9/9/24

Lecture 2 (9/9/24)
• Reading for today: Ch2, 43-53
Ch2, 53-64
• Homework #2 & #3 OUTLINE
WATER
Properties
The 4 S’s
NEXT Shape
Size
Solubility
• Reading: Ch3, 70 Hydrogen Bond
Properties explained
Ch1, 13-19
Ch4, 106-107 Molecular Forces Important for Life
Other Electrostatic interactions
• Homework #4 Salt bridges
van der Waals Forces
Hydrophobic Effect (Dispersion or induced
dipole–induced dipole)
– Consequences
Stability (pH); Last of 4 S’s

Quantifying Thermodynamics
S P
Chemistry of Life: Biochemistry

For Free Energy, DG: Ice ⇌ Water

Magnitude of DG depends on:

DG = DH – TDS
§ DH—total energy added (DH > 0) or released
(DH < 0); can be related to bonds
§ DS—change in entropy, more randomness
(DS > 0) or more order (DS < 0); Positive
changes in entropy make DG more negative.
Negative changes in entropy make DG more
positive.

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Quantifying Thermodynamics
S P
Chemistry of Life: Biochemistry
The interplay of enthalpy and entropy in the simple
ice/water reaction, as a function of the temperature:
Ice ⇌ Water
–5.4 –6.0 –6.6

+5.6 +6.0 +6.4

Properties of Water
1) Water has a high boiling point and relatively
low melting point; its range in the liquid state
is large
2) The heat of vaporization is high (more heat to
change to vapor state than to raise temperature of
the liquid state)
3) Liquid is more dense than the solid (e.g., most
metals and other substances the solid is more
dense)
4) High viscosity relative to its molecular weight
(MW)
5) High surface tension

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WATER

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Figure 2.15 Surface Tension

Properties of Water

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WATER
The 4 S’s for Water:
Shape
Size
Solubility
Stability

Most of the properties of water are explained

or due to its shape, in other words, its
structure

Shape of Water
• sp3 hybridized orbitals:
2 are bonding
2 are filled non-bonding

• Distorted tetrahedral (equal angles of

109.5°): due to repulsion of electrons
in filled orbitals

.5 °
104

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Shape of Water
Permanent DIPOLE

Size of Water
Very compact structure:
2.0 Å in diameter
though van der Waals
diameter of oxygen atom is
2.8 Å

The O–H bond is

relatively short (0.96 Å)
though van der Waals
diameter of hydrogen atom 2.0 Å
is 2.4 Å

What are these discrepancies due to?

ELECTRONEGATIVITY OF OXYGEN

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Solubility of Water: Hydrogen Bonding

These dipoles interact with each other in a special kind of non-covalent bond:
THE HYDROGEN BOND.

Bit of a misnomer but named as such because it appears though two oxygen
atoms of two water molecules share a hydrogen

Its not at all equal: the water with the covalent bond to hydrogen is called the
DONOR. The opposite water molecule is called the ACCEPTOR

DONOR ACCEPTOR

Solubility of Water: Hydrogen Bonding

THREE important aspects d+ d–
that make H-bonds unique:

1) Electrostatic: dipole- d–
dipole interaction d+

2) Partial electron sharing:

partial covalency

3) Directional: geometry 0.96 Å 1.84 Å

2.8 Å

This is a stronger bond

than this (due to optimizing
the covalency)
.
…

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Rings of Water “Flickering Clusters”

Molecules of Water Molecules
Since one H-bond is
energetically equivalent
to another, they are
constantly being
broken and made

On average,
liquid water at
25 °C has
about 3.5
hydrogen
bonds per
molecule

Structure of Ice

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Properties of Water – explained

1) Water has a high boiling point and relatively low
melting point; its range in the liquid state is large
2) The heat of vaporization is high
• Ave number of H-bonds in liquid water is ~3.5, but in
steam ~0
3) Liquid is more dense than the solid
• Ave number of H-bonds in liquid water is ~3.5, but in ice
its 4, but the tetrahedral-like geometry takes over
4) High viscosity relative to its molecular weight (MW)
• liquid water with ~3.5 H-bonds/molecule is sticky
5) High surface tension
6) Water is also a great SOLVENT

Solvation of Ions

Cations

Anions

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Hydrogen Bonding of Polar Molecules

with and without Water Water to
ketones/
aldehydes

Water to alcohols

Water to
carboxylic acids
Water to amines

Typical Bond Energies

(kcal · mol-1)

} ~95

4.7

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WATER

The 4 S’s for Water:

✓ Shape
✓ Size
✓ Solubility
Stability
Before we discuss the 4th “S” of water, we need to take
an important tangent and discuss the other very
important non-covalent forces that operate constantly
on macromolecules

Molecular Forces
Important for Life
The 4 NON-covalent “bonds”:

}
H-bonds
Salt bridges Electrostatic
van der Waal’s interactions
Hydrophobic effect

