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2.  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 Contents 2

3. INTERMOLECULAR BINDING FORCES 3

4.  Attractive forces (F A )  long range interaction  n= ~6 or 7 for H, N, ~3 or 4 for Cl  Cohesive : btw same molecules  Adhesive : btw different molecules  Repulsive forces (F R )  short range interaction  electron clouds interact Intermolecular Binding Forces 4 Potential Energy - 0 + J.T.G. Overbeek, J. Colloid Interf. Sci. 58, 408 (1977).

5.  Collision diameter  The distance between molecules at which the attractive and repulsive forces just balance each other  The most stable distance Intermolecular Binding Forces 5 http://www.one-school.net/Malaysia/UniversityandCollege/SPM/revisioncard/physics/forceandmotion/elasticity.html

6. 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) van der Waals forces Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5 th edition, 23 p. 6

7. van der Waals forces http://www.chemprofessor.com/imf.htm 7 Permanent dipolesTemporary electric dipoles Liquefaction of gases

8. Attractions & Repulsions http://www.chemprofessor.com/imf.htm 8 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 a nother, while the like partial charges repel one another. Molecules will tend to move so as to maximize attractions and minimize r epulsions Molecules – Attractions & Repulsions

9. 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 Hydrogen Bond Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5 th edition, 24 p. 9

10. Hydrogen bond in Protein http://www.3redravens.net/ibbio/Chap05notes.html 10

11. 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 Ion-dipole & ion-induced dipole http://www.science.uwaterloo.ca/~cchieh/cact/applychem/hydration.html, http://www.chemprofessor.com/imf.htm, 11

12. 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 (-CH 2 )  Hydrophobic exclusions Hydrophobic interaction http://academic.brooklyn.cuny.edu/biology/bio4fv/page/hydropho.htm 12

13. Various Forces and Bonding 13 ClassUnit 1Unit 2 Energy (Kcal/mole) bonding Van der Waals forces Keesom forcesDipole 1~7 Physical bonding (intermolec ular interaction) Debye forcesDipoleInduced dipole1~3 London forcesInduced dipole 0.5~1 Ion-dipoles forcesIonDipole1~7 Ion-induced dipole forcesIonInduced dipole- Hydrogen bondH atomO, N, F2~8 Ionic bondIon 100~200 Chemical bonding (atomic bonding) Covalent bondPolar atom 50~150

14. STATES OF MATTER 14

15. Three primary states of matter  Gases, liquids and crystalline solids Potential Energy + Kinetic or Thermal Energy (proportional to Temp) States of Matter http://www.chemistryexplained.com/Fe-Ge/Gases.html, http://www.chemprofessor.com/phase.htm 15

16.  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 The Gaseous State http://www.chemistryexplained.com/Fe-Ge/Gases.html Davidson College Chemistry Resources, Dr. Nutt's Course CHE 115: Principles of Chemistry 16 Pressure Volume

17.  Charles’ Law  V = T × constant when pressure is held fixed  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 States of Matter Davidson College Chemistry Resources, Dr. Nutt's Course CHE 115: Principles of Chemistry 17 Temp Volume

18.  Ideal Gas Law Boyle’sV ∝ 1/P (when n and T are held fixed) Charles’V ∝ T (when n and P are held fixed) Avogadro’sV ∝ n (when P and T are held fixed) SummaryV ∝ nT/P States of Matter Ideal Gas Law PV =nRT http://www.chem1.com/acad/webtext/gas/gas_6.html 18

19.  The Van der Waals Equation for Real Gases  The other effect that van der Waals needed to correct for are the intermolecular attractive forces. Real Gases Ideal gas pressureIdeal gas volume http://www.chem1.com/acad/webtext/gas/gas_6.html 19

20.  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  P O 2 (80mmHg)  inspired air  P CO 2 (35~45mmHg)  respiratory function  oxidation of carbon ingested as a food  high : Hyperventilation, low : Poor ventilation  H 2 O + CO 2  H + + HCO 3 -  pH ↓  acidemia Arterial Blood Gases 20

21.  The solid states fixed shape, incompressible, strong intermolecular forces the atoms vibrate in fixed positions three main types : crystalline, amorphous, and polymeric The Solid States Physicochemical Principles of Pharmacy, 4 th EDITION, 8-10 p. 21  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

22.  Crystalline Solid  Arranged in fixed geometric pattern or lattices  There are seven basic or primitive unit cells The Solid States Physicochemical Principles of Pharmacy, 4 th EDITION, 8-10 p. 22

23.  Crystal bonding The Solid States http://www.britannica.com/EBchecked/media/2488/Chemical-bonding-in-crystalline-solids 23

24.  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 The Solid States 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 24 (a) form I and (b) form IV of sulfathiazole Powder X-ray diffraction patterns of aspartame hemihydrate cobaltacarborane crystals

25.  Amorphous Solids  Glasses, supercooled liquid  the molecules are arranged in random manner as in the liquid state  No definite MP  Changing its hardness at the range of several degrees  More soluble and more bioavailable than its crystalline form The Solid States R.J. Behme, D. Brooks, R.F. Farney and T. T. Kensler, J.Pharm. Sci. 74, 1041, 1985. 25

26.  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 The Solid States 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

27.  The Liquid State A liquid, like a gas, has no shape of its own, but it does have a definite volume. Liquid State Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5 th edition, 32 p. "Generalized Thermodynamic Relationships". Thermodynamics (5 th ed.). New York, NY: McGraw-Hill, Inc  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. 27

28.  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. Liquid State Figure; http://science-hamza.blogspot.com/2010_11_01_archive.html 28

29. Liquid State Figure; http://science-hamza.blogspot.com/2010_11_01_archive.html  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 29

30.  Liquid to Gas  For molecules to leave the surface of a liquid → The energy(ΔH v ) must be supplied to overcome attractive forces  Solid to Liquid  To increase the interatomic or intermolecular distance → The energy(ΔH f ) must be supplied to overcome attractive forces Changes in State  M.W.  intermolecular force  ΔH v  B.P.  Vapor Pressure  M.W.  intermolecular force  ΔH f  M.P. 30

31. Changes in State Q Q. Which polymer shows the higher M.P. ? Linear Branched Unsaturated bond Saturated bond Even number Odd number Tran-formation Cis-formation 31

32.  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. Eutectic Mixture Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5 th edition, 23 p 32

33.  Gibbs' phase rule  Giving the lowest number of independent variables that must be specified to describe a solid, liquid, or gaseous system.  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) The Phase Rule Ex) For HCl aqueous solution C = 2 (HCl and H 2 O), P = 1 (Liquid) ∴ F = 2 – 1 + 2 = 3 Three independent variables need to be specified this system Temperature, Pressure, Concentration 33

34.  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 Supercritical Fluid State Martin’s Physical Pharmacy and Pharmaceutical Sciences, 5 th edition, 42-43 p. http://eng.ege.edu.tr/~otles/SupercriticalFluidsScienceAndTechnology/