Organic Chemistry Fifth Edition

WEEK-1
Amino Acids
PROF. SBW
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dibawah: KIMIA PANGAN
BARU SEM 2012/2013
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• BAGI MHSW BARU SEM 2
• TERLAMBAT > 5 MENIT, JANGAN
MASUK, KARENA SDR AKAN
DIUSIR DARI RUANGAN.
• KERJAKAN LATIHAN DIBLOG,
AGAR MUDAH LULUSNYA.
• QUIS 15-20 MENIT SETELAH
KULIAH KE-3
Today’s Lecture
Topics Covered:
1. Amino Acids - Classification & Physical Properties
2. Stereochemistry of a-Amino Acids
3. Common a-Amino Acids: Review of Structure
4. Effect of pH on the Structure of a-Amino Acids
5. Isoelectric Point of Amino Acids
27.1
Classification of Amino Acids
Classification of Amino Acids
amino acids are classified as a, , , etc. to
indicate where the nitrogen atom is relative to the
carboxylic acid:
O
H
H
O
N a
H
N
H
O
H
a
O
N
-Amino Acid
a-Amino Acid
H
O

N
H


H
a
-Amino Acid
O
a-Amino Acids are Most
Ubiquitous in Nature
H
H
O
N a
N
O
H
a
O
N
-Amino Acid
a-Amino Acid
H
O

N
H

H
H
O

H
a
-Amino Acid
O
Revision: Amines are Brønsted Bases
N
H
X
N
X
Amines are electron-rich and have a reactive
lone pair, which can form a covalent bond to
a proton to form an ammonium ion.
Amino Acids Exist as Zwitterions
While their name implies that amino acids
are compounds that contain an amine (—
NH2) and a carboxylic acid (-CO2H), these
groups are actually present as their
conjugate acid (—NH3+) and conjugate base
(—CO2–), respectively.
Amino Acids Exist as Zwitterions
Basic
Amine
H
H
O
N a
H
H
H
H
O
H
O
N a
Acidic
Carboxylic
Acid
H
O
H
N a
Resonance-Stabilized Zwitterion
O
O
Zwitterions Defined
Zwitterionic Compounds/Zwitterions
neutral compounds having formal unit electrical
charges of opposite sign. Some chemists restrict
the term to compounds with the charges on nonadjacent atoms. Sometimes referred to as inner
salts, dipolar ions (a misnomer), e.g. +H3N-CH2CO2ammonioacetate (glycine).
IUPAC Compendium of Chemical Terminology
Amino Acids Exist as Zwitterions
H
H
O
H
H
N
N
H
O
O
H
O
What evidence do we have for this
behavior………
Properties of Glycine Reflect
its Zwitterionic Structure
High Water Solubility
glycine is soluble in water but not in nonpolar solvents.
High Melting Point
when heated to 233°C it decomposes
before it melts.
Properties of Glycine Reflect
its Zwitterionic Structure
The physical properties
of glycine are
consistent with this
structure
H
O
H
O
H
N
H
H
O
N
H
O
Polar Zwitterion
27.2
Stereochemistry of a-Amino
Acids
Chirality, Chiral & Stereogenic Centers
Chirality
the term describing an object
superimposable on its mirror image
that
is
Chiral Center
an atom that has four nonequivalent atoms or
groups attached to it. At various times, chiral
centers have been and are called asymmetric
centers or stereogenic centers
not
Fisher Projections and the
D/L Stereochemical
Convention
30°
B
D
A
A
A
B
B
C
A
D
D
C
C
B
D
C
Fisher
Projection
With the Exception of Glycine,
a-Amino Acids are Chiral Molecules
Glycine
H
H
has no stereogenic
center and is therefore
achiral
All Other A.A.s
have a stereogenic
center and are therefore
chiral
O
N
H
O
H
H
H
O
O
H
H
H
N
N
H
O
R
H
O
H
H
R
Non- superimposable isomers
(enantiomers)
Configuration of a-Amino Acids in Nature
Most of the a-amino acids in proteins
have the L-configuration at their
a carbon
O
R
H
CO2
CO2
a
O
NH3
H3N
a
C
R
H
H3N
H
R
Fischer
Projection
of L-Amino Acid
Configuration of a-Amino Acids in Nature
O
R
O
H
NH3
O
H3N
CO2
H
R
O
H3N
H3N
C
CO2
H
H
R
R
Occurrence of a-Amino Acids in Nature
More than 700 amino acids occur naturally,
but 20 of them are especially important.
