k  Ae  Ea / RT THE NEED FOR AN "ACTIVATION ENERGY"

1. Gas phase reactions

Consider the simple gas phase H-atom exchange reaction:

H + H-H  H-H + H

For simplicity, consider a collision that results from motion along the line of
centers of the atoms involved. To keep track of the atoms during collision,
label them a, b, c.

Ha H H H H H H Hb H
b c a b c a c

High K.E. High P.E., High K.E.

low K.E.
“activated complex” (transition state complex)

The kinetic energy of the collision must be sufficient to equal the increase in
potential energy of the activated complex.
The P.E. along the reaction pathway is determined by two inter-nuclear
distances, rab and rbc.
Transition state
 THE REACTION ENERGY SURFACE

Figure 6-6, pg 239,

E&C

“transition state complex”

The reaction is
reduced to motion
P.E. along one
reactants products dimension: the
“reaction
coordinate”
Reaction coordinate (RC)
2. Reactions in solution (the Transition State Theory; Eyring Theory)

A + B  products

A + B A-B Products

Solvent “cage” Transition state complex

1. Idea of a collision is inappropriate in solution; more like a “reactive
encounter”, but the idea of a high energy intermediate at a transition
state along a reaction coordinate is retained to explain the T dependence
of k
2. The energy for formation of the transition state complex is derived from
solvent collisions with the A, B pair in a solvent cage

3. The “transition state theory” for reactions in solution focuses attention

on the activated complex, and assumes that it is in effective equilibrium
with the reactants with respect to all degrees of freedom except the
reaction coordinate; an assumption justified, in part, by the success of the
theory.
A+B [AB]‡ products [AB]‡ = activated complex

rate = [AB]‡ (rate of crossover) ()

Rate of crossover = the frequency of decomposition of AB‡

 = "transmission coefficient" = fraction of [AB]‡ crossing forward  1

The frequency of decomposition of the activated complex

The vibrational energy in a bond (one-dimensional harmonic oscillator) of

the activated complex is
Evib = kBT = hh = planck’s constant = 6.6 x 10-27 erg.sec;  = frequency
of vibration)
 = kBT/h
The activated complex has an energy sufficiently great that the nuclei
separate during a single vibration, and the frequency of decomposition is
just the vibrational frequency 
 An estimate of the lifetime of the activated complex:

 = kBT/h = [1.38 x 10-16 erg-deg][298]/[6.6 x 10-27 erg-sec = 6.2 x 1012 s-1

The lifetime = 1/1.6 x 10-13 s !

Back to the problem of determining the rate constant

rate = [AB]‡ (rate of crossover) ()

rate = [AB]‡  (kBT/h)

Because [AB]‡ is assumed to be in thermal equilibrium with the reactants

K‡ = [AB]‡ / [A] [B] [AB]‡ = K‡ [A][B]

rate = (kBT/h)  K‡ [A] [B]

Thus the transition state theory of the rate constant gives

k = (kBT/h)K‡
 A thermodynamic description of the rate constant

k B T 
k= K
h
using the relationship between the equilibrium constant and the free energy,
 G o
 -
K =e RT

Where Go‡ is the free energy of formation of the activated complex

from the reactants.

A+B products
k B T -  Go
k= e RT
h

 G o  = G o  - G oA - G oB
 k B T -  Go
k= e RT
h
G o  = H o   T S o 
k B T -  H o   S o 
k= e RT e R
h

This result has two important applications in Biochemistry:

(1) Experimental measurements of k(T) give values for Ho‡ and So‡,
from which a molecular model of the transition state can be deduced.

(2) From a model of the transition state transition state and

corresponding information on Go‡, Ho‡ and S‡ for forming the
activated complex, the full power of thermodynamics can be applied
to analyze the effect of variables such as P, ionic strength, solvent
properties, etc on the reaction rate. A change in a variable that
stabilizes the transition state complex relative to reactants (reduces
the magnitude of Go‡), will increase the rate.
 Comparison of the TST equation for k with the Arrhenius equation

Arrhenius TST
k B T -  H o   S o 
k  Ae  Ea / RT k= e RT e R
h
Ea
k B T H
o
ln k  ln A  S o 
RT ln k  ln  
h RT R
These equations to refer to the same rate constant at all temperatures, so the
temperature dependence be the same. Taking A , So‡ and Ho‡ to be
temperature independent

d ln k E d ln k H o   H o   RT 
 a  T    
d 1 / T  R d 1 / T  R  R 
Comparing,

Ea  H o   RT Ea  H o 
Substituting the first expression into the Arrhenius equation, and equating k
given by the TST theory,
S o
k BTe
A e R
h
Experimental determination of Go‡, Ho‡ and So‡

k B T - Go
1. Go‡ Determined from k at any T: k= e RT
h

2. Ho‡ and So‡ d ln k  H o   RT 

  
d 1 / T   R 

(H o   RT )
slope  
lnk R

G o   H o   TS o 

1/T
G o   H o 
S o  
T
INTERPRETATION OF THE TST PARAMETERS IN MOLECULAR
TERMS

Elementary reversible chemical reaction

kf
A+B products Go<0 (Keqm > 1), Ho >0; requires So > 0
kr

A+B [AB] products k B T -  Go

‡
k= e RT
h
1. Free energy of activation, Go‡
 Gof = Go - GoA - GoB

 Gor = Go - Goprod

 Go =  Gof -  Gor
 G f o / RT
 G o / RT e kf
K e   Gr o / RT

e kr
2. Enthalpy of activation, Ho‡
kf
A+B products Ho > 0 A+B [AB]‡ products
kr
Ho‡ is generally > 0 , because covalent bonds are being broken in the
transition state

