Kendall Houk
Encyclopedia
Kendall Newcomb Houk is a Professor of Chemistry and the Saul Winstein
Chair in Organic Chemistry at the University of California, Los Angeles
.
and computational organic chemistry
. His group is involved in developing rules to predict reactivity through a better understanding of organic reaction
s 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, the quantitative modeling of asymmetric reactions used in synthesis, the mechanisms and dynamics of pericyclic reaction
s and competing diradical
processes, including a new theory of 1,3-dipolar cycloadditions, the mechanisms of organometallic reactions, 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. He is also a member of the California Nanosystems Institute.
s 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 reaction
s of substituted cyclobutene
s. 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 rearrangement
s, 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.
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. Many others have been designed, and experiments have shown various levels of success.
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.
Saul Winstein
Saul Winstein was the Canadian chemist who discovered the Winstein reaction, in which he argued a non-classical cation was needed to explain the stability of the norbornyl cation. This fueled a debate with Herbert C. Brown over the existence of delocalized cations such as this. Richard F...
Chair in Organic Chemistry at the University of California, Los Angeles
University of California, Los Angeles
The University of California, Los Angeles is a public research university located in the Westwood neighborhood of Los Angeles, California, USA. It was founded in 1919 as the "Southern Branch" of the University of California and is the second oldest of the ten campuses...
.
Education
- Ph.D. Harvard UniversityHarvard UniversityHarvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
, Organic Chemistry, (1968)
Research advisor, R.B. WoodwardRobert Burns WoodwardRobert Burns Woodward was an American organic chemist, considered by many to be the preeminent organic chemist of the twentieth century...
, "The 6 + 4 cycloaddition reaction" - M.S. Harvard UniversityHarvard UniversityHarvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
(1966) - A.B. Harvard UniversityHarvard UniversityHarvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
(1964), Magna cum laude
Research advisor, R. A. Olofson
Research and Teaching Appointments
- Assistant Professor, Louisiana State UniversityLouisiana State UniversityLouisiana State University and Agricultural and Mechanical College, most often referred to as Louisiana State University, or LSU, is a public coeducational university located in Baton Rouge, Louisiana. The University was founded in 1853 in what is now known as Pineville, Louisiana, under the name...
, Baton Rouge, 1968 - Associate Professor, Louisiana State UniversityLouisiana State UniversityLouisiana State University and Agricultural and Mechanical College, most often referred to as Louisiana State University, or LSU, is a public coeducational university located in Baton Rouge, Louisiana. The University was founded in 1853 in what is now known as Pineville, Louisiana, under the name...
, Baton Rouge, 1972–1975 - Professor, Louisiana State UniversityLouisiana State UniversityLouisiana State University and Agricultural and Mechanical College, most often referred to as Louisiana State University, or LSU, is a public coeducational university located in Baton Rouge, Louisiana. The University was founded in 1853 in what is now known as Pineville, Louisiana, under the name...
, 1975–1980 - Professor, University of PittsburghUniversity of PittsburghThe University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of...
, 1980–1986 - Professor, University of California, Los AngelesUniversity of California, Los AngelesThe University of California, Los Angeles is a public research university located in the Westwood neighborhood of Los Angeles, California, USA. It was founded in 1919 as the "Southern Branch" of the University of California and is the second oldest of the ten campuses...
, 1986–present - Saul WinsteinSaul WinsteinSaul Winstein was the Canadian chemist who discovered the Winstein reaction, in which he argued a non-classical cation was needed to explain the stability of the norbornyl cation. This fueled a debate with Herbert C. Brown over the existence of delocalized cations such as this. Richard F...
Chair in Organic Chemistry, University of California, Los AngelesUniversity of California, Los AngelesThe University of California, Los Angeles is a public research university located in the Westwood neighborhood of Los Angeles, California, USA. It was founded in 1919 as the "Southern Branch" of the University of California and is the second oldest of the ten campuses...
, 2009–present
Research interests
Kendall Houk's research focuses on theoreticalTheoretical chemistry
Theoretical chemistry seeks to provide theories that explain chemical observations. Often, it uses mathematical and computational methods that, at times, require advanced knowledge. Quantum chemistry, the application of quantum mechanics to the understanding of valency, is a major component of...
and computational organic chemistry
Computational chemistry
Computational chemistry is a branch of chemistry that uses principles of computer science to assist in solving chemical problems. It uses the results of theoretical chemistry, incorporated into efficient computer programs, to calculate the structures and properties of molecules and solids...
. His group is involved in developing rules to predict reactivity through a better understanding of organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
s 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, the quantitative modeling of asymmetric reactions used in synthesis, the mechanisms and dynamics of pericyclic reaction
Pericyclic reaction
In organic chemistry, a pericyclic reaction is a type of organic reaction wherein the transition state of the molecule has a cyclic geometry, and the reaction progresses in a concerted fashion. Pericyclic reactions are usually rearrangement reactions...
s and competing diradical
Diradical
A diradical in organic chemistry is a molecular species with two electrons occupying two degenerate molecular orbitals . They are known by their higher reactivities and shorter lifetimes. In a broader definition diradicals are even-electron molecules that have one bond less than the number...
processes, including a new theory of 1,3-dipolar cycloadditions, the mechanisms of organometallic reactions, and the molecular dynamics
Molecular dynamics
Molecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
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. He is also a member of the California Nanosystems Institute.
