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Amino acids as amphoteric compounds
• Acidity
• Basicity
• pKa
• Electronic and structural features that influence acidity and basicity
General Structure of Amino Acid• Building blocks of proteins
• Carboxylic acid group• Amino group• Side group R gives unique characteristics
Amino acids are polar
• Due to presence – polar covalent bonds– N, O and H atoms - are capable to form
hydrogen bonds with water– Carry charges COO- and NH3
+
The water solubility of amino acids vary to some extend, depending of side chain
Carries positive charge when pH<6
Learning Check• Classify the following amino acids as hydrophobic
(nonpolar), hydrophilic (polar, neutral), acidic, or basic:
A. Lysine (polar basic)
B. Leucine (nonpolar)
C. Serine (polar neutral) D. Aspartate (polar acidic)
The structure is dependent on pH – due to presence -COOH and -NH2
Can act as acid (proton donor) and base (proton acceptor)
• R – COOH R – COO- + H+
• R – NH3+ R – NH2 + H+
pKa of –COOH [1.8-4.3], therefore at pH 7 is COO-
pKa of –NH2 [9.1-12.5], therefore at pH 7 is NH3+
conjugate base
conjugate acid
acid
base
Zwitterion• At a particular pH, the amino acid carries no
net charge and is called a zwitterion.
• Zwitterion …. dipolar ion – has 1 positive and 1 negative charge
• Amphoteric (ampholytes)
• pH, at which the amino acid has a net charge of zero is called the isoelectric point (pI),
• At the isoelectric point (pI), the + and – charges are equal.
pH and ionization (1)
H+ OH–
+ H3N–CH2–COOH + H3N–CH2–COO– H2N–CH2–COO–
Positive ion zwitterion Negative ion
Low pH neutral pH High pH
In solutions more basic than the pI, the —NH3+ in the amino acid donates a proton and become (-NH2) . In solution more acidic than the pI, the COO- in the amino acid accepts a proton and become (-COOH).
By rearranging the above equation we arrive at the Henderson-Hasselbalch equation:
pH = pKa + log[A-]/[HA]
At the point of the dissociation where the concentration of the conjugate base [A-] = to that of the acid [HA]:
pH = pKa + log[1]
The log of 1 = 0. Thus, at the mid-point of a titration of a weak acid:
pKa = pH
The term pKa is that pH at which an equivalent
distribution of acid and conjugate base (or base and conjugate acid) exists in solution.
The Henderson-Hasselbalch Equation
• For an amino acid with only one amine and one carboxyl group, the pI can be calculated from the mean of the pKa of this molecule:
KCOOH=[R - COO-] [H+]
[R - COOH]; K =
[R - NH2] [H+]
[R - NH3+]NH3
+
pI = 2
=2,36 + 9,6
= 5,982
pKCOOH + pK NH3+
pI = 2
=2,36 + 9,6
= 5,982
pKCOOH + pK NH3+Leucine:
pKa of –COOH [1.8-4.3] pKa of –NH2 [9.1-12.5]
pI = (pKa1 + pKa2)/2
pH and Ionization (2)• Acidic amino acids such as aspartic acid have a second
carboxyl group that can donate and accept protons. • If there were three titratable groups or other dissociating
side chain groups, the pI equation would involve all three pKa's and the denominator would be "3“
• The pI for aspartic acid occurs at a pH of 2.8
pI = (pKa1 + pKa2 + pKa3)/3
Glu ionization in water. • Indicate ionizable
groups.– Predict ionization of this
amino acid at pH=1.0– Predict ionization of this
amino acid at pH=10.0– Predict ionization of this
amino acid at pH=7.0
pKa(COOH) pKa(NH2) pKa(R)
Glutamic Acid
Glu 2.19 9.67 4.25
Learning Check
Peptides and Proteins
Oligopeptide :a few amino acids
Polypeptide : many amino acids
Amino terminal-
N-terminal-
Carboxyl terminal-
C-terminal
Tetrapeptide
1. Acid-base behavior of a peptide:
N-terminal, C-terminal, R-groups
2. Peptides have a characteristic titration curve and a characteristic pI value
Acidity of organic compounds
• Proton can be formed during break ofC-H, N-H, O-H or S-H bonds.
• Acidity of organic compounds increases in the following way:
C-H acids < N-H acids < O-H acids < S-H acids
Acidic properties
• Strength of an acid depends on the stability of the formed anion.
• If the formed anion is stable, it does not form the stable undissociated acid molecule and therefore there are H+ in the medium.
Stability of acid anions depends on• Electronegativity of
the atom to which hydrogen is attached.
• Radius of the atom to which hydrogen is attached.
• Delocalization of negative electric charge.
Acidity and electronegativity• The more electronegative an
element is, the more it helps to stabilize the negative charge of the conjugate base.
• Acidity increases as the atom to which hydrogen is attached becomes more electronegative.
Thus, acidity increases:
CH4 < NH3 < H2O < HF
(pKa values are 48, 38, 16 and 3 respectively)
Basicity and and pKa values
• Basicity is related to the ability of a compound to use its nonbonding electrons to combine with a proton.
• A strong base has a large pKa.
Basicity and electronegativity
• Basicity will decrease as an atom becomes more electronegative.
• Oxygen is more electronegative than nitrogen, therefore its electrons are less likely to be donated to a proton.
Basicity and electronic properties
• Proton can attach to the free electron pair.
• Basicity increases where electrons are not delocalizated.
• Basic properties increase in the row:
S-H < O-H < N-H
.. .. ..
Delocalization effects
• Delocalization of charge in the conjugate base anion through resonance is a stabilizing factor and will be reflected by an increase in acidity.