Chemical Reaction Engineering

Lecture 6

Lecturer : 郭修伯
This course focuses on “Nonelementary reaction kinetics”.
 Elementary vs. nonelementary
• Elementary: the reaction orders and stoichiometric
coefficients are identical.
• Nonelementary reaction kinetics: no direct
correspondence between reaction order and stoichiometry.
• Four topics will be introduced in this course:
– Pseudo-steady-state hypothesis (PSSH)
– Polymerization
– Enzymatic reactions
– Bioreactors
 Nonelementary reaction
• Gas-phase decomposition of azomethane
(AZO)
(CH 3 ) 2 N 2  C2 H 6  N 2

From experimental observation:

when AZO at pressure greater than 1 atm: rN 2  C AZO First - order reaction

2
when AZO at pressure below 50 mmHg: rN 2  C AZO Second - order reaction

Why? What happened?

 (CH 3 ) 2 N 2  C2 H 6  N 2

Theory of Lindemann (1922)

• Collision or interaction between molecules
forms an activated molecule, [(CH3)2N2]*
(CH 3 ) 2 N 2  (CH 3 ) 2 N 2 
k1
(CH 3 ) 2 N 2  [(CH 3 ) 2 N 2 ]*

The activation can occur when translational kinetic enery is transferred into energy
stored in internal degrees of freedom, particularly vibrational degrees of freedom.

Collision, photo, ...etc. Energy stored in internal

Translational kinetic energy
degrees of freedom

The concentration of the active intermediate is very difficult to measure,

because AZO* is highly reactive and very short-lived (~ 10-9 s).
 Active intermediate
• The energy must be absorbed into the chemical bonds where
high-amplitude oscillations will lead to bond ruptures, molecular
rearrangement, and decomposition.
• The sources of the energy:
– photochemical effects of similar phenomena
– molecular collision or interaction.
• Types of active intermediates
– free radicals (one or more unpaired electrons, e.g., H•)
– ionic intermediates (e.g., carbonium ion)
– enzyme-substrate complexes
– etc.
 2
(CH 3 ) 2 N 2  (CH 3 ) 2 N 2 (CH 3 ) 2 N 2  [(CH 3 ) 2 N 2 ]
k1 * rAZO*  k1C AZO

[(CH 3 ) 2 N 2 ]*  (CH 3 ) 2 N 2 

k2
(CH 3 ) 2 N 2  (CH 3 ) 2 N 2 rAZO*   k 2C AZO C AZO*
Deactivated through collision with another molecule

[(CH 3 ) 2 N 2 ]* 
k3
C2 H 6  N 2 rAZO*   k3C AZO*

We wanted to know why the orders of reation of rN2 are different at low and high pressures.
rN 2  k3C AZO *
Difficult to measure

Actually, these are series reactions (multiple reactions): What’s next?

CAZO*
q 3
rj   rij rAZO*   riAZO *  k1C AZO  k 2C AZO C AZO*  k3C AZO*
2 relate to
i 1 i 1
Measurable concentration
 Pseudo-Steady-State Hypothesis (PSSH)

• The active intermediate molecule has a very

short lifetime  low concentration
the rate of formation = the rate of disappearance

The net rate of formation of the acrive intermadiate is zero:

*
ractive intermediate  0

2
rAZO*  k1C AZO  k 2C AZO C AZO*  k3C AZO*  0
2
k1C AZO rN 2  k3C AZO* 2
k1k3C AZO
C AZO*  rN 2 
k3  k 2C AZO k3  k 2C AZO
 2
k1k3C AZO
rN 2 
k3  k 2C AZO

At low concentration: k 2C AZO  k3 rN 2  k1C AZO

2

Second - order reaction

k1k3
At high concentration: k 2C AZO  k3 rN 2  C AZO  kC AZO
k2

First - order reaction

The reaction is apparent first-order at high azomethane concentrations and

apparent second-order at low azomethane concentration
 Reaction mechanism
The active intermediate,
AZO*, is formed from AZO
2
k1C
C AZO*  AZO

k3  k 2C AZO

The active intermediate, AZO*, The active intermediate, AZO*,

decomposes spontaneously collides with azomethane, AZO
 The Stern-Volmer equation

