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Learning objectives• At the end of this lecture, students should be able to:1. Characterize electrolytes2. List properties of acid and bases3. Describe electrolyte ionization phenomena4. Calculate pH and pKa equations for solutions and salts5. Identify the importance of ionization
What is electrolytes?
• Electrolyte: a substance (acid, base or salt) that ionizes to positive ions (cations) and negative ions (anions) in aqueous solution.
Properties of electrolytes
• Exhibit anomalous colligative properties compared with nonelectrolytes• irregular and inconsistent colligative properties
• Can conduct an electric current• cations and anions get distributed throughout
the solution• ions are free to move and carry electrons
Bronsted-Lowry concept• Acid is a substance, charged or uncharged, that is capable of
donating a proton.• Base is a substance, charged or uncharged, that is capable of
accepting a proton.
Strength of acids and bases• The relative strengths of acids and bases depend on:• The tendencies of the substances to give up or take on protons• Type of solvent
• HCl in water vs HCl in glacial acetic acid• Acetic acid in water vs acetic acid in liquid ammonia
Strong acids and strong bases• Example: Hydrochloric acid
HCl + H2O H3O+ + Cl-
• A strong acid because it has strong tendency to ionize.• Extent of ionization is pH-independent
Weak acids and weak bases• Example: phenol in water
• Weak tendency to ionize.• Ionization is pH-dependent
Ionization of weak acids
Consider the following rxn
HA + H2O H3O+ + A-
•What is the rate of forward rxn, Rf?
•What is the rate of reverse rxn, Rr?
k1
k2
• A balance will be attained when the two rates are equal
Rf = Rr
• Concentrations of products and reactants are not necessary equal at equilibrium; the speeds of the forward and reverse rxn are what are the same.
• Equation for Ka can be represented in a more general form:
C= initial molar concentrationX= represent [H3O+] and [A-] because both are formed in equimolar concentration
HA + H2O H3O+ + A-
(c) x x
• Rearrangement:
-log [H+] = ½(-log Ka –log c)
pH= ½ pKa - ½ log c• This equation is useful for calculating the pH of a weak acid in
water if c (molar concentration) and pKa for weak acid is known.
• Example 4 (Applied Physical Pharmacy, Amiji & Sandmann)
• Calculate the pH of a 0.1 M solution of a weak acid at 25°C. pKa of acid is 4.76 at 25°C
• Rearrangement gives
pH= pKa + log [A-]
[HA]
• This equation can be used to calculate the ratio of ionized form to the unionized form of drug in fluids (eg physiologic fluids).
• Example 5 (Applied Physical Pharmacy, Amiji & Sandmann)
• Salicylic acid is an organic weak acid with pKa of 3.0.• Calculate the ratio of ionized:unionized of this drug in
stomach with pH 1.2.• Ratio of unionized form:ionized• Percent of unionized form in stomach
Ionization of weak bases• Consider the rxn:
B + H2O OH- + BH+
• So,
Kb = [OH-] [BH+]
[B]• This leads to
[OH-]= √Kbc
• To change the ionization expression for bases to Ka, the equilibrium is written as follows:
BH+ B + H+
K1/k2= Ka = [B] [H+]
[BH+]
•How to calculate pH using Ka?*Clue: take log of equation, then equate [H+] to [B] (because they are equimolar).*pH of protonated weak base can be calculated using this equation.
• Example 6 (Applied Physical Pharmacy, Amiji & Sandmann)
• Calculate the pH of a 0.1 M solution of a weak base (triethylamine) at 25°C. pKa of base is 9.72 at 25°C
• To calculate the ratio of freebase to the ionized form of drug in fluids (eg physiologic fluids).
pH= pKa + log [B]
[BH+]
• Example 7 (Applied Physical Pharmacy, Amiji & Sandmann)
• Calculate the approximate percentage of codeine present as free base in the small intestine (pH 6.5). pKa codeine= 7.9.
• A salt is formed by an acid-base rxn involving proton donation or proton acceptance.