These 20 amino acids are the building blocks
of proteins. All are a-amino acids.
They differ in respect to the group attached to
the a carbon.
These 20 are listed in Table 27.1. tolong cari
sendiri.
The Nature of a-Side Chain Determines
the Physical Properties of Amino Acids
O
H3N
R
CO2
O
H
H3N
H
R
The major differences among the side chains concern:
Size and shape
Electronic characteristics
Essential a-Amino Acids can be
Subdivided According to the Nature of
Side Chain
General categories of a-amino acids
1. Non-polar side chains
2. Polar but non-ionized side chains
3. Brønsted acidic side chains
4. Brønsted basic side chains
Essential a-Amino Acids can be
Subdivided According to the Nature of
Side Chain
General categories of a-amino acids
1. Non-polar side chains
2. Polar but non-ionized side chains
3. Brønsted acidic side chains
4. Brønsted basic side chains
Non-Polar Side Chains: Glycine
O
Glycine
(Gly, G)
H3N
H
CO2
O
H
H3N
H
H
Glycine is the simplest amino acid and is achiral
Non-Polar Side Chains: Alanine
O
Alanine
(Ala, A)
H3N
Me
CO2
O
H
H3N
H
Me
Alanine, valine, leucine, and isoleucine have alkyl
groups as side chains, which are non-polar and
hydrophobic
Non-Polar Side Chains: Valine
O
Valine
(Val, V)
H3N
Me
CO2
O
H3N
H
H
Me
Me
Me
Non-Polar Side Chains: Leucine
O
Leucine
(Leu, L)
H3N
O
H
Me
CO2
Me
H3N
Me
Me
H
Non-Polar Side Chains: Isoleucine
O
Isoleucine
(Ile, I)
H3N
Me
CO2
O
H3N
H
H
Me
Me
Me
Non-Polar Side Chains: Methionine
O
H3N
Methionine
(Met, M)
CO2
O
H3N
H
H
Me
S
S
Me
the side chain in methionine is non-polar, but the
presence of sulfur makes it somewhat
polarizable.
Non-Polar Side Chains: Proline
Proline
(Pro, P)
H2
N
O
CO2
O
H2N
H
H
Among the 20 essential amino acids,
proline is the only amino acid that contains
a secondary amine function. Its side chain
is non-polar and cyclic.
Non-Polar Side Chains: Phenylalanine
O
Phenylalanine
(Phe, F)
H3N
CO2
O
H3N
H
The side chain in phenylalanine (a nonpolar amino acid) is a benzyl group.
H
Non-Polar Side Chains: Tryptophan
O
Tryptophan
(Trp, W)
H3N
CO2
O
H3N
H
H
NH
NH
The side chain in tryptophan (a non-polar
amino acid) is larger and more polarizable
than the benzyl group of phenylalanine.
Essential a-Amino Acids can be
Subdivided According to the Nature of
Side Chain
General categories of a-amino acids
1. Non-polar side chains
2. Polar but non-ionized side chains
3. Brønsted acidic side chains
4. Brønsted basic side chains
Polar, Non-Ionized Side Chains: Serine
O
Serine
(Ser, S)
H3N
CO2
O
H3N
H
H
OH
HO
The hydroxymethyl (-CH2OH) side chain in
serine can be involved in hydrogen bonding
and can behave as a nucleophile.
