, electron transfer, catalysis).
2. Uptake, transport and storage of metals in organisms.
3. Role of non-metals such as P, S, Se, I and halides.
4. Metal toxicity and detoxification; environmental chemistry (heavy metals).
5. Medicinal inorganic chemistry: metal-based drugs (cisplatin), chelation therapy, MRI contrast agents (Gd), radiopharmaceuticals (^99mTc).
6. Model compounds that mimic active sites; biomimetic catalysts; nitrogen fixation and photosynthesis research.

Overview of the Role of Metal Ions in Biological Systems

Metal Ions in Biological Processes and their Biochemical Significance

• Iron: O₂ transport (Hb), storage (Mb), electron transfer (cytochromes, Fe–S proteins), enzymes (catalase, peroxidase, cytochrome P450). Deficiency → anaemia.
• Copper: cytochrome c oxidase (terminal step of respiration), Cu/Zn-SOD, tyrosinase (melanin), ceruloplasmin; deficiency → anaemia, Menkes disease; excess → Wilson's disease.
• Zinc: over 300 enzymes (carbonic anhydrase, carboxypeptidase, alcohol dehydrogenase), insulin storage, zinc-finger proteins; deficiency → poor growth, delayed wound healing.
• Magnesium: chlorophyll; Mg–ATP complex is the true substrate of kinases; stabilises ribosomes and nucleic acids.
• Calcium: bones and teeth, blood clotting, muscle contraction, nerve signalling.
• Cobalt: vitamin B₁₂ (cobalamin) — deficiency causes pernicious anaemia. Molybdenum: nitrogenase, xanthine oxidase. Manganese: photosystem II, Mn-SOD.

Types of Bioinorganic Compounds

1. Metalloproteins: proteins containing a tightly bound metal ion — transport and storage proteins (haemoglobin, myoglobin, transferrin, ferritin) and electron-transfer proteins (cytochromes, ferredoxins, blue copper proteins).
2. Metalloenzymes: enzymes whose activity requires a firmly bound metal at the active site (carbonic anhydrase – Zn; catalase – Fe; SOD – Cu/Zn). Metal-activated enzymes bind the metal loosely (e.g. Mg²⁺ with kinases).
3. Metalloporphyrins and related macrocycles: haem (Fe), chlorophyll (Mg), cobalamin (Co, corrin ring).
4. Ionophores: small molecules that carry ions across membranes, e.g. valinomycin (K⁺), and siderophores (iron carriers of microbes).
5. Biominerals: hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ in bones, CaCO₃ in shells, magnetite in magnetotactic bacteria.

Transport of Metal Ions (Fe, Mg, Zn and Cu) in Organisms

Metal ions cannot cross lipid membranes freely, and free Fe and Cu are toxic (they produce free radicals). So organisms use special transporters, carrier proteins, chaperones and storage proteins.

Iron:

• Dietary Fe³⁺ is reduced to Fe²⁺ in the gut and taken up by intestinal cells through the divalent metal transporter (DMT1); exported into blood by ferroportin and re-oxidised to Fe³⁺.
• In blood, Fe³⁺ is carried by transferrin (a glycoprotein with two Fe³⁺ sites, each bound by 2 Tyr, 1 His, 1 Asp and a carbonate ion as synergistic anion). Cells take it up by receptor-mediated endocytosis; acidity in the endosome releases iron.
• Iron is stored in ferritin — a hollow shell of 24 protein subunits holding up to about 4500 Fe atoms as hydrated iron(III) oxide-phosphate.
• Bacteria secrete siderophores (e.g. enterobactin, with very high affinity for Fe³⁺) to capture iron.

Magnesium: absorbed in the intestine and reabsorbed in the kidney through specific Mg²⁺ channels/transporters (e.g. CorA in bacteria, TRPM channels in humans); Mg²⁺ is mostly inside cells, bound to ATP and nucleic acids.

Zinc: two families of transporters — ZIP proteins bring Zn²⁺ into the cytoplasm and ZnT proteins move it out or into organelles. In blood Zn²⁺ is carried mainly by albumin; inside cells it is buffered by metallothionein.

Copper: Cu²⁺ is reduced to Cu⁺ and taken up by the transporter Ctr1; inside the cell, copper chaperones deliver Cu⁺ to targets (e.g. CCS to SOD). P-type ATPases ATP7A and ATP7B pump copper out; defects cause Menkes disease (ATP7A, copper deficiency) and Wilson's disease (ATP7B, copper accumulation in liver and brain). In plasma, copper is carried mainly by ceruloplasmin.

