Small chiral organic molecules can catalyse reactions with the same selectivity as enzymes, by forming a temporary, precisely shaped complex with the substrate.
Cat + S <-> [Cat-S]#
[Cat-S]# -> Cat + P
ee% depends on transition-state fit
- Substrate — prochiral substrate molecules diffusing toward the small-molecule catalyst.
- Catalyst loading — mol% of organocatalyst (e.g. a proline derivative) present in the reaction vessel.
- Binding affinity — how tightly the catalyst's hydrogen-bonding or enamine pocket holds the substrate.
- Reaction temperature — thermal energy driving the transition state over its barrier faster at higher settings.
Organocatalysts avoid trace-metal contamination, which is critical when the product is a pharmaceutical intended for human dosing.