High-intensity ultrasonic wave applied to water Light

wave compression microsize bubbles

Temperature rising

Chemical reaction in the bubbles

Generation of intermediates

The intensity of the light given off, I, is proportional to the rate of reaction of
an activated water molecule formed in the microbubble.
放出的光
H 2O  H 2O  hv
* k3
intensity  (rH O* )  k3C H O*
2 2
 When either carbon disulfide or carbon tetrachloride is added to the water,
the intensity of sonoluminescence increases an order-of-magnitude.
聲納冷光

intensity  ( rCS * )  k 4CCS *

*
CS 2 
k4
CS 2  hv
2 2

However, when an aliphatic alcohol, X, is added to the solution, the intensity

of sonoluminescence decreases with increasing concentration of alcohol.

Relative intensity I0/I

I0
 A  BC X
I
Alcohol concentration Cx

Sugget a mechanism consistent with experimental observation

I0 Set CX = (X) I 1
 A  BC X 
I I 0 A  B( X )

The active intermediate

collides with alcohol
X  intermediate  deactivation product
清除者
X is called a “scavenger” to deactivate the active intermediate

intensity  (CS 2 ) Active intermediate was probably formed from CS2

*
M  CS 2  CS 2  M
M is a third body (CS2, H2O, etc.)
 Purposed
mechanisms:
*
Activation: M  CS 2 
k1
CS 2  M
*
Deactivation: M  CS 2 
k2
CS 2  M
*
Deactivation: X  CS 2 
k3
CS 2  X
Luminescence:
*
CS 2 
k4
CS 2  hv I  k 4CCS *
2

*
Using PSSH on CS2*: ractive intermediate  0
* * *
rCS *  k1 (CS 2 )(M )  k 2 (CS 2 )(M )  k3 ( X )(CS 2 )  k 4 (CS 2 )  0
2

I  k 4CCS *
2

k 4 k1 (CS 2 )( M ) No alcohol (X=0) k 4 k1 (CS 2 )( M )

I I0 
k 2 ( M )  k3 ( X )  k 4 k2 (M )  k4

I0 k3 This equation and similar equations involving

 1 ( X )  1  k ( X )
I k2 (M )  k4 scavengers are called Stern-Volmer equations.
 Chain reaction
• A chain reaction consists of the following sequence:
– Initiation
• formation of an active intermediate
– Propagation or chain transfer
• interaction of an active intermediate with the reactant or
product to produce another active intermediate
– Termination
• deactivation of the active intermediate
 PSSH applied to thermal cracking of ethane
The thermal decomposition of ethane to ethylene, methane, butane and
hydrogen is believed to proceed in the following sequence:

Initiation: C2 H 6 
k
 2CH 3 
C2 H 6
 r1C2 H 6  k1C2 H 6 [C2 H 6 ]

Propagation: CH 3  C2 H 6 

k2
CH 4  C2 H 5   r2C2 H 6  k 2 [CH 3 ][C2 H 6 ]

C2 H 5  
k3
C2 H 4  H  r3C2 H 4  k3[C2 H 5 ]

H  C2 H 6 
k4
C2 H 5   H 2  r4C2 H 6  k 4 [ H ][C2 H 6 ]

Termination: 2C2 H 5  

k5
C4 H10  r5C2 H 5   k5C2 H 5 [C2 H 5 ]2

(a) Use the PSSH to derive a rate law for the rate of formation of ethylene
(b) Compare the PSSH solution in Part (a) to that obtained by solving the complete set
of ODE mole balance
The rate of formation of ethylene rC2 H 4  k3 [C2 H 5 ] Purpose: replace [C2H5•]

The net rates of reaction of active intermediates CH3•, C2H5•, H• are (PSSH):

rC2 H 5   r2C2 H 5   r3C2 H 5   r4C2 H 5   r5C2 H 5   r1C2 H 6  k1C2 H 6 [C2 H 6 ]

 r2C2 H 6  r3C2 H 4  r4C2 H 6  r5C2 H 5   0  r2C2 H 6  k 2 [CH 3 ][C2 H 6 ]

rCH 3   2r1C2 H 6  r2C2 H 6  0
r3C2 H 4  k3[C2 H 5 ]
rH   r3C2 H 4  r4C2 H 6  0
substitute
 r4C2 H 6  k 4 [ H ][C2 H 6 ]

 r5C2 H 5   k5C2 H 5 [C2 H 5 ]2

2k1
[CH 3 ] 
1
 2k  2
k2 [C2 H 5 ]   1 [C2 H 6 ]
k 2 [CH 3 ][C2 H 6 ]  k5 [C2 H 5 ]2  0  k5 