Polar, Non-Ionized Side Chains:
Threonine
O
H3N
Threonine
Me
(Thr, T)
CO2
O
H3N
H
H
OH
HO
Me
The side chain in threonine can be involved in
hydrogen bonding, but is somewhat more
crowded than in serine
Polar, Non-Ionized Side Chains: Cysteine
O
Cysteine
(Cys, C)
H3N
CO2
O
H3N
H
H
SH
HS
Cysteine is a thiol. In proteins, the side chains of
two remote cysteine residues can be joined, via
oxidation, to form a S-S bond, or disulfide
bridge.
Polar, Non-Ionized Side Chains: Tyrosine
O
H3 N
Tyrosine
(Tyr, Y)
CO2
H3 N
O
H
H
HO
OH
The side chain of tyrosine is similar to that of
phenylalanine but can participate in hydrogen
bonding
Polar, Non-Ionized Side Chains:
Asparagine
O
Asparagine
(Asn, N)
H3N
H2N
CO2
O
H
O
H3N
H
H2N
O
The side chains of asparagine and glutamine
(next slide) terminate in amide functions that
are polar and can engage in hydrogen
bonding.
Polar, Non-Ionized Side Chains:
Glutamine
O
H3N
Glutamine
(Gln, Q)
CO2
O
H3N
H
H
H2N
O
H2N
O
Essential a-Amino Acids can be
Subdivided According to the Nature of
Side Chain
General categories of a-amino acids
1. Non-polar side chains
2. Polar but non-ionized side chains
3. Brønsted acidic side chains
4. Brønsted basic side chains
Brønsted Acidic Side Chains: Aspartic
Acid
O
Aspartic Acid
(Asp, A)
H3N
O
H
O
CO2
O
H3N
O
O
Aspartic acid and glutamic acid (next slide)
exist as their conjugate bases at biological
pH. They are negatively charged and can
form ionic bonds with positively charged
species.
H
Brønsted Acidic Side Chains: Glutamic
Acid
O
H3N
Glutamic Acid
(Glu, U)
CO2
O
H3N
H
H
O
O
O
O
Essential a-Amino Acids can be
Subdivided According to the Nature of
Side Chain
General categories of a-amino acids
1. Non-polar side chains
2. Polar but non-ionized side chains
3. Brønsted acidic side chains
4. Brønsted basic side chains
Brønsted Basic Side Chains: Lysine
O
H3N
Lysine
(Lys, K)
CO2
H3N
O
H
H
H3N
H3N
Lysine and arginine (next slide) exist as
their conjugate acids at biological pH.
They are positively charged and can form
electrostatic interactions with negatively
charged species
Brønsted Basic Side Chains: Arginine
O
Arginine
(Arg, G)
H3N
H
H2N
H3N
O
H
N
CO2
H
N
H
H
N
H2N
N
H
H
Arginine is a derivative of lysine: it
contains a basic guanidine group.
H
New Functional Group: Guanidine
H
H
N
N
H
Me
N
N
H
Me
H
Me
N
N
H
Me
pKa = 13.6
Guanidinium Ion
Guanidine
Guanidine is a
significantly
stronger base
thantriethylamin
e
H
Et
Et
Et
N
N
Et
Triethylamine
Et
Et
H
pKa = 10.7
Brønsted Basic Side Chains: Histidine
O
Histidine
(His, H)
H3 N
CO2
H3 N
O
H
H
N
NH
NH
N
Histidine is a basic amino acid, but less basic
than lysine and arginine. Histidine can interact
with metal ions and can help move protons from
one site to another.
Protonation of Imidazole
q. Which nitrogen atom is protonated in the imidazole
ring of histidine?
