UNIT- II

kiran
 2. Physical properties of drug
1. Thermodynamics: molecules:

The Zeroth law of Dielectric constant

thermodynamics
Induced Polarization
First law
Dipole moment
Second law
Refractive index
Third law of thermodynamics
Molar refraction
Free energy functions and
applications. Optical rotator dispersion
1 – ZEROTH LAW OF
THERMODYNAMICS
Thermodynamics: Thermodynamics is defined as the study of flow of heat or any
other form of energy into or out of a system, as it undergoes a physical or chemical
composition.
Zeroth Law :
One of the most fundamental areas of physics is thermodynamics. Thermodynamics
is the study of energy exchanges between different systems and has a vast number
of applications in science and engineering.
We’ll begin by introducing the Zeroth Law of Thermodynamics.
It was introduced after the 1st and 2nd law had been already established and thus
the name.
Consider 3 different objects enclosed in an insulating container as shown:
1) Object C is brought into contact with object A until they both reach the same
temperature T ’ and the properties of both objects are stable. When this occurs we
say both objects are in Thermal Equilibrium. Two objects are in thermal
Equilibrium if and only if they have the same temperature.
2) We now place object C in contact with object B and observe that both objects also
come to thermal equilibrium at the same temperature T’.
3) When object A and B are placed in contact experimentally we find that nothing
happens! The properties of both objects remained unchanged.
Thus, we conclude:
Zeroth Law of Thermodynamics: If objects A and B are separately in
thermal equilibrium with a third object C, then A and B are in thermal
equilibrium with each other (same temperature).
2 – FIRST LAW OF
THERMODYNAMICS
The first law of thermodynamics is a statement of the law of conservation of
energy.
It expresses the fact that although energy can be transformed from one kind to
another, it can neither be created nor destroyed.
This fact can be expressed in the form of Einstein’s equation.
Energy = (change in mass) x (velocity of light) 2
E= m. c 2
The first law of thermodynamics states that the total energy of a system and
its immediate surroundings (isolated, system) remains constant during any
operation.
The change in the internal energy of a system is equal to the heat added to the
system minus the work done by the system.
The statement can be expressed mathematically as:
ΔE=Q-W
Where, ΔE = internal energy
Q = heat absorbed (or given-to the system)
W = work done by the system
Since the system is isolated, no exchange of heat or mass takes place, i.e., the
system cannot experience any change in the internal energy. In other words, the
internal energy of an isolated system is constant.
Explanation:
Heat absorbed (Q):
Heat input is necessary before work is done by the system.
By convention, heat input is designated as positive sign, +Q. If the heat is
produced by the system (output), then Q is designated as negative sign, i.e., -Q.
Capital letter, Q, signifies a finite change in its quantity. lnfinitesimal change is
denoted by ‘q’.
The amount of heat absorbed vari4es depending on the path used to carry out
the process.
Hence, Q is an inexact differential.
Work done (W):
A system does work after absorbing heat.
By convention, work is done by the system and hence it is denoted by negative
sign, -W.’
If work is done on the system (eg:’ compression of piston etc.), then W is
designated as positive sign, +W.
Capital letter, W, signifies finite change in quantity.
Infinitesimal change is denoted by ‘w’.
The amount of work done by the system varies depending on the path used to
carry out the process.
Therefore, W is inexact differential.
The units are joules (J).
One joule is the work done when a force of 1 newton is moved through a
distance of l metre in the direction of force.
When a gas is heated, some of the heat energy is the internal energy increases,
particularly by increasing the velocities of the molecules.
The remaining heat energy is utilized for providing work of expansion.
Internal energy (ΔE):
Internal energy results from the motion of molecules, atoms, electrons and nuclei
in a system on account of kinetic and potential energies.
It is difficult to evaluate the internal energy in absolute terms, but changes in the
internal energy can be determined.
It is obtained from the measurable properties such as pressure (P), volume (V)
and temperature (T).
Any two variables can be fixed to obtain E. Internal energy depends only on the
initial and final conditions.
ΔE= E2-E1
Where, E2= internal energy of the system at final state
E1= internal energy of the system at initial state)
Limitations of First Law:
1) First law of thermodynamics put no restriction on the direction of flow of heat.
2) First law does not tell whether a specified change (or process including a
chemical reaction) can occur spontaneously.
3) First law does not tell that heat energy cannot be completely converted into an
equivalent amount of work without producing some change elsewhere.
3 – SECOND LAW OF
THERMODYNAMICS
 Second law, of thermodynamics states that whenever a spontaneous
process takes place, it is accompanied by an increase in the total energy
of the universe.
In the above statement, universe means the system and its surroundings. So
second law of thermodynamics can be expressed as:

According to second law:

When a spontaneous process occurs, the entropy (entropy is a measure of
randomness of the molecules in the system) of the system and the
surroundings increase.
In case of a reverse process, the entropy of the system is constant.
Since the entire universe is undergoing spontaneous change, the second law can
be restated that the entropy of the system is constantly increasing.
4 – THIRD LAW OF
THERMODYNAMICS
The third law third law of thermodynamics states that the entropy of a
pure crystalline substance is zero at absolute zero temperature.
In Crystals, the arrangement of ions or molecules shows the greatest
orderliness at absolute zero temperature. Hence the entropy becomes zero,
S=0.
For example, water above 100 °C at one atmosphere exists as a gas. In this
state, the randomness of molecules indicates the highest disorder or entropy.
When the system is cooled, the water vapour condenses to form liquid. The
molecules have restricted movement. In other words disorderliness is less or
entropy decreases.
On further cooling, the water molecules join to form the ice crystals The water
molecules are highly ordered and hence entropy of the system is very low as
shown below.
Thus, the entropy of a substance varies directly with temperature. The lower
the temperature, the lower is the entropy.
Accordingly, absolute zero is the temperature at which the kinetic energy of
molecules becomes zero. Since, it is independent of molecular mass of gas, it
is same for all ideal gases.
Applications:
Since, S=0 at absolute zero temperature, the third law of thermodynamics
permits the calculation of absolute entropy of pure substances at any
temperature.
Limitations:
Third law of thermodynamics cannot be applied to super-cooled liquids,
because their entropy is probably not zero at 0 K.
5 – FREE ENERGY
FUNCTIONS & IT’S
APPLICATIONS
 Besides, enthalpy (H), internal energy (E) and entropy (S), there are two other types of
thermodynamic functions, which depend on the state of matter of the system. These
are:
1. Helmholtz Free Energy or Work Function, A
2. Gibbs Free Energy, F
Free energy functions are more convenient to apply and use E, H and S in their
evaluations.
Whenever a physical or chemical reaction is occurring, the freed energy decreases.
This free energy is released to the surroundings. Such energy may be allowed to do
useful work. Hence it is a useful function in many ways.
Free energy is defined as the energy that is freed to do useful work in any
reaction.
Applications:
The reaction mixture may be solid, gas, liquid or any other process. A few
examples of such natural processes are listed here.
(a) Falling of water can be made to do work, owing to the difference in the
potential energy at the two levels. Hydroelectric power generators convert the
work into power generation.
(b) Electric work can be done because of the difference in the electric potential.
(c) Steam engine can also do useful work by operating between two reservoirs, one
at steam temperature and other at room temperature.
Significance of Free Energy:
Free energy is denoted by F. It is a thermodynamic state quantity, i.e., it is defined
for a state. It does not depend on the path taken by the system to arrive at this state.
As per the free energy concept, a spontaneous process is accompanied by a loss in
the free energy at constant temperature and pressure.
When the system finally reaches equilibrium, the net change in free energy is equal
to zero. Mathematically, the following statements can be expressed.
(a) AF = 0 indicates equilibrium. Hence no useful work is expected
(b) AF < 0 indicates non equilibrium and spontaneous process. Useful work is
expected from the system.
(c) AF > O indicates non equilibrium condition, but non spontaneous process. Hence
useful work cannot be expected. Instead work has to be done on the system.
It can be concluded that when a spontaneous process reaches equilibrium, the free
energy value will be minimum, as the free energy continuously decreases.
6 – DIELECTRIC
CONSTANT
 Dielectric constant of a substance is a measure of its efficiency to induce
dipoles in another molecule.
It is influenced by inter-atomic and intermolecular attractions.
Applications:
(a) Polarity scales: Dielectric constant is widely used for measuring polarity of
solvents. As per the values of dielectric constants, solvents can be arranged in the
form of a scale. The scale is with one (1) for vacuum at one end and may be
about 78.5 for water at the other end. Such a scale helps the pharmacist to select
a solvent with appropriate polarity.
(b) Solubilisation of drugs: Drugs are either nonpolar or semipolar. When a
nonpolar molecule is added to water, dipolar water molecules induce a partial
charge on the nonpolar molecule by attracting and replelling the electrons.
This leads to induced dipoles, which facilitates the solubility of drugs in water. Now
the dipolar and induced dipoles interact through proper orientation. Such a
mechanism is responsible for the solubility of drugs in water. Solvents with high
dielectric constants also dissolve ionic compounds most rapidly. The higher the
magnitude of the dielectric constant, the greater the solvation energy of the
solvent, hence, greater is the solubility. These principles are employed in the
preparation of solutions for liquid orals and injections.
(c) Selection of a solvent for the solubility of the drugs.
7 – INDUCED
POLARIZATION
The process of transforming non-polar molecules into polar molecules is known
as polarization.
Polarizability is defined as the ease with which an ion or a molecule can be
polarized by any external force.
The process of inducing the polarization in non polar molecules by external force
is called induced polarization.
The external force may be an electric field, light energy or another molecule.
In the influence of electric field, dipoles can also have induced dipoles which
facilitate further alignment of negatively charged centres closer to positively charged
centres. This is called induced dipole moment.
Maximum dipole moment occurs when the molecules are oriented in a perfect
manner.
But perfect orientation in absolute terms is not possible, because the thermal
energy or agitation do not allow the molecules to orient in a proper manner.
Based on the above analogy, if nonpolar molecules are placed in a suitable
solvent such as water, the dipolar water molecules induce dipoles in non polar
molecules.
This temporary induced dipole moment is proportional to the field strength of
the capacitor and induced polarizability.
In general, large size molecules and ions have largerpolarizability because
electrons are loosely held.
Clausius-Mosotri equation expresses the relationship between induced
polarizability of a molecule and dielectric constant.
 The equation is represented as:

Where, n =number of molecules per unit volume

αp = induced polarizability
£= dielectric constant
8 – DIPOLE MOMENT
Dipolar molecule is defined as the one in which the regions of positive and
negative charges are well separated due to uneven distribution of electrons in the
molecule.

Although a molecule is represented by the presence of regions of positive and

negative charges, these are balanced. Thus the molecule as a whole does not
possess charge.
Examples of dipolar molecules are water, hydrochloric acid etc. In water, oxygen
is an electronegative atom that has a greater tendency to draw the shared pair of
electrons towards it. As a result, hydrogen atom assumes positive charge as the
shared electron pair is away from it. Thus positive and negative centres are
developed in a molecule.
Applications:
(1) Solubilisation of drugs: When a solute is added to a solvent such as water, the
permanent dipoles of water strongly interact with the solute. This type of interaction
enhances the solubility of solute in a variety of ways.
(2) Crystalline nature of solids: If solids are dipolar molecules, the dipole moment
contributes to the orientation of molecules in solution. The same arrangement will be
subsequently incorporated into the crystal lattice of the solids. For example, ice
crystals are organised through their dipole forces.
(3) Drug-receptor interactions: Dipole forces are believed to contribute for the
interaction of drugs with receptors.
(4) Therapeutic activity of drugs: Permanent dipole moments can be correlated with the
biological activity.
(5) Chemical structure of compounds: Dipole moment of a substance provides valuable
information regarding the chemical structure of molecules in a) Deciding ionic nature
of the bond b) Identifying shapes of the molecules. c) Identifying the shape and bond
angle. d) Deciding the arrangement of groups.
9 – REFRACTIVE INDEX &
MOLAR REFRACTION
When a ray of light passes from one medium to another, it shows refraction, i.e., a
change in the direction.
If the light ray passes from a less dense medium ( for example, air) to a denser
medium (for example, water), it refracts towards the normal. The bending of light
either towards the normal (A) or away from the normal (B) is shown in the Figure
below.
Snell's law states that the refractive index (n) of the liquid is a constant ratio of
the sin of the angle of incidence to that of the refraction. It is given by:

The refractive index is a characteristic of a liquid. According to wave theory,

the velocity of light decreases when it passes from a rare mcdium through a
dense medium. Hence,

Refractive index is greater than one for substances denser than air, because the
velocity of light in air (numerator) is always higher than the value in the liquid
medium (denominator).
 The mechanism of interaction is as follows:
i) When incident light strikes a liquid, the light photons interact with the
molecules causing imbalance of electron cloud.
ii) Thus induced dipoles are generated.
iii) Since a part of the supplied energy is spent, the velocity of light in
that liquid decreases.
iv) The greater the refractive index of a liquid, the greater the dipolar
induction.
Factors affecting refractive index:
1) The refractive index decreases with increase in the wavelength of light used. The
refractive index of liquid decreases as the temperature increases. For measuring
the refractive index of gases, pressure should be held constant.
Applications:
1) Refractive index is used to identify a substance.
2) The purity of a substance can be measured.
3) Concentration of a substance dissolved in a liquid can be determined.
4) The dielectric constant can be determined.
5) The molar polarizability of a substance can be determined.
6) Refractive index is also helpful in calculating the molar refraction.
Determination of Refractive Index:
Several refractometers are available for the determination of refractive index.
Abbe's refractometer is a quick and convenient instrument.
Small quantity of sample is adequate for the determination.
The construction and the optical system of Abbe’s refractometer are given in
figure below.
The apparatus is provided with a water Jacket to control the temperature of
measurement.
Light source should be followed as per manufacturer’s instructions.
Method:
A drop of liquid is placed upon the surface of the prism A. On clamping the
prisms A and B, the liquid drop spreads as a thin film.
Now a mirror M reflects the light and directs towards the prism system.
On reaching the ground surface of A, the light is scattered into the liquid film.
A particular ray going along the grazing incidence (i.e., at an angle slightly less
than 90°) will pass through the prism B at an angle equal to critical angle (e).
According to critical angle phenomenon:
The critical ray emerging from the upper prism at an angle is viewed by means of
a telescope.
Actually, the telescope is fixed and the prism box is rotated so as to get the
coincidence of critical angle with the cross wires of the eyepiece.
The setting of the prism to a definite critical angle gives a definite value of
refractive index.
When viewed through a telescope, the field of view is divided into bright and dark
portions.
When the edge of the bright portion coincides with the cross-wire of the
telescope, the scale reading gives the refractive index of the liquid.
9 – OPTICAL ROTATION
 Optical activity is the ability of certain substances to rotate the plane of a plane-
polarized light. Optically active substances are the substances which can rotate
the plane of plane-polarized light either to right-side or to left-side.
Optical rotatory dispersion is the variation in the optical rotation of a substance
with a change in the wavelength of light. Optical rotatory dispersion can be used
to find the absolute configuration of metal complexes.
Explanation:
Ordinary light transmits its rays in all directioiis, i.e., in all planes.
When light is allowed to pass through a polarizing prism (Nicol prism), light
vibrations in only one plane are transmitted. Such a light beam is known as
plane-polarized light.
When certain liquids and solutions are placed in the path of plane polarised light,
its velocity may decrease or increase.
The change in velocity results in a corresponding change in the rotation of plane-
polarized light through a certain angle, i.e., angle of rotation.
When viewed through the path of beam, if the rotation of plane-polarized light
takes place in clock-wise direction (towards the right), it is called as
dextrorotatory.
If the rotation of plane-polarized light takes place in anticlockwise direction
(towards left), then the rotation is called as laevorotatory.
Optical rotation is prefixed with the symbols, (+) for dextrorotation and (—) for
laevorotation.
Optical rotation, depends on the density of the optically active substance, because
each molecule provides an equal but small contribution to the rotation.