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 reactionPericyclic reaction
In organic chemistry, a pericyclic reaction is a type of organic reaction wherein the transition state of the molecule has a cyclic geometry, and the reaction progresses in a concerted fashion. Pericyclic reactions are usually rearrangement reactions...
s 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 reaction
Electrocyclic reaction
In organic chemistry, an electrocyclic reaction is a type of pericyclic rearrangement reaction where the net result is one pi bond being converted into one sigma bond or vice-versa...
s of substituted cyclobutene
Cyclobutene
Cyclobutene is a cycloalkene. It is used in the chemical industry as a monomer for synthesis of some polymers and for a range of chemical syntheses.- External links :*...
s. Transition state calculations for the reaction of cyclobutenes led to the theory of "torquoselectivity
Torquoselectivity
Torquoselectivity is a special kind of stereoselectivity observed in electrocyclic reactions in organic chemistry, defined as "the preference for inward or outward rotation of substituents in conrotatory...
," as he named it, a stereoselectivity
Stereoselectivity
In chemistry, stereoselectivity is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during the non-stereospecific creation of a new stereocenter or during the non-stereospecific transformation of a pre-existing one...
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
Kinetic isotope effect
The kinetic isotope effect is the ratio of reaction rates of two different isotopically labeled molecules in a chemical reaction. It is also called "isotope fractionation," although this term is somewhat broader in meaning...
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
Diels-Alder reaction
The Diels–Alder reaction is an organic chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can proceed even if some of the atoms in the newly formed ring are not carbon...
, Cope
Cope rearrangement
The Cope rearrangement is an extensively studied organic reaction involving the [3,3]-sigmatropic rearrangement of 1,5-dienes. It was developed by Arthur C. Cope...
and Claisen rearrangement
Claisen rearrangement
The Claisen rearrangement is a powerful carbon-carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen...
s, 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 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. 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 carbeneCarbene
In chemistry, a carbene is a molecule containing a neutral carbon atom with a valence of two and two unshared valence electrons. The general formula is RR'C:, but the carbon can instead be double-bonded to one group. The term "carbene" may also merely refer to the compound H2C:, also called...
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.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. Collaborations with Doubleday are now revealing mechanistic details of Diels-Alder, 1,3-dipolar, and carbene cycloadditions.Administrative Experience
- Chairman of the UCLA Department of Chemistry and Biochemistry from 1991-1994.
- Director of the Chemistry Division of the NSFNational Science FoundationThe National Science Foundation is a United States government agency that supports fundamental research and education in all the non-medical fields of science and engineering. Its medical counterpart is the National Institutes of Health...
from 1988-1990. - Director, UCLA Chemistry-Biology Interface Training Program, NIHNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
-supported training grant. 2002–present - Chair, AAAS Chemistry Section, 2005
- Senior Editor, Accounts of Chemical ResearchAccounts of Chemical ResearchAccounts of Chemical Research is a peer-reviewed scientific journal, published since 1968 by the American Chemical Society. ACR is currently indexed/abstracted in: Chemical Abstracts Service , British Library, CABI, EBSCOhost, Proquest, PubMed, SCOPUS, SwetsWise and Web of Science.The current...
, 2006–present - Chair of the NIHNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
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 Chemistry
- Consulting Editor, Topics in Current Chemistry
Professional Societies
- American Association for the Advancement of Science
- American Chemical Society
- Royal Society of Chemistry
- International Society of Quantum Biology
- International Academy of Quantum Molecular Science
- World Association of Theoretical Organic Chemistry
- 2009 American Chemical Society Fellow
Awards
- 2010 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 SciencesAmerican Academy of Arts and SciencesThe American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
- 2001 Fellow of the Japanese Society for the Promotion of Science (JSPS)
- 2000 Lise Meitner Lecturer (Hebrew University, Jerusalem Israel)
- 2000 Lady Davis Fellowship (Technion in HaifaHaifaHaifa is the largest city in northern Israel, and the third-largest city in the country, with a population of over 268,000. Another 300,000 people live in towns directly adjacent to the city including the cities of the Krayot, as well as, Tirat Carmel, Daliyat al-Karmel and Nesher...
, IsraelIsraelThe State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
) - 1999 honorary doctorate (Dr. rer. nat. h. c.) from the University of Essen, Germany
- 1999 Tolman Medal (American Chemical Society Southern California Section)
- 1998 Faculty Research Lecturer, UCLA
- 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
- 1990 Distinguished Lecturer, Montana State University
- 1989 Frank Burnett Dains Lecturer, University of Kansas
- 1988 Arthur C. Cope Scholar Award
- 1988 Fellow of the American Association for the Advancement of Science
- 1987 First Merck Frosst Lecturer, University of Sherbrooke, Canada
- 1987 Phillips Distinguished Lectureship, Haverford College
- 1987 Castle Lecturer, University of South Florida
- 1986 Organic Synthesis Distinguished Lecturer, Colorado State University
- 1984 Winstein Lecturer, University of California, Los Angeles
- 1983 Akron Section of the American Chemical Society Award
- 1983 Frontiers of Chemical Research Lecturer, Texas A&M University
- 1982 von Humboldt U.S. Senior Scientist Award
- 1982 A.D. Little Lecturer, Northeastern University
- 1980 Mobay Lecturer, University of Pittsburgh
- 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