1. Hydrogen bonding potential Specific heat, heat of vaporization
Properties of water
Polarity
Hydrogen bonding potential
Specific heat, heat of vaporization
Nucleophilic
Ionization
It is the unique combination of properties of water that make it the perfect solvent for biological systems. We will discuss each of these properties in more detail.
It is the unique combination of properties of water that make it the perfect solvent for biological systems. We will discuss each of these properties in more detail.

2. Water and pH Water - one of the most important molecules in life.
70% of the bodies mass is water
2/3 of total body water is intracellular (55-66% body weight of men and 10% less for women)
The rest is interstitial fluid of which 25% is in the blood plasma.
pH - The body tightly controls both the volume and pH of water.
The bicarbonate system is crucial for blood maintenance
changes of pH greater than 0.1 are dangerous and can lead to coma -diabetics

3. Life on Earth would not be possible without water Its chemical and physical properties actually defy some fundamental laws of physics Almost all biochemical reactions require water!

5. Water is an ideal biological solvent
Water is close to a tetrahedral shape with the unshared electrons on the two sp3-hybridized orbital are in two corners and the hydrogen in others
Compared to a tetrahedron, CH4 (109o) or NH3 the bond angle is smaller (109.5o and 107o vs.104.5o)
Due to the bent shape of the molecule, there is an uneven distribution of electrons.
It is a polar molecule,
-a dipole

6. Water is a polar molecule
Water has a dipole moment
“like dissolves like”
Water is assymmetric. It has an electron rich and an electron poor side to it.
Think about carbon dioxide and ammonia. CO2 is nonpolar whereas NH3 is polar. NH3 is highly soluble in water whereas CO2 is much less soluble.
Oxygen is more electronegative than hydrogen so there is an uneven distribution of charge in this H-O bond
Uneven distribution is called a dipole and the bond is said to be polar

7. Water has hydrogen bonding potential
H-bonds are non-covalent, weak interactions
H2O is both a Hydrogen donor and acceptor
One H2O can form up to four H-bonds
Water molecules attact one another.
Orientation is important.
H-bond 20 kJ mol-1
O-H bond 460 kJ mol-1
When all four optimal H-bonds are formed per water, ice is formed.

8. What makes this molecule important?
solvent ability - easily disrupts ionic compounds
dielectric constant (D) is high (measure of the ability to keep ions apart) F = Kq q 1 2 D r
Coulombs Law - The force of attraction
between two charged pairs

9. What makes this molecule important?
solvent ability - easily disrupts ionic compounds
dielectric constant (D) is high (measure of the ability to keep ions apart) F = Kq q 1 2 D r
Coulombs Law - The force of attraction
between two charged pairs
K = proportionality constant
8.99 x 109 J.M.C2
q = charge and sign of ion
D = 75.5 (water), 24.3 (EtOH)1.9 (Hexane), 2.4 (interior of protein).

10. What makes this molecule important?
solvent ability - easily disrupts ionic compounds
dielectric constant (D) is high (measure of the ability to keep ions apart) F = Kq q 1 2 D r
Coulombs Law - The force of attraction
between two charged pairs
large electronegativity creates a strong ionic type bond (dipole).
Liquid water has a higher density than solid water (ice). Is this normal? Think of why this is important?
orderliness - solvating shells
ability to take place in many hydrogen bonds (up to 4 at a time)

11. What makes this molecule important?
solvent ability - easily disrupts ionic compounds
dielectric constant (D) is high (measure of the ability to keep ions apart) F = Kq q 1 2 D r
Coulombs Law - The force of attraction
between two charged pairs
- Strong nucleophile -
to prevent unwanted attack by water, proteins often “hide” reactions from water by creating a hydrophobic core
Specific heat and heat of vaporization is high for water due to extensive H bonding

12. Water and H-bonds High specific heat
Lots of heat is needed to break H-bonds and raise H2O temperature. Therefore, H2O is a good insulator.
High heat of vaporization
Lots of heat is needed to vaporize H2O. Therefore, sweat cools.
High specific heat of water in multicellular organisms helps minimize temperature fluctuations – important for biological function.
H-bonding of water is the reason for these unusual properties of liquid water.

