Enzyme catalysis

From Wikipedia, the free encyclopedia

 

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Visualization of ubiquitylation

Enzyme catalysis is the increase in the rate of a chemical reaction by the active site of a protein. The protein catalyst (enzyme) may be part of a multi-subunit complex, and/or may transiently or permanently associate with a Cofactor (e.g. adenosine triphosphate). Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions at room temperature and pressure. A key driver of protein evolution is the optimization of such catalytic activities via protein dynamics.^[1]

The mechanism of enzyme catalysis is similar in principle to other types of chemical catalysis. By providing an alternative reaction route the enzyme reduces the energy required to reach the highest energy transition state of the reaction. The reduction of activation energy (Ea) increases the amount of reactant molecules that achieve a sufficient level of energy, such that they reach the activation energy and form the product. As with other catalysts, the enzyme is not consumed during the reaction (as a substrate is) but is recycled such that a single enzyme performs many rounds of catalysis.

Induced fit

Enzyme changes shape by induced fit upon substrate binding to form enzyme-substrate complex. Hexokinase has a large induced fit motion that closes over the substrates adenosine triphosphate and xylose. Binding sites in blue, substrates in black and Mg²⁺ cofactor in yellow. (PDB: 2E2N​, 2E2Q​)

 

The different mechanisms of substrate binding

The favored model for the enzyme-substrate interaction is the induced fit model.^[2] This model proposes that the initial interaction between enzyme and substrate is relatively weak, but that these weak interactions rapidly induce conformational changes in the enzyme that strengthen binding.

The advantages of the induced fit mechanism arise due to the stabilizing effect of strong enzyme binding. There are two different mechanisms of substrate binding: uniform binding, which has strong substrate binding, and differential binding, which has strong transition state binding. The stabilizing effect of uniform binding increases both substrate and transition state binding affinity, while differential binding increases only transition state binding affinity. Both are used by enzymes and have been evolutionarily chosen to minimize the activation energy of the reaction. Enzymes that are saturated, that is, have a high affinity substrate binding, require differential binding to reduce the energy of activation, whereas small substrate unbound enzymes may use either differential or uniform binding.^[3]

These effects have led to most proteins using the differential binding mechanism to reduce the energy of activation, so most substrates have high affinity for the enzyme while in the transition state. Differential binding is carried out by the induced fit mechanism - the substrate first binds weakly, then the enzyme changes conformation increasing the affinity to the transition state and stabilizing it, so reducing the activation energy to reach it.

It is important to clarify, however, that the induced fit concept cannot be used to rationalize catalysis. That is, the chemical catalysis is defined as the reduction of Ea^‡ (when the system is already in the ES^‡) relative to Ea^‡ in the uncatalyzed reaction in water (without the enzyme). The induced fit only suggests that the barrier is lower in the closed form of the enzyme but does not tell us what the reason for the barrier reduction is.

Induced fit may be beneficial to the fidelity of molecular recognition in the presence of competition and noise via the conformational proofreading mechanism .^[4]

Mechanisms of an alternative reaction route

These conformational changes also bring catalytic residues in the active site close to the chemical bonds in the substrate that will be altered in the reaction. After binding takes place, one or more mechanisms of catalysis lowers the energy of the reaction's transition state, by providing an alternative chemical pathway for the reaction. There are six possible mechanisms of "over the barrier" catalysis as well as a "through the barrier" mechanism:

Proximity and orientation

Enzyme-substrate interactions align the reactive chemical groups and hold them close together in an optimal geometry, which increases the rate of the reaction. This reduces the entropy of the reactants and thus makes addition or transfer reactions less unfavorable, since a reduction in the overall entropy when two reactants become a single product.

This effect is analogous to an effective increase in concentration of the reagents. The binding of the reagents to the enzyme gives the reaction intramolecular character, which gives a massive rate increase.

For example:

Similar reactions will occur far faster if the reaction is intramolecular.

The effective concentration of acetate in the intramolecular reaction can be estimated as k2/k1 = 2 x 105 Molar.

However, the situation might be more complex, since modern computational studies have established that traditional examples of proximity effects cannot be related directly to enzyme entropic effects.^[5][6][7] Also, the original entropic proposal^[8] has been found to largely overestimate the contribution of orientation entropy to catalysis.^[9]

Proton donors or acceptors

Proton donors and acceptors, i.e. acids and base may donate and accept protons in order to stabilize developing charges in the transition state.This typically has the effect of activating nucleophile and electrophile groups, or stabilizing leaving groups. Histidine is often the residue involved in these acid/base reactions, since it has a pKa close to neutral pH and can therefore both accept and donate protons.
Many reaction mechanisms involving acid/base catalysis assume a substantially altered pKa. This alteration of pKa is possible through the local environment of the residue.

