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Chapter 23: Catalysis Chem 109C

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Catalyst and Catalysis: Introduction Chem 109C

Catalyst is a compound that by its addition to a reaction increases

the rate of the reaction without itself being consumed or
changed at the end of the reaction (cycle).
The reaction is then called being catalyzed
catalyzed.
The phenomenon of catalyst in accelerating reaction is called
catalysis.

Me Me
Ph3PAuNTf 2 (5 mol %)
HN O MsOH (1.2 equiv), 4 MS N O
Me Me
CH2Cl2
Me quantitative (NMR)/ 61% (isolated) Me
H+
Ph3PAu+

Me Me
Me
HN O HN O
HN O H+
Me Me
Au Me
Me PPh3
Me Au Ph3PAu+ Me
MsO
PPh3
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Catalyst and Catalysis: Introduction Chem 109C

Catalyst increases the reaction rate by providing a pathway with

lower free energy of activation (reaction kinetics)

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Catalysis in Organic Reactions Chem 109C

In organic reactions, several ways to accelerate reactions by

catalysts:
Increase electrophilicity
Increase nucleophilicity
Increase leaving ability as a nucleofuge (decrease electrophilicity)
Increase the stability of a transition state

Four types of catalysis:

acid catalysis
base catalysis
nucleophilic catalysis
metal-ion catalysis

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Acid Catalysis: Ester Hydrolysis Chem 109C

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Acid Catalysis Chem 109C

Specific-acid catalysis and general acid catalysis

Specific-acid catalysis: proton is fully transferred before the slow step of
the reaction (typically strong acidic conditions, two-stages)
General acid catalysis: proton transfer to the reactant during the slow
step of the reaction (typically under weak acidic conditions, one stage)

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Acid Catalysis Chem 109C

General-acid catalysis vs
vs. specific-acid catalysis

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Base Catalysis Chem 109C

General-base catalysis vs
vs. specific-base catalysis

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Nucleophilic Catalysis Chem 109C

The catalyst is nucleophile and forms a covalent bond with

reactants/intermediates
Also called covalent catalysis

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Metal--Ion Catalysis
Metal Chem 109C

Lewis acid catalysis (metal ions are Lewis acids)

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Metal--Ion Catalysis
Metal Chem 109C

Examples:

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Metal--Ion Catalysis
Metal Chem 109C

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Intramolecular Reactions Chem 109C

1000
times
faster

Effective molarity (EM) is the concentration of the reactant that would

be required in an intermolecular reaction for it to achieve the same
rate as intramolecular reaction 23--13
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Intramolecular Reactions Chem 109C

R = Me, EM = 2.3 x 104 M

iPr,, EM = 1.3 x 106 M
R = iPr

EM = 2.2 x 105 M

EM = 1 x 107 M

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Intramolecular Catalysis Chem 109C

A catalyst is embedded or covalently bonded to substrates

Also called anchimeric effect/assistance
Due to intramolecularity,
y, the catalysis
y should be more efficient.

70000 times
Faster in the
Trans isomer

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Intramolecular Catalysis: Example Chem 109C

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Intramolecular Catalysis: Example Chem 109C

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Catalysis in Biological Reactions Chem 109C

Most biological catalysts are enzymes (belongs to globular proteins)

Substrates and active sites (where the reaction occurs)

Substrates bound to the active site

Specificity (molecular recognition)
Lock-and-key model
Induced-fit model

Hexokinase
Red: before binding
Blue: after binding

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Enzyme Catalysis Chem 109C

How do enzymes do catalysis?

Reacting groups are brought together in a proper orientation

Some of the amino acid side chains as well as bounded metal ions as
catalyst

Stabilizing the transition states and intermediates via van der Waals
interactions, electrostatic interactions, and H-bonding.
Naming of enzymes
End typically with ase
ase , indicating breaking the bond
Peptidase: breaking the peptide bond
Esterase: breaking the ester bond
Synthase
Synthesizing instead of breaking it down.

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Carboxypeptidase A Chem 109C

Metalloenzyme
y
(enzymes containing
tightly bound metal
ions)
Hydrolyze C-terminal
except lysine and
arginine.

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Serine Proteases Chem 109C

Trypsin, chymotrypsin and elastase are members of endopeptidases

known as serine proteases

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Serine Proteases Chem 109C

Proposed
mechanism for
chymotrypsin-
catalyzed
hydrolysis

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Lysozyme Chem 109C

Catalyze the hydrolysis of the bacterial cell wall NAM-NAG bond

(NAM: N-Acetylmuramic acid)

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Protein pH
pH--Rate Profile Chem 109C

lysozyme

The pHs at which the enzyme are 50% active corresponds to the
pKa of enzyme
enzymes
s catalytic groups (as long as those values are at
lease 2 units apart.
Why pKa of Asp52 is 3.8 but pKa of Glu35 is 6.7 instead of 4.25 in
its free form?

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Glucose--6-Phosphate Isomerase
Glucose Chem 109C

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Aldolase Chem 109C

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