October 6, 2021 Update
While these (not so accurate) predictions for the Nobel were initially published by our team on October 1st, we are excited to congratulate this year’s Nobel Prize laureates, Benjamin List (Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany) and David W.C. MacMillan (Princeton University, USA) on their breakthrough work in chemical synthesis using organocatalysts. Read More
While many factors will play a significant role in the committee’s decision on who will win 2021’s Nobel Prize in Chemistry, some level of ingenuity, citations, and patent activity for their work must be considered. Clearly, macro trends like the current global pandemic and the rise of AI or digitalization will drastically alter the scientific landscape, and assessing top candidates in light of these considerations is critical to successful predictions.
Lead candidates
♦ RNA chemical modification: 400+ publications, 20+ patents and 700+ citations*
Dr. Katalin Karikó and Dr. Drew Weissman
The development of N1-methylpseudouridine as a uridine analog allows RNA to incorporate it to avoid immune detection, increases the persistence of the RNA, and improves its ability to enter cells. Dr. Karikó and Dr.Weissman have published more than 400 articles and 20 patents, and their most cited article has been referenced more than 700 times. Modified RNA bases are crucial in the effectiveness of mRNA vaccines for COVID-19, and their joint patents were licensed by both Pfizer/BioNTech and Moderna for use in their vaccines. The use of modified nucleosides in oligonucleotides may either be recognized for the Nobel Prize in Medicine or Chemistry.
♦ Chemical synthesis of DNA: 1,400+ publications, 90+ patents and 12,000+ citations*
Dr. Marvin Caruthers and Dr. Leroy Hood
For biological chemistry, the development of methods for DNA synthesis has truly been groundbreaking. In fact, nearly 1,400 articles in the CAS Content CollectionTM have been published by these two authors. Dr. Caruthers and his colleagues developed methods to prepare DNA chemically (outside of cells or organisms). Dr. Hood and his colleagues used the chemistry of Dr. Caruthers to automate DNA synthesis and sequencing, allowing DNA to be prepared on a large scale. Without these methods, genetic engineering, genome sequencing, and DNA fingerprinting, among other technologies, would be difficult if not impossible. Their most cited article has been referenced over 12,000 times.
♦ Click and bioorthogonal chemistry: 1,200+ publications, 90+ patents, and 10,000+ citations *
Dr. Barry Sharpless, Dr. Morten Meldal, and Dr. Carolyn Bertozzi
Click chemistry and bioorthogonal chemistry is another lead candidate for this year’s Nobel Prize. The term “click chemistry” was coined by Professor Sharpless in 1999 and elaborated in an article, Click Chemistry: Diverse Chemical Function from a Few Good Reactions, published in 2001 (which has been cited over 10,000 times in the CAS Content Collection as of mid-2021).
Click chemistry is a set of rapid and specific reactions for assembling fragments into more complex structures. The archetypical click reaction is the cycloaddition of azides and alkynes to form 1,2,3-triazoles, originally discovered by Professor Rolf Huisgen. Dr. Sharpless and Dr. Meldal found that copper catalysts rendered the cycloaddition more selective and facile, making it useful for preparing small molecules, pharmaceuticals, antibodies, and polymers.
Bioorthogonal reactions are a subset of click reactions useful for chemistry in living things; they must assemble molecules rapidly and selectively at low concentrations in water and at near-ambient temperatures. The term “bioorthogonal” was coined by Dr. Bertozzi in the early 2000s; she and her research group developed two of the first biorthogonal reactions, the Staudinger ligation and strain-promoted azide-alkyne cycloadditions (cycloadditions not requiring copper, which, in many forms, is toxic to cells). Dr. Bertozzi has used biorthogonal chemistry to help understand the functions and structures of carbohydrates and glycans (carbohydrate-functionalized peptides) in biology; carbohydrates not only function as energy sources for organisms but also help to control protein-protein interactions and immunity. A Twitter poll by the editor of Nature Chemistry, Stuart Cantrill, chose bioorthogonal chemistry as the most likely subject of the Nobel Prize in Chemistry in 2021.
♦ Metal-organic frameworks: 2,400+ publications, 330+ patents and 7,000 citations*
Dr. Omar M. Yaghi, Dr. Makoto Fujita
Finally, the invention of metal-organic frameworks (MOF) has been an important and novel development in inorganic chemistry. Metal-organic frameworks are regular three-dimensional polymers with metals connected by organic linkers. Because the linkers and metals can be changed to adjust the pore sizes and shapes in a predictable manner, they have many potential uses, such as gas separation and storage, drug delivery, heterogeneous catalysis; since 2000, over 40,000 documents have been published with metal-organic frameworks in the CAS Content Collection, with the number of documents published yearly increasing over time.
Two of the chemists most associated with metal-organic frameworks research are Professor Omar Yaghi and Professor Makoto Fujita. Professor Yaghi and his colleagues have prepared a large variety of MOF, characterized them, and showed potential uses. The Fujita group has studied a variety of covalent networks; in addition, Professor Fujita’s group has also developed a method using MOF to obtain structural data for molecules on small scale without crystals using MOFs.
Other notable candidates
There are a variety of other important topics which, while we may see as less likely to be awarded the Nobel Prize in Chemistry in 2021, are likely to be considered for the award, either this year or in later years. A variety of other biological chemistry developments, for example, may be awarded the Nobel Prize in Chemistry.
Bioinorganic chemistry, for example, is the understanding of how metals are used in biology; it may also help to desired artificial photosynthetic systems and includes the development of the clinically important platinum antitumor agents. Professor Harry Gray and Professor Stephen Lippard are the most likely nominees (a third subject, Professor Richard Holm, died earlier in 2021.)
The field of chemical biology, the use of synthetic chemistry to understand and manipulate biology, has been important to our understanding of biology; Professor Stuart Schreiber and Professor Peter Schultz have used chemistry in natural products and proteins, respectively, to disentangle biological pathways. (In some views, chemical biology could be awarded a Nobel Prize paired with biorthogonal chemistry based on their common purposes.)
Finally, in organic chemistry, the Buchwald-Hartwig coupling to prepare arylamines from aryl halides and amines has been important in the development and synthesis of pharmaceutical agents; the chemists after which it is named, Professor Stephen Buchwald and Professor John Hartwig, have also helped to discover and optimize a variety of other organometallic reactions useful for making molecules.
The reproducible synthesis of nanoparticles whose sizes and structures are finely controlled, called nanocrystals or (for semiconducting light-emitting nanoparticles) quantum dots, by Professor Taeghwan Hyeon, Professor Moungi Bawendi, and Professor Christopher B. Murray developed has enabled their widespread use in biological imaging, light-emitting diodes, and displays.
Chemically amplified photoresists, developed by Dr. C. Grant Willson, Dr. Jean Fréchet, and Dr. Hiroshi Ito, have enabled the reliable manufacturing of computer processors with smaller features, enabling faster and more powerful electronic devices (Dr. Ito, however, died in 2009).
Finally, atom-transfer radical polymerization (ATRP), developed by (among others) by Dr. Krzysztof Matyjaszewski, Dr. Jinshan Wang, and Dr. Mitsuo Sawamoto, has enabled the predictable synthesis of polymers in a variety of shapes and with narrow size distributions by using less reactive initiating units and copper catalysts to limit how many reactive groups are present at once during polymerization.
For a more in-depth discussion of these ideas and other notable expert opinions, see what my colleague, Dr. Angela Zhou, had to say in a recent C&EN webinar on predicting who will win. (#chemnobel)
* Publications only include authored or co-authored pieces by the listed scientists, patents only include inventors with the listed scientists and citations only include their most cited paper