Donna Blackmond | |
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Born | Pittsburgh, PA, United States | April 19, 1958
Education | B.S. Chemical Engineering, University of Pittsburgh, 1980 M.S. Chemical Engineering, University of Pittsburgh, 1981 Contents |
Scientific career | |
Fields | Chemical Engineering Chemistry |
Institutions | The Scripps Research Institute Imperial College London University of Hull Max Planck Institute University of Pittsburgh University of Essen |
Donna Blackmond FRS (born April 19, 1958) is an American chemical engineer and the John C. Martin Endowed Chair in Chemistry at Scripps Research in La Jolla, CA. Her research focuses on prebiotic chemistry, the origin of biological homochirality, and kinetics and mechanisms of asymmetric catalytic reactions. Notable works include the development of Reaction Progress Kinetic Analysis (RPKA), analysis of non-linear effects of catalyst enantiopurity, biological homochirality and amino acid behavior. [1]
Blackmond was born on April 19, 1958, in Pittsburgh, Pennsylvania, where she attended University of Pittsburgh and received her undergraduate and master's degree in chemical engineering. She received the Ph.D. in chemical engineering from Carnegie-Mellon University in 1984. She became a professor of chemical engineering at the University of Pittsburgh shortly after graduating and was promoted to associate professor with tenure in 1989. Blackmond remained in academia for 8 years before moving on to the associate director position at Merck & Co., Inc. Her main responsibility at the company was to set up a laboratory for research and development in the kinetics and catalysis of organic reactions. She was a research group leader at the Max-Planck-Institut für Kohlenforschung in Mülheim an-der-Ruhr, Germany, professor and chair of physical chemistry at the University of Hull in Kingston-upon-Hull, UK, and professor of chemistry and chemical engineering and chair in Catalysis at Imperial College London, UK. Blackmond is now a professor of chemistry, department chair, and the John C. Martin Endowed Chair in Chemistry at the Scripps Research Institute in La Jolla, California. Her most current research applies the quantitative aspects of her chemical engineering background to the synthesis of complex organic molecules by catalytic routes, particularly asymmetric catalysis. [1]
Blackmond has pioneered the methodology of Reaction Progress Kinetic Analysis (RPKA), which is used for rapid determination of concentration dependences of reactants. [1] RPKA allows for in situ measurements to produce a number of rate equations that enable analysis of a reaction using a minimal number of experiments. The purpose for this type of analysis is to help understand what the driving force of a reaction might be and describe possible mechanistic pathways. [2] This technique distinguishes rate processes occurring on the catalytic cycle from those occurring off the cycle. Notable applications of RPKA include asymmetric hydrogenation, asymmetric organocatalytic reactions, palladium catalyzed carbon-carbon and carbon-nitrogen bond forming reactions, and transition-metal catalyzed competitive reactions. [1]
Nonlinear effects describe the non-ideal relationship between enantiomeric excess (ee) of products of a reaction and the ee of the catalyst, a phenomenon first observed by Henri Kagan. Kagan developed mathematical models to describe this non-ideal behavior, MLn models. [3] Blackmond has performed studies that have led to an understanding of reaction rate and its relationship to catalyst ee. Many proposed mathematical models have been tested in the Blackmond lab, which have helped determine possible mechanistic features of reactions, including the Soai reaction. [4] The Soai reaction is of abiotic synthetic interest because it is an autocatalytic reaction, which rapidly produces a large amount of enantiopure products. [5] Blackmond was the first to use Kagan's ML2 model to study the non-linear effects of this reaction. She was the first to conclude that a homochiral dimer was the active catalyst in promoting homochirality for the Soai reaction. [4]
More recently, Blackmond has extended kinetic models to describe the origin of biological homochirality. She has shown solutions of mostly enantiopure amino acids can be produced from nearly racemic mixtures via solution-solid partitioning of the enantiomers. The discovery that eutectic mixtures could be manipulated, depending on the components of the mixture, allows for changes to the crystal structure and solubility of substances. Amino acids crystallize in one of two ways, as a mixture of D and L enantiomers (racemic compound) or as separate enantiomers (conglomerate) . [6] For nonracemic, nonenantiopure mixtures of molecules under ternary phase equilibrium, partitioning of enantiomers occurs between the liquid and solid phases depending on the form that the crystals take.
