Kendall Houk

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Kendall Newcomb Houk
HoukPicture03 2.jpg
Born (1943-02-27)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
Notes
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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.

Education

Research and Teaching Appointments

Research interests

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 more than 900 articles in refereed journals and is among the 100 most-cited chemists.6 He is also a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the International Academy of Quantum Molecular Sciences, and California Nanosystems Institute.7


Mechanism and understanding of pericyclic reactions

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.

Enzyme design and biological catalysis

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 and Stephen Mayo 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.89 Many others have been designed, and experiments have shown various levels of success.

Transition state force fields

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.

Carbene reactivity

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.

Supramolecular chemistry

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

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.11121314 Collaborations with Doubleday are now revealing mechanistic details of Diels-Alder, 1,3-dipolar,14 and carbene cycloadditions.

Administrative Experience

  • Chairman of the UCLA Department of Chemistry and Biochemistry, 1991-1994
  • Director of the Chemistry Division of the NSF, 1988-1990
  • Director, UCLA Chemistry-Biology Interface Training Program, NIH-supported training grant, 2002–2011
  • Chair, AAAS Chemistry Section, 2005
  • Senior Editor, Accounts of Chemical Research, 2006–present
  • Chair of the NIH Synthesis and Biological Chemistry Study Session, 2008
  • Member of the NIH Medicinal Chemistry Study Section, 1988–1991
  • Member of NRC Board of Chemical Sciences and Technology
  • Advisory board of the Chemistry Division of the National Science Foundation
  • Advisory board of the Petroleum Research Fund
  • Advisory boards of journals including Accounts of Chemical Research, the Journal of Organic Chemistry, Chemical and Engineering News, and the Journal of Computational Chemistry15
  • Consulting Editor, Topics in Current Chemistry

Professional Societies

  • UCLA Molecular Biology Institute
  • California NanoSystems Institute
  • American Chemical Society
  • American Association for the Advancement of Science
  • National Academy of Sciences
  • Royal Society of Chemistry
  • International Society of Quantum Biology
  • International Academy of Quantum Molecular Science
  • World Association of Theoretical Organic Chemistry

Awards16

  • 2012 Elected to the Royal Society of Chemistry
  • 2012 Robert Robinson Award of the Royal Society of Chemistry
  • 2010 Elected to National Academy of Sciences
  • 2009 ACS Arthur C. Cope Award
  • 2009 American Chemical Society Fellow
  • 2009 Saul Winstein Chair in Organic Chemistry
  • 2003 ACS Award for Computers in Chemistry and Pharmaceutical Research
  • 2002 American Academy of Arts and Sciences
  • 2001 Fellow of the Japanese Society for the Promotion of Science (JSPS)
  • 2000 Lady Davis Fellowship (visiting professor) (Technion in Haifa, Israel)
  • 1999 honorary doctorate (Dr. rer. nat. h. c.) from the University of Essen, Germany
  • 1999 Tolman Award (American Chemical Society Southern California Section)
  • 1998 Schrödinger Medal (World Association of Theoretical and Computational Organic Chemistry)
  • 1998 Bruylants Chair from the University of Louvain-la-Neuve in Belgium
  • 1993 Visiting Erskine Fellow (University of Canterbury, Christchurch, New Zealand)
  • 1993 Herbert Newby McCoy Award, UCLA
  • 1991 James Flack Norris Award in Physical Organic Chemistry
  • 1988 Arthur C. Cope Scholar Award
  • 1988 Fellow of the American Association for the Advancement of Science
  • 1987 Phillips Distinguished Lectureship, Haverford College
  • 1983 Akron Section of the American Chemical Society Award
  • 1982 von Humboldt U.S. Senior Scientist Award
  • 1978 LSU Distinguished Research Master Award
  • 1975-1977 Alfred P. Sloan Foundation Research Fellowship
  • 1974-1975 Visiting Professor, Princeton University
  • 1972-1977 Camille and Henry Dreyfus Teacher-Scholar Grant

