CHEMICAL PROPERTIES OF WATER
Water is Nucleophilic

The __________ pairs on the oxygen atom in water make water nucleophilic (__________
lovers). Nucleophiles attack _______________ (electron lovers) during substitution or addition.

Water is a weak nucleophile, but it’s concentration in a cell is so high that it could attack many
macromolecules and cause the macromolecules to be _______________ (degraded by water).
o
R
+
H3N
Hydrolysis of a peptide releases its monomeric units (amino acids):
O
CH C
O

+
NH CH C
R
O
R
hydrolysis
+
H2O
-
condensation
H3N
O
O
CH C
O
-
+
+
H3N
CH C
R
Notice that the equilibrium lies far to the right – so why aren’t all proteins destroyed by
hydrolysis in the cell?
o
The linkages between monomers in cells are rather stable at cellular _____ and
_______________.
o
The reaction __________ of hydrolysis is slow enough that hydrolysis is not that
favorable over the life of the cell.
o
The chemical potential energy of __________ is used to overcome the unfavorable
thermodynamic barrier.
o
Enzymes that catalyze synthesis reactions of macromolecules keep water out of their
__________ sites.
Ionization of Water

Recall the self-ionization of water:

We learned last year that the concentration of hydronium and hydroxide ions was 1 x 10–7 M for
each, resulting in the following for the derivation of Kw:
Kw = [H3O+][OH–] = (1 x 10–7 M)2 = 1 x 10–14 M2
o
Your Principle of Biochemistry textbook approaches Kw from the perspective of the
concentration of pure water. Knowing the molar mass of water, one can calculate the
concentration of pure water in 1 L of water:
O
-
o
The ionization constant of water has been determined to be 1.8 x 10–16 M under standard
conditions (1 atm and 25°C). If the ionization of water is represented as follows,
H2O <=> H+ + OH–
one can calculate Kw using an equilibrium expression and solving for Kw:
pH Scale

The concentration of _______________ (H+) affects many biochemical processes, like…
o
the transport of _______________ in the blood,
o
the _______________ of reactions by enzymes, and
o
the generation of _______________ energy during respiration and photosynthesis.

Recall the equations that relate pH and [H3O+]:

Physiological pH is _____, but the blood of patients suffering from certain diseases can have
acidosis, when the blood is __________ physiological pH. If the blood is above physiological
pH, patients are suffering from _______________.

Ex: Calculate the pH of 0.225 M trichloroacetic acid.
Strong and Weak Acids

Recall that strong acids and strong bases completely _______________ in water.
HCl + H2O
o
The equilibrium is shifted completely to the _______________, favoring complete
ionization.

Many organic acids are weak acids, therefore they do _____ completely dissociate in water.
CH3COOH + H2O
o
The equilibrium favors the __________, which is the _______________ form of the acid,
not the ionized form.
o
In order to study the pH of weak acids and bases, an equilibrium expression must be
devised and an interpretation of its constant is necessary:
o
The Ka for acetic acid is 1.76 x 10–5 M, a rather small value. To make interpreting weak
acid and base equilibrium values easier, a pKa is calculated:
pKa = –log[Ka] =
o
pH is a measure of acidity, therefore pKa is a measure of the strength of an acid or base.
An acid with a low pKa is _______________ than one with a high pKa. For example:

Acid/Base
Ka
pKa

H3PO4
6 x 10–3
2.2 (acidic)

CH3COOH
2 x 10–5
4.8

H2CO3
4 x 10–7
6.4
–8
7.2
–

H2PO4
6 x 10

CH3NH3+
2 x 10–11
10.7

HPO4–
2 x 10–13
12.7 (basic)
Ex: Calculate the pH of 0.0750 M methanamine (pKa = 10.66).
The Henderson-Hasslebalch Equation

Consider the generic dissociation of a weak acid to establish the following equilibrium:
HA <=> H+ + A–

Write the Ka expression.

Take the logarithm of both sides.

Since log (x y) = log x + log y…

Solve for – log [H+].

Replace the negative logarithms with previously defined pH and pKa:

This is the Henderson-Hasslebalch equation. Its usefulness will be exemplified later.

pKa values of weak acids can be determined using titration.
o
If a weak acid has one proton, then it takes a 1:1 ratio of the acid to a strong base to
neutralize the acid. At the midpoint the titration curve is rather flat, and half of the acid
molecules have been dissociated. Therefore [HA] = [A–]. Insert this into the HendersonHasslebalch equation:

Polyprotic acids such as H3PO4 have three pKa values, as seen in the list above. That means the
curves will have three flat midpoints!
Buffers

Buffers resist changes in _____. To make a buffer, one needs a solution that contains a
__________ acid, and a salt containing it’s _______________.
o
Ex: An acetic acid buffer must contain a solution of _______________ __________ and
__________ _______________.
o

__________ buffers can be created as well.
The most effective buffering occurs when the concentration of the weak acid and its conjugate
base are _________. This is when the _____ equals _____.

Buffer capacity is the _______________ of strong acid or strong base required to change the pH
of 1 L of the buffer by _____ pH unit.

The blood plasma of mammals has a pH buffered at _____. Evidence of a strong physiological
buffer is the buffering capacity:
o
The addition of 1 mL of 10 M HCl to a 1 L sample of water changes the pH to _____.
o
The addition of 1 mL of 10 M HCl to a 1 L sample of human blood plasma changes the
pH to _____.

The pH of blood is mostly regulated by the CO2  H2CO3  HCO3– buffer system:
CO 2 (g)

CO 2 (aq)
H2CO 3
-
HCO 3
According to _______________ _______________, a system at equilibrium will __________ to
relieve a stress applied to the system.
o
If the pH of the blood drops (H+ ions have been added), then the equilibrium shifts
__________, using HCO3– in the blood to combine with the H+ ions to form carbonic
acid. The removal of the H+ raises the pH. Carbonic acid then decomposes to form
aqueous CO2, which then enters the gaseous phase in the lungs and is exhaled.
o
If the pH of the blood rises (H+ ions have been removed), then the equilibrium shifts
__________, forcing inhalation of gaseous CO2 and dissolving the CO2 into the blood.
The CO2 reacts with water in the blood to produce H2CO3, which then releases H+ ions
into the blood forming HCO3– ions, dropping the pH.

Within cells, both _______________ and _______________ help to buffer against pH changes.
In blood, _______________ is the strongest buffer other than the CO2  H2CO3  HCO3–
buffer system.

Ex: Acetic acid has a pKa of 4.756. What volume (in mL) of 0.100 M acetic acid and 0.100 M
sodium acetate are required to prepare 1.00 L of 0.100 M buffer solution having a pH of 5.8?