Alkyl Halide Medicines Flashcards
Relationship between leaving group strength and activation energy
The stronger the leaving group = the lower the activation energy = the faster the rate limiting step
Racemic Mixture Outline
50:50 mix of R and S enantiomer configurations. An optically inactive substance. Result of a Sn1 reaction as due to leaving group detatching before nucleophile attaches it has a 50-50 chance of adding on either dside of C (inverting or maintaining chirality)
Inversion of chirality Outline
Due to the nucleophile attaching to the side opposite the leaving group the product of the reaction will have the opposite configuration ad it’s reactant. Result of a Sn2 reaction
How is DNA used in nucleophilic substitution
Guanine 7 contains a lone pair of electrons (is a nucleophile). Interacts with drugs resulting in change of gene expression (mutation) or cell death (eg when methyl chloride triggers cell death)
Organo-halogen drugs interactions with DNA
During nucleophilic substitution halogens replace Guanine 7 on DNA arresting DNA replication causing cell death
Methylenations Outline
The adding of a methyl (CH3 group onto different substances) from an electrophilic group to a nucleophile. Electrophilic group acts as leaving group
Natural electrophilic methyl donating substance
S-acetylmethionine (SAM). Acts as a good donor as it’s methyl group is attached to a Sulfur substituent. The S is very positively charged and increadibly stable. This makes it very willing to donate the methyl group with a proton to the negatively charged nucleophile
Why we can’t use synthetic methyl halides
They’re toxic and release in an uncontrolled fashion
Example of nucleophilic substitution with SAM
noradrenaline to adrenaline (with SAM as leaving group). Nucleophile is attached to nor adrenaline, SAM acts as leaving group detaching from methyl. noradrenaline joins with methyl forming adrenaline
