Byron Hempel Chemistry Biological-Chemistry BS 2014 Teaches Environmental Engineering at University of Arizona and Climbs Mount Lemmon.
This interview is part of a series conducted by the department called, "UK Chemistry Alumni: Where Are They Now." This interview was coordinated by Dr. Arthur Cammers.
This interview is part of a series conducted by the department called, "UK Chemistry Alumni: Where Are They Now." This interview was coordinated by Dr. Arthur Cammers.
Arthur Cammers: Steven, remind me again when you graduated ... I remember that I was DUS at the time.
By Olaoluwapo Onitiri
Many in the world emigrate from their homes due to hardships caused by wars. This was no different for Ghady Kanaan, who emigrated from Lebanon to the United States. He is graduating this May with a degree in chemistry, has already published research as an undergraduate with Mark Watson, associate professor of chemistry, and is working on another with Folami Ladipo, associate professor of chemistry.
Chemistry graduate students qualify for academic travel funding (typically to conferences) once each fiscal year (July 1 – June 30). The department will provide the initial $500. Additionally, the department will match up to $500 of what the advisor provides.
To request funding:
Arthur Cammers: I know you love the great outdoors ... and I know you are super curious about science. What's the back story? What influences created the current Anna?
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 Chemistry (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
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.
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
