ZhangZhangChemChem 109C109CChapter 23: CatalysisChapter 23: Catalysis

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ZhangZhangChemChem 109C109CCatalyst and Catalysis: IntroductionCatalyst and Catalysis: Introduction

Catalyst is a compound that by its addition to a reaction increasesincreases Catalyst is a compound that by its addition to a reaction increases increases the rate of the reaction without itself being consumed or the rate of the reaction without itself being consumed or changed at the end of the reactionchanged at the end of the reaction (cycle).

The reaction is then called being catalyzed The reaction is then called being catalyzed. The phenomenon of catalyst in accelerating reaction is called

catalysis.

N O

Me

MeHN O

Me

Me

Ph3PAuNTf2 (5 mol %)MsOH (1.2 equiv), 4 Å MS

CH Cl

H+

Ph3PAu+

MeMe quantitative (NMR)/ 61% (isolated)CH2Cl2

HN O

Me

MeHN O

Me

H+ HN O

Me

Me

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Me

MeAu

PPh3

Me

Me AuPPh3

Me

MeMsOPh3PAu+

ZhangZhangChemChem 109C109CCatalyst and Catalysis: IntroductionCatalyst and Catalysis: Introduction

Catalyst increases the reaction rate by providing a pathway with Catalyst increases the reaction rate by providing a pathway with lower free energy of activation (reaction kinetics)

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ZhangZhangChemChem 109C109CCatalysis in Organic ReactionsCatalysis in Organic Reactions

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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ZhangZhangChemChem 109C109CAcid Catalysis: Ester HydrolysisAcid Catalysis: Ester Hydrolysis

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ZhangZhangChemChem 109C109CAcid CatalysisAcid Catalysis

Specific-acid catalysis and general acid catalysis 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 slowGeneral 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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ZhangZhangChemChem 109C109CAcid CatalysisAcid Catalysis

General-acid catalysis vs specific-acid catalysis General-acid catalysis vs. specific-acid catalysis

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ZhangZhangChemChem 109C109CBase CatalysisBase Catalysis

General-base catalysis vs specific-base catalysis General-base catalysis vs. specific-base catalysis

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ZhangZhangChemChem 109C109CNucleophilic CatalysisNucleophilic Catalysis

The catalyst is nucleophile and forms a covalent bond with The catalyst is nucleophile and forms a covalent bond with reactants/intermediates

Also called covalent catalysis

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ZhangZhangChemChem 109C109CMetalMetal--Ion CatalysisIon Catalysis

Lewis acid catalysis (metal ions are Lewis acids) Lewis acid catalysis (metal ions are Lewis acids)

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ZhangZhangChemChem 109C109CMetalMetal--Ion CatalysisIon Catalysis

Examples: Examples:

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ZhangZhangChemChem 109C109CMetalMetal--Ion CatalysisIon Catalysis

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ZhangZhangChemChem 109C109CIntramolecular ReactionsIntramolecular Reactions

1000 1000 times times fasterfasterfasterfaster

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Effective Effective molaritymolarity (EM) is the concentration of the reactant that would (EM) is the concentration of the reactant that would be required in an intermolecular reaction for it to achieve the same be required in an intermolecular reaction for it to achieve the same rate as intramolecular reactionrate as intramolecular reaction

ZhangZhangChemChem 109C109CIntramolecular ReactionsIntramolecular Reactions

R = Me, EM = 2.3 x 10R = Me, EM = 2.3 x 104 4 MMR = R = iPriPr, EM = 1.3 x 10, EM = 1.3 x 106 6 M M

EM = 2.2 x 10EM = 2.2 x 105 5 MMEM 2.2 x 10EM 2.2 x 10 M M

EM = 1 x 10EM = 1 x 107 7 M M

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ZhangZhangChemChem 109C109CIntramolecular CatalysisIntramolecular Catalysis

A catalyst is embedded or covalently bonded to substrates Also called anchimeric effect/assistance Due to intramolecularity, the catalysis should be more efficient.y, y

70000 times70000 timesFaster in the Faster in the Trans isomerTrans isomer

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ZhangZhangChemChem 109C109CIntramolecular Catalysis: ExampleIntramolecular Catalysis: Example

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ZhangZhangChemChem 109C109CIntramolecular Catalysis: ExampleIntramolecular Catalysis: Example

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ZhangZhangChemChem 109C109CCatalysis in Biological ReactionsCatalysis in Biological Reactions

Most biological catalysts are enzymes (belongs to globular proteins) 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

HexokinaseRed: before binding

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Blue: after binding

ZhangZhangChemChem 109C109CEnzyme CatalysisEnzyme Catalysis

How do enzymes do catalysis? 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 Some of the amino acid side chains as well as bounded metal ions as catalyst

Stabilizing the transition states and intermediates via van der WaalsStabilizing the transition states and intermediates via van der Waals interactions, electrostatic interactions, and H-bonding.

Naming of enzymes End typically with ‘ase’ indicating breaking the bondEnd typically with ase , indicating breaking the bond

Peptidase: breaking the peptide bond Esterase: breaking the ester bond

SynthaseSynthase Synthesizing instead of breaking it down.

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ZhangZhangChemChem 109C109CCarboxypeptidaseCarboxypeptidase AA

Metalloenzyme y(enzymes containing tightly bound metal ions)

Hydrolyze C-terminal except lysine and arginine.

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ZhangZhangChemChem 109C109CSerine ProteasesSerine Proteases

Trypsin, chymotrypsin and elastase are members of endopeptidases known as serine proteases

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ZhangZhangChemChem 109C109CSerine ProteasesSerine Proteases

Proposed Proposed mechanism for chymotrypsin-catalyzedcatalyzed hydrolysis

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ZhangZhangChemChem 109C109CLysozymeLysozyme

Catalyze the hydrolysis of the bacterial cell wall NAM-NAG bond Catalyze the hydrolysis of the bacterial cell wall NAM-NAG bond (NAM: N-Acetylmuramic acid)

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ZhangZhangChemChem 109C109CProtein pHProtein pH--Rate ProfileRate Profile

lysozymelysozyme

The pHs at which the enzyme are 50% active corresponds to the pKa of enzyme’s catalytic groups (as long as those values are atpKa of enzyme 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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its free form?

ZhangZhangChemChem 109C109CGlucoseGlucose--66--Phosphate Phosphate IsomeraseIsomerase

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ZhangZhangChemChem 109C109CAldolaseAldolase

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