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.

 

Linking molecular structure with excited-state photochemical dynamics is crucial for engineering efficient organic solar cells and related photochemical applications. Two molecular dye systems are currently under investigation in our lab: carboalkoxyphenylporphyrins in solution-cast thin films and a new family of highly fluorescent thiazolothiazole viologen dyes. The singlet exciton diffusion lengths of solution-cast porphyrin thin films with various alkyl chain lengths have been examined. Modifications of peripheral solubilizing groups help orientate porphyrins in solution processed thin films and influence molecular orientation. The photoluminescent singlet decay lifetime of pristine porphyrin films and films lightly doped with [6,6]-phenyl-C61-butryic acid methyl ester (PCBM) were used in a 3D exciton diffusion Monte Carlo simulation to extract the exciton diffusion parameters and the nanocomposition. Longer alkyl chain derivatives yielded increased PL decay lifetimes and lengthened exciton diffusion lengths (L_D) for octyl and hexyl containing porphyrin derivatives. GIWAXS and XRD data indicates that molecular organization is strongly dependent upon the peripheral carboalkoxy substituent, and that nematic molecular organization resulted in an increase in the exciton diffusion length. Our findings are an important step toward a deeper understanding of the exciton diffusivity and molecular packing relationship. We have also synthesized a class of extended viologen dye structures that incorporate a thiazolo[5,4-d]thiazole backbone. The dyes exhibit both reversible yellow to dark blue electrochromism and high fluorescence quantum efficiency that is deactivated upon electrochemical reduction. The fused bicyclic thiazolothiazole heterocycle allows the alkylated pyridinium groups to remain planar, strongly affecting their electrochemical properties. The electrochromic and strongly fluorescent properties make these materials attractive for molecular electronics, biomolecular sensing, and other photochemical applications.

 

Although “ordered” organic π-conjugated assemblies outperform “disordered” ones in many optoelectronic device applications, we are far from being able to port the well-understood supramolecular recipes of π-systems from solution to solid-state device environments. For the past several years we have been exploring hydrogen bond (H-bond) directed self-assembly of π-systems along these lines, for example, to enhance their absorption and charge transport properties for organic photovoltaic (OPV) applications. Various examples of oligothiophenes outfitted with heterocycles capable of forming H-bonded “rosettes” will be discussed in this context. The second part of the talk will introduce new monomers derived from [2.2]paracyclophane (pCp) that are capable of robust H-bond directed self-assembly into one-dimensional nanostructures in solution and the solid state. The design introduces transannular (intramolecular) H-bonds between pairs of pseudo-ortho-positioned amides as a way to preorganize the molecules for intermolecular H-bonding with two neighbors. The result is formation of homochiral, one-dimensional pCp stacks that show supramolecular polymer signatures in solution.

Abstract: The philosophy of science studies how individual scientific concepts, models, theories, and experiments all influence the development of scientific knowledge. My research in the philosophy of nanoscience applies methods from philosophy of science to understanding how problems raised by nanoscience have changed our understanding of concepts, theories, and models from physics, materials science, and inorganic chemistry. For instance, studying the synthesis, simulation, and characterization of mixed-metal nanoclusters raises questions about whether these objects count as alloys. In this talk, I examine some keys questions from philosophy of science for chemistry and nanoscience and highlight some results from my approach to answering these questions. Bio: Julia Bursten is a second-year assistant professor of philosophy at the University of Kentucky specializing in philosophy of the physical sciences. Her research studies how theories and models work in nanoscience, chemistry, and materials science, and why theories in these sciences often work differently than theories in areas like quantum physics and biology.