François P. Gabbaï, Arthur E. Martell Chair of Chemistry and Distinguished Professor at Texas A&M University, became fascinated with Lewis acids during his PhD, when he studied under Professor Alan H. Cowley, who held the Robert A. Welch Chair of Chemistry at the University of Texas at Austin. The intrinsic properties of Lewis acids—electron-deficient molecules with a propensity to bond with electron-rich anions—piqued his interest and have retained it for over two decades.
His current work, supported by The Welch Foundation, focuses on developing bismuth-based Lewis acids to transport chloride ions across biological membrane mimics. Chloride is an essential electrolyte that maintains the body’s balance between acid and base. Humans have a natural balance in their healthy tissues, where the concentration of chloride is much lower inside than outside each cell. Therefore, the ability to modulate concentrations of chloride ions across biological interfaces such as cell membranes has far-reaching implications.
One possible application of chloride-transport research is cancer therapy. For example, using an artificial chloride transporter to disrupt cancer cells’ natural chloride balance may be an effective way to program the death of those cancer cells. This creates a very motivating backdrop for Dr. Gabbaï’s research, which focuses on the interaction of Lewis acids with anions across many materials and applications.
“My group remains very fundamentally oriented in terms of its research. We are fascinated just by the bonds formed between two atoms. We are nerds. We look very carefully at the way acids and bases associate, the base being the anion and the acid being the Lewis acid, for example, bismuth. And sometimes we look at very, very niche situations. Having the Welch Foundation grant allows us to depart a little bit from the mainstream and look at these more unique topics. The stability that The Welch Foundation provides is very important for us.”
Dr. Gabbaï’s group in the past challenged the notion that Lewis-acid chemistry could only be carried out in a nitrous environment. They decided to test the organometallic chemistry between a Lewis acid and a base in water, which is not a typical environment because water, as a base, could interfere with the reaction. So, the team made boron compounds and threw them in water to see whether they could still capture anions. With this research, they learned to tune the properties of Lewis acids such that they remain available to bind with a base even in the presence of water.
Recently, Dr. Gabbaï and his team characterized a bond between two atoms that is stable at two lengths. This is very remarkable because a bond is typically stable at only one length. But they used a phosphine oxide (the Lewis base) and a carbenium ion (the Lewis acid) to create a bond that was bistable, with two forms of the bond (the Lewis adduct). Tying this new discovery back into his other work, Dr. Gabbai said, “It’s not applied yet to anion transport, but we are thinking about using some of these systems also, again, to fall back into anion-transport topics.”
In another previous investigation, Dr. Gabbaï’s group worked to detect low concentrations of anions like fluoride or cyanide in water, which has many applications in clean water treatment.
“Many of my efforts over the past 25 years have been supported by The Welch Foundation. I would say that The Welch Foundation is central to everything that we do in the lab, even if not directly connected to the topic. We use the synthetic expertise, for example, that we develop as part of the Welch program on other projects. There is always synergy.”