Water, Hydrogen Bonding, and Solvent Properties in Biology

Water in Biological Systems

• Water evolved in an aqueous environment; it provides UV protection in early life and supports countless biochemical reactions.
• Body water content varies with metabolic status, age, and gender: typically between 55% and 80% of body mass.
• Water intake is continuous (food, drinks) and water is continuously eliminated via breathing, urination, sweating, and bowel movements; hydration is essential for homeostasis.
• Water is present throughout the body:
  • Cytoplasm is largely water-filled.
  • Interstitial spaces and blood tissue are predominantly water-rich (approximately 90% water in these tissues).
• Physiological roles of water include: hormone and neurotransmitter synthesis in the brain, saliva formation, lubrication of mucous membranes, regulation of body temperature via sweating and respiration, protection as a brain/spinal cord shock absorber, fetal amniotic fluid, digestion, oxygen delivery, and waste elimination.
• Thirst mechanism is linked to changes in blood volume and osmolarity; reduced blood volume raises osmolarity, activating osmoreceptors in the hypothalamus and thirst center to restore homeostasis.

Water's Molecular Structure and Dipole Nature

• Water is H₂O: two hydrogens covalently bonded to one oxygen. Oxygen has atomic number 8.
• Electron distribution follows the octet rule: outer orbitals accommodated as 2s²2p⁴; two unpaired electrons on oxygen form covalent bonds with the two hydrogens; two lone pairs of electrons remain.
• Oxygen is more electronegative than hydrogen, pulling electron density toward itself and creating a dipole moment:
  • Hydrogen becomes partially positive (δ⁺).
  • Oxygen becomes partially negative (δ⁻).
• Water’s geometry is a distorted tetrahedral shape with a bond angle of about 105° (ideal sp³ angle is 109.5°).
• This polarity enables water to act as an excellent solvent and to form hydrogen bonds.

Hydrogen Bonding: Donor, Acceptor, Strength, and Dynamics

• Hydrogen bond (HB) is an electrostatic attraction between a hydrogen bonded to an electronegative atom (donor) and another electronegative atom (acceptor).
• In water, each molecule can act as both HB donor and HB acceptor due to its two δ⁺ hydrogens and two lone pairs on oxygen.
• HB donor/acceptor examples:
  • Water as HB donor: the hydrogen attached to oxygen participates as donor to another electronegative atom.
  • Water as HB acceptor: the lone pairs on oxygen accept HB from another molecule.
• HB energetics:
  • Between neutral atoms: typically 4–6 kJ/mol.
  • With one charged atom involved: 6–10 kJ/mol.
• Directionality and strength:
  • HB strengths are greatest when H-bonded atoms and the HB acceptor/donor are in a straight line; bending (non-axial geometry) weakens HB.
• Number and lifetime:
  • In liquid water, about 3.4 HB per molecule on average at any instant (structure is dynamic).
  • HB lifetimes are short, around 1–20 picoseconds; bonds are constantly breaking and reforming.
• Bond lengths:
  • HB length around 0.17 nm (longer than a covalent O–H bond).
  • Covalent O–H bond length is shorter, around ~0.096 nm.
• Water as a universal HB medium underpins many properties of water and biological macromolecules.

Water as a Solvent: Solubility Rules and Examples

• Water is an ideal biological solvent due to its dipole and HB network; it readily dissolves:
  • Charged species (ions) and polar substances via hydration shells and HB interactions.
  • Sugars and many biochemicals with hydroxyl groups that can HB with water.
• Water dissolves salts by hydrating constituent ions (cation and anion) and reducing lattice energy; the dielectric environment lowers inter-ionic attractions.
• Hydration shells form around solutes: surrounding water molecules reorient to maximize HB interactions with solute.
• Hydrophobic solutes are poorly soluble due to ordering water around nonpolar groups, which reduces entropy; this drives hydrophobic aggregation.
• Examples of solubility:
  • Ethanol (CH₃CH₂OH) is highly soluble due to its hydroxyl group enabling HB with water.
  • Glucose and glycerol dissolve well due to multiple OH groups capable of HB.
  • Carboxyl-containing molecules like glycine can be protonated/deprotonated, forming charged species that dissolve via HB and electrostatic interactions.
• Nonpolar, hydrophobic substances (e.g., oils, long aliphatic/aromatic chains) are poorly soluble in water unless they are part of an amphipathic molecule that can form micelles or lipid bilayers.
• Amphipathic molecules (polar head, nonpolar tail) form micelles in water, sequestering hydrophobic tails in the core and exposing polar heads to the solvent to regain entropy.
• Lipid bilayers in biology form from amphipathic lipids: polar heads face outward (aqueous environment), nonpolar tails face inward, creating a hydrophobic interior.

