Enzyme Mimics (Artificial Enzymes)

Reproduce the enzymes 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
Kogas crown ethers

 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

-cyclodextrin

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 1930s

Very expensive & thought to be toxic

1970s 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)
O

NH2

HO

O P O
N
PLP

OH

+
NH2

alanine

HO

O P O
N

O
O

OH
O
pyruvic acid

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
O
OH

Compete for CD

increase hydrophobicity
further rate increase
(15 000x)

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

Make a TS mimic

Reaction to Study:
O

O2N
OMe

H
H

O
O2N
OH

Mimic:

O2N

P
O

Mimics tetrahedral-like transition state

Screen for
antibodies
against your
TS analogue

O2N

O2N
OMe

O
H

O2N
OH

Catalyzes rxn by forcing

substrates into a TS-like
geometry (i.e. binding &
proximity effects)

 Catalytic antibodies are good for simple reactions, but

are limited by:
Accuracy transition state analogue
Screening

Applications: detoxification of cocaine