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Chemistry Department Seminar

Development and Biological Evaluation of Selective Small-Molecule Inhibitors of the Human Cytochrome P450 1B1

Hachey

Abstract: The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this resistance phenotype. Thus, an approved CYP1B1 inhibitor may be of immense benefit to cancer patients struggling against chemotherapy-resistant disease.

However, developing selective inhibitors of CYP1B1 is challenging due to the existence of approximately fifty related cytochromes P450 found in humans which share similar structural features. Confounding this fact, CYP1B1 preferentially binds substrates of low three-dimensional complexity and with high lipophilicity, which from a synthetic viewpoint are relatively nondescript, making rational inhibitor design difficult.

This work offers new synthetic approaches toward the solution to the challenge of developing selective CYP1B1 inhibitors. The first part of the work describes the discovery and mode of action of a previously unknown inhibitor of CYP1B1 active at sub-nanomolar concentrations, and with unprecedented selectivity compared to existing inhibitors. Next, the pharmacokinetic optimization of this lead compound was undertaken resulting in an improved lead with excellent metabolic stability for future applications in disease models, and with the long-term goal of translation into the clinic for use in human patients. Together, the development of a series of new molecular entities is described which enable the exquisite control of the activity of this medically relevant enzyme and is an important step toward the development of drug candidates.

Date:
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Location:
CP 114
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Organic Semiconductor Thin Films: Crystal Growth and Interactions With Halide Perovskites

Rand_Photo

Abstract: In this seminar, we will focus on our recent work on two different thin film systems – metal halide perovskites and organic semiconductors.For one, through proper control of processing, we are able to realize pinhole free organic semiconductor films with single crystal grains with mm dimensions. We have found that transport in these films is considerably improved compared to disordered films, and that organic solar cells incorporating these long-range-ordered films exhibit highly delocalized, and band-like charge transfer (CT) states, contributing to noticeably lower energy losses. We will discuss these aspects and our understanding to-date of which molecules are amenable to the formation of such films, and how to propagate their growth. Also, organic hole transport materials (HTMs) are ubiquitous in halide perovskite solar cells, but what is less well known is that shallow HTMs that facilitate hole extraction from the perovskite also enable halogen transport. We will present our understanding of this phenomenon, as well as impacts to devices with regard to Au diffusion.

Bio: Barry Rand earned a BE in electrical engineering from The Cooper Union in 2001. Then he received MA and PhD degrees in electrical engineering from Princeton University, in 2003 and 2007, respectively. From 2007 to 2013, he was at imec in Leuven, Belgium, ultimately as a principal scientist, researching the understanding, optimization, and manufacturability of thin-film solar cells. Since 2013, he is in the Department of Electrical Engineering and Andlinger Center for Energy and the Environment at Princeton University, currently as a Professor. Prof. Rand’s research interests highlight the border between electrical engineering, materials science, chemistry, and applied physics, covering electronic and optoelectronic thin-films and devices. He has authored over 160 refereed journal publications, has 25 issued US patents, and has received the 3M Nontenured Faculty Award (2014), DuPont Young Professor Award (2015), DARPA Young Faculty Award (2015), and ONR Young Investigator Program Award (2016).

Date:
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Location:
CP 114
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Strategies to Increase Diversity, Equity, and Inclusion in Chemistry Learning Environments and Curriculum

Shanina Sanders JohnsonDr. Shanina Sanders Johnson
Ph
.D., Hampton University
B.S., University of North Carolina at Chapel Hill
At Spelman since 2011, promoted to Associate Professor recently

AbstractDr. Johnson's work has involved implementing culturally relevant pedagogies into organic chemistry lecture and laboratories. Activities that provide context to chemistry have been created and implemented to allow for incorporation of student background, interests, and experiences into the curriculum. These strategies allow students to see the relevance of science, reflect on their science identity, and connect their personal experiences and knowledge to their learning. Additionally, allowing for cultural context in the curriculum supports diversity within the classroom on multiple levels. This type of strategy is ultimately aimed at not only diversifying chemistry but also ushering in social change that provides for a more equitable field.  