1
 2k1  2
 rC2 H 4  k3 [C2 H 5 ]  k3  [C2 H 6 ]
 k5 
The rate of disappearance of ethane  rC2 H 6  k1[C2 H 6 ]  k 2 [CH 3 ][C2 H 6 ]  k 4 [ H ][C2 H 6 ]

Purpose: replace [CH3•] and [H•]

The net rates of reaction of active intermediates CH3•, C2H5•, H• are (PSSH):

rC2 H 5   r2C2 H 5   r3C2 H 5   r4C2 H 5   r5C2 H 5   r1C2 H 6  k1C2 H 6 [C2 H 6 ]

 r2C2 H 6  r3C2 H 4  r4C2 H 6  r5C2 H 5   0  r2C2 H 6  k 2 [CH 3 ][C2 H 6 ]
rCH 3   2r1C2 H 6  r2C2 H 6  0 r3C2 H 4  k3[C2 H 5 ]
rH   r3C2 H 4  r4C2 H 6  0  r4C2 H 6  k 4 [ H ][C2 H 6 ]
substitute
 r5C2 H 5   k5C2 H 5 [C2 H 5 ]2

1
k3  2k1  2 1
[ H ]    [C2 H 6 ] 2 1
k 4  k5   2k  2

2k  rC2 H 6  (k1  2k1 )[C2 H 6 ]  k3  1 [C2 H 6 ]

[CH 3 ]  1  k5 
k2
 1 1
 2k  2
 2k  2
rC2 H 4  k3  1 [C2 H 6 ]  rC2 H 6  (k1  2k1 )[C2 H 6 ]  k3  1 [C2 H 6 ]
 k5   k5 
For a constant-volume batch reactor :
1 1
dCC2 H 4  2k1  2 dCC2 H 6  2k1  2
 k3  CC 2 H 6    (k1  2k1 )CC2 H 6  k3  CC2 H 6 ]
dt  k5  dt  k5 

For given initial concentration of C2H6 and temperature,

these two equation can be solved simultaneously

We obtain the concentration - time relationship using PSSH

Other methods can also be used…...

C2 H 6 
k1
2CH 3  H  C2 H 6 
k4
C2 H 5   H 2
CH 3  C2 H 6 
k2
CH 4  C2 H 5  2C2 H 5  
k5
C4 H10
C2 H 5  
k3
C2 H 4  H 
1. Mole balances: 2. Rate laws for each species:
(Batch) All these O.D.Es can be
dC1
 r1 r1  k1C1  k 2C1C2  k 4C1C6 solved simultaneously
C2H6
dt
dC2
CH3• dt  r2 r2  2k1C1  k 2C2C1
dC3
 r3 r3  k 2C1C2
CH4 dt
dC4 2
C2H5•  r4 r4  k 2C1C2  k3C4  k 4C1C6  k5C4
dt
dC5
C2H4  r5 r5  k3C4
dt The comparisons of the results obtained
dC6 from the two methods are shown on
H•  r6 r6  k3C4  k 4C1C6
dt page. 351.
dC7 r7  k 4C1C6 The two results are identical, indicating
H2  r7
dt the validity of the PSSH under
dC8 1 2
C4H10  r8 r8  k 5 C 4 these conditions
dt 2
 Reaction pathways
The second method is more frequently recently used due to the increase in computing power.

The key is to identify which intermediate reactions are important in the

overall sequence in predicting the end products.

The study of reaction pathways

 Reaction pathways - smog formation
Nitrogen and oxygen react to form nitric oxide in automobile engines.
The NO from automobile exhaust is oxidized to NO2 in the presence of peroxide radicals:
ROO  NO  R O  NO2
Nitrogen dioxide is then decomposed photochemically to give nascent oxygen:
NO2  hv  NO  O
which reacts to form ozone:
O  O2  O3
The ozone then involves in a whole series of reactions with hydro-carbons in the atmosphere
to form aldehydes, various free radicals, and other intermediates, which react further to
produce undesirable products in air pollution: e.g.
O3  olefin  aldehydes  free radicals 2
O3  CH 2  CHCH  CH 2 
hv
CH 2  CHCHO  HCHO
3
O3  RCH  CHR  RCHO  R O  HC O severe eye irritants
hv R  HC O R  O2  ROO P.354
Finding the reaction mechanism ...

