The ring that never closed.

The ring that never closed.

The scheme ended with an imidazopyridine. Our 2018 QNRF Undergraduate Research Experience Program proposal was built around making substituted members of that family and examining their biological activity. I joined the team as an undergraduate chemistry researcher. There were two synthesis routes in the plan, with the expected products to be characterized before biological evaluation. By the time we completed the final report in 2021, we had to record that the intended imidazopyridines had not been obtained by the proposed route.

What we could isolate and investigate were imines, commonly called Schiff bases. The final report describes three such compounds and their spectroscopic characterization. They had initially occupied an intermediate position in the chemistry, but they presented questions of their own. We began examining how they responded to anions, particularly cyanide, using colour and spectroscopy instead of treating the unsuccessful ring closure as the end of the work.

One experiment gave a particularly visible answer. A yellow sensor solution shifted toward orange when cyanide was added under the conditions recorded in the report. In the UV–visible spectrum, the band near 380 nm diminished as a new band near 450 nm grew. The reported detection limit for that sensor was 1.42 × 10⁻⁵ M. Other Schiff-base compounds gave different responses to cyanide and hydroxide. Those differences mattered: a striking colour in a test tube was a useful starting observation, but it did not by itself establish selectivity or performance in an environmental sample.

The proposal had also envisaged biological evaluation. Colleagues in the biology team investigated compounds designated CMP5 and CMPB in triple-negative breast-cancer cell lines. The final report describes stronger effects of CMP5 than CMPB in several cell proliferation and migration experiments. Its measurements of SURVIVIN and c-MYC transcripts made the picture more complicated. In some treated cells, c-MYC expression increased when a reduction had been expected. Some gene-expression comparisons were not statistically significant under the reported analysis. These were in vitro experiments; they did not establish direct PRMT5 target engagement or the efficacy of a cancer treatment.

Then laboratory access became another experimental constraint. COVID-19 restrictions interrupted the later work, and the planned protein-level follow-up, including comparison with Western blot measurements, was not completed. The final document therefore contains something more complicated than an unsuccessful reaction scheme followed by a new success: it contains measurable chemical behaviour, exploratory cellular effects and mechanistic questions that were still unanswered when the project ended.

Our original proposal treated the Schiff bases as intermediates on the route to imidazopyridines. We could not complete the intended ring closure, but we isolated imines whose spectra and anion responses we could characterize. By the final report, those measurements occupied more space than the intended products. The change in direction was forced by the results: the chemistry we had actually achieved was more interesting to investigate than another account of the product we had failed to make.