Conditions	Acids	Bases
Hydrophobic environment	Increase pKa	Decrease pKa
Adjacent residues of like charge	Increase pKa	Decrease pKa
Salt bridge (and hydrogen bond) formation	Decrease pKa	Increase pKa

pKa can also be influenced significantly by the surrounding environment, to the extent that residues which are basic in solution may act as proton donors, and vice versa.

For example:

Catalytic triad of a serine protease

The initial step of the serine protease catalytic mechanism involves the histidine of the active site accepting a proton from the serine residue. This prepares the serine as a nucleophile to attack the amide bond of the substrate. This mechanism includes donation of a proton from serine (a base, pKa 14) to histidine (an acid, pKa 6), made possible due to the local environment of the bases.

It is important to clarify that the modification of the pKa’s is a pure part of the electrostatic mechanism.^[10] Furthermore, the catalytic effect of the above example is mainly associated with the reduction of the pKa of the oxyanion and the increase in the pKa of the histidine, while the proton transfer from the serine to the histidine is not catalyzed significantly, since it is not the rate determining barrier.^[11]

Electrostatic catalysis

Stabilization of charged transition states can also be by residues in the active site forming ionic bonds (or partial ionic charge interactions) with the intermediate. These bonds can either come from acidic or basic side chains found on amino acids such as lysine, arginine, aspartic acid or glutamic acid or come from metal cofactors such as zinc. Metal ions are particularly effective and can reduce the pKa of water enough to make it an effective nucleophile.

Systematic computer simulation studies established that electrostatic effects give, by far, the largest contribution to catalysis.^[10] In particular, it has been found that enzyme provides an environment which is more polar than water, and that the ionic transition states are stabilized by fixed dipoles. This is very different from transition state stabilization in water, where the water molecules must pay with "reorganization energy".^[12] In order to stabilize ionic and charged states. Thus, the catalysis is associated with the fact that the enzyme polar groups are preorganized ^[13]

The magnitude of the electrostatic field exerted by an enzyme's active site has been shown to be highly correlated with the enzyme's catalytic rate enhancement^[14][15]

Binding of substrate usually excludes water from the active site, thereby lowering the local dielectric constant to that of an organic solvent. This strengthens the electrostatic interactions between the charged/polar substrates and the active sites. In addition, studies have shown that the charge distributions about the active sites are arranged so as to stabilize the transition states of the catalyzed reactions. In several enzymes, these charge distributions apparently serve to guide polar substrates toward their binding sites so that the rates of these enzymatic reactions are greater than their apparent diffusion-controlled limits.

For example:

Carboxypeptidase catalytic mechanism

The tetrahedral intermediate is stabilised by a partial ionic bond between the Zn2+ ion and the negative charge on the oxygen.

 

Covalent catalysis

Covalent catalysis involves the substrate forming a transient covalent bond with residues in the enzyme active site or with a cofactor. This adds an additional covalent intermediate to the reaction, and helps to reduce the energy of later transition states of the reaction. The covalent bond must, at a later stage in the reaction, be broken to regenerate the enzyme. This mechanism is utilised by the catalytic triad of enzymes such as proteases like chymotrypsin and trypsin, where an acyl-enzyme intermediate is formed. An alternative mechanism is schiff base formation using the free amine from a lysine residue, as seen in the enzyme aldolase during glycolysis.

Some enzymes utilize non-amino acid cofactors such as pyridoxal phosphate (PLP) or thiamine pyrophosphate (TPP) to form covalent intermediates with reactant molecules.^[16][17] Such covalent intermediates function to reduce the energy of later transition states, similar to how covalent intermediates formed with active site amino acid residues allow stabilization, but the capabilities of cofactors allow enzymes to carryout reactions that amino acid side residues alone could not. Enzymes utilizing such cofactors include the PLP-dependent enzyme aspartate transaminase and the TPP-dependent enzyme pyruvate dehydrogenase.^[18][19]

Rather than lowering the activation energy for a reaction pathway, covalent catalysis provides an alternative pathway for the reaction (via to the covalent intermediate) and so is distinct from true catalysis.^[10] For example, the energetics of the covalent bond to the serine molecule in chymotrypsin should be compared to the well-understood covalent bond to the nucleophile in the uncatalyzed solution reaction. A true proposal of a covalent catalysis (where the barrier is lower than the corresponding barrier in solution) would require, for example, a partial covalent bond to the transition state by an enzyme group (e.g., a very strong hydrogen bond), and such effects do not contribute significantly to catalysis.

Metal ion catalysis

A metal ion in the active site participates in catalysis by coordinating charge stabilization and shielding. Because of a metal's positive charge, only negative charges can be stabilized through metal ions.^[20] However, metal ions are advantageous in biological catalysis because they are not affected by changes in pH.^[21] Metal ions can also act to ionize water by acting as a Lewis acid.^[22] Metal ions may also be agents of oxidation and reduction.^[23]

Bond strain

This is the principal effect of induced fit binding, where the affinity of the enzyme to the transition state is greater than to the substrate itself. This induces structural rearrangements which strain substrate bonds into a position closer to the conformation of the transition state, so lowering the energy difference between the substrate and transition state and helping catalyze the reaction.

