Chemistry

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Interface and Depth-dependent Study of Halide Perovskite Semiconductors for Improved Optoelectronics
(2026-04-20) Huang, Zixu; Ginger, David
Lead halide perovskites are one of the most promising candidates for solar cells with high absorption coefficients, tunable bandgaps, and excellent charge transport properties. However, these materials still suffer from issues such as phase segregation and interfacial defects, leading to reduced solar cell’s stability. Here we develop a variety of instrument-based techniques to study perovskite phase segregation and the interface chemistry of perovskite. We observed both vertical and lateral cation segregation on mixed-cation perovskite, with non-emissive δ-CsPb(IxBrx)3 cluster on the surface, and FA-rich perovskite underneath, leading to accelerated light-induced degradation on those heterogeneities. Then we found perovskite surface passivation with AEAPTMS vacuum treatment greatly enhances perovskite device’s performance, due to the AEAPTMS-FA+ reaction on the perovskite surface. Finally, we developed a fast, in-situ and nondestructive method toprobe the degradation behavior on the buried interface with UV treatment. With multiwavelength excitation, we can study the depth-dependent information on perovskite and the HTL site is most affected by UV exposure.
Theory of Momentum-Resolved Crystal Excitations in the Electron Microscope
(2026-04-20) Rossi, Andrew W; Masiello, David J
As atomic and nanoscale materials continue to advance and reveal novel physical properties, the development of reliable and precise characterization techniques has become increasingly crucial. Motivated by recent experimental advances in electron energy loss spectroscopy (EELS) performed inside electron microscopes, this dissertation presents a general theoretical framework to describe the momentum-resolved inelastic electron scattering of wide-field electrons from two-dimensional materials, spanning from atomic crystals to nanophotonic arrays. The formalism incorporates fully-retarded electromagnetic interactions, which are required to accurately model nanophotonic material responses. By accounting for the energy–momentum dependence of the probing electron’s polarization and relativistic kinematics, the theory establishes selection rules for scattering processes within and beyond the first Brillouin zone, reveals optically dark transitions outside the light cone, and illustrates the roles of electron velocity and scattering geometry. Building on this theory and recent advances in structuring the transverse phase of electron beams, pinwheel free electron states carrying well-defined pseudoangular momentum (PAM) are also introduced. These beams enable direct detection of chiral phonons, a long-standing challenge for conventional characterization techniques. Taken together, this work establishes a pathway for tailoring the polarization and symmetry of free electron probes to selectively couple to targeted material excitations, enabling precise investigation of emergent material properties.
Expanding Polymer Design Tools: Molecular Fluxionality and Topological Crosslinks for Novel Polymer Networks
(2026-04-20) Sun, Peiguan; Golder, Matthew
Polymer materials have profoundly transformed our lives over the past century. While we derive significant benefits from their convenience, the escalating plastic waste crisis necessitates a deeper comprehension of the molecular structure-property correlation inherent in plastic materials. Consequently, it is imperative to devise novel motifs and building blocks for sustainable polymers that will shape the materials of the future. In this dissertation, I expanded polymer design toolkit by introducing two novel motifs. Starting with the first incorporation of molecular ball joint, bullvalene, into polymer networks. Since its initial conception, bullvalene has captivated scientists due to its remarkable fluxionality. It undergoes rapid low barrier sigmatropic rearrangements, resulting in a molecule devoid of a permanent structure at room temperature. Recent breakthroughs in synthesis have reignited the interest in its application in the solution state. I explored bullvalene’s fluxionality in bulk polymer materials using dynamic mechanical analysis. Through this research, we demonstrated bullvalene as a unique low-force covalent mechanophore. Its introduction enhanced the polymer’s energy dissipating mechanism and facilitated the formation of stronger glass structures during the glass transition process. Furthermore, I investigated the interplay between polymer topology and network hierarchy to devise a class of material that has not yet been officially defined by IUPAC. This network was constructed using cyclic polymers as topological crosslinks to toughen existing polymer materials. By employing ring expansion metathesis polymerization process, I successfully synthesized cyclic polymers at scale. These cyclic polymers were subsequently dissolved along with linear polymer precursors and cured into unique semi-interpenetrating polymer networks. The bulk properties of these networks were assessed through mechanical testing and molecular dynamic simulations. The results demonstrated that the networks consisted of cyclic polymers exhibiting enhanced toughness and stiffness compared to control networks composed of linear polymers. This dissertation presents two distinct pathways for designing novel polymer materials that hold great promise for the development of next-generation energy dissipating and robust polymer materials.
