Lecture 2

Eman El-Marakby, Phd

Lecturer of Pharmaceutics &
Industrial Pharmacy,
Faculty of Pharmacy, Ain Shams
University
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In this lecture you will learn:

■ Solubility and the process of dissolution

■ Energy change during dissolution
■ Types of intermolecular forces
■ Classification of solvents

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Solubility :
Is the concentration of a solute in a
saturated solution at a certain
temperature.
Or
it is the spontaneous interaction of two or
more substances to form a homogenous
molecular dispersion.

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■ When excess solid is brought into contact with a
liquid, molecules of solids are removed from its
surface till

Molecules at certain Molecule

temp
leaving s
solid returnin
g to solid

Saturated
solution

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■ This dynamic equilibrium was confirmed by:

Prepare a saturated sodium iodide solution ( 127I)

→filter → add to the clear filtrate sodium iodide ( 131I)
⇨ filter → radioactivity was noticed in solution
indicating the exchange between the solid and the
saturated solution of NaI

Excess undissolved solid Saturated

solution

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 Rate of transfer of ions or molecules from solid state
to solution

Dissolution

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■ The rate of solution (dissolution) and
amount which can be dissolved
(solubility) are not the same.
■ ← Solubility ← dissolution
rate

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 The Process of Dissolution
1. The solute molecule is separated from other similar molecules.

2. The solvent molecules are separated sufficiently from other

molecules to create space to accommodate the solute
molecule.

3. The solute molecule becomes surrounded by solvent molecules

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Energy changes

∆G = ∆H - T∆S

∆G = Gibb’s free energy (measure of energy free in

system to do work)
∆H = Change in enthalpy of system (amount of heat
absorbed or evolved as system changes its
thermodynamic state)

T = Thermodynamic temperature (absolute temp.)

∆S = Change in entropy (measures the degree of

disorder or randomness) 9
 ∆G = ∆H - T∆S

In case of ideal solutions

∆H = Zero

∆G depend on T∆S

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 In most real systems, for a process of
dissolution to occur spontaneously

∆G
Must be
negative

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 ∆G = ∆H - T∆S
As T∆S is usually +ve, then dissolution will
occur if

∆H is
negative,
Zero or
slightly +ve
(its value less
than T∆S
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Example
In the case of crystalline solid dissolving in
liquids

∆H = ∆Hcl + ∆Hsolv
∆Hcl = Change in crystal lattice enthalpy (heat
absorbed when molecules or ions of crystalline
solute are separated by infinite distance against
intermolecular attractive forces). It is always +ve.

∆Hsolv = Change in solvation enthalpy. Heat absorbed

or evolved when solute molecules are immersed in
solvent, most commonly –ve (heat evolved). 13
 The Process of Dissolution
1. The solute is separated from other similar molecules.

+ ∆Hcl

2. The solvent molecules are separated sufficiently from other

molecules to create space to accommodate the solute
molecule.

3. The solute molecule becomes surrounded by solvent molecules

+ ∆Hsol

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If
∆Hcl > ∆Hsolv
∆H is +ve and the process is endothermic.

If
there is affinity between solute and
solvent, -ve ∆HSolv is so great, it is > +ve
∆Hcl
∆H is -ve and the process is exothermic.

∆H = ∆Hcl + ∆Hsolv
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Thus
Dissolution will occur only if the solute and
solvent are sufficiently attractive to overcome
the solute-solute and solvent-solvent interaction.

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■ There are two main types of forces that can
occur in a compound

Intramolecul Intermolecul
ar forces ar forces

H--O--H H--O--H
H--O--H

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 The intermolecular bonds between solvent
and solutes:
■ Van der Waals forces:
(1) Dipole-dipole (Keesom force)
(2) Dipole-induced dipole (Debye force)
(3) Induced dipole-induced dipole (London force)

■ Hydrogen bonds
■ Ion-Dipole forces (e.g. NaCl in H 2O)

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1. Dipole-dipole force (Keesom force)

Polarized
(partial ionic
character) Permanent Polar
dipole compound

The strength of the dipole-dipole force depends

on polarity, ↑ polar each molecule, the stronger
.the magnetic force present 19
CCl4

Methane
(CH4)

Non polar
CHCl3

CH2Cl2 CH3Cl

Polar 20
2. Dipole-induced dipole force (Debye force)
What would happen if we mixed HCl with argon, which
has no dipole moment?