However, the strain effect is, in fact, a ground state destabilization effect, rather than transition state stabilization effect.^{[10][24][page needed]} Furthermore, enzymes are very flexible and they cannot apply large strain effect.^[25]

In addition to bond strain in the substrate, bond strain may also be induced within the enzyme itself to activate residues in the active site.

For example:

Substrate, bound substrate, and transition state conformations of lysozyme.

The substrate, on binding, is distorted from the half chair conformation of the hexose ring (because of the steric hindrance with amino acids of the protein forcing the equatorial c6 to be in the axial position) into the chair conformation[26][page needed]

 

Quantum tunneling

These traditional "over the barrier" mechanisms have been challenged in some cases by models and observations of "through the barrier" mechanisms (quantum tunneling). Some enzymes operate with kinetics which are faster than what would be predicted by the classical ΔG^‡. In "through the barrier" models, a proton or an electron can tunnel through activation barriers.^[27][28] Quantum tunneling for protons has been observed in tryptamine oxidation by aromatic amine dehydrogenase.^[29]

Interestingly, quantum tunneling does not appear to provide a major catalytic advantage, since the tunneling contributions are similar in the catalyzed and the uncatalyzed reactions in solution.^{[28][30][31][32]} However, the tunneling contribution (typically enhancing rate constants by a factor of ~1000^[29] compared to the rate of reaction for the classical 'over the barrier' route) is likely crucial to the viability of biological organisms. This emphasizes the general importance of tunneling reactions in biology.

In 1971-1972 the first quantum-mechanical model of enzyme catalysis was formulated.^{[33][34][third-party source needed]}

Active enzyme

The binding energy of the enzyme-substrate complex cannot be considered as an external energy which is necessary for the substrate activation. The enzyme of high energy content may firstly transfer some specific energetic group X₁ from catalytic site of the enzyme to the final place of the first bound reactant, then another group X₂ from the second bound reactant (or from the second group of the single reactant) must be transferred to active site to finish substrate conversion to product and enzyme regeneration.^[35]

We can present the whole enzymatic reaction as a two coupling reactions:

${\displaystyle {\ce {{S1}+ EX1 -> S1EX1 -> {P1}+ EP2}}}$

(1)

${\displaystyle {\ce {{S2}+ EP2 -> S2EP2 -> {P2}+ EX2}}}$

(2)

It may be seen from reaction (1) that the group X₁ of the active enzyme appears in the product due to possibility of the exchange reaction inside enzyme to avoid both electrostatic inhibition and repulsion of atoms. So we represent the active enzyme as a powerful reactant of the enzymatic reaction. The reaction (2) shows incomplete conversion of the substrate because its group X₂ remains inside enzyme. This approach as idea had formerly proposed relying on the hypothetical extremely high enzymatic conversions (catalytically perfect enzyme).^[36]

The crucial point for the verification of the present approach is that the catalyst must be a complex of the enzyme with the transfer group of the reaction. This chemical aspect is supported by the well-studied mechanisms of the several enzymatic reactions. Let us consider the reaction of peptide bond hydrolysis catalyzed by a pure protein α-chymotrypsin (an enzyme acting without a cofactor), which is a well-studied member of the serine proteases family, see.^[37]

We present the experimental results for this reaction as two chemical steps:

${\displaystyle {\ce {{S1}+ EH -> {P1}+ EP2}}}$

(3)

${\displaystyle {\ce {{EP2}+ {H-O-H}-> {EH}+ P2}}}$

(4)

where S₁ is a polypeptide, P₁ and P₂ are products. The first chemical step (3) includes the formation of a covalent acyl-enzyme intermediate. The second step (4) is the deacylation step. It is important to note that the group H+, initially found on the enzyme, but not in water, appears in the product before the step of hydrolysis, therefore it may be considered as an additional group of the enzymatic reaction.

Thus, the reaction (3) shows that the enzyme acts as a powerful reactant of the reaction. According to the proposed concept, the H transport from the enzyme promotes the first reactant conversion, breakdown of the first initial chemical bond (between groups P₁ and P₂). The step of hydrolysis leads to a breakdown of the second chemical bond and regeneration of the enzyme.

