Catalysis

Facts and Figures about Catalysts

Life cycle on the earth– Catalysts (enzyme) participates most part of life cycle

e.g. forming, growing, decaying– Catalysis contributes great part in the processes of converting sun energy to

various other forms of energies e.g. photosynthesis by plant CO2 + H2O=HC + O2

– Catalysis plays a key role in maintaining our environment

Chemical Industry– ca. $2 bn annual sale of catalysts– ca. $200 bn annual sale of the chemicals that are related products– 90% of chemical industry has catalysis-related processes– Catalysts contributes ca. 2% of total investment in a chemical process

Catalysis

• Catalysis– Catalysis is an action by catalyst which takes part in a chemical reaction process and

can alter the rate of reactions, and yet itself will return to its original form without being consumed or destroyed at the end of the reactions (This is one of many definitions)

Three key aspects of catalyst action taking part in the reaction

• it will change itself during the process by interacting with other reactant/product molecules altering the rates of reactions

• in most cases the rates of reactions are increased by the action of catalysts; however, in some situations the rates of undesired reactions are selectively suppressed

Returning to its original form• After reaction cycles a catalyst with exactly the same nature is ‘reborn’• In practice a catalyst has its lifespan - it deactivates gradually during use

Catalysis action - Reaction kinetics and mechanism

Catalyst action leads to the rate of a reaction to change. This is realised by changing the course of reaction (compared to non-catalytic reaction)

– Forming complex with reactants/products, controlling the rate of elementary steps in the process. This is evidenced by the facts that

• The reaction activation energy is altered

• The intermediates formed are different from those formed in non-catalytic reaction

• The rates of reactions are altered (bothdesired and undesired ones)

– Reactions proceed under less demanding conditions • Allow reactions occur under a milder conditions, e.g. at lower temperatures for those

heat sensitive materials

reactant

reaction process

uncatalytic

product

ener

gy

catalytic

Types of catalysts– Classification based on the its physical state, a catalyst can be

• gas • liquid• solid

– Classification based on the substances from which a catalyst is made• Inorganic (gases, metals, metal oxides, inorganic acids, bases etc.)• Organic (organic acids, enzymes etc.)

– Classification based on the ways catalysts work• Homogeneous - both catalyst and all reactants/products are in the same phase (gas or liq)• Heterogeneous - reaction system involves multi-phase (catalysts + reactants/products)

– Classification based on the catalysts’ action• Acid-base catalysts• Enzymatic• Photocatalysis• Electrocatalysis, etc.

Catalysis: General Mechanistic Outlook

Alternate Case

Van’t Hoff Intermediate

Comparative Activation Energy Analysis

Acid Catalyzed Reactions

Mechanism for Acid-base Catalysis

Acid Catalyzed Reaction

At low pH At high pH At an optimized condition

Acid-Base Catalysis Graphical Representation

Acid Catalyzed Fast Pre-equilibria

fSH = fraction of protonated substrate

Base Catalyzed reaction under fast pre-equilibrium

Alternate A-B Catalyzed Reaction (Van’t Hoff Intermediate)

Graphical Representation

Hydrolysis of Aspirin and its ester Derivative

Enzyme Kinetics• measurement of velocity = reaction rate

• compare enzymes under different conditions, or from different tissues or organisms– understand how differences relate to physiology/function of organism– e.g., physiological reason for different Km values

• compare activity of same enzyme with different substrates (understand specificity)

• measure amount or concentration of one enzyme in a mixture by its activity

• measure enzyme purity (specific activity = amount of activity/amount of protein)• study/distinguish different types of inhibitors

– info about enzyme active sites and reaction mechanism– development of specific drugs (enzyme inhibitors)

Enzyme Catalysis

• Six major classes of reaction catalyzed enzymes are Classified as– Oxidoreductase– Transferase– Hydrolase– Lyases– Isomerases– Ligases

Enzyme Catalysis

Lock and Key Theory• Enzymes are Exact Size fit for

substrates -- conformational changes do not occur when substrate binds during the reaction.