Development of chemoproteomic methods for profiling the conformational dynamics of protein kinases
(2026-04-20) Brush, Daniel; Maly, Dustin J
Protein kinases are regulated by local structural and microenvironmental features that are not fully captured by existing chemoproteomic methods, and comprehensive maps of lysine reactivity across the human kinome remain limited. Here, we developed a kinobead-coupled DIA-MS workflow to quantify kinase lysine reactivity in electrophile-treated samples by monitoring the intensity depletion of unmodified lysine-containing peptides. Using immobilized DB65 kinobeads to enrich folded kinases, we consistently quantified >1,000 lysines across >100 protein kinases and achieved ~4-fold deeper lysine coverage per kinase than previously reported proteome-wide lysine-reactivity datasets. Applying this framework to multiple lysine-reactive electrophile classes generated quantitative kinase engagement landscapes and showed that electrophile choice probes distinct subsets of kinase lysines. Formaldehyde- and activated ester-based labeling produced different patterns of kinase lysine engagement, indicating that kinase lysine behavior is not captured by a single global reactivity axis. Extending the same readout to lysine-reactive fragment electrophiles further showed that fragments do not broadly engage kinase lysines, but instead concentrate high-magnitude liganding responses at a smaller subset of sites, consistent with increased dependence on molecular recognition. Within this panel, a squarate ester fragment, ASQ, displayed a scout fragment-like profile, combining near-baseline median behavior with a distinct high-magnitude responder tail. Together, these studies establish a scalable platform for profiling chemically distinct kinase lysine environments and prioritizing candidate lysines for future mechanistic and covalent ligand discovery studies.
Structural and kinetic investigation into the roles of scaffolding and phosphopriming on GSK3 pathway insulation
(2026-04-20) Jameson, Noel; Zalatan, Jesse
The kinase GSK3 is key regulator of multiple signaling pathways, including differentiation, energy homeostasis, and development. Its involvement in many distinct pathways causes the potential for crosstalk, where the upstream signal from one pathway inappropriately activates the downstream response of another. To phosphorylate specific substrates, GSK3 recognizes pre-phosphorylated, or ‘phosphoprimed’ sequence motifs on substrate proteins. Phosphopriming ensures that GSK3 substrates have already been acted upon by upstream kinases within specific signaling pathways, making GSK3 activity dependent on pathway activation. Using structural and quantitative biochemical studies, we found that substrate phosphopriming has large effects on GSK3 catalysis that do not cause detectable changes in crystal structures. These results indicate that subtle or transient structural changes in and around the GSK3 active site may play a crucial role in directing GSK3 towards specific substrates. Alongside phosphopriming, scaffold proteins coordinate GSK3 with specific substates, promoting phosphorylation. In the Wnt signaling pathway, the scaffold protein Axin specifies GSK3 to interact with the Wnt substrate β-catenin, preventing GSK3 crosstalk into other pathways. We sought to investigate if Axin also insulates GSK3 from external signals. Using quantitative biochemical analysis and cell culture studies, we found that Axin prevents GSK3 phosphorylation at Ser9, a crucial step of both Insulin and Growth factor signaling. In doing so, Axin protects GSK3 from insulin and growth factor pathways, preventing crosstalk. To determine if other GSK3-dependent pathways use the same insulation mechanism as Axin, we used interactome labeling to find scaffolds that compete with Axin for GSK3 binding. We discovered that the Hedgehog scaffold SUFU competes with Axin to coordinate GSK3, and that SUFU can be displaced by Axin in vivo. Taken together, these findings resolve how phosphopriming enables GSK3 catalysis, uncovers how Axin insulates GSK3 from other pathways, and characterizes developmental scaffold proteins compete for the same GSK3 binding interface to define distinct subpopulations.
Protein design for cyclic peptide and small molecule binding
(2026-04-20) Hanna, Stephanie; Baker, David
Proteins can bind diverse classes of ligands and the presence of these ligands can induce a response in the cell. Particularly, for the design of systems where the interaction of a ligand with intracellular binding partners can elicit a response, the ligand must be able to cross the cell membrane. To achieve this aim, I explored two classes of ligand: cyclic peptides and small molecule HIV protease inhibitors. I designed protein binders for each of these ligand classes. For one cyclic peptide, I utilized a library of designed homodimeric scaffold proteins as the protein binding component and demonstrated their response to the cyclic peptide in mammalian cells. For HIV protease ligands, I explored the application of deep learning based protein design tools to generate backbones, design sequences and predict the ligand-protein complex. While two libraries of designs were screened for binding via yeast display with a biotinylated ligand, further development of the design pipeline is necessary to obtain protein binders with high affinity to these ligands.
