Lectures 2 & 3: An introduction to the molecules of life
1. The molecules of life comprise macromolecules and small molecules
2. Understanding the molecules of life: chemical structures and bonding
a. Connectivity versus conformation
b. The nature of atoms
c. Covalent bonding and formal charges
d. Ionic bonding
e. Electronegativity and hydrogen bonds
f.
The bonding continuum and bond polarity
3. Organic molecules and how to draw them
a. The molecules of life are organic molecules
b. The geometries of organic molecules
c. Drawing organic molecules
d. Understanding “arrow-pushing” notation
4. Stereochemistry and the molecules of life
a. Stereoisomers and enantiomers
b. Drawing stereoisomers
c. The tragedy of thalidomide
d. Geometric isomers
e. The role of geometric isomers in vision
5. The molecular components of HIV
Professor David Liu and Brian Tse, Life Sciences 1a
page 23
The Richness of Organic Structures
HO
H H
H
OH
O
O
=
HO
C
C
H C
H
O
OH
Ribose
C5O5H10
One bonding
scheme out of
> 200 isomers
of C5O5H10
O H
O
C
H
H
C
O
H
H
Three other examples of isomers of C5O5H10:
H
O
H C
O
H
C H
H C
C O
C
H O
H H
H O
H
O
H C C C C C H
H
H
O H H O
H
H
O H
O
H
H
O
H
O
H O H
H
C
C
C
C
H
O H H O
C
H
H
• The number, geometries, and stability of bonds made to carbon atoms impart
enormous structural diversity into organic molecules
2. Organic molecules and how to draw them
The molecules of life are organic molecules
In general, the molecules of life contain a carbon backbone. Molecules containing carbon
are aptly named organic molecules, and their study is the subject— frequently feared by
undergraduates— called organic chemistry. Carbon’s ability to form four covalent bonds
enables carbon skeletons to adopt an enormous diversity of three-dimensional shapes, sizes,
and flexibilities. Consider ribose, the simple sugar that is found in the backbone of RNA.
Even though ribose contains only five carbon atoms, five oxygen atoms, and ten hydrogen
atoms, it is only one of more than 200 different ways to connect these atoms in a way that
satisfies our bonding principles! The different structures that can be assembled from the
same chemical formula (in the case of ribose, C5O5H10) are called isomers.
Professor David Liu and Brian Tse, Life Sciences 1a
page 24
Geometries of Organic Molecules
Tetrahedral
Methane
Trigonal (planar)
Ethylene
Linear
Acetylene
• A carbon atom adopts a geometry determined by its number of bonding partners
(4 = tetrahedral, 3= trigonal, 2 = linear), as dictated by e–/e– repulsion
The geometries of organic molecules
Within organic molecules, each carbon atom and its bonding electrons generally assume
one of three types of geometries: tetrahedral, trigonal, or linear. These geometries can all be
predicted by appreciating that the negatively charged electrons within covalent bonds repel
each other, and therefore distribute themselves around their shared carbon atom to maximize
their mutual separation. A carbon atom that makes four single covalent bonds to four other
atoms such as the carbon in methane (CH4) lies in the center of a tetrahedron, a four-sided
solid with each face consisting of an equilateral triangle. This tetrahedral geometry maximizes
the average distance between electrons in the four bonds. In a perfectly symmetric
tetrahedron, the angle between any two bonds made to the same carbon atom is 109 degrees.
Likewise, carbon atoms that make one double bond and two single bonds to a total of three
other atoms adopt a trigonal geometry in which the angle between any two bonds is roughly
120°, maximally spreading the arrangement of the single and double bonds. As a result,
carbon atoms that make bonds to three other atoms occupy the same plane as those other
atoms. For example, both of the carbon atoms in ethylene (H2C=CH2) adopt trigonal
geometries. You may notice that not only do the three bonding partners of each carbon atom
lie in the same plane, but that all six atoms in ethylene are coplanar. Ethylene demonstrates
an important additional feature of trigonal carbon atoms: when two trigonal carbon atoms are
connected by a double bond, all six of the atoms connected to both carbons lie in the same
plane. As we described earlier, this required six-atom coplanarity arises from the shape of the
electron clouds that form a double bond. In order for the double bond to form, the angle
between the two trigonal planes must be close to zero. We will return to the biological
implications of this requirement shortly.