Hydrophobic Effect and Its Role in Biomolecular Assembly

• Hydrophobic effect arises because water reorganizes around nonpolar regions to maximize HB opportunities, which reduces entropy (unfavorable).
• To regain entropy, nonpolar regions aggregate, expelling water and forming less-ordered, more stable assemblies (micelles, lipid bilayers, protein hydrophobic cores).
• Visual analogy used in lecture: a party scenario where an external “teacher” disrupts free mixing, causing water to constrain order around nonpolar tails; aggregation reduces ordered water shells and increases overall entropy.
• Hydrophobic pockets in enzymes/receptors help bind hydrophobic substrates (e.g., steroid hormones) or hydrophobic ligands by stabilizing the nonpolar regions through van der Waals and reduced solvent exposure.
• Hydrophobic interactions are weak individually (like Van der Waals) but collectively contribute substantially to the stability and architecture of biomolecules.

Noncovalent Interactions: Ionic, Hydrogen Bond, Van der Waals, and Hydrophobic Effects

• Overview: noncovalent interactions need no actual electron sharing; they arise from charge distribution and molecular orientation.
• Ionic interactions: attractive forces between permanently charged species or between ions and permanent dipoles.
• Hydrogen bonds: interactions between dipoles where a hydrogen attached to an electronegative atom interacts with another electronegative atom; no actual electron sharing.
• Van der Waals (dispersion/induced dipole) forces: attractive forces that occur at close proximity due to transient dipoles; can also lead to steric hindrance at very short distances (repulsion).
• Hydrophobic effect: entropic drivers where water restructures around nonpolar regions; drives aggregation of nonpolar groups to minimize disrupted HB network.
• Biological significance:
  • Ionic interactions help stabilize protein folds and molecular complexes.
  • Hydrogen bonds stabilize secondary structures in proteins (e.g., α-helix, β-sheet) and base pairing in DNA (A–T with two HB; G–C with three HB).
  • Van der Waals interactions contribute to the stacking and binding of macromolecules (e.g., DNA base stacking, substrate binding in enzymes).
  • Hydrophobic effects shape protein folding, lipid micelle formation, and lipid bilayer organization.
• An integrated view: many biomolecular interactions involve a combination of these forces; no single force acts alone in complex systems.

Protein and Nucleic Acid Structure: Hydrogen Bonding in Action

• Hydrogen bonds stabilize secondary structures within proteins by linking backbone atoms across parts of the polypeptide chain.
• In DNA, base pairing is HB-driven: A–T forms two HBs; G–C forms three HBs, contributing to duplex stability and enabling replication and transcription processes.
• Enzyme–substrate interactions often rely on a balance of HB, ionic, and van der Waals interactions within binding pockets.

Water Phases: Ice, Liquid Water, and Vapor

• Ice (hexagonal): the most common crystalline form, where each water molecule forms four HB (tetrahedral network) resulting in a rigid lattice with low entropy.
• Ice is less dense than liquid water, which explains why ice floats on water.
• Liquid water: a dynamic HB network with ~3.4 HB per molecule on average; high cohesion and surface tension due to ongoing HB formation and breakage.
• Vapor: water molecules have minimal HB interactions, high entropy, and no stable HB network.

Break Time and Q&A Highlights (Contextual Insights)

• Covalent bond vs hydrogen bond: covalent bonds involve actual sharing of electrons; HB involves electrostatic attraction between dipoles without electron sharing.
• The line style in diagrams is often used to distinguish covalent (solid line) from hydrogen bonds (dotted line).
• Linear HB geometry yields stronger HB than bent geometry due to optimal electrostatic interaction.

Water as a Solvent: Practical Implications and Examples

• Solubility depends on the ability of solutes to form HB with water or to be stabilized by hydration shells.
• Hydrophobic solutes disrupt water HB networks, causing ordered water shells and reduced entropy; aggregation reduces these ordered shells and increases entropy.
• Amphipathic molecules form micelles or lipid bilayers to minimize unfavorable water interactions with nonpolar regions.
• Examples: salt dissolution in water; glucose and glycerol dissolve well due to multiple OH groups; aliphatic hydrocarbon chains and oils are poorly soluble due to nonpolar nature.

Osmosis and Osmotic Pressure

• Osmosis: movement of water across a semipermeable membrane from a region of lower solute concentration to higher solute concentration to equalize solute levels.
• Osmotic pressure: the pressure required to prevent water from moving across the membrane; proportional to solute concentration.
• Terms:
  • Isotonic: equal osmolarity inside and outside the cell; stable cell size.
  • Hypertonic environment: higher external solute concentration; water moves out; cells shrink (crenation in RBCs).
  • Hypotonic environment: lower external solute concentration; water moves in; cells swell and may burst.
• Everyday analogy: raisins swell in water (endosmosis); grapes placed in very sugary solutions shrink (exosmosis).

