Intermolecular Forces, Water Solubility, and Molecular Recognition
Major concepts
 The attractions that molecules have for each other are based on their charge distributions,
which can be determined from their structures
 Some intermolecular forces are stronger and some are weaker
 A compound is water soluble if its IMFs allow it to effectively be surrounded by water molecules
 “Like dissolves like”
 Enzymes recognize molecules by their unique shape and IMF profile
Vocabulary
 Intermolecular force
 Hydrogen bonding
 Dipole/dipole interactions
 Instantaneous dipole
 Solubility
 Molecular recognition
Students should be able to:
 Recognize which types of IMF a molecule is capable of having based on its structure
 Apply VSEPR and resonance to determine a molecular dipole
 Distinguish between molecules that are highly water soluble and highly water insoluble based
on their structures
 Explain the principles of molecular recognition and their significance in biological systems
Daily Problems
1. Which of the following pairs of molecules are capable of hydrogen bonding with each other?
Acceptor (A), Donor (D), Both (B)
A
A
A
B
Yes
No
B
Yes
B
B
A
B
A
Yes
Yes
2. Which of these molecules has/have a molecular dipole moment? Draw an arrow to represent the
dipole moment(s) or write “no molecular dipole.”
no molecular
dipole.. they
cancel
Overall molecular
dipole: individual
bond dipoles add
up or cancel each
other out in
molecular dipole
3. Why is it not possible to rank Hydrogen bonding as always a stronger or weaker intermolecular force
than van der Waals (induced dipole) interactions?
Even though van der Waals forces are weak, they can add up. In this example, the many van der Waals
forces between hydrocarbons are overall more powerful than one H-bond.
4. Why is it incorrect to say that “a water molecule has hydrogen bonding.” What is a better way to say
what you mean?
We can never talk about just one molecule with intermolecular forces. To have intermolecular forces,
there must be multiple molecules to interact. Better to say that two water molecules are capable of Hbonding to each other.
5. Would you expect these molecules to be water soluble or water insoluble?
no
no
“like dissolves like”
water soluble:
-ionic
yes
yes
-highly polar
-many H-bond acceptors
and donors
no
Cumulative problems
6. You might expect this compound to have a dipole moment based on its Lewis Dot structure, but it
doesn’t. Explain, using its “real” electron distribution.
If we just consider this
structure, the molecular
dipole would be as shown.
If we consider the resonance hybrid, the dipoles cancel out.
7. When we say that the nucleic acid bases guanine and cytosine “base pair”, we are saying that they
recognize each other with complementary intermolecular forces, which hold them together, like a
magnet. Below are their structures , aligned in the proper orientation to each other. Using your
knowledge of resonance , redraw them in the more aromatic looking structures. Indicate partial charges
on the base pairing atoms to show how they align so strongly.
Notice how the acceptors are
electron rich and the donors are
electron poor.
Also notice the perfect
alignment to maximize
closeness of all H-bonding
partners.
8. Material Science: Teflon is the “non-stick” polymer that coats many frying pans. Most compounds
are either more attracted to aqueous-like compound or hydrocarbon-like compounds. Teflon, on the
other hand, does not stick to oily (hydrocarbon) substances, and water beads up on the surface because
of its bad intermolecular interactions with Teflon. Explain why Teflon is both hydrophobic and
lipophobic based on its structure:
F F
F
F F
F
F F
F
F
F
F F
F
F
F F
F
F
F F
F
F
F F
F
Hydrophobic: fluorine has lone pairs that hold closely to the nucleus as it is the most electronegative
atom. This makes it a bad H-bond acceptor, so water does not form any H-bonds.
Lipophobic: fluorine lone pairs are so stabilized to the nucleus that no instantaneous dipoles exist,
leading to minimal van der Waals forces with non polar molecules such as oils.
9. Nutrition: Vitamins are labeled as “water-soluble” or “fat-soluble” based on their storage in the body.
Water soluble vitamins are excreted quickly in the urine; fat-soluble vitamins are stored for longer
periods in body-fat reserves and therefore do not need to be consumed daily. Based on structure alone,
it is possible to determine fat vs. water solubility. Which of the following molecules is/are most likely to
be excreted quickly?
HO
OH
O
H
OH
vitamin A
N
Vitamin B6
O
OH
HO
NH2
O
excreted quickly=
water soluble
N
HO
Vitamin B3
OH
Vitamin C
O
Vitamin K
R
O
10. Enzymes: Enzymes are proteins, which are large molecules made up of many amino acids. Amino
acids contain a variety of functional groups. Enzymes bind to smaller molecules through the
intermolecular forces we have been discussing. The way that enzymes “recognize” which small
molecules to bind to is through having complementary IMFs in their active sites.
In the figure below--taken from Proceedings of the National Academy of Science, 97,2011-2016 (Feb
2000) by Wolfenden and coworkers--the small molecule is in red and the groups from the enzyme are in
black. The interactions between the enzyme and molecule are given by colored dashed lines, and the
interactions between the protein and other parts of the protein are given in black dashed lines.
Describe the types of IMFs observed. How does this set of IMFs make this enzyme very selective for
binding this small molecule rather than any other?
*
*
*
/
*
*
/
*
*
*
Overall, the molecule
fits perfectly in the
pocket (active site) so
that is excludes water
and maximizes IMF.
*
* = H-bonds
/ = ionic interaction
Extension problem
11. Water can hydrogen bond to acetic acid (vinegar) by placing its most negative area (lone pair) next
to the most positive area (hydrogen atom) of acetic acid. This forms a fairly strong interaction, which is
close to becoming a bond. What if the interaction became a full bond, and the existing H-O bond broke,
as illustrated by arrows? What would the products be?
δ-
δ+