ÌÇÐÄvlog¹Ù·½Èë¿Ú

Jianguo Mei is currently Richard and Judith Wein Professor of ÌÇÐÄvlog¹Ù·½Èë¿Ú at Purdue University. His research interest centers on the design and development of semiconducting polymers for flexible electronics and bioelectronics. He has published over 100 peer-reviewed papers with over 14000 citations, 4 book chapters, and 18 granted US patents. Dr. Mei is a recipient of an NSF CAREER award, the Office of Naval Research Young Investigator Award (ONR YIP), the ACS PMSE Young Investigator, the ACS Division of Organic ÌÇÐÄvlog¹Ù·½Èë¿Ú (DOC) Academic Young Investigator, and Purdue’s Teaching for Tomorrow Fellowship. He is also a co-founder of Ambilight Inc, a venture-backed startup (Series C) dedicated to the commercialization of roll-to-roll manufactured thin-film electrochromic for smart windows.

Abstract: The concept of organic electronics emerged in the late 1980s. The promise of solution-processing, mechanical flexibility, light weight and low cost has been driving the development of organic semiconductors and electronics. Three decades of continuous efforts from the community have nurtured the technological maturity of a number of organic electronics. Part of my research group has been actively pursuing the development of polymer-based electrochromic technology. In this talk, I will share our journey of moving electrochromic technology from lab to fab. In particular, I will introduce our latest development of highly conductive transparent organic conductors (TOCs) and ultra-high contrast transparent-to-colored electrochromic polymers.

Prof. Sachin Handa is currently a tenured associate professor in the chemistry department at the University of Louisville. In less than four years, he completed his Ph.D. in 2013 and then worked as a postdoc fellow with Prof. Bruce Lipshutz from 2013-2016. He started his independent career in 2016. His research interests are green chemistry, energy, nanocatalysis, and photochemistry. Recently, he has received the NSF CAREER award, Ralph E. Powe Junior Faculty Enhancement Award in Physical Sciences by Oak Ridge Associated Universities, and Peter J. Dunn Award for Green ÌÇÐÄvlog¹Ù·½Èë¿Ú and Engineering Impact in the Pharmaceutical Industry. Besides fundamental research, his research significantly focuses on synthetic problems associated with the pharmaceutical industry. Currently, his research is funded by NSF, Novartis Institutes for BioMedical Research, Novartis Pharmaceuticals Switzerland, AbbVie, Takeda, and Biohaven Pharmaceuticals. He also serves on editorial boards of various journals, such as ACS Sustainable ÌÇÐÄvlog¹Ù·½Èë¿Ú and Engineering, Green ÌÇÐÄvlog¹Ù·½Èë¿Ú Letters & Reviews, and Molecules.

Abstract

Water appears to be the only solvent for life to occur on this planet; nonaqueous solvents may support life elsewhere in the universe.

