The conventional framework for understanding reactivity and selectivity in organic reactions fails for reactions influenced by dynamic effects. Our work has identified three types of dynamic effects that we expect to be common in ordinary organic reactions in solution. We propose their detailed mechanistic investigation in diverse reactions.
The aim of this research is to identify experimental examples and develop experimentally-based evidence for each type of dynamic effect. This includes the characterization of observations associated with dynamic effects and the development of new experimental tests for dynamic effects. We also aim to establish examples of these types of dynamic effects in enzymatic and organometallic reactions. Overall, our goal is to provide a sufficient experimental phenomenology to foster understanding, allowing other workers to recognize when dynamic effects play a role in their reactions. Finally, mechanistic studies are proposed with the aim of understanding and controlling selectivity in some important new reactions. The health-relatedness of this work derives from its impact on the understanding of reactions important in the synthesis of medicinally important substances and reactions important in biosynthetic pathways. The synthesis of pharmaceuticals and the manipulation of biological pathways depend on the rational design and control of chemical reactions, which in turn depend on the understanding of chemical reactions. Our research is providing fundamental news ways to understand reactions that should aid in their invention, development, and regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM045617-19
Application #
7741759
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Hagan, Ann A
Project Start
1991-01-01
Project End
2011-03-31
Budget Start
2009-12-01
Budget End
2011-03-31
Support Year
19
Fiscal Year
2010
Total Cost
$246,239
Indirect Cost
Name
Texas A&M University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
Aziz, Hannah R; Singleton, Daniel A (2017) Concert along the Edge: Dynamics and the Nature of the Border between General and Specific Acid-Base Catalysis. J Am Chem Soc 139:5965-5972
Kurouchi, Hiroaki; Andujar-De Sanctis, Ivonne L; Singleton, Daniel A (2016) Controlling Selectivity by Controlling Energy Partitioning in a Thermal Reaction in Solution. J Am Chem Soc 138:14534-14537
Patel, Ashay; Chen, Zhuo; Yang, Zhongyue et al. (2016) Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A. J Am Chem Soc 138:3631-4
Nieves-Quinones, Yexenia; Singleton, Daniel A (2016) Dynamics and the Regiochemistry of Nitration of Toluene. J Am Chem Soc 138:15167-15176
Plata, R Erik; Singleton, Daniel A (2015) A case study of the mechanism of alcohol-mediated Morita Baylis-Hillman reactions. The importance of experimental observations. J Am Chem Soc 137:3811-26
Biswas, Bibaswan; Singleton, Daniel A (2015) Controlling Selectivity by Controlling the Path of Trajectories. J Am Chem Soc 137:14244-7
Bogle, Xavier S; Singleton, Daniel A (2012) Dynamic origin of the stereoselectivity of a nucleophilic substitution reaction. Org Lett 14:2528-31
Andujar-De Sanctis, Ivonne L; Singleton, Daniel A (2012) Racing carbon atoms. Atomic motion reaction coordinates and structural effects on Newtonian kinetic isotope effects. Org Lett 14:5238-41
Bogle, Xavier S; Singleton, Daniel A (2011) Isotope-induced desymmetrization can mimic isotopic perturbation of equilibria. On the symmetry of bromonium ions and hydrogen bonds. J Am Chem Soc 133:17172-5
Quijano, Larisa Mae M; Singleton, Daniel A (2011) Competition between reaction and intramolecular energy redistribution in solution: observation and nature of nonstatistical dynamics in the ozonolysis of vinyl ethers. J Am Chem Soc 133:13824-7

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