Page - (000028) - in Biomedical Chemistry: Current Trends and Developments

Unimolecular nucleophilic substitutions (SN1) occur when a carbocation intermediate is stable enough to be transiently formed. In this case, the rate determining step involves reaction of only one species: the substrate where the substitution will take place (Scheme 1.1.6). Scheme 1.1.6: General reaction for a SN1 reaction mechanism. A carbocation may be easily formed on tertiary carbons because the carbocation is stabilized through inductive effect by vicinal carbons (R = alkyl or aryl groups). With this in mind, the more electronegative moiety is able to heterolytically cleave its bond to the carbon atom. Since the carbocation is planar, there is no preference for the nucleophile on which side to attack, resulting in a mixture of enantiomers if the product in question in chiral. In enzymes, this does not happen because the active sites are chiral themselves, restricting addition to only one side. This type of mechanism is typical of tertiary alkyl halides substitutions and allylic phosphates. For example, geranyl diphosphate cleaves at the C-O bond and the corresponding allylic carbocation, well stabilized by resonance, is attacked by water which deprotonates to produce geraniol (Scheme 1.1.7). Scheme 1.1.7: SN1 reaction mechanism of geranyl diphosphate forming geraniol. 1.1.4.1.3 Phosphate Group Transfer – the Grey Area of Nucleophilic Substitutions in Biological Systems Nucleophilic substitutions are not restrained to carbon atoms.