Likely exam questions

1. (Long, 8 marks) Define bioinorganic chemistry and give its scope. Give an overview of the role of metal ions in biological systems.
2. (Long, 8 marks) Describe the transport and storage of iron and copper in living organisms.
3. (Short, 4 marks) Distinguish between metalloproteins and metalloenzymes with examples.
4. (Short, 4 marks) Write the biochemical significance of zinc and magnesium.
5. (Short, 4 marks) What are siderophores?

Syllabus topics (RTMNU)

• Essential and Trace elements in biological processes
• Metalloporphyrins with special reference to structure and role of iron in Haemoglobin and Myoglobin in transport of Oxygen
• Biological role of Na+, K+ and Ca2+ metal ions
• Sodium and potassium pump
• Hypo and hypercalcemia
• Calcium triggering and calcium pump

Essential and Trace Elements in Biological Processes

Essential elements are those without which an organism cannot grow or complete its life cycle; their deficiency causes specific disorders that are cured by supplying them.

• Bulk/major elements (of living matter): C, H, O, N, P, S.
• Macro-minerals (needed in large amounts, more than about 100 mg per day for humans): Na, K, Ca, Mg, Cl, P.
• Trace elements (needed in small amounts): Fe, Zn, Cu, Mn, Co, Mo, Cr, Se, I, F; ultra-trace: Ni, V, B (in plants), Si.

Dose–response: every essential element has an optimum range; both deficiency and excess are harmful (Bertrand's rule). Excess fluoride, for example, causes fluorosis.

Metalloporphyrins: Structure and Role of Iron in Haemoglobin and Myoglobin

Porphyrin: a large planar macrocycle of four pyrrole rings linked by methine (=CH–) bridges; the four N atoms bind a metal ion at the centre. Haem = iron(II) protoporphyrin IX.

Myoglobin (Mb): a single polypeptide chain (153 amino acids) folded into 8 α-helices (A–H) with one haem in a hydrophobic pocket. Found in muscles; stores oxygen.

Haemoglobin (Hb): a tetramer of two α and two β chains (α₂β₂), each similar to myoglobin and each carrying one haem — so one Hb carries 4 O₂. Found in red blood cells; transports oxygen from lungs to tissues.

Coordination of iron: Fe(II) is bound to four porphyrin N atoms (equatorial) and to the proximal histidine (His F8) below the plane (5-coordinate). The sixth position, on the opposite side, binds O₂. The distal histidine (His E7) hydrogen-bonds bound O₂, prevents oxidation to Fe(III) and reduces CO binding.

Mechanism of O₂ binding (Perutz):

1. Deoxy-Hb: Fe(II) is high-spin, too large for the porphyrin hole, and sits about 0.4–0.6 Å out of the plane (domed).
2. On binding O₂, Fe(II) becomes low-spin (smaller) and moves into the plane of the ring, pulling His F8 with it.
3. This movement shifts the F-helix and changes the subunit contacts — the T (tense, low affinity) state changes towards the R (relaxed, high affinity) state.
4. So binding of O₂ at one haem makes binding at the others easier — cooperativity, giving a sigmoidal O₂-saturation curve. Bound O₂ is often described as Fe(III)–superoxide (Fe³⁺–O₂⁻).

Biological Role of Na⁺, K⁺ and Ca²⁺

• Na⁺ (main extracellular cation, about 145 mM outside vs about 10–15 mM inside): controls osmotic pressure and water balance of body fluids, nerve impulse (action potential), absorption of glucose and amino acids by Na⁺-linked co-transport.
• K⁺ (main intracellular cation, about 140 mM inside vs about 4–5 mM outside): maintains resting membrane potential, activates enzymes (pyruvate kinase), protein synthesis, heart rhythm.
• Ca²⁺: bones and teeth (about 99% of body calcium), muscle contraction, blood clotting (factor IV), nerve transmission (release of neurotransmitters), cell signalling, enzyme activation.

Sodium and Potassium Pump

The Na⁺/K⁺-ATPase in the plasma membrane maintains high K⁺ inside and high Na⁺ outside, against their concentration gradients, using ATP (active transport).