Use both Figure 7-2 and Table 7-2 on page 354.

We will use the same idea to study “Polymerization”

A polymer is a molecule made up of repeating structural (monomer) units.

Polymerization is the process in which monomer units are linked together by chemical
reaction to form long chains. The polymer chains can be linear, branched, or cross-linked.
 Polymerization reactions

Step reactions Chain reactions

(Condensation reaction) (Addition reaction)

Require bifunctional or polyfunctional monomers Require an initiator

Copolymers: polymers made up of two or more repeating units

Alternating Q  S Q  S Q  S 
Block Q Q Q  S  S  S 
Random Q  S Q  S  S Q 

Graft Q Q Q Q Q Q 
S S S S 
Statistical follow certain laws
 Step polymerization reactions
• It requires that there is at least a reactive functional group on each end
of the monomer
• Example: NH  (CH )  COOH amino-caproic
2 2 5
– has an amine group at one end and a carboxyl group at the other
acid
– common functional groups are -OH, -COOH, -COCl,-NH 2
• The molecular weight usually builds up slowly.
• It is not meaningful to use conversion of monomer as a measure.
– The reaction will still proceed even though all the monomers has been
consumed.
• We measure the progress by the parameter p which is the fraction of
functional groups.
 Degree of polymerization
M0  M
p = fraction of functional groups that have been reacted
M0
M = concentration of functional groups

The number of average degree of polymerization is M0 1

Xn  
the average number of structural units per chain: M 1 p

The number average molecular weight, M n is the average molecular weight of a structure
unit, M s times the average number of structral unit per chain, X n plus the molecular weight
of the end group, M eg :
M n  X n M s  M eg
 Interests to step polymerization
• Conversion of the functional groups
• Degree of polymerization
• Number average molecular weight
• Distribution of chain lengths, n, (i.e. molecular
weight, Mn)
Determining the concentration of polymers for step polymerization

Determine the concentration and mole fraction of polymers of chain length j in terms of
initial concentration of ARB, M0, the concentration of unreacted functional groups M,
the propagation constant k and time t.

Set P1  A  R  B P2  A  R2  B ... Pj  A  R j  B

Reaction Rate laws

r1P1 Two ways :
2 P1  P2 2
 r1P1  2kP1 , r1P2    kP1
2
A-R-B
2 B-R-A
P1  P2  P3  r2 P1  r2 P2  r2 P3  2kP1 P2

P1  P3  P4  r3 P1  r3 P3  r3 P4  2kP1 P3
r4 P2
P2  P2  P4 2
 r4 P2  2kP2 , r4 P4    kP2
2

2
...
The net rate of reaction of P1, P2, and P3 for the first 4 reactions are:
2
r1  rP1  2kP1  2kP1 P 2 2kP1 P3
2 2
r2  rP2  kP1  2kP1 P 2 2kP2
r3  rP3  2kP1 P2  2kP1 P 3 2kP2 P3

Continue... 
r1  rP1  2kP1  Pj
j 1


P
j 1
j  Total concentration of functional groups = M

r1  rP1  2kP1M
Similarly, for j 2
j 1
r j  k  Pi Pj i  2kPj M
i 1
For a batch reactor,
M0
M 2
dP1 1 M 0 kt  1 
The mole balance on P1:  2kP1M P1  M 0  
dt  1  M 0 kt 
j 1
rj  k  Pi Pj i  2kPj M
i 1
M0
M
dP 1 M 0 kt dP2 2 1   1 
2
r2  2  kP1  2kP2 M  kM 0    2kM 0 P2  
dt dt  1  M 0 kt   1  M 0 kt 
B.C.
t = 0, P2=0
2
generalizing  1   M 0 kt 

P2  M 0    
 1  M 0 kt   1  M 0 kt 
j 1 M0  M
2 p
 1   M 0 kt  M0

Pj  M 0     Pj  M 0 1  p  p j 1
2

 1  M 0 kt   1  M 0 kt 
 Chain polymerization reactions
• Chain polymerization requires an initiator (I) and
proceeds by adding one repeating unit a time :
I  M  R1
M  R1  R2
M  R2  R3
M  R3  R4
...

