BIOCHEMISTRY I

Midterm exam schedule (Chap 2-7)

4/24 (Fri) 8pm
No withdrawal allowed!

 Key term report submission:

3/4
3/9.
3/16.
3/23.
4/1.
4/8.

Chap 2. aqueous system.

Chap 3. amino acids, peptides, and proteins
Chap 4. tertiary and quaternary structure of proteins
Chap 5. protein functions
Chap 6. enzymes
Chap 7. carbohydrates and glycobiology

# Quizes
3/23 (Mon): Chapter 2 and 3
4/6 (Mon): Chapter 4 and 5

2 | Water and Aqueous Solutions

2013 W. H. Freeman and Company

2013 W. H. Freeman and Company

CHAPTER 2
Water and Aqueous Solutions
Learning goals:

What kind of interactions occur between molecules

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
How buffers work and why we need them
How water participates in biochemical reactions

Water is the most abundant substances in

living system, 70% or more of the weight of
most organisms
All aspects of cell structure and function are
adapted to the physical and chemical
properties of water

Hydrogen bonding gives water its unusual properties

Water has higher melting point, boiling point, and heat of

vaporization than most other common solvents
: Hydrogen bonding

FIGURE 2-1a Structure of the water molecule. (a) The dipolar

nature of the H2O molecule; the two hydrogen atoms have localized
partial positive charges (+) and the oxygen atom has a partial
negative charge ().

Hydrogen Bonds
Strong dipole-dipole or charge-dipole interaction that arises
between an acid (proton donor) and a base (proton acceptor)
Typically 46 kJ/mol for bonds with neutral atoms,

and 610 kJ/mol for bonds with one charged atom

Typically involves two electronegative atoms (frequently
nitrogen and oxygen)
Hydrogen bonds are strongest when the bonded molecules are
oriented to maximize electrostatic interaction

Ideally the three atoms involved are in a line

Hydrogen Bonding in Water

Water can serve as both
an H donor
an H acceptor
Up to four H-bonds per water molecule gives water its
anomalously high boiling point
anomalously high melting point
unusually large surface tension
Hydrogen bonding in water is cooperative
Hydrogen bonds between neighboring molecules are weak
(20 kJ/mol) relative to the HO covalent bonds (420 kJ/mol)

Ice: Water in a Solid State

Water has many different crystal forms;
the hexagonal ice is the most common
Hexagonal ice forms a regular lattice,
and thus has a low entropy
Hexagonal ice contains more hydrogen
bonds/water molecule
Thus, ice has lower density than liquid water;
and, ice floats

Water forms hydrogen bonds with polar solutes

- Water is a polar solvent

: charged or polar compounds can be readily dissolved.
- Chloroform and benzene are nonpolar solvents

- Hydrophilic compounds: dissoves easily in water.

- Hydrophobic compounds: nonpolar molecules

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

Hydrogen Bonds: Examples

Biological Relevance of Hydrogen Bonds

Water dissolves many salts

High dielectric constant reduces attraction
between oppositely charged ions in salt crystal;
almost no attraction at large (> 40 nm) distances
Strong electrostatic interactions between the
solvated ions and water molecules lower the
energy of the system

Entropy increases as ordered crystal lattice is

dissolved

The strength of ionic interaction (F):

Q1Q2
F= r2

Q: magnitude of charge
: dielectric constant
r: the distance between charged groups
For water, at 25 C, = 78.5: weak ionic interaction
For benzene, = 4.6 : strong ionic interaction
Ionic attractions or repulsion operate only over short distances

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

Solubility of Polar and Nonpolar Solutes

Why are nonpolar molecules poorly soluble in water?

Low solubility of hydrophobic solutes

can be explained by entropy
Bulk water has little order:
high entropy
Water near a hydrophobic solute is highly ordered:
low entropy

Low entropy is thermodynamically unfavorable, thus

hydrophobic solutes have low solubility.

Water surrounding nonpolar solutes has

lower entropy

Origin of the Hydrophobic Effect (1)

Consider amphipathic lipids in water

Lipid molecules disperse in the solution; nonpolar

tail of each lipid molecule is surrounded by ordered
water molecules
Entropy of the system decreases
System is now in an unfavorable state

Origin of the Hydrophobic Effect (2)

Nonpolar portions of the amphipathic molecule aggregate so that
fewer water molecules are ordered
The released water molecules will be more random and the
entropy increases
All nonpolar groups are sequestered from water, and the released
water molecules increase the entropy further
Only polar head groups are exposed and make energetically
favorable H-bonds

Hydrophobic effect favors ligand binding

Binding sites in enzymes and receptors are often
hydrophobic
Such sites can bind hydrophobic substrates and
ligands such as steroid hormones
Many drugs are designed to take advantage of the
hydrophobic effect

van der Waals Interactions

van der Waals interactions have two components:
Attractive force (London dispersion) depends on
the polarizability
Repulsive force (Steric repulsion) depends on the
size of atoms
Attraction dominates at longer distances (typically
0.40.7 nm)
Repulsion dominates at very short distances
There is a minimum energy distance (van der Waals
contact distance)

Biochemical Significance of
van der Waals Interactions
Weak individually
easily broken, reversible

Universal
occur between any two atoms that are near each other

Importance
determines steric complementarity
stabilizes biological macromolecules (stacking in DNA)
facilitates binding of polarizable ligands

Examples of Noncovalent Interactions

Name and briefly define four types of

noncovalent interactions that occur between
biological molecules.

