It has to fold into a three-dimensional structure to be able to develop a function in the organism. That is why Francis Crick, one of the discoverers of the DNA molecule structure, once said: “If you want to understand the function, study the structure”. Likewise, if you want to obtain a function, acquire a structure. And this is precisely what a research group at the Universitat Jaume I in Castelló has done. They have developed a more effective and selective method to construct compounds whose form guarantees certain functions of biological interest.
The method, which has earned the “hot paper” status by the editorial board of the prestigious scientific journal Angewandte Chemie International Edition where the research will be published, consists in constructing a template on which the molecule with the desired structure is assembled. Specifically the objective was to form a macrocycle, that is, a ring-shaped molecule. The annular structure is fundamental when it comes to achieving certain properties. In fact numerous drugs, such as anti-carcinogenics or antibiotics, have a cyclic structure.
Now the question is, how can a ring on a molecular scale be constructed? To date, there have been mainly two approaches. One of them relies on chance: group the molecules that are to integrate the final compound together and wait for them to assembly and form an annular structure. “That’s almost like dropping a thread and hoping it will form a circle when it lands. Some statistical laws intervene here, but they do not guarantee more than 10% effectiveness for that to happen”, indicates Santiago Luis, professor of the Department of Inorganic and Organic Chemistry at UJI and the researcher responsible for the study. In short, only 10 out of 100 molecules end up forming a ring shape.
The second approach involves the use of templates around which the molecular ring is assembled. Those most widely used to date have been the positively or negatively charged atoms. The problem is that these spherical templates offered by nature have fixed diameters and this results in a limited set of templates which leaves little room for refinements. “These spherical systems oblige us to make completely symmetric molecules, and what we’re really interested in is in playing with form”, adds Santiago Luis.
The novelty of this technique presented by the UJI researchers lies in the fact that it is the first time that an anionic organic template (negatively charged) is used to prepare ring-structured pseudoprotein compounds. The idea is to construct a molecule which acts as a chemical negative for the molecule that we wish to obtain, thus serving as a structure around which the latter can be constructed. This works in a similar fashion to the way jewellers create a circular mould around which molten gold takes the ring shape intended.
“The election of an appropriate molecular template allows us to obtain these structures with high selectivity and effectiveness. We are talking about effectiveness between 80% and 100%”, Santiago Luis affirms. The main contribution of the UJI group work is, precisely, to leave behind the work with set molecular templates and open the way to directed template modification. This is why the editors of Angewandte Chemie International Edition are interested in highlighting this finding.
“What we’ve done is to conceptually prove that we can design and construct anionic organic templates that we can use perfectly well to favour a given chemical reaction”, Santiago Luis concludes.
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