CHEM 4512/6502

Fall 2012
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Fundamental Concepts
Biochemistry is the Organic Chemistry of Life!

This is designed to highlight fundamental concepts from Organic Chemistry and
Biochemistry I that will be helpful to you throughout the semester. You may find that
some of these concepts are briefly reviewed in class, and this is intended only as an
additional help to you and not intended to be a complete list. For more detail, please
refer to an Organic Chemistry textbook and your Biochemistry textbook.

Acid and Base Chemistry
Brnsted-Lowry Definitions:
Acid: a proton (H
+
) donor
Base: a proton (H
+
) acceptor

Lewis Definition:
Acid: accepts a pair of electrons
Base: donates a pair of electrons

Stereochemistry
To assign stereochemistry, assign priority to functional groups in order of decreasing
atomic number.

e.g. S > O > N > C > H

3
H >
2
H >
1
H

Where there is a double or triple bond, both atoms are considered to be duplicated or
triplicated.
e.g.

Once established, place the lowest priority group behind the plane of the paper. The
direction of rotation around the other three substituents provides the assignment.
Clockwise = R; Counterclockwise = S. An example is shown below. Also included below
are correct ways to depict stereochemistry, and two examples of how NOT to depict
stereochemistry. Correct answers to questions regarding stereochemistry will only follow
the format of the first three; the latter two will not receive credit.
HCl H
+
+ Cl
-
-
OH + H
3
O
+
2 H
2
O
R
2
R
1
OH
+ ZnCl
2
R
2
R
1
H
O
ZnCl
2
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All the proteinogenic amino acids are S except for one.can you determine which one it
is?

Nomenclature for prochiral sp
3
centers. Prochiral sp
3
centers have three rather than
four unique substituents on a carbon (C
aacd
rather than C
abcd
). They can be thought of as
precursors to chiral centers: replacement of a duplicated substituent with a unique
substituent now makes the center chiral. To assign stereochemistry (proR or proS): do
the replacement test with a heavier isotope (e.g. for the example below, substitute
2
H for
1
H). If the replacement of an atom or ligand generates an S stereocenter, that
atom/ligand is proS; and proR if an R stereocenter is created.

Note: An enzyme, being chiral, can distinguish between prochiral substituents.

Nomenclature for prochiral sp
2
centers. Prochiral sp
2
centers have three unique
substituents. To assign stereochemistry, assign priority to these three groups. If
rotation about them is clockwise, you are looking at the re face; if counterclockwise, then
you are looking at the si face.


Chemical Bonding
Taken from: Scudder, P. H., Electron Flow in Organic Chemistry, Wiley, New York
(1992)

Valence Electrons. The valence electrons are the electrons in the outermost shell.
When forming chemical bonds, atoms strive to reach an inert gas configuration by the
gain, loss, or sharing of electrons. Shared electron pairs are indicated by dashes.
Unshared electrons are indicated by dots. Pairs of unshared electrons are referred to as
lone pairs.

H
2
N CO
2
H
CH
3
H
H
2
N CO
2
H
H H
3
C
L-Alanine
S
D-Alanine
R
H
2
N CO
2
H
H H
proR
proS
N
H
R
H
2
N
O
1
2
3
si face
N
H
R
NH
2
O
1
2
3
re face
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Formal Charge. The formal charge on an atom is equal to the number of valence
electrons in the isolated atom minus the number of unshared electrons minus one-half of
the number of shared electrons. Below are some examples of ions and neutral species
found in Bioorganic Chemistry and Biochemistry. You should practice your ability to
calculate the formal charge of each.

The overall charge of a molecule is the sum of the charges on its atoms.

e.g. azide = N
3
-
=

Octet Rule. An atom from the first row of the periodic table cannot be assigned more
than 8 electrons in its valence shells, and a hydrogen atom cannot be assigned more
than 2 electrons (to achieve the configuration of helium). Third row elements (e.g. P and
S) achieve an octet but may also expand their valence shell and have up to twelve
electrons (10 for P and 12 for S).

Electronegativity. Electronegativity is the tenacity with which atoms attract electrons.

F > O > N > C S > H P

Note that the electronegativity of an atom can be affected by what else is bound to it.
The carbon atom of a CF
3
group is much more electronegative than the carbon atom of
a CH
3
group. In the CF
3
group, three highly electronegative fluorines withdraw electron
density from the carbon atom, which in turn will draw electron density from whatever that
carbon atom is bound to.

Drawing Lewis Structures. In order to predict reaction products, one must keep track
of electrons in molecules. Lewis dot structures can help serve this purpose. Bear in
mind, too, that in a reaction mechanism, double-headed curved arrows symbolize
electron movement. You must be able to draw a proper Lewis structure complete with
formal charges accurately and quickly (more on drawing mechanisms are included
below). Your command of the curved arrows must also be automatic. These two points
cannot be overemphasized since all explanations of how a reaction occurs will be
expressed in the language of Lewis structures and curved arrows.

A Lewis structure must contain the proper number of electrons, the correct distribution of
those electrons over each of the atoms, and the correct formal charge. You need to
show all valence electrons; lone pairs will be shown as two dots, and shared electrons in
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a bond, shown as lines. If you use or see an abbreviation for a structure (e.g. CH
3
O
-
),
you must be cognizant of its Lewis structure and know (a) where the lone pairs are
located, (b) where the shared, bonded electrons are located, and (c) the formal charge
of each atom.

