CHAPTER 1

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 medium for life
• Life evolved in water (UV protection)

• Organisms typically contain 70–90% water

• Chemical reactions occur in aqueous milieu

• Water is a critical determinant of the structure and

function of proteins, nucleic acids, and membranes
 Structure of the Water Molecule
• Octet rule dictates that there are four electron pairs
around an oxygen atom in water
• These electrons are in four sp3 orbitals
• Two of these pairs covalently link two hydrogen atoms
to a central oxygen atom
• The two remaining pairs remain nonbonding (lone
pairs)
• Water geometry is a distorted tetrahedron
• The electronegativity of the oxygen atom induces a net
dipole moment
• Because of the dipole moment, water can serve as
both a hydrogen bond donor and acceptor
 Hydrogen Bonds
• Strong dipole-dipole or charge-dipole interaction that arises
between an acid (proton donor) and a base (proton acceptor)
• Typically 4–6 kJ/mol for bonds with neutral atoms,
and 6–10 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 H–O 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 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
 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
 Physics of Noncovalent Interactions
Noncovalent interactions do not involve sharing a pair of electrons.
Based on their physical origin, one can distinguish between:
• Ionic (Coulombic) Interactions
– Electrostatic interactions between permanently charged species, or
between the ion and a permanent dipole
• Dipole Interactions
– Electrostatic interactions between uncharged, but polar molecules
• van der Waals Interactions
– Weak interactions between all atoms, regardless of polarity
– Attractive (dispersion) and repulsive (steric) component
• Hydrophobic Effect
– Complex phenomenon associated with the ordering of water
molecules around nonpolar substances
Examples of Noncovalent Interactions
 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
Hydrogen Bonds: Examples
Biological Relevance of Hydrogen Bonds
 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
0.4–0.7 nm)
• Repulsion dominates at very short distances
• There is a minimum energy distance (van der Waals
contact distance)
Origin of the London Dispersion Force

• Quantum mechanical origin

• Instantaneous polarization by fluctuating charge
distributions
• Universal and always attractive
• Stronger in polarizable molecules
• Important only at a short range
 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
 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
Affects 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
• 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
Effect of Extracellular Osmolarity
 Ionization of Water
 H+ + OH-
H2O 
• 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 M•cm)
• 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 (oxonium) ions.
• 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
 Ionization of Water:
Quantitative Treatment
Concentrations of participating species in an equilibrium process
are not independent but are related via the equilibrium constant:
[H +
]•[OH-
]

H2O  H + OH
+ -
Keq = ————
[H2O]

Keq can be determined experimentally, it is 1.8•10–16 M at 25C.

[H2O] can be determined from water density, it is 55.5 M.

• Ionic product of water:

 - 14 2
K w  K eq  [H 2 O]  [H ][OH ]  1 10 M

•In pure water [H+] = [OH–] = 10–7 M

 What is pH?
• pH is defined as the negative
pH = -log[H+] logarithm of the hydrogen ion
concentration
• Simplifies equations
K w  [H  ][OH - ]  1 10 14 M 2 • 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
+ H2O
Keq O • Weak electrolytes dissociate
H3C H3C + H3O+
OH O- only partially in water.

K a  K eq  [H 2 O] • Extent of dissociation is
determined by the acid
[H  ][CH 3COO - ]
Ka   1.74 10 5 M dissociation constant Ka.
[CH 3COOH]

• We can calculate the pH if the

 [CH 3COOH]
[H ]  Ka  Ka is known. But some
[CH 3COO  ]
algebra is needed!
Dissociation of Weak Electrolytes:
Example
What is the final pH of a solution when 0.1 moles of
acetic acid is added to water to a final volume of 1L?
O O
H3C
Ka • We assume that the
H 3C + H+
OH O- only source of H+ is
0.1 – x x x the weak acid
[ x ][ x ]
Ka   1.74 10 5 M
[0.1 - x] • To find the [H+], a
2 6 5 quadratic equation
x  1.74 10  1.74 10 x
must be solved
x 2  1.74 10 5 x  1.74 10 6  0
x = 0.001310, pH = 2.883
Dissociation of Weak Electrolytes:
Simplification

O O • The equation can be

Ka
H3C H 3C + H+ simplified if the amount of
OH O-
dissociated species is much
0.1 – x x x
0.1 x x less than the amount of
undissociated acid
Ka 
[ x ][ x ]
 1.74 10 5 M • Approximation works for
[0.1]
sufficiently weak acids and
x 2  1.74 10 6 bases
• Check that x < [total acid]
x = 0.00132, pH = 2.880
 pKa measures acidity
• pKa = –log Ka (strong acid  large Ka  small pKa)
 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
Weak acids have different pKas
Henderson–Hasselbalch Equation:
Derivation
[H  ][A - ]
HA 
 H + + A- Ka 
[HA]
[HA]
[H ]  K a
+

[A - ]

[HA]
- log[H  ]  -logK a  log
[A-]

-
[A ]
pH  pK a  log
[HA]
 Biological Buffer Systems
• Maintenance of intracellular pH is vital to all cells
– Enzyme-catalyzed reactions have optimal pH
– Solubility of polar molecules depends on H-bond donors and acceptors
– Equilibrium between CO2 gas and dissolved HCO3– depends on pH

• Buffer systems in vivo are mainly based on

– phosphate, concentration in millimolar range
– bicarbonate, important for blood plasma
– histidine, efficient buffer at neutral pH

• Buffer systems in vitro are often based on sulfonic acids of cyclic

amines
– HEPES HO
N N
– PIPES
SO3Na
– CHES
Water as a Reactant in Biochemistry

condensation reaction

hydrolysis
Water bound to proteins is
essential for their function

hemoglobin
Water bound to proteins is
essential for their function

cytochrome f
Water bound to proteins is
essential for their function

L-arabinose-binding protein of bacterium

 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
•The way water can participate in biochemical reactions
 homework
1.Self introduction
Name , nationality, email address or contact number, a photo
Back ground: where you read your middle school , high
school, what courses you have learned, expertise,
Academic experience, etc, within 300 words,
2. List all your reasons why water is important for life?
3. Anything else you want to say. within 300 words

Hand written or printed version

To be collected on 16th or 23rd April 2019 , Tuesday