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(lecture 1 part of lecture 3):

This course will provide you with an overview of cell and molecular biology and will
demonstrate the biochemical unity across all organisms.

Necessarily, that means a lot of chemistry, and I will point out along the way some
differences in emphasis between chemists and biologists.

There are many different elements on earth, such as iron, carbon, oxygen; all
elements are made up of atoms. The two most common elements in biology are
hydrogen and carbon. Everything revolves around carbon chemistry in biology.

Atoms are made up of the nucleus at the center and surrounding electrons. The
nucleus has positively charged protons and neutral neutrons. Electrons are
negatively charged. Note that there is always the same number of protons and
electrons in an individual atom of an element, so the charges are balanced. For
example: 6 protons plus 6 electrons for carbon. Also note that electrons are
arranged in shells around the nucleus, H has one shell, carbon has two shells.
Electrons in different shells are at different distances from the nucleus.

All the elements are listed in the periodic table by their number of protons, because
that is what gives each element its identity. It is called the atomic number and is
always listed next to the abbreviation of the element. Another very important
number is given for each element, the mass number. This is simply the number of
protons plus neutrons. This is a convention, we could also give the mass in grams,
but that would be unwieldy, because it would be such a tiny number. The unit for
atomic mass is Dalton (Da or D).

Something else you might notice in a more advanced textbook, is that the mass
numbers are rarely whole numbers, e.g. for carbon it is 12.03. This is because many
elements have different isotopes. Two isotopes have the same number of protons,
but a different number of neutrons, e.g. 14C has two more neutrons than the
standard 12C. Isotopes have the same chemical properties, but isotopes with more
neutrons are often unstable (radioactive), and because of that have important uses
in medicine and biology.

Now we look at chemical bond formation. Whenever you link together atoms, only
electrons are important. The most important chemical bond is the covalent bond.
Atoms linked together by covalent bonds are called molecules. To understand
covalent bond formation its important to distinguish electron localization in shells
and orbitals. Shells are made up of orbitals, and orbitals comprise two electrons, a
pair of electrons. Bonds are stable, when shells and orbitals are filled with electrons.
Because the inner shells are always filled, they can be ignored. The periodic table is
made up of rows and columns. Elements in the same row have all their electrons in
the same shell, therefore they have a similar size. Elements in the same column have

the same number of electrons in their outermost shell, and therefore similar
chemical properties.

Lets start with the simplest molecule, H2, and look at its covalent bond formation.
Electrons like to be in pairs, they are really unhappy when there is only one electron
in an orbital, actually youll never find a single hydrogen atom. Instead, they form a
new orbital by sharing electrons from two hydrogen atoms, and that is the covalent
bond in H-H. This is stable, because its full.

We can say: a covalent bond is made of 2 electrons; these 2 electrons are shared,
that is, one electron comes from each atom; atoms can form bonds until their
outermost shell is filled.

Lets look at some other covalent bonds. For example carbon, its the sixth element,
therefore 6 protons, and 6 electrons: 2 are in the first shell, which we can ignore, the
other 4 are lonely, because 8 electrons can fit into the second shell. Therefore
carbon can form 4 covalent bonds (has a valence of 4). Draw methane: each line
represents two electrons, one covalent bond. Then nitrogen and oxygen, also
include double and triple bonds. Only rare gases cannot form any bonds, because
their shells are already completely filled.

The shape of a molecule is determined by the shape of the orbitals that make up the
covalent bonds, e.g. methane looks like a tetrahedron.

There are different ways to depict structures, all useful, but the most important one
is the structural formula, where each line represents two electrons and therefore
one covalent bond.

In H-H, electrons are equally distributed, we call this a nonpolar covalent bond

This is not true in water: there electrons spend most of their time close to oxygen,
because oxygen is more electronegative. What does that mean?

Electronegativity is a measure of how strongly electrons are attracted to the
nucleus. C-H bond is regarded as nonpolar (even though C has 5 more protons than
H, Hs electronegativity is very similar, because its one electron is in the first shell,
much closer to the nucleus than Cs electrons in the second shell). In the second
shell, all electrons have the same distance from the nucleus, therefore elements with
more protons are more electronegative (O more electronegative than C); therefore
the polar bond is particularly strong in O-H and C-O.

This has many very important consequences: H-O-H can become OH- and H+, NH3
can become NH4+ (acids and bases)

The biggest consequence of polar covalent bonds is the hydrogen bond, the
electrostatic attraction between the partial positive and negative charges of two
water molecules.

Properties of water: Cohesion explaining how water can rise in trees; meniscus and
surface tension; liquid water is denser than ice allowing survival of larger organisms
in lakes; water moderates temperature, because hydrogen bond formation or
disruption buffers heat energy.

