1
Contents
 Intermolecular Binding Forces

Attraction and Repulsion
 Intermolecular Attractive Forces

Electrostatic attraction
- Van der Wall Forces, Hydrogen Bonds and Ionic interaction
 States of Matter



The Gaseous State - Blood gases
The Solid State - Crystalline solids, Amorphous solids, Polymeric solids
Liquid State - Vapor Pressure, Surface Tension
 Changes in State



The Factors Affect Intermolecular Force
Eutectic Mixture
The Phase Rule
2
INTERMOLECULAR BINDING
FORCES
3
Intermolecular Binding Forces




long range interaction
n= ~6 or 7 for H, N, ~3 or 4 for Cl
Cohesive : btw same molecules
Adhesive : btw different molecules
Potential Energy
+
0
 Attractive forces (FA)
 Repulsive forces (FR)


short range interaction
electron clouds interact
J.T.G. Overbeek, J. Colloid Interf. Sci. 58, 408 (1977).
4
Intermolecular Binding Forces
 Collision diameter


The distance between molecules at which the attractive and repulsive forces
just balance each other
The most stable distance
http://www.one-school.net/Malaysia/UniversityandCollege/SPM/revisioncard/physics/forceandmotion/elasticity.html
5
van der Waals forces
van der Waals Forces
 Keesom forces : Dipole-dipole.
(water, hydrochloric acid, alcohol, phenol)
 Debye forces : Dipole-induced dipole.
(ethylacetate, methylene chloride, ether)
 London forces : Induced dipole-induced dipole.
(carbon disulfide, carbon tetrachloride, hexane)
Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5th edition, 23 p.
6
van der Waals forces
Permanent dipoles
Temporary electric dipoles
Liquefaction of gases
http://www.chemprofessor.com/imf.htm
7
Attractions & Repulsions
Molecules – Attractions & Repulsions
Dipole-dipole attractions occur over
longer distances than induced dipole
attractions, so they take place among
larger groups of molecules.
The opposite partial charges attract one
another, while the like partial charges
repel one another.
Molecules will tend to move so as
to maximize attractions and minimize
repulsions
http://www.chemprofessor.com/imf.htm
8
Hydrogen Bond
Hydrogen Bonds



a special type of dipole-dipole attraction (exceptionally short and polar)
small size and large electrostatic field of Hydrogen atom
Change materials properties : boiling point, dielectric constant,
three dimensional array of inter- or intra- molecular structures
Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5th edition, 24 p.
9
Hydrogen bond in Protein
http://www.3redravens.net/ibbio/Chap05notes.html
10
Ion-dipole & ion-induced dipole
Ion-dipole and ion-induced dipole
 The partial charges on a polar molecule are attracted to ions
with the opposite charge
 Ion-dipole forces
 Ion-induced dipole forces
http://www.science.uwaterloo.ca/~cchieh/cact/applychem/hydration.html, http://www.chemprofessor.com/imf.htm,
11
Hydrophobic interaction
Hydrophobic interaction
 Forces of attraction between nonpolar atoms and molecules in water
 Nonpolar groups tends to interact with each other than
being attracted to water
 Hydrophobic chain (-CH2)
 Hydrophobic exclusions
http://academic.brooklyn.cuny.edu/biology/bio4fv/page/hydropho.htm
12
Various Forces and Bonding
Unit 1
Unit 2
Energy
(Kcal/mole)
Keesom forces
Dipole
Dipole
1~7
Debye forces
Dipole
Induced
dipole
1~3
London forces
Induced
dipole
Induced
dipole
0.5~1
Ion-dipoles forces
Ion
Dipole
1~7
Ion-induced dipole forces
Ion
Induced
dipole
-
Hydrogen bond
H atom
O, N, F
2~8
Ionic bond
Ion
Ion
100~200
Covalent bond
Polar atom
Polar atom
50~150
Class
Van der
Waals
forces
bonding
Physical
bonding
(intermolec
ular
interaction)
Chemical
bonding
(atomic
bonding)
13
STATES OF MATTER
14
States of Matter
Three primary states of matter  Gases, liquids and crystalline solids
Potential Energy + Kinetic or Thermal Energy (proportional to Temp)
http://www.chemistryexplained.com/Fe-Ge/Gases.html, http://www.chemprofessor.com/phase.htm
15
The Gaseous State
 The Gaseous State
Gases : molecules that have kinetic energy that produces rapid motion,
that are held together by weak intermolecular forces
no regular shape, compressible, invisible for many gases
Gases are described through the use of four physical properties :
pressure(P), volume(V), number of particles(n, moles) and temperature(T).
 Boyle’s Law
 PV = constant
when temperature is held fixed
Volume
Pressure
http://www.chemistryexplained.com/Fe-Ge/Gases.html
Davidson College Chemistry Resources, Dr. Nutt's Course CHE 115: Principles of Chemistry
16
States of Matter
 Charles’ Law
 V = T × constant when pressure is held fixed
Volume
Temp
 Avogadro’s Hypothesis
 V =n × constant

