Chelation

Chelation and complexation

1. Chelation and Complexation SABEER KANDEL

2. We will be learning about: Chelation: Routes of administration Examples Factors affecting Pharmaceutical uses Side effects Complexation : Complex formation Types More about topic

3. Chelation Chelating agent : Organic/ inorganic compounds capable of binding metal ions to form complex ring-like structure “chelates”. Chelation therapy : Medical procedure that involves administration of chelating agents to remove heavy metals from body.

4. More about chelation Route of administration : Intravenous Intramuscular Oral Depending on agents and type of poisoning Common chelating agents: EDTA Ethylenediaminetetraacetic acid= Pb DMSA Dimercaptosuccinic acid= Pb , As, Hg Deferoxamine and Deferasirox = Fe poisoning and overload Dimercaprol ( british anti-Lewisite :BAL )= Pb , Hg, As Penicillamine =Cu, Ar , Pb

5. Factors affecting stability and formation Endogenous factors: Hemoglobin, cytochromes pH Net ionic charge of chelator : Determines its AD and ability to reach site of binding Possible Side effects : Dehydration Hypocalcaemia Allergic reaction

6. Pharmaceutical uses Antidote for metal poisoning : heavy metals and toxic metals Removing trace metals from pharmaceutical preparations EDTA removes calcium ion from hard water Also prevents oxidative degradation of ascorbic acid However, Essential metals are also lost from body and vitamin C and E are also lost Poor clinical recovery May be hepatotoxic and neurotoxic

7. Complexation Process of Complex formation. Complex consists of: central metallic atom/ion Surrounded by ligands It occurs via: Hydrophobic interaction : involves vander waal’s force Charge transfer system : interaction between electron donor and acceptor

8. Classification Are of three types: Metal ion complex : metal + electron donor Organic molecular complex: donor and acceptor held by weak force Inclusion or occlusion ion complex : one component of complex is trapped in cage like structure of another It is to be noted that chelation is a kind of complexation

9. More about topic Urine test to be done before chelation Vitamin E and C also removed so must be supplemented In vivo and in vitro effects vary due to endogenous factors Newer strategy: Combination therapy Uses two structurally different chelators Lipophilic (intracellular) and lyophobic (extracellular) Enhanced effect

10. References Ansel et al, Pharmaceutical Dosage Forms And Drug Delivery System (7 th Ed.) Lippincott Wilhams and Wilkins 227 East Washington Square, Philadelphia pp.266-267 Florence AT, Attwood D, Physiochemical Principle of Pharmacy , 4 th Ed