1. Molecular Modeling Computational Chemistry
Lewis Structures, Bonds, Shapes, Polarity, Stereochemistry
Dr. Ron Rusay

2. Lewis Structures (Named after Prof. G. N. Lewis, UC Berkeley)
Represent the arrangements of localized valence electrons (bonded & non-bonded) among atoms in a molecule.
Follows the rule of eight, which relates stability of a compound to noble gas electron configuration.
Shows bonds and relates to 3-dimensional shapes in molecular structures.
Particularly useful for covalent molecules.

3. Lewis Electron-Dot Drawings
Periods 2 & 3

4. Photo Bancroft Library, University of California/LBNL Image Library
Professor Gilbert Newton Lewis (circa 1940)
Notes from Lewis’s notebook
and his “Lewis” structure.
G.N. Lewis
Photo Bancroft Library, University of California/LBNL Image Library
Footnote:
G.N. Lewis, despite his insight and contributions to chemistry, was never awarded the Nobel prize.

5. Lewis Structures For simple Lewis structures: NH3, for example:
Draw the individual atoms using dots to represent the valence electrons.
Put the atoms together so they share PAIRS of electrons to make complete octets. Cannot use more than the total number of valence electrons.
NH3, for example:

6. MUST know where the atoms are located relative to each other.
Lewis Structures
Draw Lewis Structures for the following:
CH3CH2OH Ethyl alcohol (Ethanol)
CH4
Methane
CF4
Carbon Tetrafluoride
How many total electrons in each & where to place them?
MUST know where the atoms are located relative to each other.

7. .. .. .. .. Lewis Structures C H CH4 Methane Ethyl Alcohol (Ethanol)
CF4
Carbon Tetrafluoride .. C F
equals 1 pair of e-s

8. Lewis Structures H H H N . . H H . . . . N N Ammonia H H C H + . . O
Urea H
Note the carbon “double bond”;
equals 2 pairs of e-s
Ammonium Ion

9. Important Bond Numbers
(Neutral Atoms!)
one bond H F Cl Br I O
two bonds N
three bonds C
four bonds

10. Important Bond Numbers
(Neutral Atoms / Normal electron distribution)

11. Lewis Structures → Molecular Shapes
For simple Lewis structures:
Draw the individual atoms using dots to represent the valence electrons.
Put the atoms together so they share PAIRS of electrons to make complete octets.
NH3, for example:
Eg. Ammonia:

12. Shapes of Molecules
View: What is the shape of a molecule? George Zaidan and Charles Morton

13. Lewis Structures → Molecular Shapes Classic Worldwide Model: VSEPR “Valence Shell Electron Pair Repulsion”
Basis of the model: Molecular structure’s shape is determined by minimizing electron pair repulsions through maximizing separations.

14. Lewis Structures → Molecular Shapes Molecular Models for C, H, N, O
Fundamental repeating shapes found in every biological molecule
C =black
H = gray
N = blue
O = oxygen
pink = generic atom

15. Lewis Structures → Molecular Shapes Molecular Models for C, H, N, O
Fundamental repeating shapes found in every biological molecule
C =black
H = gray
N = blue
O = oxygen
pink = generic atom

16.
Lewis Structures → Molecular Shapes MolView: Visual On-line Molecular Modeling
Bonding, Lewis Structures, Molecular Modeling: Computational Experiments, Instructions, & Manual pp

18. Polar Covalent Bonds
Electrons tend to shift away from lower electronegativity atoms to higher electronegativity atoms.
The greater the difference in electronegativity, the more polar the bond.

19. Bond Polarity
A molecule, such as HF, that has a center of positive charge and a center of negative charge is polar, and has a dipole moment. The partial charge is represented by  and the polarity with a vector arrow.

20. Computational Chemistry
Polarity: Molview (
Figure: 08-07
Color coded electron density distribution: red-highest, blue lowest, green balanced
NOTE: These colors may vary from model to model.

21. Polarity /Visual Portrayal
0.143 nm
0.094 nm
0.158 nm
Figure: 08-07
Color coded electron density distribution: blue-lowest, red highest, green balanced
NOTE: These colors do vary.

22. Molecular Polarity & Dipole Moment
When identical polar bonds
point in opposite directions,
the effects of their polarities
cancel, giving no net dipole
moment. When they do not
there is a net effect and a net
molecular dipole moment,
designated d.

23. Molecular Dipole Moment
The vector sum of the magnitude and the direction of the individual
bond dipole determines the overall dipole moment of a molecule

24. Polarity & Physical Properties Chloroform (polar) vs
Polarity & Physical Properties Chloroform (polar) vs. Carbon tetrachloride (non-)
An electrically
charged rod
attracts a stream
of chloroform but
has no effect on a
stream of carbon
tetrachloride.