Acids, Bases, and pH: Autoionization of Water and Buffers

• Definitions:
  • Arrhenius acid: donates a proton (H⁺) in solution; Arrhenius base: accepts a proton (H⁺).
  • Conjugate pairs: acid/base conjugates formed after donation/acceptance of a proton.
• Water as an amphoteric solvent: water can donate a proton (H⁺) becoming OH⁻, or accept a proton, becoming H₃O⁺ (hydronium).
• Autoionization of water:
  • Primary reaction:
  • Hydronium (H₃O⁺) and hydroxide (OH⁻) are produced in small amounts and quickly equilibrate.
• Ionic product of water (Kw):
  • In standard chemistry, at 25°C,
  • K_w = [ ext{H}^+][ ext{OH}^-] \,\approx\, 1.0\times 10^{-14} \,\text{M}^2.
  • The lecture notes show a value around 1.8×10⁻¹⁶ (not the standard value); the correct textbook value at 25°C is 1.0×10⁻¹⁴. This discrepancy is noted for cross-check.
• pH and pOH:
  • ext{pH} = -\log{10} [\text{H}^+],\quad \text{pOH} = -\log{10} [\text{OH}^-]
  • At 25°C: ext{pH} + \text{pOH} = 14.
  • Neutral pH corresponds to [H⁺] = [OH⁻] = 1.0×10⁻⁷ M.
• Molarity of water:
  • One liter of water has approximately 1000 g; molecular weight of water is 18 g/mol;
  • [\text{H}_2\text{O}] = \frac{1000\ ext{g/L}}{18\ ext{g/mol}} \approx 55.5\ ext{M}.
• Example problem (lecture walkthrough): Given [H⁺] = 10⁻⁵ M, calculate [OH⁻] using Kw, then pH and pOH. Steps:
  • • Then compute pH = −log([H⁺]), pOH = −log([OH⁻]); verify pH + pOH ≈ 14.
• Practical implications:
  • Blood, urine, and other body fluids have characteristic pH ranges (e.g., human blood is ~7.35–7.45) due to buffering systems.
  • Negative log scale means small changes in [H⁺] correspond to large pH changes.
• Negative pH: theoretically possible for very strong acidic solutions with extremely high [H⁺], yielding pH < 0.

Proton Mobility in Water: The Grotthuss Mechanism (Proton Hopping)

• Proton hopping describes rapid transfer of protons through the hydrogen-bond network of water and hydrated species, increasing ionic mobility beyond what would be expected from simple diffusion.
• Conceptually, a hydronium ion (H₃O⁺) donates a proton to a neighboring water molecule, which becomes H₃O⁺, and the original donor becomes OH⁻; this relay continues rapidly through the network.

Key Takeaway Equations and Values to Memorize

• Water structure and HB basics:
  • \text{H}_2\text{O} with two δ⁺ hydrogens and one δ⁻ oxygen; HB donor/acceptor roles for each molecule.
• Hydrogen bond energetics:
  • Neutral HB: E_{HB} \approx 4-6\ \text{kJ/mol}
  • Charged involvement HB: E_{HB} \approx 6-10\ \text{kJ/mol}
• HB network in water:
  • Liquid water HB per molecule: ~3.4
  • HB lifetime: ~1-20\ \text{ps}
• Water autoionization and Kw:
  • K_w = [\text{H}^+][\text{OH}^-] \approx 1.0\times 10^{-14} at 25°C (standard reference value)
  • \text{pH} = -\log{10}[\text{H}^+]\; ; \; \text{pOH} = -\log{10}[\text{OH}^-]
  • \text{pH} + \text{pOH} = 14 at 25°C
• Molarity of water:
  • [\text{H}_2\text{O}] \approx \frac{1000\ \,\text{g/L}}{18\ \,\text{g/mol}} \approx 55.5\ \text{M}
• Hydrophobic effect visualization:
  • Water reorganizes around nonpolar groups to maximize HB opportunities; aggregation reduces water ordering and increases entropy.
• Solubility rule of thumb:
  • Polar/charged substances dissolve well in water; nonpolar substances (hydrocarbons, lipids) do not unless part of amphipathic structures (micelles, bilayers).

Quick Practice Questions (Based on Transcript Content)

• If [H⁺] = 1.0×10⁻⁶ M, what is [OH⁻]? What is pH and pOH? (Use K_w = 1.0\times10^{-14} at 25°C.)
• Why does ice float on liquid water?
• Describe the difference between a covalent O–H bond and a hydrogen bond using the water molecule as an example.
• Explain why salt dissolves in water using the concepts of hydration shells and dielectric constant.
• What is the hydrophobic effect and how does it relate to micelle formation?
• Calculate the pH if [H⁺] = 1.0×10⁻⁵ M.
• Explain the significance of the A–T and G–C hydrogen bonds in DNA stability and replication.

Connections to Real-World Relevance

• Understanding water’s properties helps explain hydration strategies, drug design (hydrophobic pockets and ligand binding), and the behavior of biological membranes.
• The hydrophobic effect is central to protein folding, membrane formation, and the function of many signaling molecules.
• Knowledge of pH, Kw, and buffer systems is essential in medical, environmental, and biochemical contexts, including digestion, blood chemistry, and lab assays.

Final Notes and Takeaways

• Water’s unique combination of polarity, HB capabilities, and solvent power underpins almost all biology.
• Weak noncovalent interactions, when combined, yield strong, highly specific biomolecular architectures and processes.
• The balance between enthalpy (HB, ionic interactions) and entropy (HB network, hydrophobic hydration) governs structure formation from proteins to membranes to nucleic acids.