This grant supports Dr. Dina C. Merrer's undergraduate research program at Barnard College. The Merrer group elucidates the mechanisms (pathways) of extremely exothermic organic reactions with low or zero activation energies using experimental and computational techniques. The group has thus far determined that dihalocarbenes add to strained carbon-carbon (C-C) bonds such as those in cyclopropene and benzocyclopropene substrates in a one-step manner, through a single transition state that undergoes post-transition state branching of the pathway to several products. The formation of multiple products in an organic chemical reaction typically signifies the existence of multiple reaction mechanisms. However, when multiple products appear to derive from the same pathway, using traditional transition state theory (TST) to describe the reaction is inadequate. Formation of the products is instead controlled by molecular dynamics. Molecular dynamics include the motions, velocity, acceleration, and momenta of the reacting molecules as well as the way in which these factors change molecular shape and potential energy over the course of the reaction. The substrates in the carbene addition reactions must possess a threshold amount of strain energy to induce dynamic control, and this threshold lies between 30 and 40 kcal/mol. As detailed in this grant, the group plans to: (a) determine the threshold strain energy in C-C multiple-bond systems required to observe dynamic control, and (b) determine the limits of reactivity of halocarbenes with C-C single bonds. These two goals will be examined via mechanistic and dynamic studies of halocarbene reactions with three classes of strained substrates: (1) cyclopropenes, cyclooctyne, and cycloheptyne; (2) trans-bicyclo[n.1.0]alkanes; and (3) norbornadiene and bridgehead olefins with strain energies between 30 and 40 kcal/mol. This research will be conducted at Barnard College, a liberal arts college for women affiliated with Columbia University. A liberal arts environment provides exceptional opportunities to overlap research with the education of undergraduate students. These research projects provide educational opportunities for the PI's student co-workers not afforded them in the formal laboratory curriculum. These include using both classical (product studies) and modern (laser flash photolysis and computational chemistry) physical organic techniques. To date, 14 Barnard undergraduates have participated in the research funded by the PI's past NSF grant, nine of whom have since graduated. Of these nine students, six have begun or will begin advanced-degree programs in chemistry, biochemistry, medicine, or public health. This grant's research will extend the chemistry community's understanding of carbene addition mechanisms and the extent to which these mechanisms are governed by reaction dynamics, as well as provide the PI with increased opportunities to excite and encourage bright and capable women to pursue careers in science.
In the broadest sense, research in the Merrer group provides understanding of chemical reactions that release significant amounts of energy. Understanding inherent chemical reactivity enables predictability of these reactions. Predictability of reactions and the factors that influence those results enable chemists to utilize reactions in specific ways, whether it is to synthesize a new pharmaceutical or consumer product, or harnessing the energy that is released in a reaction for new energy sources. Specifically, we investigate the mechanisms at the electronic level between carbon-centered reactive species called carbenes and molecules that contain very strained carbon-carbon bonds. We are thus chemical detectives: we know the compounds we put into a reaction, we can characterize the three-dimensional structure(s) of the product(s) we generate from the reaction, and we conduct strategic experiments and high-level calculations on the reaction to determine the part of the reaction we cannot see (i.e., precisely where the electrons move during the reaction). We then assemble the pieces of information from these crucial experiments and calculations to construct a plausible description of precisely which bond(s) are made and broken during the reaction and how the electrons and energy are transferred from start to finish. Prof. Merrer and her undergraduate research students at Barnard College have used the funding from this NSF grant to investigate the pathways of dichlorocarbene (CCl2) and phenylchlorocarbene (PhCCl) additions to several strained organic compounds: cyclopropene, benzocyclopropene, cyclooctyne and related derivatives, adamantene, and homoadamantene (Figure 1). We use a combination of in-lab classical and contemporary experiments as well as modern computational modeling of our reactions on the computer to determine these reactions’ pathways. We have found that carbene reactions with the most strained of these compounds (cyclopropene, benzocyclopropene) are governed by the molecular motions and energy transfer processes – known as reaction dynamics – rather than adhering to traditional Transition State Theory. For the least strained of these compounds (cyclooctyne and its derivatives), dynamics may control the reactions. The intermediate-strained compounds adamantene and homoadamantene react with carbenes in a novel stepwise manner through intermediates that contain two unpaired electrons (biradicals) (Figures 2 and 3). For all of these carbene addition reactions, a substantial amount of energy is released – approx. 100 kilocalories per mole. Additionally, these reactions have little or no activation barriers to start them; the reactions are nearly spontaneous. The Merrer group’s investigations provide knowledge about the inherent chemical reactivity of two exceedingly reactive species – chlorocarbenes and strained carbon-carbon bonds. This basic research gives insight into the how and why of these reactions, for potential applied use by other scientists. One of the benefits to conducting undergraduate research is to provide students with an opportunity to conduct high-quality, intellectually-stimulating research that shapes their careers, their outlook on their careers, and their outlook on themselves as scientists. As the independent women’s college affiliated with Columbia University, Barnard College gives its female students full opportunities to achieve these goals. In the Merrer group, 19 outstanding, bright women have participated in the research covered by this grant since June 2009, four of whom are members of a group underrepresented in chemistry. In addition to the students’ research experience in the laboratory, they have collaborated and interacted with Columbia University chemists and conducted laser flash photolysis (LFP) measurements at Rutgers University and Colby College. Merrer group students also have presented their research annually at the spring National Meeting of the American Chemical Society and serve as co-authors on peer-reviewed publications in the chemical literature. All told, Prof. Merrer has supervised the research of 38 students in 14 years at Barnard College. Of the 28 Merrer research students who have graduated from Barnard, 15 have earned or are currently pursuing Ph.D.’s, M.D.’s, or both. The four current Merrer group members are chemistry or biochemistry majors who each plan on advanced study in chemistry or medicine as well. Clearly, faculty-directed undergraduate research in the sciences, particularly for women, is invaluable to their development as scientists and physicians.