From Fundamentals to Applications: Advancing Ion Mobility and Mass Spectrometry for Molecular Characterization
(2026-04-20) Martynova, Alice; Bush, Matthew F
This dissertation describes new mass spectrometry (MS) and ion mobility-mass spectrometry (IM-MS) methodologies and fundamental investigations aimed at enhancing molecular characterization across diverse chemical systems. Mass spectrometry is a powerful analytical technique that measures ions' mass-to-charge (m/z) ratios, enabling determination of molecular mass and elemental composition. The structural information obtainable from MS can be further enhanced by coupling with ion mobility (IM), a gas-phase separation technique in which charged ions are separated based on their size, shape, and charge. From IM measurements, ions' collision cross-sections (CCS or Ω) can be determined, providing an additional dimension of structural information beyond mass alone. The work presented herein advances the quantitative assessment of IM data, improves calibration strategies for Traveling Wave Ion Mobility (TWIM) instruments, investigates fundamental electrospray ionization processes, demonstrates the utility of native MS for probing protein-ligand interactions, and develops computational approaches for predicting collision cross sections of structurally diverse molecules.Chapter 2 presents a systematic evaluation of separation parameters and calibration strategies for a high-resolution Traveling Wave-SLIM (TW-SLIM) ion mobility system. We systematically evaluate the impact of traveling wave (TW) parameters on analysis time, peak-to-peak resolution, resolving power, and root-mean-square deviations of calibration residuals for calibrant ions using a SLIM-based high-resolution ion mobility platform. We identify a regime at which ions travel at the wave velocity rather than being separated based on mobility as a unifying explanation for degradation in both separation quality and calibration accuracy. We also compare trinomial and shifted-exponential calibration functions and introduce a novel approach using the shifted-exponential function that reduces bias from limited precision in reference CCS values by approximately four-fold. Applying our novel approach and optimized parameters, we assess the precision of CCS values for small molecule drugs and demonstrate baseline separation of protonation-induced verapamil conformers, achieving highly precise relative CCS values, typically under 300 parts per million (ppm), marking significant progress in isomer-specific assays and molecular identification. Chapter 3 details the application of native mass spectrometry to characterize drug binding to human liver fatty acid binding protein 1 (hFABP1). This work, part of a collaborative study, demonstrates that drugs form ternary complexes with hFABP1 and endogenous lipids. Native MS served multiple critical roles: monitoring copurifying molecules during protein purification, confirming the binding stoichiometry of the fatty acid probe DAUDA with hFABP1, and providing unambiguous verification of ternary complex formation. Using native MS, we directly detected DAUDA-hFABP1-diclofenac ternary complexes, demonstrating that drugs can bind to hFABP1 without fully displacing endogenous lipids. These results have implications for understanding how FABP1 binding may alter drug metabolism and clearance in the liver. Chapter 4 systematically examines how ammonium acetate concentration affects electrokinetic nano-electrospray ionization and native MS performance across 2 mM to 1000 mM in both positive and negative polarities, using droplet size, flow rate measurements, and native mass spectra of intact proteins as diagnostics. Droplet size and flow rate depended strongly on concentration but were independent of polarity, while voltage–current relationships differed markedly between modes: negative mode operated under a narrower window, limiting accessible concentrations to below approximately 800 mM. In positive mode, the adverse effects of sodium chloride on spectral quality decreased monotonically with increasing ammonium acetate concentration, with continued improvement up to 1000 mM; in negative mode, this approach was substantially less effective, as the high concentrations required exceeded the stable operating window. These results establish that ionization polarity is a primary variable in native MS method development and that positive and negative mode nanoESI operate under fundamentally different constraints when nonvolatile salt contamination is present. Chapter 5 introduces MobileMesh, an open-source Python library that calculates collision cross sections using triangle mesh representations of electron density isosurfaces, eliminating the need for element-specific parameterization. Characterizing petroleum at the molecular level requires analytical techniques sensitive to both elemental composition and molecular structure, and existing computational methods for calculating CCS rely on element-specific parameters that must be recalibrated across different ion classes, limiting their accuracy for the structurally diverse and heteroatom-rich species found in petroleum. MobileMesh addresses this limitation using specular scattering algorithms adapted from ray casting techniques in computer graphics, leveraging the Open3D library for high-performance triangle mesh operations. MobileMesh was evaluated against experimental helium CCS for radical cations of polycyclic aromatic hydrocarbons, a class of ions particularly challenging for traditional methods due to their delocalized charge and open-shell electronic structure, yielding strong agreement with experimental values without any element-specific fitting. By relying exclusively on stable, open-source software, MobileMesh reduces computational requirements from tens of thousands of processor cores to seconds on a single desktop computer, making electron density isosurface-based CCS calculations broadly accessible to the ion mobility community for the first time. Overall, the methods and findings presented in this dissertation advance the quantitative rigor of ion mobility measurements, deepen our understanding of electrospray ionization processes, demonstrate the utility of native MS for probing protein-ligand interactions, and introduce computational approaches for predicting collision cross sections of structurally diverse molecules. Collectively, these contributions provide practical guidance and new tools that can be broadly adopted by the IM-MS community to enhance molecular characterization workflows.
Inducing Chirality in CdS Nanocrystals with Biomolecules
(2026-04-20) Lowe, Christopher; Cossairt, Brandi M
Chiral CdE (E=S, Se, Te) nanocrystals (NCs) are an emerging class of materials with potential applications in optoelectronics, bioimaging, and sensing. Among the strategies for generating chiral CdE NCs, which include 1) chiral molecule templated nucleation and growth, 2) assembly of CdE NCs into chiral arrangements, and 3) chiral ligand exchange on the surface of the NCs, the latter is most attractive for biological applications because it enables direct interfacing between high-quality NCs and chiral biomolecules. Although ligand exchange with cysteine has been shown to induce chirality in CdE NCs, no prior studies have demonstrated the use of intrinsically chiral biomolecules, like peptides and proteins, to generate chiroptical responses in these materials. Chapter 1 reviews the synthetic tunability of CdE NCs and current approaches of synthesizing chiral nanostructures. It then introduces the structural complexity of biomolecules and highlights existing strategies for assembling hybrid biomolecule:CdE systems. The relevant chiral length scales of proteins and NCs are compared, motivating an interfacing strategy that couples biomolecular chirality with the surface-sensitive electronic structure of CdE NCs. Chapter 2 establishes an aqueous ligand exchange process in which glycine (the only achiral amino acid) serves as a versatile intermediate for displacement by cysteine (Cys)-containing elastin-like polypeptides. This exchange results in clear chirality transfer, evidenced by circular dichroism (CD) signals at the QD electronic transitions. The resulting polypeptide-bound QDs also exhibit thermally reversible coacervation, characterized by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). Chapter 3 extends this glycine-mediated exchange strategy to CdS nanorods (NRs) and examines how Cys concentration and local coordination environment influence NR optical properties, including UV-Vis absorbance, CD, and photoluminescence. These studies reveal that Cys derivatives can be detected at µM concentrations and suggest that both internal and n-terminal Cys residues are capable of inducing strong chiroptical responses. Chapter 4 applies these insights to protein-induced chirality in glycine-capped CdS NRs of two lengths. Incubation with a designed helical repeat protein containing four internal Cys residues (DHR-4Cys) rapidly displaces glycine and produces CD signals corresponding to the NR electronic transitions. NR length is found to have minimal influence on the resulting g-factors. TEM analysis reveals a substantial protein-derived ligand shell, and secondary structure analysis confirms that the protein remains folded upon binding. Remarkably, induced chirality is observed at nM protein loadings, corresponding to roughly two proteins per NR. This work represents the first demonstration of chirality induction in CdE NCs using an ordered protein scaffold.
