Research Description

Synthesis, isolation, characterization and use: Our research group at Dalhousie is absorbed with synthetic chemistry based around the naturally occurring polypyrrolic framework. Our synthetic chemistry background and experience encompass: natural products isolation and synthesis; design, synthesis and evaluation of new molecular systems with enriched optical and photochemical properties; manipulations of and new routes towards pyrrole- and dipyrrin-containing frameworks and complexes; and the construction of macromolecules via self-assembly and through the painstaking step-wise formation of covalent bonds. The photochemical properties of many of the systems that the Thompson groups designs facilitate applications in materials and biomolecular sciences, e.g. sensors, tags, photodynamic therapy/inactivation. The Thompson group is involved in several collaborations where researchers with expertise in other disciplines provide insight that complements our synthetic expertise. Such associations provide trainees with opportunities across a wide variety of research areas and demonstrate that organic and natural products chemistry is key to many areas of science. A synergistic yet entirely separate program investigates medicinal aspects of tripyrrolic prodigiosin-based frameworks. 

Dipyrrinato complexes: The Thompson group develops synthetic methods that advance the utility of the dipyrrolic dipyrrinato construct. Boron complexes of dipyrrins are known as BODIPYs, and are applied as fluorescent tags/dyes in molecular biology, with increasing use in electronic materials and emerging nanotechnologies. Our group develops enabling synthetic methodology that allows the synthesis of new dipyrrinato ligands and complexes featuring previously-unattainable substituents and thereby exhibiting novel and enhanced electronic properties. Invited talks include Gordon, ACS, International Porphyrin and Phthalocyanine Conferences. We pioneered Cl-BODIPYs, a new genre of BODIPYs designed to be facile to substitute at boron, thus expanding the repertoire of BODIPYs in photophysical and biochemical/tagging applications. We developed unprecedented methodology to remove and/or amend the –BF2 moiety of F-BODIPYs, thus enabling new photophysical applications. We synthesized and characterized the parent (unsubstituted) dipyrrin, despite its inherent instability and claims by others that this compound was elusive. We developed a quantitative-yielding bench-top route to F-BODIPYs that requires neither special apparatus nor anhydrous solvents. We developed a probe to evaluate ligand donicity of dipyrrins and aza-dipyrrins. we developed pyrrolide-based Ru(II) trials that exhibit unprecedented light: dark toxicity profiles. Our invited article in Chemical Reviews, Advances in the Chemistry of Dipyrrins and their Complexes (ChemRev2007, 107, 1831-1861), was described by reviewers as a “truly outstanding, landmark review” and a “fine, timely and important review”. This review remains a go-to resource in the field, as demonstrated by continued citation (more than 600 citations March 2021). According to the Web of ScienceTM, as of March 2015 (and ongoing to the present time), this highly cited paper receives enough citations to place it in the top 1% of its academic field based on thresholds for the field and publication year, demonstrating the lasting impact of our contribution to this area.

Natural product-derived prodigiosenes: The Thompson group is an expert in the synthesis of derivatives of the natural product prodigiosin, drawing upon our organic chemistry expertise. One of our designs is a lead compound for breast cancer and leukemia, following impressive in-vivo hollow fibre assays and toxicity profiles in mice. Other analogues are antimalarials and/or antimicrobials. We collaborate extensively to evaluate activity and build structure activity relationships, to guide us in the design and synthesis of variants with improved and more selective activities. 

Development of new synthetic methods: We design and develop synthetic methods to efficiently prepare needed functionalities and structural frameworks. As examples, we developed: a route to new annulated bis(pyrrole)s with skeletons akin to natural product indolic analogues; a chemoselective route to ester debenzylation; a thiono-ester route to protected pyrrole; and synthetic strategies utilizing the rich chemistry of sulfur to temper the nucleophilicity of pyrroles.