Professor David Liu and Brian Tse, Life Sciences 1a
page 25
Non-Carbon Atoms Adopt
Analogous Bonding Geometries
N
C
H
Linear
Hydrogen
Cyanide
Trigonal
planar
O
H3 C
C
CH3
Acetone
• The geometries of non-carbon atoms can be deduced by treating non-bonded
electron pairs as “bonds” that are subject to e–/e– repulsion
Finally, carbon atoms that make one triple bond and a single bond adopt a linear geometry.
For example, in acetylene the angle between the two H-C bonds is 180 degrees, maximizing
the separation of the electrons in each bond.
The tetrahedral, trigonal, and linear geometries of carbon also apply to other types of
atoms. Nitrogen and oxygen atoms within molecules assume geometries similar to those of
carbon if you consider their non-bonded electron pairs to be single covalent bonds. For
example, the triply bonded nitrogen atom of HCN adopts a linear geometry, while the doubly
bonded oxygen atom of H3C-CO-CH3 (acetone) adopts a trigonal geometry.
Professor David Liu and Brian Tse, Life Sciences 1a
page 26
Ribose Depicted Six Ways
Computer-created models:
Representations that can be drawn by hand:
H
H
O C
H
C
O H
O
C
H
H
H C C H
O O
H
H
HO
CH2
OH
O
CH
CH
CH CH
HO
OH
O
HO
HO
OH
OH
Standard drawing
• What do these lines mean?
Drawing organic molecules
Scientists depict organic molecules in several different ways. The widespread availability of
powerful computers makes accurate, three-dimensional models of organic molecules very
accessible to research scientists and students alike. You will have the opportunity to create
and explore models of organic structures on computers in an upcoming LS1a laboratory unit.
Among the three computer-generated models of ribose shown above, the first is the simplest
and conveys the basic bonded structure of ribose with the most clarity. The second computergenerated model is similar to the first but shows an approximate boundary of electron density
around each atom. The third model depicts each atom’s electron density as a colored solid.
This last model is known as a space-filling model and although it provides an excellent sense of
the volume occupied by a molecule’s electrons, its opacity can hide important structural
features of a molecule.
In many cases, a computer-generated model is not convenient or necessary. Without the
assistance of a computer, ribose can be drawn by hand in several different ways, also shown
above. While the first drawing of ribose is the most complete because every bond and atom is
drawn explicitly, it is rarely used because its clutter obscures the essential features of ribose
and it is too laborious to draw. The second drawing is less cluttered and still names each atom
but requires that you imagine the bonds between atoms within common groups such as
–CH2–.
Professor David Liu and Brian Tse, Life Sciences 1a
page 27
Standard Drawing Convention for
Organic Molecules
• Lines are covalent bonds
• Intersections and termini of lines represent carbon atoms
• Each carbon atom is bonded to enough implied hydrogen atoms to
satisfy the octet rule (four bonds total to each neutral carbon atom)
• All non-C, non-H atoms must be shown explicitly (P, O, N, Cl, etc.)
H
C C
C H
H
C
C
C C
C C
C
C N
H
H
C
H
H
H
O
C
C
C
C
C
O
C
H
O
O
H
HO
H
H
C
H
H
H
H C
C
C
C
C
C
O
H
H
H H H
H
H
C
H
N
H
The third drawing is the easiest to create, the least cluttered, and the best at conveying the
basic shape of an organic molecule (indeed, it most closely resembles the first two computergenerated models of ribose). It is also the way in which organic chemists most frequently depict
molecular structures. To fully deduce the structure of molecules drawn using this third
convention requires understanding that (i) lines represent covalent bonds; (ii) carbon atoms lie
at the intersection and termini of all lines, and (iii) all carbon atoms are bonded to enough
implied hydrogen atoms to complete their four-bond requirement. Therefore, the end of a line
signifies a –CH3 group, two lines meeting at an common point signifies a –CH2– group, and three
lines meeting at a common point signifies a carbon connected to one hydrogen and three other
atoms. All atoms other than C or H must be labeled with their periodic table symbols. This
drawing convention can also be used to depict carbon atoms involved in double bonds and triple
bonds. Make sure you can interpret and draw standard organic structures such as the examples
shown here, as this skill will prove useful throughout your studies in the molecular sciences.
