Lecture 1 - Tagged.pdf

LECTURE 1: o Brief review of thermodynamics o Properties of water o Introduction to the hydrophobic effect Appling: 2016 edition, pp. 19-30 and 50-60, Mathews: 4th edition, pp. 26-39 and 58-69 BRIEF REVIEW OF BASIC THERMODYNAMICS Consider a bimolecular reaction:...

LECTURE 1: o Brief review of thermodynamics o Properties of water o Introduction to the hydrophobic effect Appling: 2016 edition, pp. 19-30 and 50-60, Mathews: 4th edition, pp. 26-39 and 58-69 BRIEF REVIEW OF BASIC THERMODYNAMICS Consider a bimolecular reaction: A+B C+D If we start only with reactants A and B, and wait an infinite period of time, the concentration of A, B, C and D will each reach a constant value. When this happens we are at equilibrium. We can define a constant, Keq, which describes the ratio of the concentrations of reactants and products that exists at equilibrium. Keq = [C][D] / [A][B] The value of Keq is determined by the intrinsic relative chemical stabilities of the reactants and products. There is another term, G, which quantitatively expresses the driving force for a reaction in terms of entropy and enthalpy. G = H - TS (G = Gibbs free energy) When G < 0, the reaction proceeds spontaneously in the forward direction; when G = 0, the system is at equilibrium and there is no net reaction; when G > 0, the reaction will not proceed spontaneously in the forward direction. A reaction may be favorable either because there is a favorable enthalpic change (H < 0), or a favorable entropic change (S > 0). Remember: a favorable entropic change corresponds to an increase in disorder. Not surprisingly, Keq can be related to G. If we define a standard state of 1M concentration of each reactant and product, including water (which is actually 55.5 M), the following holds: Go = -RTlnKeq = Ho - TSo (R is the gas constant: 8.3 J/deg.mol) Thus Go expresses the free energy change for going from 1M reactants and products to equilibrium. In thinking about why things happen in biological systems, we must consider the free energy change experienced by the system (enthalpy and entropy). This is true not only of chemical reactions, but also of events like protein folding, the association of substrates with enzymes, and assembly of lipids into membranes. In addition, a thermodynamically unfavorable reaction can be driven by being coupled to a favorable one. In biological systems, this second reaction is frequently hydrolysis of ATP. As you continue through the various sections of this course, you will recognize that reactions (in metabolism for instance) that require ATP are examples of such “thermodynamic coupling.” WATER STRUCTURE AND PROPERTIES It’s easy to overlook the role of water in biochemistry, since we rarely see it written out. But almost all of what happens in biology is aqueous chemistry. Consider that the molar concentration of water in a biological sample is approximately 55 M. Many fundamental aspects of the structures of proteins and membranes are governed by interactions between the components of these structures, and water. Importantly, the concentrations of proteins, substrates, and even salts are far lower than the high concentration of water. This is why water is boss. Water is a very simple molecule, but as a substance water has very unusual properties. For its size, water is quite viscous, has a high boiling point, and has a high heat of vaporization. Therefore water is a liquid over a very large temperature range; this makes it a good solvent for biological reactions. The properties of water result directly from its structure. Because the hydrogens and the oxygen aren't arranged linearly, water has a permanent dipole moment (see below). The water molecule as a dipole. Ball-and-stick geometry of water showing the asymmetric structure and the dipole moment due to the electronegativity of the oxygen atom. Four sp3 orbitals are directed toward the corners of a tetrahedron; two of the electron pairs of oxygen are nonbonded and the other two electrons are shared with the two hydrogen atoms. For example, compare the dipole moment of water (1.84 Debye) with the dipole moment of a symmetrical molecule like ethylene (0 Debye). Due to its dipole moment, each water molecule can interact electrostatically with up to 4 other water molecules--provided the molecules are oriented "properly" (see below). This interaction is called a hydrogen-bond, because a proton (hydrogen) is effectively shared between 2 electronegative (electron-rich) centers (oxygens). The net effect of the extensive hydrogen-bonding in water is that water is somewhat ordered. While this order is entropically unfavorable, the favorable enthalpy resulting from the hydrogen bonds compensates for it. It is water's order that causes its high boiling point, viscosity, etc. The fact that water is a dipole, and its strong tendency to hydrogen-bond, means that polar/charged molecules can interact favorably with water (through hydrogen bonds or charge-dipole interactions), increasing their solubility. Such molecules will thus be soluble in water. This is an important factor in stabilizing protein and membrane structures. The hydrogen-bond is one of several kinds of weak, non-covalent electrostatic interactions which are important in stabilizing the structure of biological macromolecules. We will return to these interactions in more detail later. (Note that the components of biological molecules don't only hydrogen-bond with water, but also with each other, as we will see in the structures of the -helix and the DNA double-helix). THE HYDROPHOBIC EFFECT Favorable interactions with water (hydrogen bonds) help maintain biological structures. However, unfavorable interactions with water are also important in stabilizing biological structures. Think about what happens when you put a molecule of a nonpolar (NP) substance like pentane (C5H12) or cooking oil into water. Water molecules can't hydrogen-bond with pentane (because carbon is not very electro- negative). To maintain their normal number of hydrogen-bonds, water molecules near to the nonpolar molecule must become more ordered. You can imagine that as more nonpolar molecules are added, the situation becomes "worse", from an entropic point of view. This is reflected in the thermodynamics for the addition of pentane to water: Go = Ho - TSo = (-0.48) - (-7.37) = +6.89 kcal/mol (note unfavorable entropy term) Now consider what happens when many nonpolar molecules come together and form a "glob". Now much of the total nonpolar surface area is buried and need not be exposed to water at all. Some water molecules at the water-glob interface are still ordered, and the nonpolar molecules are now more ordered than they were when they were dispersed throughout the water. However, many more water molecules are now less ordered than they were before the glob formed. The entropy of the system has thus increased. The tendency of nonpolar substances to self-associate in water is known as the hydrophobic effect, and it is an entropic effect. The hydrophobic effect is the major force stabilizing biomembranes; it is also a major force driving protein folding and in some cases, driving enzyme interactions with substrates. We will revisit the hydrophobic effect in future sections, since it underlies the thermodynamic properties of most biochemical changes. N N N P N P P P N N P P