Heterocyclic chemistry: Not just what you do but how you think about it


Heterocyclic chemistry is linked to a number of scientific discoveries and breakthroughs, both directly and indirectly. Professor Colin Suckling of the University of Strathclyde discusses the links and the thinking behind it

There are fashions in science just as much as in any well-populated walk of life. Sometimes they are associated with following up genuinely new discoveries that are of long-term significance. Perhaps the discovery of the structure of DNA is the strongest example of this in the context of heterocyclic chemistry. Other times there is a neat new idea for which the significance is exaggerated by the discoverers hoping to get more recognition for it. I can think of several examples but I will not cite them because I do not wish to demean the scientists involved. It’s probably fair to say that most of the useful and practical heterocyclic chemistry accessible to everyday laboratories has been discovered now. That being the case, new and significant discoveries of reactions are relatively rare. Such discoveries as come along are usually relatives of well-established reactions.

The value of heterocyclic chemistry

This does not mean that there is no longer any interest or value in heterocyclic chemistry, quite the contrary. It’s precisely because it is mature and capable of making highly sophisticated designed chemical compounds that it retains power and importance in science. I’ve described in previous Special Reports how various new compound classes have been discovered with value in many different applications ranging from therapeutics to television screens. In both of these applications and everything on the spectrum of technology in between there are new developments that depend upon heterocyclic chemistry. In this note, however, I want to point out not the physical manifestations of the chemistry in terms of compounds in bottles but a relatively new and powerful way of thinking about not only chemistry but also biology.

Everything is connected

According to John Henry Newman’s “Idea of a University” each subject should look after itself drawing its own boundaries and, by implication, guarding them. That 19th century concept is quite the opposite of how we need to think today. New things and useful things happen at the interface of conventional scientific disciplines and when these disciplines mix. This is by no means a new idea either but what has changed that is relevant to heterocyclic chemistry is a relatively new sub-discipline called “Chemical Biology”. Chemical biology has become an extremely important area in the application of heterocyclic chemistry. Essentially what it does is to use small, specially designed and synthesized heterocyclic compounds to investigate how the big molecules of biology work together. Put another way, the heterocyclic compounds probe the mechanism of action of biological systems. Because, as I’ve explained before, the structure of a heterocyclic compound can be exquisitely tuned to its purpose the chemical biological approach is a powerful way to investigate significant aspects of basic biology.

Theory and practice

What I find most attractive about chemical biology from the point of view of an academic scientist interested both in basic science and practical applications is that chemical biology bridges these two endeavours. In our own work, for example, we have designed some anti-infective compounds to be fluorescent so that we can follow their passage in the target infectious agent, typically a fungus or a parasite. This gives us important information about how our compounds work. In another project we have some very effective potential therapeutic compounds that treat inflammatory diseases but until recently, we did not understand how they worked. Thanks to a collaboration with the US Army Laboratory, AMRID, we have found out a good deal about their mechanism of action using a variety of techniques within the chemical biology domain. In both cases, if we’d simply kept our heads down as chemists we’d have made little progress. Because we’ve opened out into chemical biology to complement our medicinal chemistry studies we have potentially a much more useful product because we know how it works. So it’s not just what you do in the laboratory, it’s the way that you think about it.


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