Abstract: The (4+3)-cycloaddition reaction is a quick and efficient entry to seven-membered rings, and those that are larger and smaller as well.  This presentation will focus on our contributions to this area from both a historical and present-day perspective.  This latter aspect will be dominated by our work on the cycloaddition reactions of oxidopyridinium ions.

Research: http://faculty.missouri.edu/~harmatam/

Michael Harmata was born in Chicago in 1959.  He attended St. Michael the Archangel grammar school, Thomas Kelly High School, and the University of Illinois-Chicago, where he received his AB degree in chemistry with a math minor in 1980, working in the labs of Jacques Kagan and graduating with honors and highest distinction and all that great stuff that doesn’t matter anymore.  He earned his PhD under the tutelage of Scott E. Denmark at the University of Illinois in Urbana, Illinois in early 1985, working on carbanion-accelerated Claisen rearrangements.  He then did an NIH postdoc with Paul A. Wender at Stanford University where he performed some of the first work on the synthesis of the neocarzinostatin chromophore.  He began his independent career at the University of Missouri-Columbia in 1986, where he is now the Norman Rabjohn Distinguished Professor of Chemistry.  He has been contributed significantly to the areas of (4+3)-cycloaddition reactions, benzothiazine chemistry, pericyclic reactions of cyclopentadienones, chiral molecular tweezers, silver-catalyzed chemistry, and more.

Abstract: Although the conversion of oleaginous biomass to the fatty acid methyl esters (FAMEs) that constitute biodiesel is a mature technology, feedstock availability issues as well as challenges stemming from the high oxygen content of FAMEs have limited the widespread application of biodiesel. Consequently, attention has shifted to processes capable of catalytically deoxygenating oleaginous biomass to afford fuel-like hydrocarbons. Deoxygenation via decarboxylation/decarbonylation (deCO_x) represents a promising alternative to the hydrodeoxygenation (HDO) processes typically employed to achieve this transformation, as deCO_x does not necessitate the high pressures of hydrogen and the problematic sulfided catalysts required by HDO.

To date, the majority of deCO_x reports involve Pd or Pt catalysts, the cost of which may be prohibitive. However, Ni-based catalysts have been shown to be capable of affording comparable results to precious metal-based formulations [1]. Recently, we have observed that the promotion of Ni with other earth-abundant metals – such as Cu – leads to considerable improvements in activity, selectivity and resistance to coking [2]. Results of Temperature Programmed Reduction (TPR) and X-ray Photoelectron Spectroscopy (XPS) measurements suggest that these improvements can be attributed to the ability of the aforementioned metal promoters to improve the reducibility of Ni. This results in an increased amount of Ni⁰, which is believed to be the active phase in the deCO_x reaction.

Ni catalysts promoted in this manner afford remarkable results in the conversion of a wide variety of ­model, waste and/or highly unsaturated lipids – including tristearin, triolein, yellow grease, brown grease, hemp seed oil and algal FAMEs – to fuel-like hydrocarbons [3-6]. Indeed, using a fixed-bed reactor operated using industrially-relevant reaction conditions, close to quantitative yields of diesel-like hydrocarbons are obtained. In addition, as shown in Figure 1, a catalyst employed has displayed remarkable stability and recyclability in a run comprising two 100 h time on stream cycles [5].  

Mentoring has been identified as an effective tool not only for attracting and retaining students from groups traditionally underrepresented in STEM disciplines, but also for improving their academic performance. However, additional benefits could be obtained by housing mentoring initiatives in research centers as opposed to in traditional academic departments. Therefore, a mentoring initiative based at the University of Kentucky Center for Applied Energy Research is striving to test this hypothesis [7]. Recently, providing the participating students access to international research opportunities has become a focus of this mentoring program.

References

[1] T. Morgan, D. Grubb, E. Santillan-Jimenez, M. Crocker. Top. Catal., 2010, 53, 820.

[2] R. Loe, E. Santillan-Jimenez, A.F. Lee, M. Crocker, et al. Appl. Catal. B: Environ., 2016, 191, 147.

[3] E. Santillan-Jimenez, R. Pace, T. Morgan, C. McKelphin, M. Crocker, et al. Fuel, 2016, 180, 668.

