Ionic equilibriaWan Rosalina Wan Rosli, PhD

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

• Tend to show rapid chemical reaction compared with nonelectrolyte solution

ACID AND BASES THEORIES

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 ELECTROLYTES

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.

• Try solving for the ratio k1/k2 with [H2O] constant at 55.3 moles/liter.

Ka= k1/ k2= ?

• 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

• Now the equation becomes Ka= x2/c • Rearrangement:

x2= Kac x= [H3O+]= √Kac

• 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

•How to calculate pH using Ka?

*Clue: take -log of equation

• 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.

• To calculate the pH of organic weak base (free base)

pH= ½ pKw + ½ pKa - ½ log [B]

• 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.

IONIZATION OF SALTS

• 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

• Example in Amiji and Sandmann:

•What is the pH of 0.01 M magnesium stearate in water. pKa= 5.75.

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

• Example in Amiji & Sandmann• What is the pH of 0.1M epehedrine sulfate, pKa for

ephedrine= 9.36

IONIZATION OF POLYPROTIC ELECTROLYTES

• 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.

IONIZATION OF AMPHOTERIC ELECTROLYTES

• 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

WHY LEARNING THIS IS SO IMPORTANT?

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.

CONCLUSION

• 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.

THANK YOU