1. 2-Amino Acids & Zwitterions
Naturally occurring amino acids are 2-amino acids (alpha-amino acids) with the general formula R-CH(NH2)-COOH. With the exception of glycine (where R = H), all natural 2-amino acids have four different groups attached to the central alpha carbon and are therefore chiral.
H2N-CH(R)-COOH <=> +H3N-CH(R)-COO- This dipolar ion containing both a positive and a negative formal charge is called a zwitterion.
Why Amino Acids Have Exceptionally High Melting Points
Amino acids are crystalline solids with melting points typically above 200 degrees C. This is because they exist as zwitterions that assemble into a giant ionic lattice held together by strong electrostatic ionic attractions between oppositely charged -NH3+ and -COO- groups, requiring vast thermal energy to disrupt.
2. Isoelectric Point (pI) & Response to pH Changes
Behavior When pH is Altered
- In Strongly Acidic Solution (pH < pI, excess H+):
The basic -COO- group accepts a proton to become -COOH:
+H3N-CH(R)-COO- + H+ <=> +H3N-CH(R)-COOH
The molecule carries a net positive charge (+1). In gel electrophoresis, it migrates towards the negative cathode. - In Strongly Alkaline Solution (pH > pI, excess OH-):
The acidic -NH3+ group loses a proton to hydroxide ions:
+H3N-CH(R)-COO- + OH- <=> H2N-CH(R)-COO- + H2O
The molecule carries a net negative charge (-1). In gel electrophoresis, it migrates towards the positive anode.
3. Zwitterion Equilibrium Diagram
4. Protein Structure Levels
Proteins are biopolymers constructed from amino acids linked together by peptide bonds (-CONH-).
| Structural Level | Description | Types of Bonds Responsible |
|---|---|---|
| Primary (1 degree) | The specific linear sequence of amino acids in the polypeptide chain. | Strong covalent peptide bonds (-CONH-). (Cleaved only by harsh reflux with 6 M HCl for 24 hours). |
| Secondary (2 degree) | Local regular folding of the polypeptide chain into alpha-helices or beta-pleated sheets. | Hydrogen bonding between C=O of one peptide link and N-H of another peptide link along the backbone. |
| Tertiary (3 degree) | The overall 3-dimensional folding of the entire polypeptide chain into its active globular or fibrous shape. | Four R-group interactions:
1. Disulfide bridges: Covalent -S-S- bonds between cysteine residues. 2. Ionic salt bridges: Between -COO- and -NH3+ groups. 3. Hydrogen bonds: Between polar R-groups (-OH, -NH2). 4. van der Waals dispersion forces: Between non-polar hydrocarbon R-groups. |
5. Enzymes & Active Site Stereospecificity
Enzymes are globular proteins that act as biological catalysts. The reactant molecule (substrate) binds to a specific region called the active site.
Stereospecificity of Enzyme Active Sites
Because proteins are constructed exclusively from chiral L-amino acids, the 3D active site itself is a chiral cavity. Consequently, enzymes display absolute stereospecificity: only ONE enantiomer of a chiral substrate can fit into the active site with its functional groups aligned to form intermolecular bonds (lock-and-key model). The mirror-image enantiomer cannot bind properly and remains unreacted.
6. DNA Nucleotides, Complementary Base Pairing & Cisplatin
Deoxyribonucleic acid (DNA) is a macromolecule that encodes genetic information. A single DNA strand is a polymer of nucleotides, each consisting of:
1. A phosphate group
2. A 2-deoxyribose sugar molecule
3. A nitrogenous base (Adenine, Thymine, Cytosine, or Guanine)
Complementary Base Pairing in the Double Helix
DNA consists of two antiparallel polynucleotide strands held together in a double helix by hydrogen bonds between complementary base pairs:
- Adenine (A) pairs with Thymine (T) via TWO hydrogen bonds.
- Guanine (G) pairs with Cytosine (C) via THREE hydrogen bonds.
Action of the Anticancer Drug Cisplatin
Cisplatin, [Pt(NH3)2Cl2], is a square planar platinum(II) complex used in cancer chemotherapy:
- Inside cancer cells, water molecules displace the two chloride ligands in a ligand substitution reaction.
- The platinum ion binds coordinately to nitrogen lone pairs on two adjacent guanine bases on a DNA strand.
- This coordinate cross-linking causes a kink in the DNA double helix, preventing the strands from unwinding and halting DNA replication. Fast-dividing cancer cells undergo programmed cell death (apoptosis).
7. Worked Examples
(a) As a solid at room temperature.
(b) In aqueous solution at pH 1.
(c) In aqueous solution at pH 13.
Solution:
- (a) Solid at room temperature: Exists as a zwitterion:
CH3-CH(NH3+)-COO- - (b) At pH 1 (strongly acidic): Carboxyl group is protonated:
CH3-CH(NH3+)-COOH (cation, net charge +1) - (c) At pH 13 (strongly alkaline): Amino group loses a proton:
CH3-CH(NH2)-COO- (anion, net charge -1)
Calculate the total number of hydrogen bonds holding the two strands together in this segment.
Calculation:
Each A-T base pair is held by 2 hydrogen bonds: 15 * 2 = 30 hydrogen bonds.
Each G-C base pair is held by 3 hydrogen bonds: 25 * 3 = 75 hydrogen bonds.
Total hydrogen bonds = 30 + 75 = 105 hydrogen bonds.