The proposed chemical mechanism does not depend on the concentration of the substrates or products in the medium. However, a shift in their concentration mainly causes free energy changes in the first and final steps of the reactions (1) and (2) due to the changes in the free energy content of every molecule, whether S or P, in water solution. This approach is in accordance with the following mechanism of muscle contraction. The final step of ATP hydrolysis in skeletal muscle is the product release caused by the association of myosin heads with actin.^[38] The closing of the actin-binding cleft during the association reaction is structurally coupled with the opening of the nucleotide-binding pocket on the myosin active site.^[39]

Notably, the final steps of ATP hydrolysis include the fast release of phosphate and the slow release of ADP.^[40][41] The release of a phosphate anion from bound ADP anion into water solution may be considered as an exergonic reaction because the phosphate anion has low molecular mass.

Thus, we arrive at the conclusion that the primary release of the inorganic phosphate H₂PO₄⁻ leads to transformation of a significant part of the free energy of ATP hydrolysis into the kinetic energy of the solvated phosphate, producing active streaming. This assumption of a local mechano-chemical transduction is in accord with Tirosh’s mechanism of muscle contraction, where the muscle force derives from an integrated action of active streaming created by ATP hydrolysis.^[42][43]

Examples of catalytic mechanisms

In reality, most enzyme mechanisms involve a combination of several different types of catalysis.

Triose phosphate isomerase

Triose phosphate isomerase (EC 5.3.1.1) catalyses the reversible interconvertion of the two triose phosphates isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.

Trypsin

Trypsin (EC 3.4.21.4) is a serine protease that cleaves protein substrates after lysine or arginine residues using a catalytic triad to perform covalent catalysis, and an oxyanion hole to stabilise charge-buildup on the transition states.

Aldolase

Aldolase (EC 4.1.2.13) catalyses the breakdown of fructose 1,6-bisphosphate (F-1,6-BP) into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP).

Enzyme diffusivity

The advent of single-molecule studies led in the 2010s to the observation that the movement of untethered enzymes increases with increasing substrate concentration and increasing reaction enthalpy.^[44] Subsequent observations suggest that this increase in diffusivity is driven by transient displacement of the enzyme's center of mass, resulting in a "recoil effect that propels the enzyme".^[45]

Reaction similarity

Similarity between enzymatic reactions (EC) can be calculated by using bond changes, reaction centres or substructure metrics (EC-BLAST).^[46]

Catalysis

From Wikipedia, the free encyclopedia

An air filter that utilizes low-temperature oxidation catalyst used to convert carbon monoxide to less toxic carbon dioxide at room temperature. It can also remove formaldehyde from the air.

Catalysis (/kəˈtælɪsɪs/) is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst^[1] (/ˈkætəlɪst/), which is not consumed in the catalyzed reaction and can continue to act repeatedly. Often only tiny amounts of catalyst are required in principle.^[2]

In general, the reactions occur faster with a catalyst because they require less activation energy. In catalyzed mechanisms, the catalyst usually reacts to form a temporary intermediate which then regenerates the original catalyst in a cyclic process.

Catalysts may be classified as either homogeneous or heterogeneous. A homogeneous catalyst is one whose molecules are dispersed in the same phase (usually gaseous or liquid) as the reactant molecules. A heterogeneous catalyst is one whose molecules are not in the same phase as the reactants, which are typically gases or liquids that are adsorbed onto the surface of the solid catalyst. Enzymes and other biocatalysts are often considered as a third category.

Technical perspective

In the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change.^[1] A catalyst may participate in multiple chemical transformations. The effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons (which reduce the catalytic activity) or promoters (which increase the activity and also affect the temperature of the reaction).^[1]

Catalyzed reactions have a lower activation energy (rate-limiting free energy of activation) than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature and for the same reactant concentrations. However, the detailed mechanics of catalysis is complex. Catalysts may affect the reaction environment favorably(like heat), or bind to the reagents to polarize bonds, e.g. acid catalysts for reactions of carbonyl compounds, or form specific intermediates that are not produced naturally, such as osmate esters in osmium tetroxide-catalyzed dihydroxylation of alkenes, or cause dissociation of reagents to reactive forms, such as chemisorbed hydrogen in catalytic hydrogenation.

Kinetically, catalytic reactions are typical chemical reactions; i.e. the reaction rate depends on the frequency of contact of the reactants in the rate-determining step. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst and its "activity". In heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst. Analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts.

Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, or destroyed by secondary processes. In heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a solid–liquid system or sublimate in a solid–gas system.

Background

The production of most industrially important chemicals involves catalysis. Similarly, most biochemically significant processes are catalysed. Research into catalysis is a major field in applied science and involves many areas of chemistry, notably organometallic chemistry and materials science. Catalysis is relevant to many aspects of environmental science, e.g. the catalytic converter in automobiles and the dynamics of the ozone hole. Catalytic reactions are preferred in environmentally friendly green chemistry due to the reduced amount of waste generated,^[3] as opposed to stoichiometric reactions in which all reactants are consumed and more side products are formed. Many transition metals and transition metal complexes are used in catalysis as well. Catalysts called enzymes are important in biology.