13. Other bonds can also be Polar
Water is assymmetric. It has an electron rich and an electron poor side to it.
Think about carbon dioxide and ammonia. CO2 is nonpolar whereas NH3 is polar. NH3 is highly soluble in water whereas CO2 is much less soluble.
Fig. 2.2

14. Water is nucleophilic Water weakly ionizes
Water participates in many chemical reactions
it is electron rich
it is a weak nucleophile
it is present in high concentration
Water weakly ionizes
“the ultimate fate of proteins is destruction by hydrolysis.”
How are biopolymers made, then?
Peptide bonds are kinetically stable. Require hydrolases for catalysis.
ATP is required for biosynthesis.
Enzyme active sites exclude water.

15. CO2 buffers our blood
Water reacts with CO2 to form an important blood buffer
We breath in and out gaseous CO2
In the blood, CO2 reacts with water to form the buffering compound H2CO3 –carbonic acid
Disturbances in blood buffering system leads to acidosis (pH below 7.1) or alkalosis (pH above 7.6)
Bleeding in lungs – death!
“a few good men”
Phosphoric acid is trivalent. It requires three equivalents of base to completely titrate.
What are the predominant species of phosporic acid at physiological pH? (monobasic and dibasic) pKa is 7.2
What are the effective buffering ranges of phosphoric acid? (pKa +/- 1 pH unit)

16. CO2 buffers our blood
Primary buffering compounds at physiological pH is H2CO3 (carbonic acid) and HCO3- (bicarbonate)
Phosphoric acid is trivalent. It requires three equivalents of base to completely titrate.
What are the predominant species of phosporic acid at physiological pH? (monobasic and dibasic) pKa is 7.2
What are the effective buffering ranges of phosphoric acid? (pKa +/- 1 pH unit)

17. We will come back to this after we talk about pH and buffers
CO2 buffers our blood
We will come back to this after we talk about pH and buffers

18. Noncovalent Bonds
The London dispersion force is the weakest intermolecular force.
temporary attractive force that results when the electrons in two adjacent atoms occupy positions that make the atoms form temporary dipoles.
sometimes called an induced dipole-induced dipole attraction.
cause nonpolar substances to condense to liquids and to freeze into solids when the temperature is lowered sufficiently.

19. Noncovalent Bonds - London forces
Because of the constant motion of the electrons, an atom or molecule can develop a temporary (instantaneous) dipole when its electrons are distributed unsymmetrically about the nucleus.
A second atom or molecule, in turn, can be distorted by the appearance of the dipole in the first atom or molecule (because electrons repel one another) which leads to an electrostatic attraction between the two atoms or molecules

20. Noncovalent Bonds - van der Waals
the van der Waals force is the attractive or repulsive forces between molecules (or between parts of the same molecule) other than those due to covalent bonds or to the electrostatic interaction of ions with one another or with neutral molecules
The term includes:
dipole–dipole forces
London (instantaneous dipole–induced dipole) forces
induced-dipole induced-dipole (dispersion forces)

21. Noncovalent interactions in biomolecules
Ionic
H-bond
van der Waals
Hydrophobic
Ionic>H-bond, hydrophobic>van der Waals
Salt bridges in the interior of proteins are very strong because water can’t break them up.
There are many forms of H-bonds.
Large biomolecules can have a large number of van der Waals interactions. Cumulatively they are important for maintaining structure.
Hydrophobic interactions are also cumulative. They are important in protein folding and maintenance of sturcture.
H-bonds in biomolecules 2 to 7 kJ mol-1
Van der Waals forces 0.8 to 1.3 kJ mol-1
Hydrophobic 3 kJ mol-1

22. Noncovalent Bonds – van der Waals
The major noncovalent interactions in cells are electrostatic (ionic), hydrophobic, hydrogen bonds, and van der Waals.
Remember:
London forces are minimal unless tight association occurs
Most covalent bonds are 8 to 10 times stronger yet the overall shape and effectiveness of large molecules are due to the much weaker non-covalent bonds.

