After more than six decades, Queen’s University chemistry professor emeritus Victor Snieckus continues to patrol the laboratory.

After more than six decades, Queen’s University chemistry professor emeritus Victor Snieckus continues to patrol the laboratory.

Watching Victor Snieckus dash around a classroom is enough to make you wish that you too were almost 80 years old. Surrounded by a gaggle of current and former students, each of whom would be just a fraction of his age, the Queen’s University chemistry professor emeritus leads them with an aplomb shaped by decades’ worth of laboratory work, thoughtful reflection and rich personal history. The audience eagerly follows every move as he jots equations on a blackboard or juggles ideas to spark debate. Nor are those ideas confined to chemistry — at various turns he will cite the 19th century Russian romantic composer Alexander Borodin, who was also a prominent figure in the field of aldehydes, and 1960s music legend Carlos Santana, whose notions of success in life apparently resonate with Sneickus’ own.

Directed ortho metalation can been carried out on aromatic and heteroaromatic compounds in conjunction with halogen dance reactions, which provide the ability to migrate elements such as iodine to a thermodynamically stable anion.

Directed ortho metalation can been carried out on aromatic and heteroaromatic compounds in conjunction with halogen dance reactions, which provide the ability to migrate elements such as iodine to a thermodynamically stable anion. Photo credit: Snieckus Innovations

A demonstration of the power and advantage of directed ortho metalation for synthesis, whereby individual functional groups can be selected as part of a cross-coupling strategy.

A demonstration of the power and advantage of directed ortho metalation for synthesis, whereby individual functional groups can be selected as part of a cross-coupling strategy. Photo credit: Snieckus Innovations

In fact, after a short time spent with the man everyone knows as Vic, it is tempting to wonder if the secret of his own success might be bottled in some way. And if it could, rest assured that he would undoubtedly revel in the process of synthesizing it and then provide the finished product to you without taking any royalties. Indeed, that attitude might ultimately turn out to be the essence of the secret itself.

Born in 1937 in what was then the very sizeable independent state of Lithuania, Snieckus and his parents traversed the tattered landscape of postwar Europe until a family connection enabled them to emigrate to Canada. Arriving in rural Alberta in 1948, he recounts his life from that point forward as a series of crucial encounters with intellectual mentors of one sort or another. Snieckus vividly recalls the day in the early 1950s when a chemistry teacher dazzled him with the brilliant blue colour change of a cobalt reaction. His passion for the field kindled, the flame was subsequently fanned by instructors at the universities of Alberta, California in Berkeley and Oregon in Eugene. He returned to Canada for post-doctoral work at the National Research Council, then to the University of Waterloo and finally to Queen’s, which he never left.

Along the way Snieckus acquired a taste for the challenges surrounding the synthesis of various agents, a specialty that spawned his life-long love affair with lithium. More specifically, much of Snieckus’ seemingly boundless energy has been invested in the technique of metalation, whereby a metal atom attaches to an organic molecule in order to foster synthetic reactions. More specifically, his work has focused on lithiation, the process whereby atoms of this metal attach themselves to organic molecules. Snieckus explored the subject extensively for a 2005 book series, The Science of Synthesis, which he co-edited.

“The chemistry starts with a strong base in a group of heteroatoms, coordinates the lithium complexes, acidifies the hydrogen, then causes a deprotonation event that yields lithiation,” he says.

The most practical application of this technique is directed ortho metalation (DoM), which makes it possible to carry out substitutions in aromatic complexes. Such molecular arrangements are commonly found in drugs and drug candidates, where DoM expertise can accelerate an agent’s progress to commercial potential. Elsewhere, Snieckus fondly recalls taking on an assignment from the giant multinational Monsanto, which was struggling to come up with a chemical treatment for a fungus called Gaeumannomyces graminis var. tritici. It causes the disease Take-all, which devastates the roots of grass and cereal plants in temperate climates. “We solved this problem by simply sending one compound to Monsanto,” he says, adding that this particular one was enough for the company to extract an active agent. “They found the molecule that attacks the fungus.”

For Snieckus, such accomplishments are not merely a matter of problem solving; Monsanto’s happy outcome was the result of his own group’s understanding of the problem’s molecular foundation. This observation represents his defence of “pure” science and the often-abstract discoveries that follow from it, which are nevertheless essential to the concrete accomplishments sought by industry and society in general. Speaking to the prestigious German academic body Beilstein-Institut, Snieckus expanded on this approach. “For academic synthetic organic chemists, the challenge is to avoid repetitive, me-too chemistry evident in the plethora of papers appearing of reactions that vary only in the conditions, catalysts and ligands and pay little heed to showing that the reported method has advantages over previously published results from other and even their own laboratories,” he says. “If me-too chemistry is avoided and fundamental mechanism is understood, serendipity will have a greater opportunity that, in turn, will lead to discovery of new chemistry.”

