Monday, May 31, 2010

Click chemistry with Big Pharma

There is the click chemistry report by Luke Timmerman from Xconomy (5/19/2010).

It tells the pharma's take on click chemistry and the phone rings on the desk of technology transfer leader of Scripps: Integrated Diagnostics, Life Technologies, Roche, Waltham, ImmunoGen, Seattle Genetics, and Millennium: The Takeda Oncology Company.

Click chemistry as a philosophy existed before a really wonderful reaction was in place. After the miracle reaction was discovered, there is still more convincing work to do. "We (chemists) are trained as most experts to do the hardest things and do them well", stated Dr. Finn, but "we 're going to find or create the easiest reactions". Giving some thoughts, one might just agree that "it's a lot harder to invent a process that works all the time, than it is to make the process that's really difficult work a few times".  

The goal is to obtain function or properties through structures. But our ability (or inability) is poor in predicting what structure would deliver a desired function. The solution is libraries of compounds and screening aided by some "designing". This is THE reason why easier reactions are needed and applied, by big pharm. 

What makes the report more fun is really the other things - scientists, personality, truthful thinking, straight talk, and a lot of character.

By Sharpless, the "sincere-but-absent-minded professor": “I’m sort of the old mad dog who doesn’t believe in a lot of stuff. I have a hard time with biotechnology and green chemistry. It’s hard for me.” 

More: “The point of chemistry is in the middle where everything gets connected. Function is what matters. To me, it wouldn’t matter if you can make malignancies regress with three different types of inorganic salts as long as they weren’t toxic."
Smile, or laugh.

Wednesday, May 26, 2010

Click chemistry into undergraduate labs

I have to say it is somewhat disappointing to see the currrent status of click chemistry in undergraduate labs. One has yet to identify a laboratory in which click chemistry is in use for undergraduate organic chemistry experiment. A few publications in Journal of Chemical Education should give a good starting point.

Back in 2008 researchers from Scripps Institute and other colleges published a wonderful click chemistry paper (J. Chem. Edu. 2005, 1833). It was tailored and tested to be robust undergruduate procedures in click chemistry. It should be an excellent opportunity for touching on some uptodate organic chemistry. Click chemistry between azide and terminal acetylenes can be introduced with Diels-Alder reaction.

Another publication covers alternative reaction media of Diels-Alder reaction as green chemistry solutions (J. Chem. Edu. 2009, 488). Both solventless-room temperature and water-as-solvent conditions are close to click chemistry standards.

A third paper deals with "Synthesis of Imidazolium Room-Temperature Ionic Liquids" (J. Chem. Edu. 2009, 856). It intends to use the synthesis to demonstrate the concepts of green chemistry and click chemistry.  

We look forward to the change. 

Sunday, May 23, 2010

Craig Hawker named to Royal Society for macromolecules work including click chemistry

May 20th, 2010, Craig Hawker  was elected to Britain's prestigious Royal Society. Currently the society includes more than 60 Nobel Laureates.

The right-side bar takes you to Dr. Hawker's laboratory page - he is the director of the Materials Research Lanboratory and a professor of chemistry, biochemistry and materials in USCB.

By the Royal Society: "Craig Jon Hawker is one of the world's foremost pioneers in the design and synthesis of functionalized macromolecules." His publication of dendrimer synthesis using click chemistry demonstrated a beautiful example of click chemistry application in extremely demanding context - one of the most influential publications from Sharpless group.

Peng Wu, Alina K. Feldman, Anne K. Nugent, Craig J. Hawker,* Arnulf Scheel, Brigitte Voit, Jeffrey Pyun, Jean M. J. Frechet, K. Barry Sharpless,* and Valery V. Fokin*, Efficiency and Fidelity in a Click-Chemistry Route to Triazole Dendrimers by the Copper(i)-Catalyzed Ligation of Azides and Alkynes, Angew. Chem. Int. Ed. 2004, 3928.

Wednesday, May 19, 2010

Click chemistry and green chemistry

Click chemistry, in a broader sense, is about using easier reactions to make compounds for certain functions, drugs or materials or anything else. Let us say it is almost purely a scientific term. Green chemistry has been in place for long as a scientific term without much significane until reacent times when everything wants or needs to be "green". To be scientific, not fancy here, I try to connect and compare these two, using the "Twelve Principles of Green Chemistry", by Anastas and Warner.

1.Prevention - It is better to prevent waste than to treat or clean up waste after it has been created.
Click chemistry can do a good job in here since the reaction is addition and high-yielding.
2.Atom Economy - Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
Click chemistry is particularly good at this.
3.Less Hazardous Chemical Syntheses - Wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.
Azide and Copper(1+) do not fit the bill but there are other good reactions in click chemistry - and the reactions are growing.
4.Designing Safer Chemicals- Chemical products should be designed to effect their desired function while minimizing their toxicity.
EPA recently launched ToxRefDB (Toxicity Reference Database) but obviously this type of testing takes time. 
5.Safer Solvents and Auxiliaries - The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.
Click chemistry is good for this, especially the tolerance of water as the solvent.
6.Design for Energy Efficiency - Energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.
Click chemistry is good here - a lot of reactions can be done without much heating.
7.Use of Renewable Feedstocks - A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.
Yet to see the relevance.
8.Reduce Derivatives - Unnecessary derivatization (use of blocking groups, protection/ deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.
Click chemistry wins big for its superior selectivity and tolerance of most functional groups.
9.Catalysis - Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
Click chemistry does well, either by chemical or light catalysts.
10.Design for Degradation - Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.
Yet to establish the relevance.
11.Real-time analysis for Pollution Prevention - Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.
Yet to establish the relevance.
12.Inherently Safer Chemistry for Accident Prevention - Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.
Azides do not play well but there are other types of click reactions such as ene - thiol etc.

Well, green chemistry right now is as big as one can imagine, although many doubts exist among chemists. Let us wait and see.

Sunday, May 16, 2010

Notable oligonucleotide modification using click chemistry

Glen Research, the oligo company, has made some notable claims, finally. In the recent "The Glen Report" (Vol 22, Nnumber 1, May 2010), the company announced its move towards oligonucleotide modification using click chemistry. 

It mentioned the earlier concerns and reluctnace and today's final launch in collaboration with the German company Baseclick whose IP is based on the technology developed by Thomas Carell et al in University of Munich (see the right-side bar?). 

This move is based on the maturation of the nucleic acid click chemistry and the availabilty of necessary reagents, such as alkyne phosphoramidites and catalyst solutions.  

Some noteworthy claims are made: " we now enthusiastically endorse click chemistry. We also expect that it will rapidly become the premiere mothod for oligonucleotide conjugation."

Let us see how soon it will knock out the common post-synthetic labeling methods like amine - NHS ester or thio - iodoacetamide / maleimide. 

Thursday, May 6, 2010

Click chemistry in journal special issues

The purpose is to provide a list of journal special issues on the topic of click chemistry, with links following the titles. They are invaluable resources where a lof of information about click chemistry is compiled in one place. Hope it helps both active practitioners and beginners.

Macromolecular Rapid Communications, 2008, Vol 29, Issue 12-13, special issue: click chemistry in polymer science, issue edited by WH Binder
Australian Journal of Chemistry, 2007, Vol 60, Nomber 6, research front: click chemistry
Chemical Society Reviews, 2010, 39, 1223, highlights the latest applications of click chemistry, guest edited by Finn nand Fokin
QSAR & Combinatorial Science, 2007, Vol 26, Issue 11-12, special issue: click chemistry
Molecules, 2010, special issue click chemistry, in development
Polymers, 2010, special issue click chemistry in polymer science, in development