Topicity HDYK & hands (webpage)

From WikidChem

How Do You Know? (hdyk): The question is whether Liver Alcohol Dehydrogenase removes one of the methylene Hydrogens preferentially. It does, and we can prove this if we design an experiment.

If, somehow, you could acquire ethanol where the pro-S hydrogen was always deuterium, you could test whether LAD preferentially removes the pro-R hydrogen by examining the final aldehyde product with NMR spectroscopy. If the aldehyde product also always has deuterium, it is possible to say the LAD only removes the pro-R hydrogen. If the LAD had not discriminated between the pro-S and pro-R hydrogens, then the amount of deuterium remaining in the aldehyde product should have been halved.

However, this approach becomes problematic because it is difficult to find ethanol that always has a deuterium in the pro-S position. We can resolve this if we crowd the reaction with "H2" (thereby using the law of mass action; i.e. the rate of a chemical reaction is directly proportional to the product of concentrations of available reactants) and then make it go in the reverse direction. (starting with an aldehyde with deuterium). If we then enable the reaction to proceed in the forward direction by removing the excess "H2", we find that all of the deuterium we produce is within the aldehyde.

   * Good that you called the source of the new hydrogen "H2", since it actually is a different molecule in biological systems. Hopefully we'll get to this next semester, if not you'll see it in biochemistry. - JMM

This implies the enzyme discriminates perfectly between the pro-S and pro-R hydrogens and always adds/removes hydrogens from the same site. It does not say which site it actually removes hydrogens from, however, as the same result would have been equally plausible if the enzyme only removed pro-S hydrogens.

The solution to this particular problem involves using multiple enzymes. If we use one enzyme to add "H2" and another to remove hydrogens, we can tell if the two enzymes interact with the same hydrogen or not by marking the hydrogens as either H or D. (However, it seems as if it is still necessary to know the hydrogen that one of enzymes affects as a standard of comparison; One of the questions I still have about this is how they found the orientation (affecting pro-S or pro-R) of the first "frame of reference" enzyme.)

   * You're right that this is not trivial. It involves using a molecule that has a different (non-H) group that can be replaced by D to give ethanol in a process whose stereochemical outcome is predictable. We'll discuss such reactions next semester. Ultimately this has to trace back to transformations involving a compound of know absolute configuration (à la Fischer and his "genealogical" system). - JMM

The hands part of the website involves an observation and a number of questions:

Observation: The two hands are Constitutional homomers because each hand has the same parts joined in the same order.

1. How do we consider the two hands in the webpage external link: https://webspace.yale.edu/chem125/125/Stereo/topicity.htm with regards to Configuration?

Answer: They are Configurational enantiomers, as the hand on the left is a left hand, and the one on the right is a right hand. The two can be mirror images of each other, and it would be necessary to break certain "bonds" to get them to superimpose.

2. What about with regard to Conformation?

Answer: The hands are Conformational diastereomers because they are bent at slightly distinct angles. (note- even if they were bent at the same angles, the hands would still be mirror images of each other and therefore not superimposable). They can be easily transformed into corresponding Conformational shapes, however, so they might be regarded as different phases of vibration within one "same" energy minimum (in chemical language).

Here, however, our nomenclature runs into problems- when these two hands are in corresponding conformations, they cannot be said to be Conformationally enantiotopic, but then if we call them Conformationally homotopic, we need to remember the two hands are not superimposable.

It is important to remember enatiomerism is a property of how objects are connected configurationally, and not their specific, mutable shape at one point.

JYW 5:35 PM 12/7/06 last modified by J Michael McBride (mcbride) on Dec 9, 2006 4:10:41 PM