Presentation on steriochemistry

1. Review of Chemical Foundation

2. The Carbon Atom

3. Versatility of Carbon Bonding

7. Macromolecules Are the Major Constituents of Cells
Many biological molecules are macromolecules, polymers of high
molecular weight assembled from relatively simple precursors.
Proteins, nucleic acids, and polysaccharides are produced by the
polymerization of relatively small compounds with molecular weights of
500 or less. The number of polymerized units can range from tens to
millions.
Synthesis of macromolecules is a major energy-consuming activity of
cells.
Macromolecules themselves may be further assembled into
supramolecular complexes, forming functional units such as ribosomes.

9. Three-Dimensional Structure
Is Described
by Configuration and
Conformation

10. Configuration refers to the order that is determined by
chemical bonds. The configuration of a polymer
cannot be altered unless chemical bonds are broken
and reformed.
Conformation refers to order that arises from the
rotation of molecules about the single bonds. These
two structures are studied below.

11. The covalent bonds and functional groups of a biomolecule
are, of course, central to its function, but so also is the
arrangement of the molecule’s constituent atoms in three-
dimensional space—its stereochemistry.
A carbon-containing compound commonly exists as
stereoisomers, molecules with the same chemical bonds but
different stereochemistry—that is, different configuration, the
fixed spatial arrangement of atoms.
Interactions between biomolecules are invariably
stereospecific, requiring specific stereochemistry in the
interacting molecules.

14. A carbon atom with four different substituents is said to be
asymmetric, and asymmetric carbons are called chiral
centers.
A molecule with only one chiral carbon can have two
stereoisomers; when two or more (n) chiral carbons are
present, there can be 2n stereoisomers.
Some stereoisomers are mirror images of each other; they
are called enantiomers. Pairs of stereoisomers that are not
mirror images of each other are called diastereomers.

18. Given the importance of stereochemistry in
reactions between biomolecules, biochemists must
name and represent the structure of each biomolecule
so that its stereochemistry is unambiguous.
For compounds with more than one chiral center,
the most useful system of nomenclature is the RS
system.
In this system, each group attached to a chiral
carbon is assigned a priority. The priorities of some
common substituents are

20. For naming in the RS system, the chiral atom is
viewed with the group of lowest priority pointing away
from the viewer.
 If the priority of the other three groups (1 to 3)
decreases in clockwise order, the configuration is (R)
(Latin rectus, “right”); if in counterclockwise order, the
configuration is (S) (Latin sinister, “left”).
In this way each chiral carbon is designated either
(R) or (S), and the inclusion of these designations in the
name of the compound provides an unambiguous
description of the stereochemistry at each chiral center.

22. Plane-Polarized Light
• Ordinary light: light vibrating in all planes
perpendicular to its direction of
propagation
• Plane-polarized light: light vibrating only in
parallel planes
• Optically active: refers to a compound that
rotates the plane of plane-polarized light

23. Plane-Polarized Light
– plane-polarized light is the vector sum of left
and right circularly polarized light
– circularly polarized light reacts one way with
an R chiral center, and the opposite way with
its enantiomer
– the result of interaction of plane-polarized light
with a chiral compound is rotation of the plane
of polarization

24. Plane-Polarized Light
• Polarimeter: a device for measuring the
extent of rotation of plane-polarized light

26. Can You Make Your
Own Polarimeter
?????

28. Specific Rotation
• To have a basis for comparison, define
specific rotation, [α]D for an optically
active compound
• [α]D = observed rotation/(pathlength x
concentration)
= α/(l x C) = degrees/(dm x g/mL)
• Specific rotation is that observed for 1
g/mL in solution in cell with a 10 cm path
using light from sodium metal vapor (589
nanometers)

29. Optical Activity
– observed rotation: the number of degrees, α, through
which a compound rotates the plane of polarized light
– dextrorotatory (+): refers to a compound that rotates
the plane of polarized light to the right
– levorotatory (-): refers to a compound that rotates of
the plane of polarized light to the left
– specific rotation: observed rotation when a pure
sample is placed in a tube 1.0 dm in length and
concentration in g/mL (density); for a solution,
concentration is expressed in g/ 100 mL

30. D-L System
3 Carbon Sugar ??
Used particularly often for naming sugars and aminoacids:

31. D-L System

32. D-L System

33. The simplest aldose, glyceraldehyde, contains one chiral center
(the middle carbon atom) and therefore has two different optical
isomers, or enantiomers.
By convention, one of these two forms is designated the D isomer,
the other the L isomer.
As for other biomolecules with chiral centers, the absolutec
configurations of sugars are known from x-ray crystallography.
To represent three-dimensional sugar structures on paper, we often
use Fischer projection formulas.

