Lecture 2 Flashcards
“Big picture” items
- Water is a structurally simple molecule with
complicated properties - Water is the cause of the hydrophobic effect
- Water can dissociate into protons and hydroxyl ions
- The proton concentration determines the pH
- The cell controls the pH of its content and compartments
- Biochemists control the pH with buffers
- pH is important in many cellular events
- Cells store energy through a proton gradient across membranes
Covalent bonds
link atoms in molecules together and are
obviously essential
Non-covalent interactions
play also a key role in living organisms.
Examples of processes where non-covalent interactions are
important:
- The dissolution of salt in water
- The three-dimensional structure of proteins
- Base-pairing and base-stacking in the DNA double helix
- The aggregation of lipids into membrane bilayers
- The affinity of sugar molecules for taste receptors
- The binding of a medicine to its target protein
Non-covalent interactions between neutral molecules
- interactions between permanent dipoles ( weak 1/r^3)
- dipole-induced dipole interactions (weaker 1/r^5)
- london dispersion forces (weakest 1/r^6)
Neutral molecules where the center of gravity of the negative charges does not coincide with the center of gravity of the positive charges are said to have a “dipole”.
“van der Waals interactions”
While covalent bonds range typically between 300 and 500 kJ / mol,
non-covalent interactions mentioned above range from 20 (top) to 0.3 (below) kJ / mol.
The non-covalent interactions mentioned above are collectively known as:
water molecule
The water molecule is nonlinear and carries a permanent dipole moment.
“van der Waals envelope”
is the effective “surface of the molecule”. This surface is obtained by making a sphere with a “van der Waals radius” centered on each atom
Two atoms from different molecules rarely come closer together than the sum of their van der Waals
radii – with the very important exception of the “hydrogen bond”.
The O-O distance
~2.74 Å in an H-bond is smaller than the sum of :
(i) the O-H covalent bond distance of ~0.97 Å
+ (ii) the H vdW-radius of ~1.2 Å
+ (iii) the O vdW-radius of ~1.4 Å,
since this sum is: 0.97 + 1.2 + 1.4 = ~ 3.6 Å.
Water molecules interact with other water molecules
As ice, each water molecule interacts tetrahedrally with four
other water molecules
The arrangement of water molecules in
bulk liquid water is very dynamic.
Liquid water consists of a rapid fluctuating, three-dimensional network of
hydrogen-bonded H2O molecules
Water hydrogen bonding to other molecules
Biomolecules are surrounded by bulk water.
All surface-exposed hydrogen-bond donors and acceptors of biomolecules are engaged in hydrogen bonds with surrounding water molecules.
Hydrogen bonds in general
In general:
A hydrogen bond can be represented as D-H….A, where:
D-H = weakly acidic “donor” group, such as O-H, N-H
A = weakly basic “acceptor” atom such as O, N
Ions in solution are solvated by water molecules
The permanent dipoles of water molecules interact very favourably with charged ions
in solution, forming a “hydration shell”.
Several complex enthalpic and entropic factors contribute to ΔG of dissolving a salt.
Many salts, like NaCl, do dissolve very well in water.
(But not all salts! E.g. your kidney stones are made up of insoluble calcium oxalate).
Ions solvated by water molecules
The water dipoles interact favourably with positive and negatively charged ions.
In actual fact:
• There are many more waters in the first hydration shell than depicted, and
additional waters in a second shell.
• The waters in the hydration shells remain very dynamic.
• They change hydrogen bond patterns, orientation and position all the time.
Hydrophobic interactions
Hydrophobic interactions cause non-polar groups to
come together in aqueous solutions.
They are extremely important in biology. They
contribute for instance to:
- Folding of protein molecules into compact conformations
- Binding of small hydrophobic molecules to hydrophobic
clefts on the protein surface - Stacking of bases in the DNA double helix and in RNA
tertiary structures - The formation of the lipid bilayer surrounding cells
Hydrocarbons and water
Thermodynamic Changes for Transferring Hydrocarbons from Water to Nonpolar Solvents (at 18° C)
The ΔG for these processes are negative, hence the process will proceed to the right.
That means that these hydrocarbons do not like to dissolve in water.
NOTICE THAT ΔH IS ZERO (red stars).
THIS MEANS:
NO ENTHALPY DIFFERENCE FOR THIS TRANSFER PROCESS.
THESE ARE ENTROPY-DRIVEN PROCESSES!
The entropy S is smaller (thus, less favorable) for a hydrocarbon in water than
when surrounded by hydrocarbons….
Two amphiphilic hydrocarbons
(Molecules with both polar and nonpolar segments are called “amphiphilic”)
Such molecules are at the same time hydrophilic and hydrophobic.