Formation of the complex

is endothermic, and the
rate increases with
increasing T
d ln k  H o   RT 
  
d 1 / T   R 
If Ho‡ > 0, rate increases
with T
H o  H of   H ro 
2. Entropy of activation, So‡
kf
A+B products So >0 A+B [AB]‡ products
kr
In a bimolecular reaction, So‡ is generally negative due to the
loss in entropy upon forming a single species (the activated complex)
from 2 species (the reactants).
In general, the more “ordered” the activated complex with
respect to the reactants, the higher the Go‡ and the lower the k

S o  S of   S ro 
A physical change: protein folding/unfolding at 298K where Ho  0; So < 0

The rate of folding is fast, and

increases strongly with temperature
around 298K

native

‡
Intermediate with H-
? bonds broken;
increase in S

unfolded
THE EFFECTS OF EXPERIMENTAL VARIABLES ON REACTION RATES: a
means of exploring the transition state structure

k B T -  Go
k= e RT
h
Goreactants
Goproducts

Any change that lowers the Go‡ relative to Goreactants (increases K‡) will
increase the forward reaction rate constant
1. Ionic strength. For reactions involving ionic species, changes in ionic
strength will change k
2. Pressure. If the transition state has a molecular volume different than
the total volume of the reactants, pressure will change k.
3. Solvent effects. For reactions involving ionic species, changes in solvent
dielectric constant will change k (see old exam)
1. Ionic reactions and the effect of ionic strength
Rate constants for reactions between ionic, but not neutral, species are
strongly dependent on ionic strength.

Consider an elementary reaction between ionic species M and N

M+N [MN]‡ → products
Ionic solution are very non-ideal with respect to electrolyte concentration,
so activity coefficients must be included in the equilibrium constant for
formation of the activated compex:

  [ MN ]  M N
K  [ MN ]  K  [ M ][ N ]
 M  N [ M ][ N ]  

k B T
rate  [MN ]
h

k T  
rate  B K  M  N [ M ][ N ]
h 
k B T   M  N
k= K
h 
 k B T   M  N
k= K
h 

log  i  0.5Z i2 ( I )1/ 2 Debye-Huckel equation for the activity coefficient of

ions for water at 298K; Z = valence of i

The activity coefficient decreases with increasing ionic strength due to the
attractive interactions ( < 1) with counterions in solution (the ion cloud!)

Changes in k due to changes in ionic strength: the principle

Recall
o
i  i  RT ln Ci  RT ln  i
 i  RT ln Ci  RT (2.303)(0.5) Z i2 ( I )1/ 2
o

The molar free energy of an ion in solution, including the activated

complex, decreases with increasing ionic strength

If the activated complex decreases in free energy more than the reactants
upon an increase in ionic strength, k will increase, and vice-versa.
 The math
k B T   M  N log  i  0.5Z i2 ( I )1/ 2
k= K
h 
 M N k BT 
k = ko Where k o  K , the rate constant at low ionic
 
T strength (at I 0,  = 1)

log k  log ko  log  M  log  N  log  

Using the Debye-Huckel equation for log and Z   Z M  Z N
log k  log ko  0.5( I )1/ 2 {Z M2  Z N2  ( Z M  Z N ) 2 }
log k  log k o  ( I )1/ 2 {Z M Z N }
1. If either ZM or ZN = 0, Z‡2 = (Z2M+Z2N) is the same as the charged reactant, and
Go‡ is independent of I.

2. If ZM and ZN are of opposite sign, Z‡2 < (Z2M+Z2N), and Go‡ increases with
increasing I (and k smaller), because the free energy of the reactants will be
lowered more than the complex.

3. If ZM and ZN are of the same sign, Z‡2 > (Z2M+Z2N), and logic the reverse of 2.
Ionic strength dependence of k: experimental data verifying the TST prediction

log k  log ko  ( I )1/ 2 {Z M Z N }

-
2. Pressure dependence of an enzyme reaction rate

fast fast
E + S ES ES ‡
EP E+P

The overall reaction rate will be effected by anything that changes the free
energy of the activated complex ES‡ relative to the ES complex, that is,
anything that changes the “equilibrium”

ES ES‡

Suppose that the molecular volume of the enzyme changes in forming the
activated complex such that

V(ES) ≠ V(ES‡)

In this case, the free energy of the activated complex will depend on
pressure
 G  
   V  V   V   V (ES )
 P T
 G  
   V 
 P T
G  ( P ) P

 d ( G  )  V   dP (assuming V 
is pressure independent)
G o ( P 1) 1

(a familiar equation now applied to an

G   G o   V  ( P  1)
activated complex)
G‡ is the free energy of activation at P atmospheres. The rate constant at
pressure P is then

k BT  G  / RT k BT  G o / RT  V  ( P 1) / RT

k e  e e
h h
 V  ( P 1) / RT k BT  G o / RT
k  ko e Where ko  e , the rate constant at P =1atm
h

ln k  ln k o  V  ( P  1) / RT
 0 ln k  ln ko  V  ( P  1) / RT
ln(k) – ln(ko)

A volume change in forming the

slope   V  / RT
activated complex can be directly
measured from the pressure
dependence of the rate constant

P-1
For pyruvate kinase, V‡ = +30 cm3/mole. For reference, the molar volume
of the enzyme is around 20,000 cm3/mole. Thus the volume change on
activation is around 1%. The rate is reduced with pressure, because the
volume change is positive.

At the bottom of the Mariana trench (depth of 30,000 ft), P = 1000 atm. At
this pressure k/ko = 0.27; The enzyme rate constant is reduced by about
70%. Has the enzyme for organisms that reside at the bottom evolved for a
reduced volume of activation?