(1) Hydrogen bonds: weak electrostatic attractions between one

electronegative atom (such as oxygen or nitrogen) and a
hydrogen atom covalently linked to a second electronegative
atom
(2) electrostatic interactions: relatively weak charge-charge
interactions (attractions of opposite charges, repulsions of
like charges) between two ionized groups
(3) hydrophobic interactions: the forces that tend to bring two
hydrophobic groups together, reducing the total area of the
two groups that is exposed to surrounding molecules of the
polar solvent (water)
(4) van der Waals interactions: weak interactions between the
electric dipoles that two close-spaced atoms induce in each
other.

Weak interactions are crucial to macromolecular structure and function

Hydrogen bond
Ionic interaction
Hydrophobic interaction
Van Der Waals interaction

continually forming and breaking

=> individually insignificant but cumulatively very significant

Effects of Solutes on Properties of Water

Colligative Properties
Boiling point, melting point, and osmolarity
Do not depend on the nature of the solute, just the
concentration: number of solute particles

Noncolligative Properties
Viscosity, surface tension, taste, and color
Depend on the chemical nature of the solute

Cytoplasm of cells are highly concentrated

solutions and have high osmotic pressure

Osmotic Pressure

Osmosis => water movement across a semipermeable membrane

driven by differences in osmotic pressure.
Isotonic solution
Hypertonic solution
Hopotonic solution

Effect of Extracellular Osmolarity

Ionization of Water
H+ + OHH2O
O-H bonds are polar and can dissociate heterolytically

Products are a proton (H+) and a hydroxide ion (OH)

Dissociation of water is a rapid reversible process
Most water molecules remain un-ionized, thus pure water has
very low electrical conductivity (resistance: 18 Mcm)
The equilibrium is strongly to the left
Extent of dissociation depends on the temperature

Proton Hydration
Protons do not exist free in solution.
They are immediately hydrated to form hydronium ons.
A hydronium ion is a water molecule with a proton associated with
one of the non-bonding electron pairs.
Hydronium ions are solvated by nearby water molecules.
The covalent and hydrogen bonds are interchangeable. This
allows for an extremely fast mobility of protons in water via
proton hopping.

Proton Hopping

Water chain in cytochrome f, which is part of the energy-trapping machinery of

photosynthesis in chloroplasts. Proton hopping is involved in movement of protons.

Ionization of Water:
Quantitative Treatment
Concentrations of participating species in an equilibrium process
are not independent but are related via the equilibrium constant:
+][OH-]
[H
H+ + OHH2O
Keq =
[H2O]
Keq can be determined experimentally, it is 1.81016 M at 25C.
[H2O] can be determined from water density, it is 55.5 M.

Ionization of water is expressed by an equilibrium constant

Keq =

[H+][OH-]
[H2O]

Keq =

[H+][OH-]
[55.5 M]

at 25C

Ion product of water, Kw

( 55.5 M )( Keq ) = [H+][OH-] = Kw

Kw = [H+][OH-] = 1.0 X 10-14 M2

Neutral pH:
equal amount of [H+] and [OH-] as in pure water.
[H+] = [OH-] = 10-7 M

What is pH?
pH = -log[H+]

pH is defined as the negative

logarithm of the hydrogen ion
concentration
Simplifies equations

K w [H ][OH- ] 11014 M2 The pH and pOH must always

add to 14
log[ H ] log[ OH- ] 14 In neutral solution, [H+] = [OH]
and the pH is 7
pH pOH 14
pH can be negative ([H+] = 6 M)

pH scale is logarithmic:
1 unit = 10-fold

pH of Some Common Liquids

Dissociation of Weak Electrolytes:

Principle
O
H3C

+ H2O

Keq

H3C

OH

+ H3O+

O-

K a K eq [H 2 O]

[H ][CH3COO- ]
Ka
1.74 10 5 M
[CH3COOH]

[H ] Ka

[CH3COOH]
[CH3COO ]

Weak electrolytes dissociate

only partially in water.
Extent of dissociation is
determined by the acid
dissociation constant Ka.
We can calculate the pH if the
Ka is known. But some
algebra is needed!

pKa measures acidity

pKa = log Ka (strong acid large Ka small pKa)

Weak acids have different pKas

Imidazole pKa = 7.0

Protonated? Deprotonated?
At pH = 8.0
At pH = 6.0

pKa=6.0

Buffers are mixtures of weak acids

and their anions (conjugate base)
Buffers resist change in pH
At pH = pKa, there is a 50:50 mixture of acid and

anion forms of the compound

Buffering capacity of acid/anion system is greatest

at pH = pKa
Buffering capacity is lost when the pH differs from

pKa by more than 1 pH unit

Acetic Acid-Acetate as a Buffer System

HendersonHasselbalch Equation:
Derivation
[H ][A - ]
Ka
[HA]

HA
H+ + A-

[HA]
[H ] K a
[A - ]
+

[HA]
- log[H ] -logK a log
[A-]
-

[A ]
pH pK a log
[HA]

Chapter 2: Summary
In this chapter, we learned about:
The nature of intermolecular forces
The properties and structure of liquid water
The behavior of weak acids and bases in water