Chapter 26 (Amino Acids)

A compound possessing a terminal carboxylic acid (—COOH) group and a terminal amine (—NH2) group. The amine group (—NH2) of amino acids is termed an amino group.

The most common type of amino acid found in nature that possesses the amino group on the α-Carbon. The 20 most common α-amino acids have the (S)-configuration at the α-Carbon (except for Cysteine and Glycine).

(S)-Configuration L-Configuration • Cysteine = (R)-Configuration • Glycine = Achiral

• D-Configuration ⟶ (R)-Configuration • L-Configuration ⟶ (S)-Configuration

• Top: Carboxylic Acid Group (—COOH) • Bottom: R Group (—R) • Left: Amino Group (—NH2) • Right: Hydrogen (—H) Wedges are assigned to the horizontal substitutents of the Fischer projections (i.e. the amino group and the Hydrogen).

• Top: Carboxylic Acid Group (—COOH) • Bottom: R Group (—R) • Left: Hydrogen (—H) • Right: Amino Group (—NH2) Wedges are assigned to the horizontal substitutents of the Fischer projections (i.e. the amino group and the Hydrogen).

Zwitterionic Form: The amino group is protonated to form an ammonium group (—NH3+) and the carboxylic acid group is deprotonated to form a carboxylate group (—CO2–). The Zwitterionic form of amino acids is the most stable state within neutral conditions.

α-Ammonium Carboxylic Acid: The amino group is protonated to form an ammonium group (—NH3+) and the carboxylic acid group remains protonated to form a carboxylic acid (—CO2H). pKa of α-Carboxylic Acid ≈ 2: The carboxylic acid group remains protonated under strongly acidic conditions.

pH < 2 α-Ammonium Carboxylic Acid

pH > 10 α-Amino Carboxylate

α-Amino Carboxylate: The amino group remains deprotonated to form an amine group (—NH2) and the carboxylic acid group is deprotonated to form a carboxylate (—CO2–). pKa of Ammonium ≈ 9–10: The amino group remains deprotonated under basic conditions.

pKa ≈ 2 The pKa of α-Carboxylic Acids (of amino acids) is lower than typical carboxylic acids (pKa ≈ 4) due to the ammonium-facilitated stabilization of the α-Amino Acid’s conjugate base.

The electron-withdrawing character of the α-ammonium (—NH3+) substituent stabilizes the negative charge on the amino acid’s conjugate base. The positive charge on the α-ammonium substituent allows it to delocalize the carboxylate group’s negative charge.

• Aldehyde Reaction w/ NH3 + HCN • Acidic/Basic Nitrile Hydrolysis

Amino Acid Synthesis The Amino Acid Synthesis mechanism yields a racemic mixture of both amino acid enantiomers (since the aldehyde starting reagent is achiral).

• NH3, HCN • H2SO4, H2O, Δ

• NH3 adds to the aldehyde’s carbonyl Carbon to yield an imine. • HCN protonates the imine’s Nitrogen to yield an iminium cation. • CN– adds to the iminium’s central Carbon to yield a tetrahedral Aminonitrile intermediate. • Nitrile Hydrolysis yields an amino acid (by replacing the cyanide group with a carboxylate group and protonating the amino group).

The amide bond that connects connects one amino acid’s carboxylic acid group to another amino acid’s amino group. The peptide bond is a CCarbonyl—N bond that is planar, relatively short, and resistant to rotation.

• Planar: Conjugation between the Nitrogen lone-pair and the carbonyl π electrons. • Short: Strong conjugation across the amide group due to the readily donatable Nitrogen lone-pair electrons. • High Barrier to Rotation: Strong conjugation across the amide group that requires large activation energy to overcome.

Trans Configuration The trans configuration places the α-Carbons of adjacent amino acids on opposite sides of the peptide bond, which minimizes steric repulsion.

The cis configuration creates steric strain/repulsion between the α-Carbons of adjacent amino acids (by placing these Carbons on the same side of the peptide bond).

The end of the peptide chain that contains the amino group (—NH2).

The end of the peptide chain that contains the carboxylic acid group (—CO2H).

The naming of peptides always begins from the N–terminus and ends at the C–terminus. N’ ⟶ C’