Nitrogen- and Phosphorus-Containing Compounds

Amino Acids, Peptides, and Proteins

  • Amino acids are dipolar molecules that come together through a condensation reaction to form peptides.
  • Larger, folded peptides are called proteins

  • Amino Acid: contains an amino group a carboxyl group attached to a single carbon atom
    • Alpha carbon in this chain is considered a chiral center since it has four different groups.
    • Glycine is the simplest amino acid, and its R group is an H atom.
    • All natural amino acids except for glycine are optically active and are L-isomers
      • Fischer projections are always drawn with the amino group on the left
      • Amino acids have (S) configurations
        • Except for cysteine which has (R) configuration since there is a Sulfur involved.

  • Amphoteric molecules since they have an acidic carboxyl group and a basic amino group.
  • Dipolar Ion or Zwitterion: when an amino acid is put into solution, it takes on both charges from the carboxyl group being deprotonated and the amino group being protonated.
  • All amino acids have zwitterion state properties that are common, but their distinction is defined by the R group.
  • 20 eukaryotic proteogenic amino acids can be grouped into five categories:
    • Nonpolar nonaromatic: tend to have side chains that are saturated hydrocarbons
      • E.g. – alanine, valine, leucine, isoleucine, glycine, proline, and methionine
      • Both aromatic and non-aromatic nonpolar are hydrophobic and tend to be found within the interior of proteins.
    • Aromatic: tryptophan, phenylalanine, tyrosine
    • Polar: tend to have terminal groups containing oxygen, nitrogen, or sulfur
      • E.g.- serine, threonine, asparagine, glutamine and cysteine
    • Negatively charged (Acidic): Terminal carboxylate anions in their R groups
      • E.g. – aspartic acid and glutamic acid
    • Positively charged (Basic): protonated amino group in their R groups
      • E.g. – arginine, lysine, and histidine
  • Amino acids undergo condensation reaction to form peptide bonds.
  • Polypeptides are molecule that are formed from peptide bonds
  • Amides have two resonance structures for its amide bond, and the true structure is a hybrid between these two.
    • One resonance structure has a double bond between the nitrogen atom and the carbonyl carbon. The other has a double bond is between the oxygen and carbonyl carbon
    • Double bond between the carbon and nitrogen limits the rotation of this bond and thus increases the rigidity and stability of the backbone for proteins.

Synthesis of a-Amino Acid

Strecker Synthesis
  • Step 1: Start with aldehyde, ammonium chloride (NH4Cl), and potassium cyanide (KCN).
    • Carbonyl oxygen is protonated which increases the electrophilicity of the carbonyl carbon.
    • Ammonia then attacks the carbonyl carbon to from an imine
    • Imine carbon is susceptible to nucleophilic addition reaction and is thus attacked by the CN anion to form a nitrile group (carbon triple bonded to nitrogen).
    • Final molecule at end of step one is aminonitrile (contains an amino group and a nitrile group).
  • Step 2: nitrile nitrogen is protonated which increases the electrophilicity of the nitrile carbon
    • Water molecule attacks the carbon which leads to both imine and hydroxyl groups on the same molecule
    • Imine is attacked by another water and a carbonyl is formed
    • Overall step is performed in aqueous acid and can be accelerated by using heat.
  • Both L & D amino acids are generated through this process. Produces a racemix mixture.

Gabriel Synthesis
  • Starts with acidic potassium phthalimide is reacted with diethyl bromomalonate (secondary carbon bonded to a bromine)
    • Set up is similar to an SN2 mechanism with the phthalimide as the nucleophile, the secondary substrate carbon as the electrophile and bromine as the leaving group.
      • Produces a phthalimidomalonic ester
      • Potassium phthalimide is a large nucleophile which prevents the substrate carbon from undergoing multiple substitutions since it creates steric hindrance.
  • Alpha carbon is then easily deprotonated in a basic solution. This deprotonated molecule can then act as a nucleophile and attack the substrate carbon of a bromoalkane.
    • SN2 mechanism: leaving group is the bromide anion.
  • Molecule is then hydrolyzed with a strong base and heat.
    • Phthalimide moiety is removed as phthalic acid
    • Final product is a dicarboxylic acid with an amine on the alpha carbon
  • Dicarboxylic acid is decarboxylated through the addition of acid and heat.
    • Carbon dioxide molecule is lost and this results in the formation of the complete amino acid.

Phosphorus-Containing Compounds

  • Phosphoric Acid forms the high-energy bonds that carry ATP
  • Phosphoric acid is sometimes referred to as a phosphate group or inorganic phosphate, denoted by Pi.
    • Inorganic phosphate is found in either HPO42- or H2PO4
  • Phosphorus is also found in the backbone of DNA: phosphodiester bonds link the sugar moieties of the nucleotides.
    • Pyrophosphate: ester dimer that is released when a new nucleotide joins a growing strand of DNA
      • Denoted PPi (P2O74-)
      • This molecule provides the energy for the formation of the new phosphodiester bond.
  • Nucleotides such as ATP, GTP are referred to as organic phosphates

  • Phosphoric acid has three acidic hydrogens.
  • Most strongly acidic environment is with H3PO4. If conditions change to mildly acidic, then it will lose proton relatively easily (pKa of 2.15).
  • In weakly basic solutions H2PO4 will lose a second proton to become HPO32- (pKa of 7.20)
  • Phosphate exists in strongly basic solutions. (pKa of 12.32)
  • For a pH of seven, dihydrogen phosphate and hydrogen phosphate predominate in equal proportions.
  • Since adjacent groups on a nucleotide triphosphate experience large repulsion, and the fact that the phosphate can stabilize up to three negative charges by resonance, the energy released when a phosphate is cleaved is high.