Transcript Fyzikální a analytická chemie - Institute of Medical Biochemistry and

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Catalysis
Basic Medical Chemistry
and Biochemistry
Winter
term – 1st year
Institute of Medical
Biochemistry
Medical Chemistry and Biochemistry
Category I
© Institute of Medical Biochemistry and Laboratory Diagnostics of the General University Hospital and of The
First Faculty of Medicine of Charles University in Prague - 2005-2016
Catalysis
 Catalytic
processes
 Homogeneous and heterogeneous catalysis
http://en.wikipedia.org/
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Catalysis

Catalysis is the process, in which the rate (not equilibrium) of a chemical reaction is
increased (decreased, respectively) by means of a chemical substance known as a
catalyst.

Unlike other reagents that participate in the chemical reaction, a catalyst is not
consumed.

The catalyst may participate in multiple chemical transformations, although in
practice catalysts are secondary processes.

it changes the reaction mechanism, it changes the activation energy, it is involved in
the formation of the activation complex
A+B→AB vs.
A+B+K→ABK→AB+K
EAB
EAB – activation energy without catalysis
EABK – activation energy with catalysis
GAB – Gibbs energy of the reaction
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EABK
GAB
products
4
Example:
Catalytic production of sulphuric acid
Sulfuric acid is produced from sulfur, oxygen and water via the contact process.
In the first step, sulfur is burned to produce sulfur dioxide.
(1) S(s) + O2(g) → SO2(g)
This is then oxidised to sulfur trioxide using oxygen in the presence of a
vanadium(V) oxide catalyst.
(2) 2 SO2 + O2(g) → 2 SO3(g) (in presence of V2O5)
Finally the sulfur trioxide is treated with water (usually as 97-98% H2SO4
containing 2-3% water) to produce 98-99% sulfuric acid.
(3) SO3(g) + H2O(l) → H2SO4(l)
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Affecting of a Catalytic Process
• Temperature
• Pressure
• Concentration of substrate
• Amount of catalyzer
• Ionic strenght
• pH
• Activator
• Inhibitors
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Principles of catalysis
A catalyst works by providing an alternative reaction pathway to the reaction
product.
The rate of the reaction is increased (decreased) as this alternative route has a
lower (higher) activation energy than the reaction route not mediated by the
catalyst.
Catalysts do not change the favorableness of a reaction: they have no effect on
the chemical equilibrium of a reaction because the rate of both the forward and
the reverse reaction are both affected
2 H2O2 → 2 H2O + O2 (ultraviolet radiation, Fe3+, ..)
• Fe2+ + H2O2 → Fe3+ + OH· + OH− (Fenton reaction)
• Fe3+ + H2O2 → Fe2+ + OOH· + H+
Catalysis impacts the environment by increasing the efficiency of industrial
processes, but catalysis also directly plays a direct role in the environment. A
notable example is the catalytic role of Chlorine free radicals in the break down of
ozone. These radicals are formed by the action of ultraviolet radiation on
chlorofluorocarbons (CFCs).
Cl· + O3 → ClO· + O2
ClO· + O· → Cl· + O2
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Examples of catalyst activities
Decomposition of 2 mols of H2O2 to 2 H2O and O2
Ea [kJ . mol-1]
Uncatalyzed reaction
75
Catalyzed by colloid platinum (inorganic)
49
Catalyzed by enzyme catalase
8

