Sifat molekul

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)

Where is :

U(r) = potential energy for r meter

distances between atoms, Joule

q1 and q2 = charges different atoms,

coulomb

ε0 = permitivity constants,

8,85410-12 Coulomb2N-1m-2

r = distance between atoms

r

qqrU

0

21

4

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

9

Polar

Polar or Non Polar Non Polar

Polar or Non Polar

Fig. 4—2. 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 4—2. 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 4—3.

Dielectric Constant & Polarization

parallel conducting plates

(Figure 4—3)

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)

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.


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 4—3).

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.

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, Clausius—Mossotti equation :

pn

3

4

2

1

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.


Molekul p x 1024 cm3

H2O

N2

HCl

HBr

HI

HCN

1,68

1,79

3,01

3,5

5,6

5,9

Polarizabilities

Clausius-Massotti equation :

ip

pPN

nMM

3

4

3

4

2

1-

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 :


question sample

mol/cm 5,4643,1

119

28,4

18,4

2

1- P 3

i

M

MPi

2

1-

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, .

MPPP i

2

10

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

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

Slop A= 4N2/9k T

APP i

1

The total molar polarization, P. is the

sum of induction and permanent dipole

effects:

Because P0 depends on the

temperature, T :

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 drug—receptor 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

CONCLUSION

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Sifat molekul