Prepared by Lawrence Kok http://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
Mirror image ( right, left handed )
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 insomnia
and 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)
(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 source http://www.chemconnections.org/organic/chem226/Labs/opt-rotation/ibupro-resolution-09.html
IB Keywords Enantiomers - pair of non superimposable isomers + mirror image + diff 3D Isomers - compounds with same MF + SF but diff spatial arrangement Racemic - 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 History of Thalidomide 1954 - Thalidomide for insomnia and morning sickness . 1961 - Withdrawn, teratogenicity , birth defects result if drug is taken during pregnancy. 1990 - FDA approved for erythema nodosum leprosum, leprosy (skin disease) 1998 - FDA approved for multiple myeloma , (cancer of plasma cells in the blood) Sources and pictures from FDA/other contributors http://www.cancer.gov/cancertopics/druginfo/lenalid omide http://bloodjournal.hematologylibrary.org/content/108/10/3233/F1.expansion.html http://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/ Lenalidomide Why 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 deformities
Click HERE for info/source http://www.rsc.org/chemistryworld/news/2010/march/11031001.asp http://news.bbc.co.uk/2/hi/science/nature/8562998.stm http://news.sciencemag.org/sciencenow/2010/03/-thalidomide-ranks-as-one.html Scientists discovered How Thalidomide caused Malformed Limbs
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 licenses http://creativecommons.org/licenses/ Prepared by Lawrence Kok Check out more video tutorials from my site and hope you enjoy this tutorial http://lawrencekok.blogspot.com