Prepared byLawrence Kokhttp://lawrencekok.blogspot.com

Stereoisomerism and Optical Isomerism Stereoisomerism are isomer with same Molecular Formula + Structural Formula but different in spatial arrangement ( different 3 Dimensional shapes )

Optical Isomers (Organic)

• Chiral, asymmetrical carbon• 4 different gps attached to carbon central• Non superimposable• Mirror image ( right, left handed )• Enantiomers• Identical chemical/physical properties • 2 enantiomers rotate plane of polarised light to diff directions

Optical isomers (Thalidomide) tragedy due to Mirror Image

• Thalidomide exist as optical isomers • Enantiomers (R) and (S)• (R) effective against insomniaand morning sickness• S teratogenic, birth and limb defect

In nature, our body synthesises enzyme which have active site for only one enantiomer• Drug company, synthesise drug with R and S ( racemic mix) • (R) is effective but (S) has side effect• Enzyme recognises only one enantiomer due to active site

Mirror image of thalidomide caused limb deformation• (S) enantiomer causes limb defects and severe shortening of the arms /legs.• (R) enantiomer is effective drug• Body will convert (R) to (S) by racemisation process, producing a racemic mixture (R)/(S)

source:http://dermatology.cdlib.org/93/reviews/thalidomide/hsu.htmsource:http://chemwiki.ucdavis.edu/index.php?title=Special:Userlogin&returntomypage=y

• (S) enantiomer, effective as reducing fever and pain relief• (R) enantiomer has no side effect!• Most drugs in racemic mixture equal (R) and (S)• Cheaper to synthesise racemic mix than pure enantiomer• Single enantiomer appears to be more effective than racemic mix • Clinical trial is essential to ensure no harmful side effect

Mirror Image of Ibuprofen (pain killer drug) has no side effect

sourcehttp://www.chemconnections.org/organic/chem226/Labs/opt-rotation/ibupro-resolution-09.html

IB KeywordsEnantiomers - pair of non superimposable isomers + mirror image + diff 3DIsomers - compounds with same MF + SF but diff spatial arrangementRacemic - equal (50/50)% mixture of both enantiomers S and R ( optically inactive ), no net rotation of plane-polarized light, rotations cancel out.History of Thalidomide 1954 -   Thalidomide for  insomnia and morning sickness.1961 -   Withdrawn, teratogenicity, birth defects result if  drug is taken during pregnancy.

1990 - FDA approved for erythema nodosumleprosum,  leprosy (skin disease) 1998 -  FDA approved for multiple myeloma, (cancer of plasma cells in the blood) 

Sources and pictures from FDA/other contributorshttp://www.cancer.gov/cancertopics/druginfo/lenalidomidehttp://bloodjournal.hematologylibrary.org/content/108/10/3233/F1.expansion.htmlhttp://animalculescience.blogspot.com/

Video, Thalidomide, Enantiomers/Mirror Image/Chiral Carbon

Thalidomide making a come back after named as the greatest disaster in medical history

Click HERE to view the Return of Thalidomide/ LenalidomideWhy even though it is so deadly to pregnant women?

• 2004 - Lenalidomide derived from Thalido able to strengthen immune cells and effective against blood cancers• 2011 - Thalidomide + Lenalidomide inhibit formation of new blood vessels ( anti-angiogenic) of tumor cells, Tumors unable to grow/spread due to lack of nutrition. Researchers testing thalidomide in trials for other HIV and Crohn’s disease.

March 2010 - Published in Science by Takumi Ito.Click HERE for info/source

• Defect Limb due to Thalidomide• (S) enantiomers binds /inactivates the protein cereblon, which is important in limb formation. Inactivation, leads to a teratogenic effect on LIMB DEFORMITIES

Published in Science .....• Hiroshi Handa /Takumi Ito - Developed tiny beads with Thalidomide attached.• Thalidomide beads mix with cells extract• Protein Cereblon was bounded on beads• ack of Protein Cereblon during embryo development, causes limb deformitiesClick HERE for info/sourcehttp://www.rsc.org/chemistryworld/news/2010/march/11031001.asphttp://news.bbc.co.uk/2/hi/science/nature/8562998.stmhttp://news.sciencemag.org/sciencenow/2010/03/-thalidomide-ranks-as-one.html

Scientists discovered How Thalidomide caused Malformed Limbs

Optical Isomers have• Same MF, SF but differ in spatial arrangement.• Same physical/chemical properties• Differentiated using polarimeter, optically active enantiomers, rotate plane of polarised light in diff direction

Polarimeter

picture fromhttp://www.creation-science-prophecy.com/amino/

IB Keywords

• Optically active enantiomers rotate plane of polarised light (clock/anticlockwise)

• Enantiomers have same physical/chemical properties

• Enantiomers present in equal amt (racemic mix), one enantiomer will rotate light to one dir, another will rotate to same degree but opposite dir (rotation cancel out each other), OPTICALLY INACTIVE

• Natural products (body) produce only one pure enantiomer (optically active)

• Synthetic products produce 2 enantiomers, (racemic mix), (optically inactive)

Video, Polarimeter in distinguishing optically active enantiomers

Acknowledgements

Thanks to source of pictures and video used in this presentation

Thanks to Creative Commons for excellent contribution on licenseshttp://creativecommons.org/licenses/

Prepared by Lawrence Kok

Check out more video tutorials from my site and hope you enjoy this tutorialhttp://lawrencekok.blogspot.com