Enhancing Stimulated Raman Scattering Microscopy Capabilities for Biological Imaging
(2026-04-20) Wong, Brian; Fu, Dan
Drug discovery and development remain a time- and cost-intensive task, over 90% of drugs that pass preclinical trials, ultimately fail to gain FDA approval. A factor in this high failure rate is that methods capable of monitoring drug systems and environments remain challenging. Traditional biochemical assays to understand drug properties provide insights into bulk cell-drug interactions and cannot provide spatially resolved information. Therefore, technologies capable of understanding drug responses at the cell-to-cell level may provide invaluable information to enhance drug discovery efforts. However, microscopy technologies that are informative of drug-cell interactions typically employ bulky fluorescent probes that are likely to interfere with drug behavior. Many label-free technologies promise to overcome this shortcoming but have limited capacity for high spatial resolution, rich chemical information, and/or live imaging. Stimulated Raman scattering (SRS) microscopy allows for such capability by acquiring vibrational signatures of all compounds while not requiring sample preparation or exogenous probes. As such, SRS has seen increasing adoption for label-free chemical imaging for diverse applications such as drug product stability, drug distribution in cells and tissues, drug-induced phenotypic responses, and Raman-based histology. While SRS microscopy offers a powerful, label-free solution for chemical imaging, its broader application has been constrained by inherent trade-offs between imaging speed, spectral coverage, and spatial resolution. This dissertation focuses on enhancing the technical and methodological capabilities of SRS microscopy to address these limitations and expand its utility in pharmaceutical research In this dissertation, I document the novel applications of SRS to advance the understanding of drug and cell interactions. Beyond typical SRS applications, this dissertation presents instrumental and computational enhancements to the SRS platform. Collectively, these advancements in SRS capabilities and applications establish SRS as a versatile tool in biological imaging.
Boron-mediated Transition-metal Catalyzed Selective Synthesis of Diverse Alkenes
(2026-04-20) yang, langxuan; Lalic, Gojko GL
The stereoselective synthesis of alkenes has been one of the central objectives in organic chemistry. Significant advances in synthetic methodology have made mono-and disubstituted alkenes widely accessible from a variety of readily available precursors. However, increased steric hindrance in more highly substituted alkenes limits the effectiveness of these methods, and as a result, the efficient and selective synthesis of highly substituted alkenes remains a formidable challenge. Boron exhibits unique reactivity that enables highly chemo- and stereoselective transformations and facile access to diverse functional groups, making organoboron compounds versatile intermediates in organic synthesis. Herein, we reported three new boron-mediated transition-metal catalyzed reactions that highly regio- and stereoselectively afford diverse alkenes with valuable functionality.The first reaction, described in Chapter 1, is a method for the synthesis of allylic alcohols via a copper-catalyzed reductive coupling of terminal alkynes with α-chloro boronic esters, followed by in situ oxidation of the boronic ester to an alcohol. The reaction is highly E-selective and exhibits broad functional group tolerance. Mechanistic studies suggest that cross-coupling of the alkenyl copper intermediate with the α-chloro boronic ester proceeds via a stereospecific 1,2-metalate shift. With support from mechanistic insights, we established a robust synthesis of chiral allylic alcohols from terminal alkynes and readily accessible enantioenriched organoboron precursors. Following this development, Chapter 2 describes a highly regio- and diastereo-selective synthesis of trisubstituted alkenes via nickel-catalyzed hydroalkylation of alkynyl boronamides. In this transformation, boryl groups serve as versatile directing groups that can control the regioselectivity of the hydroalkylation and enables productively replacement via cross-coupling. Preliminary studies support the hydrometalation mechanism and the formation of alkyl radical intermediates. Finally, Chapter 3 described a regiodivergent and stereoselective synthesis of tetrasubstituted alkenes via palladium catalyzed direct trifunctionalization of terminal alkynes using organoboranes and allylic carbonates as coupling partners. Incorporation of the allylic electrophile can be accomplished with either branched and linear selectivity and with excellent diastereo- and enantioselectivity, allowing access to a range of highly complex 1,4-dienes. Experimental evidence supports that enantioselective allylic substitution proceeds through a dynamic kinetic resolution and inner-sphere reductive elimination pathway. Proposed mechanism involves alkynyl boron-ate formation followed by a palladium-promoted 1,2-metalate shift that controls the regio- and diastereoselectivity of the alkene formation. Notably, these three strategies exploit distinct properties of boron to achieve desired regio- and stereocontrol: the first and third employ stereoselective 1,2-metallate shift of tetracoordinated boron-ate complexes, whereas the second relies on intrinsic electronic bias between carbon and boron.
