pka and acid dissociation constant

Introduction : Dissociation constant.
Dissociation of molecules in water.
Acid dissociation constant.
Theoretical background.
Conjugate acid & Conjugate base.
Handerson-Hasselbalch equation.
Factors affecting pKa values.
Experimental determination.
Application & Significance.
Conclusion.
References.

1. Acid Dissociation
Constant
pK
a
By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )

2. Synopsis
Introduction : Dissociation constant.
Dissociation of molecules in water.
Acid dissociation constant.
Theoretical background.
Conjugate acid& Conjugate base.
Handerson-Hasselbalch equation.
Factors affecting pK
a values.
Experimental determination.
Application & Significance.
Conclusion.
References.

3. Introduction
Dissociation Constant:
A dissociation constant is a specific type of
equilibrium constant that measures the
tendency of larger objects to separate or
dissociate into smaller components. Example
–A complex fall apart into it’s constituent
molecules or when a salt splits up into it’s
component ions.
In some special cases of salt, the
dissociation constant is also known as
ionization constant.

4. Dissociation of molecules in
water
Water is the most
important component
for life on earth
because of it’s unique
physiochemical
properties.
It also has a unique
solvent property & thus
known as the ‘universal
solvent’.
It shows a dipole
structure & hence is
polar in nature. It has
the ability to form
hydrogen bond.

5. Substances that dissociate in water into cations &
anions are called electrolytes.
These ions facilitates conductance of electric
current.
Salts of alkali metals (e.g. LiCl, KCl, NaCl) & salts
of organic acids (e.g. sodium acetate) dissociate
completely.
Many acids, however, when dissolved in water, do
not dissociate totally but establish an equilibrium
between dissociated & undissociated components.
E.g. Acetic acid.
CH
3COOH + H
2O
CH
3COO
-
+ H
3O
+
Acetic acid
CH3COOH
H
2
O
Acetate ion CH
3COO
-
H
3O
+

6. On molar basis, such compounds are termed as
‘weak electrolytes’, which dissociate partially &
have a lower capacity to carry an electric current.
On the other hand, ‘strong electrolytes’ are those
that dissociate completely.

8. Water is a weak electrolyte
Water dissociates as follows:
H
2O H
+
+ OH
–
In partial dissociation of weak electrolyte H
2O,
the constant for above equilibrium equation can be
written as:
K
eq = [H
+
] [OH
-
]
[H
2O]
Where, K
eq = physical constant or equilibrium
constant.
At 25
o
C the value of K
eq for water is very small.
Thus the concentration of water molecules is
almost constant.
K
eq x [H
2O] = [H
+
] [OH
-
]
It is also termed as ionic product of water
denoted by K
w.

9. K
wis also known as autoprotolysis constant of
water.
At 0
o
C K
whas a value 1.14 x 10
-15
& at 100
o
C K
whas a value 5.45 x 10
-13
Many biomolecules of biological importance are
weak electrolytes. E.g. amino acids, peptides,
proteins, nucleosides, nucleotides & nucleic acids.
Their biochemical function depends upon their
state of ionization at the prevailing cellular or
extra-cellular pH.
E.g. The catalytic site of an enzyme suppose
contain functional group as carboxyl or amino
group. To enable the catalytic function of these
enzymes, the amino acid side chain in the protein
need to be in specific ionized state.

10. Acid dissociation constant
An acid dissociation constant K
a(also known as acidity
constant or acid ionization constant) is a quantitative
measure of strength of an acid in the solution. It is
the equilibrium constant for a chemical reaction known
as dissociation in the context of acid-base reaction.
The equilibrium can be written symbolically as below:
HA H
+
+ A
–
Here, HA is a weak acid that dissociates into H
+
cation & A
–
anion. Hence, the dissociation constant
may be written as:
K
a= [H
+
] [A
–
]
[HA]
A logarithmic measure of K
ais more common &
convenient term used in practice. pK
a is the negative
log of K
a& is also referred to as acid dissociation
constant.

11. Theoretical background
The acid dissociation constant for an acid is a
direct consequence of thermodynamics of the
dissociation reaction taking place.
The pK
avalue is directly related to the standard
energy change in the reaction, thus it alters with
change in temperature.
When the reaction is endothermic, the pK
avalue
decreases with increasing temperature.
When the reaction is exothermic, the pK
avalue
increases with the decreasing temperature.
The larger is the value of pK
a, the smaller is the
extent or degree of dissociation & vice versa.

12. Conjugate acid & Conjugate
base
Bronsted & Lowrydefined acid & base on the basis
of proton exchange concept.
According to them, an acid is a proton donor & a
base is a proton acceptor.
Thus, a weak acid & it’s base i.e. the anion
formed after dissociation are referred to as
Conjugate pair.
It may be described by following equations & few
examples:
conjugate acid conjugate
base + H
+
e.g. CH
3-CHOH -COOH H
+
+ CH
3-
CHOH -COO
–
lactic acid
lactate ion
CH
3-CO -COOH H
+
+ CH
3-
CO -COO
–

14. Handerson-Hasselbalch
Equation
It defines the relationship between, pH, pK
a&
concentration of Conjugate acid & Conjugate base.
conjugate acid conjugate base +
H
+
At equilibrium,
K
a= [H
+
] [conjugate base]
[conjugate acid]
Rearranging above equation & taking log on both
the sides, we get,
log 1 = log 1 + log
[conjugate base]
[H
+
] K
a
[conjugate acid]
pH = pK
a+ log [conjugate base]

15. At half neutralization, when ratio of concentration
of [conjugate base] / [conjugate acid] is 1 : 1 ,
pH equals the pK
a of acid as log 1 = 0.
Thus, the pH of the solution can be predicted
when pK
a value & concentration of acid & base are
known & conversely it is possible to calculate the
equilibrium constant when pH of the solution is
known.
These calculations find application in many
different areas of chemistry, biology, medicine &
geology.

