Pyrroles, Dipyrrins and Prodigiosenes: Oh My!

Nitrogen heterocycles are essential components of many naturally occurring molecules with biological or medicinal activity. Dr. Alison Thompson,  Professor of Chemistry, and her group are dedicated to finding new uses for these building blocks and producing new molecules with superior properties and therapeutic efficacy. 

Alison faces many challenges in achieving her goals, including the development of alternative and improved methodology for the preparation of functionalized pyrroles; the synthesis and applications of dipyrrins and dipyrrinato complexes; and the synthesis and biological evaluation of prodigiosin derivatives (prodigiosenes).

Often imbedded in functional materials, pyrroles also constitute the core of many natural products with biological activities and medicinal properties, making the easy preparation and manipulation of functionalized pyrroles essential. Pyrrolic chemistry is a challenging area in which there is significant reliance upon traditional reactions. The Thompson group’s work with pyrroles has enabled them to access scaffolds that were previously unavailable or difficult to obtain and they (and other chemists around the world) use some of their new procedures in the construction of dipyrrins and prodigiosenes.

Alison recognized early in her career that dipyrrins were ripe for further exploration. Although dipyrrins are extensively utilized as intermediates in the synthesis of tetrapyrroles, relatively little is known about the amenability of dipyrrins towards derivitization or their ability to tolerate the routine conditions required for the functional group interconversion or elaboration of appended groups. As well, the complexation chemistry of dipyrrinato ligands is surprisingly undeveloped beyond the formation and applications of boron difluoride (BODIPY) complexes. Alison’s group has recently embarked upon a project to prepare alkali dipyrrin complexes, which were previously unknown, and investigate their utility in reactions that are inaccessible when free-bases or hydrobromide salts are used. Their current work involves the synthesis and characterization of several series of dipyrrinato alkali complexes, along with an investigation of the physical properties and reactivity of these compounds.

Most drugs used against cancer are “anti-proliferative”, rather than “anti-cancer”, meaning that these drugs simply cause the death of cells, both cancerous and normal. As such, it is the degree with which these drugs are taken-up by cancer cells, compared to normal cells, that dictates the selectivity of the drug for cancerous cells over normal cells. In actuality, drug selectivity for cancer cells is usually rather modest and side-effects are frequently severe. Alison’s group is trying to prepare and evaluate prodigiosene conjugates whereby the conjugate portion selectively targets breast cancer tissues. Their current research efforts involving prodigiosenes are geared towards pursuing the synthesis of conjugates containing moieties that specifically target breast cancer cells and thus further improving the physiological profile.

Alison’s group is currently funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada and the Canadian Institutes of Health Research (CIHR).