The angle of rotation is normally expressed as specific rotation and
mathematically expressed in IP as:
 The reasons for the change in the direction of plane-polarized light explained on
molecular basis.
The plane-polarised light interacts in a molecule and produce electronic polarization.
This electric field rotates the plane of vibration.
Applications:
1) Specific rotation is used to identify a substance whether optically active or not. If the
substance is optically active, based on the direction of rotation and magnitude, a
substance can be identified.
2) The purity of the substance can be measured.
3) The concentration of a substance dissolved in a solvent can be determined.
Method of Determination of Optical Activity:
Optical activity is measured using polarimeter.
The optical parts and find their arrangement in a polarimeter are given in the figure.
Polarimeter consists of two Polarizing elements (or polaroid) one of which is fixed
(polariser) and the other is an analyser.
It can be rotated and mounted within a graduated circular scale in order to measure
its orientation with respect to the polariser.
When the planes of polarization of the two elements (prisms) are mutually
perpendicular, no light is transmitted through the system.
Liquid can be directly filled in the sample tube.
If the substance is a solid, accurately weighed portion is transferred into a
volumetric flask and dissolved in water or other solvent, as specified.
A portion of the solvent is used for blank determination.
The sample solution is filled in the sample tube.
Care should be taken so that end-windows will not be strained, while screwing
the caps.
Any air bubble that may appear in the sample tube should be accommodated in
the bubble trap at the centre of the tube.
Complete filling of the sample tube is essential.
It is better to use long sample tube to get maximum difference in the optical
rotations between two samples.
The light source is usually a sodium vapour lamp.
On introducing an optically active sample between the polarizing elements, the
balance is disturbed.
It is necessary to re-balance by turning the analyser (scale).
When two halves are of equal intensity, it is the balanced position.
Then scale reading indicates the angle of rotation.
The extent to which the scale is rotated is a direct measure of the sample’s
optical activity.
This is normally obtained by the difference between the readings obtained with
and without the sample.
The direction of rotation is noted.
The angle of rotation can be substituted in the appropriate equation (13 or 14) to
obtain the specific rotation.
The direction of rotation and specific rotation is reported together for a given
substance in a given solvent.
 Enthalpy
Heat content is also known as enthalpy and denoted by at symbol ‘H’.
Enthalpy is a thermodynamic state function similar to pressure, volume etc.
Enthalpy is evaluated because it is a fixed value for a system at a particular
state (initial and final).
Applications:
1. Any changes in the heat in a chemical reaction are expressed by enthalpy of
reaction and enthalpy of formation, heat of combustion, heat of neutralization etc.
Reactions which take place with evolution of heat are called exothermic reactions.
In these reactions, H is negative, i.e., heat is evolved. Reactions that take place with
the absorption of heat are called endothermic reactions. In these reactions, H is
positive, i.e., heat is absorbed.
2. Similarly during physical transformation of phases, molar heat of fusion (Hf),
molar heat of vaporization (HV), molar heat of transition etc., are estimated.
 Enthalpy changes also occur during the following processes.
- Dissolution of solute
- Formation of micelles
- Chemical reactions
- Adsorption onto solids
 Entropy

Entropy is a measure of randomness of the molecules in the system.

At room temperature, every substance possesses certain amount of randomness
or irregular motion of its molecules.
When such a gas is placed in a cylinder fitted with a piston, some of gas
molecules, which are aligned in right direction of piston, will push the piston.
Molecules which are in other directions do not contribute to drive the piston
away.
When heat is supplied to a system, it is impossible to convert all the heat energy
into work, because of disorderliness of the molecules.
The process of melting or evaporation can be explained by entropy
factor.

Thus melting of a solid or evaporation of a liquid is accompanied by

increase in entropy, or disorderliness.
end