Table of Contents
Fundamentals of Biochemistry
Biochem 380 - Fall 2006
Lecture 005
Outline
- Announcements
- Questions about previous lecture
- Section 2.4: Nonpolar Substances in Water
- Section 2.5: Noncovalent Interactions
- Section 2.6: Water is Nucleophilic
- Section 2.7: Ionization of Water
Announcements
- Lecture 4 notes are online
- Quiz scores and answer key will be posted later today
- Reminder: assigned homework problems for Chapter 2:
Questions
- Any questions on the material from the previous lecture?
Section 2.4: Nonpolar Substances in Water
- We have seen how water provides the environment for living cells. However, one of the four classes of
biomolecules, lipids, have nonpolar hydrocarbon chains that are largely insoluble in water
- Nonpolar molecules are hydrophobic (water-avoiding). This produces familiar macroscopic behaviors
such as the segregation of oil from water.
- But most lipid biomolecules are not completely hydrophobic. They usually have a hydrophilic
portion that allows them to interact with water and polar molecules to some degree.
Amphipathic Molecules
- Molecules that have both hydrophobic and hydrophilic regions are amphipathic
- An example of an amphipathic molecule is the synthetic detergent sodium dodecyl sulfate (SDS):
- SDS has a 12-carbon hydrophobic tail and a polar sulfate group. Detergents such as SDS associate
with water through the polar regions and trap oil and grease through interactions with their hydrophobic tails
- SDS is also used in an analytical technique (SDS-PAGE) to separate proteins by mass.
The SDS molecules bind to hydrophobic side chains to give the protein a cumulative negative charge. This is
discussed in more detail in Section 3.7
Molecules with Long Nonpolar Groups are Mostly Insoluble
- If the hydrophobic portion of amphipathic molecule is fairly small, it can still dissolve in water.
As shown in Table 2.1, one-, two- and three-carbon alcohols remain very soluble in water
- However, with increasing size of the hydrocarbon groups, the solubility rapidly diminishes
Monolayers and Micelles
- When large numbers of amphipathic molecules such as SDS interact with water, they can form macroscopic
structures such as monolayers and micelles:
- A monolayer results from the detergent molecules spreading out over the surface of water, with their
polar regions in contact with the surface and their hydrophobic tails sticking up above
- A micelle is a spherical structure surrounded by water, formed by an aggregate of molecules
with all of their hydrophobic tails pointing inward
Section 2.5: Noncovalent Interactions
- With even just a handful of atoms, the potential variety and subtlety of interactions is extraordinary.
The 'ball and stick' view of atoms and molecules is a gross simplification
- The actual electronic structure consists of a set of molecular orbitals that satisfy the Schroedinger equation.
More realistic modeling of atomic interactions requires large and complex calculations using Quantum Mechanics
(QM) theory
- Simpler models are useful in chemistry and biochemistry, but it's important to be aware of
their limitations
- In addition to covalent bonding, there are a number of noncovalent interactions between atoms.
Although these interactions are much weaker than covalent forces, the weak interactions between many atoms
add up and have a significant effect on the structure and activity of biomolecules.
Types of Noncovalent Interactions
- There are 4 types of noncovalent interactions that we will discuss:
- Charge-Charge Interactions
- Hydrogen Bonds
- Van der Waals Forces
- Hydrophobic Interactions
Charge-Charge Interactions
- Charge-Charge interactions are electrostatic interactions between two charged particles. The potential
energy of these interactions is determined by Coulomb's Law:
- The energy E is proportional to the product of the charges q1 and q2
and inversely proportional to the distance between them (r) and the Dielectric constant (D).
- The dielectric constant represents the reduction of energy caused by the local environment,
relative to a vacuum. For biomolecules, the local environment is water, and its dielectric constant
is relatively high (~80), compared to many other mediums
- Charge-charge interactions are among the stronger of the noncovalent forces when they are not
weakened by water. One example is a salt bridge than can form between oppositely-charged groups
in the hydrophobic interior of proteins
Hydrogen Bonds
- Hydrogen bonds are another kind of electrostatic interaction that we have already seen in section
2.2. Because the bond involves partial sharing of electrons from the acceptor atom, it has
some aspects of a covalent bond, but is much weaker
- Hydrogen bonds in biomolecules are very important for determining structure, even though they are
weaker than those between water molecules. In later chapters, we'll see how hydrogen bonds help to determine
the secondary structure of proteins and nucleic acids.
- Under certain conditions, the intramolecular hydrogen bonds in biomolecules can be broken in
favor of hydrogen bonds formed with water molecules. This can greatly alter the original structure of
a molecule such as a protein, causing it to be denatured
Van der Waals Forces
- Van der Waals forces describe short range forces that are significant only when atoms are
close together. There are two types of van der Waals forces: attractive forces and repulsive ones.
- The attractive forces, also called London dispersion forces, result from induced dipoles
that form between the electron clouds of opposing atoms. They are very weak, around 0.4 kJ/mol at 3 A.
- The repulsive forces result from interpenetration of the core electron shells of the atoms, which
violates the exclusion rule of only two electrons per orbital. These forces become huge at close distance and
essentially define the spatial boundaries of atoms
- Although weak individually, multiple van der Waals interactions between complementary surfaces of
biomolecules add up to produce a large influence on molecular structure
Hydrophobic Interactions
- Hydrophobic interactions cause non-polar molecules to be excluded from water.
Unlike electrostatic interactions, they are not produced by explicit forces. Instead, thermal
movements produce more stable arrangements of polar and nonpolar aggregates.
- This is promoted by a total increase in entropy, where ordering of water molecules around
individual nonpolar molecules is reduced by aggregation of nonpolar molecules,
reducing their total surface area:
- Micelles are one example of this. The burying of non-polar groups of proteins within their interior
is another.
Summary of Noncovalent Interaction Energies
Section 2.6: Water is Nucleophilic
- Another important property of water is its chemical reactivity as a nucleophile. A nucleophile
is an electron-rich molecule that is attracted to positively-charged or electron-deficient species,
which correspondingly are called electrophiles
- An example of the nucleophilic properties of water is the attack on the carbonyl carbon in a peptide
bond:
- The equilibrium of the reaction is strongly to the right, indicating the natural tendency for proteins
to be hydrolyzed by water
- This potentially could be a problem for the stability of biomolecules in the aqueous environment of cells.
Fortunately, the rate of the hydrolysis reaction is very slow in the absence of a catalyst
Section 2.7: Ionization of Water
- Under normal conditions, a small portion of water molecules are ionized
- This results from a reaction between two water molecules in which one gains a proton to become
a positively-charged hydronium ion, and the other loses a proton to become a
negatively-charged hydroxide ion:
- The mechanism for the reaction is shown below:
- Here we see another example of a nucleophilic attack of a water oxygen, this time on the hydrogen of
another other water molecule
Equilibrium of Water Ionization
- The equilibrium constant for water ionization under standard conditions is 1.8 x 10-16M:
- Since there are 55 moles of water in 1 liter, this results in a convenient value of 1 x 10-14
for the product of the hydronium and hydroxide concentrations:
- This constant, Kw, is called the ion product for water. This means that for pure
water, there are equal concentrations of [H+] and [OH-], each with a value of
1 x 10-7M. This is the basis for the pH scale.
Questions
References
Next Lecture: Sections 2.8 - 2.10