 

This event is cosponsored by the College of A&S Dean’s Office.

Date:
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Location:
CP 114
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Organic Semiconductor-Incorporated Perovskites (OSiP) - A New Family of Hybrid Electronic Materials

Dr. Letain Dou

Abstract: Halide perovskites are exciting new semiconductors that show great promising in low cost and high-performance optoelectronics devices including solar cells, LEDs, photodetectors, lasers, etc. However, the poor stability is limiting their practical use. In this talk, I will present the development of a new family of stable organic-inorganic hybrid electronic materials, namely, Organic Semiconductor-Incorporated Perovskites (OSiP). Energy transfer and charge transfer between adjacent organic and inorganic layers are extremely fast and efficient, owing to the atomically-flat interface and ultra-small interlayer distance. Moreover, the rigid conjugated ligands dramatically enhance materials’ chemical stability and suppresses solid-state ion diffusion and electron-photon coupling, making them promising for many applications. Based on this, we demonstrate for the first time an epitaxial halide perovskite heterostructure with near atomically-sharp interface, which pave the way for perovskite nanoelectronics and nanophotonics. Finally, using this stable and solution-processable OSiPs, we demonstrate the fabrication of high-quality thin films, which enable highly stable and efficient solar cells and LEDs.

Bio: Dr. Letian Dou is currently the Charles Davidson Associate Professor of Chemical Engineering at Purdue University. He obtained his B.S. in Chemistry from Peking University in 2009 and Ph.D in Materials Science and Engineering from UCLA in 2014. From 2014 to 2017, he was a postdoctoral fellow at the Department of Chemistry, University of California-Berkeley and Materials Science Division, Lawrence Berkeley National Laboratory. His research interest includes the design and synthesis of organic-inorganic hybrid materials and low-dimensional materials, fundamental understanding of the structure-property relationships, as well as applications in high performance electronic and optoelectronic devices. He is a recipient of AIChE Owens Corning Early Career Award (2022), NSF CAREER Award (2021), Advanced Materials Rising Stars Award (2021), Office of Naval Research Young Investigator Award (2019), Highly Cited Researcher in Cross-Fields (2019-2022), MIT Technology Review Innovators Under 35-China Award (2018), and MRS Graduate Student Award (2014).

Date:
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Location:
CP 114
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Manipulating Supramolecular Interactions in Solution and Soft-Matter Formulations

 

Kumari_profile

Abstract: Supramolecular gelation is a fascinating self-assembly process that closely mimics important natural and biological events. The supramolecular nature of such materials imparts the system with reversibility and adaptivity. The individual or collective contributions of various non-covalent interactions, such as hydrogen bonding, π π stacking, metal–ligand coordination, host–guest interactions, and van der Waals interactions, are at the focal point of the structural evolution during an assembly process. Supramolecular gels have been studied extensively in the last few decades, mostly by exploiting the functional outputs for technological and medicinal applications. In comparison, pure structural investigations of supramolecular gel materials are rather limited. The lack of convincing structural data has multiple implications. The two most crucial factors for structural investigations are the experimental time scale and the sensitivity of the measurements towards structural evolution. Herein, we will investigate self-assembly processes of supramolecular nanoassmeblies under ambient versus non-ambient conditions. Specifically, we will probe how real-time measurements give valuable insights about nucleation and self-assembly of materials. The information obtained yields valuable information about structure-function correlation of materials which could have applications in several areas, including pharmaceutics and personal care. 

Kumar_Photo

Bio: Dr. Harshita Kumari, is an Associate Professor in the Division of Pharmaceutical Sciences at University of Cincinnati. Dr. Kumari’s work in the area of solution chemistry of supramolecular complexes is widely recognized. She integrates neutron scattering with supramolecular chemistry to unravel structural altercations in solution.