The molecular weight in a chain usually builds up rapidly once a chain is initiated.
 Free-radical polymerization
• The basic steps in free-radical polymerization:
– Initiation
• formation of an active intermediate
– Propagation or chain transfer
• interaction of an active intermediate with the reactant or
product to produce another active intermediate
– Termination
• deactivation of the active intermediate
 Initiation
• An initiation step is needed to start the polymer chain growth.
• It can be achieved by adding a small amount of a chemical
that decomposes easily to form free radicals:

• Initiators can be monofunctional

I 2 
k0
2and
I form the same free
radicals, or they can be multifunctional and form different
radicals.
• For monofunctional initiators, the reaction sequence between
monomer and initiator:

I  M 
ki
R1
 Propagation
• The propagation sequence between a free radical R1 with a
monomer unit is:
R1  M 
kp
R2
R2  M 
kp
R3

• In general: R  M  kp
R j 1
j
• The specific reaction rate kp is assumed to be identical for
the addition of each monomer to the growing chain.
• The specific reaction rate ki is often taken to be equal to kp.
 Chain transfer
• The transfer of a radical from a growing polymer
chain can occur in the following ways:
– Transfer to a monomer
R j  M 
km
Pj  R1
• A live polymer Rj transfers its free radical to the monomer
to from the radical R1 and a dead polymer Pj
– Transfer to another species
Rj  C 
kc
Pj  R1

– Transfer of the radical to the solvent

Rj  S 
ks
Pj  R1
 Chain transter (cont…)
• The species involved in the various chain transfer
reactions are all assumed to have the same reactivity as
Ri.
• The choice of solvent in which to carry out the
polymerization is important.
– For example, ks is 10000 times greater in CCl4 than in
benzene.
• The specific reaction rates in chain transfer are all
assumed to be independent of the chain length.
 Termination
• Termination to form dead polymer occurs
primarily by two mechanisms:
– Addition (coupling) of two growing polymers:
R j  Rk 
ka
Pj  k
– Termination by disproportionation:
R j  Rk 
kd
Pj  Pk
 Free-radical polymerization reaction
• For example: the polymerization of styrene at 80 C
initiated by 2,2-azobisisobutyronitrile:
k a  k p  k m  k s ~ ki
Initiation
Chain transfer (solvent)

Chain transfer (monomer)

Propagation

Addition (termination)

Initial concentration: 0.01 M for initiator, 3 M for the monomer, and 7 M for the solvent
 Rate laws for chain polymerization
• Initiation:
– Only a certain fraction f will be successful in initiating
polymer chains. The rate law for the formation of the
initiator free radical:
rIf  2 fk 0 ( I 2 )
• f is the fraction of initiator free radical successful in
initiating chaining and has a typical value in the range 0.2
to 0.7.
– The rate law for the formation of R1 in the initiation step:
rR1  ri  ki ( M )( I )
 Rate laws at the initiation step
Using the PSSH for the initiator free radical, I,

rIf  2 fk 0 ( I 2 ) rR1  ri  ki ( M )( I )

ri  2 fk 0 ( I 2 )  ki ( M )( I )  0

2 fk0 ( I 2 )
(I )   ri  2 fk0 ( I 2 )
ki ( M )

Identical!
 Rate laws for R1
• In general: R1  R j 
ka
Pj 1
• The total loss of R1 radicals is found by adding the loss
of R1 radicals in each reaction. The rate of disappearance
of R1 by termination addition is given by:
2
 r1t  k a R1  k a R1 R2  k a R1 R3  ...  k a R1 R j  ...

 r1t  k a R1  R j
j 1

• The net rate of disappearance of the free radical R1:

    
 r1  ri  k p R1M  k a R1  R j  k d R1  R j  k m M  R j  kc C  R j  k s S  R j
j 1 j 1 j 2 j 2 j 2

initiation + propagation + termination (addition) + termination (disproportionation) + chain transfer

 Rate laws for Rj (j  2)
• In general, the net rate of disappearance of live
polymer chains with j monomer units (species j, j2)

 r j  k p M ( R j  R j 1 )  ( k a  k d ) R j  Ri  k m MR j  kc CR j  k s SR j
i 1

We will then use PSSH to solve polymerization problems.

