Water

Water is a Polar Molecule - O-H bond distance is 0.958 A (1A = 10^-10 m) and the angle formed by the 3 atoms is 104.5 degrees - Oxygen contains 4 sp3 orbitals, which 2 are occupied by hydrogen and pairs of electrons occupy the other 2

- Water molecules form hydrogen bonds: water is polar in which the oxygen atom with its unshared electrons carries a partial negative charge of -0.66e and the hydrogen atom carries a partial positive charge of 0.33e (e is the charge of the electron). Neighboring water molecules orient themselves so that the O-H bond of one water molecule (+’ve end) points towards the electron pair of another water molecule (-‘ve end). This intermolecular association is called a hydrogen bond. H-bonds are characterized by an H - - - A distance that is at least 0.5A shorter than the calculated van der Waals distance (distance of closest approach between two nonbonded atoms). For ex. H-bonds = 1.8A, VDW = 2.6A). The energy of individual H-bond is small (around 20KJ/mol).

The effects of water on the conformation of macromolecules - Macromolecules are synthesized in a linear form, but biological function requires that they assume the proper conformation. The folding structure must be stable must be the most energetically favorable. The number of possible conformations for a polypeptide or nucleic acid is virtually limitless. Many biochemists study structure and the “folding” process- these occur largely in aqueous medium. Folding is complicated, but must be driven energetically favourable nature of the folded

- Ice is a Crystal of Hydrogen-Bonded Water Molecules: Each water molecule is tetrahedrally is surrounded by 4 nearest neighbors to which it is H-bonded. This causes water to have an open structure that expands from freezing (ice is less dense than water at 0 degrees). Ice has a larger volume than water but the mass stays the same when it’s in liquid form or solid. When water freezes the volume increases thus its density decrease and vice versa. The melting of ice represents the collapse of the tetrahedral orientation of H-bonded water molecules.

The structure of Liquid Water is Irregular - Liquid water reorients itself many times. The H-bonds are distorted, so the networks of linked molecules are irregular and varied. These networks continually break up and re-form. Liquid water consists of a rapidly fluctuating, 3D network of H-bonded water molecules. The number of H-bonds depends on temperature, where liquid water at 0 degrees has approximately 85% as many H-bonds as water in ice. Water doesn’t not exist as individual molecules but as oligomers – trimers, tetramers and etc. The oligomers are highly transient or dynamic as the H-bonds break and form on the timescale of 10^-11 seconds. This is a very high entropy situation. -Effects of oligomeric nature on properties of water: It behaves like it has a higher molecular weight (high melting points and boiling points). It is more viscous than liquids than lack H-bonds.

structure-usually this is taken as the lowest energy conformation and depends on non-covalent forces and effects, many involving water. Solubility and molecular interactions/recognition will also depend on these factors. What are these forces or effects, and what is water’s role? Bond Energies and Electrostatic Interactions

-Covalent bonds are quite stable. The non-covalent interactions fall into a couple of classes. -Ionic interactions are between molecules that have opposite charges. Ionic interactions can be quantified by Coulomb’s Law: the force (F) between any two charged particles will be:

where: q1 and q2 are the charges on the particles r is the distance between the particles e (epsilon) is the “dielectric constant” of the medium; it is related to its polarity but is, in fact, defined by Coulomb’s law. Note: effect of dielectric constant, e - - a high dielectric constant reduces the strength of the interaction

F q1q2

4r 2

- The medium can reduce the strength between charged particles. Vacuum has no medium gives a dielectric constant of 1. Water has a very high dielectric constant. This means that an interaction between these two charged groups on the surface of a protein where it is totally aqueous It’s going to be less energetic.

Ion Solvation by H2O - Why is water so effective at reducing the force between ions? Polar water molecules orient around ions to make favourable charged-dipole interactions. Water basically shields’ the charge interaction between other charged molecules. These hydration shells are relatively stable and effectively reduce the density of charge on the particles, reducing their strength of interaction and making them more soluble.

H-Bonds - H-bonds are next strongest – we already considered the nature of H-bods and looked at H-bonds that involve H2O. Note, many H-bonds don’t involve water. Eg. Alpha helix of protein and interaction of lysozyme with bacterial peptidoglycan.

