Topicity LAD (webpage)
From WikidChem
Topicity is a term that refers to the environment in which a given atom, functional group, or molecule resides. It can refer to the constitution, conformation, or configuration of a given group. Thus, although all protons are essentially the same (they all have a +1 charge and a mass of 1.67 * 10^-27 kg, for example), they can be said to be inequivalent in terms of their behavior if their topicities differ. (Note: Topicity comes from the Greek "topos", meaning place, and the suffix -ity, meaning expressing a state or condition; thus, topicity can be thought of as the "placeness" of an atom or group.) There are certain possible options for the topicity of a group. They are similar to those for chirality. They are: Homotopic - A group is said to be homotopic to another group if its environment is superimposable on that of another group. Heterotopic- A group is generally said to be heterotopic to another group if its environment is different than that of another group. Subcategories of heterotopicity include: enantiotopic - A group is said to be enantiotopic to another group if its environment if their mirror images are not superimposable (like chirality - enantiomers). diastereotopic - A group is said to be diastereotopic to another group when its environment is completely different than the environment of another group.
The reason this last distinction is important is because diastereotopic groups will always react completely differently, whereas enantiotopic groups will react identically unless they are reacting with a molecule that happens to be chiral.
Remember, a molecule cannot be said to be universally homo-, hetero-, enantio-, or diastereotopic; this nomenclature is only relevant when we are asking the question, "Compared to what?"
To examine the concept of topicity, let's consider the Liver Alcohol Dehydrogenase enzyme. For some great diagrams, refer to this website: external link: https://webspace.yale.edu/chem125/125/Stereo/topicity.htm
When we look at the methyl protons of ethanol, we see that they are all constitutionally homotopic (they are all single bonded to a central carbon atom). They are also configurationally homotopic, becuase if we rotate about the C-C bond we can make any of the positions equivalent. However, when we consider conformation, this is not the case. As you can see, the gauche and anti protons are diastereotopic to each other (since one is far closer to the hydroxyl group than the other). The gauche and gauche' groups are enantiotopic to each other since they are the same distance from the hydroxyl group, but on opposite sides. However, in real life this distinction is somewhat trivial since the energy barrier to rotation on this bond is very small (so the sites are practially equivalent).
Next, let's look at the methylene protons. They are also constitutionally homotopic. However, they are not configurationally homotopic, because you cannot rotate them about the C-C bond such that they become equivalent. They remain mirror images; therefore they are configurationally enantiotopic. By similar logic, they are also conformationally enantiotopic.
