Saturday, March 27, 2010

Click chemistry book review - Cumulenes in Click Reactions

By an industrial chemist, this book has collected, cataloged, classified and summarized many types of click reactions under the umbrella of cumulene click chemistry. The author, being a true expert monitoring the field since 60s, has extensively covered the reactions in a very balanced manner, by describing the main features of the reactions and giving carefully selected examples. They all point to original journal publications for further reading. The book clearly demonstrates how vast the field is and how many reactions can potentially be regarded and / or developed into true click chemistry. Although the author states no intention of exclusiveness, it is quite exclusive in my opinion. And it is updated as well - even if we admit that the click chemistry field grows extremely fast these days.

Saturday, March 20, 2010

Click chemistry highlighted in Chemical Society Reviews Special Issue

Chem. Soc. Rev., 2010, DOI: 10.1039/c003740k

I would say it is a feast - a colletion of the most representative pieces of click chemistry. It  is certainly a must-read for both active practitioners and the ones who are looking to step in.  

Edited by Drs Finn and Fokin and writen by leading groups, this special issue highlights the most recent status of click chemistry and its applications in several major fields. By doing so it effectively reinforces the importance of click chemistry concept. 

The three fields are covered: biomolecules, materials, and different environments. In each of them click chemistry has been demonstrated to be a powerful and growing tool. As the editors pointed out (again): "the more tolerant the connection reaction between molecular building blocks, the more diverse the blocks that can be brought to bear on any problem, and the more likely it will be that solutions to the problem can be found and produced in quantity. If indeed it is useful function that is the goal, then keeping chemistry simple is a useful rule to remember."

"In this deliberate eschewing of more subtle synthetic techniques is an implicit challenge to organic chemists that make complex structures by complex methods (can complex structures be made by simple methods?)......." Quite a challenge to say the least.

Click chemistry: function follows form.   

Monday, March 15, 2010

Click chemistry builds molecular library for antituberculosis agents

The authors identified a potent and selective mPTPB inhibitor I-A09 with highly efficacious cellular activity, from a combinatorial library of bidentate benzofuran salicylic acid derivatives assembled by click chemistry. They demonstrated that inhibition of mPTPB with I-A09 in macrophages reverses the altered host immune responses induced by the bacterial phosphatase and prevents TB growth in host cells. The results provide the necessary proof-of-principle data to support the notion that specific inhibitors of the mPTPB may serve as effective antiTB therapeutics.

This is another good example that a small library, 80 in this case, built by click chemistry, yields an inhibitor with IC50 at 1.26 uM in a single selection round. Notably, the products were collected by simple centrifugation after 48 hr reaction, assessed by liquid chromatography–mass spectrometry to be at least 70–100% pure and used directly for screening without further purification.

Also, the effective strategy is used again here for the acquisition of active site-directed, potent, and selective PTP inhibitors  - tethering a nonhydrolyzable pTyr mimetic to an appropriately functionalized moiety in order to engage both the active site and a unique nearby subpocket. This strategy of utilising click chemistry has been reported a few times and proves to be productive.

PNAS, 2010, 4573.

Thursday, March 4, 2010

BARAC - yet another strain-promoted copper-free click chemistry

Believe it or not, this one is called BARAC. 

Click chemistry is certainly not "done". This time, instead of electronic properties, Bertozzi group looked at the strain energy by introducing some level of double bond nature into the octyne ring structure. The choice was amide bond which displays well-known partial double bond nature (C=N). "Brushing against the line between stability and reactivity without crossing it", this is another beautiful example of "rational design" in physical organic chemistry. "Gratifying", The click reaction rate was superior, 12-fold faster than DIFO the difluoro-version. The group then evaluated BARAC derivatives in their "traditional" cell glycobiology imaging where cell surface carries glycan azide. It demonstrates superior performance than DIFO and DIBO. Modular and scalable synthesis of BARAC offers more opportunities and wider applications of this new copper-free click chemistry. 

Champagne finished, time to work on the next click chemistry.

Journal of the American Chemical Society, 2010, DOI 10.1021/ja100014q

Monday, March 1, 2010

Click chemistry patent - cyclopeptide imaging agents

US 7666392 B2

A good example of the application of click chemistry in biomedicine and diagnostics.

This patent by Hartmuth Kolb et al, was issued on February 23, 2010.
The title reads as "Click chemistry derived cyclopeptide derivatives as imaging agents for integrins". It described radiolabeled cyclic peptides and their use in imaging, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomagraphy (SPECT). The graph shows one example where two units of cyclic peptides, via a PEG linker, are conjugated to the radiolabel by triazole click chemistry. It is obviously advantageous to introduce the radiolabels by the "near-perfect" click chemistry.

Note Dr. Kolb is one of the authors of the influential article "Diverse Chemical Function from a Few Good Reactions".
Kolb, Finn, Sharpless, Angew. Chem. Int. Ed. 2001, 40(11), 2004