A catalyst works by providing an alternative reaction pathway to the reaction product. The rate of the reaction is increased as this alternative route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below.

2 H₂O₂ → 2 H₂O + O₂

This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available. This reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms. Upon the addition of a small amount of manganese dioxide, the hydrogen peroxide reacts rapidly. This effect is readily seen by the effervescence of oxygen.^[4] The manganese dioxide is not consumed in the reaction, and thus may be recovered unchanged, and re-used indefinitely. Accordingly, manganese dioxide catalyses this reaction.^[5]

General principles

Units

Catalytic activity is usually denoted by the symbol z ^[6] and measured in mol/s, a unit which was called katal and defined the SI unit for catalytic activity since 1999. Catalytic activity is not a kind of reaction rate, but a property of the catalyst under certain conditions, in relation to a specific chemical reaction. Catalytic activity of one katal (Symbol 1 kat = 1 mol/s) of a catalyst means one mole of that catalyst (substance, in Mol) will catalyse 1 mole of the reactant to product in one second. A catalyst may and usually will have different catalytic activity for distinct reactions. See katal for an example.

There are further derived SI units related to catalytic activity, see the above reference for details.

Typical mechanism

Catalysts generally react with one or more reactants to form intermediates that subsequently give the final reaction product, in the process regenerating the catalyst. The following is a typical reaction scheme, where C represents the catalyst, X and Y are reactants, and Z is the product of the reaction of X and Y:

X + C → XC

(1)

Y + XC → XYC

(2)

XYC → CZ

(3)

CZ → C + Z

(4)

Although the catalyst is consumed by reaction 1, it is subsequently produced by reaction 4, so it does not occur in the overall reaction equation:

X + Y → Z

As a catalyst is regenerated in a reaction, often only small amounts are needed to increase the rate of the reaction. In practice, however, catalysts are sometimes consumed in secondary processes.

The catalyst does usually appear in the rate equation. For example, if the rate-determining step in the above reaction scheme is the first step

X + C → XC, the catalyzed reaction will be second order with rate equation v = k_cat[X][C], which is proportional to the catalyst concentration [C]. However [C] remains constant during the reaction so that the catalyzed reaction is pseudo-first order: v = k_obs[X], where k_obs = k_cat[C].

As an example of a detailed mechanism at the microscopic level, in 2008 Danish researchers first revealed the sequence of events when oxygen and hydrogen combine on the surface of titanium dioxide (TiO₂, or titania) to produce water. With a time-lapse series of scanning tunneling microscopy images, they determined the molecules undergo adsorption, dissociation and diffusion before reacting. The intermediate reaction states were: HO₂, H₂O₂, then H₃O₂ and the final reaction product (water molecule dimers), after which the water molecule desorbs from the catalyst surface.^[7][8]

Reaction energetics

Generic potential energy diagram showing the effect of a catalyst in a hypothetical exothermic chemical reaction X + Y to give Z. The presence of the catalyst opens a different reaction pathway (shown in red) with a lower activation energy. The final result and the overall thermodynamics are the same.

Catalysts work by providing an (alternative) mechanism involving a different transition state and lower activation energy. Consequently, more molecular collisions have the energy needed to reach the transition state. Hence, catalysts can enable reactions that would otherwise be blocked or slowed by a kinetic barrier. The catalyst may increase reaction rate or selectivity, or enable the reaction at lower temperatures. This effect can be illustrated with an energy profile diagram.

In the catalyzed elementary reaction, catalysts do not change the extent 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 (see also thermodynamics). The second law of thermodynamics describes why a catalyst does not change the chemical equilibrium of a reaction. Suppose there was such a catalyst that shifted an equilibrium. Introducing the catalyst to the system would result in a reaction to move to the new equilibrium, producing energy. Production of energy is a necessary result since reactions are spontaneous only if Gibbs free energy is produced, and if there is no energy barrier, there is no need for a catalyst. Then, removing the catalyst would also result in reaction, producing energy; i.e. the addition and its reverse process, removal, would both produce energy. Thus, a catalyst that could change the equilibrium would be a perpetual motion machine, a contradiction to the laws of thermodynamics.^[9]

If a catalyst does change the equilibrium, then it must be consumed as the reaction proceeds, and thus it is also a reactant. Illustrative is the base-catalysed hydrolysis of esters, where the produced carboxylic acid immediately reacts with the base catalyst and thus the reaction equilibrium is shifted towards hydrolysis.

The SI derived unit for measuring the catalytic activity of a catalyst is the katal, which is moles per second. The productivity of a catalyst can be described by the turnover number (or TON) and the catalytic activity by the turn over frequency (TOF), which is the TON per time unit. The biochemical equivalent is the enzyme unit. For more information on the efficiency of enzymatic catalysis, see the article on enzymes.

