Sunday, October 13, 2013

Nobel Prize or not

Well, the 2013 Nobel Prize went to computational chemistry. 
Entirely deserving.

The prediction of Click Chemistry in the race settles.
Probably too much prediction going on in this "tricky" business: 
Thomson Reuters, Sciencewatch: Modular click chemistry 
Radio "The voice of Russia": Complex reactions just a click away
The San Diego Union - Tribune: Scripps chemist vies for second Nobel

The field should contribute to something more significant in application, discovery of some drugs, some important materials, etc. 
A ton of publications do not necessarily signify the chemistry. Needless to say, some publications do not really reflect the philosophy / spirit of click chemistry. 
Fairly speaking, the field is too young for a Nobel Prize. Likely someday it will but no more predictions please. 

Let us focus on some really significant work.  


Saturday, June 29, 2013

Chirality in drugs

“Asymmetric catalysis” won the Nobel chemistry prize in 2001 for Dr Knowles, Dr Noyori and Dr Sharpless. The pursuit of chiral drugs has been feverish for ever. Among resolution, separation, chiral synthesis, biocatalysis, etc. there is the effort of using enzyme to synthesize its own inhibitor. The Economist reported such an effort in the article "telling right from left", September 19, 2002, stated as following:

Dr Sharpless goes even further. People are not very good at making medicines, he says. Life is short, while conventional drug-discovery is a long and uncertain process. So why not put nature, which is much more patient and sophisticated at doing the job, to work directly? Just as a mould can be used to make a copy of a three-dimensional object, Dr Sharpless proposes to use biological targets as templates to guide the formation of their own perfect drugs. He calls the method “click chemistry”, because of the ease with which the molecular building-blocks fit together. He and his colleagues have already used it in the laboratory to identify a molecule that blocks an enzyme related to Alzheimer's disease. Sometimes the best ideas are also the most obvious.


Sunday, April 28, 2013

Energetic / click chemistry and chemical industry

Energetic chemistry resides at the core of click chemistry concept. The energetic nature gives high reactivity, short cycle times, clean reactions, less purification, therfore cost-saving. At the same time energetic chemistry is highly underutilized due to the obvious concerns about the very same energetic nature. It is particularly true in chemical industry and pharmaceutical industry. 

Things probably will change through a few means: demonstration of long-term success and safety by the existing hazardous chemistry specialty companies; education and business development with pharmaceutical companies; and most of all, competition pressure and overall cost-benefit calculation.

Where and when the decision has to be made, it will be. As history often shows, changes happen under pressure not by forward thinking.

Friday, April 26, 2013

Novasep azide chemistry & click chemistry

Novasep has high expertise in azide chemistry, including several hundred ton annual usage 
of sodium azide and large scale azide reactions. 

One example is the in-situ generation of explosive gas methylazide (N:C ratio 3:1) for CuAAC click chemistry. 

Sunday, April 21, 2013

Phosphaalkyne azide click chemistry

Dalton Trans 2013, Choong et al   3/21/13

1,3-cycloaddition of phosphaalkynes & azides to triazaphosphole
Uncatalyzed, regioselective, quantitative or near-quantitative yield

Near click chemistry except necessary protection of P(III) from oxidation. 

Triazaphospholes as polydentate ligands in metalloorganic, dendrimer, polymer context 


Saturday, April 6, 2013

Human Cholesterol-binding proteins, a lot more

Hulce, Cognetta, Niphakis, Tully & Cravatt
Nature Methods 2013, 10(3), 259
A lot more proteins bind to cholesterol than previously known.

Sunday, March 31, 2013

Coupling biocatalysis and click chemistry

DOI: 10.1039/C3CC38674K
1,2,3-triazoles: pharmacophores and ligands
Impressive driving force and selectivity.

Friday, March 29, 2013

Azide chemistry, energetic chemistry, hazardous chemistry, click chemistry

The spring-loaded energetic chemicals, azides and acetylenes, provide the necessary driving force of the "ideal" and non-stoppable triazole formation reaction, the most prominent of click chemistry concept. It is practiced in many academic groups worldwide, maybe in some pharmaceutical, biotech companies as well. Azides are often used to introduce amino groups in organic synthesis. Scanning any issue of JACS or JOC, one would see a bunch. 

In discovery chemistry where properties are sought, azide chemistry is good, click chemistry is wonderful.

When it comes to pharmaceutical or fine chemicals production, however, one tries to avoid azides as much as possbile, simply due to the very energetic nature of it. Azides are hazardous, no question about it - particularly when it come to large scale production. 
The avoidance however could add more steps of synthesis. Not good.

Double edged sword. Something has to give? 

A few companies have had success with many hazardous chemistries, up to metric ton scale. This competence separates them from competition. Extensive testing helps: impact & friction sensitivity, thermal stability, dust explosivity, reaction calorimetry. Stepwise scale-up helps: from lab to kilolab to pilot to plant. Engineering with prevention and in-case scenario in mind helps. Everyone's commitment and best training helps. Seamless work as a team helps. 

One day when a product by azide click chemistry is so successful and needs to be made by tons, it can be made.   

Sunday, March 24, 2013

Craig Hawker receives ACS Award in Polymer Chemistry

Feburary 2013 

Hawker, director of the Materials Research Laboratory at the University of California, Santa Barbara, has had an impact on the field of dendrimer chemistry, block copolymer, controlled free-radical polymerization - many of which are practical to be in commercial markets. 

He was one of the ground-breakers in convergent growth dendrimer synthesis. He was the first to introduce and apply click chemistry concept to dendrimer and material synthesis. See the 2004 key article by Hawker Group and Sharpless Group. 

Tuesday, January 1, 2013

In situ click chemistry 10 years mark

Happy New Year 2013

C&EN did a brief piece "revisiting 2002" and took a look at in situ click chemistry. Some key points:

Original publication by Scripps Group in Angew Chem Int 2002, 1053 
Acetylcholinesterase directs the synthesis of its own potent inhibitor when induced-and-fit
Difficulties: large quantity of protein, little quantity of inhibitor, slow reaction, etc
Ten years have seem a few successes but limited adoption

Copper catalyzed version (CuAAC) enjoyed widespread popularity
Original publication by the Group in Angew Chem Int 2002, 2596
Forget Not the Key ----  
Fast "molecular discovery" for functions