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Chapter 9 Catalysis9.1 General principles of catalysis

Turnover number: the average number of reactants that a catalyst acts on before the catalyst loses its activity. The catalyst increases rate of reaction (decreases activation energy). The thermodynamics of a catalyzed reaction are unaffected by the catalyst.A heterogeneous catalyst: one that does not dissolve in the solution. Ex) Pd/CA homogeneous catalyst: one that dissolves in the solution.All calaysts operate by the same general principle – that is, the activation energy of the rds must be lowered in order for a rate enhancement to occur.

9.1.1 Binding the transition state better than the ground state

Substrate: any material (reactant) used in a catalytic reactionActivated complex: simply referred to as the transition stateRate enhancement: the ratio of the rate constant for the catalyzed reaction to that for the uncatalyzed one.

To achieve catalysis, the catalyst must stabilize the transition state more than it stabilizes the ground state. That is, the transition state must be bound better than the ground state.

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9.1.3 A spatial temporal approach

To achieve catalysis, the catalyst must stabilize the transition state more than it stabilizes the ground state. That is, the transition state must be bound better than the ground state.

Another explanation for catalysis: spatial temporal postulate, many intramolecular reactions are often much faster than corresponding intermolecular reactions.

-> the rate of reaction between functionalities A and B is proportional to the time that A and B reside within a critical distance. The longer that A and B spend together in

the correct geometry for reaction, the greater that probability.When bound to the catalyst, the distance between A and B is closer than when they are free in solution, and inherently the transition state brings A and B close because bonds are beginning to form.

In summary, binding is the key element in the most widely accepted theory of how catalysis is achieved. Greater binding of the transition state relative to the ground stateis all that needs to be invoked to give a rate enhancement.

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9.2 Forms of catalysis9.2.2 Proximity as binding phenomenon

Intermolecular aminolysis (k1; 1/M·s)

Intramolecular cyclization (k2; 1/s)

Effective molarity (E.M.) or intramolecularity; ratio of the first order to second order rate constants for the analogous reactions.

-> tell us the effective concentration of one of the components in the intramolecular reaction

1.3 x 10-4 /M·s

0.17/s -> a rate enhancement of 1200

5Entropies of translation and rotation

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Gem-dimethyl effect: sterically compress two groups together and preorganizetwo reactants in proximity

R R

decrease of angleclose

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Tetrahedral intermediate -> infinitely stable

E.M. = 1011-1012Twisted amide-> very reactive

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9.2.3 Electrophilic catalysis

Electrophilic catalysis includes simple electrostatics, hydrogen bonding, acid catalysis,and electrophilic metal coordination.

Electrostatic interactions

Oxyanion hole

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150-fold rate enhancement

Cation-π interactions

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Metal ion catalysis

2 x 1016-fold rate enhancement

pKa of metal-bound water = 7.2 (108 more acidic than water itself)

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9.2.4 Acid-base catalysis; 9.3에서설명

9.2.5 Nucleophilic catalysis

Nucleophilic catalysis arise when a nucleophile binds to a reactant and enhances its rate of reaction. -> less common than electrostatic catalysis

N

NMe2

NH

NMe2

DMAP; N,N'-dimethylaminopyridine

better electrophile and more reactive than the starting acid halide or anhydride

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9.2.6 Covalent catalysis

Iminium ion

enamine

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9.2.7 Strain and distortionWhen a substrate binds to a catalyst that is more complementary in structure or electronic characeristics to the transition state, the substrate may distort in order to optimize binding interactions. That is, because the catalyst is designed to optimally bind the transition state, it necessarily is not optimal for the most stable structure of the ground state. -> distortion as a strain on the substrate -> the strain raises the energy of the substrate -> diminish activation energy

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The chair is distorted into a conformation resembling a half-chair

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9.3 Brønsted acid-base catalysis9.3.1 specific catalysis

The specific acid is defined as the protonated form of the solvent in which the reaction is being performed. eg) H3O+, CH3CNH+, CH3SO(H+)CH3

The specific base is defined as the conjugate base of the solvent.eg) HO-, -CH2CN, CH3SOCH2

-

The specific acid catalysis refers to a process in which the reaction rate depends uponthe specific acid, not upon other acids in the solution.

The specific base catalysis refers to a process in which the reaction rate depends uponthe specific base, not upon other bases in the solution.

kobs = k[H3O+]/KaRH+

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added acid (AcOH in H2O)

If the acid catalysis is involved in an equilibrium prior to the rds, and it is not involved in rds, then the kinetics of the reaction will depend solely upon the concentration of the specific acid. This is true even if an added acid (AcOH) is involved in protonatingthe reactant.Why? When a prior equilibrium is established, [RH+] determines the rate of the reaction. The concentration of RH+ depends solely upon the pH and the pKa of RH+, and does not depend upon the concentration of the acid HA that was added to solution.