The Hydrophobic Effect - Hydrophilic and hydrophobic molecules or groups: As a general rule, hydrophilic groups are polar and hydrophobic groups are nonpolar - Hydrophobic Effect: the tendency of water to minimize its contact with hydrophobic (nonpolar) molecules. This turns out to be critical to structure and conformational stability - e.g. oil and vinegar don’t make a solution, or even a stable suspension, but a two-phase system. Why? Oil non-polar, other is polar. - Thermodynamics of a simple model system—the transfer of methane from water to benzene (see also Table 2-2) The transfer is unfavorable in terms of enthalpy (DH is +) but favourable in terms of entropy (DS is +) i.e. it is entropy-driven

CH CH4(H O) 4(C H )2 6 6

DH = +11.7 kJ/mol

-TDS = -22.6 kJ/mol

DG= DH-TDS = -10.9 kJ/mol

Other Electrostatic Interactions - Charge-dipole, as in ion solvation: (sodium chloride). Proteins have lots of these interactions too. Alpha helices have strong dipoles. - Dipole-dipole (van der Waals) interactions - There are permanent dipoles and transient dipoles. The transient can have slight charge on molecules that cause interactions but are very short-lived. - The weakest are London dispersion forces – both dipoles are transient

- Methane dissolved in water. Benzene is than added to the solution. The methane would migrate to benzene. The change in heat is positive. Moving methane from water to benzene absorbed heat. The entropy is much larger and the free energy is negative. This is a spontaneous process. Thus the methane travelling to benzene is entropically driven. Molecular Explanation of the Hydrophobic Effect - Hydrogen Bonds and Other Weak Interactions Influence Biological Molecules - Many weak interactions can have major contributions to biological structure. Weak electrostatic forces include ionic interactions, H-bonds and VDW forces. Strength of the interaction between 2 charged groups is less than the energy of covalent bonds but more than hydrogen bonds. VDW forces are between neutral molecules that arise from permanent or induced dipoles. Permanent dipole interactions are weaker than ionic interactions. Permanent dipoles also induce dipole movement in neighboring groups, which distorts the electron distribution. This interaction is weaker than dipole-dipole interaction. London dispersion forces are very weak and they fall off rapidly with distance. Hydrophilic Substances Dissolve in Water - What happens when a hydrophobic group (molecule of methane or droplet of oil) is solvated or suspended in water? Interactions of water with nonpolar molecule “freezes” water molecules into a “cage” structure, with stable H-bonds. So the water molecules interacting with non-polar solutes gain order, or lose entropy. This is overwhelmingly unfavorable. If a bunch of these coalesce, the hydrophobic surface area exposed to water is reduced, the number of immobilized water molecules is reduced, entropy is increased! Imagine that all those hydrophobic groups are the hydrophobic side chains of a polypeptide—the hydrophobic effect drives the condensation of the molecule, helping to create structure.

a) Detergent b) Phospholipid

Factors that Affect the Strength of the Hydrophobic Effect

• Temperature—since entropy contributes to G as –TS, at lower temperature the hydrophobic effect is weaker; some proteins are cold-labile

• Concentration of water—addition of water-miscible organic solvents (e.g. alcohols, acetone, acetonitrile (CH3CN)) weakens the hydrophobic effect—there is less water in the solvent. This decreases the hydrophobic effect.

Ions present in the solvent--the Hofmeister series (developed in 1888). When you take different ions, the ions has different effects

Amphiphilic/Amipathic Molecules and Water - Some molecules have both amphiphilic and amphipathic portions. How do they exist in water? Micelles and bilayers sequester the hydrophobic groups away from the water. The geometry of the molecules determines the gathering of the complex of the molecules. One tail gives a micelle and 2 tails give a bilayer.

Red- kosmotropes Green - chaotropes

- reduce protein solubility - increase protein solubility Diffusion and Dialysis - Diffusion: all molecules in solution can diffuse due to random movements; small molecules diffuse more rapidly than large molecules. The rate of diffusion for a particular molecule can be quantified by its “diffusion coefficient”, D. The higher D, the faster the molecule diffuses. - Dialysis: semi-permeable dialysis membranes allow the passage of small molecules (like buffers or salt) while retaining larger ones (like proteins). Small molecules will equilibrate across the membrane.