Her current research focuses on integrating principles of modern biophysics into material and formulation science towards the development of novel skin care, oral care and hair care products. Her research projects focus on understanding mechanisms of delivery and deposition of actives onto the skin/hair and elucidating the parameters to control them. In addition, her research focuses on developing methods to construct novel nanometric delivery vehicles, based on the principles of self-assembly and molecular recognition. Her work is published in several peer reviewed journals.

Date:
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Location:
CP 114
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48th Annual Naff Symposium

Oxidative Stress in Neurodegeneration: Focus on Alzheimer Disease

Schedule of Events - April 21, 2023

8:00am

Registration and Continental Breakfast
WT Young Library Gallery

8:30am

Welcome -

Dr. Eli Capilouto, President, University of Kentucky

Dr. Robert DiPaola, Provost, University of Kentucky

Dr. Lisa Cassis, Vice President for Research, University of Kentucky

Dr. Mark Lovell, Chair, Department of Chemistry, University of Kentucky

Dr. D. Allan Butterfield, Organizer, 48th Naff Symposium, University of Kentucky

9:00am

Prof. Barry Halliwell, National University of Singapore
"Is ergothioneine a factor against neurodegeneration and a promotor of healthy ageing?"

10:15am

Prof. Marzia Perluigi, Sapienza University of Rome
"Redox imbalance and metabolic defects in the brain of Down Syndrome: a synergistic path to Alzheimer's neurodegeneration"

11:30am

Lunch & Break

1:30pm

Prof. Mark Mattson, Johns Hopkins University
"Sculptor and Destroyer"

2:45pm

Break & Poster Session Set-Up
WT Young Library Gallery; Jacobs Science Building, Atrium

3:30pm

Poster Session
Jacobs Science Building, Atrium

4:45pm

Presentation of Poster Awards
Jacobs Science Building, Atrium

5:00pm

Close-off of the 48th Naff Symposium
Jacobs Science Building, Atrium

 

Speakers

Prof. Barry Halliwell

National University of Singapore

D. Phil. (Oxford), D. Sc. (London) Chairman, BMRC Advisory Council (BMAC), Agency for Science, Technology & Research (A*STAR) Distinguished Professor, Department of Biochemistry , National University of Singapore (NUS) Senior Advisor, Academic Appointments and Research Excellence, Office of the Senior Deputy President and Provost, NUS Programme Leader, Neurobiology Research Programme, Life Sciences Institute

Professor Halliwell graduated from Oxford University with BA (first class honours) and D.Phil degrees. He holds a Doctor of Science degree from the University of London. He was a faculty member with King’s College London (1974-2000) and held a prestigious Lister Institute Research fellowship. He was a Visiting Research Professor of Internal Medicine and Biochemistry at the University of California Davis (1995-1999). He now holds several key positions in Singapore, as indicated above. Professor Halliwell is recognized for his seminal work on the role of free radicals and antioxidants in biological systems, being one of the world’s most highly-cited researchers with a Hirsch-Index of 168 (Based on Scopus, Jan 2023). His Oxford University Press book with John Gutteridge Free Radicals in Biology and Medicine, now in its fifth edition (2015) is regarded worldwide as an authoritative text. He was honoured as a Citation Laureate (2021) for pioneering research in free-radical chemistry including the role of free radicals and antioxidants in human disease. The distinction is awarded by Clarivate to researchers whose work is deemed to be of “Nobel Class” as they are among the most influential, even transformative, in their fields. He was one of 16 scientists (only three in Chemistry) listed in the 2021 Hall of Citation Laureates.

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Prof. Marzia Perluigi

Sapienza University of Rome

Marzia Perluigi, PHARMAD, Head of Laboratory of Redox Biochemistry in Neuroscience (LRBN). Professional appointments: Professor of Biochemistry, Department of Biochemical Sciences “A. Rossi Fanelli – Medical School Sapienza University of Rome” Fields of Expertise: Biochemistry and cell biology.