34. The stereoisomers of monosaccharides of each carbon-chain length
can be divided into two groups that differ in the configuration about the
chiral center most distant from the carbonyl carbon.
Those in which the configuration at this reference carbon is the same
as that of D glyceraldehyde are designated D isomers, and those with the
same configuration as L glyceraldehyde are L isomers.
When the hydroxyl group on the reference carbon is on the right in the
projection formula, the sugar is the D isomer; when on the left, it is the L
isomer.
Of the 16 possible aldohexoses, eight are D forms and eight are L.
Most of the hexoses of living organisms are D isomers.

36. • D,L designation refers to the configuration of the
highest-numbered asymmetric center.
• D,L only refers the stereocenter of interest back
to D- and L-glyceraldehyde!
• D,L do not specify the sign of rotation of plane-
polarized light!
• D-sugars predominate in nature.

37. The notation was extended to a-amino acids : L
enantiomers are those in which the NH2 group is on
the LHS of the Fischer projection in which the
carboxyl group appears at the top.
Conversely, the D enantiomers are those in which
the NH2 group is on the RHS. Thus (+)-alanine and
(-)-serine are L-amino acids.

39. Distinct from configuration is molecular conformation, the
spatial arrangement of substituent groups that, without breaking any
bonds, are free to assume different positions in space because of the
freedom of rotation about single bonds.
In the simple hydrocarbon ethane, for example, there is nearly
complete freedom of rotation around the C-C bond.
Many different, interconvertible conformations of ethane are possible,
depending on the degree of rotation.
Two conformations are of special interest: the staggered, which is
more stable than all others and thus predominates, and the eclipsed,
which is least stable.

40. We cannot isolate either of these conformational forms,
because they are freely interconvertible.
However, when one or more of the hydrogen atoms on each
carbon is replaced by a functional group that is either very
large or electrically charged, freedom of rotation around the C-
C bond is hindered.
This limits the number of stable conformations of the ethane
derivative.

42. Interactions between Biomolecules Are Stereospecific
Biological interactions between molecules are stereospecific: the
“fit” in such interactions must be stereochemically correct.
The three-dimensional structure of biomolecules large and small
the combination of configuration and conformation—is of the utmost
importance in their biological interactions: reactant with enzyme,
hormone with its receptor on a cell surface, antigen
with its specific antibody, for example.
The study of biomolecular stereochemistry with precise physical
methods is an important part of modern research on cell structure and
biochemical function.

43. In living organisms, chiral molecules are usually present in
only one of their chiral forms.
For example, the amino acids in proteins occur only as their
L isomers; glucose occurs only as its D isomer.
In contrast, when a compound with an asymmetric carbon
atom is chemically synthesized in the laboratory, the reaction
usually produces all possible chiral forms: a mixture
of the D and L forms, for example. Living cells produce
only one chiral form of biomolecules because the enzymes
that synthesize them are also chiral.

44.  Stereospecificity, the ability to distinguish between
stereoisomers, is a property of enzymes and other proteins and
a characteristic feature of the molecular logic of
living cells.
 If the binding site on a protein is complementary to
one isomer of a chiral compound, it will not be
complementary to the other isomer, for the same reason that a
left glove does not fit a right hand.

45. Chirality in the Biological World
– a schematic diagram of an enzyme surface
capable of binding with (R)-glyceraldehyde
but not with (S)-glyceraldehyde

47. Physical Foundations of Biochemistry

48. Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with Their
Surroundings
The molecules and ions contained within a living organism
differ in kind and in concentration from those in the
organism’s surroundings.
A Paramecium in a pond, a shark in the ocean, an
erythrocyte in the human bloodstream, an apple tree in an
orchard—all are different in composition from their
surroundings and,
 Once they have reached maturity, all (to a first
approximation) maintain a constant composition in the face of
constantly changing surroundings.

