Study guide: Water and Biomolecular Interactions

📋 Course Outline

1. Water Structure and Dielectric Properties
2. Hydrogen Bonding in Water
3. Water Shapes Biomolecular Structure
4. Noncovalent Forces in Biomolecules
5. Multiple Forces Stabilize DNA
6. Water as a Nucleophile
7. Group Transfer and Enzyme Coupling
8. Water Ionization

📖 1. Water Structure and Dielectric Properties

🔑 Key Concepts & Definitions

• Dipole: A molecule whose electrical charge is distributed asymmetrically across its structure.

★ Must-know

• A water molecule has a slightly skewed tetrahedral geometry, with oxygen at the center and a 105° angle between its hydrogen atoms.

• Water’s high dielectric constant decreases the attraction between charged particles compared with water-free environments of lower dielectric constant, enabling water to dissolve large quantities of salts.

Further detail

• At 25°C, the dielectric constant is 78.5 for water, 24.3 for ethanol, 1.9 for hexane, and approximately 1 for a vacuum.

📖 2. Hydrogen Bonding in Water

🔑 Key Concepts & Definitions

• Hydrogen bond: A bond formed when a partially unshielded hydrogen covalently bound to oxygen or nitrogen interacts with an unshared electron pair on another oxygen or nitrogen atom.

★ Must-know

• Hydrogen bonding contributes to water’s relatively high viscosity, surface tension, and boiling point.

Further detail

• Each molecule in liquid water associates through hydrogen bonds with an average of 3.5 other water molecules.

• Hydrogen bonds between water molecules are transient, have a half-life of a few picoseconds, and require about 4.5 kcal/mol to rupture.

• Aldehydes, ketones, and amides can accept hydrogen bonds through oxygen lone pairs, while alcohols, carboxylic acids, and amines can both donate and accept hydrogen bonds.:

  • Aldehydes
  • Ketones
  • Amides
  • Alcohols
  • Carboxylic acids
  • Amines

📖 3. Water Shapes Biomolecular Structure

🔑 Key Concepts & Definitions

• Hydrophobic interaction: The tendency of nonpolar compounds to self-associate in an aqueous environment, reducing disruption of favorable interactions among surrounding water molecules.

★ Must-know

• Most biomolecules are amphipathic, with regions rich in charged or polar groups and regions with hydrophobic character.

• Proteins tend to bury hydrophobic amino-acid side chains in their interior and place charged or polar side chains on their water-contacting surfaces.

Further detail

• In phospholipid bilayers, charged head groups contact water while hydrophobic fatty acyl chains cluster together and exclude water.

• 🔄 Hydrophobic association follows this sequence:

  1. Hydrophobic groups restrict the orientations of nearby water molecules.
  2. The restricted orientations decrease water’s entropy.
  3. Nonpolar molecules cluster or become buried, minimizing exposed surface area and restricted water.

💡 Memory Hook

Hydrophobic contact orders nearby water → nonpolar groups cluster and become buried.

📖 4. Noncovalent Forces in Biomolecules

🔑 Key Concepts & Definitions

• Salt bridge: An electrostatic interaction between oppositely charged groups within or between biomolecules.
• van der Waals forces: Attractions between transient dipoles generated by rapid electron movement in neutral atoms.

★ Must-know

• Covalent bonds are the strongest forces holding molecules together, while noncovalent forces contribute to the structure, stability, and functional competence of macromolecules.

Further detail

• Salt bridges are comparable in strength to hydrogen bonds but act over larger distances and can facilitate the binding of charged molecules and ions to proteins and nucleic acids.

• van der Waals forces are weaker than hydrogen bonds, act typically over 2 to 4 Å, and decrease as the sixth power of the distance between atoms.

📖 5. Multiple Forces Stabilize DNA

★ Must-know

• Each DNA strand is held together by covalent bonds, while the two strands of the double helix are held together by noncovalent interactions.

Further detail

• The DNA double helix is stabilized by hydrogen bonds between nucleotide bases in Watson-Crick base pairing and by van der Waals interactions between stacked purine and pyrimidine bases.

• DNA presents charged phosphate groups and polar ribose hydroxyl groups to water while burying relatively hydrophobic nucleotide bases inside the double helix.

• The extended DNA backbone maximizes the distance between negatively charged phosphates, minimizing unfavorable electrostatic interactions.

📖 6. Water as a Nucleophile

🔑 Key Concepts & Definitions

• Nucleophile: An electron-rich molecule that attacks an electron-poor atom using a lone pair of electrons.
• Hydrolysis: The cleavage of amide, glycoside, or ester bonds in a biopolymer through nucleophilic attack by water.

📝 Essential Points

• Biologically important nucleophiles include:

  • Water
  • Oxygen atoms of phosphates
  • Oxygen atoms of alcohols
  • Oxygen atoms of carboxylic acids
  • Sulfur of thiols
  • Nitrogen atoms of amines
  • Nitrogen atom of histidine’s imidazole ring

• Common electrophiles include:

  • Carbonyl carbons of amides
  • Carbonyl carbons of esters
  • Carbonyl carbons of aldehydes
  • Carbonyl carbons of ketones
  • Phosphorus atoms of phosphoesters

• Proteases catalyze protein hydrolysis into component amino acids, while nucleases catalyze hydrolysis of phosphoester bonds in DNA and RNA.

💡 Memory Hook

Hydrolysis consumes water; polymer formation can release it.

📖 7. Group Transfer and Enzyme Coupling

★ Must-know

• Enzymes can couple an energetically unfavorable group-transfer reaction to a thermodynamically favorable reaction such as ATP hydrolysis, producing an overall reaction whose free-energy change favors biopolymer synthesis.

• Enzymes accelerate reactions toward equilibrium, but reaction thermodynamics determine the equilibrium point rather than the reaction rate.

Further detail

📐 Formula - A group-transfer reaction transfers group G from donor D to acceptor A: $\mathrm{D{-}G + A \rightleftharpoons A{-}G + D}$.

• Glycogen hydrolysis transfers glucosyl groups to water, while glycogen phosphorolysis transfers glucosyl groups to orthophosphate.

• Enzyme activity control, enzyme sequestration in specific organelles, and active-site exclusion of water help determine when biopolymers are synthesized or degraded and facilitate their synthesis.

💡 Memory Hook

Coupling an unfavorable transfer to favorable ATP hydrolysis can favor biosynthesis.

📖 8. Water Ionization

★ Must-know

• Water can act as either an acid or a base, and its slight ionization is represented as an intermolecular proton transfer that forms hydronium and hydroxide ions.

Further detail

📐 Formula - Water ionization is represented by $\mathrm{H_2O + H_2O \rightleftharpoons H_3O^+ + OH^-}$.