N
N
H
a. This one

N
N
H
H+
H+
H
H
N
N
aromatic
imidazolium
ion
H
N
N
H
nonaromatic
iminium
ion
Protonation of Histidine
O
H3N
O
O
+H+
H3N
O
H
H
-H-
N
H
N
N
N
H
H
27.3
Acid-Base Behavior of Amino Acids
Effects of pH on Structure of Glycine
At low pH, that is in strongly acidic solution, glycine is
protonated and exists as a monocation.
H
O
H
N
H
H
O
What Happens when
pH of Solution Increases?
As the pH of solution increases, the concentration of
hydroxide ions also increases. At a give point, the
most acidic group in the ion shown below will be
deprotonated.
H
O
H
Typical
Typical
N
H
ammonium
carboxylic
H
O
ion: pKa ~9
acid: pKa ~5
Which is these groups
is the stronger acid?
Glycine is a Stronger Acid than Acetic
Acid
As the pH of solution increases the carboxylic acid is
deprotonated to form a neutral zwitterion.
H
O
H
N
H
H
O
increasing
pH
H
O
H
N
H
O
The pKa of glycine is 2.34. This is lower than acetic
acid (4.76) because of the presence of the electron
withdrawing ammonium substituent.
Isoelectric Point
Isoelectric point
The pH value at which the net electric charge
of an elementary entity is zero. pI is a
commonly used symbol for this kind-ofquantity. It should be replaced by pH(I)
because it is a pH determined under that
particular condition.
• Zwitterionic structure is neutral and its value of pH is called
isoelectric point.
Nilai pKa dan pI dari gugus asam
amino bebas dan protein @ 25 0C
Kurva titrasi asam amino dengan
basa (NaOH) dan Asam (HCL)
REAKSI GUGUS ASAM DAN BASA
DARI ASAM AMINO BILA
DITITRASI
ZWITTER ION
ATAU SALING
MENETRALKAN
Calculation of Isoelectric Point
H
O
H
N
H
OH
pKa = 2.37
H
O
H
The pH(I) is the numerical
average of the pKa values
for the carboxylic acid and
the ammonium group.
N
H
O
9.60+2.37/2 = 5.97
pKa = 9.60
H
The pH(I) of glycine is
5.97
O
N
H
O
What Happens when
pH of Solution Rises Above pH(I)?
As the pH of solution increases above the
isoelectric point, a proton is removed from the
ammonium group (pKa = 9.3) of the zwitterion to
generate the anionic form of the amino acid.
H
O
H
N
H
H
pH increases
above pH(I)
O
O
N
H
O
Anion
The Overall Charge of Amino Acids
Changes as a Function of pH
H
O
H
H
H
O
H
N
H
O
H
O
Cation (+1)
N
H
N
O
Neutral Zwitterion (0)
Increasing pH
H
O
Anion (-1)
Isoelectric Points of Essential a-Amino
Acids
General categories of a-amino acids
1. Amino acids with neutral side chains
2. Amino acids with ionizable side chains
Neutral Side Chains: Glycine
O
Glycine
(Gly, G)
H3N
H
CO2H
OH
H
pKa1 = 2.34
pKa2 = 9.60
pH(I) = 5.97
H3N
H
H
Neutral Side Chains: Alanine
O
Alanine
(Ala, A)
H3N
Me
CO2H
OH
H
pKa1 = 2.34
pKa2 = 9.69
pH(I) = 6.00
H3N
H
Me
Neutral Side Chains: Valine
O
Valine
(Val, V)
H3N
Me
CO2H
OH
H3N
H
H
Me
Me
pKa1 = 2.32
pKa2 = 9.62
pH(I) = 5.96
Me
Neutral Side Chains: Leucine
O
H3N
Leucine
(Leu, L)
CO2H
OH
H
Me
Me
