1. Amino acids as amphoteric compounds
Acidity
Basicity
pKa
Electronic and structural features that influence acidity and basicity

2. General Structure of Amino Acid
Building blocks of proteins
Carboxylic acid group
Amino group
Side group R gives unique characteristics

3. 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

7. Carries positive charge when pH<6

9. 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)

10. Can act as acid (proton donor) and base (proton acceptor)
The structure is dependent on pH – due to presence -COOH and -NH2
R – COOH  R – COO- + H+
R – NH3+  R – NH2 + H+
acid
conjugate base
conjugate acid
base
pKa of –COOH [ ], therefore at pH 7 is COO-
pKa of –NH2 [ ], therefore at pH 7 is NH3+

11. 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.

12. pH and ionization (1) H+ OH–
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).
H+ OH–
+ H3N–CH2–COOH + H3N–CH2–COO– H2N–CH2–COO–
Positive ion zwitterion Negative ion
Low pH neutral pH High pH

13. By rearranging the above equation we arrive at the Henderson-Hasselbalch equation:
pH = pKa + log[A-]/[HA]

14. The Henderson-Hasselbalch Equation
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.

15. pKa of –NH2 [ ]
pKa of –COOH [ ]
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:
pI = (pKa1 + pKa2)/2
Leucine:

16. pH and Ionization (2) The pI for aspartic acid occurs at a pH of 2.8
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

19. Learning Check 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

20. Peptides and Proteins Oligopeptide :a few amino acids
Carboxyl terminal-
C-terminal
Amino terminal-
N-terminal-
Oligopeptide :a few amino acids
Polypeptide : many amino acids

21. Tetrapeptide Acid-base behavior of a peptide:
N-terminal, C-terminal, R-groups
Peptides have a characteristic titration curve and a characteristic pI value

23. Acidity of organic compounds
Proton can be formed during break of C-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

24. 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.

25. 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.

26. 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)

27. 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.

28. 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.

29. 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 .. .. ..

30. 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.