1. The pump (E₁ form) binds 3 Na⁺ from inside the cell and ATP.
2. ATP phosphorylates the pump (aspartate residue) → conformational change to E₂; 3 Na⁺ released outside.
3. E₂ binds 2 K⁺ from outside; dephosphorylation returns the pump to E₁, releasing 2 K⁺ inside.

Net per ATP: 3 Na⁺ out, 2 K⁺ in — it is electrogenic (inside becomes negative). Significance: resting potential and nerve impulses, cell volume control, secondary active transport of sugars and amino acids. It is inhibited by ouabain/digitalis (cardiac glycosides used in heart failure). Selectivity of carriers depends on ionic radius and hydration energy of Na⁺ vs K⁺.

Hypocalcaemia and Hypercalcaemia

Normal blood (serum) calcium is about 8.5–10.5 mg/dL (about 2.2–2.6 mM), regulated by parathyroid hormone (raises), calcitonin (lowers) and vitamin D (increases absorption).

Calcium Triggering and Calcium Pump

Calcium triggering: resting cytoplasmic Ca²⁺ is kept very low (about 10⁻⁷ M) compared with outside (about 10⁻³ M). A signal (nerve impulse, hormone) opens Ca²⁺ channels in the plasma membrane or the sarcoplasmic/endoplasmic reticulum, raising cytoplasmic Ca²⁺ about 10–100 times. Ca²⁺ binds to sensor proteins — calmodulin (4 Ca²⁺ sites, EF-hand motifs) or troponin C in muscle — which change shape and switch on processes: muscle contraction, enzyme activation, secretion of neurotransmitters and hormones. Ca²⁺ is ideal as a trigger because it binds flexibly to O-donor ligands with fast on/off rates and changes protein shape.

Calcium pump: to end the signal, Ca²⁺-ATPases pump Ca²⁺ back: SERCA (into the sarcoplasmic reticulum, 2 Ca²⁺ per ATP) and PMCA (out of the cell, 1 Ca²⁺ per ATP); a Na⁺/Ca²⁺ exchanger also helps. Muscle then relaxes.

Likely exam questions

1. (Long, 8 marks) Describe the structure of haemoglobin and myoglobin and explain the role of iron in the transport of oxygen, including cooperativity.
2. (Long, 8 marks) Explain the biological role of Na⁺, K⁺ and Ca²⁺ ions. Describe the sodium–potassium pump and calcium triggering.
3. (Short, 4 marks) Distinguish between essential bulk elements and trace elements with examples.
4. (Short, 4 marks) What are hypocalcaemia and hypercalcaemia?
5. (Short, 4 marks) Compare haemoglobin and myoglobin.

Syllabus topics (RTMNU)

• Structure and function of metalloproteins (e.g., hemoglobin, myoglobin, carbonic anhydrase)
• Mechanism of action of metalloenzymes (e.g., zinc, copper, iron-containing enzymes)
• Role of metal ions in enzyme catalysis (electron transfer, redox reactions)
• Iron-sulfur clusters and their biological roles
• Active site structure and metal ion binding in enzymes

Structure and Function of Metalloproteins: Haemoglobin, Myoglobin and Carbonic Anhydrase

Metalloproteins are proteins with one or more metal ions bound at specific sites by amino-acid side chains (His N, Cys S, Asp/Glu O, Tyr O) or by prosthetic groups such as haem.

Haemoglobin and myoglobin (summary): Fe(II)-haem bound to proximal His; O₂ binds at the sixth site; Mb (monomer) stores O₂ in muscle with a hyperbolic binding curve; Hb (α₂β₂ tetramer) transports O₂ cooperatively (sigmoidal curve, T ⇌ R change triggered by movement of Fe into the porphyrin plane) and also carries some CO₂ and H⁺ (Bohr effect).

Carbonic anhydrase (CA): a zinc metalloenzyme (molar mass about 30,000) present in red blood cells, kidney and plants.

• Active site: Zn²⁺ bound to three histidine imidazole N atoms and one water molecule in a tetrahedral arrangement, at the bottom of a cone-shaped cavity.
• Function: CO₂ + H₂O ⇌ HCO₃⁻ + H⁺ — removal of CO₂ from tissues, its release in lungs, pH balance, formation of aqueous humour and gastric acid. One of the fastest enzymes known (about 10⁶ reactions per second per molecule).