when P and T are held fixed
1.00 mole of an ideal gas at 1.00 atm and 0℃(Standard Temperature and
Pressure, STP) occupies 22.4 L
Davidson College Chemistry Resources, Dr. Nutt's Course CHE 115: Principles of Chemistry
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States of Matter
 Ideal Gas Law
V
V
V
V
Boyle’s
Charles’
Avogadro’s
Summary
Ideal Gas Law
∝
∝
∝
∝
1/P
T
n
(when n and T are held fixed)
(when n and P are held fixed)
(when P and T are held fixed)
nT/P
PV =nRT
http://www.chem1.com/acad/webtext/gas/gas_6.html
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Real Gases
 The Van der Waals Equation for Real Gases

The other effect that van der Waals needed to correct for
are the intermolecular attractive forces.
(𝑃+
𝑎
𝑉2
)( 𝑉 − 𝑏 ) = 𝑅𝑇
Ideal gas pressure Ideal gas volume
http://www.chem1.com/acad/webtext/gas/gas_6.html
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Arterial Blood Gases
 Blood Gases

Gases are dissolved in the blood on the basis of the solubility of a gas in plasma

Related to atmospheric conditions and to biological and catalytic metabolic activity

The amount of gas is proportinal to the partial pressure of the gas in equalibrium

PO2 (80mmHg)  inspired air

PCO2 (35~45mmHg)
 respiratory function
 oxidation of carbon ingested as a food
 high : Hyperventilation, low : Poor ventilation

H2O + CO2  H+ + HCO3-  pH ↓  acidemia
20
The Solid States
 The solid states
fixed shape, incompressible, strong intermolecular forces
the atoms vibrate in fixed positions
three main types : crystalline, amorphous, and polymeric



Crystalline Solid
The molecules or atoms are arranged in repetitious three-dimensional lattice units
Ex) Ice, sodium chloride, menthol
 Polymorphs : The substances can exist more than one crystalline form
Amorphous Solids
The molecules are arranged in random manner as in the liquid state
Ex) Insulin
Polymeric Solids
A long chain of covalent-bonded atoms
Ex) Polyvinyl alcohol, Methyl cellulose
Physicochemical Principles of Pharmacy, 4th EDITION, 8-10 p.
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The Solid States
 Crystalline Solid

Arranged in fixed geometric pattern or lattices

There are seven basic or primitive unit cells
Physicochemical Principles of Pharmacy, 4th EDITION, 8-10 p.
22
The Solid States
 Crystal bonding
http://www.britannica.com/EBchecked/media/2488/Chemical-bonding-in-crystalline-solids
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The Solid States
 Polymorphs

The substants can exist more than one crystalline form

Occurs with different solvents, impurities, supersaturation, temperature, ions.

Different property : stabilities, melting points, solubilities and so on.

Monotropic vs Enantiotropic

DSC, IR, XRD
(a) form I and (b) form IV of sulfathiazole
Powder X-ray diffraction patterns
of aspartame hemihydrate
Advanced Drug Delivery Reviews Volume 48, Issue 1, 16 May 2001, Pages 3–26,
Polymorphism and phase transformations in cobaltacarborane molecular crystals, José Giner Planas, May 2007
cobaltacarborane crystals
24
The Solid States
 Amorphous Solids
Glasses, supercooled liquid


