1. Chapter 2 : Water
Lets Jump into …. Water. Opening figure: fatty acid in a clathrate with waters of hydration (more dense than surrounding water) around the carboxyl.

2. Learning goals:
What kind of interactions occur between different type of molecules in water.
Why water is a good medium for life
Why nonpolar moieties aggregate in water
How dissolved molecules alter properties of water
How weak acids and bases behave in water: to be able to solve weak acid problems with the Henderson-Hasslebalch equation.
How buffers work and why we need them
How water participates in biochemical reactions

3. Structure
Review

4. ICE
Review

5. Common H-bonds in Biochemistry
Review

6. Some Biologically Important H-bonds
The last two are important in protein and nucleic acid structure.

7. H-bond Strength and Alignment
Review

8. Importance of Hydrogen Bonds
Source of unique properties of water
Structure and function of proteins
Structure and function of DNA
Structure and function of polysaccharides
Binding of substrates to enzymes
Binding of hormones to receptors
Matching of mRNA and tRNA
“I believe that as the methods of structural chemistry are further applied to physiological problems, it will be found that the significance of the hydrogen bond for physiology is greater than that of any other single structural feature.”
–Linus Pauling, The Nature of the Chemical Bond, 1939

9. Water as a Solvent
Water is a good solvent for charged and polar substances
amino acids and peptides
small alcohols
carbohydrates
Water is a poor solvent for nonpolar substances
nonpolar gases
aromatic moieties
aliphatic chains

10. Polarity (or not) of some common biochemicals

11. Solvation and Hydration Spheres
The cartoon only shows waters of hydration being one layer thick. But in reality it is more for a couple of layers.

12. Review

13. Flickering Clusters and Clathrate Cages
What is important is that the flickering cluster life time is in nano-seconds, so it’s really “flickering”. The clathrate water around a non polar surface last longer, but with no more bond energy than flickering clusters.

14. The Hydrophobic Effect
Refers to the association or folding of nonpolar molecules in the aqueous solution
Is one of the main factors behind:
protein folding
protein-protein association
formation of lipid micelles
binding of steroid hormones to their receptors
Does not arise because of some attractive direct force between two nonpolar molecules

15. Fatty acids in water begin to form micells which are fairly stable
Fatty acids in water begin to form micells which are fairly stable. This can take time, but in the lab we can make this happen faster in a sonicator….adding sound energy to facilitate fatty acids movement until they find others and the hydrophobic interactions take over.

16. Substrates Must Displace Water to Bind Enzymes
Substrates usually bind into pockets rather than slight indents, so the waters interacting with the substrate must be pushed aside as the substrate enters the pocket (or clefts which we will do in Chapter 6 with Chymotrypsin).

17. Approximate Bond Strength, kJ/mole
12-30 20
<40
0.4 – 4.0
Distance,nm
0.3
0.25 -
0.2
The weak bonds are Exceptionally Important !

18. Water Bound to Hemoglobin
Each red dot is a water molecule.
Hb purified from water Hb with Water Removed

19. Proton Hop and Hydronium

20. Water Bound in a Protein Channel (Cytochrome f)
Facilitates Proton Hopping – see later in Photosynthesis
Cytochrome f is in cholorplasts. You are familiar with cytochromes a, b and c in the mitochondria.
Proton hopping by Hydroniums.

21. Solutes decrease vapor pressure, review.

22. Osmotic Pressure
Review

23. Cell Response to Osmotic Pressures

24. Plants Use Osmotic Pressure
Venus fly-trap uses osmotic pressure to cause movement and trap the insect.

25. Plants Use Osmotic Pressure
Review
Protection Against Wind

26. Ionization of Water Keq = [H+][OH-] / [H2O] = 1.8 x 10-16 M
Concentration of water - one liter = 1,000g
Mole Wt Water =
[H2O] = 55.5 M
Kw = [H+][OH-] = Keq x [H2O] = 1 x M2
for pure water [H+] = [OH-]
so, [H+] = 10-7 M
pH is negative log [H+] , for pure water = 7.0
Review

28. Most life and biochemistry is near neutral and into the acid
Most life and biochemistry is near neutral and into the acid. What is the pH inside a cell? Of the stomach?

29. pH = pKa + log ( [A-] / [HA] )
Weak Acids
HA ↔ H+ + A-
K e = [H+][A-] / [HA] = Ka
Henderson-Hasselbalch Equation Rearranges Ka
pH = pKa + log ( [A-] / [HA] )
when pKa = pH … [A-] = [HA]
Weak acids try to hold on to the proton…dependent on pH. Know this well, we will be doing problems with the Henderson Hasselbalch equation which you had in General Chemistry. What about strong acids: what happens when HCl for example is added to water? All this is review !

