MCAT Organic Chemistry Review

Nitrogen- and Phosphorus-Containing Compounds


In this chapter, we spent a lot of time looking at biologically active molecules—but did you notice that these molecules are simply applications of the general principles that we have been learning throughout the chapters of this book? By applying your knowledge of the reactions and properties of different types of molecules, you can understand how biological processes work and how complex organic chemistry mechanisms work, like those of the Strecker and Gabriel syntheses. Many of these processes will fall into categories of reactions that we’ve seen before over and over—nucleophilic substitution, nucleophilic addition, and condensation reactions are just a few examples. The MCAT doesn’t ask you to memorize tables of reactants or regurgitate hundreds of named reactions from scratch. Instead, the MCAT asks you to look at the bigger picture and understand the trends—which you’ve now learned!

Concept Summary

Amino Acids, Peptides, and Proteins

·        The α-carbon of an amino acid is attached to four groups: an amino group, a carboxyl group, a hydrogen atom, and an R group. It is a chiral stereocenter in all amino acids except glycine.

·        All amino acids in eukaryotes are L-amino acids. They all have (S) stereochemistry except cysteine, which is (R).

·        Amino acids are amphoteric, meaning they can act as acids or bases.

o   Amino acids get their acidic characteristics from carboxylic acids and their basic characteristics from amino groups.

o   In neutral solution, amino acids tend to exist as zwitterions (dipolar ions).

·        Amino acids can be classified by their R groups.

o   Nonpolar nonaromatic amino acids include alanine, valine, leucine, isoleucine, glycine, proline, and methionine.

o   Aromatic amino acids include tryptophan, phenylalanine, and tyrosine. Both nonpolar nonaromatic and aromatic amino acids tend to be hydrophobic and reside in the interior of proteins.

o   Polar amino acids include serine, threonine, asparagine, glutamine, and cysteine.

o   Negatively charged amino acids contain carboxylic acids in their R groups and include aspartic acid and glutamic acid.

o   Positively charged amino acids contain amines in their R groups and include arginine, lysine, and histidine.

o   Nonpolar nonaromatic and aromatic amino acids tend to be hydrophobic and reside in the interior of proteins.

o   Polar, negatively charged (acidic), and positively charged (basic) amino acids tend to be hydrophilic and reside on the surface of proteins, making hydrogen bonds with the aqueous environment.

·        Peptide bonds form by condensation reactions and can be cleaved hydrolytically.

o   Resonance of the peptide bond restricts motion about the C–N bond, which takes on partial double-bond character.

o   Strong acid or base is needed to cleave a peptide bond.

·        Polypeptides are made up of multiple amino acids linked by peptide bonds. Proteins are large, folded, functional polypeptides.

Synthesis of α-Amino Acids

·        Biologically, amino acids are synthesized in many ways. In the lab, certain standardized mechanisms are used.

·        The Strecker synthesis generates an amino acid from an aldehyde.

o   An aldehyde is mixed with ammonium chloride (NH4Cl) and potassium cyanide. The ammonia attacks the carbonyl carbon, generating an imine. The imine is then attacked by the cyanide, generating an aminonitrile.

o   The aminonitrile is hydrolyzed by two equivalents of water, generating an amino acid.

·        The Gabriel synthesis generates an amino acid from potassium phthalimide, diethyl bromomalonate, and an alkyl halide.

o   Phthalimide attacks the diethyl bromomalonate, generating a phthalimidomalonic ester.

o   The phthalimidomalonic ester attacks an alkyl halide, adding an alkyl group to the ester.

o   The product is hydrolyzed, creating phthalic acid (with two carboxyl groups) and converting the esters into carboxylic acids.

o   One carboxylic acid of the resulting 1,3-dicarbonyl is removed by decarboxylation.

Phosphorus-Containing Compounds

·        Phosphorus is found in inorganic phosphate (Pi), a buffered mixture of hydrogen phosphate (HPO42−) and dihydrogen phosphate(H2PO4).

·        Phosphorus is found in the backbone of DNA, which uses phosphodiester bonds. In forming these bonds, a pyrophosphate (PPi, P2O74−) is released. Pyrophosphate can then be hydrolyzed to two inorganic phosphates.

·        Phosphate bonds are high energy because of large negative charges in adjacent phosphate groups and resonance stabilization of phosphates.

·        Organic phosphates are carbon-containing compounds that also have phosphate groups. The most notable examples are nucleotide triphosphates (such as ATP or GTP) and DNA.

·        Phosphoric acid has three hydrogens, each with a unique pKa. The wide variety in pKa values allows phosphoric acid to act as a buffer over a large range of pH values.

Answers to Concept Checks

·        10.1

1.    All amino acids, except glycine, have chiral α-carbons. Because the R group of glycine is a hydrogen atom, it is not chiral and therefore is not optically active.

2.    Amphoteric molecules can act as acids or bases. Carboxylic acids give amino acids their acidic properties because they can be deprotonated. Amino groups give amino acids their basic properties because they can be protonated.

3.    Peptide bonds are formed by a condensation reaction, in which water is lost, and cleaved hydrolytically by strong acid or base.

4.    The C–N bond of an amide is planar because it has partial double-bond character due to resonance. Double bonds exist in a planar conformation and restrict movement.

·        10.2

1.    An aldehyde, ammonium chloride (NH4Cl), and potassium cyanide (KCN) are used to make the aminonitrile; water is used to hydrolyze the aminonitrile to form the amino acid.

2.    Strecker synthesis is a condensation reaction (formation of an imine from a carbonyl-containing compound and ammonia, with loss of water), followed by nucleophilic addition (addition of the nitrile group), followed by hydrolysis.

3.    Gabriel synthesis begins with potassium phthalimide and diethyl bromomalonate, followed by an alkyl halide. Water is then used to hydrolyze the resulting compound to form the amino acid. While acids and bases are used at various times as catalysts, they are not main reactants.

4.    Gabriel synthesis proceeds through two SN2 reactions, hydrolysis, and decarboxylation.

·        10.3

1.    Inorganic phosphate contains a very negative charge. When bonded to other phosphate groups in a nucleotide triphosphate, this creates repulsion with adjacent phosphate groups, increasing the energy of the bond. Further, inorganic phosphate can be resonance-stabilized.

2.    Organic phosphates are carbon-containing molecules with phosphate groups; the most common examples are nucleotides, like those in DNA, ATP, or GTP.

3.    The three hydrogens in phosphoric acid have very different pKa values. This allows phosphoric acid to pick up or give off protons in a wide pH range, making it a good buffer over most of the pH scale.

Shared Concepts

·        Biochemistry Chapter 1

o   Amino Acids, Peptides, and Proteins

·        Biochemistry Chapter 6

o   DNA and Biotechnology

·        Biochemistry Chapter 9

o   Carbohydrate Metabolism I

·        General Chemistry Chapter 10

o   Acids and Bases

·        Organic Chemistry Chapter 4

o   Analyzing Organic Reactions

·        Organic Chemistry Chapter 8

o   Carboxylic Acids