The Nobel Prize in Chemistry 2013 The Alliance of functional theory and John A. Pople (Northwestern University, Evanston) for his development of compu- Newton’s Apple and tational methods in quantum chemistry. With a bit of theoretical chauvinism, we would like to Schrödinger’s Cat add to the list the Nobel Prize to William N. Lipscomb (Harvard University, Cambridge) in 1976 for his stud- by Jean-Marie André ies on the structure of boranes illuminating problems n Wednesday, 9 October 2013, which was of chemical bonding, which were discoveries issued the scheduled date of the official announce- from his investigations on electron poor bonds, and Oment of the Nobel Prize in Chemistry, the those in the mythic year 2000, which honored Alan J. permanent secretary of the Royal Swedish Academy Heeger (University of California, Santa Barbara), Alan of Sciences, Professor Staffan Normark announced G. MacDiarmid (University of Pennsylvania) and Hideki that the 2013 Nobel Prize in Chemistry was to be Shirakawa (University of Tsukuba) for the discovery awarded jointly to Martin Karplus (Harvard and and development of conductive polymers. The quest Strasbourg), Michael Levitt (Stanford), and Arieh for the synthesis of electrically conducting polymers Warshel (University of Southern California at Los was a sort of chemical Holy Grail during the fifties Angeles) for the development of multiscale models and the golden sixties. As a beautiful symbol of this for complex chemical systems. quest, the physicist Heeger was rewarded along with the inorganic chemist MacDiarmid and the organic It was a somewhat unexpected announcement, and chemist Shirakawa. a nice surprise, because once again the Nobel Prize in Chemistry was awarded for research of a more “theo- The Winners retical” nature and joined the awards to • William Francis Giauque (University of California, Martin Karplus Berkeley) in 1949 for his contributions in the field of Martin Karplus was born in chemical thermodynamics, Vienna in 1930 into an old • Linus Carl Pauling (Caltech, Pasadena) in 1954 for Austrian Jewish family. After his research into the nature of the chemical bond of the Anschluss in 1938, he left and its application to the elucidation of the structure his native Austria and immi- of complex substances, grated to the United States via • Robert S. Mulliken (University of Chicago) in 1966 Switzerland and France. As a for his fundamental work concerning chemical bonds teenager, he was very inter- and the electronic structure of molecules by the ested in ornithology, which molecular orbital method, immersed him in the fascinat- Mahmoud. Alexander Photo: © Nobel Foundation. • Lars Onsager (Yale University, New Haven) in 1968 ing world of research.1 Naturally oriented towards for the discovery of the reciprocal relations bearing his biology, he quickly realized that to develop a valid name, which are fundamental for the thermodynamics approach to biology at its most fundamental level, of irreversible processes, he had to acquire a strong background in chemistry, • Ilya Prigogine (Université libre de Bruxelles and physics and mathematics. He thus decided to follow University of Texas, Austin) in 1977 for his contribu- the chemistry and physics programs at Harvard. His tions to non-equilibrium thermodynamics, particularly multiple interests brought him to Caltech where he the theory of dissipative structures, met the great masters of the time, Delbrück, Feynman, • Kenichi Fukui (Kyoto University) and Roald and Pauling. He obtained his PhD in 1953 under the Hoffmann (Cornell University, Ithaca) in 1981 for their direction of the lattermost; the topic of his research theories, developed independently, concerning the was the hydrogen bonding in the simple model HFH-. course of chemical reactions, Already, it was an opportunity for him to develop a • Rudolph Marcus (Caltech, Pasadena) in 1992 for his method close to the “atoms in molecules” approach, contributions to the theory of electron transfer reac- but he did not publish it. For his postdoc, he joined tions in chemical systems, Charles Coulson in Oxford. This was the time of the • and in 1998, Walter Kohn (University of California, birth of Nuclear Magnetic Resonance (NMR). He found Santa Barbara) for his development of the density- a strong interest in this new technique and chose to 2 CHEMISTRY International March-April 2014 return to the University of Illinois where Slichter and sen for the name of this original software had been Gutowsky were developing this technique for its appli- HARMM (for HARvard Macromolecular Mechanics), cations in chemistry. but was inevitably softened to CHARMM (Chemistry The Karplus equation at HARvard Macomolecular Mechanics). His work on retinal will point out the difficulty of publishing theoretical results applied to biology, a where A, B, and C are empirical parameters, relates the problem that remains today: if the theory is in