stereoisomer

Molecule of the Day: Thalidomide

Thalidomide (C13H10N2O4) is a white powder that is insoluble in water under standard conditions. It was marketed in the late 1950s to the early 1960s as a morning sickness drug for pregnant women, but eventually gained infamy and was withdrawn from the market after it was shown to be responsible for many congenital defects in infants whose mothers consumed it.

Thalidomide was first developed in West Germany during the 1950s, and was found to be a highly effective antiemetic (drug that reduces vomiting and nausea). It was then marketed as a drug to treat morning sickness, which is a common physiological effect of pregnancy. As drug testing regulations were less stringent then, extensive human trials were not required for drugs to be produced and sold. Some companies even claimed that thalidomide was “completely safe” and had “no adverse effect on both mother and child”.

However, this was proven wrong, and thalidomide was withdrawn from the market in most countries in the early 1960s due to public pressure. Sadly, it was too late; an estimated 10,000 children were born with deformities during this period due to their mothers’ thalidomide usage. Birth defects caused by thalidomide included heart and eye deformities, underdeveloped or missing limbs, as well as brain damage.

It is believed that thalidomide produces these effects by binding to cereblon, a protein that is critical in limb formation and myeloma cell proliferation in foetuses. Additionally, it inhibits angiogenesis (the development of blood vessels), which is critical in the formation of limbs as they contain highly complex systems of blood vessels.

While the S-isomer (below right) of thalidomide was found to be responsible for these congenital defects, the problem cannot be solved by administering the R-isomer (below left); thalidomide racemises in the body to form a mixture of stereoisomers via keto-enol tautomerisation. Hence, S-thalidomide will still be formed in vivo even if pure R-thalidomide is administered.

To synthesise thalidomide, phthalic anhydride and glutamic acid are first reacted to form the corresponding phthalimide, which is then dehydrated to form the cyclic acid anhydride. It is then reacted with urea to produce thalidomide.

Requested by anonymous

Medschoolmanic's Guide to Surviving Organic Chemistry

Almost every pre-med I know has a common enemy: Organic Chemistry. Why is it that we hate this class so much? Is it trying to visualize everything in 3D? Is it the nomenclature? Is it because we have no idea where the hell hydrogen is going!?

NEVER FEAR! Because Organic Chemistry is doable! All you have to do is follow these simple tips. 

Keep reading

Carbohydrates, like Glucose and Furanose are great ways to test you’re knowledge of Ochem reactions, stereochemistry, and biology (metabolism). 

Glucose reacts like an Aldehyde 

- Oxidized to Carboxylic Acid, Reduced to primary Alcohol. 

Ketones can only be reduced to 2ndary alcohols

Know the fisher projection and ring structure of Glucose well. 

Streochem 

  • Chiral center is any atom with 4 different entities attached to it.
  • Enantiomers are mirror images of each other. That means ALL chiral centers in one enantiomer is reversed in the other.
  • You can’t have stereoisomers if you don’t have a chiral center.
  • Diastereomers - more than one chiral center, inversion of stereochemistry on some but not all of its chiral centers. For examples, diastereomers would have stereochemistries of ®-® vs ®-(S). Another example of diastereomers would be ®-®-(S)-® vs ®-®-®-®.
  • In rings, it is easier to assign stereoisomers as cis/trans rather than R or S. Cis is having the same groups on the same side of the ring. Trans is having the same groups on different sides of the ring.
  • A compound will have a total of 2#chiral centers stereoisomers if it is not meso.
  • Meso compounds may have chiral centers, but as a molecule, they are achiral and optically inactive.
  • Meso compounds reduce the total number of stereoisomers.
  • Stereoisomers have the same chemical properties.
  • Enantiomers have the same physical properties.
  • Diastereomers have different physical properties.
  • Note: in biological molecules, people use D and L for R and S, respectively.
  • Caution: D and L (absolute configurations) are NOT the same as d and l (relative configuration). Read the section below on rotation of polarized of light for more details.


Remember: Anything around a single bond can rotate freely so remember to rotate things around single bonds to find internal planes of symmetry for possible Meso compounds 

Glucose is catabolized in Glycolysis, ATP activates the substrate, Glucose, in substrate phosphorylation allowing it to be broken into two 3 carbon chains, pyruvate.  

anonymous asked:

Chemistry Question: Can you help me understand optical isomerism, like how to identify chiral carbons in molecules and visualising the isomers in 3D? Sorry if any of my terminology seems dodgy - English chemistry education terms might be slightly different (not sure)

Chiral basically means that all of the substituents around the center carbon are different. CHBr2Cl (Dibromochloromethane) isn’t chiral cause there’s one hydrogen, one chloride, and two bromine atoms. CHBrClF (Bromochloroflouromethane) is chiral cause the four substituents around the carbon are all different. But anything DIRECTLY bonded to double/triple bonds isn’t chiral either cause you treat the atom/s (from a double bond) as two single bonds with the same atoms. (there’s one exception below)

Also if the substituents are different alkanes/alkenes/alkynes bonded to the central carbon then it’s also considered chiral. Like this (but remember that the double/triple bond cannot be directly bonded to the central carbon):

In a ring structure, a carbon is chiral if it’s asymmetric like this; it’s kinda hard to describe so I drew (another) picture:

Both the carbons attached to OH and NH2 are chiral, but I’m only going to look at the carbon attached to OH (or C1). C1 is considered chiral cause it’s attached to one hydrogen, a hydroxyl group, and two different “substituents”. To determine that you have to draw the arrows (as shown above) until they’re perpendicular to the carbon you’re looking at (C1 in this case) and if both collections of atoms are different then it’s chiral.  So you have OH, H, CH2/CH2/CH2, and CH2/CH-NH2/CH2. My professor/s did it differently, but I like this way better.

