Approximation

Overview
(1)What and Why is “Approximation”?

(2)Intramolecular Reactions and Intramolecular

Catalysis (Anchimeric Assistance)

(3)Induce Approximation

(4) Specificity

(5) Heterogeneous Catalysis

 Introduction

Binding Interaction and Mechanisms

 Binding Phenomena

? ?
• “Binding” is akin to solvation

• an intermolecular interaction between a receptor and

a substrate

• hint: how solvents affect a SN1 reaction?

• Other terms: Approximation, Proximation

What happen during the binding process?

Situation: Chymotrypsin
Intramolecular Catalysis

Intramolecular Reactions and

Anchimeric Assistance
 Anchimeric Assistance

• Catalysis (enzymatic): bring reactant together at the active site of

the catalyst (enzyme)

Q1: magnitude of the rate enhancement

Q2: possible mechanism suggested from the rate enhancement

• Binding of substrate and the catalyst either by covalently link or

reversible binding force

• Anchimeric assistance: a group adjacent to the reaction center that

affect the reaction rate - INTRAMOLECULAR
 Hydrolysis of
Tetramethylsuccinanilic Acid

(a)

(b)

• Comparison between intra- and intermolecular reaction

• Usually dramatic increases of reaction rate

 Examples of Reactions

• hydrolysis of tetramethylsuccinanilic acid

• hydrolysis of o-carboxyphosphate ester

• migration of acetyl in 2’-acetyluridine

• aminolysis of phenyl acetate

• hydrolysis of substituted phenyl succinates

• intramolecular formation of phenyl ester

 Effective Molarity (E.M.)
• Intramolecular reactions often undergo faster than
intermolecular reactions

• Reduce the entropy of activation (as well as enthalpy)

• Rate enhancement calculated from their rate constant, k

• Effective Molarity, M = kintra / kinter

• E.M. reflects the concentration of a reactant of an

intermolecular reaction required as a pseudo-first order
relative to first order intramolecular reaction

kintra
A B C D

kinter
A B C D
 Hydrolysis of
Tetramethylsuccinanilic Acid

(a)

(b)

• Comparison between intra- and intermolecular reaction

• Dramatic increases of reaction rate

• Rate different: k1/k2 = 1.6 x 108 M

 Hydrolysis of
Tetramethylsuccinanilic Acid

(a)

(c)

• methyl substituted groups bring the reacting into

relationship
• catalyzed, faster reaction 1,200 times
Hydrolysis of o-Carboxyphoshonate Ester

• Intramolecular reaction on benzene (aryl)

• The rate of reaction could be affected by the position of group

(anchimeric)
 Hydrolysis of o-Carboxyphoshonate Ester

(a)

e ri f i c a tion
Est
s t h e lost
cause
re a c t ivity!!
of
(b)

• o-COOH (anchimeric) speed up the reaction

• Intramolecular proton transfer

• No hydrolysis product after 77,960 h for p-COOH

• Rate different: k1/k2 > 7 x 107

Migration of Acetyl Between 2’- and 3’- of
2’-Acetyluridine

Uridine

• 2’-acetyluridine a component of ribose

• Acyl group intramolecular transfer to adjacent hydroxyl

• It’s happen quite rapidly in base condition

Migration of Acetyl Between 2’- and 3’- of
2’-Acetyluridine

(a)

(b)
Migration of Acetyl Between 2’- and 3’- of
2’-Acetyluridine

• Suggested mechanism of acetyl transfer between 2’- and 3’-

substituted

• Rate different: k2/k1 > 350,000 times

• note: it is not longer kintra / kinter

 E.M. for Intramolecular Aminolysis of
Phenyl Ester
• Intermolecular reaction between phenyl ester and amines
• Second order rate constant, kinter = 8 x 10-3 M-1 min-1
• Intramolecular reaction of phenyl γ-(N,N-dimethylamino)butyrate
• First order rate constant, kintra = 10 min-1

(a)

(b)