The catalyst stabilizes the transition state more than it stabilizes the starting material. It decreases the kinetic barrier by decreasing the difference in energy between starting material and transition state. It does not change the energy difference between starting materials and products (thermodynamic barrier), or the available energy (this is provided by the environment as heat or light).

Materials

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 hydrolysis and its reverse. Multifunctional solids often are catalytically active, e.g. zeolites, alumina, higher-order oxides, graphitic carbon, nanoparticles, nanodots, and facets of bulk materials. Transition metals are often used to catalyze redox reactions (oxidation, hydrogenation). Examples are nickel, such as Raney nickel for hydrogenation, and vanadium(V) oxide for oxidation of sulfur dioxide into sulfur trioxide by the so-called contact process. Many catalytic processes, especially those used in organic synthesis, require "late transition metals", such as palladium, platinum, gold, ruthenium, rhodium, or iridium.

Some so-called catalysts are really precatalysts. Precatalysts convert to catalysts in the reaction. 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.

Chemical species that improve catalytic activity are called co-catalysts (cocatalysts) or promotors in cooperative catalysis.

Types

Catalysts can be heterogeneous or homogeneous, depending on whether a catalyst exists in the same phase as the substrate. Biocatalysts (enzymes) are often seen as a separate group.

Heterogeneous catalysts

The microporous molecular structure of the zeolite ZSM-5 is exploited in catalysts used in refineries

Zeolites are extruded as pellets for easy handling in catalytic reactors.

Heterogeneous catalysts act in a different phase than the reactants. Most heterogeneous catalysts are solids that act on substrates in a liquid or gaseous reaction mixture. Diverse mechanisms for reactions on surfaces are known, depending on how the adsorption takes place (Langmuir-Hinshelwood, Eley-Rideal, and Mars-van Krevelen).^[10] The total surface area of solid has an important effect on the reaction rate. The smaller the catalyst particle size, the larger the surface area for a given mass of particles.

A heterogeneous catalyst has active sites, which are the atoms or crystal faces where the reaction actually occurs. Depending on the mechanism, the active site may be either a planar exposed metal surface, a crystal edge with imperfect metal valence or a complicated combination of the two. Thus, not only most of the volume, but also most of the surface of a heterogeneous catalyst may be catalytically inactive. Finding out the nature of the active site requires technically challenging research. Thus, empirical research for finding out new metal combinations for catalysis continues.

For example, in the Haber process, finely divided iron serves as a catalyst for the synthesis of ammonia from nitrogen and hydrogen. The reacting gases adsorb onto active sites on the iron particles. Once physically adsorbed, the reagents undergo chemisorption that results in dissociation into adsorbed atomic species, and new bonds between the resulting fragments form in part due to their close proximity. In this way the particularly strong triple bond in nitrogen is broken, which would be extremely uncommon in the gas phase due to its high activation energy. Thus, the activation energy of the overall reaction is lowered, and the rate of reaction increases.^{[citation needed]} Another place where a heterogeneous catalyst is applied is in the oxidation of sulfur dioxide on vanadium(V) oxide for the production of sulfuric acid.

Heterogeneous catalysts are typically "supported," which means that the catalyst is dispersed on a second material that enhances the effectiveness or minimizes their cost. Supports prevent or reduce agglomeration and sintering of the small catalyst particles, exposing more surface area, thus catalysts have a higher specific activity (per gram) on a support. Sometimes the support is merely a surface on which the catalyst is spread to increase the surface area. More often, the support and the catalyst interact, affecting the catalytic reaction. Supports are porous materials with a high surface area, most commonly alumina, zeolites or various kinds of activated carbon. Specialized supports include silicon dioxide, titanium dioxide, calcium carbonate, and barium sulfate.

Electrocatalysts

In the context of electrochemistry, specifically in fuel cell engineering, various metal-containing catalysts are used to enhance the rates of the half reactions that comprise the fuel cell. One common type of fuel cell electrocatalyst is based upon nanoparticles of platinum that are supported on slightly larger carbon particles. When in contact with one of the electrodes in a fuel cell, this platinum increases the rate of oxygen reduction either to water, or to hydroxide or hydrogen peroxide.

Homogeneous catalysts

Homogeneous catalysts function in the same phase as the reactants, but the mechanistic principles involved in heterogeneous catalysis are generally applicable. Typically homogeneous catalysts are dissolved in a solvent with the substrates. One example of homogeneous catalysis involves the influence of H⁺ on the esterification of carboxylic acids, such as the formation of methyl acetate from acetic acid and methanol.^[11] One high-volume process requiring a homogeneous catalyst is hydroformylation, which adds carbon monoxide to an alkene to produce an alkyl aldehyde. The aldehyde can be converted to various products such as alcohols or acids (for e.g. detergents) or polyols (for plastics such as polycarbonate or polyurethane). For inorganic chemists, homogeneous catalysis is often synonymous with organometallic catalysts.^[12]