Mechanism of Action of Metalloenzymes: Zinc, Copper and Iron Enzymes

1. Zinc enzyme — carbonic anhydrase:

1. Zn²⁺ (a Lewis acid) lowers the pK_a of bound water from about 15.7 to about 7, so at body pH it loses a proton (helped by a nearby His acting as proton shuttle) → Zn–OH⁻.
2. CO₂ enters a hydrophobic pocket near zinc; the strongly nucleophilic Zn–OH⁻ attacks the carbon of CO₂ → Zn–OCO₂H (bicarbonate bound).
3. Water displaces HCO₃⁻, regenerating Zn–OH₂; the cycle repeats.

Another Zn enzyme, carboxypeptidase A (Zn bound to 2 His, 1 Glu and water), hydrolyses the C-terminal peptide bond: Zn polarises the C=O of the peptide and activates water.

2. Copper enzymes: copper cycles between Cu(I) and Cu(II) for electron transfer and O₂ chemistry.

• Cu/Zn superoxide dismutase: Cu(II) + O₂^•− → Cu(I) + O₂; Cu(I) + O₂^•− + 2H⁺ → Cu(II) + H₂O₂ (zinc is structural).
• Tyrosinase (type 3 dinuclear Cu): uses O₂ to hydroxylate tyrosine → DOPA → dopaquinone (melanin).
• Cytochrome c oxidase: Cu_A, haem a, haem a₃–Cu_B centre reduces O₂ to 2H₂O using 4 electrons and 4 H⁺.
• Copper proteins are grouped as type 1 (blue, e.g. plastocyanin, electron transfer), type 2 (normal) and type 3 (dinuclear, e.g. haemocyanin, tyrosinase).

3. Iron enzymes:

• Catalase (haem Fe): 2H₂O₂ → 2H₂O + O₂. Fe(III) reacts with H₂O₂ to give a high-valent oxo-iron (Fe(IV)=O porphyrin radical, "compound I"), which oxidises a second H₂O₂ to O₂.
• Peroxidase: uses H₂O₂ to oxidise organic substrates by the same compound I.
• Cytochrome P450: haem Fe with cysteine thiolate ligand; activates O₂ to hydroxylate drugs and steroids (R–H → R–OH) in the liver — important in drug metabolism.

Role of Metal Ions in Enzyme Catalysis: Electron Transfer and Redox Reactions

1. Lewis-acid catalysis: metal ions polarise substrates (C=O, P–O) and activate water as hydroxide (Zn²⁺, Mg²⁺).
2. Template/orientation: metal holds substrates in correct position (Mg²⁺–ATP in kinases).
3. Electron transfer: metals with two easily accessible oxidation states — Fe(II)/Fe(III) in cytochromes and Fe–S proteins, Cu(I)/Cu(II) in blue copper proteins — carry electrons in respiration and photosynthesis. Fast transfer is favoured by small structural change between the two oxidation states (entatic state).
4. Redox catalysis and O₂ activation: Fe, Cu and Mn activate O₂ or H₂O₂ (oxidases, oxygenases, catalase, SOD); Mo and Fe in nitrogenase reduce N₂ to NH₃; Co in vitamin B₁₂ enzymes forms Co–C bonds.
5. Structural stabilisation of the active-site conformation (Zn in SOD, Ca in many enzymes).

Iron–Sulphur Clusters and their Biological Roles

Fe–S proteins contain iron bound to cysteine sulphur and often to inorganic sulphide (S²⁻). They are mainly electron carriers with low (negative) redox potentials.

Roles: electron transfer (photosynthesis, respiration, nitrogen fixation — nitrogenase contains Fe–S clusters and the FeMo-cofactor); non-redox catalysis — in aconitase a [4Fe–4S] cluster binds citrate and helps convert it to isocitrate (Krebs cycle); sensing of iron and oxygen; DNA repair enzymes.

Active Site Structure and Metal Ion Binding in Enzymes

The active site is a pocket where the metal is held by specific amino-acid side chains; its geometry and ligands decide the metal's reactivity.

• Ligand choice (HSAB): hard ions (Mg²⁺, Ca²⁺) prefer O donors (carboxylate, phosphate); borderline/soft ions (Zn²⁺, Cu⁺, Fe²⁺) prefer N (His) and S (Cys, Met) donors.
• Geometry: tetrahedral Zn in carbonic anhydrase; distorted tetrahedral Cu in plastocyanin; square-pyramidal/octahedral Fe in haem enzymes.
• Open coordination site: one site is often occupied by water or empty for substrate binding.
• Entatic (rack) state: the protein forces the metal into a strained geometry between those preferred by its two oxidation states, making electron transfer or catalysis fast (e.g. blue copper proteins).
• The surrounding protein provides hydrophobic pockets, hydrogen bonds and proton shuttles that tune the redox potential and selectivity.