[4] E. Santillan-Jimenez, R. Loe, M. Garrett, T. Morgan, M. Crocker. Catal. Today, 2018, 302, 261.

[5] R. Loe, M. Maier, M. Abdallah, R. Pace, E. Santillan-Jimenez, M. Crocker, et al. Catalysts, 2019, 9, 123.

[6] R. Loe, K. Huff, M. Walli, R. Pace, Y. Song, E. Santillan-Jimenez, M. Crocker, et al. Catalysts (IN PRESS).

[7] E. Santillan-Jimenez, W. Henderson. 124^th American Society for Engineering Education Annual Conference Proceedings, 2017, Conference Paper ID #17681.

Abstract:

Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis at atomic resolution remains ambiguous. The three dimensional structure of protein is not always adequate to provide a complete understanding of protein function. We use atomistic molecular dynamics simulations to complement experiments to understand how protein conformational dynamics are coupled to allosteric function. We analyze multi-dimensional simulation trajectories by mapping key dynamical features within individual macrostates as residue-residue contacts. In this talk, we will discuss computational studies on members of a ubiquitous family of enzymes that regulate many sub-cellular processes. The effects of distal mutations and substrate binding are observed at locations far beyond the mutation and binding sites, implying their importance in allostery. The results provide insights into the general interplay between enzyme conformational dynamics and catalysis from an atomistic perspective that have implications for structure based drug design and protein engineering.

Abstract:

Polymerizing monomers into periodic two-dimensional (2D) networks provides structurally precise, layered macromolecular sheets that exhibit desirable mechanical, optoelectrotronic, and molecular transport properties. 2D covalent organic frameworks (COFs) offer broad monomer scope but are generally isolated as powders comprised of aggregated nanometer-scale crystallites. I will discuss 2D COF formation using a two-step procedure, in which monomers are added slowly to pre-formed nanoparticle seeds. The resulting 2D COFs are isolated as single-crystalline, micron-sized particles. Transient absorption spectroscopy of the dispersed COF nanoparticles provides two to three orders of magnitude improvement in signal quality relative to polycrystalline powder samples and suggests exciton diffusion over longer length scales than those obtained through previous approaches. These findings will enable a broad exploration of synthetic 2D polymer structures and properties.

ABSTRACT: What are the thermodynamic driving forces that influence the free energy of membrane protein folding and association in lipid bilayers? For soluble proteins, the burial of hydrophobic groups away from aqueous interfaces is a major driving force, but membrane-embedded proteins cannot experience hydrophobic forces, as the lipid bilayer lacks water. A fundamental conundrum thus arises: how does a greasy protein surface find its greasy protein partner in the greasy lipid bilayer to fold faithfully into its native structure? Recently, a structurally stable and functional monomeric form of the normally homodimeric Cl^-/H⁺ antiporter CLC-ec1 was designed by introducing tryptophan mutations at the dimer interface. We have used this to develop a new model system for studying reversible dimerization in membranes for free energy measurements, which encompasses the thermodynamic properties of protein interactions in the membrane environment. To quantify monomer vs. dimer populations across a wide range of protein densities, we developed a method that quantifies the capture of subunits into liposomes from large equilibrium membranes single-molecule photobleaching by total internal reflection microscopy.  With this, we are able to determine that CLC-ec1 has a free energy of dimerization of -11 kcal/mole in 2:1 POPE/POPG membranes.  We are now investigating why this complex is so stable, dissecting the changes in enthalpy and entropy while varying protein interactions or the composition of the lipid solvent.  The results from this study will provide a physical foundation for the development of informed strategies aimed at correcting protein mis-folding or regulating protein interactions in membranes in physiologically and pathological situations.

Conductive polymer electrodes have exceptional promise for next generation electronic and electrochemical devices due to inherent mechanical flexibility, printability, biocompatibility, and low cost. Yet conductive polymers continue to suffer from lower conductivity than conventional semiconductors, which ultimately can limit performance.  Electrical conductivity can be increased by increasing the total number of carriers through a charge transfer reaction – oxidation or reduction.  The first half of this talk will focus on the use of spectroscopic methods to evaluate the effects of chemical, electronic, and physical structure changes of organic semiconductors that accompany charge transfer reactions at interfaces, with consequences on device performance. 