Organocatalysis

Whereas transition metals sometimes attract most of the attention in the study of catalysis, small organic molecules without metals can also exhibit catalytic properties, as is apparent from the fact that many enzymes lack transition metals. Typically, organic catalysts require a higher loading (amount of catalyst per unit amount of reactant, expressed in mol% amount of substance) than transition metal(-ion)-based catalysts, but these catalysts are usually commercially available in bulk, helping to reduce costs. In the early 2000s, these organocatalysts were considered "new generation" and are competitive to traditional metal(-ion)-containing catalysts. Organocatalysts are supposed to operate akin to metal-free enzymes utilizing, e.g., non-covalent interactions such as hydrogen bonding. The discipline organocatalysis is divided in the application of covalent (e.g., proline, DMAP) and non-covalent (e.g., thiourea organocatalysis) organocatalysts referring to the preferred catalyst-substrate binding and interaction, respectively.

Photocatalysts

Photocatalysis is the phenomenon where the catalyst can receive light (such as visible light), be promoted to an excited state, and then undergo intersystem crossing with the starting material, returning to ground state without being consumed. The excited state of the starting material will then undergo reactions it ordinarily could not if directly illuminated. For example, singlet oxygen is usually produced by photocatalysis. Photocatalysts are also the main ingredient in dye-sensitized solar cells.

Enzymes and biocatalysts

In biology, enzymes are protein-based catalysts in metabolism and catabolism. Most biocatalysts are enzymes, but other non-protein-based classes of biomolecules also exhibit catalytic properties including ribozymes, and synthetic deoxyribozymes.^[13]

Biocatalysts can be thought of as intermediate between homogeneous and heterogeneous catalysts, although strictly speaking soluble enzymes are homogeneous catalysts and membrane-bound enzymes are heterogeneous. Several factors affect the activity of enzymes (and other catalysts) including temperature, pH, concentration of enzyme, substrate, and products. A particularly important reagent in enzymatic reactions is water, which is the product of many bond-forming reactions and a reactant in many bond-breaking processes.

In biocatalysis, enzymes are employed to prepare many commodity chemicals including high-fructose corn syrup and acrylamide.

Some monoclonal antibodies whose binding target is a stable molecule which resembles the transition state of a chemical reaction can function as weak catalysts for that chemical reaction by lowering its activation energy.^[14] Such catalytic antibodies are sometimes called "abzymes".

Nanocatalysts

Nanocatalysts are nanomaterials with catalytic activities. They have been extensively explored for wide range of applications. Among them, the nanocatalysts with enzyme mimicking activities are collectively called as nanozymes.^[15]

Tandem catalysis

In tandem catalysis two or more different catalysts are coupled in a one-pot reaction.

Autocatalysis

In autocatalysis the catalyst is a product of the overall reaction, in contrast to all other types of catalysis considered in this article. The simplest example of autocatalysis is a reaction of type A + B → 2 B, in one or in several steps. The overall reaction is just A → B, so that B is a product. But since B is also a reactant, it may be present in the rate equation and affect the reaction rate. As the reaction proceeds, the concentration of B increases and can accelerate the reaction as a catalyst. In effect, the reaction accelerates itself or is autocatalyzed.

A real example is the hydrolysis of an ester such as aspirin to a carboxylic acid and an alcohol. In the absence of added acid catalysts, the carboxylic acid product catalyzes the hydrolysis.

Significance

Left: Partially caramelised cube sugar, Right: burning cube sugar with ash as catalyst

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A Ti-Cr-Pt tube (~40 μm long) releases oxygen bubbles when immersed in hydrogen peroxide (via catalytic decomposition), forming a micropump.^[16]

Estimates are that 90% of all commercially produced chemical products involve catalysts at some stage in the process of their manufacture.^[17] In 2005, catalytic processes generated about $900 billion in products worldwide.^[18] Catalysis is so pervasive that subareas are not readily classified. Some areas of particular concentration are surveyed below.

Energy processing

Petroleum refining makes intensive use of catalysis for alkylation, catalytic cracking (breaking long-chain hydrocarbons into smaller pieces), naphtha reforming and steam reforming (conversion of hydrocarbons into synthesis gas). Even the exhaust from the burning of fossil fuels is treated via catalysis: Catalytic converters, typically composed of platinum and rhodium, break down some of the more harmful byproducts of automobile exhaust.

2 CO + 2 NO → 2 CO₂ + N₂

With regard to synthetic fuels, an old but still important process is the Fischer-Tropsch synthesis of hydrocarbons from synthesis gas, which itself is processed via water-gas shift reactions, catalysed by iron. Biodiesel and related biofuels require processing via both inorganic and biocatalysts.

Fuel cells rely on catalysts for both the anodic and cathodic reactions.

Catalytic heaters generate flameless heat from a supply of combustible fuel.

