Chemical kinetics

Chemical kinetics, also known as reaction kinetics, is the study of rates of chemical
processes. Chemical kinetics includes investigations of how different experimental
conditions can influence the speed of a chemical reaction and yield information about the
reaction's mechanism and transition states, as well as the construction of mathematical
models that can describe the characteristics of a chemical reaction. In 1864, Peter Waage
and Cato Guldberg pioneered the development of chemical kinetics by formulating the
law of mass action, which states that the speed of a chemical reaction is proportional to
the quantity of the reacting substances.

Rate of reaction
Chemical kinetics deals with the experimental determination of reaction rates from which
rate laws and rate constants are derived. Relatively simple rate laws exist for zero-order
reactions (for which reaction rates are independent of concentration), first-order
reactions, and second-order reactions, and can be derived for others. In consecutive
reactions the rate-determining step often determines the kinetics. In consecutive first-
order reactions, a steady state approximation can simplify the rate law. The activation
energy for a reaction is experimentally determined through the Arrhenius equation and
the Eyring equation. The main factors that influence the reaction rate include: the
physical state of the reactants, the concentrations of the reactants, the temperature at
which the reaction occurs, and whether or not any catalysts are present in the reaction.

Factors affecting reaction rate

Nature of the reactants

Depending upon what substances are reacting, the time varies. Acid reactions, the
formation of salts, and ion exchange are fast reactions. When covalent bond formation
takes place between the molecules and when large molecules are formed, the reactions
tend to be very slow. Nature and strength of bonds in reactant molecules greatly
influences the rate of its transformation into products. The reactions which involve lesser
bond rearrangement proceed faster than the reactions which involve larger bond
rearrangement.

Physical state

The physical state (solid, liquid, or gas) of a reactant is also an important factor of the
rate of change. When reactants are in the same phase, as in aqueous solution, thermal
motion brings them into contact. However, when they are in different phases, the reaction
is limited to the interface between the reactants. Reaction can only occur at their area of
contact, in the case of a liquid and a gas, at the surface of the liquid. Vigorous shaking
and stirring may be needed to bring the reaction to completion. This means that the more
finely divided a solid or liquid reactant, the greater its surface area per unit volume, and
the more contact it makes with the other reactant, thus the faster the reaction. To make an
analogy, for example, when one starts a fire, one uses wood chips and small branches—
one doesn't start with large logs right away. In organic chemistry, On water reactions are
the exception to the rule that homogeneous reactions take place faster than heterogeneous
reactions.

Concentration

Concentration plays a very important role in reactions according to the collision theory of
chemical reactions, because molecules must collide in order to react together. As the
concentration of the reactants increases, the frequency of the molecules colliding
increases, striking each other more frequently by being in closer contact at any given
point in time. Think of two reactants being in a closed container. All the molecules
contained within are colliding constantly. By increasing the amount of one or more of the
reactants it causes these collisions to happen more often, increasing the reaction rate
(Figure 1.1).

Temperature

Temperature usually has a major effect on the rate of a chemical reaction. Molecules at a
higher temperature have more thermal energy. Although collision frequency is greater at
higher temperatures, this alone contributes only a very small proportion to the increase in
rate of reaction. Much more important is the fact that the proportion of reactant molecules
with sufficient energy to react (energy greater than activation energy: E > Ea) is
significantly higher and is explained in detail by the Maxwell–Boltzmann distribution of
molecular energies.

The 'rule of thumb' that the rate of chemical reactions doubles for every 10 °C
temperature rise is a common misconception. This may have been generalized from the
special case of biological systems, where the Q10 (temperature coefficient) is often
between 1.5 and 2.5.

A reaction's kinetics can also be studied with a temperature jump approach. This involves
using a sharp rise in temperature and observing the relaxation rate of an equilibrium
process.
Catalysts

Generic potential energy diagram showing the effect of a catalyst in an hypothetical

endothermic chemical reaction. 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.

A catalyst is a substance that accelerates the rate of a chemical reaction but remains
chemically unchanged afterwards. The catalyst increases rate reaction by providing a
different reaction mechanism to occur with a lower activation energy. In autocatalysis a
reaction product is itself a catalyst for that reaction leading to positive feedback. Proteins
that act as catalysts in biochemical reactions are called enzymes. Michaelis-Menten
kinetics describe the rate of enzyme mediated reactions. A catalyst does not affect the
position of the equilibria, as the catalyst speeds up the backward and forward reactions
equally.

