1. Enzyme Mimics (Artificial Enzymes)
Reproduce the enzyme’s function
Mimic a chemical reaction
Chemical transformation (covalent bonds)
&/or
Molecular recognition
Mimic binding (H-bonding, hydrophobic, ionic, etc)
We have already seen two biomimetic catalytic systems:
Organocatalysis with proline
Koga’s crown ethers

2. Several examples of mimics found in research and industry:
Things to consider:
Needs to be an initial binding step
Size: important for binding & release of product
To be truly catalytic, there needs to be turnover
Several examples of mimics found in research and industry:
We will look at:
Cyclodextrins
Cryptands
Catalytic antibodies

3. Cyclodextrins 6 (), 7 (), or 8 () glucose units Hydrophobic cavity
Stable & water soluble
Tunable (modify to change properties)
Several examples of its use for biomimetic catalysis:
Condensation rxns
Redox chemistry
etc
cavity

4. Research on cyclodextrin started in the 1930’s
Very expensive & thought to be toxic
1970’s → non-toxic, but still $2000/kg
Now → cheap! → 1000 tons/y
Several industrial applications
Self-tanning lotions, laundry drier sheets, flavorings, etc.
Produced by environmentally-friendly technologies & renewable materials
Starch → cyclodextrin (action of CTGase)

5. Mimic of Ribonuclease A
Hydrolyses RNA using two His residues for acid/base catalysis (no general agreement on how)
Mimic the Rib A system by attaching imidazole groups on cyclodextrin

6. Can use similar chemistry to a condensation reaction:

7. An Artificial Transaminase
Recall transamination of AAs with pyridoxal phosphate (PLP)
Use cyclodextrin to perform the same chemistry with a covalent linkage to a PLP derivative

8. An Artificial Transaminase (Coenzyme Bound)
Rates:
phenylpyruvic acid 100x faster than pyruvic acid
increase hydrophobicity → further rate increase (15 000x)
Compete for CD

9. Other Coenzyme mimics
Benzoin condensation with thiazolium ion mimic (recall exp. 7, dilantin synthesis):
(note the use of a  cyclodextrin)

10. Some more mimics
NADH mimic
Flavin mimic
Dimeric

11. Cryptands
Cryptands are multi-dendate ligands that bind cations (“buried”)
Similar to a crown ether, but usually more selective and they exhibit stronger binding
Nobel Prize 1987

12. Example: Hydrolysis of ATP (mimics ATPase)
Binding via electrostatic forces & H-bonding
cryptand
Hydrolysis of ATP 500x

13. Catalytic Antibodies
Exploit the excellent binding abilities that antibodies possess
Molecular recognition
Construct a transition state analogue → screen for antibodies against this molecule

14. Reaction to Study: Mimic: Make a TS mimic
Mimics tetrahedral-like transition state

15. Screen for antibodies against your TS analogue
Catalyzes rxn by forcing substrates into a TS-like geometry (i.e. binding & proximity effects)

16. Applications: detoxification of cocaine
Catalytic antibodies are good for simple reactions, but are limited by:
Accuracy → transition state analogue
Screening
Applications: detoxification of cocaine