PURITY IS A VIRTUE, and it is all the more desirable when you are dealing with chemical reactions. A research team at University College Dublin has come up with a way to make a pure chemical or "building block" that could help boost the design and discovery of new therapeutic agents, writes CLARE O'CONNELL
“Our interest has been in trying to develop new processes and trying to make them more selective,” says Pat Guiry, professor of synthetic organic chemistry at UCD.
His team was looking at the actions of metal-bound compounds called “ligands”, and a class of chromium-containing ligands were showing some promise in helping to speed up reactions.
“We had looked at many processes that other people had looked at, and we found that our ligands were particularly selective, but we hadn’t found them to outshine others in any process,” he explains.
But then they started to use them in a type of reaction called “homoallenylation”. That changed the game and the team’s chromium ligands suddenly started to rise up the league.
In particular, their approach resulted in a clean and user-friendly chemical product from the reaction, which had previously stumped chemists working on it.
“This is a particular reaction where with one reagent and one substrate there is always the possibility of getting two products, and in the literature this has been looked at by many researchers over the last 20 years but it always suffered from the problem of people getting mixtures, neither one product or the other, but always both,” explains Guiry, who directs the university’s Centre for Synthesis and Chemical Biology.
That resulting mixture made the reaction and its products more difficult and expensive to use in chemical synthesis, which was a barrier to them being used in industry, he notes.
“The problem when you get the mixture is that they are incredibly difficult to separate and that difficulty in separation has meant that people don’t use those particular products very often as a key building block in natural product synthesis or in the pharmaceutical industry.”
By developing a way to ensure the reaction’s end result is pure on many levels, the researchers have made this chemical building block more available to drug discovery.
“Where our work sits in context is that we have now developed a process that makes this building block that no-one has been able to make before [in such a] selective way, and then that building block can be be transformed by a number of chemical reactions to make products that are interesting,” says Guiry, who worked with Dr Vincent Coeffard and Miriam Aylward, funded by Science Foundation Ireland and Ircset.
He likens their discovery to coming up with a new Lego block to offer to people who want to build something. “It makes it possible to add this to the other reactions that people use to design and make drugs, so it will be of interest to the pharmaceutical and the biomedical industries and it’s of interest to chemists because now there is a new way of making these compounds. It’s through reactions that people in the pharmaceutical industry make the drugs that they eventually sell, so having this new reaction and building block will help feed into their pipeline and may in the future give rise to more drugs that will keep the industry going.”
The news excited interest in chemical circles when details of the reaction were published late last year in the journal Angewandte Chemie. The UCD researchers have gone on to develop several further chemicals from their building block, capitalising on its purity. "Anyone can make mixtures," says Guiry. "The real trick is to make things pure."