BICH lecture

Solubility: Charge, Dipole Moment, and Hydrogen Bonding

  • Water as a solvent for solutes is influenced by three sequential criteria:
    • Net charge of the solute
    • Net dipole moment (polarity)
    • Hydrogen bonding capacity
  • For polar solutes with a net charge, water is an excellent solvent due to strong electrostatic interactions and hydrogen bonding.
  • For nonpolar solutes, water is a poor solvent; water tends to solvate nonpolar solutes by forming structured water around them (ice-like cages or clathrates), which decreases the entropy of the system.
  • Net charge and dipole moment:
    • If two solutes have the same net charge, compare their net dipole moments; larger dipole moments imply higher polarity and typically higher solubility in water.
    • Hydrogen bonding capacity: more hydrogen bond donors/acceptors lead to greater solubility in water.
  • Water’s role as a solvent for ions and polar molecules is emphasized by its unusually high polarity; the net dipole moment of water is approximately extμextwater = 1.85.ext{μ}_{ ext{water}} \,= \, 1.85.
  • Water is a poor solvent for nonpolar molecules such as oils and triglycerides; those nonpolar solutes dissolve poorly in water.
  • When nonpolar solutes dissolve in water, water forms an ice-like cage around the solute (clathrate).
    • This cage results from water molecules hydrogen-bonded to four neighbors around the nonpolar solute.
    • The process increases the solute’s entropy somewhat but causes a larger decrease in the entropy of water.
    • Consequently, oil and water do not mix spontaneously under normal conditions.
  • Example experiment: vegetable oil mixed with water separates into oil and water phases; the triglyceride’s nonpolar tails minimize contact with water.
  • Term to know: clathrate (or clathrate cage) — water’s organized structure around a nonpolar solute; essential for understanding hydrophobic effects.
  • Amphiphiles (e.g., fatty acids like palmitate) have both hydrophilic and hydrophobic components; the hydrophobic tail drives interactions with nonpolar environments, while the hydrophilic head interacts with water.

Water: Unique Physical Properties and Implications for Life

  • Water exhibits several unusual properties that support life:
    • High melting point and high boiling point (due to extensive hydrogen bonding network).
    • High specific heat capacity and high heat of vaporization.
    • High surface tension and viscosity.
  • These properties can be related to water’s bent geometry, strong polarity, and extensive hydrogen bonding.

Micelles, Detergents, and Thermodynamics of Amphiphiles

  • Amphiphiles with hydrophobic tails and hydrophilic heads can form micelles in water when the concentration exceeds the critical micelle concentration (CMC).
  • Formation process:
    • Below the CMC: fatty acids (e.g., palmitate) predominantly reside at the air–water interface with tails in the air and heads facing water.
    • Above the CMC: micelles form with a hydrophobic interior (tails) and a hydrophilic, water-contacting surface (head groups).
    • Palmitate is a fatty acid (carboxylic acid) with a pKa ≈ 4.5.
  • Thermodynamics of micelle formation:
    • Micellization is endothermic (requires heat input).
    • It is entropically driven: formation releases ordered water molecules around hydrophobic tails, increasing the entropy of water by freeing it from clathrates.
    • Net entropic gain:
    • ΔS_water is large and positive upon micelle formation.
    • ΔSfattyacid becomes negative (organization into micelles reduces the fatty acid’s own entropy).
    • Overall, the positive ΔS of water dominates, driving spontaneous micellization once the CMC is reached.
  • Thermodynamic criterion for spontaneous assembly:
    • rac{\Delta G}{\Delta H - T\Delta S}
    • At equilibrium, ΔG=0\Delta G = 0, so the temperature at which micellization becomes favorable satisfies T=ΔHΔST = \frac{\Delta H}{\Delta S}.
  • Consequences for biological membranes: lipid bilayers and membrane organization are examples of entropy-driven, self-assembly processes.

Palmitate as an Example of Detergent-like Amphiphiles

  • Palmitate (palmitic acid) forms micelles when above the CMC; micelles solvate nonpolar tails in the interior and place carboxylate groups on the exterior in contact with water.
  • Detergency arises because micelles solubilize nonpolar substances (grease, oils) into their hydrophobic cores.
  • Historical note: fatty acids were used as detergents; saponification of triglycerides liberates fatty acids that function as detergents.
  • The micelle model explains how soap cleans greasy residues from clothes and skin: nonpolar residues are solubilized in micelle interiors and rinsed away when water is present.

Water Interactions with Ions and Polar Molecules

  • Water reorganizes around ions and charged species:
    • Water orders around cations and around anions, leading to favorable solvation.
  • The propensity of water to order itself around solutes is a central feature enabling many biological phenomena, including the assembly of lipid-based structures and protein folding.