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Catalysis is the increase in rate of a chemical reaction due to an added substance known as a catalyst. Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quickly, very small amounts of catalyst often suffice; mixing, surface area, and temperature are important factors in reaction rate. Catalysts generally react with one or more reactants to form intermediates that subsequently give the final reaction product, in the process of regenerating the catalyst.
Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the general subject of organic synthesis, there are many different types of synthetic routes that can be completed including total synthesis, stereoselective synthesis, automated synthesis, and many more. Additionally, in understanding organic synthesis it is necessary to be familiar with the methodology, techniques, and applications of the subject.
Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction in which one or more new elements of chirality are formed in a substrate molecule and which produces the stereoisomeric products in unequal amounts."
Homochirality is a uniformity of chirality, or handedness. Objects are chiral when they cannot be superposed on their mirror images. For example, the left and right hands of a human are approximately mirror images of each other but are not their own mirror images, so they are chiral. In biology, 19 of the 20 natural amino acids are homochiral, being L-chiral (left-handed), while sugars are D-chiral (right-handed). Homochirality can also refer to enantiopure substances in which all the constituents are the same enantiomer, but some sources discourage this use of the term.
Biocatalysis refers to the use of living (biological) systems or their parts to speed up (catalyze) chemical reactions. In biocatalytic processes, natural catalysts, such as enzymes, perform chemical transformations on organic compounds. Both enzymes that have been more or less isolated and enzymes still residing inside living cells are employed for this task. Modern biotechnology, specifically directed evolution, has made the production of modified or non-natural enzymes possible. This has enabled the development of enzymes that can catalyze novel small molecule transformations that may be difficult or impossible using classical synthetic organic chemistry. Utilizing natural or modified enzymes to perform organic synthesis is termed chemoenzymatic synthesis; the reactions performed by the enzyme are classified as chemoenzymatic reactions.
In chemistry, transfer hydrogenation is a chemical reaction involving the addition of hydrogen to a compound from a source other than molecular H2. It is applied in laboratory and industrial organic synthesis to saturate organic compounds and reduce ketones to alcohols, and imines to amines. It avoids the need for high-pressure molecular H2 used in conventional hydrogenation. Transfer hydrogenation usually occurs at mild temperature and pressure conditions using organic or organometallic catalysts, many of which are chiral, allowing efficient asymmetric synthesis. It uses hydrogen donor compounds such as formic acid, isopropanol or dihydroanthracene, dehydrogenating them to CO2, acetone, or anthracene respectively. Often, the donor molecules also function as solvents for the reaction. A large scale application of transfer hydrogenation is coal liquefaction using "donor solvents" such as tetralin.
The Hajos–Parrish–Eder–Sauer–Wiechert and Barbas-List reactions in organic chemistry are a family of proline-catalysed asymmetric aldol reactions.
Asymmetric hydrogenation is a chemical reaction that adds two atoms of hydrogen to a target (substrate) molecule with three-dimensional spatial selectivity. Critically, this selectivity does not come from the target molecule itself, but from other reagents or catalysts present in the reaction. This allows spatial information to transfer from one molecule to the target, forming the product as a single enantiomer. The chiral information is most commonly contained in a catalyst and, in this case, the information in a single molecule of catalyst may be transferred to many substrate molecules, amplifying the amount of chiral information present. Similar processes occur in nature, where a chiral molecule like an enzyme can catalyse the introduction of a chiral centre to give a product as a single enantiomer, such as amino acids, that a cell needs to function. By imitating this process, chemists can generate many novel synthetic molecules that interact with biological systems in specific ways, leading to new pharmaceutical agents and agrochemicals. The importance of asymmetric hydrogenation in both academia and industry contributed to two of its pioneers — William Standish Knowles and Ryōji Noyori — being collectively awarded one half of the 2001 Nobel Prize in Chemistry.
Chiral Lewis acids (CLAs) are a type of Lewis acid catalyst. These acids affect the chirality of the substrate as they react with it. In such reactions, synthesis favors the formation of a specific enantiomer or diastereomer. The method is an enantioselective asymmetric synthesis reaction. Since they affect chirality, they produce optically active products from optically inactive or mixed starting materials. This type of preferential formation of one enantiomer or diastereomer over the other is formally known as asymmetric induction. In this kind of Lewis acid, the electron-accepting atom is typically a metal, such as indium, zinc, lithium, aluminium, titanium, or boron. The chiral-altering ligands employed for synthesizing these acids often have multiple Lewis basic sites that allow the formation of a ring structure involving the metal atom.
