Objectives:

TO DISCUSS:
 Definition of ACID and BASE
Properties of Acids and Bases

(ACID-BASE Reaction/ Equilibrium)

Applications of Acids and Bases
pH and Buffers
INTRODUCTION:

INORGANIC SUBSTANCES

ACIDS BASES

SALT
Neutralization product of
Acid and Base
 Ammonia
ACID
Vinegar

Lemon Juice
or
Baking Soda

BASE Bleach

Coke / Soda
DEFINITION

ArrHenius Dissociation Theory

“Hydrogen ion and Hydroxyl ion”

Bronsted – Lowry Theory

“Proton”

Lewis Theory
“Electron-pair”
 ARRHENIUS THEORY
“Hydrogen ion and Hydroxyl ion”

Liberates hydrogen ion (H+) as the only positive ions in an

aqueous solution (Water – H20) forming HYDRONIUM
ION [H3O]

Liberates Hydorxyl ions (OH-) as the only negative ions in

an aqueous solution (Water – H20)
 ARRHENIUS THEORY
“Hydrogen ion and Hydroxyl ion”

Acid- base reaction

HCl + H2O H3O + Cl -

HNO3 + H2O H3O + NO3 -

CH3COOH + H2O H3O + CH3COO -

Equilibrium
Acid-base pair or conjugate pair
 ARRHENIUS THEORY
“Hydrogen ion and Hydroxyl ion”

MONOBASIC ACIDS – Liberates ONE Hydrogen

per molecule
 Examples:
HCl, HNO3, CH3COOH, HBr, HI
POLYBASIC ACIDS – Dissociates in more steps and
yields more than one hydrogen ions per molecule
 Examples:
Dibasic – H2SO4
Tribasic – H3PO4
 ARRHENIUS THEORY
“Hydrogen ion and Hydroxyl ion”

Acid- base reaction

NaOH Na + + OH -

KOH K + + OH -

NH3 + H2O NH4 + OH -

 ARRHENIUS THEORY
LIMITATION:
 This concept is limited by the fact that nonhydroxide-containing
compounds which function as bases or produce hydroxide ions
in an aqueous solution are not covered by the definition.
 This concept does not lend itself to extension to nonaqueous
systems.
 It is for the reason that broader concepts of acid-base reactions
have been sought, resulting in those of:
 BRONSTED-LOWRY THEORY
(Protonic Concept of Acidity)
 LEWIS THEORY
BRONSTED – LOWRY THEORY
“Proton”

A substance (charged or uncharged) that is capable of

DONATING PROTONS
“Proton DONOR”

A substance (charged or uncharged) that is capable of

ACCEPTING PROTON from an acid
“Proton ACCEPTOR”
 BRONSTED – LOWRY THEORY
“Proton”

Ionizes to produce a PROTON

and the CONJUGATE BASE

Form CONJUGATE ACID when

the base ACCEPTS a PROTON
 BRONSTED – LOWRY THEORY
“Proton”
Acid- base reaction

HCl + NH3 NH4 + Cl -

HCl + CH3COO - CH3COOH + Cl -

NH4+ H20 H3O + NH3

Acid- base reaction

NH3 + H20 OH - + NH4

 NOTE
Certain species may act as either an ACID or BASE

CHEMICAL CONDITIONS determine which type of

reaction predominates.

WATER, in the presence of a STRONG BASE reacts as a

PROTON DONOR. In the presence of an ACID it reacts as
a PROTON ACCEPTOR
GENERAL
RULE

STRONGEST ACIDS  WEAKEST CONJUGATE BASE

STRONGEST BASE  WEAKEST CONJUGATE ACID

 BRONSTED-LOWRY THEORY helps explain how

readily a substance donates and accepts protons,
a property that determines its RELATIVE
STRENGTH
 STRONG ACID - - STRONG BASE
 WEAK ACID - - WEAK BASE
 LEWIS THEORY
“Electron-pair”

A molecule or an ion that ACCEPTS an ELECTRON PAIR from

another atom
“Electron-pair ACCEPTOR”

A substance (charged or uncharged) that is capable of

DONATING AN AELECTRON PAIR from an acid
“Electron-pair DONOR”
 NOTE

RULE:
ALL BRONSTED ACIDS ARE LEWIS ACIDS
BUT NOT ALL LEWIS ACIDS ARE BRONSTED ACIDS

ALL BRONSTED BASES ARE LEWIS BASES

BUT NOT ALL LEWIS BASES ARE BRONSTED BASES
 LEWIS THEORY
“Electron-pair”