The major research interest is the study of the role of oxidative stress in Down Syndrome (DS) and Alzheimer Disease (AD). Projects involve both the analysis of post-mortem brains, biological fluids and cellular and animal models of the diseases. In particular, current projects focus on defects of energy metabolism, failure of protein quality control (UPS and autophagy), impairment of mitochondrial activity, both in DS and AD. Further, preclinical studies are ongoing to test the neuroprotective effects of selected compounds able to prevent/slow the onset of dementia.

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Prof. Mark Mattson

Johns Hopkins University

Mark Mattson is the former Chief of the Laboratory of Neurosciences at the National Institute on Aging, and is now on the faculty of Neuroscience at Johns Hopkins University School of Medicine. His research has advanced an understanding of the cellular signaling mechanisms that control the formation and plasticity of neuronal networks in the brain, and cellular and molecular mechanisms of brain aging and neurodegenerative disorders. His research has also elucidated how the brain responds adaptively to challenges such as fasting and exercise, and he has used that information to develop novel interventions to promote optimal brain function throughout life. Dr. Mattson is among the most highly cited neuroscientists in the world with more than 900 publications and 200,000 citations. He was elected a Fellow of the American Association for the Advancement of Science and has received many awards including the Metropolitan Life Foundation Medical Research Award and the Alzheimer’s Association Zenith Award.

Mattson is the author of the book The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.


2023 Naff Symposium Committee

Prof. Allan Butterfield - Chair

Prof. Marcelo Guzman - (Chemistry)

Prof. Daret St. Clair - (Toxicology/Cancer Biology)

Date:
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Location:
WT Young Library Auditorium
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Exit Seminar: "Nanomaterial Synthesis and Real Time Investigation of Thermal Effects on Nanomaterial and Nano-Interfaces for Real World Applications"

AbstractAs interest in nanomaterials and nanotechnology continues to grow, so does the need for more efficient and economical synthesis methods to keep up with the demand. Nanomaterials, having at least one critical dimension measuring less than 100 nm, could exhibit unique properties compared to their bulk counterparts. These unique properties, which include electrical, optical, thermal, mechanical, and magnetic properties, influence the integration and utilization of these materials into devices and applications. The applications for nanomaterials are seemingly endless as they have functions in energy, biomedical, environmental, and many more. Working to develop different morphologies and sizes of nanomaterials will further help expand its utility. With the use of advanced characterization techniques such as in situ transmission electron microscopy (TEM), real time studies on the effects of external forces on nanomaterials are possible under controlled environments. This will give insight on how nanomaterials will perform in real world applications and will allow for the development of superior nanomaterials and applications.

The three sections of this talk will focus on the solid-state synthesis of crystalline nanomaterials with specific morphology as well as the real time observation of thermal treatments on the stability and degradation of nanomaterials via in situ TEM. The first two sections concentrate on the hydrothermal and chemical vapor deposition synthesis and materials characterization of nanomaterials with magnetic and semiconductor properties. The third section focuses on the in situ observation of the reaction of nanomaterial and nano-interfaces as they are subjected to increased temperatures within the TEM. The works presented here show the versatility of nanomaterial syntheses and demonstrate the application of real time advanced electron microscopy techniques to further study the structure-property relationships of nanomaterials.

Graduate Student Profile

Date:
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Location:
CP-114
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Exit Seminar: "The Application of Photoelectron Spectroscopies in Analyzing the Impact of Interfacial Energetics on Perovskite Solar Cells"

Abstract: In recent years, organic-inorganic metal halide perovskites (HP) have garnered tremendous attention in photovoltaic research. This attention is attributed to their low cost and excellent optoelectronic properties, including large absorption coefficients, tunable bandgaps, long charge carrier diffusion lengths, and low trap state densities. Inverted p-i-n architecture perovskite solar cells (PSCs) are of intense interest and are generally regarded as more amenable to low-temperature solution processing. Nevertheless, the development of inverted PSCs is lagging the conventional architecture devices. Imperfect energy level alignments and charge carrier recombination, especially at the interface between perovskite and electron transport layers (ETLs), are two main factors suppressing the power conversion in inverted PSCs.