Induced Fit Theory• Enzymes flexible -- conformational

changes can occur when substrate binds during the reaction, to get maximal complementarity to the transition state.

Initial velocity

The initial velocity increases with [S] at low [S].

Enzyme Kinetics

Michealis-Menten Model

1. First step: The enzyme (E) and the substrate (S) reversibly and quickly form a non-covalent ES complex.

2. Second step: The ES complex undergoes a chemical transformation and dissociates to give product (P) and enzyme (E).

3. v=k2[ES]4. Many enzymatic reactions follow Michaelis–Menten

kinetics, even though enzyme mechanisms are always more complicated than the Michaelis–Menten model.

5. For real enzymatic reactions use kcat instead of k2.

The Enzyme-Substrate Complex (ES)

• The enzyme binds non-covalently to the substrate to form a non-covalent ES complex– The ES complex is known as the Michaelis complex.– A Michaelis complex is stabilized by molecular

interactions (non-covalent interactions).– Michaelis complexes form quickly and dissociate

quickly.

Assumptions1. k1,k-1>>k2 (i.e., the first step is fast and is always at equilibrium).

2. d[ES]/dt ≈ 0 (i.e., the system is at steady state.)

3. There is a single reaction/dissociation step (i.e., k2=kcat).

4. STot = [S] + [ES] ≈ [S]

5. There is no back reaction of P to ES (i.e. [P] ≈ 0). This assumption allows us to ignore k-2. We measure initial velocities, when [P] ≈ 0.

Michealis-Menten Equation

M-M Eqn• The final form of M-M equation in the case of a single

substrate is

• kcat (turnover number): how many substrate molecules can one enzyme molecule convert per second

• Km (Michaelis constant): an approximate measure of substrate’s affinity for enzyme

][]][[

SKSEkv

m

totcat

Linear representation of Enzyme Kinetics

Lineweaver Burk Plot Eadie Plot

Concentration of Various Species

Zoomed outlook

Two Substrate Enzyme Kinetics

Enzyme Inhibitors

Reversible versus Irreversible • Reversible inhibitors interact with an enzyme

via non-covalent associations • Irreversible inhibitors interact with an enzyme

via covalent associations

Classes of InhibitionTwo real, one hypothetical

• Competitive inhibition - inhibitor (I) binds only to E, not to ES

• Noncompetitive inhibition - inhibitor (I) binds either to E and/or to ES

• Uncompetitive inhibition - inhibitor (I) binds only to ES, not to E. This is a hypothetical case that has never been documented for a real enzyme, but which makes a useful contrast to competitive inhibition

Competitive Inhibition

Uncompetitive Inhibition

Non-Competitive InhibitionE ES E + P

E I ESI

Example of Irreversible Inhibition

Effect of pH on Enzyme Kinetics

Low pH High pH

Photochemical Processes and Kinetics

• Photochemical process – The initiation of a chemical reaction through the absorption of a photon by an atom or molecule.

Jablonski Diagram

Franck Condon Principle

Photochemical ProcessesAfter population of S1, the fate of the excited species

via photophysical processes:(1) Thermal equilibration of the vibrational Energy =

vibrational relaxation (VR, ~100 fs)(2) Fluorescence: A radiative transition to lose the

excess electronic energy through emission of a photon. (10-9 to 10-6 s)

(3) Intersystem crossing (ISC): A change of spin state to T1, which is forbidden by quantum mechanics.

• Rate of S1 VR > fluorescence ~ ISC.• T1 VR(4) Phosphorescence from T1 to S0, a spin

forbidden transition occurs in 10-6 to seconds timescales.

(5) Internal conversion: A non-radiative process, the S1 state decays to high vibrational levels of S0 followed rapid VR.

Fluorescence and Fluorescence Quenching

Photochemical Process