Snieckus continues to adhere to this outlook, perhaps now more than ever. In 2004 he co-authored a paper in Angewandte Chemie that explored the implications of the complex-induced proximity effect, an aspect of deprotonation that is useful to planning organic syntheses. As recently as this past June he was among the coordinators of the largest ever Boron in the Americas conference at Queen’s, which included more than 150 participants discussing the latest perspectives on boron-related chemistry.

This penchant for bringing the virtues of pure research to the applied needs of industry inspired the venerable industrial chemist and Queen’s University benefactor Alfred Bader to approach Snieckus a decade ago, just as he was being promoted to emeritus status. Snieckus intended to carry on as if little had changed but Bader had a more tempting suggestion. “He gave us $1.5 million in seed capital to create a company that would solve these kinds of synthetic problems for a paying clientele,” recalls Snieckus.

The resulting firm, Snieckus Innovations (SI), was set up in the university’s research park in 2007. Operating like a contract research office, a staff made up of doctoral-level chemists began to synthesize materials in amounts ranging from milligrams to multi-grams. The products included heterocyclic building blocks, aromatic building blocks and complex molecules generated from the group’s compound library, which features some 5,000 “on-the-shelf” highly pure compounds, including about 500 building blocks or fragments.

Snieckus says some of the collaborations struck through SI have been open-ended and downright freewheeling, such as their ongoing work with Boston-based Vertex Pharmaceuticals. “We were trying to sort out their research priorities when one chemist finally said to us, ‘just do something new’,” recalls Snieckus. “That’s music to us.”

Other clients, such as the pharmaceutical giant Pfizer, turned to SI specifically as a source of expertise in directed ortho metalation, which had been demonstrated in a scientific paper published more than a decade earlier.

As an academic unit, SI can qualify for funding from the federal Natural Sciences and Engineering Research Council, which would be off-limits to a typical commercial laboratory. Besides ensuring confidentiality for its customers, SI also allows them to retain the intellectual property rights to the final product. That stipulation was important to Monsanto, which now markets Latitude, a fungicide containing silthiofam, the ingredient that eliminates Take-all from farm fields. Another client, Bristol-Myers Squibb, likewise worked with SI to develop drugs it now markets to treat HIV infections and high blood pressure.

Most recently Environment Canada approached the company to synthesize molecules pertaining to oil sands extraction, research that the government department wanted to keep in the country. “It was connected with the Fort McMurray fire, which was spewing out polycyclic aromatic hydrocarbons,” says Snieckus. “They needed analytical data on those agents and wanted to find out what the products were when they degraded.”

As contented as Snieckus has been with his academic career, this latest chapter of his life highlighted by SI has enabled him to become even more fulfilled by raising the profile and respectability of industrially oriented chemistry. This kind of undertaking is often dismissed as little more than dull efforts to improve a business’s bottom-line but when it comes to the sophisticated task of synthesis, Snieckus is fond of quoting Sir John Cornforth, who won the 1975 Nobel Prize in Chemistry for his work on the stereochemistry of enzyme-catalyzed reactions. “Problems about pollution from the by-products of a process are nowadays taken into consideration in the planning, not tackled retrospectively,” Cornforth argued in a 1992 lecture that Snieckus regards as a classic. “And no nonsense about the pure ideal of total synthesis limits the choice of raw materials or methods. Anyone who has helped to plan an industrial synthesis tends to pity the poverty of the criteria that an academic synthesis must meet. Work of this sort ought to be held in greater respect and published more often than, alas, it is.”

Snieckus repeatedly echoes this sentiment and if there is a secret to this ongoing enthusiasm for his chosen subject, it lies in this ability to nurture a passion for work that even knowledgeable observers regularly regard as passionless. He therefore reserves his greatest respect for the Italian chemist Primo Levi, who survived the horrors of Auschwitz and went to write novels, essays and poems that conveyed a passion for the many different facets of science that Snieckus is only to happy to showcase. “For me chemistry represented an indefinite cloud of future potentialities that enveloped my life to come back in black volutes torn by fiery flashes, like those that had hidden Mount Sinai,” wrote Levi in his definitive book The Periodic Table. “Like Moses, from that cloud I expected my law, the principle of order in me, around me, and in the world.”