Organic semiconductors (OSCs), including π-conjugated polymers and small molecules, display distinct advantages in terms of low-cost, lightweight, wide variety, easy solution-processed manufacturing as well as excellent mechanical flexibility. The molecule design produces numerous organic semiconductors with desired properties in application of various advanced organic electronics devices. However, the performance of OSCs-based devices is left behind their inorganic counterparts due to the lower carrier density and mobility. Molecular doping which provides a route to significantly enhance the electric properties, attracts attentions progressively.

Tuo Liu’s work during his PhD focused on the applications of photoelectron spectroscopies on the studies of perovskite solar cells and organic semiconductor-based electronics. The first work carried out how the surface ligands impact interfacial energetics and charge carrier dynamics at methylammonium lead iodide (MAPbI3)/C60 interfaces. The frontier electronic energy levels at perovskite/C60 interface are directly probed by ultraviolet photoelectron spectroscopy (UPS) and low energy inverse photoelectron spectroscopy (LEIPS), providing evidence of interfacial energetics reconstruction caused by surface ligands with different dipoles. Ultrafast absorption/reflectance spectroscopies and transient photovoltage/photocurrent are utilized in comprehensively picturing the charge dynamics in films and devices. The following work reports the doping mechanism in the photoactivated p-doping of hole-transporting material (HTM) to enhance hole extraction for perovskite/textured silicon tandem solar cells, making the device performance less sensitive to the variation of hole transport layer thickness. Last several collaborations works are based on the doping behaviors in different doped organic semiconductors, with applications in organic solar cells and thermoelectrics.

Graduate Student Profile

Date:
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Location:
CP114
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Exit Seminar: "Cell-engineered Vesicles for Therapeutic Delivery and Immunomodulatory Applications"

Abstract: Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems,  biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes  can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. Cell-engineered vesicles (CEVs) are smaller in size, can be generated in high yields, easily loaded with both lipophilic as well as hydrophilic cargo, and exhibit cell-targeting specificity both in vitro as well as in in vivo.

Cell-engineered vesicles generated from immune cells offer additional advantages as immunomodulatory therapeutic agents. Herein, we demonstrate that macrophage-engineered vesicles (MEVs) generated from macrophages, immune effector cells, can modulate the physiological states of immune cells including macrophages and microglia. While MEVs generated from anti-inflammatory (M2) macrophages re-program neuro-toxic pro-inflammatory (M1) macrophages towards M2-like phenotype, MEVs generated from M1 macrophages re-polarize M2  macrophages towards an anti-tumor M1-like phenotype. In addition, in vitro and in vivo delivery of cargo is facilitated by the ability of these vesicles to selectively target the same cell type from which they originated.

Programming cell-engineered nanovesicles through the targeted over-expression of specific membrane-bound ligands transforms them into a more potent immunomodulatory as well as therapeutic delivery platform. We tailored membrane-derived nanovesicles to have unique immunomodulatory features, including the potential to regulate immune cell polarization in both directions. These programmable nanovesicles adorned with certain membrane-bound ligands are capable of targeting particular cell types. Using programmed nanovesicles produced from macrophages enhances immune cell reprogramming to both proinflammatory and anti-inflammatory cells. Additionally, the incorporation of cancer cell-targeting moieties into the vesicle membrane enhanced the transport and absorption of therapeutically loaded nanovesicles, hence increasing their effectiveness.

Graduate Student Profile

Date:
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Location:
CP114
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"An Overview of Environmental Research at the U.S Army Engineer Research and Development Center"

Dr. Ferguson will be presenting a broad overview of her research portfolio and Dr.'s. Glasscott and Kimball will briefly discuss their specific research. The presentation will shed light on an alternative career path and should be of interest to a broad array of students. 

Date:
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Location:
CP 114
Type of Event (for grouping events):
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