BIOSC 1000 Lecture 2Outline of Last Lecture1. Introduction to the Course2. Foundations of BiochemistryOutline of Current Lecture1. Biochemistry of Water2. The pH scale3. Acid StrengthCurrent Lecture1. Biochemistry of Water- Structure of Water – properties of H2O are unusual for its low molecular weight and simple form – this implies that attractive intermolecular forcesbetween H2O molecules are usually strong compared to other similar-size molecular compounds.o Two covalent O-H bonds (shared electron pairs in σ (sigma) molecular orbits)o Two other orbitals hold lone pairs of electronso O nucleus attracts electrons >> H nucleuso O is much more electronegative than Ho O-H bond polarity plus 2 lone pairs of electrons lead to separated partial charges (permanent dipole on molecules) o δ- charge on O atom, and δ+ charge on both H atomso This partial charge separation makes water molecules “polar” –even though the water molecules are net uncharged overall, soliquid water sticks together very strongly - Hydrogen Bonds– unequal charge distribution results in an electrostatic interaction between O atoms of water molecules with H atoms of other water molecules. Very weak interactions o Hydrogen bonds are the most stable when O- - - -H—O is ≈linear(when nuclei are in a straight line along both bonds)o Each hydrogen bond is relatively weak, but numerous H-bonds sum to give substantial cohesive properties to liquid water- Each H2O molecule can share up to 4 H-bonds at once. o In ice, each H2O is fixed in space in the crystal lattice and each H2O forms H-bonds with 4 other H2O molecules, so this rigid spacing increases the occupied volume.o Liquid water is very dynamic; any single H-bond is very transient,so water molecules exist in “flickering clusters”o At any given moment, liquid water molecules form H-bonds with ≈3.4 other water molecules nearby. Each water molecule can donate up to 2 H-bonds and accept up to 2 H-bonds at any one time. On average 3.4/ 4 for the liquid state, and 4 / 4 in ice.o Water is cohesive, owing to the enormous number of H-bonds between water moleculeso Hydrogen bonding networks will include other solutes (alcohols, proteins, nucleic acids, ions)- Molecular interactions with Watero Water interacts electrostatically with charged and polar solutes o Hydrophilic- polar or ionic, dissolve easily in water  Sugars, salts, alcohols, many proteins, nucleic acidso Hydrophobic- nonpolar, cannot readily dissolve in water Alkanes, chloroform, benzene, lipids, oils, waxeso Amphipatic- contains both polar and nonpolar components Proteins, soap, detergent, phospholipids- Hydrogen Bondso Requires an electronegative donor (N, O, S,) with covalently attached Ho Requires an electronegative acceptor (N, O, S) with full or partialcharge Carbon’s electronegativity is TOO WEAK to be a good H-bond donor or acceptoro There must be a straight line between the H-bond and covalent bondo Weak and easily broken and formed – dynamic!- Ionic Interactions – attraction between oppositely charged ions or molecules o Water dissolves salts by replacing solute-solute bonds with water-solute interactionso As salts dissolve, entropy (∆S) increases. This means there is more disorder, which results in a favorable change in free energy- The Hydrophobic Effecto Nonpolar molecules do not dissolve in polar solvents to any significant extent. Instead, water forms highly ordered “cages” around non-polar molecules, decreasing entropy of water phase.o As individual hydrophobic groups are placed into water, the water surrounding them must be ordered -- ∆S negative, so ∆G positive, this is unfavorable.o As hydrophobic molecules collide, they stick together and require only a single outside shell of water – this one cage contains less total water than the sum of two individual cages – this releases some water molecules from ordered cages-- ∆S positive, so ∆G negative, this is favorable.o The Hydrophobic Effect – entropy-based free energy effect for close packing of hydrophobic molecules Micelles- all hydrophobic groups are sequestered from water; ordered shell of H2O molecules is minimized, and entropy is further increased.- Van der Waals interactions—random variations in electronic clouds of any two atoms can create a transient dipole. This leads to a weak attractive force that brings the two atoms closer togethero At the point where the attractive force is maximal, the atoms aresaid to be in van der Waals contact.o Van der Waals radii are often represented to scale like this in space-filling viewso Atoms are like rocks – they cannot occupy the same space at thesame time. o Individually weak – very numerousoo- Noncovalent interactions summary o Individually weak (compared to covalent bonds) but have an enormous cumulative effect as these interactions are quite numerouso Precise orientation of interactions provides specificity of biomolecular recognitiono Individually weak bonds are easily broken and alternatives can form, providing flexibility to biological structures – this is critical for biological recognition and other functions o Crystal structures have told us a lot about how water interacts with protein surfaces. Hemoglobin can become coated in water aka “primary solvent”- Water as a reactant or product of biochemical reactionso Not only does water assist in the formation macromolecular structures, water also is a DIRECT participant in many biochemical reactions: A condensation reaction eliminates water and is usually endergonic- Example: synthesis of ATP A hydrolysis reaction adds water to break a bond and is usually exergonic- Example: cleavage of an RNA- Ionization of Watero Water is capable of weakly and reversibly ioning to generate H+ and OH- ions. H2O <-> H+ + OH-  Molecules that contribute H+ after ionization are ACIDS A reaction for the dissociation of a proton from an acid: HA + H2O <-> H3O+ + A- Since the concentration of water is effectively constant, it is easier to write: HA <-> H+ + A-- The equilibrium constanto k1 = the forward rate constant; k2 = the reverse rate constant (in sec-1)oo A reaction is said to be at equilibrium when the rates of product and reactant formations become equal. But the chemical reaction has not stopped. (Keq) = the equilibrium constant o The equilibrium constant for water is:o Kw= 1.0 x 10-14M2 = [H+][OH-]2. The pH scale- p=