Professor David Liu and Brian Tse, Life Sciences 1a
page 28
Common Groups Found in Organic
Molecules
O
CH3
Me
methyl
O
OH
hydroxyl
O
N
H
amide
NH2
amino
carbonyl
O
OH
carboxylic acid
NH3
ammonium
O
carboxylate
O
O
O P
O
phosphate
Organic chemistry is full of nomenclature, or naming systems for molecules. The
nomenclature needed to unambiguously name the rich diversity of organic molecules is so
complex that it is easy to spend much more effort learning nomenclature than is really
necessary to appreciate and understand organic molecules. Those of you who will take
organic chemistry courses in the future will become acquainted with nomenclature; for now, a
very small, but useful, subset of names for groups of atoms commonly found within organic
molecules is shown above. We will refer to these simple groups during the rest of this course
and therefore you should become familiar with their names.
Professor David Liu and Brian Tse, Life Sciences 1a
page 29
Representations of 3-D Structures On Paper
CH3
H2C
HC
O
O
HN
C
C
C
HC
CH
C
H2
S O
C
H2C
N
O
N
CH2
H3C
C
H2
C
O
CH3
C N
O
N
C C
N
H2C CH
2
N
HN
N
N
CH3
N
N
S O
O
Sildenafil (Viagra)
• Multiple perspectives are
required to fully
appreciate the structures
of three-dimensional
molecules in twodimensional depictions
(stay tuned for lab)
Even with properly drawn structures, it can be challenging to accurately envision threedimensional structures using two-dimensional representations. For example, in the 2-D
representation of Viagra’s structure (above), it is not apparent if the four rings of atoms in the
structure are all coplanar, or if they exist in different planes to form a more complex shape.
Only when the structure is viewed from multiple perspectives is the non-planar, complex shape
of Viagra apparent. In the laboratory for this course, you will have the opportunity to explore
three-dimensional models of complex small molecules and macromolecules using computers.
You are also encouraged to build plastic models of molecules using model sets to increase your
familiarity with organic structures.
Professor David Liu and Brian Tse, Life Sciences 1a
page 30
Understanding “Arrow-Pushing” Notation
• Reaction mechanism: a description of the individual steps by which bonds
are broken and made during a reaction
• “Arrow pushing” is a formalism for drawing reaction mechanisms
Simple Rules to Understand Arrow Pushing
1) One arrow represents the movement of one PAIR of valence electrons
2) The arrow begins where the electrons start (electron-rich atoms or bonds),
and ends where they are going (electron-poor atoms or bonds)
3) An arrow that starts at an atom represents moving a lone pair
4) An arrow that starts at the center of a bond represents breaking that bond
5) An arrow that ends at an atom represents forming a new covalent bond or
a new lone pair
6) An arrow that ends at a bond represents adding a second (or third) bond
The molecules of life are not inert. Most life processes require the chemical
transformation of organic starting molecules into new products. The simple knowledge of the
starting materials and products of a chemical reaction is often insufficient to achieve a deep
understanding of the process. Instead, scientists strive to elucidate the mechanism of a
reaction, which refers to the individual steps by which bonds are broken and made during a
transformation. Knowledge of a reaction’s mechanism is crucial to understanding how a
process works and how scientists can intervene in the process to facilitate or shut down a given
reaction. As we will see later in the course, for reactions that take place within an HIV-infected
cell, knowledge of reaction mechanism enables scientists to develop specific drugs to interfere
with reactions required for HIV replication.
Scientists normally depict reaction mechanisms using a notation called “arrow pushing”
(also known as “curved arrow formalism”). Although you will learn how to write your own
arrow-pushing mechanisms when you take organic chemistry, it is useful for this course for you
to learn how to interpret a given arrow-pushing mechanism.
There are really only two essential rules underlying arrow pushing. First, one arrow
represents the movement of one pair of valence electrons. Second, each arrow begins where
the electrons start, and ends where the electrons are going during a given mechanistic step.
The electrons that are most likely to move in a mechanistic step are those associated with
electron-rich atoms or bonds. As you may have guessed, typically these electrons end up
associated with electron-poor atoms or bonds.
Professor David Liu and Brian Tse, Life Sciences 1a
page 31
Arrow-Pushing Examples
• Arrows move in a way that preserves bonding rules (e.g., 4 bonds to neutral C)
Deprotonation of a carboxylic acid by an amine
O
H
H
H
N
H
O
C
O
H
H
CH3
N
H
H
O
C
CH3
Hydrolysis of an amide
O
O
O
H3C
C
O
N
H
H
H3C
CH3
O
C
H
H
O
N
H
CH3
H
H
H O
H3C
H
C
N
H
O
H
CH3
O
H
Note: lone pair electrons not involved in a mechanistic step are often
not drawn but are shown here for clarity.