In certain organic molecules, specific substituents can have an influence on reaction rate
in neighbouring group participation.

Agitating or mixing a solution will also accelerate the rate of a chemical reaction, as this
gives the particles greater kinetic energy, increasing the number of collisions between
reactants and therefore the possibility of successful collisions.

Pressure

Increasing the pressure in a gaseous reaction will increase the number of collisions
between reactants, increasing the rate of reaction. This is because the activity of a gas is
directly proportional to the partial pressure of the gas. This is similar to the effect of
increasing the concentration of a solution.
Equilibrium

While chemical kinetics is concerned with the rate of a chemical reaction,

thermodynamics determines the extent to which reactions occur. In a reversible reaction,
chemical equilibrium is reached when the rates of the forward and reverse reactions are
equal and the concentrations of the reactants and products no longer change. This is
demonstrated by, for example, the Haber–Bosch process for combining nitrogen and
hydrogen to produce ammonia. Chemical clock reactions such as the Belousov–
Zhabotinsky reaction demonstrate that component concentrations can oscillate for a long
time before finally attaining the equilibrium.

Free energy

In general terms, the free energy change (ΔG) of a reaction determines whether a
chemical change will take place, but kinetics describes how fast the reaction is. A
reaction can be very exothermic and have a very positive entropy change but will not
happen in practice if the reaction is too slow. If a reactant can produce two different
products, the thermodynamically most stable one will generally form except in special
circumstances when the reaction is said to be under kinetic reaction control. The Curtin–
Hammett principle applies when determining the product ratio for two reactants
interconverting rapidly, each going to a different product. It is possible to make
predictions about reaction rate constants for a reaction from free-energy relationships.

The kinetic isotope effect is the difference in the rate of a chemical reaction when an
atom in one of the reactants is replaced by one of its isotopes.

Chemical kinetics provides information on residence time and heat transfer in a chemical
reactor in chemical engineering and the molar mass distribution in polymer chemistry.

Applications

The mathematical models that describe chemical reaction kinetics provide chemists and
chemical engineers with tools to better understand and describe chemical processes such
as food decomposition, microorganism growth, stratospheric ozone decomposition, and
the complex chemistry of biological systems. These models can also be used in the
design or modification of chemical reactors to optimize product yield, more efficiently
separate products, and eliminate environmentally harmful by-products. When performing
catalytic cracking of heavy hydrocarbons into gasoline and light gas, for example, kinetic
models can be used to find the temperature and pressure at which the highest yield of
heavy hydrocarbons into gasoline will occur.
Differential Rate Laws
Concepts

In many reactions, the rate of reaction changes as the reaction progresses. Initially the
rate of reaction is relatively large, while at very long times the rate of reaction decreases
to zero (at which point the reaction is complete). In order to characterize the kinetic
behavior of a reaction, it is desirable to determine how the rate of reaction varies as the
reaction progresses.

A rate law is a mathematical equation that describes the progress of the reaction. In
general, rate laws must be determined experimentally. Unless a reaction is an elementary
reaction, it is not possible to predict the rate law from the overall chemical equation.
There are two forms of a rate law for chemical kinetics: the differential rate law and the
integrated rate law.

The differential rate law relates the rate of reaction to the concentrations of the various
species in the system.

Differential rate laws can take on many different forms, especially for complicated
chemical reactions. However, most chemical reactions obey one of three differential rate
laws. Each rate law contains a constant, k, called the rate constant. The units for the rate
constant depend upon the rate law, because the rate always has units of mole L-1 sec-1 and
the concentration always has units of mole L-1.

Zero-Order Reaction

For a zero-order reaction, the rate of reaction is a constant. When the limiting reactant is
completely consumed, the reaction abrupts stops.

Differential Rate Law: r=k

The rate constant, k, has units of mole L-1 sec-1.

First-Order Reaction

For a first-order reaction, the rate of reaction is directly proportional to the concentration
of one of the reactants.

Differential Rate Law: r = k [A]

The rate constant, k, has units of sec-1.

Second-Order Reaction
For a second-order reaction, the rate of reaction is directly proportional to the square of
the concentration of one of the reactants.

Differential Rate Law: r = k [A]2

The rate constant, k, has units of L mole-1 sec-1.

These three behaviors are illustrated in the following plots. The graph at the left shows
concentration-time plots for zero-order (red line), first-order (green line), and second-
order (blue line) reactions. The corresponding rate-concentration plots are shown at the
right.