No definite MP



the molecules are arranged in random manner as in the liquid state
Changing its hardness at the range of several degrees
More soluble and more bioavailable than its crystalline form
R.J. Behme, D. Brooks, R.F. Farney and T. T. Kensler, J.Pharm. Sci. 74, 1041, 1985.
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The Solid States
 Polymeric Solids
 A long chain of covalent-bonded atoms
 Secondary bonds hold groups of
polymer chains together to form the
polymeric material
 Polymers has a wide variety of properties
 The physical properties of a polymer



The size or length of the polymer chain
Different side groups
Long chain branches
Principles of Materials Science and Engineering, William F. Smith, McGraw-Hill , Inc., New York
Rubinstein, Michael; Colby, Ralph H. (2003). Polymer physics. Oxford ; New York: Oxford University Press. p. 5-6
26
Liquid State
 The Liquid State
A liquid, like a gas, has no shape of its own, but it does have a
definite volume.
 Vapor Pressure

The pressure of the saturated vapor above the liquid

The vapor pressure increases with rising temperature.
(independent with other factors)

Clausius Clapeyron Eq : the relationship btw the vapor
pressure and the absolute temperature of liquid.
Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5th edition, 32 p.
"Generalized Thermodynamic Relationships". Thermodynamics (5th ed.). New York, NY: McGraw-Hill, Inc
27
Liquid State
 Boiling Point


The temperature at which the vapor pressure of the liquid equals the external
or atmospheric pressure
① The boiling point of a compound, like ② the heat of vaporization and
③ the vapor pressure at a definite temperature
 Provides a rough indication of the magnitude of the attractive force.
Figure; http://science-hamza.blogspot.com/2010_11_01_archive.html
28
Liquid State
 Surface Tension(γ)




A property of the surface of a liquid that allows it to resist an external force
The force in the liquid surface tends to minimize the surface area
Caused by cohesion of like molecules
The forces of attraction within the liquid molecules are smaller than
those between liquid and contact solid, (Cohesion<Adhesion)
 the solid is readily wetted
Figure; http://science-hamza.blogspot.com/2010_11_01_archive.html
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Changes in State
 Liquid to Gas
 For molecules to leave the surface of a liquid
→ The energy(ΔHv) must be supplied to overcome attractive forces
M.W.
intermolecular force
ΔHv
B.P.
Vapor Pressure
 Solid to Liquid
 To increase the interatomic or intermolecular distance
→ The energy(ΔHf) must be supplied to overcome attractive forces
M.W.
intermolecular force
ΔHf
M.P.
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Changes in State
Q. Which polymer shows the higher M.P. ?
Linear
Unsaturated bond
Even number
Tran-formation
Branched
Saturated bond
Odd number
Cis-formation
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Eutectic Mixture
 Eutectic mixture



Eutectic point : The lowest temperature at which the existence of the liquid
phase is possible. At a particular composition the eutectic mixture having
the lowest melting point. The crystallinity change at this point.
Microcrystalline dispersions: reduction in crystalline size, increased solubility
and dissolution rate
Menthol-Testosterone, Lidocane-Prilocaine, chloramphenicol–Urea,
Sulfathiazole–Urea, Niacinamide–Ascorbic acid.
Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5th edition, 23 p
32
The Phase Rule
 Gibbs' phase rule
 Giving the lowest number of independent variables that must be
specified to describe a solid, liquid, or gaseous system.
F = P (C− 1) + 2 −C (P− 1)



𝑭 = 𝑪 − 𝑷 + 𝟐
P : the number of phases in thermodynamic equilibrium
C : the number of components(chemically independent constituents of the
system)
F : The number of degrees of freedom(intensive variables which are
independent of each other)
Ex) For HCl aqueous solution
C = 2 (HCl and H2O), P = 1 (Liquid)
∴F=2–1+2=3
Three independent variables need to be specified this system
Temperature, Pressure, Concentration
33
Supercritical Fluid State
 The Supercritical Fluids
 Intermediate properties btw those of liquids and gases
 Gaslike : having better ability to permeate solid substances
 Liquidlike : having high densites that can be regulated by pressure
and can dissolve materials
 By changing the pressure and temperature of the fluid, the properties
can be “tuned” to be more liquid- or more gas-like
Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5th edition, 42-43 p.
http://eng.ege.edu.tr/~otles/SupercriticalFluidsScienceAndTechnology/