As a result of these two rules, arrows that start or end at atoms versus bonds refer to
different pairs of electrons; it is therefore crucial that these arrows are drawn precisely. When
an arrow starts at an atom it represents the movement of a lone pair of electrons on that atom
(for example, the blue arrow in the top example above). When an arrow starts in the center of
a bond, in contrast, it represents the two electrons that make up the covalent bond.
Movement of these electrons of course results in the breaking of that bond (for example, the
red arrow in the top example).
The fate of these electron pairs set in motion is revealed by where an arrow ends.
Terminating an arrow at an atom refers to the formation of a new covalent bond with that
atom (for example, the blue arrows in both examples above). When an arrow starts at a bond
connected to an atom and ends at the same atom, however, the meaning is that an electron
pair is moving from a covalent bond to become a new lone pair associated with that atom (for
example, the first red arrow in both examples).
In contrast, ending an arrow at an existing bond signifies that an additional covalent bond
is forming between the two atoms connected by the existing bond. If the existing bond is a
single bond, the result is the formation of a double bond. For example, the second red arrow
in the bottom example shows a lone pair on a negatively charged oxygen atom forming a
second covalent bond between that oxygen atom and a connected carbon atom. A carbonyl
group (C=O) results.
Carefully study every detail of the examples above until the movement of electrons and
the changes in bonding are clear to you. You should also understand why each of the charges
shown above agrees with our understanding of formal charges.
Professor David Liu and Brian Tse, Life Sciences 1a
page 32
Lectures 2 & 3: An introduction to the molecules of life
1. The molecules of life comprise macromolecules and small molecules
2. Understanding the molecules of life: chemical structures and bonding
a. Connectivity versus conformation
b. The nature of atoms
c. Covalent bonding and formal charges
d. Ionic bonding
e. Electronegativity and hydrogen bonds
f.
The bonding continuum and bond polarity
3. Organic molecules and how to draw them
a. The molecules of life are organic molecules
b. The geometries of organic molecules
c. Drawing organic molecules
d. Understanding “arrow-pushing” notation
4. Stereochemistry and the molecules of life
a. Stereoisomers and enantiomers
b. Drawing stereoisomers
c. The tragedy of thalidomide
d. Geometric isomers
e. The role of geometric isomers in vision
5. The molecular components of HIV
Professor David Liu and Brian Tse, Life Sciences 1a
page 33
Stereochemistry and Its Depiction
• Isomers: non-identical molecules with the same chemical formula (e.g., C5O5H10)
• Stereoisomers: isomers with identical atomic connectivities
• Enantiomers: two stereoisomers that are mirror images (enantios = opposite)
CH3
HO
NH2
O
Alanine
(a protein building block)
below
the page
CH3
CH3
HO
NH2
Enantiomers
O
L-Alanine
HO
above
the page
NH2
O
D-Alanine
1. Stereochemistry and the molecules of life
Stereoisomers and enantiomers
Some isomers at first glance appear to be identical molecules, but in reality are not. For
example, shown here are two different isomers of a protein building block called “alanine”. If
you examine these two isomers, called L-alanine and D-alanine, you will see that the atom-toatom connectivities of the two isomers are identical. The molecules themselves, however, are
not identical— they are mirror images of each other and cannot be superimposed. Two
molecules that share identical atomic connectivities but are nevertheless not identical are
called stereoisomers. Stereoisomers that are mirror images of each other are called
enantiomers (from enantios, Greek for “opposite”). Enantiomers share the same relationship
as the left and right members of a pair of gloves. Because mirror images of alanine are not
superimposable, alanine is classified as a chiral molecule (from cheira, the Greek word for
“hand”). Molecules that are not chiral are achiral.
Given that stereoisomers share a common atomic connectivity, special conventions are
needed to draw them in a way that unambiguously identifies their stereochemical
configuration, or stereochemistry. In addition to simple lines and atom labels, two new kinds
of lines are used to distinguish different stereoisomers. When drawing chemical structures,
scientists use a thick line (sometimes drawn as a solid wedge-shaped line) to indicate a bond
that extends above the plane of the paper. Likewise, a dashed line (sometimes drawn as a
dashed wedge) indicates a bond that extends below the plane of the paper. By adding a third
dimension of depth to the standard organic molecule drawings you have studied earlier, this
convention can specify the stereochemistry of any molecule.
