Lowrie Lecture II - Pablo Debenedetti
Thermodynamic and Kinetic Models of the Emergence of Biological Homochirality
Chiral asymmetry choices exhibited by molecules that are present in living organisms constitute a scientifically challenging set of observations. Such geometric preferences favoring one enantiomer over its mirror image are obvious in the observed structures of amino acids, sugars, and the biopolymers that they form. These facts automatically generate fundamental questions about how those chiral asymmetries arose spontaneously in the terrestrial biosphere. We have formulated thermodynamic and kinetic models of chiral amplification that provide molecular-level insight into possible scenarios for the emergence of chiral imbalance in a prebiotic and presumably racemic world.
In the thermodynamic case, we model the phase behavior of a ternary mixture composed of two enantiomeric forms of a chiral molecule and a non-chiral liquid solvent. The mean-field solution of the model allows the calculation of a ternary phase diagram, a prominent feature of which is the existence of two symmetric triple points involving coexistence of a liquid phase enriched in one of the enantiomers, a racemic crystal, and an enantiopure crystal. Over broad ranges of initial composition, including liquid mixtures containing almost equal amounts of the two enantiomers, thermodynamic equilibrium results in liquid-phase chiral amplification, in agreement with experimental observations.
The kinetic model involves an auto-catalytic reaction leading to the formation of a chiral compound, inhibition, and molecular diffusion. Numerical solution of the model via kinetic Monte Carlo allows the identification of two types of behavior. In one, the system evolves towards a mixture containing equal amounts of the two chiral enantiomers. In the symmetry-broken regime, the system evolves spontaneously towards large excess of one or the other chiral enantiomers.
Pablo Debenedetti is the Class of 1950 Professor in Engineering and Applied Science, Professor of chemical and Biological Engineering, and Vice Dean of the School o Engineering and Applied Science at Princeton University. He received his undergraduate education at the University of Buenos Aires, and in 1985 obtained his Ph.D. degree in chemical engineering at the Massachusetts INstitute of Technology. Debenedetti's research interests include the thermodynamics and statistical mechanics of liquids and glasses; the structure and thermodynamics of water and aqueous solutions; protein thermodynamics; the theory of nucleation; and metsatbility. He is the author of one book, "Metastable Liquids", and more than 200 scientific articles. "Metastable Liquids"was named "best scholarly book in Chemistry by the Association of American Publishers (1997). Debenedetti's professional honors include the National Science Foundation's Presidential Young Investigator AWard (1987), the Camille and Henry Dryfus Teacher-Scholar Award (1989), a Guggenheim Memorial Foundation Fellowship (1991), the Professional Progress (1997) and Walker (2008) Awards from the American Institute of Chemical Engineers, the John M. Prausnitz Award in Applied Chemical Thermodynamics (2001), the Joel Henry Hildebrand Award in the Theoretical and Experimental Chemistry of Liquids from the American Chemical Society (2008), the Distinguished Teacher Award from Princeton's School of Engineering (2008), and the President's Award for Distinguished Teaching (2008), Princeton's highest distinction for teaching. In 2008 Debenedetti was named one of 100 Chemical Engineers of the MOdern Era by the American Institute of Chemical Engineers. He is a member of the National Academy of Engineering and the American Academy of Arts and Sciences, and a fellow of the American Association for the Advancement of Science.