• When salt is added to water, the solution can be neutral, acidic or basic (depend on salt).• Interaction of ions of salts with ions of water is called hydrolysis
Salts of strong acids and strong bases• Salts of this class do not undergo
hydrolysis• [H+] and [OH-] unchanged• Example: NaCl
Salts of weak acids and strong bases• These salts completely ionize in aqueous solution.• Hydrolysis rxn results in basic pH
NaA Na+ + A-
The conjugate ion A- interact with water, results in alkaline soln
H2O + A- HA + OH-
• Example of salt: Sodium acetate• Calculation of pH uses the equation:
pH= ½ pKw + ½ pKa - ½ log [A-]
• Example from Amiji and SandmannWhat is the pH of a sodium acetate solution with pKa of 4.76 and concentration of salt is 0.1M?
Special cases• For the rxn of weak acid with calcium or magnesium hydroxide
(molecules with valence >1), concentration of salt is multiplied by number of moles required to react with 1 mole of strong base.
MgS2 Mg2+ + 2S-
[S-]= 2CpH= ½ pKw + ½ pKa - ½ log nC
Salts of strong acids and weak bases• These salts completely ionize in aqueous solution.• Hydrolysis rxn results in acidic pH
BHCl BH+ + Cl-
The conjugate ion BH+ interact with water, results in acidic soln
BH+ + H2O B + H+
• Salt example: ephedrine hydrochloride• The equation for pH calculation
pH= ½ pKa - ½ log [BH+]• Example from Amiji & Sandmann• Calculate the pH of 0.1M ephedrine hydrochloride in water,
pKa= 9.36
Special cases• For the rxn of weak base with sulfuric acid (molecules with
valence >1), concentration of salt is multiplied by number of moles required to react with 1 mole of strong acid.
(Eph)2 SO4 2 EpH+ + SO4-
[Eph+]= 2CpH= ½ pKa - ½ log nC
• Polyprotic electrolyte:• Polyprotic acid = capable of donating two or more
protons• Polyprotic base = capable of accepting two or more
protons Ionizes in stages
• What if capable of donating/accepting only one proton?
• Example: ionization/ protolysis of phosphoric acid
H3PO4 + H2O = H3O+ + H2PO4- 1 (K1: 7.5 x 10-3)
H2PO4- + H2O = H3O+ + HPO4
2- 2 (K2: 6.2 x 10-8)
HPO42- + H2O = H3O+ + PO4
3- 3 (K3: 2.1 x 10-13)
The primary protolysis is the greatest and succeeding stages become less complete
• Each of the species formed by ionization can also act as a base.
• In general, if the parent acid is HnA, there are n + 1 possible species in soln.
• Remember: phosphoric acid can function as acid and also a base.
• This means that it is an ampholyte/ amphoteric electrolyte• a species that can function either as acid or base
• Important ampholyte: amino acids and proteins• Example: glycine hydrochloride
+NH3CH2COOH + H2O +NH3CH2COO- + H3O+
+NH3CH2COO- + H2O NH2CH2COO- + H3O+
• The species +NH3CH2COO- is amphoteric as it reacts with water to form
+NH3CH2COO- + H2O +NH3CH2COOH + OH-
• The amphoteric species is a zwitterion because it carries both a positive and negative charge, and the whole molecule is electrically neutral
+NH3CH2COO-
• The pH where the zwitterion concentration is maximum is known as the isoelectric point• The net charge of the molecule is zero• No migration of protein in applied electrical field
Importance of ionization in pharmacy
• Many drugs are weak electrolytes• Degree of ionization is important and have physiologic
implication• Affect absorption, transport and excretion of drugs• Generally: ionized forms are more water soluble and unionized
form is more lipid soluble.• pH of environment determine ratio of ionized: unionized form• A small change in pH can result in big change in ratio• Affect solubility, dissolution rate, stability etc.
• Electrolytes is used extensively in pharmacy hence the properties must be understood.
• Ionization of electrolytes involve acid, base and salt.• Determination of Ka enable the determination of pKa, pH and
concentrations of reactants.• Knowledge on ionization facilitate the understanding of how
drugs react in body.