Isomers

[andruejaysin]

Could someone explain the difference between the d,l isomers and the r,s? Or are these simply different names for the same thing?

 

[fastandbulbous]

Imagine your right hand represents the shape of a molecule. Now your left hand consists of exactly the same components, placed in the same order across the hand, yet you cannot superimpose your left hand over your right hand as they're arranged differently in 3D space (try putting a left hand glove on your right hand!).

Now if a carbon atom has 4 different groups attached to it, it can be arranged in either a 'right handed' orientation, or a 'left handed' orientation which cannot be superimposed over each other in a 3D representation (referred to as optical isomers). As receptors in the body, enzymes etc are all made up from amino acids of a particular 'handedness', they respond to one optical isomer much more than the other, as the site of interaction is also a 3D structure.

d & l assignations generally refer to the direction in which they rotate a beam of polarized light when shone through a solution of the optical isomer. R & S configuration refer to the absolute configuration of the molecule as laid out in the IUPAC rules (it involves determining whether the order of size, when seen along the axis of one of the substituent bonds to the carbon atom is in a clockwise or anticlockwise direction).

As to the actual rules, I've never been able to reel them of the top of my head, so you'd need to look at a book/website about determining absolute configuration

 

[phase_dancer]

You might find something of interest in this post Isomers of MDMA

 

[andruejaysin]

I'll probably need to print that and read it a few dozen times, but that's why I love this site, even the tough questions get answered. Thanks, guys.

 

[Smyth]

You made the generalization that most enzymes respond much more to one isomer than the other. I do not disagree with this statement in principle, since in the majority of cases this is exactly what is observed. I'd just like to point out however that a racemic pair of isomers frequently display synergistic effects. This means that isomer separation is sometimes required, but is not always totally necessary.

 

[fastandbulbous]

I'd just like to point out however that a racemic pair of isomers frequently display synergistic effects.

If you mean MDA, that's because (S)-MDA goes for the SERT/DAT & causes efflux while (R)-MDA goes for the 5HT2a receptor. Other than that, I can't think of an example of the above. The less active optical isomer generally cannot interact as well with the active site of a protein, simply because it's 'the wrong shape' for optimal interaction with the active site; so unless the two different isomers target different active sites, I can't see that happening

 

[leungkachong]

Absolute config. is done by rating the groups as a function of the atomic number at the chiral centre. The higher the number, the greater the importance. In the case of ties you just keep going down the chain, and doubles bonds count as double the value of singles in weighting looking down the chains (hmm... shoddy description, remind me never to become a teacher). Rotate the lowest importance to point away from you. Now starting at the highest importance group, continuing to the second highest, and then to the third. If your going clockwise it's "R", if your going going counterclockwise it's "S" (for sinister... mwahaahah).

I wonder if there's any way you could but some group that produces steric strain to stop the umbrella-like inversion of nitrogen's p orbital w/ the 2 lone electrons that stops amines w/ 3 unique substituents from being chiral unless really low energy. (How) Could you restrict this inversion and still maintain enough of the nitrogen character to still be active, and maybe test the QSAR computational models of receptors? or something....

 

[Smyth]

In the 7-azabicycloheptane scaffold inversion barriers are unusually large. You wont see this with hydrogen, but as steric bulk increases the effect becomes more noticeable. Amides are normally planar. Well in 7-azabicycloheptane they are pyramidal. This is because nitrogen does not like the transition state where is would have to be sp2 hybridized. This is because tetrahedral gerometry is 109 deg whereas trig planar is 120 deg. Note the highly constrained bridgehead is unable to open out and this therefore makes rehybridization energetically unfavorable.

 

[CreativeRandom]

Ketamine and Dopa (used for parkinsons) are enantiomers, which is the name for these "left/right hand glove" isomers.

Why are both S and R ketamines psychoactive? Coincidence?

Interesting that R- Dopa is toxic while L-Dopa is beneficial. Perhaps an R-Dopa inhibitor would make the drug more effective as L-Dopa metabolizes into R-Dopa?

 

[BilZ0r]

^ Um, Yes, it is just a coincidence that both ketamine enantiomers are active, lots of drugs are not steroselective.

L-dopa is metabolized to R-dopa? That's news to me, any proof that this happens in any clinically relevent amounts?

 

[CreativeRandom]

It is the reason they stopped using L-Dopa as a treatment for Parkison's.

Just a small amount, but enough to cause problems.

 

[BilZ0r]

They stopped using L-Dopa? Recent articles show no hints of this.
Trends Pharmacol Sci. 2005 Jul;26(7):341-4.
The 'magic' of L-dopa: why is it the gold standard Parkinson's disease therapy?
Mercuri NB, Bernardi G.

Where are you getting your info from?

 

[CreativeRandom]

A biology textbook, 7th edition, for a college class.

 

[BilZ0r]

I don't think it's correct eh.

 

[evlove]

(+) and (-) describe optical activity

R and S describe actual structure or absolute configuration

D and L refer to the molecule's structural relationship to D- or L- glyceraldehyde (and does not always describe optical activity)

 

[fastandbulbous]

D and L refer to the molecule's structural relationship to D- or L- glyceraldehyde (and does not always describe optical activity)

Ah, right - I forgot about that (never really could see the reason for that!), only used to use absolute & optical activity designations (all amount to the same thing anyway with things like amino acids). Biochem has a certain obsessive neatness to it.

 

[stefan]

this is all slightly amusing to me, i mean, from the responses that were made, it's obvious who has taken organic chemistry and who has not. the orginal question is basic stereochemistry, however, my studies have not yet explained to me the relationship between D- and L- glyceraldehyde, but im guessing that is just acting as a standard ? ex. simililar to an internal standard in a chromotography experiment, except it is relating to molecular rotation ?

 

[fastandbulbous]

^ I think it's to do with the fact that glyceraldehyde is effectively the smallest optically active sugar molecule (a triose). Things like that are supposed to be a help for biochemistry type stereochemistry where you can end up with a shitload of chiral centres on one 'simple' molecule (try playing 'spot the chiral centre' with something like glucose. It has enough so that using the absolute configuration notation produces what looks like a crap hand at Scrabble - if I remember correctly, glucose has 4 centres of asymmetry; once you get to disaccharides like sucrose, using abs. configuration will make all but the strongest cry!)

 

[CreativeRandom]

Turned out it was just misleading. They talked about entianomers, then mentioned some strange stuff that was made to help pregnant women which was bad, and under it had examples of L-Dopa and R-Dopa. Personal research showed these were about Parkinsons. My bad.

I hear that the original naming of isomers was about optics, but currently there are many methods to do it to produce the same results every time, such as using crystallization.