Optical Detection and Control of Excitons, Spin, and Magnetism in Nanostructures
(2026-04-20) Baillie, Jacob Thomas; Gamelin, Daniel R
Coupled magnetic, electronic, and optical degrees of freedom, especially when afforded by nanostructures, have the potential to revolutionize scalable manufacturing, computing and memory storage, communication, and sensing. Two-dimensional (2D) magnets are particularly promising, but in many cases the optical spectra of such materials are complex and poorly understood. Chapter 2 reports on the optical properties of the A-type layered antiferromagnet, CrPS4. Very weak pure-electronic origins of the lattice Cr3+ are identified, across which the absorption and photoluminescence (PL) spectra mirror one another. Rich fine structure is assigned to exciton-magnon coupling, exchange splitting, and a second “defect” Cr3+. A radiative decay time of several microseconds is elucidated for this PL, consistent with the spin-forbidden 2E → 4A2 transition of lattice Cr3+. Energy migration dynamics are studied using Yb3+ dopants as deliberate traps, from which sub-picosecond inter-site hopping is estimated. This rapid hopping implies the formation and dispersion of Frenkel-type excitons based on multi-ion coupled 2E excitations. The observation of resolved magnon-coupled electronic transitions in CrPS4 may present new opportunities to explore and harness coupling between optical excitations and correlated spins in layered magnetic materials. Chapter 3 investigates the underlying magneto-optical coupling between Yb3+ and CrPS4. The collective spin properties of CrPS4 are encoded in the sharp f-f luminescence of isolated Yb3+ dopants via strong magnetic superexchange coupling between the two. The spontaneous magnetic ordering in CrPS4 induces large exchange splittings in the narrow Yb3+ f-f photoluminescence features below TN. Spin reorientation in CrPS4 via a "spin-flop" metamagnetic transition modulates the Yb3+ f-f luminescence energies and exchange splittings. This pronounced link between spin and optical properties enables the demonstration of optically driven spin-flop transitions in CrPS4. The high PL quantum yields and strong screening of the f electrons that benefit this work on CrPS4 are also advantageous for quantum applications. Chapter 4 explores interacting lanthanide dimers in Yb3+–Yb3+ and Yb3+–Er3+ molecular clusters toward 2-qubit systems. Simultaneous pair emission from Yb3+–Yb3+ dimers and its nonlinear power dependence and dynamics indicate coherent coupling. The Yb3+–Er3+ cluster exhibits inter-ion energy transfer evidenced by site-selective excitation experiments. From time-resolved PL experiments, the transfer efficiency is 56% and the incoherent electric dipole-dipole coupling strength is approximately 52 MHz. These results suggest the coherent dipole-dipole interaction in this molecular cluster may be strong enough for 2-qubit operations. Finally, Chapter 5 summarizes various strategies to synthesize ZnO nanostructures with high optical quality. Unlike the aforementioned vdW magnet and lanthanide dimer systems, ZnO already boasts extensive literature toward quantum applications and numerous synthetic routes. The preparation of optically bright nanostructures is crucial for device efficacy and integration. Various strategies toward preparing homogeneous ZnO nanostructures with high optical quality are summarized. In sum, this dissertation explores light-spin interactions in nanomaterials, with relevance to spintronic, magneto-photonic, and quantum applications.
Understanding the Role of [4Fe-4S] Clusters in Hydroxylation during the Anaerobic Biosynthesis of Ubiquinone
(2026-02-05) Gannon, Paige Marie; Rajakovich, Lauren J
Ubiquinone is an important biological cofactor which is responsible electron transporter in cellular respiration. The biosynthesis of ubiquinone in Escherichia coli occurs via both aerobic and anaerobic pathways, offering a metabolic flexibility that may aid in rapid adaptation to varying oxygen concentrations. In this biosynthetic pathway, the precursor octaprenylphenol, is hydroxylated three times. The hydroxylations in the anaerobic pathway are performed by two U32 proteins, UbiU and UbiV, which rely on iron-sulfur clusters for catalytic activity. In this work, I characterize the native clusters of both UbiU and UbiV as [4Fe-4S] clusters via CW EPR spectroscopy and UV-visible absorption spectroscopy. In the reduced form, UbiV exists as a mixed population of S=1/2 and S=3/2 ground spin states, whereas UbiU is only in the S=1/2 state. Both clusters are vulnerable to loss of an iron to form a [3Fe-4S] cluster under oxidizing conditions, and both clusters react with the strong ligand cyanide, indicating one iron site in the cluster that is coordinatively unsaturated or has an easily dissociated ligand. Upon incubation with a substrate phenol analogue and the native co-substrate prephenate, a new EPR signal is observed along with a decrease in intensity of the [4Fe-4S]1+ signal, suggesting cluster-substrate interaction or cluster decomposition. Understanding of the electronic structure of these clusters and their reactivity offers insight into the unprecedented mechanisms of anaerobic hydroxylation by U32 hydroxylases.