49. Organisms Transform Energy and Matter from Their Surroundings
For chemical reactions occurring in solution, we can define a system as all the
reactants and products present, the solvent that contains them, and the immediate
atmosphere— in short, everything within a defined region of space.
The system and its surroundings together constitute the universe.
If the system exchanges neither matter nor energy with its surroundings, it is said to
be isolated.
If the system exchanges energy but not matter with its surroundings, it is a closed
system; if it exchanges both energy and matter with its surroundings, it is an open
system.

50. living organism is an open system; it exchanges
both matter and energy with its surroundings.
Living organisms derive energy from their
surroundings in two ways: (1) they take up chemical
fuels (such as glucose) from the environment and
extract energy by oxidizing them; or (2) they absorb
energy from sunlight

51. The first law of thermodynamics, developed from physics and chemistry but fully valid for
biological systems as well, describes the principle of the conservation of energy:
in any physical or chemical change, the
total amount of energy in the universe
remains constant, although the form of the
energy may change.
Cells are consummate transducers of energy, capable of interconverting chemical,
electromagnetic, mechanical, and osmotic energy with great efficiency

53. The Flow of Electrons Provides Energy for Organisms
Nearly all living organisms derive their energy,
directly or indirectly, from the radiant energy of
sunlight, which arises from thermonuclear fusion
reactions carried out in the sun.
Photosynthetic cells absorb light energy and use it
to drive electrons from water to carbon dioxide,
forming energy-rich products such as glucose
(C6H12O6), starch, and sucrose and releasing O2 into
the atmosphere:

55. Creating and Maintaining Order Requires Work and
Energy
DNA, RNA, and proteins are informational
macromolecules.
In addition to using chemical energy to form the covalent
bonds between the subunits in these polymers, the cell must
invest energy to order the subunits in their correct sequence.
It is extremely improbable that amino acids in a mixture
would spontaneously condense into a single type of protein,
with a unique sequence.

56. This would represent increased order in a population of
molecules; but according to the second law of
thermodynamics, the tendency in nature is toward ever-
greater disorder in the universe:
the total entropy of the universe is continually increasing.
To bring about the synthesis of macromolecules from
their monomeric units, free energy must be supplied to
the system (in this case, the cell).

57. The randomness or disorder of the components of a
chemical system is expressed as entropy, S.
Any change in randomness of the system is
expressed as entropy change, S, which by convention
has a positive value when randomness increases.
J. Willard Gibbs, who developed the theory of
energy changes during chemical reactions, showed that
the free energy content, G, of any closed system can
be defined in terms of three quantities:
enthalpy, H, reflecting the number and kinds of
bonds;
entropy, S; and the
absolute temperature, T (in degrees Kelvin).

58. Gibbs free energy, G, expresses the amount of energy
capable of doing work during a reaction at constant
temperature and pressure. When a reaction proceeds
with the release of free energy (that is, when the
system changes so as to possess less free energy), the
free-energy change, G, has a negative value and the
reaction is said to be exergonic. In endergonic
reactions, the system gains free energy and G is
positive.

59. Examples of Entropy

62. Free Energy & Spontaneity
What is the name of this molecule?

63. Free Energy & Spontaneity
Source of Energy
Spontaneous Reaction Non-spontaneous Reaction

64. Energy Coupling via ATP (1/2)
Energy for Anabolism

65. The definition of free energy G
When a chemical reaction occurs at
constant temperature, the free-energy
change, G, is determined by the enthalpy
change, H, reflecting the kinds and numbers
of chemical bonds and noncovalent
interactions broken and formed, and the
entropy change, S, describing the change in
the system’s randomness:

66. Enthalpy, H,
is the heat content of the reacting system. It reflects
the number and kinds of chemical bonds in the
reactants and products.
When a chemical reaction releases heat, it is said to
be exothermic; the heat content of the products is less
than that of the reactants and H has, by convention, a
negative value.
 Reacting systems that take up heat from their
surroundings are endothermic and have positive
values of H.

