Titre : “Dynamics and Mechanisms of Cycloadditions and Sigmatropic Shifts”
Endroit : Pavillon Roger-Gaudry, salle M-415 à 16 h.
Hôte : Professeur Shawn Collins
Cette conférence sera prononcée (en anglais) par le Professeur Kendall Houk de l'Université de Californie, Los Angeles (UCLA).
Résumé : The mechanisms and dynamics of bioorthogonal and enzyme-catalyzed cycloadditions will be discussed. We have developed a Distortion/Interaction model of reactivity, and we have performed molecular dynamics simulations of these and other organic reactions in the gas phase and in solution. The factors controlling reactivities in cycloadditions of use in probing biology will be discussed. We also propose a dynamical criterion to describe mechanisms of cycloadditions. Concerted (in unison) or stepwise mechanisms are defined in terms of the timing of bonding changes. For reactions in which two new sigma bonds are formed, a dynamically concerted reaction is one in which the second bond forms within 60s fs of the formation of the first bond. A stepwise reaction is one in which the second bond begins to form more than 60fs after the first is formed. These criteria have been applied to a variety of bioothogonal cycloadditions, and mutually orthogonal cycloadditions have been predicted and tested experimentally. The dynamics of reactions as well as enzyme-catalyzed cycloadditions will be reported. The influence of solvent and enzyme on trajectories will be described.
Leading References
(1) D. H. Ess and K. N. Houk: 'Theory of 1,3-Dipolar Cycloadditions: Distortion/Interaction and Frontier Molecular Orbital Models,' J. Am. Chem. Soc. 2008, 130, 10187-10198.
(2) K. Black, P. Liu, L. Xu, C. Doubleday, and K. N. Houk: 'Inaugural Article: Dynamics, Transition States, and Timing of Bond Formation in Diels-Alder Reactions,' Proc. Natl. Acad. Sci. USA 2012, 109, 12860-12865.
(3) D. N. Kamber, Y. Liang, R. J. Blizzard, F. Liu, R. A. Mehl, K. N. Houk, and J. A. Prescher: '1,2,4-Triazines Are Versatile Bioorthogonal Reagents,' J. Am. Chem. Soc. 2015, 137, 8388-8391.
(4) M. N. Narayanam, Y. Liang, K. N. Houk, and J. M. Murphy: 'Discovery of New Mutually Orthogonal Bioorthogonal Cycloaddition Pairs Through Computational Screening,' Chem. Sci. 2016, 7, 1267-1261.
(5) A. Patel, Z. Chen, Z. Yang, O. Gutierrez, H.-w. Liu, K. N. Houk, and D. A. Singleton: 'Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A,' J. Am. Chem. Soc. 2016, 138, 3631-3634.
