It is with deep sadness that the Cyclodextrin News shares the passing of Sir Fraser Stoddart, a Giant in the world of chemistry. Professor Stoddart died on Dec. 30, 2024, at the age of 82.
Professor Stoddart was a visionary in the fields of supramolecular and carbohydrate chemistry (including cyclodextrin technology), known for his multidecade groundbreaking research and innovative contributions to the synthesis of mechanically interlocked molecules and artificial molecular machines. The entire cyclodextrin community extends its deepest condolences to Professor Stoddart’s family, friends, colleagues and students during this difficult time. The loss of this exceptional scientist is truly a great one, and he will be dearly missed by all who had the privilege of knowing him.
As carbohydrate chemists, in 1971, he wrote a seminal book on stereochemistry of carbohydrates, from which we could relatively well understand the complicated stereochemical aspects of carbohydrates. (See photo of the book cover below)
Fig. 1 Stoddart’s book on stereochemistry of carbohydrates
Professor Stoddart’s legacy will continue to inspire future generations of scientists, and his impact in chemistry will be felt for years to come. He will be remembered not only for his academic achievements, but also for his kindness, generosity, and unwavering support for young scientists around the world. He received numerous awards for his work just a few to mention:
- the Richard Feynman Prize in Nanotechnology (2007),
- the Royal Medal of the Royal Society of Edinburgh (2010), and
- the Centenary Prize from the Royal Society of Chemistry (2014).
- he was an elected fellow of the Royal Society of Edinburgh (2008),
- the American Academy of Arts and Sciences (2012), and
- the U.S.National Academy of Sciences (2014).
- knighthood as a Knight Bachelor in 2007 from h.m. Queen Elisabeth.
Stoddart shared the 2016 Nobel Prize in Chemistry with Jean-Pierre Sauvage of the University of Strasbourg and Ben L. Feringa of the University of Groningen, for their work on artificial molecular machines.
He was well known for his works on synthesis of mechanically interlocked molecules, including interlocked rings, known as catenanes, and rings encircling rods, known as rotaxanes. These molecules became the foundation for artificial molecular switches and machines and helped to establish the concept of the mechanical bond. Below is the original definition of mechanical bond by Stoddart in a 2016 book co-authored with Carson J. Bruns titled: ”The Nature of the Mechanical Bond: From Molecules to Machines”. (Figure 2)
“A mechanical bond is an entanglement in space between two or more component parts, such that they cannot be separated without breaking or distorting chemical bonds between atoms,”
Fig. 2 The Nature of the Mechanical Bond: From Molecules to Machines
Born in 1942 in Edinburgh, Stoddart earned his PhD at the University of Edinburgh in 1966 and held many positions throughout his long career in chemistry. He was a National Research Council of Canada Research Fellow at Queen’s University in Kingston, Ontario. He then moved to the University of Sheffield, where he was an Imperial Chemical Industries Research Fellow before joining the school’s academic faculty. In 1990, he moved to the University of Birmingham and in 1997 joined the faculty of the University of California, Los Angeles. Stoddart moved again in 2007 to Northwestern University and finally joined the faculty at the University of Hong Kong in 2023.
Colleagues about Stoddart:
Professor Feringa describes Stoddart as a “good friend, good colleague, and an outstanding scientist” who possessed tremendous energy and enthusiasm for chemistry.
David Leigh, who earned his PhD as part of Stoddart’s group in the 1980s at the University of Manchester says, Stoddart’s “real legacy is how he touched scientists’ lives; he just inspired whole generations of scientists and chemists. He was supportive of students, collaborators, and even his competitors”, Leigh says.
Writing in his Nobel Prize autobiography, Stoddart himself said, “I have been immensely privileged to be able to practice my hobby almost every day of my life in the presence of highly intelligent and outstandingly gifted young people.”
Fraser Stoddart and the cyclodextrins:
Sir Fraser attended the 3rd International Symposium on Cyclodextrins in Lancaster and later in the Munnich Symposium where he met József Szejtli. The meeting of these two great scientists was a mutually rewarding one and resulted in many groundbreaking discoveries in the field of cyclodextrin-related supramolecular chemistry. (Photo below was taken in the International Cyclodextrin Symposium in 1998.) Later he participated at several International Cyclodextrin Symposia, last time in Sicily in 2022.
Fig. 3 Great scientists at the Cyclodextrin Symposium
The following major fields of cyclodextrin science and technology, where Sir Fraser left his footprint behind forever:
- in 1981 he published his paper on Synthetic Enzymes. Reported on chemical studies and synthesis of models of alpha-cyclodextrin and crown ether- based artificial enzymes.
- in 1984 he published a review with >145 references, on host-guest chemistry including historical and general background, nomenclature, crown ethers and cryptands, cavitands, cyclodextrins, clathrates, and other host compounds.
- in 1985-1988 Stoddart published with his co-aouthor Dr. Alston, a number of papers on cyclodextrins as ligands for second sphere coordination of transition metal complexes. He also patented the organo-platinum-CD complexes as anticancer agents (EP 0181166 A2 14 May 1986). Please note that the results of Stoddart’s studies on second sphere coordination later found their place in an industrially useful process for gold mining and processing. (See below.)