Faculty Host: Dr. Robert Grossman

Abstract: Oxidative Phosphorylation occurs within the inner mitochondrial membrane producing ATP for the cell’s energy needs. The Electron Transport Chain carries out the transfer of electrons from electron carriers through a series of proteins to form a proton gradient across the membrane. This gradient acts as the energy source needed to put a phosphate onto ADP. With the large amounts of free electrons and oxygen within the mitochondria, an inevitable by-product of free radicals in the form of superoxide are produced. Superoxide (O-?2) is an extremely reactive radical that can go on to perform further reactions leading to the formation of more radicals. When these radicals and reactive oxygen species are kept in balance they act as signaling molecules for the cell. A network of antioxidant proteins helps the cell to keep this balance. However, when there is an overload of radicals and ROS within the cell leading to oxidative damage and becoming detrimental to the cell’s ability to survive.  The brain is made up of different types of cells, neurons, and glia, that are rich in polyunsaturated fatty acids and have an abundance of O2. The combination of these things is what allows the brain to work with such high function, but it is also this combination that can lead to unfavorable reactions. The abundance of O2 allows for higher changes of free radicals and reactive oxygen species which can interact with the polyunsaturated fatty acids in a process called lipid peroxidation. Lipid peroxidation results in the formation of 4-hydroxynonenal (HNE) which has deleterious effects within the cell.  HNE adducts to proteins on a cysteine, lysine, or histidine. When these amino acids are located towards the inside of the protein it causes a conformational change of the protein and therefore a loss in function.  The adduction of HNE to proteins has been observed in different brain related diseases such as Glioblastoma and Alzheimer Disease.  Glioblastoma is one of the most difficult forms of cancer to treat due to location of the tumor and its resistance to radiation. Oxidative damage within the tumor cells does not seem to cause the same deadly effects as it would to the surrounding cells. When tumor cells have a large amount of oxidative damage there is a need to rid the cell of the affected proteins. This is in the form of extracellular vesicles (EVs). The findings of this dissertation elucidate the mechanism by which these EVs aid in the progression of the tumor cells. EVs bleb from the surface of the cell carrying the HNE adducted proteins into the extracellular space and encounter the surrounding glial cells and neurons. When the EVs are taken up by the glial cells, such as astrocytes, this induces the production of ROS in the form of hydrogen peroxide. This ROS is key in inducing proliferation of the tumor cells and furthering radiation resistance.  Alzheimer Disease has also been shown to have HNE adducted proteins and oxidative damage. One such pathway is affected in Alzheimer disease, the Pentose Phosphate Pathway, depending on the apolipoprotein E (ApoE) allele status of the cell. There are three variations of this gene, E2, E3, or E4, with the most common being E3. Those who have ApoE4 have a higher risk of developing Alzheimer Disease. ApoE4 allele is also seen in conjunction with higher oxidative damage and HNE production within the cell. The findings in this dissertation show the correlation between the ApoE allele status and the oxidative damage.

Graduate Student Profile

Abstract: 

Site-selective modifications of target proteins using specifically designed small molecules is a powerful tool that has been extensively utilized for drug discovery. Small molecules can modify proteins either covalently or non-covalently depending on their structures and intrinsic chemical reactivity. Covalent chemical modification presents a more stable and often irreversible interaction with target proteins; unlike non-covalent binders, which form weak, reversible interactions with protein. Therefore, covalent modifiers represent an effective class of therapeutics due to their stability and irreversibility once bound to target proteins of interest. I hypothesized that tuning biocompatible, high-valent gold(III) complexes toward nucleophile-induced reductive elimination will lead to covalent protein modification by arylation. While most proteins are expressed amongst all cell types; protein overexpression is a common phenomenon in several cancer types due to their rapid proliferative phenotype and mutations compared to healthy non-cancerous cells. The nucleophilic amino acid side chains in proteins can be used as reactive handles for covalent modifications. Amongst the naturally occurring amino acids; cysteine, the most intrinsically nucleophilic, contains a highly reactive thiol functional group. This innate nucleophilicity provides a framework for covalent modification with electrophiles, which includes but is not limited to electron-deficient metal centers (e.g., Au and Pd).

Although there are previous reports successfully identifying transition metals as suitable chemical modifiers, specifically, tuning gold(III) complexes for selective binding offers a unique strategy for chemotherapeutics. Gold(III) metal centers are innately acidic and react with softer bases such as phosphorous and sulfur unlike the traditionally used late transition metals. Secondly, gold(III) complexes are known to target proteins over DNA, unlike other common transition metal complexes such as platinum and ruthenium. Combining the innate ability of gold(III) complexes to interact with proteins and the high affinity for cysteine thiols, rationale design of highly selective protein modifiers and efficient chemotherapeutics is possible.

My work focused on tuning the reactivity of cyclometalated gold(III) complexes for cysteine arylation and ligand-directed bioconjugation using Metal-mediated Ligand Affinity ÌÇÐÄvlog¹Ù·½Èë¿Ú (MLAC) have been elucidated to modify biomolecules including antibodies and undruggable protein targets such as KRAS. While developing cyclometalated gold(III) complexes discussed herein, a unique class chiral gold(III) complexes bearing diamine or phosphine ligands led to other applications including improved anticancer activity in comparison to first generation of gold(III) complexes. A key highlight is the development of stable organometallic gold(III) macrocycles with potent in vitro and in vivo anticancer action in aggressive cancer types including triple negative breast cancer (TNBC).  