In examining the plots, bear in mind that as the reaction progresses, the concentration of
reactant decreases. This corresponds to moving from right to left on the plot of reaction
rate vs concentration. In this example, the reactant has a stoichiometric coefficient of one,
so the reaction rate (plotted in the graph at the right) corresponds with the negative value
of the slope of the concentration-time curve (plotted in the graph at the left). Carefully
examine the graphs and take note of the following points:

• For a zero-order reaction (red line), the rate of reaction is constant as the reaction
progresses.
• For a first-order reaction (green line), the rate of reaction is directly proportional
to the concentration. As the reactant is consumed during the reaction, the
concentration drops and so does the rate of reaction.
• For a second-order reaction (blue line), the rate of reaction increases with the
square of the concentration, producing an upward curving line in the rate-
concentration plot. For this type of reaction, the rate of reaction decreases rapidly
(faster than linearly) as the concentration of the reactant decreases.

Integrated Rate Laws

Concepts

The differential rate law describes how the rate of reaction varies with the concentrations
of various species, usually reactants, in the system. The rate of reaction is proportional to
the rates of change in concentrations of the reactants and products; that is, the rate is
proportional to a derivative of a concentration.

To illustrate this point, consider the reaction

A → B

The rate of reaction, r, is given by

 d [A]
r=-
dt

Suppose this reaction obeys a first-order rate law:

r = k [A]

This rate law can also be written as

d [A]
r=- = k [A]
dt

This equation is a differential equation that relates the rate of change in a concentration to
the concentration itself. Integration of this equation produces the corresponding
integrated rate law, which relates the concentration to time. When you viewed
concentration-time curves in previous pages, you viewed the integrated rate laws.

d [A]
=-kdt
[A]

At t = 0, the concentration of A is [A]0. The integrated rate law is thus

[A] = [A]0 e- k t

Experimentally one almost always measures how the concentration of a reactant or

product changes as the reaction progresses. In the previous page, you saw how the
derivative of the concentration-time curve can be used to determine the differential rate
law for a reaction. While this approach might work for simple systems with numerically
exact data, this method for determining a rate law does not work well in practice. The
experimental data suffers from random error and frequently one only collects points
infrequently. Consequently it is difficult or impossible to determine the slope accurately.

A much better practical approach is to make characteristic kinetics plots. For each
integrated rate law, there is a characteristic plot that can be created which will produce a
straight line. These characteristic plots are presented in the table shown below; species A
is a reactant in the chemical reaction.

Reaction Differential Integrated Characteristic Slope of Units of

 Kinetic Rate
Order Rate Law Rate Law Kinetic Plot
Plot Constant

d [A] mole L-1 sec-

Zero - =k [A] = [A]0 - k t [A] vs t -k 1
dt

d [A]
First - = k [A] [A] = [A]0 e- k t ln [A] vs t -k sec-1
dt

d [A] = k [A]
- 2 [A] L mole-1 sec-
Second d t [A] 1+kt 1/[A] vs t k 1
=
[A]0

The series of three graphs shown below illustrate the use of the characteristic kinetic
plots. The graph on the left shows [A] vs t plots for a zero-order (red line), first-order
(green line), and second-order (blue line) reaction. The graph in the middle shows ln [A]
vs t plots for each reaction order, and the graph on the right shows 1/[A] vs t plots for
each reaction order.

Biochemical Reaction Mechanisms

1. Mechanism of action of a-chymotrypsin

2. Glycolysis: metabolism of glucose
3. Biosynthesis of steroids from squalene

Mechanism of action of a-chymotrypsin

An enzyme that hydrolyzes peptides in the digestive system

Catalytic triad: Asp102, His 57, Ser 195

His 57 His 57
CH2 CH2

H H
O O O O N Ser
N Ser 195 195
C C
N N
CH2 CH2
CH2 CH2 H
H O
Asp 102 O
Asp 102 H O
H O
N C N C
1 R R' R R'
2
 a-chymotrypsin mechanism
His 57 His 57

CH2 CH2

H H
O N O O N Ser 195
O Ser 195 C
C N
N CH2
CH2 CH2
CH2
H O
H O Asp 102
Asp 102 H O
H H C O
N C O H
R N R'
R' R
3 4

free amine + a cylated s erine amine replaced by water

Glycolysis
Metabolism of glucose to form pyruvate and ATP

Enzyme kinetics
Enzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. In
enzyme kinetics the reaction rate is measured and the effects of varying the conditions of
the reaction investigated. Studying an enzyme's kinetics in this way can reveal the
catalytic mechanism of this enzyme, its role in metabolism, how its activity is controlled,
and how a drug or a poison might inhibit the enzyme.

