1

Example Problem
Calculate DG
o
for the reaction A + B C + D at 25
o
C when the
equilibrium concentrations of [A] = 10 mM, [B] = 15 mM, [C] = 3
mM, [D] = 5 mM. Is the reaction exergonic or endergonic under
standard conditions?
This is an equilibrium!!! K
eq
= [C][D]/[A][B]

DG
o
= -RT ln K
eq
= -RT ln {[C][D]/[A][B]}
K
eq
= {[3x10
-6
M][5x10
-6
M]/[10x10
-6
M][15x10
-6
M]}
DG
o
= -(8.3145 J/K-mol)(298K) ln {0.1} = 5705 J/mol
DG
o
= 5.7 kJ/mol
Not spontaneous since free energy is positive (endergonic)
Also makes sense because the concentrations of C and D are
less than A and B.
2
Chapter 2: Water
Physical properties of water
Structure of water
Water as a solvent
Hydrophobic effect
Osmosis and diffusion
Chemical properties of water
Ionization of water
Acid-base chemistry
Buffers

3
Water is The Fundamental Chemical of Life
1. Nearly all biological molecules assume their
shapes (and functions) in response to the
physical and chemical properties of the
surrounding water molecules.
2. Most biochemical reactions happen in water.
3. Water is often directly involved in catalytic
reaction(s) supporting life. (H+, HO-)
4. The production of O
2
from water and CO
2
is a
fundamental process in plant biochemistry
(photosynthesis).
4
Structure of Water
+0.33e
+0.33e
-0.66e
d+ d+
d-
5
Hydrogen Bonding in Water
ca. 1.8
Sum of H (1.2 ) and O (1.4 ) VDW radii = 2.6
H-Bond Interaction Distance = 1.8
H-bond donor
H-bond acceptor
The oxygen atom in water has four sp
3
hybrid orbitals
Two for the lone pairs and two for the hydrogens
+0.33e
d+
-0.66e
d-
6
ICE: Each water molecule has
four H-bonds one for each of
the two hydrogen atoms
(donors) and two for each
oxygen (acceptor) atom.
Ice has lattice network of H-
bonds = Strong!
LIQUID: Water consists of
a rapidly changing 3D
arrangement of H-bonded
water molecules (3-4 H-bonds).

Density (water) = 1.0 g/ml
Density (ice) = 0.92 g/ml
Water expands on freezing
Ice Structure
7
8
Dipole moments are
created by the
separation of (partial)
charges or by the
inducement of a
charge separation
Recall that the
separation of charge
is due to differential
electronegativities of
atoms involved in
bonds
9
Molecules have a definite shape
C
O
B
A
O
H
HO
H
HO
H
OH
OH
H
H
OH
A, B, C, and O all lie in
the same plane. This is
trigonal planar
As the molecule becomes
larger the shape becomes
more complicated
And may have many
different conformations
Shape of molecules can
significantly depend on
water!
Chair
Boat
Chair
10
Geometry and Polarity
d
+
d
-

While C Cl is polar,
carbon tetrachloride is not.
The sum of the vectors
equals zero = nonpolar
molecule.
mCCl
4
: m
1
=m
2
=m
3
=m
4
Therefore, m
1
+m
2
+m
3
+m
4
= 0

mCHCl3: m
2
=m
3
=m
4
but not m
1
!
Therefore, m
1
+m
2
+m
3
+m
4
is not 0!

C
Cl
Cl
Cl Cl
m1
m2
m3
m4
C
Cl
Cl
Cl
m2
m3
m4 H
CHCl
3
is polar
11
Dipolar nature of water
Opposite orientation of waters around a cation
vs. that around an anion.
Solvation of Cations (+) and Anions (-)
12
Water of Hydration
Hydration - to be surrounded by H
2
O.
A polar molecule is hydrated by the partial charge interaction
of water molecules
A non-polar molecule is hydrated by concentric shells of
ordered shielding water molecules
Multiple hydrogen-bonds increase solubility

Hydrophilic molecules are those that love to be in
water.