Speeding up of the reaction at constant temperature approximately 10 times,
decrease of activation energy
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Catalytic cycle
term for a multistep reaction mechanism that involves a catalyst.
Reaction: A + B  C
Pre-catalyst  Catalyst (Initiation)
Compound_A + Catalyst  Compound_A_Catalyst
Compound_A_Catalyst + Compound_B  Compound_A_B_Catalyst
Compound_A_B_Catalyst  Product_C_Catalyst
Product_C_Catalyst  Product_C +Catalyst
Precatalysts: For example, Wilkinson's catalyst RhCl(PPh3)3 loses one
triphenylphosphine ligand before entering the true catalytic cycle. Precatalysts
are easier to store but are easily activated in situ. Because of this preactivation
step, many catalytic reactions involve an induction period.
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Catalysis
 The chemical nature of catalysts is as diverse as catalysis itself, although
some generalizations can be made.
 Proton acids are probably the most widely used catalysts, especially for
the many reactions involving water, including hydrolyses and its reverse.
 Multifunctional solids often are catalytically active, e.g. zeolites, alumina,
certain forms of graphitic carbon.
 Transition metals are often used to catalyze redox reactions (oxidation,
hydrogenation).
 Many catalytic processes, especially those involving hydrogen, require
platinum metals.
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Catalysis
Catalysts:
a) positive
b) negative (inhibitors)
Catalyst (depending on whether a catalyst exists in the same
phase as the substrate):
a) homogeneous
b) Heterogeneous
e.g., Pt-catalyst in cars or 2HI(g) =(Pt-catalyst)= H2 (g) +I2 (g)
(catalysis of the reaction in gaseous phase on the solid catalyzer)
or 2HI(g) =(Pt-catalyst)= H2 (g) +I2 (g)
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Active site
The active site of an catalyst (enzyme) contains the catalytic and binding sites
(hydrogen bridges, electrostatic attraction, hydrophobic reactions, van der Waals
forces).
The structure and chemical properties of the active site allow the recognition and
binding of the substrate.
The active site is usually a small pocket at the surface of the catalyst (enzyme) that
contains residues responsible for the substrate specificity (charge, hydrophobicity,
steric hindrance) and catalytic residues, which often act as proton donors or
acceptors or are responsible for binding a cofactor such as PLP, TPP or NAD. The
active site is also the site of inhibition of the catalyst (enzymes).
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Allosteric catalysts (enzymes)
Allosteric catalysts (enzymes) are enzymes that change their shape, or
conformation, upon binding of a modulator. The word allosteric comes from the
Greek allos,'other' and 'stereos', 'shape'. An allosteric enzyme is an oligomer whose
biological activity is affected by altering the conformation(s) of its tertiary structure.
Allosteric enzymes tend to have several subunits. In some cases the regulatory
site(s) and the active site are on separate subunits.
Allosteric enzymes are regulatory enzymes.
Allosteric enzymes unlike all other enzymes do not have a Km value.
An allosteric effector is a substance that modifies the behavior of an allosteric
enzyme; it may be an allosteric inhibitor or allosteric activator.
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Cofactors

A cofactor is a non-protein chemical compound that is bound (either tightly or
loosely) to an enzyme

is essentially required for catalysis.

Transfer of some atoms, groups of atoms or elelectrons in reactions
catalyzed by enzymes.
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Non-protein parts of Enzymes
Cofactors:
essential for activity of enzymes
A) coenzymes (related to vitamins) –
 non covalent bond
 small organic non-protein molecules that carry
chemical groups between enzymes
 Regeneration in reaction with an other apoenzyme
B) prosthetic group (hem)
 covalent bond
 non-protein (non-amino acid) component of a
conjugated protein that is important in the protein's
biological activity

Regeneration in reaction with a different substrate
C) Metal ions
Protein part of enzyme – apoenzyme
Catalytically active enzyme – holoenzyme
Apoenzyme + cofactor = holoenzyme.
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Cofactors
Cofactors
Enzymes
Coenzymes
Thiamine pyrophosphate (TPP)
Flavin adenine dinucleotide (FAD)
Nicotinamide adenine dinucleotide (NAD+)
Pyridoxalphosphate (PLP)
Coenzyme A (CoA)
Biotine
5'- Deoxyadenosyl cobalamin
Tetrahydropholate
Pyruvate dehydrogenase
Monoaminoxidase
Laktátdehydrogenase
Glykogenfosforylase
Acetyl CoAkarboxylase
Paruvate carboxylase
Methylmalonylmutase
Thymidylatsynthase
Metals (activators)
Zn2+
Zn2+
Mg2+
Ni2+
Mo
Se
Mn2+
K+
Carbonatanhydrase
Carboxypeptidase
Hexokinase
Urease
Nitratereduktase
Glutathionperoxidase
Superoxiddismutase
Propionyl CoA karboxylase
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Autocatalysis
A single chemical reaction is said to have undergone autocatalysis, or be
autocatalytic, if the reaction product is itself the catalyst for that reaction.
Examples:
•
Tin pest
•
Reaction of Permanganate with Oxalic Acid
•
Vinegar syndrome
•
Binding of oxygen by hemoglobin
•
The spontaneous degradation of aspirin into salicylic acid and
acetic acid, causing very old aspirin in sealed containers to smell
mildly of vinegar.
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Measurement of the Catalytic Activity
SI unit: 1 katal (abbreviation 1 kat) [mol.s-1]; l0-6 kat = µkat; l0-9 kat = nkat
for expressing quantity values of catalytic activity of enzymes and other catalysts
Catalytic transformation of 1 Mol of substrate in 1 Second.
1 International unit (abbreviation 1 IU) [mol.s-1]; IU=16,67 nkat 60 IU=1 µkat
Amount of enzyme activity which catalyzes transformation of 1 mol of substrate in
1 minute; l0-3 IU = mU
The precise definition of one IU differs from substance to substance and is established by
international agreement for each substance. There is no equivalence among different
substances; for instance, one IU of vitamin E does not contain the same number of
milligrams as one IU of vitamin A.
The activity of a catalyst can also be described by the turn over number (or TON)
and the catalytic efficiency by the turn over frequency (TOF). The biochemical
equivalent is the enzyme unit.
Turnover number (also termed kcat) is defined as the maximum number of
molecules of substrate that an enzyme can convert to product per catalytic site per
unit time.
kcat = Vmax/[E]T.
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Catalyst Carrier – Stationary phase
To increase the effectivity of the catalytic process the catalyst is distributed on a
catalyst carrier (stationary phase). It is characterized by very large area.
For Example:
Silica Gel: high surface area (around 800 m²/g)
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Reaction rate
E  S 
 ES
k1 , k 1
k 1  k 2
Km 
k1
k2