pKa1 = 2.36
pKa2 = 9.60
pH(I) = 5.98
H3N
Me
Me
H
Neutral Side Chains: Isoleucine
O
H3N
Isoleucine
(Ile, I)
Me
CO2H
OH
H3N
H
H
Me
Me
Me
pKa1 = 2.36
pKa2 = 9.60
pH(I) = 5.98
Neutral Side Chains: Methionine
O
H3N
CO2H
OH
H3N
H
Methionine
(Met, M)
Me
S
S
Me
pKa1 = 2.28
pKa2 = 9.21
pH(I) = 5.74
H
Neutral Side Chains: Proline
Proline
(Pro, P)
H2
N
O
CO2H
OH
H
pKa1 = 1.99
pKa2 = 10.60
pH(I) = 6.30
H2N
H
Neutral Side Chains: Phenylalanine
O
H3N
Phenylalanine
(Phe, F)
CO2H
OH
H3N
H
pKa1 = 1.83
pKa2 = 9.13
pH(I) = 5.48
H
Neutral Side Chains: Tryptophan
O
H3N
CO2H
OH
H3N
H
Tryptophan
(Trp, W)
NH
NH
pKa1 = 2.83
pKa2 = 9.39
pH(I) = 5.89
H
Neutral Side Chains: Serine
O
Serine
(Ser, S)
H3N
CO2H
OH
H3N
H
HO
OH
pKa1 = 2.02
pKa2 = 8.80
pH(I) = 5.41
H
Neutral Side Chains: Threonine
O
H3N
Threonine
Me
(Thr, T)
CO2H
OH
H3N
H
H
HO
OH
pKa1 = 2.09
pKa2 = 9.10
pH(I) = 5.60
Me
Neutral Side Chains: Cysteine
O
Cysteine
(Cys, C)
H3N
CO2H
OH
H3N
H
HS
SH
pKa1 = 1.96
pKa2 = 8.18
pH(I) = 5.07
H
Neutral Side Chains: Tyrosine
O
H3N
Tyrosine
(Tyr, Y)
CO2H
H3N
OH
H
HO
OH
pKa1 = 2.20
pKa2 = 9.11
pH(I) = 5.66
H
Neutral Side Chains: Asparagine
O
Asparagine
(Asn, N)
H3N
H2N
CO2H
H3N
OH
H
H2N
O
O
pKa1 = 2.02
pKa2 = 8.80
pH(I) = 5.41
H
Neutral Side Chains: Glutamine
O
H3N
Glutamine
(Gln, Q)
CO2H
OH
H3N
H
H
H2N
H2N
O
pKa1 = 2.17
pKa2 = 9.13
pH(I) = 5.65
O
Isoelectric Points of Essential a-Amino
Acids
General categories of a-amino acids
1. Amino acids with neutral side chains
2. Amino acids with ionizable side chains
Amino Acids with Acidic Side Chains have
Three pKa Values to Consider
pKa1 = 1.88
O
O
H
H
O
O
Zwitterion
O
H
O
N
H
O
H
pKa2 = 3.65
H
O
N
H
H
H
O
O
O
O
O
O
N
H
O
O
H
N
H
H
H
pH(I) is between 1.88 and
pKa3 = 9.80
Calculation of pH(I) for Amino Acids
with Acidic Side Chains
For amino acids with acidic
side chains, pH(I) is the
average of pKa1 and pKa2
1.88+3.65/2 = 2.77
The pH(I) of aspartic acid is
2.77
Ionizable Side Chains: Aspartic Acid
O
Aspartic Acid
(Asp, A)
H3N
CO2H
OH
H
HO
H3N
O
O
OH
pKa1 = 1.88
pKa2 = 3.65
pKa3 = 9.60
pH(I) = 2.77
H
Ionizable Side Chains: Glutamic Acid
O
H3N
Glutamic Acid
(Glu, U)
CO2H
OH
H3N
H
H
HO
O
HO
pKa1 = 2.19
pKa2 = 4.25
pKa3 = 9.67
pH(I) = 3.22
O
Amino Acids with Ionizable Side Chains
have Three pKa Values to Consider
H
pKa1 = 2.18
O
H
H
O
H
N
H
H
O
N
H
O
N
H
N
H
pKa3 = 8.95
H
H
O
H
H
H
H
O
H
N
N
H
O
H
O
Zwitterion
N
stronger base
H
H
pKa2 = 10.53
H
N
H
weaker base
pH(I) is between 8.95 and 10.53
Calculation of pH(I) for Amino Acids
with Basic Side Chains
For amino acids with basic side
chains, pH(I) is the average of
pKa2 and pKa3
8.95+10.53/2 = 9.74
The pH(I) of lysine is 9.74
Ionizable Side Chains: Lysine
O
H3N
Lysine
(Lys, K)
CO2
H3N
O
H
H
H3N
H3N
pKa1 = 2.18
pKa2 = 8.95
pKa3 = 10.53
pH(I) = 9.74
For amino acids with basic side chains, pH(I)
is the average of pKa2 and pKa3.