16. Dissociation constant is a
characteristic feature
The pK
avalues for different acids are definite &
constant.
Monoprotic acid:Acid that can lose only one
proton.
e.g. Acetic acid pK
a = 4.76
CH
3COOH + H
2O CH
3COO
-
+
H
3O
+
Ammonium ion pK
a = 9. 25
NH
4 H
+
+ NH
3
Polyprotic acid:Acid that can lose more than one
proton.
Diprotic acid –Acid that loses two protons.
e.g. Carbonic acid
H
2CO
3 HCO
3
-
+ H
+
pK
a = 3.77
Bicarbonate ion
HCO
3
-
CO
3
2-
+ H
+
pK
a = 10. 2

17. Triprotic acid –
e.g. Phosphoric acid pK
a = 2.15
H
3PO
4 H
2PO
4
-
+ H
+
Dihydrogen phosphate pK
a = 7. 2
H
2PO
4
-
HPO
4
2-
+ H
+
Monohydrogen phosphate pK
a = 12.4
HPO
4
2-
PO
4
3-
+ H
+

18. Factors affecting pK
avalues
In organic acid, inductive effect & mesomeric
effect affects pK
avalues. E.g. pK
avalue for
acetyl chloride CH
3COCl is 2.8 whereas for acetic
acid CH
3COOH, it is 4.7.
Structural effects can also be important. The
difference between structures of fumaric acid &
maleic acid is a classic example.
Fumaricacid Maleic acid
(E) 1,4-but-2-ene dioic
acid
(Z) 1,4-but-2-ene dioic
acid

19. pK
avalue also depend on the properties of the
medium or the solvent, whether the solution is
aqueous or non-aqueous.
pK
a value is inversely proportional to the extent or
degree of dissociation. Higher the dissociation of
acid, lower is it’s pK
a value.
The pK
a value vary with temperature.
The pK
a value & % speciation also depends on pH
values.

20. Experimental determination:
The experimental determination of pK
a value is
commonly performed by means of titration. A
typical procedure is followed at constant
temperature.
A solution of the compound is acidified with a
strong acid so that it is fully protonated.
This solution is then titrated against strong base
until all the protons are removed.
At each point during titration, pH is measured with
pH meter.
The values of concentration of conjugate base &
conjugate acid is determined by buffer region.
All the values are suitably substituted in
Handerson-Hasselbalch equation to get the pK
a
value.
For calculating pK
avalues in non-aqueous solution,

22. Application & Significance of
pK
a
A knowledge of pK
avalue is important for
quantitative treatment of systems involving acid-
base equilibria in solution.
Many applications exist in Biochemistry. E.g.
-pK
avalues of protein & amino acid side chain are
of major importance for understanding the enzyme
activity & stability of protein respectively.
-Buffer solution are used to obtain a desired
physiological pH for study of any biochemical
reaction & the selection of components for
preparing this solution depends on their pK
a
values.

23. -pK
avalue also help in isoelectric focusing, a
technique used for separation of protein by gel
electrophoresis. Different molecules have different
isoelectric points. Isoelectric points of a molecule
are function of it’s pK
avalues.
In the field of Chemistry, pK
avalues are important
to make buffer solution which are used to get a
desired pH in a solution & also helps in
understanding co-ordination complexes.
In aquatic chemistry or chemical oceanography,
where acidity of water plays a fundamental role,
knowledge of pK
avalue is must.
In Pharmacology, ionization of compound alters it’s
physical behavior & macro properties such as
solubility. These medicinal compounds are weak
acid & bases. During drug manufacture, pK
avalues
of the compounds must be known before they enter
human body.

24. pK
avalues for some common
substances
Adenine
Ascorbic acid
Benzoic acid
Cresol
Carbonic acid
Formic acid
Glycine
Hydrogen peroxide ( 90% )
Lactic acid
Oxalic acid
Phenol
Succinic acid
4. 17 , 9. 65
4. 17, 11 . 57
4. 2
10. 29
3. 77 , 10. 2
3. 7
2 . 3 , 9 . 6
11 . 7
3 . 86
1 . 3
9 . 99
4. 2 , 5 . 5

25. Conclusion
Thus acid dissociation constant is an important
aspect in Chemistry, Biochemistry, Pharmacology,
Geology, Environmental science & several other
life sciences. In living organisms, the acid-base
homeostasis & enzyme kinetics is dependent on pK
a
values of acids present in the cell. Many medicinal
compounds are weak acid & bases, hence a
knowledge of pKa is must before they enter
human body. It is a small but significant topic to
be considered while major studies.

26. References
Nelson & Cox –Principles of Biochemistry, Fourth
edition (2005)
Thomas M. Delvin –Text book of Biochemistry
with clinical co-relations, Sixth edition.
Keith Wilson & John Walker –Principles &
techniques of biochemistry.
Atkins-Chemical Principles, Fourth edition.
Skoog, Holler-Fundamentals of Analytical
Chemistry, Eighth edition.