30. pKa’s speak to the strength of the weak acids
pKa’s speak to the strength of the weak acids. Check out the difference in carboxyl pka’s. Phosphate has three pKa’s keep these in mind, we will use it later in the course.

31. A

32. Acid Base Tirations: Note that acetate has two forms:
Associated (HA)  pKa (half associated, half dissociated)  Dissociated (A-).

33. Weak acids have different pKas
FIGURE 2–18 Comparison of the titration curves of three weak acids. Shown here are the titration curves for CH3COOH, H2PO-4, and NH+4 . The predominant ionic forms at designated points in the titration are given in boxes. The regions of buffering capacity are indicated at the right. Conjugate acid-base pairs are effective buffers between approximately 10% and 90% neutralization of the proton-donor species.

34. The imidazol group of the amino acid Histidine is a weak acid (one of the nitrogens, is it the imid or azole?).

35. Enzymes have pH optima Related to their Function

36. Review

37. Water as a Reactant
Most polymerizations are dehydrations and depolymerization reactions (Ex: digestive enzymes) are hydrations.

38. Pretty Picture

39. Problem 18 in Chapter 2 1 liter of 0.1 M glycine.
a. what pH’s is glycine a good buffer due to its amino group:

40. Problem 18 in Chapter 2 1 liter of 0.1 M glycine.
a. What pH is glycine a good buffer due to its amino group:
NH3+
Glycine = CH2-COO-
pKa’s = and 9.6
So it would be good +/- 1.0 from each pKa
which would be from 1.3 to and 8.6 to 10.6 for the amino group.
The buffering region is around each pKa. Buffering capacity is dependent on pH: at pH 1.3 glycine is not a good buffer of further acid addition, but is of further hydroxide addition. What about at pH 2.3 and 9.6?

41. Problem 18 in Chapter 2 I liter of 0.1 M glycine.
NH3+
Glycine = CH2-COO-
pKa’s = and 9.6
I liter of 0.1 M glycine.
b. in a 0.1 M solution, pH 9.0 what fraction has the amino group as –NH3+ ?
Example of a Clicker Question: R-NH3+ is HA A-
H2O H+
OH-

42. Problem 18 in Chapter 2 I liter of 0.1 M glycine.
NH3+
Glycine = CH2-COO-
pKa’s = and 9.6
I liter of 0.1 M glycine.
b. in a 0.1 M solution, pH 9.0 what fraction has the amino group as –NH3+?
pH = pKa + log A/HA
9.0 = log A/HA
log A/HA =  A/HA =  0.25HA = A
HA + A = 0.1M so HA HA = 0.1 M :: 1.25HA = 0.1M
so HA = 0.08 M…and that is 80% of 0.1M so 
not asked: A = 0.02 M or 20%

43. Problem 18 in Chapter 2 I liter of 0.1 M glycine.
NH3+
Glycine = CH2-COO-
pKa’s = and 9.6
I liter of 0.1 M glycine.
c. How much 5M KOH is needed to change pH from 9 to 10 for 1 Liter of 0.1M glycine?

44. Problem 18 in Chapter 2 I liter of 0.1 M glycine.
NH3+
Glycine = CH2-COO-
pKa’s = and 9.6
I liter of 0.1 M glycine.
c. How much 5M KOH is needed to change pH from 9 to 10 for 1 Liter of 0.1M glycine?
pH = pKa + log A/HA = log A/HA
so: log A/HA = thus A/HA = 2.5  2.5HA = A
HA + A = 0.1 M  HA HA = 0.1 M  3.5HA= 0.1M
so HA at pH 10 = moles/L
from pH 9 HA is converted to A by adding OH-, that is HA is lowered from 0.08M to 0.029M or a change of moles
0.051 moles/5 moles/L = 0.01 L  10 ml of 5M KOH

45. Problem 18 in Chapter 2 I liter of 0.1 M glycine.
NH3+
Glycine = CH2-COO-
pKa’s = and 9.6
I liter of 0.1 M glycine.
d. When 99% of glycine is in its –NH3+ form, what is the pH of solution due to it’s amino group? (functionally reworded from the text)
pH = pKa + log A/HA so this is easy HA dominates, so it will be on the acid side of the pKa. A is only 1% or so the
log of A/HA ≈ thus pH = 9.6 – 2 = or 7.6

46. Things to Know and Do Before Class
General Chemical Properties of Water.
pH definition and what it means+how to calculate it.
Strong vs Weak Acids.
Henderson-Hasselbalch Equation and how to do calculations with it.
Weak bonds and their relative bond strength.
Make sure you are able to do EOC Problems calculating pH (2-5, 8), pH affects solubility (14) and uptake of aspirin (15) and rest on buffers (11): They are part of Class Clicker Questions and Case Study (aspirin).