The green carbons below are also chiral (you treat the ether linkage to the green carbon as one substituent; same with the carboxylic acid).

Because this molecule has one chiral carbon it has two stereoisomers (two non-superimposable enantiomers, S and R). The dashed/wedged hydrogen and methyl group denote the “3D” arrangement. The “S” version has the hydrogen behind the CH3 group while the “R” version has the hydrogen in front of the CH3 group, if you were to rotate the entire R version so it has the same orientation as the S version without manipulating anything else. 

So “R” will look like this after a 180 degree rotation:

You can see that it’s the enantiomer cause H/CH3 are in a switched 3D position.  

Same thing applies here:

You rotate the molecule on the right until it has the same orientation as the one on the left (and realize that the blue part is in the back this time). So the right looks like this once you rotate it back to the left’s orientation:

(green/red in front, blue in back)

One thing to note is that chiral carbons in 3D are represented by different colors for the substituents and different sizes too.

There are exceptions to the “4 different substituents around the central carbon” rule when it comes to chirality, but I forgot those (except for Allenes and certain coordination compounds). Aside from Allenes, you learn about some of those in inorganic chemistry, especially coordination compounds.

Allenes are basically compounds that consist of 3 carbons with double bonds connecting them. If R1 isn’t the same as R2 and R3 isn’t the same as R4 then it’s chiral.

I hope this helped!

Just a separating funnel with a slightly colored upper, organic layer. It contained an alkaloid derivative what was made from cinchonine. The coloration resulted from a decomposition what was caused by harsh reaction conditions. Interesting is, that only 0,05% of my compound decomposed to give this colored compound, but even in this low concentration it had an intense color as seen.

Cinchonine is an alkaloid found in Cinchona officinalis. It is used in asymmetric synthesis in organic chemistry. It is a stereoisomer and pseudo-enantiomer of cinchonidine what is similar to quinine what was isolated from the cinchona tree and found in Tonic water.

Cinchona alkaloids

3

Resolution of a compound by forming salt with an optically pure chiral acid. 

The compound what I started from is orange and when it’s protonated by an acid it turns deep red (as seen on the picture). The interesting is, that according to the experimental results only one of the stereoisomers react with the acid, the other is sterically hindered, so the other enantiomer of the acid would be need to form the salt. 

The marbles at the bottom of the flask are molecular sieves, they absorb any water what is present, and they prevent my compound from decomposition, since it’s sensitive to water.

helenebm  asked:

Hi I was wondering as you are a molecular biologist if you could tell me some creative ways to get people to learn protein structure( the anotomy of protein)

I delayed answering this for a while because I wanted more information on the target audience, for instance, if you’re talking to middle school students vs. college students, my approach would be very different based on the level of complexity you’re aiming for, but I never heard back from you and I just had a really cool idea, so I decided to answer anyways!

Proteins are made up of amino acids. There are approximately 20 naturally occuring amino acids. Some scientists recognize other molecules as amino acids, too, but when I took biochemistry, my professor only had me memorize twenty (Thanks Dr. T!). Below is a great poster that I actually bought to help me memorize my amino acids!

External image

(image source: http://fineartamerica.com/featured/amino-acids-table-dan-cojo.html)

We refer to amino acids in three different ways: (1) their molecular structure, (2) their one letter abbreviation, and (3) their three letter abbreviation. Here’s an example for Lysine:

Molecular structure:

External image

One letter abbreviation: K

Three letter abbreviation: Lys

(You’re probably wondering why we chose “K” for Lysine instead of L, right? Well, that’s because “L” represents leucine, another amino acid.)

The primary structure of a protein is the order of amino acids in a straight line, which are linked by amide bonds, which when linking two amino acids are called peptide bonds. Of course, primary structure isn’t the end of it. You have secondary, tertiary, and sometimes quaternary structure for proteins and large peptides. Here are examples of the four structures:

External image

(image source: https://www.boundless.com/physiology/textbooks/boundless-anatomy-and-physiology-textbook/general-chemistry-2/organic-compounds-39/protein-structures-317-11437/

***This link has awesome explanations of other protein stuffs***)

Okay, so now to actually answer the question! When I was in elementary school, my music teacher had this game called Composer Bingo. It was a bingo board with a bunch of classical composers on it like Bach, Beethoven, Vivaldi, etc. I was thinking you could do this with amino acids! Amino acids are the building blocks of proteins. Since there are three ways to refer to a protein (four, including the full name), you can make bingo cards with a mixture of molecular, one letter abbreviations, and three letter abbreviations and then call out the full name of the amino acid. So, if the bingo caller says Lysine, there are 3 potential answers, but your students will have to know the 3 different symbols for Lysine to actually win the game! Since there are 20 amino acids and 24 boxes (5 x 5 = 25 - 1 (free space)), you’re going to have to adjust this game by either adding additional boxes or making the card 4x4, so there are only 15 boxes. Or you could be redundant and put the same amino acid on the same card twice (I wouldn’t do it more than twice even though you could do it three times), using more than one of the symbols for the same amino acid, e.g. K and Lys on the same card.

N.B. (for those interested): Amino acids, like many organic molecules, have chiral carbons, which is an organic chemistry concept. Basically, it means they may look the same on paper, but they are different in 3-D, which causes them to have different properties, causing some to be biologically active and others to be biologically inactive. Or, both are biologically active and one might do something bad and the other good. A classic case is the drug thalidomide; one stereoisomer works wonders for morning sickness during pregnancy. The other stereoisomer is a teratogen and causes malformation of limbs. Each amino acid has an L and D isomer, but the L is the one that is pertinent in eukaryotes. D amino acids are sometimes found in more primative life forms like prokaryotes and archaea.