Examples:
Boron Trichloride, Aluminum Chloride, Ferric Chloride

Examples:
Amines, Ethers, Carboxylic Anhydrides

“Electron-pair DONOR”
 LEWIS THEORY
“Electron-pair”

The reactions of Lewis ACIDS and Lewis BASES involve

electron sharing rather than acid-base reactions
The product is described as an ADDUCT (Acid-base
complex or coordinated complex)
Functional Reaction:
L. Acid  A L. Base  :B

A : B or A - B
LEWIS THEORY
“Electron-pair”
HARD and SOFT ACID-BASE CONCEPT
 CategorizesACIDS and
HARD ACIDS
BASES according to their
properties of
SOFT ACIDS
 CHARGE
 SIZE(IONIC RADII) HARD BASES
 ELECTRONEGATIVITY
 POLARIZABILITY
SOFT BASES
HARD and SOFT ACID-BASE CONCEPT
 HIGH POSITIVE CHARGES HARD ACIDS
 SMALL SIZES

SOFT ACIDS
 UNFILLED VALENCE SHELL ORBITALS

 HIGH ELECTRONEGATIVITY
HARD BASES
 LOW POLARIZABILITY

 Harder Acids SOFT BASES

 Higher Oxidation state
HARD and SOFT ACID-BASE CONCEPT

 LOW POSITIVE CHARGES HARD ACIDS

 LARGE SIZES
SOFT ACIDS
 FILLED VALENCE SHELL
ORBITALS
HARD BASES
 LOW ELECTRONEGATIVITY

 HIGH POLARIZABILITY SOFT BASES

HARD and SOFT ACID-BASE CONCEPT

HARD ACIDS
 HIGH ELECTRONEGATIVITY

 EASILY REDUCED SOFT ACIDS

 STABLE VALENCE STRUCTURE

HARD BASES
 LOW POLARIZABILITY

SOFT BASES
HARD and SOFT ACID-BASE CONCEPT

HARD ACIDS
 LOW ELECTRONEGATIVITY

 EASILY OXIDIZED SOFT ACIDS

 EMPTY LOW-LYING ORBITALS HARD BASES

 HIGH POLARIZABILITY
SOFT BASES
HARD and SOFT ACID-BASE CONCEPT
TABLE 4-1 (John Block)
GENERAL RULE Hard, Soft, and
Borderline Categories of
HARD ACIDS SOFT ACIDS common Lewis Acids

TABLE 4-2 (John Block)

HARD BASES SOFT BASES Hard, Soft, and
Borderline Categories of
common Lewis Bases

MOST LEAST
Softness:
STABLE STABLE Increases down a Group
ADDUCTS ADDUCTS Decreases across a
Period
The reactivity of acids and bases is a function of
their strength.

Acids and Bases are classified either as strong or

weak depending on their acidity constant and
basicity constant.

WHAT IS ACIDITY CONSTANT?

WHAT IS BASICITY CONSTANT?
The strength of an ACID is the measure of
the ease of PROTON DONATION.

In the case of a BASE, the ease of

PROTONATION
[DEGREE OF DISSOCIATION]
 Degree of
Full
Dissociation Dissociation

How readily acids or

Partial
bases lose or gain
Dissociation
protons depends on
the chemical nature
of the compounds NO Dissociation
under consideration
 Acid Strength NOTE
Higher the Ka value
ACID DISSOCIATION STRONGER ACID
CONSTANT = Ka
The amount of HYDROGEN IONS
released when a given acid is dissolved in
water
NOTE:
 Acid strength is also determined by the AFFINITY of the
SOLVENT for PROTONS being donated (aka
BASICITY STRENGTH of the SOLVENT)
 KINDS OF SOLVENTS
 Protophilic (Acetone, Ether, Liquid Amonia)
 Protogenic (Formic Acid, Acetic Acid, Sulfuric Acid, Liquid HCl
and HF)
 Amphiprotic (Water and Alcohols)
 Aprotic (Hydrocrabons)