E  P
Michaelis constant Km
dP
[S]
 vo  Vmax
dt
[S]  K m
Michaelis–Menten equation
The rate of production of the product, is referred to as the reaction
rate, V in enzyme kinetics.
Vmax = maximal rate for the given catalyst concentration
(Double) Reciprocal expression
K
1
1
1

 m 
v0 Vmax Vmax [S]
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Graphical expression of
Michaelis–Menten equation
1st order
kinetic
vo
[S]  K m  vo  Vmax
0 order
kinetic
Vmax
Vmax
2
vo  Vmax
[S]
[S] V
[S]
Vmax K  max
v2o 
[S]  [S]
2[Sm]
Vmax
[S]
[S] Vmax
 Vmax

[S]  [S]
2[S] 2
Area
of catalyst
enzym
nasycen
saturation by a
substrátem
substrate
[S] mol/l
Km
Basic Med. Chem.
[S]
[S]
 Vmax
 Vmax  k[S]0
[S]  K m
[S]
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Reaction rate in Linearized Graph
1/vo
Km 1
1
1



v0 Vmax Vmax [S]
1/v0 vs. [S]
1 / V m ax
1/[S]
- 1 / Km
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Reaction rate in Linearized Graph
1/vo
Km 1
1
1



v0 Vmax Vmax [S]
1/v0 vs. [S]
1 / V m ax
1/[S]
- 1 / Km
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Competitive inhibition
Some molecules inhibit catalysis by competing for the active sites. The
strongest inhibitors are called poisons.
CH3OH  HCOOH
C2H5OH  CH3COOH
Alcohol dehydrogenase
The catalyst is competitively inhibited by a non-toxic substrate to the
prejudice of toxic substrate



The maximal rate is reached at higher [S] values
Vmax is not changed
Km is increased
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Competitive inhibition
Vmax
1/vo
vo
1 / Vmax 1 / Vmax
[S]-1
Km Km inh
Basic Med. Chem.
[S]
mol.l-1
- 1/Km - 1/Km
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Non-competitive inhibition

The inhibitor (substrate) binds to the enzyme at a site other than the
catalyst's active site (this other site is called an allosteric site).

Km is not changed (active site is free for the substate)

Vmax is decreased, because the concentration of E-S complex decreases

In this mode of inhibition, there is no competition between the
inhibitor and the substrate, so increasing the concentration of the
substrate still does not allow the maximum enzyme activity rate to be
reached.
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Non-competitive inhibition

The inhibitor (substrate) binds to the enzyme at a site other than the
catalyst's active site (this other site is called an allosteric site).

Km is not changed (active site is free for the substrate)

Vmax is decreased, because the concentration of E-S complex decreases

In this mode of inhibition, there is no competition between the
inhibitor and the substrate, so increasing the concentration of the
substrate still does not allow the maximum enzyme activity rate to be
reached.
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Non-competitive inhibition
v0
Vmax
1/vo
Vmax inh
1 / Vmax inh
1 / Vmax
1/[S]
Km
Km inh
Basic Med. Chem.
[S] mol.l-1
- 1 / Km
- 1 / Km
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