Organogold chemistry is the study of compounds containing gold–carbon bonds. They are studied in academic research, but have not received widespread use otherwise. The dominant oxidation states for organogold compounds are I with coordination number 2 and a linear molecular geometry and III with CN = 4 and a square planar molecular geometry.
In organic chemistry, the Soai reaction is the alkylation of pyrimidine-5-carbaldehyde with diisopropylzinc. The reaction is autocatalytic and leads to rapidly increasing amounts of the same enantiomer of the product. The product pyrimidyl alcohol is chiral and induces that same chirality in further catalytic cycles. Starting with a low enantiomeric excess ("ee") produces a product with very high enantiomeric excess. The reaction has been studied for clues about the origin of homochirality among certain classes of biomolecules.
Spontaneous absolute asymmetric synthesis is a chemical phenomenon that stochastically generates chirality based on autocatalysis and small fluctuations in the ratio of enantiomers present in a racemic mixture. In certain reactions which initially do not contain chiral information, stochastically distributed enantiomeric excess can be observed. The phenomenon is different from chiral amplification, where enantiomeric excess is present from the beginning and not stochastically distributed. Hence, when the experiment is repeated many times, the average enantiomeric excess approaches 0%. The phenomenon has important implications concerning the origin of homochirality in nature.
In enantioselective synthesis, a non-linear effect refers to a process in which the enantiopurity of the catalyst or chiral auxiliary does not correspond with the enantiopurity of the product produced. For example: a racemic catalyst would be expected to convert a prochiral substrate into a racemic product, but this is not always the case and a chirally enriched product can be produced instead.
In chemistry, reaction progress kinetic analysis (RPKA) is a subset of a broad range of kinetic techniques utilized to determine the rate laws of chemical reactions and to aid in elucidation of reaction mechanisms. While the concepts guiding reaction progress kinetic analysis are not new, the process was formalized by Professor Donna Blackmond in the late 1990s and has since seen increasingly widespread use. Unlike more common pseudo-first-order analysis, in which an overwhelming excess of one or more reagents is used relative to a species of interest, RPKA probes reactions at synthetically relevant conditions Generally, this analysis involves a system in which the concentrations of multiple reactants are changing measurably over the course of the reaction. As the mechanism can vary depending on the relative and absolute concentrations of the species involved, this approach obtains results that are much more representative of reaction behavior under commonly utilized conditions than do traditional tactics. Furthermore, information obtained by observation of the reaction over time may provide insight regarding unexpected behavior such as induction periods, catalyst deactivation, or changes in mechanism.
In chemistry, metal-catalysed hydroboration is a reaction used in organic synthesis. It is one of several examples of homogeneous catalysis.
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In homogeneous catalysis C2-symmetric ligands refer to ligands that lack mirror symmetry but have C2 symmetry. Such ligands are usually bidentate and are valuable in catalysis. The C2 symmetry of ligands limits the number of possible reaction pathways and thereby increases enantioselectivity, relative to asymmetrical analogues. C2-symmetric ligands are a subset of chiral ligands. Chiral ligands, including C2-symmetric ligands, combine with metals or other groups to form chiral catalysts. These catalysts engage in enantioselective chemical synthesis, in which chirality in the catalyst yields chirality in the reaction product.
Konstantin P. Bryliakov is a Russian chemist and author of monographs and over 170 research papers, textbooks, and patents. He is a professor at Russian Academy of Sciences and Novosibirsk State University.
Jordi Burés is a Full Professor of Organic Chemistry in the Department of Chemistry at The University of Manchester. His research in general is on the areas of organic and physical chemistry, specializing in Mechanistic Studies, nuclear magnetic resonance and catalysis.
A sterimol parameter is a set of vectors which describes the steric occupancy of a molecule. First developed by Verloop in the 1970s. Sterimol parameters found extensive application in quantitative structure-activity relationship (QSAR) studies for drug discovery. Introduction of Sterimol parameters into organic synthesis was pioneered by the Sigman research group in the 2010s. Benefiting from the multi-dimensional values that they carry, sterimol parameters give more accurate predictions for the enantioselectivity of asymmetric catalytic reactions than its counterparts, especially in cases when structurally complicated ligands are used.