Histidine

Our next blog assignment was to talk about an amino acid that was assigned to us. I got Histidine.

Histidine is one of the essential amino acids that is needed by the human body. It is abbreviated as His or H. Its IUPAC name is 2-amino-3-(1H-imidazol-4-yl)propanoic acid. Below is the structure of the amino acid in discussion.

Histidine has a carboxylic acid, an ammonium and an imidazole ring in its structure. Of these three functional groups, the imidazole ring is the most significant. It is a common coordinating ligand in metalloproteins, part of catalytic sites in certain enzymes and it is a nucleophile. The ring has 6 pi electrons, 4 from the 2 double bonds and 2 from a nitrogen lone pair. Histidine can exist in 4 forms, depending on the pH of the solution, and it is aromatic at all pH values.

The pKa values of the functional groups of histidine are as follows:

- carboxylic acid pKa = 1.78

- imidazole pKa = 5.97

- ammonium pKa = 8.97

The isoelectric point of the amino acid is at pH = 7.47.

Histidine can be analyzed using UV-visible absorption spectrum. The peaks represented around 220 nm result from an excitation of pi electrons in the ground state molecular orbitals to a low energy state.  

In the 15N NMR spectrum, increase in pH to about 8 causes protonation of the imidazole ring to be lost, giving rise to N-1 or N-3 tautomers. The chemical shift of N-1 drops slightly to about 190ppm while N-3 drops considerably to 145ppm. N-1 tautomer is preferred because of hydrogen bonding to neighboring ammonium. At pH 9, the chemical shifts of N-1 and N-3 are 185ppm and 170ppm respectively. Below is the 1H NMR spectrum of histidine.

Two important peptides that contain histidine in their structures that are found in mammalian cells are histidylated oligolysine (HoK) and histidylated polylysine (HpK). They aid in the transfer of nucleic acid.

Sources sited:
http://en.wikipedia.org/wiki/Histidine
http://omlc.ogi.edu/spectra/PhotochemCAD/html/histidine.html
http://www.enovatia.com/services/nmr/capillary-nmr/

Paracetamol

Our next blog post assignment was to find a synthesis of an organic compound from a chemistry publication and talk about the steps involved in the synthesis and if there were any form of Electrophilic Aromatic Substitutions occurring. Finding the publication and the article was the toughest part. I looked into many sites, including acs.pubs.org, but most of them required a fee.
Anyway, I came across the synthesis of acetaminophen, commonly known as paracetamol. It is sold as an over-the-counter drug that is used as a pain reliever and a fever reducer.

The synthesis of this compound involves 3 steps with the starting material as phenol. Below is the mechanism of how the product, paracetamol, is formed.

The very first step in the process is a nitration process. Because the -OH group is an ortho and para director and an activator of the benzene ring, the products formed from the reaction is the ortho- and the para-nitrophenol. The para-nitrophenol is taken to the next step of the reaction process where the nitro group is reduced to form 4-hydroxyaniline. This is possibly achieved by H2 with Pd-C, Fe with HCl or Sn with HCl. The last step of the process involves the addition of -COCH3 group with the help of AC2O to obtain the final desired product, paracetamol.

If you want to know more about the drug and the history behind it, here is the link to it. Enjoy!
http://www.pharmainstitute.in/drug%20of%20the%20month%20july.htm

A.E. =)