Hydrophobic molecules are those that hate to be in
water (remember oil and water dont mix).


13
Water molecules
form hydrogen-
bonds with organic
functional groups.
Note that water can
act as both a
hydrogen-bond
acceptor and donor
(simultaneously).
14
Hydrophobic Effect
Hydrophobic effect: Water surrounds hydrophobic molecules to
maximize hydrogen bonding, minimizes hydrophobic contacts.
Driving force is increased ordering of water molecules around the
hydrophobic molecule, entropically disfavored.
15
STRUCTURED WATER

A cage of water molecules surrounding a non-polar
molecule has more structure than the surrounding bulk
water.

DG = DH TDS (+TDS = MORE ORDER!)

Minimize the structuring of water,
Hydrophobic molecules cluster together,
minimizing the surface area.
Fewer water molecules are needed to organize
around a smaller surface area!!!
16
Non-polar molecules
are hydrated in a
different way (i.e.
NOT via hydrogen-
bonds to the molecule
but rather by forming
cage-like structures)
This results in the
hydrophobic effect
Non-polar molecules
tend to congregate in
these water cages
17
Aggregation of Non-Polar Molecules in Water
Reduced Surface Area = Fewer Water
Molecules in Cage
18
Amphiphiles
Many biological molecules contain both polar
and non-polar segments.
Combined hydrophobic and hydrophilic
properties
19
Amphiphiles: Polar and Non-Polar
Detergents, Fatty acids, lipid molecules
polar head; non-polar tail.
Proteins
polar and hydrophobic regions; hydrophobic
interactions are the greatest contributor to the
three dimensional shapes of proteins.
Water is more concentrated than the molecules it
surrounds so the shear numbers of ordered molecules
is much greater. The greatest entropy is a function
of both the dissolved molecule and the solvent.

20
Amphiphiles form micelles, membrane
bilayers and vesicles
To minimize the highly ordered cage of water, the
amphiphile is forced into a structure to maximize entropy.
DG = DH -TDS driven by TDS (minimize loss of entropy!)
Protein Structure: Amphiphiles and Hydrophobic
Effects
21
Ribbon Diagram of Triosephosphate Isomerase
Hydrophobic
Interior and
Pockets

Buried!
Hydrophilic
Surface
Residues

Exposed!
Protein Structure: Amphiphiles and Hydrophobic
Effects
22
Solvent Excluded Structure of Triosephosphate Isomerase
Hydrophobic
Interior and
Pockets

Buried!
Hydrophilic
Surface
Residues

Exposed!
23
Diffusion and Osmosis
Diffusion occurs by random movement of molecules into all
regions that are accessible to each molecule. This occurs
constantly and, at some point, there is an equal concentration of
molecules throughout all regions.
Osmosis is the diffusion of solvent molecules (water) across a
barrier from regions of high concentration (pure water) to regions
of lower concentration (water containing dissolved molecules).
Osmotic Pressure is the pressure necessary to stop osmosis of
solvent across a barrier. Proportional to solute concentration.
Dialysis is a useful technique for separating small molecules
from large ones using the principle of osmosis through a semi-
permeable barrier. For example, ions and other small molecules
can be gradually removed from a solution of protein via
(repeated) dialysis.
24
Diffusion
Diffusion results
from the movement
of molecules from
regions of high
concentration to low
concentration.
Diffusion equalizes
the concentration of
molecules filling the
container.
25
Osmosis
Osmosis results from
the movement of
molecules through a
semi-permiable
barrier.
Osmosis occurs so as
to equalize the
concentration of
permeable species on
both sides of barrier
Water Solution Barrier Pure Water
Water Concentration 1 < Water Concentration 2
26
Small molecules diffuse across membrane-diluted into large
volume of solvent.
Osmosis of solvent attempts to dilute the solution of larger
molecules in the dialysis membrane.
For Next Time:
27
Study Rest of Chapter 2 and Start Chapter 4.

Work through problems in Chapter 2 in
Textbook and Student Companion

Memorize the Amino Acids!!!

Labor Day, Monday Sept. 2, No Class!