Option D HL D.8

• Geometric isomerism


  Stereoisomers are compounds with the same molecular and structural formula, but a different arrangement of atoms in space
• Geometric isomers


  • Cisplatin
  • Transplatin
• Cis- and trans- forms of a drug


  One geometric isomer may have the desired pharmacological effect, while the other may be less effective or have adverse side effects
• Only the cis- form of cisplatin is effective, the trans- form has no effects whatsoever
• Cisplatin


  • Square planar molecule
  • Can react with two guanine molecules in DNA
• Optical isomers


  Stereoisomers that are chiral, or asymmetric, around one of the atoms
• Only one enantiomer of drugs exhibiting optical isomerism sometimes has the desired pharmacologic effect
• Drugs exhibiting optical isomerism


  • Thalidomide
  • Ibuprofen
  • Naproxen
  • Amphetamine
  • Taxol
• Beta-lactam ring


  Very reactive ring that opens and covalently bonds to the enzyme transpeptidase, responsible for the forming of bacterial cell walls
• If a bacterium is unable to build its cell wall, it bursts, disintegrates and dies
• Diamorphine (heroin)


  Synthetic modification of morphine where the two alcohol groups are replaced by esters
• Diamorphine vs morphine


  Diamorphine is much less polar, so it can pass the blood-brain barrier much quicker in a much larger concentration
• 1. monoacetylmorphine, a derivative of morphine, is even more effective than heroin
• Compound library


  A collection of a very large number of related compounds produced by combinatorial synthesis techniques, with associated information about their biological activity
• Combinatorial chemistry


  Uses a large number of starting reactants to create a variety of different compounds, which are then tested for biological activity
• Solid phase chemistry


  1. Very small resin beads are made as a surface for attachment and reaction of molecules

  2. Different molecules are attached to the solid beads

  3. Products are cleaved from the beads by filtration and washing
• Combinatorial chemistry


  • Mass testing and screening for biological activity
  • High efficiency
• Parallel chemistry


  Carries out the chemistry to create a single product, producing much smaller and more focused libraries
• Computer models in drug design

  Can create 3D molecules and assess the biological and other effects of compounds without the need to synthesize the chemicals
• Polarity modification to increase aqueous solubility


  Making a molecule more polar, i.e. transforming it into its ionic form, makes the chemical more soluble and facilitates its distribution around the body
• Chiral auxiliaries


  Compounds used to convert non-chiral molecules into just the desired enantiomer
• Using chiral auxiliaries


  1. Chiral auxiliary attaches to a non-chiral reactant

  2. This creates the stereochemical conditions to form only one enantiomer

  3. Chiral auxiliary is taken off the product and recycled
• Drugs synthesized using chiral auxiliaries


  • Taxol (paclitaxel)
• Effects of psychoactive drugs


  • Lysergic acid diethylamide (LSD)
  • Mescaline
  • Psilocybin
  • Tetrahydrocannabinol
• Lysergic acid diethylamide (LSD)


  • Flashbacks
  • Changes in visual and sound perception – hallucinations; good or bad trips
  • Desire to laugh
  • Hypertension, dilated pupils, change in body temperature & heart rate
  • Psychological dependence
• Mescaline


  • Subjective hallucinations
  • Anxiety, static tremors, psychic disturbances
  • Abdominal pain – muscle ache
• Psilocybin


  • Subjective hallucinations milder than with mescaline
  • Change in mood – pleasant or apprehensive
  • Inappropriate laughter, dizziness
  • Muscle weakness is common
• Tetrahydrocannabinol


  • Appetite stimulation
  • Lethargy, sluggishness
  • Anxiety and irritability
  • Psychological dependence
• Structural similarities and differences between LSD, mescaline and psilocybin


  • Benzene ring
  • Alkene (2) in LSD
  • Secondary amine in LSD and psilocybin
  • Tertiary amine in LSD
  • Tertiary amide in LSD
  • Primary amine in mescaline
  • Ether (3) in mescaline
  • Tertiary amine ion in psilocybin
  • Phosphate in psilocybin
• Arguments for and against the legalization of cannabis


  • Arguments for:
  • No more or less harming than tobacco or alcohol
  • Source of additional tax revenue
  • Arguments against:
  • Stepping stone drug – can lead to the use of harder drugs
  • Increased risk of lung cancer
  • Risk of driving or manipulation with machinery under influence, which increases the chance of an injury