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

Description

• Amino Acid: contains an amino group a carboxyl group attached to a single carbon atom
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  • 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.

Properties

• 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.
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• 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
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• 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.
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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.
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Gabriel Synthesis

• Starts with acidic potassium phthalimide is reacted with diethyl bromomalonate (secondary carbon bonded to a bromine)
  • Set up is similar to an S_N2 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.
  • S_N2 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.
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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 P_i.
  • Inorganic phosphate is found in either HPO₄^2- 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 PP_i (P₂O₇^4-)
    • This molecule provides the energy for the formation of the new phosphodiester bond.
• Nucleotides such as ATP, GTP are referred to as organic phosphates

Properties

• 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 (pK_a of 2.15).
• In weakly basic solutions H₂PO₄^– will lose a second proton to become HPO₃^2- (pK_a of 7.20)
• Phosphate exists in strongly basic solutions. (pK_a 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.