Bulk chemicals

Some of the largest-scale chemicals are produced via catalytic oxidation, often using oxygen. Examples include nitric acid (from ammonia), sulfuric acid (from sulfur dioxide to sulfur trioxide by the contact process), terephthalic acid from p-xylene, and acrylonitrile from propane and ammonia.

Many other chemical products are generated by large-scale reduction, often via hydrogenation. The largest-scale example is ammonia, which is prepared via the Haber process from nitrogen. Methanol is prepared from carbon monoxide.

Bulk polymers derived from ethylene and propylene are often prepared via Ziegler-Natta catalysis. Polyesters, polyamides, and isocyanates are derived via acid-base catalysis.

Most carbonylation processes require metal catalysts, examples include the Monsanto acetic acid process and hydroformylation.

Fine chemicals

Many fine chemicals are prepared via catalysis; methods include those of heavy industry as well as more specialized processes that would be prohibitively expensive on a large scale. Examples include the Heck reaction, and Friedel–Crafts reactions.

Because most bioactive compounds are chiral, many pharmaceuticals are produced by enantioselective catalysis (catalytic asymmetric synthesis).

Food processing

One of the most obvious applications of catalysis is the hydrogenation (reaction with hydrogen gas) of fats using nickel catalyst to produce margarine.^[19] Many other foodstuffs are prepared via biocatalysis.

Environment

Catalysis impacts the environment by increasing the efficiency of industrial processes, but catalysis also plays a direct role in the environment. A notable example is the catalytic role of chlorine free radicals in the breakdown of ozone. These radicals are formed by the action of ultraviolet radiation on chlorofluorocarbons (CFCs).

Cl^· + O₃ → ClO^· + O₂

ClO^· + O^· → Cl^· + O₂

History

Generally speaking,^[20] anything that increases the rate of a process is a "catalyst", a term derived from Greek καταλύειν, meaning "to annul," or "to untie," or "to pick up." The concept of catalysis was invented by chemist Elizabeth Fulhame and described in a 1794 book, based on her novel work in oxidation-reduction experiments.^[21] The term catalysis was later used by Jöns Jakob Berzelius in 1835^[22] to describe reactions that are accelerated by substances that remain unchanged after the reaction. Fulhame, who predated Berzelius, did work with water as opposed to metals in her reduction experiments. Other 18th century chemists who worked in catalysis were Eilhard Mitscherlich^[23] who referred to it as contact processes, and Johann Wolfgang Döbereiner^[24][25] who spoke of contact action. He developed Döbereiner's lamp, a lighter based on hydrogen and a platinum sponge, which became a commercial success in the 1820s that lives on today. Humphry Davy discovered the use of platinum in catalysis.^[26] In the 1880s, Wilhelm Ostwald at Leipzig University started a systematic investigation into reactions that were catalyzed by the presence of acids and bases, and found that chemical reactions occur at finite rates and that these rates can be used to determine the strengths of acids and bases. For this work, Ostwald was awarded the 1909 Nobel Prize in Chemistry.^[27]

Inhibitors, poisons, and promoters

Substances that reduce the action of catalysts are called catalyst inhibitors if reversible, and catalyst poisons if irreversible. Promoters are substances that increase the catalytic activity, even though they are not catalysts by themselves.

Inhibitors are sometimes referred to as "negative catalysts" since they decrease the reaction rate.^[28] However the term inhibitor is preferred since they do not work by introducing a reaction path with higher activation energy; this would not reduce the rate since the reaction would continue to occur by the non-catalyzed path. Instead they act either by deactivating catalysts, or by removing reaction intermediates such as free radicals.^[28][29]

The inhibitor may modify selectivity in addition to rate. For instance, in the reduction of alkynes to alkenes, a palladium (Pd) catalyst partly "poisoned" with lead(II) acetate (Pb(CH₃CO₂)₂) can be used.^[30] Without the deactivation of the catalyst, the alkene produced would be further reduced to alkane.^[31][32]

The inhibitor can produce this effect by, e.g., selectively poisoning only certain types of active sites. Another mechanism is the modification of surface geometry. For instance, in hydrogenation operations, large planes of metal surface function as sites of hydrogenolysis catalysis while sites catalyzing hydrogenation of unsaturates are smaller. Thus, a poison that covers surface randomly will tend to reduce the number of uncontaminated large planes but leave proportionally more smaller sites free, thus changing the hydrogenation vs. hydrogenolysis selectivity. Many other mechanisms are also possible.

Promoters can cover up surface to prevent production of a mat of coke, or even actively remove such material (e.g., rhenium on platinum in platforming). They can aid the dispersion of the catalytic material or bind to reagents .

Current market

The global demand on catalysts in 2010 was estimated at approximately 29.5 billion USD. With the rapid recovery in automotive and chemical industry overall, the global catalyst market is expected to experience fast growth in the next years.^[33]