Professor David Liu and Brian Tse, Life Sciences 1a
page 34
Enantiomers of Alanine
Mirror
(Enantiomers)
L-Alanine
Rotate 180°
(Same molecule)
Rotate 180°
(Same molecule)
D-Alanine
Mirror
(Enantiomers)
• Enantiomers cannot be superimposed
Note that, as before, hydrogen atoms are often not drawn explicitly to avoid excessive
clutter. By always keeping in mind the tetrahedral geometry of carbon atoms that make four
single bonds, you can always infer where this implicit hydrogen atom should lie relative to the
other three groups based on a correctly drawn molecule.
A quick test to determine if a molecule is chiral is to look for an atom (most often carbon)
that is bonded to four different groups. Such an atom is called a chiral center, and its
presence in a molecule almost always indicates that the molecule is chiral. In the case of
alanine, the central carbon atom is bonded to (i) a –H group, (ii) a –CH3 group, (iii) a –COOH
group, and (iv) a –NH2 group. Because all four of these groups are different, alanine is a chiral
molecule and its central carbon atom is a chiral center. We will see additional examples of
chirality in biological molecules and its consequences throughout this course.
Professor David Liu and Brian Tse, Life Sciences 1a
page 35
Chiral Centers and Chiral Molecules
Four different groups
chiral center
•
•
•
•
Not superimposable
Superimposable
Chiral
Achiral
Enantiomers
Identical structures
An atom attached to four different groups is a chiral center (asymmetric carbon)
A molecule is chiral if it cannot be superimposed on its mirror image
All chiral molecules contain at least one chiral center
A chiral center usually (but not always) indicates that a molecule is chiral
As you might imagine, enantiomers share many chemical properties. Enantiomers have the
same chemical formula, the same molecular weight, the same boiling point, the same melting
point, and under regular sunlight have the same physical appearance. In fact, enantiomers
cannot be distinguished by any test that does not use a chiral probe such as a chiral molecule
or a special light source called plane-polarized light. However, when a chiral probe is
interfaced with a chiral molecule, the resulting interactions are different depending on whether
the “left-handed” or “right-handed” enantiomer of the chiral molecule is used. Sometimes the
chiral probe will interface with the chiral molecule like a left-hand fitting a left-handed glove. If
you tried to interface a left hand with a right-handed glove, however, the fit would be poor at
best. In this example, the left hand can be used to distinguish a left-handed glove from a
right-handed glove— two objects that have an enantiomeric relationship.
Professor David Liu and Brian Tse, Life Sciences 1a
page 36
Small Molecule-Macromolecule
Interactions are Sensitive to Chirality
Enantiomers of a drug
Binding site in a protein
Binding site in a protein
• Enantiomers have identical basic properties (boiling point, melting point, color)
• In the presence of a chiral probe (e.g., a protein), enantiomers behave differently
The vast majority of the macromolecules and small molecules underlying life are chiral.
Based on your understanding of stereochemistry and chiral molecules, you may already realize
that this fact implies that two enantiomers can interact in different ways with biological
molecules. As a result, enantiomers can have very different biological properties. As a simple
example, L-alanine (the enantiomer found in natural proteins) is recognized and processed by
the cell during the course of many crucial life processes including the creation of proteins. In
contrast, D-alanine (the enantiomer of L-alanine) is not recognized by the cellular machinery
and cannot participate in these processes.