Surface Passivation of Lead Halide Perovskite Semiconductors for Improved Stability and Performance
(2026-02-05) Akrami, Farhad; Ginger, David S
Metal halide perovskites have emerged as one of the most promising classes of semiconductors for next-generation optoelectronic technologies, including solar cells, light-emitting diodes, and photodetectors. In photovoltaic devices, perovskites have achieved power conversion efficiencies that rival those of established commercial technologies. However, despite their remarkable progress, the widespread development of perovskite photovoltaics remains hindered by intrinsic instability and the presence of electronic defects, particularly those located at the surface. These surface defects play a crucial role in limiting performance, accelerating degradation, and mediating ionic and electronic processes that challenge long-term operational stability, making surface passivation a central focus in perovskite research for stable, high-efficiency devices. To address these challenges, a variety of surface passivation strategies have been developed to mitigate defect states and suppress nonradiative recombination. While these approaches have demonstrated substantial improvements in both performance and stability, their implementation across diverse perovskite compositions and synthetic routes remains nontrivial. The optimal passivation strategy often depends on subtle variations in chemistry, processing, and environmental conditions. Realizing effective passivation demands finely tuned treatment conditions that maximize benefits of defect suppression while minimizing unintended chemical or structural side effects. In this context, defect passivation represents both a scientific challenge and a technological opportunity to accelerate the path toward stable, commercially viable perovskite solar cells. This dissertation investigates how surface passivation can be used to control ion motion and optimize interfacial properties in lead halide perovskite semiconductors. First, we demonstrate how surface passivation can kinetically suppress light-induced halide migration, thereby enhancing the photostability of perovskites. Second, we investigate the effects of aminosilane-based treatments, highlighting the significance of optimized treatment conditions, while also revealing surface reactivities of these molecules with formamidinium cations, linking interfacial chemistry to changes in optoelectronic behavior. Overall, these studies establish molecular surface passivation as a powerful route to tune ion migration, stability, and performance in lead halide perovskites. They provide insights that can help bridge interfacial chemistry with the practical requirements of durable perovskite optoelectronic technologies.
The Mechanistic Roles for SUMO in Chromatin and Condensates
(2026-02-05) Reyna, Andres; Chatterjee, Champak
Histone post-translational modifications regulate DNA-templated processes in eukaryotes by shaping chromatin structure and regulating enzyme activity. The unstructured histone termini, or tails, extend outwards from the globular octameric histone core that tightly wraps ~147 bp of DNA to form the nucleosome core particle. The dynamic landscape of histone tail modifications is installed, maintained and remodeled by dedicated nuclear proteins that tune transcriptional outcomes in response to varying cellular needs. One dramatic histone modification that remains poorly studied in cells is conjugation of the histone lysine side-chain with the small ubiquitin like-modifier (SUMO) protein. Prior studies associated the presence of SUMO in chromatin with gene repression, but could not ascribe this effect to specific lysines sites in human histones. Semisynthetic access to site-specifically sumoylated histones, pioneered by our labs, has enabled biochemical investigations of the mechanistic roles for SUMO in chromatin. In this thesis, I examined the mechanistic roles for SUMO in three physiological contexts: its biochemical crosstalk with histone modifications in chromatin, its recruitment of repressive machinery through SUMO interaction motifs (SIMs) in key protein components of gene repressive complexes, and its ability to regulate the biophysical properties of biomolecular condensates in living cells. First, to address mechanisms of biochemical crosstalk, I focused on the role of sumoylation at H4 Lys12, because it is a validated site of sumoylation in several cell lines and lies in the unstructured H4 tail. By generating site-specifically sumoylated H4K12 (H4K12su) using protein semisynthesis and incorporating it into histone octamers and reconstituted mononucleosomes, we showed that sumoylation inhibits Rad6-Bre1-mediated monoubiquitylation of H2BK120. In complementary cell-based assays, I demonstrated that the in vitro biochemical effect of H4K12su could be recapitulated using SUMO-H4 linear fusions that ensure uniform sumoylation on the intact H4 tail in cells. By including both SUMO-H4 and a SUMO-H4(D1-11) construct that positions SUMO closer to Lys12, and hence closely mimics H4K12 sumoylation, I demonstrated that H4 sumoylation is inhibitory toward H2B K120 ubiquitylation, a modification required for subsequent H3K4 methylation by the Set1/COMPASS family of H3K4 methyltransferases that are associated with transcription activation and elongation. Having shown that H4K12su and its isosteres can repress H3K4 methylation by physically hindering Rad6-Bre1 binding to the nucleosome core particle and the enzymatic installation of H2BK120ub, I turned to examining the role of H4K12su in recruiting gene repressive enzyme complexes to sumoylated nucleosomes. Toward this goal, I focused on a non-canonical SIM (ncSIM) within the Co-repressor of REST1 protein (CoREST1) and established its direct binding to SUMO3. Two-dimensional 15N-1H HSQC NMR chemical shift perturbations with short ncSIM peptides were employed to map their binding to the canonical SIM-binding groove in SUMO3. Reciprocal pulldowns with