So far we talked about covalent bonds, which can be non-polar or polar, depending
on how strongly one atom attracts the electrons from the other. In extreme cases, an
atom can entirely lose or gain an electron, thereby becoming an ion. The
electrostatic attraction between ions results in the ionic bond, as in table salt (NaCl).

If you check the periodic table, salts form between elements at the edges of the
periodic table (large differences in electronegativity), especially between chlorine
on one side, and sodium (NaCl), or magnesium (MgCl2) on the other side.

A last property of water is that it facilitates chemical reactions, because it is such a
good solvent. All polar molecules and ions dissolve easily in water; they are called
hydrophilic; nonpolar molecules do not dissolve in water and are called

The hydrophobic interaction describes nonpolar molecules being forced together in
water, because being together minimizes the disruption of hydrogen bonding in the
surrounding water. Can be observed in Salad dressing thats left standing or in a
chicken soup that you let cool down (bigger and bigger oil bubbles will form; this
also illustrates the strength of the force; a little heat disrupts it).

An even weaker force that also participates in the hydrophobic interaction is the van
der Waals force, describing the attraction of nonpolar molecules to each other
because of transient dipoles (caused by the random localization of electrons in
different areas of their orbitals). Occurs between all molecules, but is only relevant
for nonpolar molecules.

Hydrogen bond, ionic bond, hydrophobic interaction, and van der Waals interaction
are all based on electrostatic attraction (attraction of opposite charges); ionic bonds
relevant in biological settings are those within proteins and are relatively weak;
ionic bonds in salt crystals are much stronger, similar to the covalent bond or even

Covalent bonds in molecules form in chemical reactions, which is written as an
equation, where the number of atoms on both sides of the equation must be equal.

For practical purposes we measure the amount of substances in moles, one mole is
the same number of molecules for any substance. You need to count molecules, it

doesnt help to add 1 gram of propane to 5 g of oxygen; instead you have to add one
molecule of propane to 5 molecules of oxygen gas (or rather multiples thereof!!). To
get one mole of a substance, just add up the atomic masses of all the atoms in a
molecule, for example for C3H8 = 3 x 12 plus 8 x 1 = 44 grams, for O2
= 2 x 16 = 32 g. Therefore to set up the burning of propane, youd have to mix 44 g of
propane with 5 x 32 = 160 g of oxygen gas.
All chemical reactions in biology occur in watery solutions, therefore one uses the
concept of molarity: a 1 molar (1 M) solution is one mole of a molecule dissolved in
water to make one liter. To make such a solution, calculate molecular mass in grams,
dissolve in less than 1 L of water; then fill to make exactly 1 L.

The concentration of acids and bases is also measured in moles/L. Acids and Bases
are so important because most biologically important compounds are acids and
bases, e.g. nucleic acids, amino acids, phospholipids, many metabolic compounds.
Acids release/donate H+ ions (protons) in solution. Weak acids like the carboxyl
group are most important in biology. They dissociate partially and reversibly.
Oxygen is more electronegative, therefore grabs electron pair and releases H+

Bases accept H+ (protons) in solution, and therefore release OH-. The amino group is
a weak base and the most important in biology. It partially and reversibly accepts
protons. N is less electronegative, therefore its free electron pair can accept H+.

In summary, both acids and bases can be characterized by the amount of protons in
solution. As for any other substance, the amount of protons in water is given in
moles/L. Tap water has a proton concentration of 10-7 M. Because this number is
very small, by convention, it was decided to use the negative logarithm of this
number, 7, which is called the pH.

What exactly does partial and reversible mean?
Lets look at the weak acid acetic acid: If you make a 0.5 M acetic acid solution in
water, acetic acid is only very partially dissociated (mostly undissociated), and has a
pH of about 2.5 (the point on the y-axis of the titration curve). That acetic acid is
largely undissociated at this point can be shown with a titration curve. In a titration
curve, you measure the pH after adding increasing amounts of NaOH (equivalent to
removing protons from the solution). You would expect the pH to rise quickly and
dramatically. However, this is not the case. Instead, the pH rises very slowly,
because there is a big reservoir of undissociated acetic acid, which keeps releasing
protons. Likewise, adding acid at pH6 would reverse this process and slowly lower
the pH, because added protons would reform undissociated acetic acid and are
thereby removed. That is the reason why dissociated acetic acid (acetate) is also
called the conjugate base, because it can accept protons.
So weak acids act as buffers, because over a certain range the pH does not change
much, even though you add a lot of base. As can be seen from the titration curve, a
weak acid on its own can only buffer added base. If you want to make a buffer that
buffers in both directions, you have to add equal amounts of weak acid and its
conjugate base to reach the half-equivalence point of the titration curve.

Buffers are very important in biology, because it is important for the function of
many molecules that the pH is constant. Thats why our blood and intracellular
fluids are buffered.

What else can you read off from a titration curve? The protonation state, e.g. at pH7,
the COOH group discussed here will largely be COO-