If the hydrophobic segments are substantial, these segments tend to cluster together.
ex: palmitate, oleate
The hydrophobic effect and amphiphilic molecules
The water molecules next to the hydrophobic alkyl chains are restricted in rotational freedom – although they are still very mobile.
Clustering of amphiphilic molecules
Cluster of lipid
molecules:
Only lipid portions at the edge of the cluster are in contact with water.
In the cluster, fewer water molecules are in contact with the lipid portions than in the
sum of three individual lipids.
Hence, fewer water molecules are restricted in rotational
freedom. Therefore, the entropy of the system is increased by
clustering lipids.
Micelle formation of amphiphilic molecules
All hydrophobic groups are sequestered from water.
Compared to the cluster, even fewer water molecules are in
contact with the lipid portions than in the sum of individual
lipids.
Hence, fewer water molecules are restricted in rotational
freedom. Therefore, the entropy of the system is further
increased.
The principles for forming lipid bilayers by amphiphilic molecules are the same.
Amphiphilic hydrocarbons aggregate in water
Which type of aggregate actually forms is dependent on: • the properties and shape of the amphiphile, • pH, • temperature, • concentration of ions, • and other factors.
Chemical properties of water
The neutral water molecule has a very slight tendency to ionize:
H2O = H+ + OH-
In actual fact, the H+ ion does not exist in bulk water but is associated with a
water molecule to form a H3O+ hydronium ion.
The H+ ion is also called the “hydrogen ion” and is, of course, simply a proton.
Ionization of water
- The H-bonding within water facilitates its ionization.
- In 1 liter of pure water (55.5 moles) there are at any time:
1x10-7 moles of H3O+ and an equal amount of OH- - We often use the symbol H+ instead of H3O+
Since the concentration of bulk water is 55.5 M water, and is not changing much upon ionization:
55.5 × Keq = [H+][OH-
] = [10-7][10-7] = Kw = 1×10-14
Kw is called the “ion product of water”.
Ionization of water
Note: These numbers (that is, 55.5, 10-7 and 10-14) are
important to remember.
pH scale
When dealing with numbers that can be very large and very small, it is convenient to use logarithms.
For the hydrogen ion concentration, the scale was defined as the “pH” scale by Søren Sørenson in 1909:
So, in pure water:
[H+] = 10-7, hence the pH = -log[H+] = 7
pH scale
The pH of the solutions inside and outside the cell is critical for living organisms.
Acids and bases
An acid is a substance that can donate a proton
A base is a substance that can accept a proton
Many acids and bases are only partially deprotonated or protonated in aqueous solutions.
Those acids and bases are called “weak” acids and bases.
In living organisms numerous such acids and bases occur.
[Base] = [Acid]
pH = pKa
Buffering and buffers
Even small pH-changes in biological systems are important!
• The stability and structure of proteins can be altered dramatically by sometimes relatively small changes in pH.
- The DNA double helix separates into individual strands due to deprotonation of the guanine base at higher pH values. At pH 9.0, half the double helix is separated into single strands.
- The activity of enzymes can differ by one or more orders of magnitude when the pH changes by two units.
• The oxygen-binding capacity of hemoglobin is dependent on pH. This is used to enhance the efficiency of transporting oxygen from the lungs to muscles.
• Influenza virus can only infect humans because the virus senses a pH difference of about 1-2 pH units in a particular organelle which is ready to
destroy the virus.
Proton power
Protons are used in biology for a wide range of processes.
For instance, protons can be used to:
• Induce a large conformational change of a protein.
• Store energy – as a proton concentration difference across a membrane
Influenza virus
Influenza Virus has two main surface proteins:
haemagglutinin (H) and neuraminidase (N).
Influenza virus infection depends on pH
• The pH of fluids surrounding cells, and of the cytosol inside
the cell, is around 7.
• However, in the organelles called endosomes, the pH is
lower.
• This pH difference is exploited by the influenza virus. It enters
cells via “endosomes” which have a pH of about 6.
• In this organelle with lower pH, the influenza virus cell surface
protein “haemagglutinin”
undergoes a spectacular
conformational change, enabling the flu virus to infect a cell
Energy is stored as a proton gradient across a membrane
KEY point: protons cannot cross a lipid membrane
Low Proton concentration in the cytoplasm
High Proton concentration in
the periplasm
cytplasm= inside cell
periplasm= the space between the two membranes of many bacterial cells
ATPase:
A very BIG multi-protein complex inserted into the membrane across which a proton gradient has been created.
α, β, γ, δ, ε, a,
b2 and c are all different ATPase “subunits”
Energy is stored as a proton gradient across a membrane
Driven by the proton gradient across the membrane, part of the enzyme rotates and while doing so generates ATP:
ADP + Pi ➔ ATP
