27.3 Acid-Base Behavior of Amino Acids

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27.3Acid-Base Behavior of Amino Acids
2
Recall

• While their name implies that amino acids are
  compounds that contain an NH2 group and a CO2H
  group, these groups are actually present as NH3
  and CO2 respectively.
• How do we know this?

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Properties of Glycine

• The properties of glycine
• high melting point (when heated to 233C it
  decomposes before it melts)solubility soluble
  in water not soluble in nonpolar solvent

more consistent with this
than this
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Properties of Glycine

• The properties of glycine
• high melting point (when heated to 233C it
  decomposes before it melts)solubility soluble
  in water not soluble in nonpolar solvent

more consistent with this
called a zwitterion or dipolar ion
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Acid-Base Properties of Glycine

• The zwitterionic structure of glycine also
  follows from considering its acid-base
  properties.
• A good way to think about this is to start with
  the structure of glycine in strongly acidic
  solution, say pH 1.
• At pH 1, glycine exists in its protonated form
  (a monocation).

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Acid-Base Properties of Glycine

• The zwitterionic structure of glycine also
  follows from considering its acid-base
  properties.
• A good way to think about this is to start with
  the structure of glycine in strongly acidic
  solution, say pH 1.
• At pH 1, glycine exists in its protonated form
  (a monocation).

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Acid-Base Properties of Glycine

• Now ask yourself "As the pH is raised, which is
  the first proton to be removed? Is it the proton
  attached to the positively charged nitrogen, or
  is it the proton of the carboxyl group?"
• You can choose between them by estimating their
  respective pKas.

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Acid-Base Properties of Glycine

• Now ask yourself "As the pH is raised, which is
  the first proton to be removed? Is it the proton
  attached to the positively charged nitrogen, or
  is it the proton of the carboxyl group?"
• You can choose between them by estimating their
  respective pKas.

typical ammonium ion pKa 9
typical carboxylic acid pKa 5
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Acid-Base Properties of Glycine

• The more acidic proton belongs to the CO2H group.
  It is the first one removed as the pH is raised.

typical carboxylic acid pKa 5
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Acid-Base Properties of Glycine

• Therefore, the more stable neutral form of
  glycine is the zwitterion.

typical carboxylic acid pKa 5
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Acid-Base Properties of Glycine

• The measured pKa of glycine is 2.34.
• Glycine is stronger than a typical carboxylic
  acid because the positively charged N acts as an
  electron-withdrawing, acid-strengthening
  substituent on the a carbon.

typical carboxylic acid pKa 5
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Acid-Base Properties of Glycine
A proton attached to N in the zwitterionic form
of nitrogen can be removed as the pH is increased
further.

• The pKa for removal of this proton is 9.60.This
  value is about the same as that for NH4 (9.3).

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Isoelectric Point pI

• The pH at which the concentration of the
  zwitterion is a maximum is called the isoelectric
  point. Its numerical value is the average of the
  two pKas.
• The pI of glycine is 5.97.

pKa 2.34
pKa 9.60
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Acid-Base Properties of Amino Acids

• One way in which amino acids differ is in respect
  to their acid-base properties. This is the basis
  for certain experimental methods for separating
  and identifying them.
• Just as important, the difference in acid-base
  properties among various side chains affects the
  properties of the proteins that contain them.
• Table 27.2 gives pKa and pI values for amino
  acids with neutral side chains.

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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 2.34pKa2 9.60pI 5.97
Glycine
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 2.34pKa2 9.69pI 6.00
Alanine
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 2.32pKa2 9.62pI 5.96
Valine
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 2.36pKa2 9.60pI 5.98
Leucine
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Table 27.2 Amino Acids with Neutral Side Chains
O
H
pKa1 2.36pKa2 9.60pI 5.98


H3N
O
Isoleucine
C
C
CH3CHCH2CH3
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Table 27.2 Amino Acids with Neutral Side Chains
O
H
pKa1 2.28pKa2 9.21pI 5.74


H3N
O
Methionine
C
C
CH3SCH2CH2
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 1.99pKa2 10.60pI 6.30
Proline
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 1.83pKa2 9.13pI 5.48
Phenylalanine
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 2.83pKa2 9.39pI 5.89
Tryptophan
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Table 27.2 Amino Acids with Neutral Side Chains
O
H
pKa1 2.02pKa2 8.80pI 5.41


H3N
O
Asparagine
C
C
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 2.17pKa2 9.13pI 5.65
Glutamine
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Table 27.2 Amino Acids with Neutral Side Chains
pKa1 2.21pKa2 9.15pI 5.68
Serine
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Table 27.2 Amino Acids with Neutral Side Chains
O
H
pKa1 2.09pKa2 9.10pI 5.60


H3N
O
Threonine
C
C
CH3CHOH
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Table 27.3 Amino Acids with Ionizable Side Chains
O
H
pKa1 1.88pKa2 3.65pKa3 9.60 pI 2.77


H3N
O
Aspartic acid
C
C

• For amino acids with acidic side chains, pI is
  the average of pKa1 and pKa2.

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Table 27.3 Amino Acids with Ionizable Side Chains
O
H
pKa1 2.19pKa2 4.25pKa3 9.67 pI 3.22


H3N
O
Glutamic acid
C
C
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Table 27.3 Amino Acids with Ionizable Side Chains
pKa1 2.20pKa2 9.11pKa3 10.07 pI 5.66
Tyrosine
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Table 27.3 Amino Acids with Ionizable Side Chains
pKa1 1.96pKa2 8.18pKa3 10.28 pI 5.07
Cysteine
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Table 27.3 Amino Acids with Ionizable Side Chains
pKa1 2.18pKa2 8.95pKa3 10.53pI 9.74
Lysine

• For amino acids with basic side chains, pI is the
  average of pKa2 and pKa3.

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Table 27.3 Amino Acids with Ionizable Side Chains
pKa1 2.17pKa2 9.04pKa3 12.48pI 10.76
Arginine
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Table 27.3 Amino Acids with Ionizable Side Chains
pKa1 1.82pKa2 6.00pKa3 9.17 pI 7.59
Histidine