앞과 동일

Specific acid catalyzed reactions

A-는반응에관여하지않음.따라서 rate law에포함되지않음

KaHA = [A-][H3O+]/[HA]KaRH+ = [R][H3O+]/[RH+]

[HA] 항 없음

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kobs = kKaRH /[H3O+]

Specific base catalyzed reactions

KaRH =[R-][H3O+]/[RH]

BH+는반응에관여하지않음.따라서 rate law에포함되지않음

[B] 항 없음

23 page에서 다시 설명

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Kinetic plots

The hallmark of specific acid or specific base catalysis is that the rate depends on the pH and not on the concentration of various acids or bases. This always means that an equilibrium involving the acid or base occur prior to rds, and the acid or base is not involved in rds itself.

specific acid catalysis specific base catalysis

kobs = k[H3O+]/KaRH+ kobs = kKaRH /[H3O+]

logkobs = logk –pH-logKaRH+ logkobs = logk +pH+logKaRH+

added acid added base

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9.3.2 General catalysisIn case that the proton transfer is involved in rds, not in a prior equilibrium -> general catalysis

When an acid is involved in rds, -> general acid catalysisWhen a base is involved in rds, -> general base catalysisThe term ‘general’ refers to the fact that any acid or base we added to the solution will affect the rate of the reaction.

The term ‘specific’ refers to the fact that just one acid or base, that from the solvent, affects the rate of the reaction.

HA는반응에관여함.따라서 rate law에포함

Ka = [A-][H3O+]/[HA]

kobs = k[HA] or k[H3O+][A-]/Ka

- Since the acid is always regenerated after the reaction, its concentration never changes over the course of the reaction -> pseudo-first order

- the concentration of either HA or A- is in the rate expression.

General acid catalyzed reactions

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General base catalyzed reactions

B는반응에관여함.따라서 rate law에포함

kobs = k[B] or k[HO-][HB+]/Kb

- Since the base is always regenerated after the reaction, its concentration never changes over the course of the reaction -> pseudo-first order

- the concentration of either B or BH+ is in the rate expression.

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Note: ‘specific’ is used to designate the protonated or deprotonated form of the solvent (H3O+ or HO- for water), but it is also used to designate a mechanism involving an acid or base in an equilibrium prior to rds.However, sometimes hydronium or hydroxide can be involved in rds. In this case the specific acid and base are participating in general-catalysis.

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slow

실제로는 첫번째 단계가 rds따라서 HO-는 general base로 작용

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Kinetic plotsThe hallmark of specific acid or specific base catalysis is that the rate depends on the pH and not on the concentration of various acids or bases. This always means that an equilibrium involving the acid or base occur prior to rds, and the acid or base is not involved in rds itself.

general acid catalysis general base catalysis

kobs = k[HA] or k[H3O+][A-]/Ka kobs = k[B] or k[HO-][HB+]/Kb

페이지 20과비교

pH < pKa, HA로주로존재, 따라서 k의변화없음pH ~ pKa, HA와 A- (이것은반응에관여하지않음)이공존pH > pKa, HA가점차적으로 A-로바뀌어 k가지속적으로감소

general acid catalysis general base catalysis

C와mirror image

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9.3.4 Concerted or sequential general-acid-general-base catalysisBoth a general acid and a general base catalyst are required for a reaction.This is often the case with enzymes.

acid base

kobs = k[HA][B]

The rate dependence on pH is a combination of that observed for general-acid and general-base catalyst. The largest kobs is found at pH where

the product of the concentrations of HA and B is at a maximum

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9.4 Enzymatic catalysis9.4.1 Michaelis-Menten kinetics

E + S E·S P + E←→k1

→k-1

kcatE·S: Michaelis complex

SE + ←→ → P

E·S

rate = d[P]/dt = kcat[ES]

d[ES]/dt = k1[E][S] – k-1[ES] - kcat[ES] = 0

[E]0 = [E] + [ES]

k1([E]0-[ES])[S] – k-1[ES] - kcat[ES] = 0

[E] = [E]0 - [ES]

[E]0[S]Km = (k-1 + kcat)/k1[ES] =

Km + [S]

rate = d[P]/dt = kcat[ES] = kcat[E]0[S]Km + [S]

Michaelis-Menten equation

Kinetic parameters to be determined for enzymatic reactions: kcat and Km

physical processchemical process

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1. kcat: catalytic constant turnover number: the maximum number of substrate molecules converted to productsper active site per unit time or the rate constant for the conversion of the substrate to the product within the active site of the catalyst (unit; 1/s)-> proximity, acid-base catalysis, electrostatic consideration, covalent catalysis, and the

relief of strain will influence kcat.

2. Km : apparent dissociation constant that may be treated as the overall dissociation constants of all enzyme-bound species.k-1 >> kcat -> Km = k-1/k1 the dissociation constant for ES complex.

Under these circumstances, Km can provide insights into how good a receptor the catalyst is. The smaller Km means a better receptor. -> Km reflects a physical process (binding) rather than a chemical transformation.

k-1 << kcat -> Km = kcat/k1 (a very good catalyst) does not resemble the dissociation constant for ES complex

3. kcat/Km (specific constant)Km >> [S],

9.4.2 The meaning of Km, kcat and kcat/Km

kcat/Km ; apparent second order rate constant

-> this is related to how well the catalyst binds the substrate and how well the catalyst turnsover the substrate to product. -> Information on both binding and catalysis

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9.4.3 Enzyme active sites

Proposed mechanism

Ricin A is a potent cytotoxin from 아주까리

attacks ribosomes, hydrolyzing the N-glycoside linkageof specific adenosine nucleotides in oligonucleotides

general acid

general base-> enhances nucleophilicity of water

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Rate enhancement: 104-105

Vmax: 2.24 x 10-5 M/sKm: 4.69 x 10-5 M