23. Ionic Bonds or salt bridges... into the 21st century?
Simple magnetic attraction between
Carboxy and amino groups, metals…
The force of attraction (F) depends on distance and relative shielding
Water and salts weaken bond
Strongest single noncovalent bond

24. Hydrogen bonds
result from the interactions of strong covalent bonds between hydrogen and a highly electronegative atom (N and O)
strongest bonds are when the arraignment is linear.
The hydrogen is “shared” by a the covalently bonded atom and another electronegative atom
You must be able to identify the donor and acceptor

25. Dipolar water dissociates in solution
association of dipolar water with typical biological side groups due to Hydrogen bonding
A-hydroxyl groups
B-keto groups
C-carboxylate ions
D-ammonium ions

26. Van der Waals (dipole-induced interactions)
Next to London dispersion forces, these are the weakest of the nonionic bonds but are important due to the large number of van der Waal interactions in a protein
These bonds originate from very small dipole moments generated in atoms as electrons move around the nucleus.

27. Van der Waals
These are small ionic, dipolar interactions
The energy of the attraction is related to the distance between nuclei
The average separation between atoms or molecules is the sum of the van der Waals radii

28. Van der Waals
Space filling models use the van der Waal Radii to depict sizes

29. van der Waals in nature
The ability of geckos to climb on sheer surfaces has been attributed to van der Waals force
A gecko can hang on a glass surface using only one toe. Efforts continue to create a synthetic "gecko tape" that exploits this knowledge
A recent study suggests that water molecules of roughly monolayer thickness (present on all surfaces) also play a role

30. Hydrophobic interactions
The association of relatively nonpolar molecular groups in an aqueous environment.
Driven by the order of water entropy
The lack of interactions with a polar molecules with decreases the randomness of the order of water. ( an increase in entropy)

31. Hydrophobic interactions
Water forms cage-like structure around hydrocarbons forming shells of highly ordered water
Shell formation is due to water forming hydrogen bonds with each other
Aggregation of hydrophobic moleculules reduces total surface area and results in less order (increase in entropy)
Minimization of the
hydrophobic portions of the molecule permits the water max degrees of freedom (a minimization of entropy increase)

32. Why are non-polar molecules insoluble in water?
Highly ordered water forms “cages: around the hydrophobic lipid

33. Why are non-polar molecules insoluble in water?
A: It is energetically unfavorable to solvate a non-polar molecule.
Non-polar (hydrophobic) compounds interfere with the structure of water - HOW?
Water molecules surrounding a hydrophobic molecule are ordered but cannot make hydrogen bonds or ionic interactions to the non-polar molecule.
This reduces the entropy (disorder) of water and is thermodynamically unfavorable and is called the hydrophobic effect.
Highly ordered water forms “cages: around the hydrophobic lipid

34. Release of ordered molecules is entropically favorable.
Molecular associations are often accompanied by the release of water molecules that are ordered at the molecular surface.
Release of ordered molecules is entropically favorable.
Highly ordered water interacting with enz & Substrate
Disorded water displaced by interaction
By solvating themselves through self association, hydrophobic molecules, decrease the level of order of the system (shells of hydration) entropy is increased!
Enzyme - Substrate interaction stabilized by hydrophobic interactions - less shells of hydration for new complex

35. Thus nonpolar molecules aggregation is not due to attraction to other hydrophobic compounds but due to inability to interact with water
Thus it is entropically favorable to have several hydrophobic pieces come together so only on shell is formed. This is the hydrophobic effect.
Very important in maintaining protein structure
hydrophobic portions of proteins are solvated by “hiding” inside the molecule away from the water.
This is the driving force for the formation of ampipathic molecules forming lipid bilayers membranes and vesicles

36. The End
Any Questions?