Professor David Liu and Brian Tse, Life Sciences 1a
page 37
Thalidomide: Enantiomers with
Different Biological Effects
chiral center
O
N
O
N
H
O
O
Thalidomide: one enantiomer
treats morning sickness…
…but the other is a
potent teratogen
The tragedy of thalidomide
A dramatic example of the ability of living systems to respond differently to enantiomers is
the tragedy of thalidomide. Thalidomide is a chiral small molecule that was widely prescribed
to pregnant women between 1957 and 1962 as a sedative and as a drug to relieve morning
sickness. It was later discovered that only one enantiomer of thalidomide is responsible for its
beneficial effects. The other enantiomer is a potent teratogen, inducing devastating physical
defects in developing fetuses. Thalidomide was originally manufactured as an equal mixture of
both enantiomers (such a mixture is called a racemate). Approximately 15,000 fetuses
worldwide were damaged by the toxic enantiomer of thalidomide. Twelve thousand of these
fetuses survived to give rise to newborns with birth defects, of which 8,000 survived past the
first year; most of these so-called “thalidomide children” are still alive but many suffer from
debilitating deformities. Subsequent studies revealed that the two enantiomers of thalidomide
could interconvert in humans, and therefore even treating pregnant women with only the
beneficial enantiomer of the drug could still lead to birth defects. Fortunately for Americans,
the newest FDA reviewer in 1960, Frances Kelsey, refused to approve thalidomide for use in
the U.S., probably preventing thousands of birth defects. This decision would earn Kelsey the
President's Award for Distinguished Federal Civilian Service (at the time, the highest civilian
award in the U.S.) in 1962 presented by President John F. Kennedy.
Professor David Liu and Brian Tse, Life Sciences 1a
page 38
Stereoisomers of Modern Drugs
O
OH
O
O
HO
O
N
O
NH H
O
OH
S
R
Ibuprofen
Both enantiomers effective;
one works slightly faster
Penicillin
One stereoisomer is effective;
others are not effective but
non-toxic
Ketoprofen
One enantiomer relieves pain
and inflammation; the other
prevents tooth disease!
Even though living systems are full of chiral probes in the form of chiral macromolecules
and chiral small molecules, not all enantiomers of chiral drugs are toxic. In fact, most
enantiomers of drugs are either similar in their activity (such as ibuprofin, the active ingredient
of Advil), or are ineffective yet are not toxic (such as penicillin). Still, the stereoisomers of
thalidomide serve as a potent reminder of the profound importance of stereochemistry in living
systems.
Professor David Liu and Brian Tse, Life Sciences 1a
page 39
Geometric Isomers
H
H
H
H
Ethylene is planar and double bonds
cannot easily be twisted
H
H
H
cis-2-pentene
H
trans-2-pentene
• When groups attached to each double-bonded carbon atom are different,
geometric isomers are possible (cis = Latin for “on this side”, trans = “across”)
• Cis and trans isomers cannot interconvert without breaking the C=C double bond
Geometric isomers
To illustrate a different kind of stereoisomerism, let’s take another look at the carboncarbon double bond. We learned that the six atoms in ethylene (H2C=CH2) all lie on the same
plane in order to satisfy the geometric requirements for the electron clouds that make up
double bonds. The six-atom coplanarity of carbon-carbon double bonds has some important
implications for the molecules of life. When each carbon atom participating in a carbon-carbon
double bond make single bonds to two different groups, the resulting molecule can exist as
one of two stereoisomers. For example, in this molecule called 2-pentene each trigonal carbon
atom makes single bonds to two distinct groups: the trigonal carbon on the left is connected to
a hydrogen and a –CH3 group; likewise, the trigonal carbon on the right is connected to a
hydrogen and a –CH2CH3 group. We can draw 2-pentene either to place the –CH3 and
–CH2CH3 groups on the same side of the double bond, or on different sides. When the groups
are on the same side of the double bond, the resulting structure is called the cis isomer (cis is
Latin for “on this side”); when the groups are on opposite sides, the resulting structure is
called the trans isomer (trans is Latin for “across”). Because the carbon-carbon double bond in
2-pentene is planar, cis-2-pentene and trans-2-pentene cannot interconvert without breaking
the carbon-carbon double bond. Breaking this double bond requires a considerable amount of
energy, and therefore both cis-2-pentene and trans-2-pentene are stable under most
conditions.
Professor David Liu and Brian Tse, Life Sciences 1a
page 40
Retinal: Geometric Isomers in Vision
trans
cis
Light
11-trans-retinal
11-cis-retinal
Light
Molecules that differ in the cis/trans geometry of one or more double bonds but that are
otherwise identical are geometric isomers. Geometric isomers are a subset of stereoisomers in
that their atom-to-atom connectivities are identical. Unlike enantiomers, however, geometric
isomers do not require a chiral probe to exhibit different behavior. Indeed, the basic physical
properties of geometric isomers including their physical lengths, boiling points, melting
temperatures, and colors are often different.