25. Ammonia and in the Ammonium Ion

26. Water

27. Polarity & Physical Properties Ozone and Waternm
The Lotus flower
Water & dirt repellancy: solubility?
Resultant Molecular Dipoles > 0
Solubility: Polar molecules that dissolve or are dissolved in like molecules
New Water-Repellent Material Mimics Lotus Leaves John Roach
for National Geographic News
February 27, 2003
Dirt-repelling paint, based on the qualities of the lotus leaf, being
developed at Bonn University.

28. Polarity & Physical Properties Solubility
Generally likes dissolves like:
Polar compounds dissolve other polar compounds & ionic compounds. Eg. ethanol and water, sodium chloride and water, sugar and water
Nonpolar compounds are soluble in other nonpolar compounds. Eg. carbon tetrachloride and oil, diesel and gasoline

29. Acetic acid Is acetic acid polar or non-polar?
Will acetic acid be miscible (dissolve) in water?
Based on the
Molview model?

30. The “Lotus Effect” Biomimicry
Wax
Scientists at the University of Bonn carried out extensive
research to show that the water droplets rolling off a lotus leaf carry away dirt particles
leaving the surface perfectly clean. This phenomena has been named the 'Lotus Effect'
and works best on rough surfaces. A report on the scientists' study was published in the
journal 'Planta'.
Contrary to popular belief, lotus leaves are not smooth at all. When examined under a
powerful microscope, the leaf cells show a bumpy surface. That makes the surface
rough. As a result, dirt particles rest only on the tips of wax crystals coating the leaf
surface. The roughness reduces the contact area between the particles and the leaf
surface.
A rough surface structure with wax crystals makes it impossible for water to stick. Due to
the friction, the water contracts at once. It forms spherical droplets to minimise the
contact area with the rough, waxy leaf surface and runs off the leaf very quickly. Since
the dirt particles only rest on the tips of the wax crystals they stick more strongly to the
water droplets than to the leaf surfaces. They are washed away when the water falls on
the leaves.
On smooth leaves, the dirt particles are pushed from one part of the leaf to the other.
This is because the dirt particles have a larger contact area where they can rest
comfortably on the flat surface. We must also keep in mind that water usually spreads
and only partially runs off the leaves -- that too, only if the leaf is tilted! The dirt
particles may get dislodged, but they are mainly displaced from one side of the leaf to
the other.
Water not only dissolves some dirt, but attracts and removes it like a snowball rolling downhill.
Lotus petals have micrometer-scale roughness, resulting in water contact angles up to 170°

31. The “Lotus Effect” Biomimicry
Isotactic polypropylene (i-PP) melted between two glass slides and subsequent crystallization provided a smooth surface. Atomic force microscopy tests indicated that the surface had root mean square (rms) roughness of 10 nm.
A) The water drop on the resulting surface had a contact angle of 104° ± 2
B) the water drop on a superhydrophobic i-PP coating surface has a contact angle of 160°.
Scientists at the University of Bonn carried out extensive
research to show that the water droplets rolling off a lotus leaf carry away dirt particles
leaving the surface perfectly clean. This phenomena has been named the 'Lotus Effect'
and works best on rough surfaces. A report on the scientists' study was published in the
journal 'Planta'.
Contrary to popular belief, lotus leaves are not smooth at all. When examined under a
powerful microscope, the leaf cells show a bumpy surface. That makes the surface
rough. As a result, dirt particles rest only on the tips of wax crystals coating the leaf
surface. The roughness reduces the contact area between the particles and the leaf
surface.
A rough surface structure with wax crystals makes it impossible for water to stick. Due to
the friction, the water contracts at once. It forms spherical droplets to minimise the
contact area with the rough, waxy leaf surface and runs off the leaf very quickly. Since
the dirt particles only rest on the tips of the wax crystals they stick more strongly to the
water droplets than to the leaf surfaces. They are washed away when the water falls on
the leaves.
On smooth leaves, the dirt particles are pushed from one part of the leaf to the other.
This is because the dirt particles have a larger contact area where they can rest
comfortably on the flat surface. We must also keep in mind that water usually spreads
and only partially runs off the leaves -- that too, only if the leaf is tilted! The dirt
particles may get dislodged, but they are mainly displaced from one side of the leaf to
the other.
Science, 299, (2003), pp , H. Yldrm Erbil, A. Levent Demirel, Yonca Avc, Olcay Mert

32. Legos of Chemical Biology
Amino Acids
Legos of Chemical Biology
Amino acids contain carbon, hydrogen, oxygen, and nitrogen, which resemble the following shapes & structural components
20 different amino acids are encoded by the genetic code, which is archived in DNA.
Hundreds of amino acids link together with amide (peptide) bonds to form proteins, which are the machinery for the chemistry of life.
There are less than 20,000 total proteins produced from humans’ entire genome, each coded by a specific gene in DNA’s ~3 billion genetic bases.