Likely exam questions

1. (Long, 8 marks) Describe the structure and mechanism of action of carbonic anhydrase. Add a note on copper-containing enzymes.
2. (Long, 8 marks) What are iron–sulphur proteins? Describe the types of Fe–S clusters and their biological roles.
3. (Short, 4 marks) Explain the role of metal ions in enzyme catalysis.
4. (Short, 4 marks) Write the mechanism of catalase.
5. (Short, 4 marks) What is the entatic state?

Syllabus topics (RTMNU)

• Toxic metals and their effects on biological systems (e.g., lead, mercury)
• Detoxification strategies (metallothioneins, phytochelatins)
• Antioxidant mechanisms involving metal ions (superoxide dismutase)
• Metal-based drugs: cisplatin, copper-based drugs, iron chelators
• Coordination chemistry in pharmacology and drug design
• Role of metal ions in cancer therapy and antibacterial treatments

Toxic Metals and their Effects on Biological Systems: Lead and Mercury

Heavy metals such as Pb, Hg, Cd and As are toxic because they bind strongly to –SH (thiol) groups of proteins and enzymes, displace essential metals (Zn, Ca, Fe) from their sites, and generate oxidative stress.

Lead (Pb):

• Sources: old lead paints, leaded petrol (banned in India), batteries, lead pipes, some cosmetics and traditional medicines, industrial emissions.
• Biochemical action: inhibits the zinc enzyme δ-aminolevulinic acid dehydratase (ALAD) and ferrochelatase (inserts Fe into porphyrin) → haem synthesis is blocked → anaemia; replaces Ca²⁺ in bones and in nerve signalling.
• Effects: anaemia, abdominal colic, "lead line" on gums, kidney damage, nerve damage (wrist drop); in children lower IQ and learning problems.
• Treatment: chelation with CaNa₂EDTA, BAL (British anti-Lewisite, dimercaprol), DMSA (succimer), D-penicillamine.

Mercury (Hg):

• Forms: metallic vapour (thermometers, dental amalgam, gold mining), inorganic salts (HgCl₂), and organic methylmercury (CH₃Hg⁺, formed by bacteria in water; accumulates in fish — biomagnification).
• Biochemical action: very strong affinity for thiol groups — inactivates enzymes and membrane proteins; methylmercury crosses the blood–brain barrier and placenta.
• Effects: nerve damage — tremors, loss of coordination, vision and hearing loss, mental disturbance; kidney damage by inorganic Hg. Minamata disease (Japan, 1950s) was caused by methylmercury in fish from industrial waste.
• Treatment: BAL, DMSA, DMPS (thiol chelators).

Other examples: cadmium (itai-itai disease, kidney and bone damage), arsenic (skin lesions, cancer; groundwater in West Bengal).

Detoxification Strategies: Metallothioneins and Phytochelatins

Metallothioneins (MTs): small proteins (about 61 amino acids) found in animals, very rich in cysteine (about 20 Cys residues, no aromatic amino acids). They bind up to 7 divalent ions (Zn²⁺, Cd²⁺) or more Cu⁺/Hg²⁺ in two metal–thiolate clusters. Roles: storage and buffering of Zn and Cu, detoxification of Cd and Hg (their synthesis is induced by these metals), protection against free radicals.

Phytochelatins (PCs): small peptides found in plants, algae and some fungi, with structure (γ-Glu-Cys)_n-Gly (n = 2–11). They are synthesised enzymatically (not by ribosomes) from glutathione by phytochelatin synthase, which is activated by metal ions. PCs bind Cd, Pb, Hg, As through thiol groups, and the complexes are moved into the vacuole. Used in phytoremediation (cleaning polluted soil with plants).

Antioxidant Mechanisms Involving Metal Ions: Superoxide Dismutase

Respiration produces reactive oxygen species (ROS) — superoxide (O₂^•−), hydrogen peroxide (H₂O₂) and hydroxyl radical (•OH). Free Fe²⁺/Cu⁺ make •OH from H₂O₂ (Fenton reaction: Fe²⁺ + H₂O₂ → Fe³⁺ + OH⁻ + •OH), which damages DNA, proteins and lipids.