HCl is a strong acid in Liquid Ammonia but a

weak acid in Glacial Acetic Acid
 Is the Ka counterpart for WEAK BASES  Kb

 Ka for weak bases is expressed as the dissociation of

the conjugate acid of the base:
 Henderson- Hasselbalch Equation
(Derivation)
 Significance:
 This is an equation linking the pH, pKa of the buffer and the
logarithm of ration of the base to that of acid
 By knowing any two parameters the third can be calculated
which is helpful in determining the status of the acid base
balance in the body
 If helps for the preparation of buffer with desired pH
 Confirming the buffer capacity of a buffer
 Conducting studies on absorption of drugs
APPLICATIONS
 Formulation of Drugs (Drug Delivery System)
 Pharmacokinetic Studies
HYDRONIUM IONS
and pH

GENERAL RULE:
 The Higher the Ka value, the MORE ACIDIC the compound
(Higher ACIDITY STRENGTH)
 As the strength INCREASES, the MORE Hydrogen Ions will
dissociate into the solution (Aqueous)
 The amount of HYDROGEN IONS can determine the
acidity of a compound
Negative LOG of Hydronium Ion
TO UNDERSTAND pH,
Let’s consider this
question

WHY IS WATER
NEUTRAL?
pH = 7
IONIZATION OF WATER
 The (keq) equilibrium constant
for the ionization of water  1.8
x 10 -16 M) at 1 atm 25deg
Celsius
 1 mole H2O is equivalent to 18
g; 1000mL (1000g) of water shall
contain  1000/18 = 55.56 M/L

 ION PRODUCT OF WATER

IONIZATION OF WATER
 [H+] = 1 x 10 -7 M

 Acidic : increased Hydronium

concentration
 the higher the Hydronium conc.
= the lower the pH
 example: HCl (0.01M = 1x10-2
M/L of H+) pH = 2
 Basic : higher Hydroxide
concentration
 Example NaOH (0.01M = 1x10-2
of OH)
 pH
COMPUTATION

 Another way of computing for pH is by using the ION

PRODUCT OF WATER
 Note that when an acid is dissolved in water the
concentration of protons increases while the concentration of
hydroxide ions decreases. This is because the ion
product constant for water (Kw) is unchanged (i.e.,
constant) and the product of the concentrations of H+ and OH
must always be 1.0 x 10–14 M2 under standard conditions
SAMPLE PROBLEMS

What is the pH of a solution whose

hydrogen ion concentration is 3.2 x 10 -4 M?

What is the pH of the solution whose

hydroxide ion concentration is 4.0 x 10-4 M?
Example:
What is the pH of a solution if 1 mL of 0.1 M
HCl is added to 99 mL of H2O?
- Compute for the amount of Hydrogen ions released in
the solution (Total volume = 100 mL)
- NOTE: HCL is a STRONG ACID  100 dissociation
- 1 part of the ACID will react completely with 1 part of
H2O
- Draw the Net equation of the reaction
Example:
What is the concentration of H+ in a
solution of 0.1 M NaOH? What is the pH of
the Solution?
- Note: NaOH is a STRONG BASE
- pKw = pH + pOH
- Kw = [H][OH]
NOTE:
JOHN BLOCK (Handout)
Table 4-3 pH and pOH Relationships

Table 4-4 The Relationship Between pH and

Hydrogen Ion Concentration
 pH
DETERMINATION

There are three methods

COLORIMETRIC METHOD

ELECTROMETRIC / POTENTIOMETRIC
METHOD

CHEMICAL METHOD
COLORIMETRIC METHOD
 Utilizes reagents called INDICATORS
 INDICATORS are usually WEAK ORGANIC ACIDS in
which the undissociated molecule has one color, and
the anion or cation produced by dissociation has
another color.
 QUALITIES derired in an indicator:
 There should be a sharp contrast between the two
colors
 The color change must be effected by a small change
of pH
 INDICATOR Range of pH and COLOR CHANGE

Meta Cresol – Purple 1.2 (RED) to 2.8 (YELLOW)

Hellige Orange 2.6 (RED) to 4.2 (YELLOW)

Bromophenol Blue 3.0 (YELLOW) to 4.6 (BLUE)

Methyl Orange 3.1 (RED) to 4.4 (YELLOW)

Bromocresol green 4.0 (YELLOW) to 5.6 (BLUE)

Methyl Red 4.2 (RED) to 6.3 (YELLOW)

