Part 1 - Assigning stereochemical configuration

Background

In order to construct a structure-function relationship of R-HPCDH and S-HPCDH, we first need to comprehend some important properties of the substrate, hydroxypropylthioethanesulfonate (HPC). Specifically, what is meant by designating HPCDHs by R- and S-?

Some molecules can exist as two non-superimposable mirror images and are called enantiomers (enantios, Greek, opposite). Their chemical bonds are connected in the same order but differ in their spatial relationship, just like your left and right hand. Hence, these molecules have a "handedness", called chiral (cheir, Greek, hand). The only way to convert one enantiomer into another is to break and reform a chemical bond (which would likely happen only with the addition of a large amount of energy). A molecule may have none or many chiral centers. Chiral centers are labeled R (rectus, Latin, right) and S (sinister, Latin, left). Often chiral centers are tetrahedral carbon atoms with four different substituents attached to them. There are various experimental techniques to determine the absolute configuration (the stereochemistry) of molecules. We will assign the chirality of atomic models by graphical visualization and a few easy steps.

Rank the substituents

Check

Atom type colors
Carbon Hydrogen Oxygen Sulfur
JMol Help

Exercises

  1. Look for the carbon that has 4 different substituents (functional groups) attached to it.

  2. run JMol scriptSubstituents are ranked according to atomic mass. The higher the atomic mass, the higher the rank. Here's the Periodic Table of the Elements if you need this information. In order to assign the stereochemistry, we want to place the lowest ranked substituent (in this case hydrogen) away from us and into the plane of the screen with the hydroxyl group (OH) at the bottom. The JMol window should resemble the depiction of the chiral carbon on the right.

  3. Rank the 3 remaining substituents. The atoms directly connected to the chiral carbon are Oxygen, Carbon and Carbon. Of these three which should be ranked first? Use the drop downs to rank the highest group.

  4. Distinguish between the two carbons by examining what they have attached to them. The carbon on the right has 3 hydrogens attached to it while the one on the left has 2 hydrogens and a Sulfur atom. Which is higher in atomic mass and therefore ranked higher, three hydrogens or two hydrogens and sulfur? Rank the final two groups accordingly using the drop downs.

  5. Check your answer to see if you're correct.

  6. Is the progression from 1st to 3rd in a clockwise (R) or counter-clockwise (S) manner?

HPCDHs that catalyze the R-form of HPC to products much better than the S-form are designated R-HPCDHs. Substrate selectivity is a common characteristic of enzymes

Proceed to part 2