1st week
• Living organisms (domains, kingdoms, definition)• Cellular foundation: Structure and function of the cell
• Chemical foundation: Biomolecules and building blocks

2nd week• Three laws of thermodynamics (1, 2)• Is a living organism at equilibrium with surrounding?
• G?
• Equilibrium constant?
• G˚?
• Chemical coupling?
• Enzymes function as catalysts. How?

Spontaneity Depends on
Enthalpy (H) & Entropy (S)Before (H1)

After (H2)

hot coffee (70 ˚C)cooled coffee (30 ˚C)

H2 - H1 > 0 ?
H2 - H1 < 0 ?

HWhere did 40 go?

H<0https://pixabay.com/ja/

Before (S1)After (S2)clean room (10)dirty room (100)S2 - S1 > 0 ?
S2 - S1 < 0 ?

SS>0Spontaneity Depends on
Enthalpy (H) & Entropy (S)Always happens
spontaneously

Temp dependent

Never happens
spontaneouslyEquilibrium and G˚

R = gas constant
T = absolute Temp

Equilibrium constant: thereactants and products are atequilibrium – experimentallymeasurable

G˚ = −RT ln Keq
G˚ :• Standard free energy change• Thermodynamic constant characteristic of each reaction
The relationship between G˚ and Keq
When Keq ≫1 (=ln > 0), G˚ is large and negative.
When Keq ≪1 (=ln < 0), G˚ is large and positive.

WaterLiving on Mars – Making cleaning water on Mars…

USA

575

Australia

493

Italy

386

Japan

374
0

https://the-martian.fandom.com/wiki/The_Martian/Film 2019/06/03

200

400

Liter/ person/ day(data360.org)
NASA space mission: 11 L600

Water Is the Medium for Life
• Organisms typically contain 70–90% water.
• Chemical reactions occur in aqueous milieu.
• Water is a critical determinant of the structure and functionof proteins, nucleic acids, and membranes.

1. Hydrogen bond and dielectric force
2. Hydrophobic effect
3. osmotic effect
4. pH

Structure of Water• 4 e- pairs in sp3 orbitals• 2 of 4 pairs covalently link two H2 atoms to a central O atom
• distorted tetrahedron• net dipole moment = hydrogen donor and accepterHydrogen Bonds• Hydrogen bonds are strong dipole-dipole or charge-dipole
interactions that arise between a covalently bound hydrogenand lone pair of electrons.
• They typically involve two electronegative atoms (frequentlynitrogen and oxygen).
• Hydrogen bonds are strongest when the bonded molecules
allow for linear bonding patterns.
• 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 4 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 theH–O covalent bonds (420 kJ/mol).

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 tophysiological problems, it will be found that the significance of the hydrogen bondfor physiology is greater than that of any other single structural feature.”–Linus Pauling, The Nature of the Chemical Bond, 1939

Biological Relevance of Hydrogen Bonds

Hydrogen Bonding by waterIce: Water in a Solid State• Water has many different crystal forms;
the hexagonal ice is the most common.
• Hexagonal ice forms an organizedlattice and thus has a low entropy.
• Hexagonal ice contains maximalhydrogen bonds/ water molecules,
forcing the water molecules into
equidistant arrangement. Thus:• ice has lower density than liquidwater• ice floats

Water as a Solventamino acids, peptides
carbohydrates
small alcohol

GoodPoor

nonpolar gases
aromatic moieties
aliphatic chains

Solubility of Polar and Nonpolar Solutes

Why are nonpolar molecules poorly soluble in water?

Four Major Noncovalent Interactions• Ionic interactions• electrostatic interactions between
permanently charged species, or between
the ion and a permanent dipole• Hydrogen bonds• 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 withthe ordering of water molecules aroundnonpolar substances

Dissolving Salts Involves Breaking Ionic Interactions
Solvation

H: strong electrostatic interactions between the solvated ions and water molecules lower
the total energy of the system•
S: entropy increases as ordered crystal lattice is dissolved•

van der Waals Interactions••••

Two components: attractive force (0.4–0.7 nm) and repulsiveforce (dependent on the size of atom)
Individually weak: easily broken, reversible
Universal: occur between any two atoms that are near eachotherStabilizes biological macromolecules (stacking in DNA)The Hydrophobic Effect• Refers to the association or interaction of nonpolar
molecules or components of molecules in the aqueoussolution• 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

a Protein or DNA(hydrophobic)
H2O

H2OH2O

H2O
H2O

https://pixabay.com/ja/

H2O

Water Surrounding Nonpolar Solutes Has Lower Entropy
High entropy

LowEntropy

Low entropy is thermodynamically unfavorable, thus hydrophobic
solutes have low solubility.