either purified SUMO3 or full-length CoREST1 as bait further confirmed their direct binding, and alanine mutation of key residues in the ncSIM hydrophobic core were found to weaken SUMO3-CoREST binding. Altogether, my results defined the binding interface between the CoREST1 protein and SUMO3 and revealed how SUMO3-CoREST1 binding may position the gene repressive LSD1–CoREST–HDAC1 complex on nucleosomes and influence its demethylase and deacetylase activities on methylated and acetylated nucleosomes, respectively. In the final part of my thesis, I broadened my studies of the SUMO-SIM interaction to investigate the fundamental biophysical properties of SUMO-dependent biomolecular condensates (BMCs), such as Promyelocytic Leukemia bodies. Toward this, I engineered a synthetic polyvalent platform consisting of poly(SUMO3) and poly(SIM) scaffolds and quantified how the SUMO3-SIM binding affinity changes the internal dynamics of BMCs and the activity of enzymes localized in BMCs. I discovered that the phase boundary (csat) for polyvalent constructs correlates well with monovalent SUMO-SIM affinities (Kd). However, condensate number and size do not correlate with Kd. Condensate stability to chaotoropes and internal mobility, as measured by Fluorescence Recovery After Photobleaching (FRAP), also showed excellent correlation with SUMO-SIM affinities. The correlation was also recapitulated in three different human cell lines and demonstrated our ability to generate BMCs with predictable properties in living cells. Finally, I demonstrated that the activity of the enzyme pyroglutamyl peptidase 1 that plays an important role in the cellular stress response could be regulated by its recruitment to engineered BMCs of different mobilities. Thus, my mechanistic studies with the small ubiquitin-like modifier protein have led me to identify negative crosstalk between H4K12 sumoylation and H2BK120 monoubiquitylation, to define the specific mode of interaction between SUMO and CoREST1, and to establish an exciting and novel modular framework for condensate formation in vitro and in living cells, that directly links SUMO-SIM affinities to predictable condensate properties and tunable enzyme activities.
Interfacial Chemistry of Metal Pnictide Magic-Sized Clusters: Connecting Structure and Function through Ligand Coordination
(2026-02-05) Sandeno, Soren; Cossairt, Brandi M
Synthesis development of colloidal quantum dots (QDs) has allowed for control over their distinct and unique optoelectronic properties. The continuous tunability in absorbance and emission profiles allowed by their quantum confinement when partnered with the robustness of a colloidal crystalline lattice has led to myriad applications in solid-state lighting, biosensing, photosensitive absorbing devices, and more recently quantum information science. These applications require meticulous and reproducible syntheses to generate materials with highly consistent properties and optoelectronic behaviors. During synthetic investigation toward these ends, researchers have discovered the existence of magic-sized clusters – molecular QDs that form at the early stages of nanocrystal nucleation and growth. Not only do these atomically precise materials serve as important reaction intermediates, but their precision has been heralded as a route toward eliminating heterogeneity from QD syntheses. Despite their presence being sufficiently documented optically, the mechanisms of conversion, true structural identities, and emissive behaviors remain understudied and ambiguous. This thesis seeks to develop a stronger understanding of magic-sized cluster structure and conversion (Chapters 2 and 3) as well as investigate new avenues for enhancing their emissive properties without disturbing their metastability (Chapters 4 and 5). After an introduction on the nucleation and growth of magic-sized clusters and QDs (Chapter 1), Chapter 2 focuses on the InP material system. The structural influence of ligand steric pressure on the In37P20(O2CR)51 cluster is investigated using a substituted phenylacetate ligand framework. It is shown that pressure at different angles in the ligand sphere induces structural perturbations in the internal lattice of the cluster. The influence of these structural changes is further investigated through reactions with P(SiMe3)3 in which para-substituents hinder ingress of reactive species thereby slowing cluster conversion whereas meta-substituents increase surface indium-indium separation distances and enhance cluster conversion rates. Leveraging this knowledge of controlled diffusion through ligand profile allowed for the isolation and complete structural characterization of a new magic-sized cluster intermediate, In26P13(O2CR)39. The relations of the structural motifs present in this new cluster are discussed. In Chapter 3, these structural conclusions are extended toward the InAs system. The synthesis of InAs QDs has been documented to proceed through a ubiquitous cluster intermediate with a distinct absorbance profile showing features at 425 and 460 nm. Synthetic modifications to reduce conformational flexibility of the surface ligands allowed for isolation and full structural characterization of this predominate magic-sized cluster intermediate thereby identifying it as In26As18(O2CR)24(PR’3)3. The crystal structure of this cluster shares important motifs with In26P13(O2CR)39 and In37P20(O2CR)51 in the form of an In14E13 (E = P, As) cage yet the overall structure of In26As18(O2CR)24(PR’3)3 is more anisotropic. Full characterization also allows for refinement of the surface suggesting a ligand sparsity in InAs could lead to higher reactivity. Beyond the structural investigations of magic-sized clusters, Chapter 4 presents a route toward leveraging their homogeneity to achieve narrow emission linewidths. Previous reports have shown that oleate-ligated magic-sized clusters of Cd3P2 (Cd3P2-450) and Cd3As2 (Cd3As2-525) have high emissive color purity with <100 meV linewidths but