- In 1988 Stoddart wrote a review with 56 references on „A century of cyclodextrins” in Carbohydrate Research.
- Between 1990-92 he conducted research on per-3,6-anhydro-cyclodextrins and this was followed by a review titled: „Cyclodextrins: inexpensive building blocks for the construction of molecular systems with mechanical links” a direction toward his Nobel-winning chemistry. He summarized his results achieved on cyclodextrin-containing rotaxanes and polyrotaxanes in a review paper. (Angew. Chem., Int. Ed. Engl., 1992, 31(7), 846-8)
- In 1993 a paper on “Self-assembly of catenanes with cyclodextrin units” was published (Angew. Chem., Int. Ed. Engl., 1993, 105(6), 854-8)
- In 1998 “Cyclodextrin-Based Catenanes and Rotaxanes” comprehensive review (Chem. Rev. 1998, 98(5), 1959-1976)
- In 1999 “Organic template-directed syntheses of catenanes, rotaxanes, and knots”. This is a review with 58 references including pseudorotaxanes and rotaxanes incorporating macrocyclic polyethers and secondary dialkylammonium salts; pseudorotaxanes, catenanes, rotaxanes, and knots incorporating pi-electron rich and deficient components; catenanes and rotaxanes incorporating amide recognition sites; and catenanes and rotaxanes incorporating cyclodextrins as their macrocyclic components. (Molecular Catenanes, Rotaxanes, Knots (1999), 143-176. Editor(s): Sauvage, Jean-Pierre!; Dietrich-Buchecker, Christiane. Publisher: Wiley-VCH Verlag GmbH, Weinheim, Germany.)
- From 2000 onward, Stoddart was working on switchable catenanes and molecular shuttles and published his results in a review in a book titled “Molecular Switches”, edited by: Ben L. Feringa! (pages: 219-248, Wiley-VCH Verlag GmbH: Weinheim, Germany. ISBN: 3-527-29965-3).
- Between 2010 -2016, he started publishing on CD-based Metal Organinc Frameworks (MOF). His seminal paper on MOF titled „Metal-Organic Frameworks from Edible Natural Products”, where his MOF architecture consisted of an arrangement of 6 gamma-CD molecules occupying each face of a cubic type assembly held together by 8-coordinate potassium K+ ions to form a 3-dimensional array. This paper appeared in Angewandte Chemie, International Edition, 49(46), 8630-8634, S8630/ 1-S8630/13 2010.
A scientist and entrepreneur: processing GOLD
Sir Fraser attempted to revolutionize the mining industry with a new technique he discovered for extracting gold with the avoidance of poisonous cyanide which is commonly used.
This new technique applies a hydrogen peroxide-based substance that combines with alpha-cyclodextrin to extract gold at ambient temperatures. To commercialize his discovery, Stoddart established a company called Cycladex. Its technique is cheaper than current methods and could eventually replace the cyanide leaching process that has been used in most gold mines for the last 120 years, causing serious environmental problems. Cyanide has been blamed for contaminating waterways and poisoning wildlife. Cycladex has won a one million US dollar grant from the National Science Foundation in the US and worked with Comstock Co., one of the world’s oldest gold mining companies, on a trial that could move the process to a commercial scale. Gold recovery using environmentally benign chemistry is imperative from an environmental perspective. Stoddart’ group reported the spontaneous assembly of a one-dimensional supramolecular complex with an extended {[K(OH2)6][AuBr4](alpha-cyclodextrin)2}n chain superstructure formed during the rapid co-precipitation of α-cyclodextrin and KAuBr4 in water. See Figure 4. below
Fig. 4 Alpha-cyclodextrin-assisted selective and efficient gold recovery developed by Stoddart (Nature Commun. 4, 1855 2013).
This discovery is an environmentally benign host–guest procedure for gold recovery from gold-bearing raw materials, making use of alpha-cyclodextrin – an inexpensive and environmentally benign starch derivative. (Liu, Z., Frasconi, M., Lei, J.et al. Selective isolation of gold facilitated by second-sphere coordination with α-cyclodextrin. Nature Commun 4, 1855 (2013). https://doi.org/10.1038/ncomms2891)
Mirror image cyclodextrins
Last and probably the most interesting, revolutionary research result of Fraser Stoddart is the synthesis and characterization of unnatural, mirror image L-cyclodextrins. This groundbreaking discovery of L-CDs, (see Figure 5 below) will undoubtedly open a new chapter in the CDs-related supramolecular chemistry, in biotechnology and pharmaceutics.
Thank you, Sir Fraser!
Fig. 5 Looking into the mirror: Structure of natural and mirror image cyclodextrins
Reflecting on Sir Fraser Stoddart’s remarkable life and career, let us honor Sir Fraser by continuing to pursue our works with the passion and curiosity that he exemplified every day. The World of Chemistry will miss Him dearly.
May He rest in peace.
Featured photo credit to Wikipedia