Origin of the Hydrophobic Effect• Consider amphipathic lipids in water.
• Lipid molecules disperse in thesolution; nonpolar tails of lipid
molecules are surrounded by orderedwater molecules.
• Entropy of the system decreases.
• The system is now in an unfavorablestate.

Origin of the Hydrophobic Effect• Nonpolar portions of the amphipathic molecule aggregate so thatfewer water molecules are ordered and entropy increases.
• All nonpolar groups are sequestered from water, and the released
water molecules increase the entropy further.
• Only polar “head groups” are exposed.

Amphiphiles Form Micelles & Bilayers• With high enough concentrationof amphipathic molecules,complete aggregation into
micelles is possible.
• All hydrophobic groups aresequestered from water; orderedshell of H2O molecules isminimized, and entropy is further
increased.

Voet and Voet et al. Principles of Biochemistry 4th edition(2013), International Student Version, Figure 2-11 (p28)Osmotic Pressure• Water moves from areas of high water concentration (low soluteconcentration) to areas of low water concentration (high soluteconcentration).
• Osmotic pressure (π) is the force necessary to resist the movement.
• Dissociated components of a solute individually influence the osmoticpressure.

Voet and Voet et al. Principles of Biochemistry 4th edition, International Student Version, Figure 2-13 (p29)

Effect of Osmotic Pressure on Cells

Nelson and Cox, Lehninger Principles of biochemistry 7th edition, International edition
Figure 2-13 (p56)

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 hasvery low electrical conductivity (resistance: 18 M•cm).
• The equilibrium is strongly to the left (low Keq).
• The extent of dissociation depends on the temperature.

Proton Hydration• Protons do not exist free in solution.
• They are immediately hydrated to form hydronium ions(H3O+).

• A hydronium ion is a water molecule with a proton associated with
one of the nonbonding 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 “protonhopping.”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.
Concentration of H2O [H2O] can be determined from water density,
55.5 M.
Density: 1000 g/L
M.W.: 18.015 g/mol• Ionic product (dissociation constant) of water:K w  K eq  [H 2 O]  [H  ][OH - ]  1 10 14 M 2• In pure water, [H+] = [OH–] = 10–7 M.

pHpH = −log[H+]• pH is defined as the negative
logarithm of the hydrogen ionconcentration.

K w  [ H  ][OH - ]  1 10 14 M 2• The pH and pOH must always addup 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).

calculation of [H+]What is the concentration of H+ in a solution of 0.1 M NaOH?
answer: 10-13 M

calculation of [OH-]
What is the concentration of OH+ in a solution with an H+concentration of 1.3 X 10-4 M?
answer: 7.7 X 10-11 M

Relationship of pH, [H+], and [OH-]pH of Some Common Liquids

Dissociation of Weak Electrolytes: Principle

OH3C+ H2OOHOKeq

H 3C+ H3O+

O-[H  ][CH 3COO - ]Ka 
 1.74 10 5 M
[CH 3COOH]• Weak electrolytes dissociate
only partially in water.
• The extent of dissociation isdetermined by the aciddissociation constant Ka.
• We can calculate the pH if theKa is known. But some algebrais 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?
OKaH3COH 3COH0.1 – x
Ka + H+O-xx[ x ][ x ] 1.74 10 5 M
[0.1 - x]

x 2  1.74 10 6  1.74 10 5 xx 2  1.74 10 5 x  1.74 10 6  0x = 0.001310,• We assume that theonly source of H+ isthe weak acid.
• To find the [H+], aquadratic equationmust be solved.

pH = 2.883 (=-log100.001310)

Dissociation of Weak Electrolytes: Simplification
OKaH3COH3 COH

0.1 – x0.1+ H+O-xxx
x[x][x]Ka 
 1.74 10 5 M
[0.1]

x  1.74 102x = 0.00132,

6pH = 2.880• The equation can be
simplified if the amount ofdissociated species is muchless than the amount of
undissociated acid.
• Approximation works for
sufficiently weak acids andbases.
• Check that x < [total acid].

pKa Measures Acidity
pKa = –log Ka

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 ofthe compound.

•Buffering capacity of acid/anion system is greatest at pH = pKa.

•Buffering capacity is lost when the pH differs from pKa by morethan 1 pH unit.

Weak Acids Have Different pKas

Nelson and Cox, Lehninger Principles of biochemistry 7thedition, International edition
Figure 2-18 (p63)Henderson–Hasselbalch 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]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 cyclicamines.
• HEPES• PIPES• CHESHONNSO3Na

Chapter 2: Summary• nature of intermolecular forces• properties and structure of liquid water• behavior of weak acids and bases in water• way water can participate in biochemical reactions

H.W: What are acidosis and alkalosis?