Bioorganic Chemistry 115 (2021) 104868 Available online 26 March 2021 0045-2068/© 2021 Elsevier Inc. All rights reserved. Review article Ronald C.D. Breslow (1931–2017): A career in review Vincent Joseph, Mindy Levine * Department of Chemical Sciences, Ariel University, Israel A R T I C L E INFO Keywords: Physical organic chemistry Cyclodextrin Biomimetic chemistry Bioorganic chemistry Origin of life ABSTRACT Reviewed herein are key research accomplishments of Professor Ronald Charles D. Breslow (1931–2017) throughout his more than 60 year research career. These accomplishments span a wide range of topics, most notably physical organic chemistry, medicinal chemistry, and bioorganic chemistry. These topics are reviewed, as are topics of molecular electronics and origin of chirality, which combine to make up the bulk of this review. Also reviewed briefy are Breslow’s contributions to the broader chemistry profession, including his work for the American Chemical Society and his work promoting gender equity. Throughout the article, efforts are made to put Breslow’s accomplishments in the context of other work being done at the time, as well as to include sub- sequent iterations and elaborations of the research. 1. Introduction The passing of Columbia University Professor Ronald Breslow in October of 2017 provides an impetus to review his long (more than 60 years), distinguished, and highly varied career in chemistry. This career included research in diverse areas of chemistry ranging from physical organic chemistry to medicinal chemistry to investigating the origin of life; resulted in more than 430 publications, 50 presentations at American Chemical Society conferences, and 20 patents; and was recognized with numerous research awards and honors, including the National Medal of Science (1991), the Priestley Medal (1999), and the Welch Award (2003). In parallel with Breslow’s signifcant research accomplishments, he devoted signifcant time to service of the chemistry profession through his work as chair of the chemistry division of the National Academy of Sciences (1974–1977) and as president of the American Chemical Society (1996); to service at Columbia University, particularly through his work on a university commission that was instrumental in turning Columbia College co-educational in 1983; and to teaching students at Columbia University, as evidenced through receipt of the Mark Van Doren Medal of Columbia University and the Columbia University Great Teacher Award (See Fig. 1). This review article focuses predominantly on Breslow’s research accomplishments, although some mention of Breslow’s service to the chemistry profession and Columbia University is discussed, and is divided by specifc research area. Within each area, the unique contri- butions of Breslow are reviewed and placed into a general scientifc context of the area. The accomplishments of other chemists are included to the extent that they provide this context. The authors apologize to any researcher whose contributions may have been inadvertently over- looked in the preparation of this manuscript. 2. Physical organic chemistry 2.1. Introduction The greatest fraction of Breslow’s work can be characterized as physical organic chemistry, and the relative importance of this research to Breslow was apparent in his description of physical organic chemistry as “the richest chemical science.”[2] Breslow’s work in physical organic chemistry focused on four main research areas: (a) synthesizing, char- acterizing, and isolating highly strained aromatic and anti-aromatic systems; (b) elucidating the mechanism of thiamine catalysis (and other related catalytic processes) in biological and synthetic systems; (c) understanding, calculating, and elucidating the mechanisms of organic reactions; and (d) predicting, isolating, and characterizing unusual carbocations. Each of these areas will be discussed in turn. 2.2. Research accomplishments 2.2.1. Highly strained aromatic and anti-aromatic systems Based on the Huckel theory of aromaticity, developed in the mid- 1800s, the smallest predicted aromatic moiety is the cyclopropenyl cation (with two π electrons; “4n + 2” with n = 0). Breslow invested * Corresponding author at: Department of Chemical Sciences, Ariel University, 65 Ramat HaGolan Street, Ariel, Israel. E-mail address: mindyl@ariel.ac.il (M. Levine). Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg https://doi.org/10.1016/j.bioorg.2021.104868 Received 2 February 2021; Accepted 23 March 2021