accor- proton-proton couplings in three consecutive bonds dance with the experimental facts, it is not interesting to their dihedral angles (ϕ), which thus provides an since the results are already known; conversely, if the efficient way to evaluate geometries by NMR, even if theoretical result is a prediction that has not yet been Karplus himself likes to recall its limitation.2 This equa- experimentally verified, it will be considered unpub- tion is nevertheless of paramount importance in deter- lishable since there is no indication that the prediction mining the structure of organic molecules. is correct. In 1960, after five years in Illinois, he accepted a It was then that Karplus’ interest for hemoglobin professor position at Columbia University with the would grow. Research on hemoglobin is a source of tempting opportunity to pursue research at the IBM Nobel Prizes: in 1965, it was the proposal of the phe- Watson Laboratory and thus take advantage of the nomenological model of allosteric control by Monod,4 powerful computer resources of this period such as Wyman and Changeux; in 1971, Perutz,5 already Nobel the IBM 650. It is here that he developed his inter- Laureate, published the X-ray structure of deoxyhe- est in the kinetics of chemical reactions. Indeed, the moglobin. Karplus approached the subject by extend- IBM 650 allowed him to perform the many numerical ing the statistical methods that he was developing at analyses of the trajectories of the simplest chemical that time.6 reactive system: In 1977, Karplus was the first, with Andrew McCammon and Bruce Gelin, to publish a simulation H + H2 → H2 + H of a protein (BPTI, Bovine Pancreatic Trypsin Inhibitor) a system of three atoms and three electrons where by molecular dynamics, a paper that will serve as a an isolated hydrogen atom is exchanged with another reference test.7 These calculations were made in 1976 one of the molecule. at the European Centre of Atomic and Molecular In 1965, a new step for this pilgrim of the temples Computation (CECAM), established on the Orsay of science and a new home at Harvard; Karplus suc- campus (Parix XI) and founded by the late Carl Moser.8 ceeded R. Bright Wilson as the Theodore William In 1996, pushed by Jean-Marie Lehn, the 1987 Nobel Richards chair, who in 1914 was the first American to Prize in Chemistry winner with Donald Cram and win the Nobel Prize in Chemistry “in recognition of Charles Pedersen “for their development and use of his accurate determinations of the atomic weight of a molecules with structure-specific interactions of high large number of chemical elements.” selectivity,” Karplus also accepted a professorship at This was the time to gradually turn to systems that the University of Strasbourg. For thirty years, he had play an important role in the living world; Karplus spent his summer holidays near Lake Annecy. developed the methods and algorithms for which he was awarded the 2013 Nobel Prize. A sabbatical Arieh Warshel leave at the Weizmann Institute in 1970 gave him the Ten years younger than opportunity to meet Ariel Warshel who followed to Karplus, Arieh Warshel was Harvard. The two researchers would then combine born in 1940 on an Israeli kib- their expertise—quantum mechanics for Karplus, and butz. Like many of his age, he classical mechanics for Warshel—to study a planar was involved in the Six-Day molecule, 1,6-diphenyl-1,3,5-hexatriene.3 In this paper, War, Israel’s war against Egypt, the π electrons of the molecule are treated quantum Jordan and Syria in 1967, and mechanically by the PPP (Pariser-Parr-Pople) method, in the Yom Kippur War, the while the σ electrons are considered as classical war waged in 1973 by Egypt objects. It is the first model to combine quantum and and Syria against Israel, on the Mahmoud. Alexander Photo: © Nobel Foundation. classical mechanics. holiest day of the year for the Jewish people. After It is interesting to note that the first option cho- his degree in chemistry from the Technion in Haifa in CHEMISTRY International March-April 2014 3 The Nobel Prize in Chemistry 2013 1966, he received his PhD at the Weizmann Institute tion.12 A visiting professor at the Weizmann from 1980 in Rehovot under the direction of Shneior Lifson. For to 1987, he moved to the Faculty of Medicine at him, molecules are just atoms with chemical bonds Stanford University. Now, he divides his time between that he conventionally treats as a set of balls con- California and Israel. After the protein field, his interest nected together by springs. At the Weizmann Institute, turned to the nucleic acids. He is the first to simulate he met Levitt who was there for a visiting stay during DNA in vacuo and in solution by molecular dynamics.13 the summer. Levitt being very familiar with scientific Levitt married an Israeli sculptor and has an Israeli programming, they encoded the classical model of passport as well as his American and British passports.