BIOINORGANIC CHEMISTRY

Note: Questions solved from csir and gate exams

41) Complexes of which of the following metals are used in the treatment of
rheumatoid ar-thritis:
1. Gold
2. Ruthenium
3. Iron
4. Copper
Explanation
* Gold salts (containing Au(I)) like Auranofin, Sodium aurothiomalate, aurothioglucose
are used to treat rheumatoid arthritis.
Additional information
Some 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 Li 2CO3, 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.* 99m Tc (in Cardiolyte) is used in radio
diagnostics. 99m Tc 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.
* Selenium sulfide used to treat seborrheic dermatitis and Tinea versicolor.
* MoS 42- (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.

Inorganic elements and their biological functions

Bulk metals - Na, K, Mg, Ca
Trace metals - Zn, Fe, Co, Ni, Cu, Mo, V - metals with low conc. are used for
biocatalysis.
* Na+ ,K + : As electrolytes, maintain the concentration gradient (osmotic balance).
Helps in active and passive transport.
Charge carriers.
* Mg 2+: Present in chlorophyll.
In energy production (ATP --->ADP);Activation of enzymes.
Information carrier; Present in endo and exo skeletons.
* Ca 2+ : Charge carrier.
In muscle and nerve functions - cell signalling. It acts as second messenger and sen-tinel
at synapse.
Present in teeth as Ca5(PO4)3(OH) (hydroxylapatite), and CaCO3,Present in endo and
exo skeletons;In activation of enzymes;In blood coagulation.
* VIV/V, Mo IV/VI, WIV/VI , Mn II/III/IV , Fe II/III , Ni I/II/III , Cu I/II : electron
transfer
* Fe and Cu: Transport and storage of dioxygen.
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.
* Co: Cobalamine, e.g. Vitamin-B12
* Mn: In photosynthesis, generation of dioxygen by splitting water. Mn is part of OEC
(Oxygen Evolving Complex) in PS II.
* Mo, Fe & V: Conversion of N2 to ammonia (nitrogen fixation).
* Zn2+: Enzymes, zincfinger proteins (genetic transcription), stabilization of proteins.
* Si(IV)Bones.
* P5+: Hydroxylapatite, ATP, cell membrane, 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.
* Ni2+:Hydrogenase and hydrolases (urease).
Bioactivity and accompanying metals
* Electron carriers Fe : cytochrome, iron-sulfur protein;Cu : blue copper protein.
* Metal storage compound Fe : ferritin (related is “transferrin” which transport iron)
Zn : metallothionein.
* Oxygen transportation agent Fe: hemoglobin (related is “myoglobin” which stores O2)
Cu: hemocyanin.
* Photosynthesis Mg: chlorophyll in PSI.Mn: part of OEC in PSII
* Hydrolase Zn: carboxypeptidase.Mg: aminopeptidase.
* Oxidoreductase Fe: oxygenase, hydrogenase.Fe, Mo: nitrogenase.
* Isomerase Fe: aconitase.Co: vitamin B12 coenzyme.

More stuff - with brief explanation

* Superoxide dismutase, present in the cytosol, is a Cu-Zn containing enzyme
catalyzing the disproportionation of O2- (superoxide) to O 22- (peroxide) and H2O.
* Hemocyanins are respiratory metalloproteins containing two copper atoms that
reversibly bind a single oxygen molecule (O 2).
* 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 HCO3- to CO2.
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).
* Normal nitrogenase enzymes contain Mo and Fe, but less common forms with
vanadium are also known. Nitrogenase enzyme catalyses conversion of N2
to ammonia.
* 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?)
* Among the metals present in human body, the most abundant is Calcium.
* 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.