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Abnormal Psychology

Stereochemistry

The structure of an organic molecule can undergo conformational changes due to free rotation around single bonds. Because of steric hindrance, different forms may possess different internal energy. For example, in the staggered form in ethane, the C-H bonds are rotated far apart, so there is less steric hindrance than occurs in the eclipsed form in which the C-H bonds are parallel to each other. For this reason the staggered from will predominate at equilibrium.

Questions involving conformational change often appear on the MCAT. Typically, the context will not directly involve ethane or cyclohexane, but more complex situations. Catalysis facilitated by conformational change occuring upon an enzyme substrate undergoing induced fit is a typical example. Also, be aware that students often miss conformation questions by forgetting the partial double bond character which may be imparted to single bonds through resonance, which will prevent free rotation.




Electricity

Intermolecular Forces

Stereochemistry

Thermochemistry

Chemical Thermodynamics and the Equilibrium State

Proteins

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 given its surroundings. 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 substitute conceptually for the internal energy changes of the system which can, in turn, substitute for the free energy changes. With occasional modification by quantum electrodynamics (as when a particular conformation allow a favorable orbital overlap), the most stable form 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.

This has been another discussion dedicated to bridging fundamental electrostatics, the particle-level of substances, and thermodynamics. You want to have a completely clear idea of the meaning of the internal energy of chemical substances to take into our discussions of thermodynamics (and later, metabolism).




Work, Energy, and Power

Electricity

The Chemical Bond

Stereochemistry

Thermochemistry

The Second Law of Thermodynamics and Heat Engines

Chemical Thermodynamics and the Equilibrium State

Let us discuss conformational changes in the thermodynamic context a bit further to continue in our preview of some important ideas which will be coming soon in thermodynamics. As a mental exercise, imagine that all of the molecules in a sample of a pure substance assumed one of the higher energy conformations.

For example, imagine the rotation of all of the molecules within a sample of ethane from the staggered to the eclipsed conformation. If the temperature has not changed, what has happened to the total internal energy of the sample? The answer is that it has increased.

The electrostatic potential energy has increased at the particle level. Would heat need to flow in or would heat flow out of the system when all the ethane molecules underwent rotation of from the staggered to the eclipsed conformation? Because volume change is not a factor in conformational differences, generally, there is no thermodynamic work occurring for these transformations (pressure volume work) so the answer is that heat flow would have to match the internal energy change, and internal energy change, as we have said, maps back to electrostatic potential energy.

Now imagine if all of the molecules were rotated back to the staggered form. The electrostatic potential energy decreased, the internal energy decreased. Where did the energy go? The answer is negative enthalpy change, i.e. heat flowed out.

Now ask yourself, which direction is more likely? Just like dropping a book on the floor and hearing the sound is more likely than the sound coming back and lifting the book back onto the table, the answer is that the direction in which heat flows out from system into the surroundings and dissipates is more likely.

One final note. Although the state in which all of the molecules are in the staggered state is more likely than the state in which all the molecules are in the eclipsed state, neither state is the most likely state for the system of ethane molecules. The most likely state is the one in which the vast majority of molecules are in the staggered state with a few in the eclipsed state. At that state, the likelihood of a bit of heat coaelescing in the system equals the likelihood of a bit of heat dissipating from the system. The rate forward is the same as the rate backward. The system is in equilibrium.




The Chemical Bond

Stereochemistry

Proteins

Here is a classic example of the relevance of conformational analysis in biochemistry. The enzyme activity of one of the most extensively studied proteins, lysozyme, involves the distortion of a hexose residue of the substrate from the chair conformation into the half chair conformation. This conformational change allows an oxygen atom of the substrate to be in the same plane as a carbocation as the mechanism progresses, enabling the oxygen to stabilize the carbocation by resonance.







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