Named Lectures17

  • 2013 Reuben Sandin Lectures, University of Alberta
  • 2013 Habberman Lectures, Marquette University
  • 2013 J. F. Bunnett Lecture, University of California, Santa Cruz
  • 2012 Marvel Lectures, University of Illinois
  • 2012 Hamilton Lecture, University of Nebraska
  • 2012 Bristol Myers Squibb Lecture, University of Pennsylvania
  • 2012 Henry Eyring Lectures, Arizona State University
  • 2012 Sherry Memorial Lectures, Georgia Institute of Technology
  • 2011 Bender Lectures, Northwestern University
  • 2009 Thomas Lecture, University of Missouri-Columbia
  • 2009 Jeremiah P. Freeman Organic Synthesis Lecturer, Notre Dame University
  • 2009 Alder Lecture, University of Cologne
  • 2008 Closs Lecture, University of Chicago
  • 2008 Chevy Goldstein Distinguished Lecture, Cal Poly Pomona
  • 2008 William A. Pryor Lecture, Louisiana State University
  • 2007 Robert Robinson Lectures, University of Oxford
  • 2005 Kenneth B. Wiberg Lecture, Yale University
  • 2004-2005 Melvin Calvin Lecture, University of California, Berkeley
  • 2004 Paul Schleyer Lecture, University of Georgia
  • 2004 Frontiers in Organic Chemistry Lecturer, University of Illinois at Urbana-Champaign
  • 2000 Lise Meitner Lecturer (Hebrew University, Jerusalem Israel)
  • 1998 Herbert C. Brown Lecture, Purdue University
  • 1998 Faculty Research Lecturer, UCLA
  • 1990 Distinguished Lecturer, Montana State University
  • 1989 Frank Burnett Dains Lecturer, University of Kansas
  • 1987 First Merck-Frosst Lecturer, University of Sherbrooke, Canada
  • 1987 Castle Lecturer, University of South Florida
  • 1986 Organic Synthesis Distinguished Lecturer, Colorado State University
  • 1984 Winstein Lecture, University of California, Los Angeles
  • 1983 Frontiers of Chemical Research Lecturer, Texas A&M University
  • 1982 A. D. Little Lecturer, Northeastern University
  • 1980 Mobay Lecture, University of Pittsburgh

References

  1. ^ Harvard HOLLIS search, author: Kendall Newcomb Houk, Thesis (Ph. D.)--Harvard University, 1968.
  2. ^ [1],[2]
  3. ^ [3],[4]
  4. ^ [5],[6]
  5. ^ [7],[8]
  6. ^ [ISI Highly Cited Researchers Version 1.5]
  7. ^ California NanoSystems Institute
  8. ^ De Novo Computational Design of Retro-Aldol Enzymes
  9. ^ Kemp elimination catalysts by computational enzyme design : Abstract : Nature
  10. ^ Gating as a Control Element in Constrictive Binding and Guest Release by Hemicarcerands
  11. ^ Doubleday, C.; Suhrada, C.; Houk, K.N. "Dynamics of the Degenerate Rearrangement of Bicyclo[3.1.0]hex-2-ene." Journal of the American Chemical Society 2006, 128 (1), 90-94
  12. ^ Hakan Gunaydin, Sergey V. Barabash, K. N. Houk, and V. Ozolins. "First-Principles Theory of Hydrogen Diffusion in Aluminum." Phys. Rev. Lett. 2008, 101, 075901. doi:10.1103/PhysRevLett.101.075901
  13. ^ Stanton, C.L.; Kuo, I.F.W.; Mundy, C.J.; Laino, T.; Houk, K.N. "QM/MM Metadynamics Study of the Direct Decarboxylation Mechanism for Orotidine-5'-monophosphate Decarboxylase Using Two Different QM Regions: Acceleration Too Small To Explain Rate of Enzyme Catalysis," Journal of Physical Chemistry B 2007, 111(43), 12573-12581.
  14. ^ a b Dynamics of 1,3-Dipolar Cycloaddition Reactions of Diazonium Betaines to Acetylene and Ethylene: Bending Vibrations Facilitate Reaction - Xu - 2009 - Angewandte Chemie Interna...
  15. ^ UCLA Department of Chemistry and Biochemistry K.N. Houk faculty profile page
  16. ^ From Professor Houk's Research Group homepage at UCLA
  17. ^ From Professor Houk's Research Group homepage at UCLA

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