Superoxide dismutase (SOD) converts superoxide into less harmful products:

• Types: Cu/Zn-SOD (cytoplasm of eukaryotes; Cu is the redox centre, Zn is structural, bridged by an imidazolate of His), Mn-SOD (mitochondria), Fe-SOD (bacteria, plants), Ni-SOD (some bacteria).
• H₂O₂ formed is removed by catalase (Fe-haem) and glutathione peroxidase (selenium enzyme).
• Mutations in Cu/Zn-SOD are linked with a form of ALS (motor neurone disease).

Metal-based Drugs: Cisplatin, Copper-based Drugs and Iron Chelators

Cisplatin, cis-[Pt(NH₃)₂Cl₂] — square planar Pt(II); its anticancer activity was discovered by Barnett Rosenberg in the 1960s. Used against testicular, ovarian, bladder and lung cancers.

1. In blood (high Cl⁻, about 100 mM) it stays neutral; inside cells (low Cl⁻) Cl⁻ is replaced by water → cis-[Pt(NH₃)₂(H₂O)Cl]⁺ (aquation).
2. The aqua complex binds the N7 atom of guanine in DNA; a second binding forms mainly 1,2-intrastrand GG cross-links.
3. DNA bends and unwinds; replication and transcription stop; the cell undergoes apoptosis.
4. The trans isomer is inactive (cannot form the same cross-links). Side-effects: kidney toxicity, nausea, nerve damage; resistance. Second-generation drugs: carboplatin (less toxic), oxaliplatin (colorectal cancer).

Copper-based drugs: copper complexes (e.g. of salicylates, Schiff bases, phenanthroline) show anti-inflammatory, anticancer and antimicrobial activity in research — Cu complexes can cleave DNA and generate ROS in cancer cells; copper is also used in intrauterine devices. In Wilson's disease, copper overload is treated with chelators (D-penicillamine, trientine) and zinc salts.

Iron chelators: patients receiving repeated blood transfusions (e.g. thalassaemia) develop iron overload, which damages the heart and liver. Chelators bind Fe³⁺ strongly and remove it: desferrioxamine (deferoxamine, a hexadentate siderophore given by injection), deferiprone and deferasirox (oral).

Coordination Chemistry in Pharmacology and Drug Design

• Chelation therapy: polydentate ligands (EDTA, BAL, penicillamine, desferrioxamine) form stable, water-soluble complexes with toxic metals that are excreted. A good chelator is selective, non-toxic and forms a complex more stable than the metal–protein complex.
• Design factors: choice of metal and oxidation state, geometry, ligand exchange rate (kinetic inertness of Pt(II), Ru(III)), lipophilicity for cell entry, and leaving groups that control activation (carboplatin's chelating dicarboxylate is released slowly).
• Diagnostics: Gd(III) complexes (e.g. Gd-DTPA) as MRI contrast agents; ^99mTc complexes for imaging.
• Other drugs: lithium carbonate (bipolar disorder), auranofin (gold, rheumatoid arthritis), sodium nitroprusside (blood pressure), bismuth compounds (stomach ulcers).

Role of Metal Ions in Cancer Therapy and Antibacterial Treatments

Cancer therapy: platinum drugs (cisplatin, carboplatin, oxaliplatin); arsenic trioxide for acute promyelocytic leukaemia; ruthenium complexes in clinical trials (less toxic, anti-metastatic); radioactive metal isotopes for radiotherapy and imaging; metal complexes as photosensitisers in photodynamic therapy.

Antibacterial treatments: silver — silver sulfadiazine cream for burns and silver nanoparticles in dressings (Ag⁺ binds thiols and DNA of bacteria); bismuth compounds (colloidal bismuth subcitrate) against Helicobacter pylori; zinc oxide ointments; copper surfaces that kill microbes; metal complexes of antibiotics with improved activity. Metal chelation also deprives bacteria of iron (siderophore-based strategies).

Likely exam questions

1. (Long, 8 marks) Discuss the toxicity of lead and mercury, and explain detoxification by metallothioneins and phytochelatins.
2. (Long, 8 marks) Explain the mechanism of anticancer action of cisplatin. Add notes on iron chelators and the role of metal ions in antibacterial treatment.
3. (Short, 4 marks) Explain the action of superoxide dismutase.
4. (Short, 4 marks) What is chelation therapy?
5. (Short, 4 marks) Why is trans-platin inactive while cisplatin is active?