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(AKA Salt Bridges)

Electrostatic Interactions
Charge – Charge interactions The strength of all these is governed by
Coulomb’s Law:
Na+ r Cl–
Force between two charged
particles = k q1q2
D r2
Where q is the charge on each particle 1 and 2, D is
the dielectric constant (unit-less; =1.0 in vacuum, ~80
in water), r is the distance between the two charges,
and k is Coulomb’s constant (9x109 J·m/C2, where
C=1.6x10-19 electron charges)

Recalling the relationship between Force

Induced dipole – Induced dipole interactions
(AKA Van der Waals interactions) and Energy (E = Force x distance (r)):
E = k q1q2 Salt Bridges
Dr

Molecular Forces
Important for Life
The 4 NON-covalent bonds:
✓ H-bonds
✓ Salt bridges
van der Waal’s interactions
} Electrostatic

Hydrophobic effect

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(AKA Salt Bridges)

Electrostatic Interactions
Charge – Charge interactions The strength of all these is governed by
Coulomb’s Law:
Na+ Cl–

r Force between two charged

particles = k q1q2
D r2
Where q is the charge on each particle 1 and 2, D is
3 the dielectric constant (unit-less; =1.0 in vacuum, ~80
r in water), r is the distance between the two charges,
and k is Coulomb’s constant (9x109 J·m/C2, where
C=1.6x10-19 electron charges)

r5 Recalling the relationship between Force

Induced dipole – Induced dipole interactions
(AKA Van der Waals interactions) and Energy (E = Force x distance (r)):
E = k q1q2 E = k q1q2
Dr D r6
r6
For partial charges, this distance dependence is exponential

van der Waals Interactions

Induced dipole – Induced dipole interactions But, as the energy is so
(AKA Van der Waals interactions)
E = k q1q2 dependent on distance,
even when at r0, its
D r6 VERY weak.

10 Å / 1 nm

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van der Waals Interactions

van der Waals Interactions

This is one example highlighting the issue of COMPLEMENTARITY, and why

this is so important in biology

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Typical Bond Energies

(kcal · mol-1)

} 95

@ ~3 Å 20

4.7

Van der Waals interactions

0.07

Hydrophobic interactions

Typical Bond Energies

(kcal · mol-1)

} 95

@ ~3 Å 20

4.7

Van der Waals interactions

0.07

Hydrophobic interactions

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Molecular Forces
Important for Life
The 4 NON-covalent bonds:
✓ H-bonds
✓ Salt bridges
✓ van der Waal’s interactions } Electrostatic

Hydrophobic effect

Hydrophobic Interactions
Hydrophobic interactions: atoms “attracted”
together due to water structure.
Nonpolar Solutes Aggregate in Water

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Hydrophobic Interactions
Structure: Nonpolar Solutes in Water

Like ICE

Hydrophilic versus Hydrophobic

Figure 2.12 Hydrophilic and
Interactions
Hydrophobic

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Hydrophobic Interactions
Figure 2.12 Hydrophilic and
Hydrophobic

x5

Hydrophobic Interactions

3 “degrees” of freedom (DoF)

Statistical mechanics has determined that
each DoF is equal to 5-6 kcal/mol at 25 °C 6 “degrees” of freedom

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Hydrophobic Interactions
For EXAMPLE
3 [CH4·10H2O] [(CH4)3 · 12H2O] + 18H2O

DG
DG?is definitely NEGATIVE: How?

Enthalpy Enthalpy DH = +45

30 H2O x 4 H-bonds 18 H2O x 3.5 H-bonds kcal/mol
each x 5 kcal/mol = 600 kcal/mol each x 5 kcal/mol = 315 kcal/mol, added in
heat release to make H-bonds plus 12 H2O x 4 H-bonds x 5 =
240 kcal/mol; Total = 555 kcal/mol
excess to
heat released to make bonds break H-
DH = –555 – (–600) bonds
= +45 TDS=114-18 TDS = +96
Entropy Entropy
3 degrees of 19 degrees of =96 kcal/mol in
freedom (DoF) x 6 kcal/mol at freedom (DoF) x 6 kcal/mol at entropic
25 °C per DoF = 18 kcal/mol 25 °C per DoF = 114 kcal/mol energy
DG = DH – TDS gained
= +45 – 96
= –51 kcal/mol

ENTROPY DRIVEN

Hydrophobic Interactions

Transfer of Hydrocarbons to Nonpolar Solvents is

Entropically Driven

Note the bottom two: Reaction in reverse is the completely entropic

positive values of +17-20 kJ/mol for putting benzene or toluene into water

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Bond Energies of Important Non-

covalent Interactions

(kcal · mol-1)

} 95

@ ~3 Å 20

4.7

Van der Waals interactions

0.07

Hydrophobic interactions (per –CH2–) 26 6

Molecular Forces
Important for Life
The 4 NON-covalent bonds:
✓ H-bonds
✓ Salt bridges
✓ van der Waal’s interactions } Electrostatic