The role of geometric isomers in vision
A striking example of life exploiting the different properties of geometric isomers is the
molecular basis of vision in animals. Examine the structure of 11-cis-retinal, a molecule that is
made by your body from vitamin A, stored in your liver, and transported to the retinas in your
eyes. You can see that 11-cis-retinal contains several carbon-carbon double bonds. As its
name implies, the double bond connected to carbon #11 in this structure exists in the cis
geometry. When a photon of visible light collides with 11-cis-retinal, the cis carbon-carbon
double bond at this position can temporarily break and reform in the trans configuration. As a
result of this geometric change, or isomerization, the shape and length of retinal changes in
response to visible light.
Professor David Liu and Brian Tse, Life Sciences 1a
page 41
Rhodopsin: A Protein &
Small Molecule Team
• The cis-trans isomerization of retinal
changes the conformation and
function of rhodopsin, initiating the
signaling cascade driving vision
cis-retinal covalently
bound to opsin
In your retina, retinal is covalently bonded with a protein called opsin. Together, the smallmolecule/protein pair is known as rhodopsin. When the 11-cis-retinal group in rhodopsin
undergoes isomerization to trans-retinal, the resulting change in the shape and length of the
retinal induces conformational changes in the protein. These changes in turn initiate a cascade
of molecular changes eventually (and very rapidly) resulting in your ability to see. Human
vision will be explored more extensively in Life Sciences 1b next semester.
Professor David Liu and Brian Tse, Life Sciences 1a
page 42
Molecular Components
of HIV
Protein
RNA
Lipid
4. The molecular components of HIV: a preview
Armed with a basic understanding of the structure of atoms and molecules, the ways in
which atoms can form chemical bonds, the special features of organic molecules, the common
methods of drawing molecules, and the importance of stereochemistry, we are now ready to
take a chemical look at the key macromolecules of life: nucleic acids, proteins, and lipids. In
the remainder of the first half of this course, we will continually return to HIV as a unifying
framework to understand how the chemical properties of these molecules of life enable their
biological roles.
HIV is an ideal target for such an analysis because of its simplicity. In fact HIV is so simple
that, despite its devastating ability to take over human cells and to replicate, most scientists
would not consider HIV to be a form of life. Nevertheless, HIV does contain each of the major
classes of biological molecules, and their collective biological roles are all necessary for HIV to
infect cells and to reproduce. We will end this lecture with a brief overview of the molecular
components of HIV.
The outside layer of an HIV virus is a membrane of molecules called lipids that contain long,
greasy carbon and hydrogen (hydrocarbon) tails and charged head groups. This lipid envelope
contains proteins that enable HIV to attach to the surfaces of a certain type of human cell
called T-cells. Ironically, T-cells are a major component of the human immune system and
normally protect human cells from foreign invaders. We will discuss in detail the chemistry and
biology of lipids later in this course.
Professor David Liu and Brian Tse, Life Sciences 1a
page 43
Key Points: An Introduction to the
Molecules of Life
• The molecules of life are macromolecules and small molecules
• Covalent bonds arise from shared valence electrons and define
the connectivity of a molecule
• Ionic and hydrogen bonds arise from electrostatics
• Organic molecules contain carbon atoms in one of three
geometries, and are drawn in a standard convention using lines
• Reaction mechanisms are described by “arrow pushing”
• Chiral molecules are not superimposable with their mirror
images (they exist as enantiomers)
• Enantiomers have different properties in a chiral setting
• Geometric isomers (cis vs. trans C=C) have distinct properties
[From the previous slide] Beneath the lipid envelope are two coats of protein. The protein
in the outer coat has several names, including Gag, p17, and the HIV matrix protein. The
protein in the inner coat is called the core antigen capsid protein, or p24 and surrounds the
core of the virus. Both Gag and p24 not only serve structural roles, but also facilitate several
of the key steps in the HIV life cycle.
Within the p24-covered core of the virus are several essential HIV proteins that catalyze key
chemical reactions necessary for HIV infection and propagation. Two of these proteins, HIV
reverse transcriptase and HIV protease, are major targets of AIDS drugs. The latter protein
will be discussed in great detail later in this course. The core of HIV also contains two copies
of the molecular blueprint of HIV, a strand of RNA that contains all of the instructions
necessary to take over a human T-cell and transform it into a factory for making thousands of
copies of the HIV virus.
In the next several lectures we will examine in detail the chemistry and biology of each of
the macromolecules of life, beginning with nucleic acids.
Professor David Liu and Brian Tse, Life Sciences 1a
page 44