67. Entropy, S,
is a quantitative expression for the randomness or disorder
in a system.
When the products of a reaction are less complex and more
disordered than the reactants, the reaction is said to proceed
with a gain in entropy.

68. A process tends to occur spontaneously only if G is
negative.
Yet cell function depends largely on molecules, such as
proteins and nucleic acids, for which the free energy of
formation is positive: the molecules are less stable and more
highly ordered than a mixture of their monomeric components.
To carry out these thermodynamically unfavorable, energy
requiring (endergonic) reactions, cells couple them to other
reactions that liberate free energy (exergonic reactions), so
that the overall process is exergonic: the sum of the free
energy changes is negative.

69. The usual source of free energy in coupled biological
reactions is the energy released by hydrolysis of
phosphoanhydride bonds such as those in adenosine
triphosphate.

76. [C] [D]
∆ G = ∆ Gº' + RT ln
At equilibrium [A] [B]
∆G = 0.
[C] [D]
K'eq, the ratio [C][D]/[A] 0 = ∆ Gº' + RT ln
[A] [B]
[B] at equilibrium, is the
equilibrium constant. [C] [D]
∆ Gº' = - RTln
[A] [B]
An equilibrium constant
(K'eq) greater than one [C] [D]
defining K'eq =
indicates a spontaneous [A] [B]
reaction (negative ∆G°').
∆ Gº' = - RT ln K'eq

77. When a reacting system is not at equilibrium,
the tendency to move toward equilibrium
represents a driving force, the magnitude of which
can be expressed as the free-energy change for the
reaction, G.
Under standard conditions (298 K 25 C), when
reactants and products are initially present at 1 M
concentrations or, for gases, at partial pressures of
101.3 kilopascals (kPa), or 1 atm, the force driving
the system toward equilibrium is defined as the
standard free-energy change, G0.

78. By this definition, the standard state for
reactions that involve hydrogen ions is [H] = 1 M,
or pH 0.
Most biochemical reactions, however, occur in
well-buffered aqueous solutions near pH 7; both
the pH and the concentration of water (55.5 M) are
essentially constant.

82. ∆Go' = − RT ln K'eq
Variation of equilibrium constant with ∆Go‘ (25 oC)
K'eq ∆ º'
G Starting with 1 M reactants &
kJ/mol products, the reaction:
4
10 - 23 proceeds forward (spontaneous)
2
10 - 11 proceeds forward (spontaneous)
0
10 = 1 0 is at equilibrium
-2
10 + 11 reverses to form “reactants”
-4
10 + 23 reverses to form “reactants”

88. Free energy of oxidation
of single-carbon compounds
In aerobic organisms, the ultimate electron acceptor in the
oxidation of carbon is O2, and the oxidation product is CO2
The more reduced a carbon is, the more energy from its oxidation

90. One caution about the interpretation of G:
thermodynamic constants such as this show
where the final equilibrium for a reaction lies
but tell us nothing about how fast that
equilibrium will be achieved.
The rates of reactions are governed by the
parameters of kinetics,

92. Transition State

93. 
Chemical Reaction
gy
er
En
n
io
at
tiv
Ac
Activation
Energy 
a.k.a., Substrate
if enzyme catalyzed

94. Chemical Reaction
Note no change in degree of spontaneity, i.e., in ∆G

95. Catalyzed Reaction
At a given temperature catalyzed Rxns can run faster because
less energy is required to achieve the transition state

96. Induced Fit (Active Site)
The Catalysis associated with Enzymes
occurs within small regions on (or within)
proteins called Active Sites

97. Subtle Application of Energy

98. Enzyme Catalytic Cycle
I
nput o
f Act
iva
En tion
erg
y

99. Mechanisms of Catalysis
Metal Ion or =
Organic Molecule
= Organic
Cofactor
Polypeptide

101. Problem
1St Reaction of Glycolysis
Use the table to :
2. Find standard transformed free energy change of this reaction
3. Couple the reaction with ATP hydrolysis
4. Write the overall Reaction
5. Calculate the standard transformed free energy change of overall reaction

107. First Exam Next Monday
Let’s try to avoid the scholastic equivalent of this!