 
Let R   R j represent th total concentration of the radical Rj.
*

j 1

    
 r1   ri  k p R1M  k a R1  R j  k d R1  R j  k m M  R j  k c C  R j  k s S  R j
j 1 j 1 j 2 j 2 j 2


 rj  k p M ( R j  R j 1 )  (k a  k d ) R j  Ri  k m MR j  k c CR j  k s SR j (j2)
i 1

 j i t )
 r  
j 1
r  k ( R * 2

Termination term

PSSH r
j 1
j 0

 ri 2 fk0 ( I 2 )
R*  
kt kt Total free-radical concentration
The net rate of monomer consumption, -rM:  rM  (ri )  ( rp )  (rm )
consumption by initiator
consumption by propagation
rp  ri
consumption by monomer chain transfer
Long Chain approximation (LCA)


2 fk0 ( I 2 )
 rM  rp  k p M  R j  k p MR  k p M
*

j 1 kt

The rate of disappearance of monomer

1 k  j 1
The net rate of formation of dead polymer Pj (by addition) is: rPj  k a  Rk R j  k

2 k 1
1 k fk ( I )
rp   rPj  ka ( R* ) 2  a 0 2
j 1 2 kt
The rate of formation of all dead polymers
 Enzymatically catalyzed reactions
• An enzyme, E, is a protein or proteinlike substance with
catalytic properties.
• A substrate, S, is the substance that chemically transformed at an
accelerated rate because of the action of the enzyme on it.
• One enzyme can catalyze only one reaction. Unwanted products
are easily controlled.
• Enzymes are produced only by living organisms (bacteria, for
example).
• Enzymes usually work under mild conditions (pH 4~9, 75 ~ 160 F).
 Enzymes
• Most enzymes are named in terms of the reactions
they catalyze (***ase), for example:
• urease: the enzyme that catalyzes the decomposition of urea
• tyrosinase: the enzyme that attacks tyrosine
• Three major types of enzyme reactions:
– soluble enzyme - insoluble substrate (e.g. laundry detergents)
– insoluble enzyme - soluble substrate (similar to packed catalytic
bed rxn)
– soluble enzyme - soluble substrate (e.g. many biological rxns)

our interest
 Enzymatically catalyzed rxn example
The proposed mechanisms of the catalytic action of urease which causes urea
to decompose into ammonia and carbon dioxide : (Levine and LaCourse, 1967)

1.The enzyme urease reacts with the substrate urea to form an enzyme-substrate complex, E•S:
S E E•S
NH 2CONH 2  urease 
k1
[ NH 2CONH 2  urease]*
2.This complex can decompose back to urea and urease:

[ NH 2CONH 2  urease ]* 

k2
NH 2CONH 2  urease
3.Or, it can react with water to give ammonia, carbon dioxide, and urease:
W P
[ NH 2CONH 2  urease]*  H 2O 
k3
2 NH 3  CO2  urease
 S  E 
k1
ES
E  S 
k2
ES
E  S  W 
k3
PE

The rate of disappearance of the substrate is:  rS  k1 ( E )( S )  k 2 ( E  S )

The net rate of formation of the E•S complex is:  rE S  k1 ( E )(S )  k 2 ( E  S )  k3 (W )( E  S )

The enzyme is not consumed by the reactions: ( Et )  ( E )  ( E  S )

PSSH  rE S  0

k1 ( Et )( S )
(E  S ) 
k1 ( S )  k 2  k3 (W )

k1k3 (W )( Et )( S )
 rS 
k1 ( S )  k 2  k3 (W )
 k1k3 (W )( Et )( S )
 rS 
k1 ( S )  k 2  k3 (W ) k’3
k3  k 2 Since the reaction of urea and urease is carried out
Km 
k1 in aqueous solution (water): (W) ~ constant

Vmax 
k3 ( Et )( S ) This is the form of the “Michaelis-Menten Equation”
 rS 
( S )  K m and Km is call the Michaelis constant

At low substrate concentration: (S) << Km -rS

Vmax ( S ) Vmax
 rS 
Km
At high substrate concentration: (S) >> Km Vmax/2

 rS  Vmax
Km (S)
V K m  S | rs Vmax / 2
In a special case, when  rS  max
2
Km is equal to the substrate concentration at which
the rate of reaction is equal to one-half the maximum rate.
 Michaelis-Menten equation
Vmax ( S )
 rS 
(S )  K m

Vmax  k3 ( Et )

Vmax and Km characterise the enzymatic reactions described by Michaelis-Menten kinetics.

