PH-PHR 216 Physical Pharmacy

INTERMOLECULAR FORCES OF ATTRACTION - like dissolves like

- essential to form solids, liquids, and gases.
- reason why different phases are formed
- drugs are composed of different phases of
matter
1. BINDING FORCES
- Cohesion - Binding between similar molecules (at
least two molecules) (strongest)
- Adhesion - Binding between different molecules
(surface lang)
- Polar molecules likes bonding with another polar
molecules
2. Dipole-Induced dipole (Semipolar) - Interaction
between a polar and non-polar molecule
(induced) (at least 8 C)
- AKA Debye Forces
- Mechanism: Induction
- e.g. Ethyl acetate, ether, methylene chloride

- Repulsive forces - any force that will act to break

this bond; act to prevent molecules from - molecules with semi-polarity (semi-miscible -
annihilating each other. (weakest) parts which impart nonpolarity in the
molecule. Molecule has both polar and non-
2. ATTRACTIVE FORCES polar parts/components:
- Caused by dipoles (polar molecules - dipole
moment ^ = Polarity ^ ) and induced-dipoles
(nonpolar molecules - equal sharing of electrons
but there are instances when those electrons
repel and go to a side of a molecule making the
other side defficient of electrons making it
partially positive. INDUCTION)
FOUR TYPES OF ATTRACTIVE FORCES
1. Van der Waals Forces 3. Induced Dipole-Induced-Dipole (Nonpolar) -
- weak forces that involve displacement of Interaction between two non-polar molecules
charge (weakest)
- Exist in all atoms and all molecules - AKA London Forces
- easy to break, weak forces - Mechanism: Dispersion
=Three Groups of Van der Waals= - Hydrophobic bonds - not miscible in water
1. Dipole-dipole (Polar) - Interaction between two - e.g. Carbon disulfide, Carbon Tetrachloride,
polar molecules (strongest) hexane
- AKA Keesom Forces
- Mechanism: Orientation
or alignment. e.g. water,
ethanol, HCl (gas), phenol
(all polar molecules)
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PH-PHR 216 Physical Pharmacy
2. Hydrogen bonds - electrostatic interaction of H - e.g. H2O+ NaCl -> NaCl (aq)
with highly electronegative atoms (S, N, Cl, F, O)
- Accounts for unusual properties of water ->
indicative of solubility in water (^ hydrogen
bonds = ^ solubility in water) (“molecule”-
organic compounds; “compound”-inorganic
compounds)
- eg. ascorbic acid - presence of diff hydroxyl
groups
- ^ C-chain = V H-bonding = V Solubility in water
- octanol - semipolar- debye (more than this =
immiscible in water)
- Strong IMF (electrostatic) - presence of additional and stronger bonds
- Partly covalent as the election of the H atom is (attractive forces) increasing the boilling point
- higher temperatures needed to break
substantially delocalized to the electronegative
4. Ion-induced dipole interaction -induced by
atom.
- e.g. in the body: DNA - Hydrogen bonds close proximity of a charged ion to the nonpolar
molecules
connects the nitrogenous bases.
- e.g. formation of iodide complex (I2 + K+I- ->
K+I3-) Adding a solubilizing agent (e.g.
povidone or potassium iodide) for the iodine to
remain in the solution.
- Nonpolar molecule + ionic compound

Relative strength of Non-Covalent Interactions (IMF)

Weakest to strongest (range = depends on nature
of the substance)
1. London Dispersion Forces - 0.0.5-40 kJ/mol
3. Ion-dipole interaction - Ionic compound and a
2. Debye Forces - 2-10 kJ/mol
polar molecule
3. Ion-induced dipole interaction 3-15 kJ/mol
4. Keesom Forces 5-25 kJ/mol
5. Hydrogen bonds - 10-40 kJ/mol
6. Ion-dipole interaction 40-600 kJ/mol
7. Ionic bond
- More polar - Higher boiling point

- salt dissolved in a polar solvent.

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PH-PHR 216 Physical Pharmacy
Pharmacological effect
- Drug-Receptor Complex - binding caused by
Intermolecular Forces of Attraction
- Stronger bond - longer half-life of the drug
- in organic medicinal chemistry

PROPERTIES OF SYSTEM
Extensive Property vs Intensive Property
1. Extensive - a property that depends on the
quantity of a matter observed
- Mass
- Length
- Volume
GUIDE
2. Intensive - a property that is independent on the
quantity of matter observed
- Temperature
- Pressure
- Density
- Viscosity
- Surface Tension
- Specific gravity
- Color
- Concentration (Molarity, Molality, Normality)

EXERCISE PROPERTIES OF SUBSTANCES

Determine Interactive forces present in the structure 1. Additive Property - depends on the total
ASA Aspirin contribution of the atoms in the molecules. e.g.
LDF - Benzene ring Molecular weight, mass; synonymous to
Keesom - Carboxylic Acids Extensive property
Hydrogen Bonding 2. Constitutive Property - depends on the
arrangement and on the number and kind of
Ascorbic Acid atoms wihtin a molecule. e.g. Refractive index,
Hydrogen Bonding optical rotation; bending light
Debye 3. Colligative Property - depends on the number of
species/particles/solutes in solution. e.g. vapor
Paracetamol pressure lowering, boiling point elevation,
Hydrogen Bonding freezing point deperssion, osmosis.
LDF
Keesom

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