Periodic Table

1
Periodic Table
2
Orbitals
Shapes of Orbitals
3
Electronic Structure
Ionic Bond - NaCl
4
Electronic Structure
Can 6C form ionic bonds?
6C 1s22s22px12py1
5
Hybridization

6
Hybridization in Carbon
sp3 hybridization CH4
6C 1s22s22px12py1
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Hybridization in Carbon
sp2 hybridization CH2CH2
6C 1s22s22px12py1
6C 1s2(2sp2)1 (2sp2)1 (2sp2)1 2pz1
8
Hybridization in Carbon
sp2 hybridization CH2CH2
9
Hybridization in Carbon
6C 1s22s22px12py1
sp hybrid orbital
10
Hybridization in Carbon
sp2 hybridization benzene C6H6
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Bond Polarity
12
Electronegativity
13
Quantitative Measure of Electronegativity
14
Calculating Kier-Hall Electronegativity
i
f
h
h
e
c
d
a
b
g
15
Consequences of Bond Polarity
Dipolar Bonding
MW 72 72 bp 28 OC
80 OC
16
Consequences of Bond Polarity
Hydrogen Bonding
H2O H2S
MW 18 34 bp 100 OC
-60 OC
17
Consequences of Bond Polarity
Hydrogen Bonding

• Each H in a hydrogen-bond is shared by two eN
  atoms
• Linear arrangement of three atoms (H plus 2
  eN) is strongest
• Each linear arrangement is 4 -5 kcal/mol

Typically form H-bond N-H.O- O-H.N
O-H.F-
Typically do not form H-bond S-H O-
P-H N O-H Cl-
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Consequences of Bond Polarity
Hydrogen Bonding - Alcohols
MW 44 46 bp -45 OC
78 OC
19
Consequences of Bond Polarity
Hydrogen Bonding - Acids
20
Consequences of Bond Polarity
Hydrogen Bonding - Structure of Proteins
and Nucleic Acids
Hydrogen Bonding in b-strands (3D structure)
21
Consequences of Bond Polarity
Inductive Effect
the transfer of electronegative effect of polar
s bonds to neighboring s bonds, causing them to
be more or less polarized.
22
Consequences of Bond Polarity
Change in Acidity or Basicity of Groups
a carboxylic acid an alcohol
a carboxylic acid a trifluoro-carboxyli
c acid
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Consequences of Bond Polarity
Inductive Effect - Influence on pKa
pKa 4.5
16.5
24
pKA and Ions in Solution
Chemical Equilibrium
At equilibrium, k1 A B k2 C
D
Le Chateliers Principle When a stress is
applied on a system at equilibrium, the system
will re-adjust to diminish the stress or
counteract the change.
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pKA and Ions in Solution
H2O Equilibrium
?
?
?
?
?
26
pKA and Ions in Solution
Acidity, basicity and neutrality and pH conditions
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pKA and Ions in Solution
Ionization and Strength of Acids and Bases
Property of Ionization The degree of ionization
of a particular compound in water is dependent on
its structure and is characteristic for that
compound.
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pKA and Ions in Solution
Ionization of a weak acid
CH3COOH H2O H3O
CH3COO-
?
?
?
?
Henderson-Haselbach Equation
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pKA and Ions in Solution
What is the physical meaning of pKA?
Unionized Acid1
Unionized Acid2
If pKA1 4 and pKA2 1 .
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Consequences of Bond Polarity
Inductive Effect - Influence on pKa
pKa 4.5
0.23
CH3COOH ClCH2COOH
pKa 4.5 2.9
31
Consequences of Bond Polarity
Inductive Effect - Additive Property
pKa CH3COOH
4.5 ClCH2COOH 2.9 Cl2CHCOOH
1.3 Cl3CCOOH 0.7
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Consequences of Bond Polarity
Inductive Effect - Distance Dependent Property