Enzymes are usually protein molecules that manipulate other molecules — the enzymes'
substrates. These target molecules bind to an enzyme's active site and are transformed
into products through a series of steps known as the enzymatic mechanism. These
mechanisms can be divided into single-substrate and multiple-substrate mechanisms.
Kinetic studies on enzymes that only bind one substrate, such as triosephosphate
isomerase, aim to measure the affinity with which the enzyme binds this substrate and the
turnover rate.
General principles

The reaction catalysed by an enzyme uses exactly the same reactants and produces
exactly the same products as the uncatalysed reaction. Like other catalysts, enzymes do
not alter the position of equilibrium between substrates and products.[1] However, unlike
uncatalysed chemical reactions, enzyme-catalysed reactions display saturation kinetics.
For a given enzyme concentration and for relatively low substrate concentrations, the
reaction rate increases linearly with substrate concentration; the enzyme molecules are
largely free to catalyze the reaction, and increasing substrate concentration means an
increasing rate at which the enzyme and substrate molecules encounter one another.
However, at relatively high substrate concentrations, the reaction rate asymptotically
approaches the theoretical maximum; the enzyme active sites are almost all occupied and
the reaction rate is determined by the intrinsic turnover rate of the enzyme. The substrate
concentration midway between these two limiting cases is denoted by KM.

The two most important kinetic properties of an enzyme are how quickly the enzyme
becomes saturated with a particular substrate, and the maximum rate it can achieve.
Knowing these properties suggests what an enzyme might do in the cell and can show
how the enzyme will respond to changes in these conditions.

Chemical mechanism

An important goal of measuring enzyme kinetics is to determine the chemical mechanism

of an enzyme reaction, i.e., the sequence of chemical steps that transform substrate into
product. The kinetic approaches discussed above will show at what rates intermediates
are formed and inter-converted, but they cannot identify exactly what these intermediates
are.

Kinetic measurements taken under various solution conditions or on slightly modified

enzymes or substrates often shed light on this chemical mechanism, as they reveal the
rate-determining step or intermediates in the reaction. For example, the breaking of a
covalent bond to a hydrogen atom is a common rate-determining step. Which of the
possible hydrogen transfers is rate determining can be shown by measuring the kinetic
effects of substituting each hydrogen by deuterium, its stable isotope. The rate will
change when the critical hydrogen is replaced, due to a primary kinetic isotope effect,
which occurs because bonds to deuterium are harder to break then bonds to hydrogen.[32]
It is also possible to measure similar effects with other isotope substitutions, such as
13
C/12C and 18O/16O, but these effects are more subtle.[33]

Isotopes can also be used to reveal the fate of various parts of the substrate molecules in
the final products. For example, it is sometimes difficult to discern the origin of an
oxygen atom in the final product; since it may have come from water or from part of the
substrate. This may be determined by systematically substituting oxygen's stable isotope
18
O into the various molecules that participate in the reaction and checking for the isotope
in the product.[34] The chemical mechanism can also be elucidated by examining the
kinetics and isotope effects under different pH conditions,[35] by altering the metal ions or
other bound cofactors,[36] by site-directed mutagenesis of conserved amino acid residues,
or by studying the behaviour of the enzyme in the presence of analogues of the
substrate(s).[37]

Transition state theory

Transition state theory (TST) explains the reaction rates of elementary chemical
reactions. The theory assumes a special type of chemical equilibrium (quasi-equilibrium)
between reactants and activated transition state complexes.[1]

TST is used primarily to understand qualitatively how chemical reactions take place. TST
has been less successful in its original goal of calculating absolute reaction rate constants
because the calculation of absolute reaction rates requires precise knowledge of potential
energy surfaces,[2] but it has been successful in calculating the standard enthalpy of
activation (Δ‡H⦵), the standard entropy of activation (Δ‡S⦵), and the standard Gibbs
energy of activation (Δ‡G⦵) for a particular reaction if its rate constant has been
experimentally determined. (The ‡ notation refers to the value of interest at the transition
state.)

Theory

Basic ideas behind the transition state theory are as follows:

1. Rates of the reactions are studied by studying activated complexes which lie at the col
(saddle point) of a potential energy surface. The details of how the complexes are formed
are not important.

2. The activated complexes are in a special equilibrium (quasi-equilibrium) with the

reactant molecules.

3. The activated complexes can convert into products which allows kinetic theory to
calculate the rate of this conversion.