1. Obtain the number of valence electrons. Add up the valence electrons contributed
from each atom; add an additional electron for a negative charge, or subtract one to
account for a positive charge.
2. Obtain the full shell count. Sum the number of electrons needed to fulfill the duets for
the hydrogens and octets for all the other elements.
3. Obtain the number of shared, bonded electrons. Subtract the total number of valence
electrons from the full shell count.
4. Obtain the number of bonds needed. A bond is the sharing of two electrons, so divide
the number of shared bonds by two.
5. Draw single bonds (each representing two electrons) between all connected atoms to
establish a skeleton, or preliminary structure. You do need to know the pattern in
which the atoms are connected for this. Count the number of bonds used in your
structure and compare this with the total number of bonds that you calculated. Place
any additional bonds between atoms with incomplete octets to satisfy general boding
trends. Only third-row elements like sulfur can exceed four bonds.

General Bonding Trends for Neutral Charge States
(please note: this is not complete and does not include alternate states for S and P)
One Bond: H, F, Cl, Br, I
Two Bonds: O, S
Three Bonds: N, P
Four Bonds: C, Si

6. Calculate the number of unshared electrons. Subtract the number of shared electrons
from the number of valence electrons.
7. Assign formal charges. Formal charge is a comparison the number of electrons an
atom owns in the Lewis Structure with the number it would have if it were free. The
atom is assigned only half of the electrons that it shares in a bond, but all of its
unshared electrons.
8. The sum of the formal charges must be equal to the total charge of the molecule. As a
cross-check, usually if an atom has more than the number of bonds listed in the
general bonding trends above, it will have a positive formal charge. If it has less, it
will bear a negative formal charge. Formal charge is a good indicator of the electron
polarization in a molecule, and is helpful is identifying electron-rich and electron-
deficient regions.
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Example:
Methoxide ion, CH
3
O
-


Valence electrons: 14
Full shell count: 22
Shared electrons: 8
# Bonds: 4
Unshared electrons: 6 oxygen started with 6 valence electrons, and in
this structure will have one bond and six unshared electrons; so its
formal charge must be -1.

Resonance Structures. Often one Lewis structure is insufficient to describe the electron
distribution in a molecule. In many cases, a resonance hybrid is necessary. All
resonance forms are valid Lewis structures. In resonance forms, only the electrons
move, not the atoms. Each resonance form does not have a separate existence, but is
part of a hybrid structure. The use of double-headed arrow () between forms
reinforces the notion of a hybrid representation of a single structure.

Please note that the forms are not in equilibrium with each other: only one hybrid exists,
not a mix of equilibrating structures.

Example: Acetate Ion (CH
3
CO
2
-
)
Two resonance forms are needed to describe this molecule. Both structures
are of equal importance; the carbon-oxygen bond lengths are equal.
Generally, the more resonance forms of similar energy an ion has, the more
stable it is.

Example: Acetamide (CH
3
CONH
2
)
Frequently, the hybrid cannot be adequately represented by equally weighted
resonance forms. The hybrid may be more like one form than the other, and
thus the resonance forms are denoted as major and minor. For acetamide,
the resonance forms represent uneven electron distribution of a polarized
multiple bond. The major resonance form will tend to have the most covalent
bonds, complete shells, and the least amount of charge separation.
Resonance forms having an electronegative atom with an incomplete octet
are insignificant.



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Functional Groups:
Be familiar with the names, structures, and properties of the following functional groups:
Alcohol
Amine
Alkene
Carbonyls
Aldehyde
Amide
Carboxylic acid
Ester
Ketone
Thioester
Disulfide
Enol
Ether
Guanidine
Imine
Imidazole
Indole
Phenol
Phenyl
Phosphate
Thiol
Thioether

Writing a Reaction Mechanism:
The arrows used to convey the mechanism of a given reaction or to demonstrate
electron flow follow a given convention.

1. The arrow moves from a nucleophilic source (or electron pair) to an electrophilic sink.
Never the opposite.
2. The nucleophile can be either negatively charged or neutral.
3. The electrophile can be either positively charged or neutral.
4. The octet rule must be followed.

INCORRECT:

CORRECT:

H
2
O: H
+
H
2
O-H
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Organic Reaction Mechanisms
You will need a firm understanding of the basic reaction mechanisms from Organic
Chemistry. It would also be helpful for you to review additional reactions from an organic
text as we progress through the course. Enzymes are highly specialized catalysts and
are bound to the same rules and principles that occur in situ.

This includes, but is not limited to the following (Think about what happens to the
stereochemistry of the reactants and products in each case):

S
N
1

S
N
2
E1

E2


Think also about oxidations, reductions, the Michael addition, the Aldol Reactions,
Claisen condensations, addition reactions, and carbonyl additions/substitutions.

Amino Acids and Proteins:
Know the 20 proteinogenic amino acids and the properties of their side chains. You
should familiarize yourself with the terms and concepts concerning protein structure and
the core structural elements of a protein: such as -helix, -sheet, turns, coils, etc.

Nucleotides:
Know the common nucleotides found in the two types of nucleic acids.

H
3
C
CH
3
Cl
CH
3
H
3
C
CH
3
CH
3
Cl
-
O
H
H
H
+
H
3
C
CH
3
OH
CH
3
H
Cl
H
3
C
H
H-O
Cl
-
H
HO
CH
3
H
H
3
C
CH
3
Cl
CH
3
H
3
C
CH
3
H
2
C
Cl
-
O
H
H
H
H
3
C CH
3
H H
Br H
H
CH
3
H
H
Et-O
CH
3
H
H H
Br
-