Nitrogen and Phosphorus Containing Compounds – Amino Acids, Peptides & Proteins

Context & Scope

• Focus of this lecture block: nitrogen- and phosphorus-containing functional groups that are biologically relevant.
• Bridges material from previous chapter on amides and foreshadows later sections on energy‐transfer (ATP, phosphates) and genetic information (nucleotides).
• Emphasis in this segment: AMINO ACIDS → their structure, stereochemistry, acid–base behavior, classification, and the chemistry of peptide bonds.

Elemental Composition of the Human Body (by mass)

• Carbon, hydrogen, oxygen together ≈ $93\%$.
• Nitrogen ≈ $3.2\%$.
• Phosphorus ≈ $1\%$.
  • Rationale for today’s focus: despite their lower abundance, N & P are indispensable for protein structure (N) and for energy/genetic molecules (P).

Amino Acids: General Structure

• Core formula: one central (α) carbon attached to
  • an amino group \ce{-NH_2} (basic).
  • a carboxyl group \ce{-COOH} (acidic).
  • a hydrogen atom.
  • a variable side chain (R group).
• Because four different substituents are present, the α-carbon is chiral (stereogenic) in every natural amino acid except glycine (R = H).
• Terminology:
  • "Dipolar/zwitterion": molecule bears both + and – formal charges simultaneously.
  • "Proteogenic": incorporated by ribosomes → 20 canonical amino acids.

Stereochemistry & Optical Activity

• Naturally occurring eukaryotic amino acids: L-isomers (amino group on the left in a Fischer projection).
• Configuration:
  • All L-amino acids have S configuration except cysteine, which is R due to the higher priority of sulfur in its side chain.

Acid–Base (Amphoteric) Behavior & Zwitterions

• Carboxyl group can deprotonate → negative charge.
• Amino group can protonate → positive charge.
• Net result in neutral aqueous solution: zwitterion (internal salt).
• pH dependence:
  • Low pH (<< pKa of \ce{-COOH} and \ce{-NH_3^+}): both groups protonated → net positive.
  • High pH (>> both pKa values): both groups deprotonated → net negative.
  • Intermediate: zwitterionic form dominates.

Classification of the 20 Standard Amino Acids

1. Non-polar, non-aromatic (hydrophobic, saturated/aliphatic chains)
   • Glycine (achiral), Alanine, Valine, Leucine, Isoleucine, Proline (secondary amine, cyclic), Methionine (thio-ether).
2. Aromatic (hydrophobic)
   • Phenylalanine, Tyrosine, Tryptophan.
3. Polar, uncharged (hydrophilic, H-bond donors/acceptors)
   • Serine, Threonine, Cysteine (thiol), Asparagine, Glutamine.
4. Negatively charged / Acidic (hydrophilic)
   • Aspartic acid (aspartate anion), Glutamic acid (glutamate anion).
5. Positively charged / Basic (hydrophilic)
   • Lysine, Arginine, Histidine (imidazole ring with pKa ≈ 6).

• Practical take-away: hydrophobic residues typically locate inside folded proteins; hydrophilic residues surface-exposed → solubility & function.

Peptide Bond Formation (Condensation / Dehydration)

• Reaction: \ce{\alpha{-}COOH + \alpha{-}NH2 \rightarrow CONH} + \ce{H2O}.
• Characterized as a condensation (loss of water) and forms an amide linkage.
• Generates dipeptide → polypeptide → protein (as chain length & folding increase).

Peptide Bond Hydrolysis (Reverse Reaction)

• Requires strong acid or strong base catalyst in vitro.
• In vivo, enzymatic cleavage (proteases) lowers activation energy under physiological conditions.

Electronic Structure & Resonance of the Amide Bond

• Two major resonance contributors:
  1. Neutral form: \ce{O=C-NH}.
  2. Charge-separated form: \ce{O^- - C=N^+H}.
• Consequences:
  • Partial double-bond character between the carbonyl carbon and the amide nitrogen.
  • Restricted rotation about the \ce{C–N} axis → planar peptide bond.
  • Contributes to overall protein backbone rigidity and the ability to adopt defined secondary structures (α-helix, β-sheet).
• Adjacent single bonds (Cα–C and Cα–N) retain free rotation, enabling conformational diversity constrained only by sterics.

Broader Connections & Significance

• Links to earlier chapter: amides were introduced as functional groups; peptide bond is a biologically central amide.
• Upcoming relevance of phosphorus: high-energy phosphoanhydride bonds (ATP) and phosphate esters (DNA/RNA) for energy transfer and information storage.
• Ethical/clinical perspective: understanding amino-acid chemistry underlies
  • Nutritional science (essential vs non-essential AAs).
  • Genetic diseases (e.g., sickle cell anemia caused by Val→Glu substitution).
  • Drug design (peptidomimetics, enzyme inhibitors).

Key Numbers & Facts for Quick Recall

• Body composition figures: C/H/O $\approx 93\%$, N $\approx 3.2\%$, P $\approx 1\%$.
• Canonical amino acids: $20$.
• Chirality exception: Gly (achiral).
• Configuration exception: Cys (R).
• Zwitterion concept central to acid–base titration curves and isoelectric point ($pI$) calculations (covered in biochemistry review).
• Peptide bond length ≈ $1.32\ \mathrm{\AA}$ (shorter than a typical C–N single bond ≈ $1.47\ \mathrm{\AA}$) — evidence of partial double-bond character.