Günter Wulff (1935 –2023): Father of Molecular Imprinting

Günter Wulff, internationally well known for his invention of Molecular Imprinting, passed away on December 11, 2023 in Erkrath-Hochdahl, Germany, not far from the University of Düsseldorf, where he made his greatest discoveries. A passionate researcher and deep conceptual thinker, he greatly advanced our understanding of polymer chemistry. Günter Wulff, internationally well known for his invention of Molecular Imprinting, passed away on December 11, 2023 in Erkrath-Hochdahl, Germany, not far from the University of Düsseldorf, where he made his greatest discoveries. A passionate researcher and deep conceptual thinker, he greatly advanced our understanding of polymer chemistry (Figure 1). Günter Wulff and schematic representation of the molecular imprinting of specific cavities in a cross-linked polymer with a template containing three different binding sites. This scheme can be found in Günter Wulff′s classic review in Angewandte Chemie.2 It has undergone many variations to this day, but its essence has not changed much. Born on February 19, 1935, Günter Wulff studied chemistry in his hometown at the University of Hamburg. For his Ph.D. he went to the University of Bonn, where he worked in the group of Rudolf Tschesche on the isolation, structure elucidation and synthesis of complex glycosides from plants. In his own independent research, Günter Wulff initially continued this work and published a number of papers, including the discovery of a novel glycoside structure of particular biochemical relevance.1 However, when he presented this work at a conference for young scientists, an elder and highly respected colleague approached him and suggested that he leave the field of his academic training and find his own topic to make his own distinctive mark. This advice changed his life and led him into the field of polymer chemistry. From the beginning, Günter Wulff was fascinated by the elegance of biomolecular catalysis, especially when crystal structures revealed structural details of how the enzyme chymotrypsin uses the three-dimensional arrangement of various catalytically active functional groups to stabilize the transition state of its proteolytic reaction – with a specific participation of the famous oxyanion hole. Wulff considered the possibility of using polymer chemistry to mimic the highly complex and sensitive natural example in a straightforward way. The pursuit of this concept led to the discovery of molecular imprinting and a deeper understanding of the many parameters that govern this process.2 Most of this work was done after he accepted an appointment to the Chair of Organic and Macromolecular Chemistry at the University of Düsseldorf. However, it took four decades of intensive synthetic and analytical work, as well as endurant optimization before the Wulff group could celebrate the breakthrough discovery of catalytically active polymers.3, 4 The best systems are macroporous crosslinked polymers polymerized around templates that resemble the transition state of the desired transformation. They are able to catalyze carbonate hydrolysis reactions with more than 400,000-fold acceleration and imprinting factors of more than 1000. In-depth studies revealed true enzyme-like properties with Michaelis–Menten kinetics and a pronounced catalytic capacity K−1TS between 108 and 109, approaching that of natural enzymes. Today imprinted polymers are discussed as new supramolecular materials with potential applications as highly selective sensor systems, chromatography and extraction phases, innovative medicinal diagnostics, enzyme mimics and catalysts.5 Many of these have already been demonstrated in the early work of Günter Wulff himself. However, Günter Wulff also returned to his favorite class of natural products – carbohydrates – and combined them synthetically with established monomers. Conventional emulsion polymerization of these novel building blocks led to new materials with superb properties as superabsorbers, which were tested as diaper materials in chemical industry.6 Since these copolymers were made from renewable natural resources, they were shown to be biodegradable. The European Union honored this highly innovative invention in 1996 with the CEREAL Prize, which Günter Wulff generously shared with the members of his group who contributed to the development. In the course of his research on branched polymers, Günter Wulff realized the potential of creating a very large number of stereogenic centers along a polymer chain derived from achiral monomer building blocks initialized by a chiral trigger event. This led to a very fruitful research program on main chain chirality of polymers, which the Wulff group carried out with living anionic copolymerization. Günter Wulff discovered the stereodirectional influence of chiral diads and became deeply involved in stereochemical events in polymeric systems.7 In this respect, he had always admired the fundamental pioneering work of Kurt Mislow and suggested that Mislow receive an honorary doctorate from the University of Düsseldorf. It was a moving scene when Mislow and his old friend Albert Eschenmoser, who gave the laudatory lecture, met in person. Kurt Mislow grew up in Düsseldorf and fled the Nazi dictatorship with his parents in 1936. With tact and empathy, Günter Wulff accompanied his guest as Kurt Mislow returned to the places of his youth after decades. Günter Wulff was also a passionate teacher who trained generations of chemistry, biology, and medical students in organic and polymer chemistry in Düsseldorf. As he hurried along the corridors, carrying his green folders with handwritten notes, everyone knew he was on his way to the lecture hall. His lectures were precise and clear, well illustrated with legible, if sometimes somewhat chaotic, notes on the blackboard. His lectures, during which he often referred to his own research, motivated many students to join his group, where he supervised them in his characteristic calm and friendly manner. His group rarely had fewer than 20 graduate students and postdoctoral fellows, and he mentored several young scientists who went on to positions in academia and industry around the world. Despite the size of his group and his many commitments, he always found time to go from lab to lab, talking to everyone and learning about the state of the research and the progress being made. Many of his former coworkers are still in touch, meeting regularly and interacting in a group on WhatsApp called "Wulffsche Flaschen" ("Flasche" means bottle in German, but is also used as a synonym for terms such as nerd or fool). A few weeks before his death, some of Günter Wulff's former coworkers presented him with an album of group photos, which he thoroughly enjoyed. Every member of the group has fond memories of the annual trips to the Conference on Macromolecular Chemistry in Freiburg, the group outings, which always included a more or less long hike – one of Günter Wulff′s passions – and the Beaujolais parties. In addition to his academic work, Günter Wulff held administrative positions at the University of Düsseldorf, including Dean of the Faculty of Mathematics and Natural Sciences from 1991 to 1992. He served on the advisory boards and editorial boards of several scientific journals, including the editorial board (Kuratorium) of Angewandte Chemie from 1995 to 2005. After his retirement in 2000, he maintained an office in the Chemistry Department and regularly participated in colloquia. He also enjoyed tending his garden and spending more time with his family, especially his grandchildren. Throughout his long academic career, Günter Wulff asked fundamental questions and engaged in projects that challenged his brilliant intellect. He left us with the whole new field of molecular imprinting, which has paved the way for sophisticated applications such as enzyme-like catalysis and artificial protein recognition, and is being studied all over the world, with more than 1,000 publications last year alone. It is not often that a researcher can claim to have founded an entire research field. Günter Wulff was one of them, and he will be sorely missed.