| Kendall Newcomb Houk | |
|---|---|
| Born | February 27, 1943 Nashville, Tennessee, United States |
| Fields | Chemistry |
| Institutions | U.C.L.A. |
| Alma mater | Harvard University |
| Doctoral advisor | Robert Burns Woodward |
| Known for | Theory of Organic Reactivity and Selectivity |
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Kendall Newcomb Houk (born 1943) is a Professor of Chemistry and the Saul Winstein Chair in Organic Chemistry at the University of California, Los Angeles.
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Kendall Houk's research focuses on theoretical and computational organic chemistry. His group is involved in developing rules to predict reactivity through a better understanding of organic reactions through computer modeling and experimental confirmation of predictions. He collaborates prodigiously with chemists all over the world. Among his current interests are the theoretical investigations and design of enzyme-catalyzed reactions, a collaboration that has recently led to the first successful design and synthesis of enzymes for non-natural reactions,[2] the quantitative modeling of asymmetric reactions used in synthesis,[3] the mechanisms and dynamics of pericyclic reactions and competing diradical processes, including a new theory of 1,3-dipolar cycloadditions,[4] the mechanisms of organometallic reactions,[5] and the molecular dynamics and reactions of hemicarcerands and other host-guest complexes. He has published over 700 articles in refereed journals and is among the 100 most-cited chemists.[6] He is also a member of the California Nanosystems Institute.[7]
Houk's work has made the transition states of pericyclic reactions nearly as familiar as ground states of organic molecules. His investigations of potential energy surfaces for pericyclic reactions for two decades have led to a thorough understanding of the geometries and energies of transition structures for all types of pericyclic reactions. These calculations show that such reactions are synchronous in the absence of unsymmetrical substituents. Houk discovered that there are normal bond lengths for transition structures of hydrocarbon pericyclic reactions. He provided an explanation of Zewail’s femtosecond dynamics measurements for hydrocarbons and made new generalizations about conical intersections involved in excited state reactions.
Houk discovered a powerful and unanticipated substituent effect in electrocyclic reactions of substituted cyclobutenes. Transition state calculations for the reaction of cyclobutenes led to the theory of "torquoselectivity," as he named it, a stereoselectivity arising from preferential direction of rotations of the terminal substituents accompanied by a torque on the breaking bond. The better the donor, the greater the preference for outward rotation. A prediction was made that a formyl group would rotate inward preferentially, to give the less stable product; Houk's group at UCLA verified this prediction experimentally. This major extension of the Woodward-Hoffmann rules has blossomed into a general principle of stereoselectivity, and experimental examples continue to be discovered in many labs.
A series of publications combining kinetic isotope effect computations with experimental measures of isotope effects in the literature or from Singleton's group have established the nature of transition states of several classic organic processes: the Diels-Alder reaction, Cope and Claisen rearrangements, peracid epoxidations, carbene and triazolinedione cycloadditions, and the osmium tetroxide bis-hydroxylation. The three-dimensional structures of transition states have become nearly as well-understood as the stable structures, largely due to his efforts.
Houk's recent work on catalytic antibodies and enzymes increased understanding of the quantitative aspects of these complex phenomena. He established quantitative comparisons of host-guest complex binding energies and of the effectiveness of enzymes in biological catalysts.
Now he has teamed with David Baker to design protein structures that will catalyze non-natural reactions. This collaboration involves the quantum mechanical design of active sites - theozymes - with catalytic units formed from side-chains of amino acids and then incorporating these into proteins that will fold to give an enzyme, a catalytic protein. A variety of computational tools have been developed to determine which design will be most active. To date, new enzymes for catalytic retro-aldol and ring-opening reactions have been predicted and established experimentally.[8][9] Many others have been designed, and experiments have shown various levels of success.
Houk pioneered the modeling of transition states with force field methods. Even before modern searching tools existed, ab initio calculations were used to locate geometries of transition states and to determine force constants for distortions away from these preferred geometries. These developments showed more generally how computational techniques could be useful tool for synthetic organic chemists. The whole concept of "transition state modeling" has developed from Houk's pioneering contributions.
Houk has provided a rigorous theoretical treatment of carbene reactivity as well as a general conceptual model for understanding reactions of these reactive intermediates. He showed how entropy control of reactivity and negative activation barriers both could be explained by a new, unified model in which reactions had no enthalpic barriers but do have significant entropic - and, therefore, free energy - barriers. The theory has had an impact on the interpretation of fast organic reactions. The group is now doing molecular dynamics simulations on carbene cycloadditions.
Houk has recently made a major contribution to the understanding of molecular recognition. The discovery that a conformational process ("gating") is the rate-determining step in complex formation and dissociation of Cram's hemicarceplexes has produced a new design element in host design. The ability to compute rates of such reactions have been first developed in his laboratories. The investigation of stabilities and mechanisms of catenanes and rotaxanes has already led to discovery of gating phenomena and electrostatic stabilization of these complexes.[10]
Dynamic effects are a recent focus of the Houk group beginning with a collaboration with Singleton using MD parameterized with semiempirical potentials and more recently using Born Oppenheimer MD and metadynamics.[11][12][13][14] Collaborations with Doubleday are now revealing mechanistic details of Diels-Alder, 1,3-dipolar,[14] and carbene cycloadditions.