KEYWORDS: Site-selective protein modification, gold complexes, covalent binders, cysteine arylation, anticancer

Graduate Student Profile

Abstract: A thiol molecule, 2,6-pyridinediamidoethanethiol (PB9), was synthesized based on the pyridine-2,6-dicarboxamide scaffold with appended cysteamine group. PB9 acts as an effective chelator for Pb(II) due to multiple binding sites (N3S2) through irreversible binding precipitating Pb(II). Removal of aqueous Pb(II) from solution was demonstrated by exploring the effects of time, initial PB9:Pb(II) ratios, pH, exposure time, and solution temperature. After 15 min the Pb(II) concentrations were reduced from 50 ppm to 0.3 ppm (99.4%) and 0.25 ppm (99.5%) for PB9:Pb ratios of 1:1 and 2:1, respectively.  Removal of >93% Pb(II) was observed over multiple pH values with negligible susceptibility for leaching over time. The thermodynamic studies reveal the removal of Pb(II) from solution is an entropically driven spontaneous process. Solution-state studies (UV-Vis, 1H-NMR, 13C NMR) along with solid-state (IR, Raman, and thermal studies) for L/Pb(II) compounds were performed. UV-vis displays a global maximum at 274 nm and a local maximum at 327 nm for ligand-to-metal charge transfer S- 3p -> Pb2+ 6p, and intraatomic Pb2+ 6s2 -> Pb2+ 6p transitions.  A Probable molecular structure designed is PB9 behaving like a bis-deprotonated ligand with an N3S2 donor set to give Pb(II) a pentagonal environment with non-stereochemically active s electrons is proposed.  However, the existence of a cyclic oligomeric (PB9)4(Pb)4 or polymer (PB9)?(Pb)? structure is evident by broad melting point, insolubility in most common solvents, and amorphous powder XRD. PB9 also exhibits high sensitivity and selectivity towards Fe3+ over other metal ions, acts as a naked-eye detector showing colorless to yellow, and by fluorescent quenching. The quenching efficiency found by Stern-Volmer is 7.42 ± 0.03 × 103 M-1 with a higher apparent association constant of 9.537 X 103 M-1. A linear range of Fe3+ (0- 80 µM) with a detection limit of 0.59 µM (0.003 ppm) was found. The obtained detection limit was much lower than the maximum allowance limit of Fe3+ (0.3 ppm) regulated by EPA in drinking water.  Since Pb(II) removal using PB9 was higher than 15 ppb (EPA limit), a separate study was conducted to explore the use of thiol molecule (AB9) which was already developed in our lab previously. Thus, 2,2'-(isophthalolybis(azanaediyl))bis-3-mercaptopropanoic acid (AB9) was coupled to amine-functionalized silica and silica-coated magnetic nanoparticles (with Fe3O4 core). Results revealed successful fabrication of AB9 on mesoporous silica and MNPs surfaces without introducing crystalline impurities. Indeed, an added advantage for AB9-MNP over AB9-silica is its superparamagnetic nature where a magnet was used to isolate the Pb(II)-containing (solid) composite from the treated water. The >99.9% removal of Pb(II) was obtained by AB9-MNPs with detectable Pb(II) dropping to below 15 ppb EPA level. The obtained equilibrium results were in good agreement with the Langmuir model suggesting a dominant chemical adsorption mechanism on AB9- composites with monolayer coverage with maximum adsorption capacities of  24.80 and 56.40 mg/g respectively for AB9-silica and AB9-MNP implying the thiol group improved the adsorption capacity of Pb(II). This eco-friendly modification with rapid magnetic separation makes these AB9-MNPs a good candidate for aqueous Pb(II) removal