✓ Hydrophobic effect

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Amphipathic Interactions
(both hydrophobic and hydrophilic)
Example: amphiphiles like Fatty Acid Anions,
detergents

=O
–O–S–O– · +Na

=O
Sodium dodecyl sulfate (C12H25O4S) (SDS)

Amphiphiles Form Micelles & Bilayers

Structure of a Micelle

Protein interiors

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Disrupters of the Hydrophobic Effect

Urea Guanidinium-HCl

Physical Properties of Water

Learning Goals: Concepts about water
• Water molecules, which are polar, can form hydrogen
bonds with other molecules.
• In ice, water molecules are maximally hydrogen bonded in a
crystalline array, but in liquid water, still with many
hydrogen bonds, they rapidly break and re-form in irregular
networks.
• Polar and ionic substances can dissolve in water.
• The attractive forces acting on biological molecules include
ionic interactions, hydrogen bonds, and van der Waals
interactions.
• The hydrophobic effect explains the exclusion of nonpolar
groups as a way to maximize the entropy of water
molecules.
• Amphiphilic substances form micelles or bilayers that hide
their hydrophobic groups while exposing their hydrophilic
groups to water.

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WATER
The 4 S’s for Water:
Shape ✓
Size ✓
Solubility ✓
Stability

The discussion of water’s stability is a

discussion of its ionization.
H2 O D H+ + OH–

2H2O D H3O+ + OH–

Ionization of Water
Proton “Transfers” Occurs Rapidly

The Positive
H Charge jumps

H
H H

+ H

Proton “transfers” are very rapid!

2H2O D H3O+ + OH–
What is the concentration of OH– and H3O+ (protons)?

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Ionization of Water
What is the concentration of OH–?
2H2O D H3O+ + OH–
Equilibrium constant for this acid
dissociation (aka deprotonation) reaction
Keq is 1.8 x 10-16 M
+ –
Keq = 1.8 x 10-16 M = [H ] [OH ]
[H2O]
[H2O]1.8 x 10-16 M = [H+] [OH–] [H2O] = 55.5 M*
55.5 M x 1.8 x 10-16 M = [H ] [OH ] since [H+] = [OH–]
+ –

55.5 M x 1.8 x 10-16 M = [H+]2

1.0 x 10-14 M2 = [H+]2
1.0 x 10-7 M = [H+]
Take the –log of both sides:
call the –log[H+] = pH
7 = pH
*1 L water = 1000 g/L ÷ 18 g/mol = 55.5 M

Ionization of Water
Relationship of pH, [H+], and [OH-]

2H2O D H3O+ + OH–

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Ionization of Water
pH Values of Common Substances

Ionization of Water
Definitions of Acids and Bases:
HA D H+ + A– If dissociation is >water: ACID
HB D H+ + B– If dissociation is <water: BASE
When B– associates with protons, it leaves a net difference in [OH–]

2H2O D H3O+ + OH–

In other words: A proton donor is an Acid (HA)

A proton acceptor is a Base (B–)

Likewise: The resulting anion from acid dissociation is

called the conjugate base (A–)
The resulting protonated base is called a
conjugate acid (HB)
These are Bronsted/Lowry definitions used in Biochemistry

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Ionization of Water
Definitions of Acids and Bases:
And the [HA] added is the
[H+] in solution.

Strong Acid HA ® H+ + A–
Strong Base H+ + B– ® HB

Protons come from pulling the water dissociation equilibrium

And the [B–] added is the
2H2O D H3O + OH
+ – [OH–] in solution.

Weak Acid HA D H+ + A–
Weak Base HB D H+ + B–
For weak acids/bases, all 3 species are in measurable
concentrations.
How do you calculate these concentrations and how
are they related to the pH?

Ionization of Water
How do you calculate these concentrations and how are they
related to the pH?

Use the Equilibrium Constant (Keq) for the dissociation reaction

HA D H+ + A–
Keq = Kd = Ka = [H+] [A–]
[HA]
since [H+] is best expressed as pH, can take –log of each side:
–
pKa = pH – log [A ]
[HA]
[A–]
pH = pKa + log
[HA]
This is called the Henderson-
Hasselbalch equation

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Ionization of Water

Ionization of Water
Dissociation Constants and pKa Values
of Some Acids

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Ionization of Water
Buffers: Titration Curves of Weak Acids

NOTICE: Adding protons, but

pH not changing very much =
BUFFER
}
}
}

Ionization of Water
Buffers: Titration of a Polyprotic Acid
H3PO4 D H+ + H2PO4– D H+ + HPO42– D H+ + PO43–
pK1 pK2 pK3

12.4

6.8

2.2

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Ionization of Water

Does this make sense? …. Go back to the reaction:

HA D H+ + A–
At low pH, [H+] is high, forcing the equilibrium to the left = more HA, less A–

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