Physical Properties Of

Drug Molecule
Physical Pharmacy Team

Molecules of drug
Almost all of drugs are organic
There more than 2 atoms (C, H, O, N, etc.)
All atoms has a different charges
Between atoms there is binding
Atom bonds at molecule influences by
their charges
Their bonds make a unique properties

Potential Energy
(Coulomb Law)
q1q2
U r

4 0 r
Where is :
U(r) = potential energy for r meter
distances
between atoms, Joule
q1 and q2 = charges different atoms,
coulomb
= permitivity constants,
0
8,85410-12 Coulomb2N-1m-2
r = distance between atoms

Effect of Potential Energy

Both atoms have different
vibration (detected by IR) :
Contracting (attractive)
Stretching (repulsive)

Dipole Moment

Dipole moment depends on the variation in distribution of

electrons along the bond, and also its length, which is why
stretching a bond can change its dipole moment.
For bonds between unlike atoms, the larger the difference
in electronegativity, the greater the dipole moment, and the
more it changes when stretched.
For identical atoms (C=C, for example) the dipole moment,
and its capacity to change with stretching, is much smaller.
Stretching frequencies for symmetrical molecules are
measured using Raman spectra.

Dipole Moment

Electronegative Vs Dipole Moment

Dipole Moment detected in IR

Polar or Non Polar

Polar

Polar or Non Polar

Non Polar

Polar or Non Polar

Fig. 42. Vectorial nature of permanent

dipole moments for (a) water, (b) carbon
dioxide, and (c) a peptide bond. The
distance r is given by the dashed line for
each molecule. The arrow represents
the conventional direction that a dipole
moment vector is drawn, from
negative to positive.

The symmetry of the molecule can also be associated with its dipole moment, which is
observed with carbon dioxide (no net dipole) in Figure 42. Likewise, benzene and
pdichlorobenzene are symmetric planar molecules and have dipole moments of zero.
Meta and ortho derivatives of benzene, however, are not symmetric and have significant
dipole moments, as listed in Table 43.

Dielectric Constant & Polarization

C = q/V

C: capasitansy (farad);
q: electrocharge(coulomb);
V: voltage (volt)

= Cx/C0
: Dielectric constants;
Cx : condensor capasitans with x agent;
C0 : standard capasitans (vakum)

parallel conducting plates

(Figure 43)

The dielectric constant is a measure of the

ability of molecule to resist charge
separation. If the ratios of the
capacitances are close, then there is
greater resistance to a charge separation.

Dielectric Constant & Polarization

The concepts of polarity and dielectric constant :

Placing a molecule in an electric field is one way to induce a

dipole. Consider two parallel conducting plates, such as the
plates of an electric condenser, which are separated by some
medium across a distance r, and apply a potential across the
plates (Figure 43).
Electricity will flow from the left plate to the right plate through
the battery until the potential difference of the plates equals that
of the battery supplying the initial potential difference.

Dielectric Constant & Polarization

When non polar agent in suitable solvent has been placed

between 2 charges capasitor, the non polar molecule able
to inducted polarization/ inducted dipole.
There have separate electrocharges for a while. Electron &
nuclei of atom move to others temporary.
This temporary condition called inducted polarization
power, p which has equal with electrocity field force
This power describe how that molecule or atom polarized
by external force such as electricity, magnetic or ray of light
From electromagnetic theory, ClausiusMossotti equation :

1 4
n p
2 3

Dielectric Constant & Polarization

Polarizabilities
Molekul

p x 1024 cm3

H2O
N2
HCl
HBr
HI
HCN

1,68
1,79
3,01
3,5
5,6
5,9

Clausius-Massotti equation :
- 1 M 4 nM p 4

N p Pi

3
2 3

M: Molecule weight, n : molecule number in

such of volume; N: Avogadro=6,023X1023 mol-1.
Pi: Inducted Polarized Molar, represent of
inducted dipole moment per mol of nonpolar
agent if there placed on condensator electricity
force field, V/m (volt per meter) = 1.

Dielectric Constant & Polarization

question sample
Chloroform (=4,8) has molecule weight 119
g/mol and density 1,43 g/cm3 at 250 . How
much inducted polarization molar power of that
agent (polarizability) ?
Answer :

-1 M
Pi

- 1 M 4,8 1 119
3
Pi

46
,
5
cm
/ mol

2 4,8 2 1,43

Permanent Dipole

Polar molecules have permanent dipoles.

The separation of positively and negatively charged
regions can be permanent, and the molecule will
possess a permanent dipole moment, .
The total molar polarization, P. is the
sum of induction and permanent dipole
effects:

1 M
P Pi P0

P0 , is the orientation polarization of the permanent dipoles,= 4N2/9kT;

k, Boltzman constant= 1.38X10-23 J0K-1

Because P0 depends on the

temperature, T :
1
P Pi A
T

Slop A= 4N2/9k

CONCLUSION
The importance of dipole interactions should not be
underestimated.
For ionic solutes and nonpolar solvents, ion induced dipole
interactions have an essential role in solubility phenomena .
For drugreceptor binding, dipole dipole interactions are
essential noncovalent forces that contribute to enhance the
pharmacologic effect.
For solids composed of molecules with permanent dipole
moments, the dipole interactions contribute to the crystalline
arrangement and overall structural nature of the solid. For
instance, water molecules in ice crystals are organized
through their dipole forces.

CONCLUSION