Vmax is dependent on total enzyme concentration.
Km is independent of total enzyme concentration.
 Michaelis-Menten kinetics example
S  E 
k1
E  S E  S 
k2
E  S E  S  W 
k3
PE
Curea (kmol/m3) 0.2 0.02 0.01 0.005 0.002
-rurea (kmol/m3s) 1.08 0.55 0.38 0.2 0.09

Vmax ( S ) 1 (S )  K m 1 Km
 rS    
(S )  K m  rS Vmax ( S ) Vmax Vmax ( S )

Km
Slope = 0.02 =
1/-rs Vmax 1.33Curea
 rS 
0.0266 C urea
1
Intercept = 0.75 =
Vmax

(1/S) (i.e. 1/Curea)

 Batch enzymatically catalyzed rxn
Artificial kidney design
dCurea Vmax Curea
A batch reactor in liquid phase:  rurea  
dt Curea  K m

K m Curea 0 Curea 0  Curea

1
ln
1 Vmax t ln 
t 1 X Intercept = Vmax Curea Vmax
Km
C  C0 (1  X )
Curea 0
Slope =  1 1 Vmax Curea 0 X
Km ln  
t 1 X Km K mt

X
t
 Inhibition of enzyme reactions
• The rate of enzyme-catalyzed reactions is affected by pH
and inhibitors.
• Three most common types of reversible inhibition:
– Competitive
• Substrate and inhibitor are usually similar molecules that compete for the same site
on the enzyme.
– Uncompetitive
• The inhibitor deactivetes the enzyme-substrate complex, usually by attaching itself
to both the substrate and enzyme molecules of the complex.
– Noncompetitive
• Enzymes containing at least two different types of sites. The inhibitor attaches to
only one type of site and the substrate only to the other.
 Bioreactors
• Microorganisms and mammalian cells are used to produce a
variety of products, such as insulin( 胰島素 ), most antibiotics(
抗生素 ), and polymers.
• Advantages:
– mild reaction conditions
– high yields
– can catalyze successive steps in a reaction for organisms
contain several enzymes
– stereospecific ( 立體的 ) catalyst (single desired isomer can be formed)
 In general, the growth of an aerobic organism follows:

[cells ]  [carbon source ]  [nitrogen source ]  [oxygen source ]  [ phosphate source ]  ...
media  conditions( pH , temperature , etc )
culture
        [CO2 ]  [ H 2O]  [ product ]  [more cells ]

Substrate cell
 More cells  Product

The rate of this reaction is proportional to the cell concentration and

the reaction is autocatalytic.
Four phases are included in cell growth:
Log cell concentration
2 3
1 4

time

• (1) Lag phase

– little increase in cell concentration
– synthesizing transport proteins for moving the
substrate into the cell
– synthesizing enzymes for utilizing the new substrate
– beginning the work for replicating the cell’s genetic
material
• (2) Exponential growth phase
– the cell’s growth rate is proportional to the cell
concentration
– the cells are able to use the nutrients most efficiently
• (3) Stationary phase
– the cell reach a minimum biological space where the
lack of one or more nutrients limits cell growth.
– many important fermentation products, including
most antibiotics, are produced in the stationary phase
• (4) Dead phase
– result of either the toxic by-product and/or the
depletion of nutrient supply
 Rate laws of bioreactors
Cells  Substrate conditions
  More cells  Pro duct

The most commonly used expression is the Monod equation for exponential growth:

rg  Cc

Cell concentration
Cell growth rate
Substrate concentration
Cs
Specific growth rate =    max
K s  Cs

Maximum specific growth reaction rate

Monod constant
 n
Cc C s  C p   max CcC s
rg   max account for inhibition
rg  1  * 
K s  Cs (one model here)  C  K s  Cs
 p 
Monod equation
where Cp* = product concentration at which all metabolism ceases and n = experimental constant

Other cell growth rates:

  C s 
Tessier equation rg   max 1  exp  Cc
  k 

 max Cc
Moser equation rg  
(1  kCs )

