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

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

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

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)

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

Can use similar chemistry to a condensation reaction:

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

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

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

Some more mimics NADH mimic Flavin mimic Dimeric

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

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

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

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

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

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