Ionizable Side Chains: Arginine
O
H3N
Arginine
(Arg, G)
NH
H2N
CO2
H3N
O
H
N
H
H
N
H2N
NH
pKa1 = 2.17
pKa2 = 9.04
pKa3 = 12.48
pH(I) = 10.76
H
Ionizable Side Chains: Histidine
O
Histidine
(His, H)
H3 N
CO2
H3 N
O
H
N
NH
NH
N
pKa1 = 1.82
pKa2 = 6.00
pKa3 = 9.17
pH(I) = 7.59
H
Properties of Amino-Acids
• Because they are zwitterions at neutral pH,
amino acids have many of the physical
properties we associate with salts:
– can form crystals
– have high melting points
– are soluble in water
– not soluble in hydrocarbon solvents
89
REAKSI GUGUS ASAM AMINO
• REAKSI DENGAN REAGEN NINHYDRIN
• Reaksi ini digunakan untuk analisa/mendeteksi adanya asam
amino bebas dari suatu bahan:
• Diukur dengan spektro @ 570 nm, warna ungu, krn
adanya seny. Hydrindantin + CO2+H2O+ aldehide
REAKSI DENGAN REAGEN
FLUORESCAMINE
• DIGUNAKAN UNTUK MENDETEKSI ASAM-2
AMINO, PEPTIDA DAN PROTEIN yang mengandung
gugus amine primer, diukur dengan spektro @ 470
nm, warnanya fluorescence tajam.
REAKSI KIMIA GUGUS ASAM AMINO
SECARA KIMIA
• LIHAT E-BOOK: FOOD CHEMISTRY OLEH
FENNEMA di BLOG SBW
• JUDUL: FOOD CHEMISTRY, 3rd EDITION,
FENNEMA, 1997. MARCEL DEKKER PUB.
SIFAT FISIKO-KIMIA ASAM AMINO YANG
LAIN
• SIFAT HIDROFOBISITAS: REAKSI KELARUTAN
ASAM AMINO DALAM AIR DAN ETANOL (LIHAT
DETAIL DI E-BOOK)
• ARTINYA MANA-2 JENIS ASAM AMINO YG LARUT
DALAM AIR DAN LARUT DALAM ETANOL.
ARGININE, VALINE, LYSINE, ALANINE LARUT
DALAM AIR.
• SIFAT OPTIK: TRP, TYR DAN Phe Mengobsorpsi
sinar pada ‫ ג‬250-300 nm dan Tyr dan Trp
berfluorescene pada lingkungan polaritas medium
larutan.
Latihan AA
• APA YANG DIMAKSUD DGN pI, kapan
terjadinya
• Jelaskan klasifikasi AA dan beri contoh
• Bagaimana proses protonasi dan deprotonasi
asam amino dapat terjadi
• Apakah beda produk pangan nabati dan
hewani ditinjau dari jenis dan jumlah asam
amino yang ada dalam ke dua produk pangan
tsb.