The second half of this talk will focus on the unique hybrid electronic-ionic conduction of conductive polymers, which has enabled novel electrochemical devices including bioelectronics.  Two key functionalities of potential-dependent doping at the polymer/electrolyte interface will be addressed: i.) rates of ion migration within the polymer and ii.) rates of charge transfer between a polymer and a redox active molecule.  The potential-dependent microstructure and relative distribution of electronic states (percent doping) are found to be critical in both mechanisms, although happen at different time scales.  For charge transfer, the presence of an inverted regime is observed for the first time, representing a path forward to redox selectivity at polymer electrodes.

Metallo-β-lactamases (MBLs) are Zn(II)-containing enzymes produced by bacteria that inactivate all b-lactam containing antibiotics, including the carbapenems, which are antibiotics of last resort. While the MBLs have been studied for over 50 years, there are no clinical inhibitors for these enzymes. Therefore, there are few antibiotics available to treat bacterial infections caused by bacteria that produce a MBL. To address this problem, a multi-institution team of synthetic organic chemists (UC San Diego), medicinal chemists (UT Austin), microbiologists and MD’s (Case Western and the Cleveland VA), and structural biologists/biochemists (Miami University) teamed together to identify and develop new potential leads. In the seminar, recent results on a new inhibitor scaffold will be presented, along with biophysical studies on several other recently reported compounds in the literature.

Abstract:

Chemistry has always been an experimental science, but its guiding principles have come from the realm of physics since the discovery of the nucleus, electrons, and the quantum mechanics that rules them.  The field of quantum chemistry has matured to the point where computations can assist in understanding results form the laboratory, or even in suggesting future experimental work.  To obtain results of sufficient accuracy, the theoretical chemist must use a large basis set to expand the orbitals and a sufficiently sophisticated many-electron wavefunction.  However, when a heavy element is involved, a third complication arises, namely relativity.  This seminar will present a computational complement to results obtained in the Yang Laboratory at the University of Kentucky for a Cerium containing molecule.  The talk is intended to teach students the connection between the Schrodinger equation and the relativistic Dirac equation.  The correct physics of the latter can be approximated in a normal quantum chemistry program solving the former equation by modification of one electron integrals.  The presentation of relativistic quantum mechanics will be qualitative - no prior understanding of Einstein is necessary!

Molecular crystals have applications in nonlinear optics, organic electronics, and particularly in pharmaceuticals, as most drugs are marketed in the form of crystals of the pharmaceutically active ingredient. Molecular crystals are bound by dispersion (van der Waals) interactions, whose weak nature generates potential energy landscapes with many local minima that may be extremely close in energy. This often results in polymorphism, the crystallization of the same molecule in several different structures. Crystal structure may profoundly influence the physical and chemical properties, including the electronic and optical properties relevant for device applications.

We perform large scale quantum mechanical simulations to predict the structure of molecular crystals and investigate the effect of crystal packing on their electronic and optical properties. The massively parallel genetic algorithm (GA) package, GAtor, relies on the evolutionary principle of survival of the fittest to find low-energy crystal structures of a given molecule. Dispersion-inclusive density functional theory (DFT) is used for structural relaxation and accurate energy evaluations. Evolutionary niching is performed by using machine learning to perform clustering on the fly. The structure generation package, Genarris, performs fast screening of randomly generated structures with a Harris approximation, whereby the molecular crystal density is constructed by replicating the single molecule density, which is calculated only once. Many-body perturbation theory, within the GW approximation and the Bethe-Salpeter equation (BSE), is then employed to describe properties derived from charged and neutral excitations.

An emerging application of molecular crystals is singlet fission (SF), the down-conversion of one photogenerated singlet exciton into two triplet excitons. SF has the potential to significantly increase the efficiency of organic photovoltaics beyond the Shockley-Queisser limit by harvesting two charge carriers from one photon. However, the realization of SF-based solar cells is hindered by the dearth of suitable materials. We aim to discover new SF materials and optimize the crystal packing of known materials to enhance SF efficiency. We predict that crystalline quaterrylene and a lesser known monoclinic crystal structure of rubrene may exhibit high singlet fission efficiency, possibly rivaling that of the quintessential SF material, pentacene. Quaterrylene has the additional advantages of high stability, a narrow band gap, and a triplet energy in the optimal range to maximize photoconversion efficiency.