pKa CH3CH2CH2COOH
4.8 ClCH2CH2CH2COOH 4.5 CH3CHClCH2COOH
4.1 CH3CH2ClCH2COOH 2.8
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Consequences of Bond Polarity
Inductive Effect - Group Electronegativities
Electron-withdrawing groups ? -CN
0.51.0
1.5 -COOH
0.251.251.00 2.5 -CHO
0.251.250 1.5 -NO2
0.51.251.25
3.0
pKa NO2CH2COOH
1.7 ClCH2COOH
2.9 COOHCH2COOH 2.8 CNCH2COOH
3.5
34
Consequences of Bond Polarity
Influence on pKa . through space effect
pKa 6.1 5.7
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pKA and Solubility in Water
36
Consequences of Bond Polarity
Inductive Effect Multiple pKA values
A molecule may have more than one pKA value!!
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Consequences of Bond Polarity
Natural Amino Acids Structure and pKA
Structure of Amino Acid Residues All
L-configuration or R geometry (except for glycine)
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Consequences of Bond Polarity
Natural Amino Acids Structure and pKA
Structure of Amino Acid Residues All
L-configuration or R geometry (except for glycine)
Acidic R Basic R Aspartic
Acid HOOCCH2 Lysine H2N(CH2)4 Glutamic
Acid HOOCCH2CH2 Arginine H2NC(NH)NH(CH2)3 H
istidine
__
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pKA Values of Natural Amino Acids
Residues pKA1 pKA2 Side-Chain pKA (group
identification) Non-Polar Glycine 2.35 9.78 Alani
ne 2.35 9.87 Valine 2.29 9.74 Leucine 2.33 9.74 Is
oleucine 2.32 9.76 Phenyalanine 2.16 9.18 Methioni
ne 2.13 9.28 Tryptophan 2.43 9.44 Hydrogen-bondin
g Serine 2.19 9.21 Threonine 2.09 9.10 Cysteine 1.
92 10.78 8.33 (thiol group) Tyrosine 2.20 9.11 10
.13 (phenol group) Asparagine 2.10 8.84 Glutamine
2.17 9.13 Acidic Aspartic Acid 1.99 9.90 3.90
(g-COOH group) Glutamic Acid 2.10 9.47 4.07
(g-COOH group) Basic Lysine 2.16 9.18 10.79
(?-amino group) Arginine 1.82 8.99 12.48
(guanidino group) Histidine 1.80 9.33 6.04
(imidazole group)
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pKA Values of Natural Amino Acids and the
Dominant Form
Amino Acid pH 3.0 pH 7.0 pH 10.0
Serine Cysteine Tyrosine Asparagine
Arginine Aspartic Acid
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Consequences of Bond Polarity
Influence on pKa of bases
CH3CH2NH2 FCH2CH2NH2
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Consequences of Bond Polarity
Inductive Effect

• depend on the eW atom or eN atom
• is distance dependent
• may be re-inforced or cancelled
• is additive
• can affect the acidity or basicity of
  molecules
• can affect the physical properties of molecules

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Consequences of Bond Polarity
Resonance Effect
pKa 9-11 5
Resonance, Aromaticity Conjugation
44
Consequences of Bond Polarity
Resonance Effect
pKa 9-11 5
H2O
H3O
H2O
H3O
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Consequences of Bond Polarity
Resonance Effect
pKa 4.2 3.4
4.5
46
Consequences of Bond Polarity
Resonance Effect
Electron-donating groups . OH, OMe, NH,
NH2, NCH3

Electron-withdrawing groups . NO2, COOH, CHO,
CN,
SO3H, SO2NH2, SO2Cl
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pKA Values of Common Organic Functional Groups
48
Application of Henderson-Hasselbach Equation
1. Amphetamine has pKA of 9.8. What form will
dominate at pH 2.8, 6.8, and 9.8?
log pH - pKA
At pH 2.8 log 2.8 9.8
-7.0 ? 10-7 ? RNH2
10-7 ? RNH3 ? RNH2 10-7 ?
? 0.00001 ? RNH3 100 - 10-5 ?
99.99999 RNH3 is an ion, therefore
ionization of amphetamine is nearly 100 at pH
2.8
At pH 6.8 log 6.8 9.8
-3.0 ? 10-3 ? RNH2
10-3 ? RNH3 ? RNH2 10-3 ?
? 0.1 ? RNH3 100 - 10-1 ?
99.9 RNH3 is an ion, therefore ionization
of amphetamine is nearly 100 at pH 6.8
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Application of Henderson-Hasselbach Equation
1. Amphetamine has pKA of 9.8. What form will
dominate at pH 2.8, 6.8, and 9.8?
log pH - pKA
At pH 9.8 log 9.8 9.8
0.0 ? 100 1 ?
RNH2 1 ? RNH3 ? RNH2 1 ?
? 50 ? RNH3 100 - 50 ?
50 RNH3 is an ion, therefore ionization of
amphetamine is 50 at pH 9.8
50
Application of Henderson-Hasselbach Equation
2. Meperidine is a narcotic analgesic. Its pKA is
8.7. It needs to be injected (iv). What pH will
you need to make the solution of meperidine?
log pH - pKA
For meperidine to go into solution fully
and easily, it should be fully ionized.
Therefore, protonated species (the conjugate acid
form, A), and not the base form B should
dominate.
? lt 0.01
or 10-2
? log lt
2.0
? pH pKA lt 2.0
? pH 8.7 lt 2.0
? pH lt 2.0 8.7
? pH lt 6.7
51
Application of Henderson-Hasselbach Equation
3. Hydrocortisone hemisuccinate has a pKA of 5.1?
It is a pro-drug form of hydrocortisone, a
steroidal anti-inflammatory molecule. Why was
hemisuccinate derivative made?
Hydrocortisone hemisuccinate
hydrocortisone
Hydrocortisone has poor solubility in
water/blood. However, the hemisuccinate form with
a pKA of 5.1 generates good solubility (100
ionized) at pH 7.2 (blood). Thus, it can be
injected directly in the vein for rapid
anti-inflammatory activity. On the other hand,
hydrocortisone or its ester derivatives (acetate,
valerate, etc) cannot be injected into the vein
directly because they will precipitate. If a
solubilized form of hydrocortisone or its ester
is prepared and injected into a vein, dangerous
possibilities of cutting of blood flow (and
possibly death) exist!