Abstract: To develop an effective battery cathode material that can be useful for future batteries, the thermal stability and ion migration dynamics need to be well understood. In situ transmission electron microscopy (TEM) is a popular and proven technique to study the evolution of local structures during the dynamic processes in the cathode materials. This dissertation will demonstrate the application of high-resolution imaging and in situ heating and biasing in the TEM to study the structure and composition, morphology change, and ion migration in the cathode materials.   The three chapters in this dissertation will be focused on the two cathode materials: zeta (?) vanadium pentoxide, and chromium intercalated sodium manganese oxide. The first project demonstrates the effect of in situ heating method, nanowire size, sodium content, and vacuum condition on the thermal stability of zeta (?) vanadium pentoxide in real-time in the TEM. The second project concentrates on in situ biasing in the TEM to study the sodium ion migration, silver exsolution, and negative differential resistance phenomenon in the zeta (?) vanadium pentoxide. The third project concentrates on the synthesis and characterization of chromium incorporated sodium manganese oxide. The works presented here show the capability of in situ TEM imaging techniques to study the dynamic changes in the structure and composition of the nanomaterials during the heating and biasing processes.

Graduate Student Profile

Abstract: Lignocellulosic biomass is pivotal in the development of renewable energy sources and materials essential to mitigate the exploitation of fossil fuels causing environmental pollution issues. The conversion of biomass into fuel requires the hydrolysis of cellulose and a biproduct of this process is the isolation of lignin as biorefinery waste. Lignin is a complex high molecular weight polymer whose structure remains undefined and critically limits potential industrial applications of lignocellulosic biomass. The advancement of analytical methods for structural elucidation of lignin and its ensemble of phenolic compounds is therefore essential to advance this field. While a variety of analytical methods play an integral role in developing our understanding of lignin, only mass spectrometry can provide exact information on the substructure of lignin, the sequence of monolignols, and linkage types. In this dissertation, the supramolecular interactions of a variety of model lignin monomers and dimers are characterized to improve mass spectrometric analysis and potential applications of lignin as a renewable source of valuable phenolics.  Mass spectrometry (MS) requires the conversion of analytes into detectable gas-phase ions, and the most widely used ionization technique for biological compounds is electrospray ionization (ESI). The primary challenge facing ESI-MS analysis of lignin is ionization because lignin compounds do not readily accept protons for positive mode analysis and negative mode analysis causes destabilization and in-source fragmentation. While protonation is unsuccessful, lithium adduction has recently been discovered as a promising method for ESI-MS sequencing of lignin compounds. Consequently, the gas-phase lithium cation basicity of synthetic monolignols and dimers were characterized by ESI-MS to improve sequencing techniques and future applications of lithium adduction.  Lignin also presents a challenge in biomass processing due to its inhibition of the enzymatic hydrolysis of cellulose for biofuel production. Supramolecular guest-host interactions have the potential to isolate lignin compounds from biomass fractions through the formation of inclusion complexes and the development of selective materials. In this work a cyclodextrin host was selected based on its remarkable ability to encapsulate guest molecules and availability on the industrial scale. The binding strength between guest and host was evaluated for lignin model dimers with cyclodextrin by ESI-MS for comparison with our collaborators ITC and computational results. The retention of electrostatically bound complexes during the ESI-MS process and lithium adduct impacts are also extensively evaluated.  Lignin compounds and metabolites additionally show biological activity, and therefore the separation of diastereomers is of interest for pharmaceutical applications. To advance biological studies, the success of chromatographic separations (HPLC) of lignin model dimers and their diastereomers is evaluated. The separative method is coupled to MS with post-column lithium adduction to identify lignin dimers. Novel determinations of lignin dimer partition coefficients are also presented, a measure of hydrophobicity important for biological studies and chromatographic method development. These fundamental characterizations of lignin model compounds are essential for the continued advancement of renewable energy and materials derived from lignocellulosic biomass.

Jonathan Rivnay

Department of Biomedical Engineering and Simpson Querrey Institute

Northwestern University, Evanston, IL

Abstract: Direct measurement and stimulation of ionic, biomolecular, cellular, and tissue-scale activity is a staple of bioelectronic diagnosis and/or therapy. Such bi-directional interfacing can be enhanced by a unique set of properties imparted by organic electronic materials. These materials, based on conjugated polymers, can be adapted for use in biological settings and show significant molecular-level interaction with their local environment, readily swell, and provide soft, seamless mechanical matching with tissue. At the same time, their swelling and mixed conduction allows for enhanced ionic-electronic coupling for transduction of biosignals. Structure-transport properties allow us to better understand and design these active materials, providing further insight into the role of molecular design and processing on ionic and electronic transport, charging phenomena, and stability for the development of high-performance devices. Such properties stress the importance of bulk transport processes and serve to enable new capabilities in bioelectronics. In this talk I will discuss the design of new organic mixed conductors and future design rules for performance and stability. I will demonstrate how such materials properties relax design constraints and enable new device concepts and unique form factors, allowing for flexible amplification systems for electrophysiological recordings, and electroactive scaffolds to modulate tissue state and/or cell fate. New materials design continues to fill critical need gaps for challenging problems in bio-electronic interfacing.