33. Proteins: Indispensible Biopolymers
Acetylcholinesterase (ACE)
ACE, an enzyme, which catalyzes a key reaction in a repetitive biochemical cycle that is crucial to neurological and physiological functions in humans…. and insects among others.
4,496 atoms; 4,404 bonds
574 amino acid residues

34. Proteins & Small Molecules
Acetylcholinesterase
Two images with Sarin, a potent nerve agent, which inhibits acetylcholinesterase, and causes convulsions and death if not antidoted with atropine.
Sarin

35. Proteins & Small Molecules
Acetylcholinesterase
The ACE enzyme has a receptor, a site in the molecule defined by the 3 amino acids in the image on the right. It binds acetylcholine, which then hydrolyzes. Sarin out competes acetylcholine, binds, and the enzyme cannot work.

36. Proteins & Small Molecules Acetylcholinesterase
The normal interaction of acetylcholinesterase with acetylcholine. This general process is similar to the way we smell and relates to many, many physiological and pharmacological processes.

37. Detecting stuff we cannot see: the Sense of Smell
Models, Theories & Interactions
Structure-Odor Relationships
Karen J. Rossiter, Chem. Rev., 1996, 96,

38. Historical view of a few smell receptors.
4 October 2004
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine for 2004
jointly to
Richard Axel and Linda B. Buck
for their discoveries of
"odorant receptors and the organization of the olfactory system"
They discovered a large gene family, comprised of some 1,000 different genes (three per cent of our genes) that give rise to an equivalent number of olfactory receptor types. These receptors are located on the olfactory receptor cells, which occupy a small area in the upper part of the nasal epithelium and detect the inhaled odorant molecules.

40. Shapes & Interactions: Mirror Images & Smell
S-(+)-d-
R-(-)-l-
S-(+)- caraway R-(-)- spearmint

41. Chirality & Carbon Atoms
Each carbon atom with four different substituents are chiral.

42. Chirality

44. Stereoisomerism Enantiomers are chiral:
i.e. They are non-superimposable mirror images.
Most physical and chemical properties of enantiomers are identical.
Therefore, enantiomers are very difficult to separate eg. Tartaric acid… Louis Pasteur:
Enantiomers can have very different physiological effects: eg. (+) and (-) carvone, Advil (ibuprofen) …… (thalidomide)

45. The small, yet critical chemical differences between the safe R+ conformation of the molecule (responsible for anti-inflammatory activity) and the dangerous S- conformation are what contribute to thalidomide's toxicity (#Liu, et al, 2004). According to Franks et al. (2004):
"the thalidomide molecule is a racaemic glutamic acid analogue, consisting of S- and R+ enantiomers that interconvert under physiological conditions (#Franks, et al, 2004). The S- form potently inhibits release of tumor necrosis factor (TNF alpha) from peripheral mononuclear blood cells, whereas the R+ form seems to act as a sedative, probably mediated by sleep receptors in the forebrain" (#Franks, et al, 2004).
Liu (2005) also suggests that the S- form of the molecule inhibits TNF alpha, which regulates apoptosis. This seems to promote unregulated cell proliferation that leads to tumor formation (#Liu, et al, 2004). Cytochrome P-450 generates thalidomide metabolites, which leads to adverse health effects (#Liu, et al, 2004). The chemical properties of thalidomide were found to be unstable in solution, because the molecule would spontaneously hydrolyze in physiological conditions over 6.0 pH (#Perri and Hsu, 2005).
between 5,000 and 7,000 infants were born with phocomelia (malformation of the limbs). Only 40% of these children survived.[4] Throughout the world, about 10,000 cases were reported of infants with phocomelia due to thalidomide; only 50% of the 10,000 survived.
In the late 1950s and early 1960s, more than 10,000 children in 46 countries were born with deformities such as phocomelia as a consequence of thalidomide use.[72] The severity and location of the deformities depended on how many days into the pregnancy the mother was; thalidomide taken on the 20th day of pregnancy caused central brain damage, day 21 would damage the eyes, day 22 the ears and face, day 24 the arms, and leg damage would occur if taken up to day 28. Thalidomide did not damage the foetus if taken after 42 days gestation.[40]
From the late 1950s – early 1960s more than 10,000 children in 46 countries were born with deformities caused by the S-(-) enantiomer.

46. chiral carbon atom