Weak dipole-induced dipole force of attraction

between the HCl molecule and the Ar atom.

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3. Instantaneous dipole-induced dipole force (London
force)

Polar molecules behave like magnets. How can a non

polar molecule (have zero dipole moment) stick
together if some attractive forces did not exist?

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They are temporarily
induced dipoles that
lasts for a very short
time

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Hydrogen bond
■ Hydrogen bonds occur in polar molecules.
■ It occurs in molecules containing a
hydrogen atom that is bonded to a N, O or F
atom.

Hydrogen bonds are much stronger than

dipole-dipole forces
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 Why intermolecular forces are important?

It explains lot of things

■ ↑ Intermolecular forces → ↑ B.P and M.P.
■ They explain the concept of solubility "like
dissolves like".

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Classification of solvents
On the bases of forces of attraction between solvent
molecules

Polar Non polar

Semipolar
-Made of Small or
strong dipole. -Made of
strong dipole. no dipole
-Form H bond character
(H2O) -Do not form H (benzene,
bond (acetone) vegetable
oil,
mineral
oil)
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There are many solvents that fit in more than one
class

■ Chloroform: has weak dipole but considered

non polar
■ Glycerin: can form hydrogen bond, considered
polar and semipolar.

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Physicochemical prediction of solubility

The concept is that:

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Polar solute Non polar
in polar solute in polar
solvent
Will dissolve to a solvent
Force of attraction
greater extent between molecules
because the of polar solvent
strength of solute- will be too great to
solvent facilitate the
interaction is insertion of the non-
comparable to polar solute in-
solute-solute between
interaction
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 Polarity of Some Solvents and
Solutes:
Dielectric Solvent Solute
constant
80 P Water Inorganic Salts, Organic
Salts
50 SP Glycols Sugars , Tannins
30 SP Methyl and Ethyl Alcohols Castor Oil, Waxes
20 SP Aldehydes, Ketones and Resins, Volatile Oils,
Higher Alcohols, Ethers, Weak Electrolytes
Esters and Oxides including Barbiturates,
Alkaloids and Phenols
5 NP Hexane, Benzene, Carbon Fixed Oils, Fats,
tetrachloride, Ethyl Ether Petrolatum, Paraffin,
Other Hydrocarbons
0 NP Petroleum Ether, Mineral Oil
and Fixed Vegetable Oils

Decreasing polarity P: Polar SP: Semipolar NP: Nonpolar30

Mechanisms of solvent action
A- Polar solvents
1- Overcome the attraction between ions in salts by its
dipole
■ Separation of cations and anions .

■ Orientation of solvent about the ions, this is

solvation (if water, it is hydration)
■ This needs the solvent to be highly polar so dipoles of
solvent are attracted and held to the solute ions.
solvent must keep charged ions apart with minimum
energy.

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2- Break covalent bond producing ionic components

Polar liquid (water) can break covalent bond → then,

similar to ionization of salt, solvation (or hydration)
follows.

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3- Form association complex with solute
■ Polar solvents can form hydrogen bonds, e.g.
solubility of low molecular wt alcohols in water
which is attributed to the ability of alcohol
molecules to become part of water-alcohol
association complex.

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3- Form association complex with solute
■ Molecules of (ether, aldehydes, ketones) do not
associate due to absence of a H atom that can form H
bond but they are polar due to the presence of
strongly electronegative oxygen which can form H
bond with water

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B- Non polar solvent
■ (ketones and alcohols) induce polarity in nonpolar
solvents.
e.g. alcohol (semipolar) dissolve in benzene (nonpolar)
through permanent dipole --induced dipole force (it
induces temporary dipole in benzene molecules
producing association complex with benzene).

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B- Non polar solvents

1- Induced dipole- induced dipole

e.g. - a hydrocarbon is dissolved in another
hydrocarbon
- an oil or fat in petroleum ether

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