CLICK-FUN

Functional Molecular Systems by Template-Guided-Click Assembly

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 Obiettivo del progetto (Objective)

'One of the most challenging tasks in current chemical research is the creation of molecular systems with defined activities, such as catalysts or target specific molecular recognition materials for separation and sensing. Current state of art in this field utilizes primarily screening and combinatorial synthesis whereas de novo design is using with the limited success rate. This project proposes an alternative, innovative approach to create the functional molecules such as artificial receptors and catalysts by combination of template-guided click chemistry assembling (TGCA). Specifically, pair of highly functionalized fragments: an azide and an alkyne is assembling on the template. For receptors the desired target molecule is used as the template whereas the transition state analogue is used for the catalyst templating. Only best combination of substrate pair due the proximity of azide and alkyne functions may undergoes click fusion (Huisgen cycloadditon, up-to-date most powerfull click chemistry tool). The resultant triazole linked hybrids accumulates the interaction sites of single partners thus should effectively recognized the template (receptor) or should possess the desired catalytic activity (analogy to catalytic antibodies). The presented idea will be utilized for the construction of receptors for the important anticancer drug taxole and its precursor as well for artificial hydrolytic enzymes. The coupling pairs of azides and acetylenes will be iteratively selected from aminoacids, di- and tripeptides and specific compounds which are known to have high affinity to desired templates, thus increasing the probability of success. This project may delivery a new approach for production of new functional molecules and the resultant receptors and catalysts may find practical application in manufacturing and analytics of taxane family (receptor, purification) and organic synthesis (artificial enzymes).'

Introduzione (Teaser)

Creating molecules to fit onto receptors is the way forward in designer chemistry. European research has developed a new technique to produce interlocking molecular units based on click chemistry.

Descrizione progetto (Article)

Catalysts change the speed of a chemical reaction without being altered themselves and they are highly specific. Without them, many reactions that we take for granted simply wouldn't happen at room temperature. Applications range from catalytic convertors in cars to super detergents and oil refining. The technology can also be used to design specific drugs.

Removing stubborn stains from a favourite shirt, for example, requires the help of catalysts. Each molecule in the oil stain is a substrate (or receptor), which combines with a tailored catalyst to form an intermediate molecule. In this form, the oil breaks up into the component soluble units. The degraded stain washes out of the clothing, releasing the catalyst to work again.

Neat specific molecules like this are a very attractive proposition to the chemicals industry. One of the biggest challenges however is to create these molecular systems by design. The EU-funded Click-fun project aimed to create artificial receptors and catalysts fusing click chemistry with design and manufacture of a template.

Click chemistry is a relatively recent philosophy whereby small molecular modules are joined together to make large designer structures, quickly and efficiently. For receptors, the target molecule is used as the template. The intermediate is the template for the catalyst. The combination of the two procedures has resulted in template-guided click chemistry assembling (TGCA) technology.

Click-fun researchers focused on joining an azide, which comprises three nitrogen atoms (N3-) together with an alkyne. Alkynes have very reactive triple bonds. The simplest of the group is acetylene used for oxyacetylene welding. The team used the most advanced powerful click chemistry tool to join the best combination of substrate pairs. The resulting molecule would then fit onto the receptor or be an effective catalyst.

The coupling pairs have huge scope in the biology world as the basic azide and ethyne groups exist in protein building blocks, amino acids. A good example of a potential templating molecule is taxol, which has so far been used as a chemotherapeutic drug. Taxol therefore has the potential for forming new complexes using click chemistry.

The Click-fun team has assembled an extensive library of azides manufactured during the project. Applications for this recent technology include the production of new functional molecules, designer catalysts for manufacturing and artificial enzymes.