Faculty Host: Dr. John Anthony

Abstract: Despite the clinical success and proven efficacies of the conventional platinum-based drugs cisplatin, carboplatin, and oxaliplatin, these drugs suffer from a number of challenges that limit their more widespread therapeutic potential. These limitations, including toxic side effects and susceptibility to cancer drug resistance mechanisms, have prompted researchers to explore alternative metal complexes as anticancer agents. In this presentation, an overview of our work on the development and understanding of rhenium-containing organometallic complexes as potential drug candidates is discussed. We will disclose our discovery that a wide range of rhenium(I) tricarbonyl complexes exhibit potent in vitro anticancer activity via diverse biological mechanisms of action. Furthermore, several classes of rhenium(I) tricarbonyl complexes that we have investigated undergo photochemical processes that can be harnessed to trigger cancer cell death selectively upon irradiation or can be used for imaging applications. For this class of compounds, we have carried out detailed biological studies to determine their mechanisms of action. Our results indicate that subtle structural modifications of these compounds can lead to significant changes in their biological properties. Lastly, in vivo studies will be presented, demonstrating that the potential of these compounds as anticancer drug candidates exists beyond in vitro cellular experiments.

University of Alabama

Abstract: We aim to apply bioinorganic and organometallic chemistry to problems that relate to green chemistry and sustainability. We are exploring how protic and electron donor groups impact catalysis. We have pursued reactivity inspired by the need for energy storage, specifically carbon dioxide reduction. Recently, we designed new pincer ligands using N-heterocyclic carbene (NHC) and pyridinol rings that can change their properties by protonation and deprotonation, rather than lengthy synthesis. The most active transition metal catalysts with these pincers use methoxy groups which balance electron donor ability with stability. This has allowed for formation of ruthenium, cobalt, and nickel complexes that perform catalytic and light driven carbon dioxide reduction. We have also demonstrated that the OH derivatives can be switched on or off for catalysis with acid concentration. One of our ruthenium complexes is record setting in terms of reaction rates and selectivity. CO₂ reduction is of fundamental importance to the impending global energy crisis, and carbon dioxide reduction (when coupled with water oxidation) can allow for a sustainable method of energy storage in solar fuels. Furthermore, we have studied our hydroxyl substituted bipyridine ligands as a part of ruthenium based anticancer metallo-prodrugs. The ruthenium complexes are light activated and show selective toxicity towards cancer cells.  

Bio: Elizabeth T. Papish was born and raised on Long Island, NY. She studied chemistry at Cornell Univ. (BA, 1997) and Columbia Univ. (PhD, 2002). She has taught at Franklin & Marshall College (2002-3), Salisbury Univ. (Asst. Prof. 2003-2007), Drexel Univ. (Asst. Prof. 2007-2012, Assoc. Prof. 2012-2013), and at the Univ. of Alabama (Assoc. Prof. 2013-2019, Full Prof. 2019-present). Her research group studies bioinorganic and organometallic chemistry with an emphasis on designing new organic ligands for the use of transition metal complexes in energy related catalysis applications and for metal-based therapies for health applications. She is the recipient of an NSF CAREER award (2009) and has been honored with the "Outstanding Research Mentor of the Year Award" at Salisbury Univ. in 2007 and with the "College of Arts and Sciences Teaching Award" for excellence in teaching and mentorship from Drexel Univ. in 2012.  In 2013, Papish and her student received the "Division of Inorganic ÌÇÐÄvlog¹Ù·½Èë¿Ú Award for Undergraduate Research" from the American Chemical Society. Her research is currently supported by NSF and NIH.

Faculty Host: Dr. Aron Huckaba