The Amphiphilic Molecule Class and Lipids (Intro to Lipids)

  • Amphiphiles consist of a hydrophilic (polar) head group and a hydrophobic hydrocarbon tail.
  • In aqueous environments, amphiphiles tend to minimize exposure of hydrophobic regions to water, driving self-assembly into structures like micelles and lipid bilayers.

Amino Acids: Alpha Amino Acids, Fischer Projections, and Isomerism

  • Amino acids found in proteins are alpha amino acids: both the carboxyl group and the amino group are attached to the same carbon (the alpha carbon).

  • Fischer projection rules (for drawing):

    • Use the longest continuous carbon chain on the vertical axis, with the most oxidized carbon at the top.
    • L corresponds to physiological pH (≈7).

  • Common amino acid features:

    • Carboxyl group pKa ≈ 2.2; amino group pKa ≈ 10.5 (typical for amino acids).
    • At pH ≈ 7, amino acids exist as zwitterions: the amino group is protonated (NH3+_3^+) and the carboxyl group is deprotonated (COO−^-), giving a net charge of 0.

  • Three-letter and one-letter abbreviations ( memorize these ): glycine (Gly, G); alanine (Ala, A); isoleucine (Ile, I); proline (Pro, P); methionine (Met, M); phenylalanine (Phe, F); tyrosine (Tyr, Y); tryptophan (Trp, W); threonine (Thr, T); lysine (Lys, K); arginine (Arg, R); histidine (His, H).

  • Glycine (Gly, G): the smallest side chain (H); greatest conformational flexibility. In collagen, every third residue is glycine to accommodate the tight packing of the triple helix.

  • Alanine (Ala, A): a small, nonpolar, aliphatic amino acid; very common in proteins.

  • Isoleucine (Ile, I): has two chiral centers; L- and D- isomers are mirror images; when converting from L to D, invert stereochemistry at both chiral centers.

  • Proline (Pro, P): unique among amino acids; side chain forms a pyrrolidine ring that links back to the amino group; cannot donate an N–H hydrogen for hydrogen bonding in an alpha helix, thus a classic

    "helix breaker"; often found at helix starts/ends; Proline is very rigid (lowest conformational flexibility).

  • Methionine (Met, M): thioether-containing, nonpolar aliphatic amino acid; start codon (AUG) for translation.

  • Aromatic amino acids (three examples):

    • Phenylalanine (Phe, F): benzene ring; absorbs UV light around 260 nm; contributes to protein absorbance around 280 nm due to combined absorption of Phe, Tyr, Trp.
    • Tyrosine (Tyr, Y): phenolic side chain (para-hydroxyl); pK_a ≈ 10.1 (some figures give ≈ 10.4); at physiological pH, phenolic OH is mostly protonated (neutral); above ~pH 11, can deprotonate to form phenolate (negative charge).
    • Tryptophan (Trp, W): indole ring; absorbs UV light around 280 nm; also fluorescent: upon absorbing a photon at 280 nm, it can emit at ~290–300 nm; fluorescence is useful for studying protein structure. Tryptophan residues tend to be buried in hydrophobic cores of globular proteins.

  • Absorbance and protein quantification:

    • The presence of Trp, Tyr, and Phe contributes to the absorbance of proteins at 280 nm.
    • A280 can be used to estimate protein concentration; commonly, an A280 ≈ 1 corresponds to ~1 mg/mL protein, though exact values depend on the protein.

Tyrosine and Its Ionization

  • Tyrosine side chain features a phenolic OH with a dissociable proton:
    • Conjugate acid form (phenol, neutral) at low pH; pK_a ≈ 10.1 (some sources list ≈ 10.4).
    • Above pH ≳ 10.1–10.4, tyrosine can deprotonate to form the phenoxide anion (conjugate base), carrying a negative charge.
  • Thus, at physiological pH (~7), Tyr is largely uncharged (neutral) in its side chain, but its ionization state changes with pH.

Lysine and Arginine: Basic Amino Acids

  • Lysine (Lys, K):
    • Side chain contains four methylene groups ending in an amino group; pK_a of this protonated amino group is around 10.5.
    • At physiological pH (~7), the side chain is typically protonated, contributing a positive charge.
  • Arginine (Arg, R):
    • Side chain contains a guanidinium group; pK_a of the guanidinium nitrogen is about 12.5.
    • At pH 7, the side chain is protonated, contributing a positive charge.
    • The guanidinium nitrogens contribute to the potential for hydrogen bonding and electrostatic interactions.
  • Histidine (His, H):
    • Contains an imidazole ring; can be protonated on the ring nitrogens to give a positive charge.
    • This makes histidine a basic amino acid with buffering capability around physiological pH; one of the ring nitrogens can be protonated.