Chlorophenol Red and
5.2 (GREEN) to 6.8 (PURPLE)
Bromocresol Purple
 INDICATOR Range of pH and COLOR CHANGE

Bromothymol Blue 6.0 (YELLOW) to 7.6 (BLUE)

Phenol Red 6.8 (Yellow) to 8.4 (RED)

Cresol Red 7.2 (YELLOW) to 8.8 (RED)

Thymol Blue 8.0 (YELLOW) to 9.6 (BLUE)

Phenolphthalein 8.3 (COLORLESS) to 10 (RED)

Thymolphthalein 9.4 (COLORLESS) to 10.6 (BLUE)

10 (FAINT YELLOW) to 11.6 (DEEP
Nitro Yellow
YELLOW)
Violet 12 (PURPLE) to 13.6 (BLUE)
POTENTIOMETRIC METHOD
 Based upon the measurement of the voltage
developed between special electrodes when
immersed in solutions
 The difference in the potential is DIRECTLY
DEPENDENT upon the presence of H3O in the
solution
 Preferred by the USP because of its ACCURACY,
RAPIDITY, and because it can be used in turbid and
jelly-like solutions and in solutions containing
pigments and proteins
CHEMICAL METHOD
 It is not used practically as a
OTHER METHODS:
method for determining pH
pH PAPER
 One means of determining
pH chemically is to compare
the rate of inversion of
sucrose with rate at which
and acid of known hydrogen-
ion concentration inverts the
sucrose under the same
conditions
 HENDERSON-HASSELBALCH
EQUATION
 Express the relationship between DISSOCIATION
CONSTANT and pH
HENDERSON-HASSELBALCH
EQUATION
 HENDERSON-HASSELBALCH
EQUATION
 When the pH of a solution is less than the pKa of an acid,
the protonated form predominates. (Remember that the
definition of pH includes a negative logarithm)
 When the pH of a solution is greater than the pKa of an
acid, the deprotonated (conjugate base) form
predominates.
BUFFERS
 Defined as solutions that can resists change in
pH following the addition of strong acids or
bases

 BUFFER CAPACITY- the capacity to resist the

change is pH

 Acetic acid and phosphoric acid  most effective

buffers used in solutions
BUFFERS
MECHANISM:
 When small amounts of hydrogen ions are introduced into
the medium they will react with the conjugate base or
basic member of the buffer to form the weak acid which,
by definitions, will be only slightly ionized.
 When small amounts of hydroxide ions are introduced
into the medium, they will react with the weak acid or
acidic member of the buffer to form water or conjugate
base
 HENCE, each component of the buffer pair will react with
either acid or base to form the other component, thereby
repressing large changes in hydrogen ion concentrations
BUFFERS
SELECTION:
 The selection of a buffer system for pharmaceutical
purposes is based on both
 CHEMICAL FACTORS – should not react with other chemicals
in the preparation
 PHARMACOLOGICAL FACTORS – should NOT INTERFERE with
the pharmacologic properties of the active ingredients
CATEGORIES
 Standard buffer systems which are designed to provide a
solution having a specific pH for analytical purposes
 Actual buffers designed to maintain pH limits in drug
preparations
SAMPLE PROBLEMS
Acetic acid has a pKa pf 4.8. How many mL
of 0.1 M Acetic acid and 0.1 M Sodium
Acetate are required to prepare 1 L of
0.1M buffer solution having a pH of 5.8.
SAMPLE PROBLEMS
 What is the pH when 100 mL of 0.1 N NaOH is
added to 150 mL of 0.2 M HAc if pKa for acetic
acid 4.76?
- Draw the net chemical equation
- Compute for the following:
- The amount of Na acetate produced from the
dissociation of Acetic acid
- The amount of Acetic acid remained after the
dissociation
ADDITIONAL READING
[John Block]
CHAPTER 4 – Pharmaceutical Aids and
Necessities
 OFFICIALAND NON-OFFICIAL ACIDS AND BASES
 ANTIOXIDANTS – Official Antioxidants
 WATERS
 Alkaline, Carbonated, Chalybeate , Lithia, Saline, Sulfur,
Siliceous waters
 Hardness of Water
 Official Waters
 PHARMACEUTICALLY ACCEPTABLE GLASS
COVERAGE OF PRELIM EXAM

LECTURE 1–3
ADDITIONAL LECTURE NOTES
 Uploaded on FB group
 Chapter 4 - [John Block]