Stereochemistry

Electricity

Intermolecular Forces

Stoichiometry

2nd Law of Thermodynamics

Amino Acids & Protein Structure

Predicting the most stable conformation of a particular organic molecule often involves simply predicting the lowest electrostatic potential energy state of the molecule understood as a system of charge densities. Where are the bonding electrons? Where are the nuclei? Which form allows the like charges to be furthest away from each other and the unlike charges closest together? Let us discuss why this kind of reasoning is thermodynamically valid. When do 'lowest energy' and 'most stable' mean the same thing? Thermodynamics deals with systems comprised of large numbers of particles. Thermodynamic attributes do not describe the behavior of individual molecules. As the molecules of which a system is comprised interconvert among conformers, the system as a whole seeks an equilibrium state, in which the system assumes the lowest free energy possible. For most problems of this type, the free energy change, enthalpy change, and internal energy change are roughly equivalent. Entropy differences are not great and volume change is minimal. In cases like this, the electrostatic potential energy changes of molecules can stand in for the internal energy change of the system, which can, in turn, stand in for the free energy change because the internal energy change leads to heat flow. Bearing the quantum electrodynamic nature of things in mind such as when a particular conformation allows a favorable orbital overlap, the most stable form, the one favored by equilibrium, will be the one in which opposite charges are as near to each other as possible and like charges as far apart as possible.

This type of reasoning becomes very important when you move on to the question of protein conformation in biochemistry. Intra-molecular forces (forces within the same molecule) of both types, attractive and repulsive, which are electrostatic in nature, play a large part in determining protein conformation, for example. The α helix, for example, depends on strong, intramolecular hydrogen bonding to stabilize the structure, which are attractive forces. Repulsive forces can be significant, as well, such as with the collagen helix, which is stabilized by steric repulsion of pyrrolidone rings of modified proline residues. These rings do not overlap when the chain assumes the helical form.