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Binding is akin to solvation

an intermolecular interaction between a receptor anda substrate

hint: how solvents affect a SN1 reaction?

Other terms: Approximation, Proximation

Binding Phenomena

What happen during the binding process?

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Situation: Chymotrypsin

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Catalysis (enzymatic): bring reactant together at the active site ofthe 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 thataffect the reaction rate - INTRAMOLECULAR

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Hydrolysis ofTetramethylsuccinanilic Acid

(a)

(b)

Comparison between intra- and intermolecular reaction

Usually dramatic increases of reaction rate

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Examples of Reactions

hydrolysis of tetramethylsuccinanilic acid

hydrolysis ofo-carboxyphosphate ester

migration of acetyl in 2-acetyluridine

aminolysis of phenyl acetate

hydrolysis of substituted phenyl succinates

intramolecular formation of phenyl ester

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Intramolecular reactions often undergo faster thanintermolecular 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 anintermolecular reaction required as a pseudo-first order

relative to first order intramolecular reaction

A B C Dkinter

C DA Bkintra

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Hydrolysis ofTetramethylsuccinanilic Acid

(a)

(b)

Comparison between intra- and intermolecular reaction

Dramatic increases of reaction rate

Rate different: k1/k2 = 1.6 x 108

M

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Hydrolysis ofTetramethylsuccinanilic Acid

methyl substituted groups bring the reacting intorelationship

catalyzed, faster reaction 1,200 times

(a)

(c)

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Intramolecular reaction on benzene (aryl)

The rate of reaction could be affected by the position of group(anchimeric)

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o-COOH (anchimeric) speed up the reaction

Intramolecular proton transfer

No hydrolysis product after 77,960 h forp-COOH

Rate different: k1/k2 > 7 x 107

Esterification

causesthelost

ofreactivity!!

(a)

(b)

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2-acetyluridine a component of ribose Acyl group intramolecular transfer to adjacent hydroxyl

Its happen quite rapidly in base condition

Uridine

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(a)

(b)

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Suggested mechanism of acetyl transfer between 2- and 3-

substituted

Rate different: k2/k1 > 350,000 times

note: it is not longer kintra / kinter

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Intermolecular reaction between phenyl ester and amines

Second order rate constant, kinter = 8 x 10-3 M-1 min-1

Intramolecular reaction of phenyl -(N,N-dimethylamino)butyrate

First order rate constant, kintra = 10 min-1

(a)

(b)