The cell death rate is:

rd  (k d  kt Ct )Cc
Specific toxic death rate constant
Specific natural death rate constant
Concentration of a substrate toxic to the cell
 Stoichiometry for cell growth
Cells  Substrate conditions
  More cells  Pro duct
• Very complex : vary with microorganism / nutrient
system; vary with environmental conditions; even
more complex when more than one nutrient contributes
to cell growth.
• May be simplified as: S cells

 Yc / s C  Y p / s P

mass of new cells formed

where Yc/s is the yield coefficient : Yc / s 
mass of substrate consumed to produce new cells
mass of product formed
where Yp/s is the product coefficient : Y p / s 
mass of substrate consumed to form product
 Produce new cells
Substrate consumption
Maintain a cell’s daily activities

mass of substrate consumed for maintenance

m typical value = 0.05 h-1
mass of cells  time

Therefore, the rate of substrate consumption for maintenance: rsm  mCC

The yield coefficient, Y’c/s , account for substrate consumption for maintenance:

mass of new cells formed

Yc/ s 
mass of substrate consumed
 During the growth phase rp  Y p / c rg

Product formation

During the stationary phase rp  Yp / s (rs )

The net rate of substrate consumption:

 rs  Ys / c rg  Ys / p rp  mCc

Consumption rate for maintenance

Consumption rate to form product

Consumption rate by cell growths

  rs  Ys / c rg  Ys / p rp  mCc

If the product is formed  rs  Ys / c rg  mCc rp  Y p / c rg

during the growth phase

If the product is formed  rsn  Ysn / p rp  mCc rp 

k p C sn Cc
during the stationary phase
K sn  C sn
where Csn is the concentration of the secondary nutrient
 Mass balance on cells
For a CSTR, a mass balance on the microorganism gives :

Rate of accumulation of cells

dCc
V  v0Cc 0  vCc  (rg  rd )V
dt

Rate of net generation of live cells

Rate of cells leaving

Rate of cells entering

 Mass balance on substrates
For a CSTR, a mass balance on the substrate gives :

Rate of accumulation of substrate

dCs
V  v0C s 0  vCs  rsV
dt

Rate of net generation of substrates

Rate of substrate leaving

Rate of substrate entering

 Mass balance on cells
For a batch system, a mass balance on the microorganism gives :

Rate of accumulation of cells

dCc
V  (rg  rd )V
dt

Rate of net generation of live cells

 Mass balance on substrates
For a batch system, a mass balance on the substrate gives :

Rate of accumulation of substrate Rate of substrate used for cell growth

dCs
In the growth phase V  rsV  Ys / c (r g )V  mCcV
dt

Rate of substrate used for maintenance

dCs
In the stationary phase V  Ys / p (r p )V  mCcV
dt

dC p
Rate of product formation V  rpV  Yp / s ( r s )V
dt
Example: bacteria growth in a batch reactor
A fermentation process is carried out in a batch reactor. Plot the concentrations of cells,
substrate, and product and growth rates as functions of time. The initial concentration is
1.0 g/dm3 and the substrate concentration is 250 g/dm3.

Values of the parameters:

C *p  93g / dm3 Yc / s  0.08 g / g

n  0.52 Y p / s  0.45 g / g
 max  0.33h 1 Y p / c  5.6 g / g
K s  1.7 g / dm 3
k d  0.01h 1
m  0.03 ( g substrate) /( g cells  h)
Mass balances Rate laws Stoichiometry
dCc  Cp 
0.52
Cc C s rp  Y p / c rg
Cells: V  (rg  rd )V rg   max 1  * 
dt  C  K s  Cs
 p 

dCs
Substrate: V  Ys / c (r g )V  rsmV r d  k d Cc
dt

dC p
Product V  Yp / c (r g )V rsm  mCc
dt
0.52
dCc  Cp  Cc C s
  max 1  *   k d Cc
dt  C  K s  Cs
 p 

0.52
dCs  Cp  Cc C s
 Ys / c  max 1  *   mCc
dt  C  K s  Cs
 p 

dC p
 Y p / c rg
dt
 Chemostats
• Chemostats are essentially CSTRs that contain
microorganisms.
• One of the most important features of the
chemostat is that is allows the operator to
control the cell growth rate.
– By adjusting the volumetric feed rate

Skip this part. Refer to Profs. Chen & Liu