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chemistry

Exit Seminar: "Translating chemistry, structure, and processing to the solid-state morphology and function of organic semiconductors through computational modeling and simulations" ech275 Tue, 10/04/2022 - 10:31 am

Chamikara Karunasena

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Abstract: The immense synthetic design space and material versatility have driven the exploration and development of organic semiconductors (OSC) over several decades. While many OSC designs focus on the chemistries of the molecular or polymer building blocks, a priori, multiscale control over the solid-state morphology is required for effective application of the active layer in a given technology. However, molecular assembly during solid-state formation is a complex function interconnecting the building block chemistry and the processing environment. Insufficient knowledge as to the how these aspects engage, especially at the atomistic and molecular scales, have so far limited the ability to predict OSC solid-state morphology, leaving Edisonian approaches as the stalwart methods. Therefore, through multiscale simulations combining atomistic quantum scale modeling and modern advanced sampling molecular dynamics (MD), we aim to establish first principles understanding required to synthetically regulate solid-state morphology of organic semiconductors (OSC) as a function of molecular chemistry and processing. In turn we try to understand the deceivingly simple yet complex mechanisms behind molecular aggregation and crystallization of OSC. Simultaneously, we develop semi-to-fully automated high-throughput schemes to automate the complex and labor-intensive analyses to generate data based on various crystal structures in different crystallization environments. Ultimately, we aim to bridge molecular-scale information revealed on solid-state physical organization, understood in the context of chromophore chemistry and the molecular environment, with the macro scale properties to uncover useful guidelines for rational design and morphology regulation of OSC systems.

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CP-114
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Exit Seminar: "Application Of Mass Spectrometry For Characterization Of Plant-Based Phenolics And Alkaloids: Paving The Way For Developing Plant-Derived Value-Added Compounds"

Graduate Student Profile

Abstract: Plant-derived compounds have the potential to produce value-added compounds with a variety of applications. For example, the lignin part of the lignocellulosic biomass, produced in large quantities as waste from the paper and pulp industries, is a rich source of phenolics with potential applications in the renewable energy sector, pharmaceutical, and chemical industries. On the other hand, plant alkaloids are the primary source for developing plant-derived therapeutics. Unfortunately, the recalcitrant nature of plant cell walls, low extraction yields of small secondary metabolites, and the lack of effective analytical methods for a rapid and accurate identification of plant-based compounds and plant’s degradation products are the major limitations in plant-based valorization efforts.


In order to address some of these challenges, this dissertation focuses on utilizing different mass spectrometry-based techniques such as UHPLC-MS, GC-MS, and direct infusion high-resolution accurate orbitrap and ion trap mass spectrometry for the detection and structure elucidation of plant-based phenolics and alkaloids in order to contribute to ongoing efforts toward valorization of plant-based compounds. Mass spectrometry-based techniques are widely used in pharmaceutical and chemical industries, and have been emerged as one of the most promising analytical techniques for the analysis of plant-based compounds.


In the second chapter of this dissertation, a mass spectrometric method based on lithium cationization was developed to sequence lignin model oligomers with mixed bonding motifs, with a potential application in facilitating the structure elucidation of lignin degradation end products with β-β and β-O-4 linkages. In the third chapter, an important lignan, syringaresinol, was characterized in bourbon whiskey. The origin of syringaresinol was investigated using a model aging experiment to further our understanding of bourbon’s chemical composition. In chapter four, the development of a mild ethanosolv treatment combined with a GC-MS method enabled the detection of several different phenolic compounds in lignocellulosic biomass, which can be potentially used to rapidly compare different biomass samples for the valorization applications. Lastly, in chapter five, synthetic methods in combination with extensive mass spectrometry-based analysis were used to semi-synthesize new plant-based alkaloids with potential applications in drug discovery and development.


Overall, these studies confirm that mass spectrometry-based techniques provide a sensitive and robust analytical platform for the analysis of plant-based products.

 

 
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CP-114
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Exit Seminar "Developments in Gold(III) Scaffolds for Protein Bioconjugation and Enhanced Anticancer Activity"

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 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

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CP-114B
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Exit Seminar "Design and Synthesis of New Organic Dithiols for Environmental Applications"

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

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CP-114B
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