their PLQYs of 7% and 0.5%, respectively, are too low to be considered applicable emitters. In this study, a ligand exchange on these clusters for stronger binding phosphinates was developed. The bidentate coordination motif of the oleate is mimicked by the phosphinate allowing for retention of the internal structure and preservation of stability. The increased binding affinity after exchange increased the PLQY of the Cd3P2-450 to 26% and the Cd3As2-525 to 9% while maintaining the narrow linewidths. Through time-resolved spectroscopy, the mechanism toward photoluminescent enhancement was determined to be phosphinates shutting down nonradiative recombination pathways. Following up on the emission augmentation of the Cd3P2-450 and Cd3As2-525 magic-sized clusters, Chapter 5 describes a synthetic route to introducing continuous tunability in these systems that rely on discrete sizes. The anion sublattice can be alloyed using different ratios of P(SiMe3)3 and As(SiMe3)3 to generate Cd3P2-xAsx clusters while maintaining the internal structure. This alloying allows for continuous tunability between the independent emission profiles of Cd3P2-450 and Cd3As2-525 with similarly narrow linewidths across the compositional gradient. Further treatment of these materials using the previously developed phosphinate exchange leads to highly emissive, continuously tunable, magic-sized materials with PLQYs reaching as high as 33%. Following the structural investigation, using the ligand-derived diffusion management that previously resulted in the isolation of In26P13, is applied to Cd3P2-450 similarly allowing for the isolation of another smaller cluster, Cd3P2-390. The structure and conversion of this new magic-sized cluster are investigated showing its direct relation to Cd3P2-450. Overall, this thesis takes a two-pronged approach to investigating the role and behavior of magic-sized clusters in many different materials systems. In the first, structural studies of III-V clusters unveil the identity of multiple previously known and unknown intermediates in the synthesis of QDs. This allows for a rich comparison of structural motifs and identifies the M14E13 icosahedral cage as a ubiquitous element in III-V and II-VI nanomaterial growth. In the second, further development of II-V cluster systems increases applicable benchmarks through improving brightness and establishing a synthetic route towards continuous tunability in magic-sized materials. It is demonstrated how the judicious choice in cluster modification can navigate the metastability and simultaneously open new avenues to improved emissive properties.
Engineering Fluidic Tools for Translational Science: Developing In Vitro Tissues and Remote Sampling Platforms
(2026-02-05) Brown, Lauren G; Theberge, Ashleigh B
This dissertation discusses the development and optimization of various open microfluidic inspired toolsfor translational science applications in studying human health and the environment. Chapter 1 introduces the field of open microfluidics and provides background into open microfluidic hydrogel patterning for tissue engineering and at-home blood sampling for downstream transcriptomic analysis. Chapter 2 describes a novel removable suspended open microfluidic platform for patterning hydrogel-based tissue constructs suspended between two posts. This platform uses microfluidic principles such as surface tension and capillary pinning to control the flow and shape of hydrogels in a suspended format to generate engineered tissue constructs with defined interfacial regions for disease and tissue junction modeling. Chapter 3 explores the use of homeRNA, a previously established kit for at-home user-based blood collection and stabilization, in high temperature settings via two pilot studies conducted in the hot summer months in the Western and South Central United States and Doha, Qatar. These pilot studies yielded RNA from homeRNA-stabilized samples of sufficient quality for use in downstream transcriptomic analysis despite exposure to temperatures greater than 37°C. Chapter 4 further establishes the robustness of homeRNA by systematically testing RNA quality from homeRNA-stabilized samples after short-term (<2 days) and long-term exposure (>2 days) to a range of temperatures above 37°C via in-lab testing and a realworld controlled shipping experiment. These samples were then sequenced using 3’ mRNA-sequencing technology, which showed little to no preferential transcript degradation of isolated RNA from homeRNAstabilized samples due to high temperatures or extended shipping times. Chapter 5 then outlines the first use of homeRNA with bulk RNA-sequencing, in which we demonstrated that homeRNA can successfully capture an LPS-induced inflammatory response that was comparable to that of stabilized venous blood. This work establishes the compatibility of homeRNA with bulk RNA-sequencing, demonstrating its potential as a useful tool for monitoring immune response via remote sampling. Lastly, Chapter 6 describes a yearlong homeRNA-based remote study to probe immune response to wildfire smoke exposure in the Western and South Central United States. This demonstrates the ability of homeRNA to be used in a fully remote and flexible study design for user-based blood collection in challenging environments. Ongoing work with this study includes investigating the gene expression profile of homeRNA-stabilized samples from 32 unique participants to elucidate the transcriptomic immune response to wildfire smoke. This dissertation presents two bioanalytical platforms that advance translational medicine by enabling more targeted biological and health-related investigations. Combined, STOMP and homeRNA collectively expand the scope of translational research in tissue engineering and remote sampling applications, thus supporting more targeted investigations into disease mechanisms, therapeutic efficacy, and environmental health impacts.
Tailoring Perovskite Quantum Dot Surface Chemistry for Single Photon Emission
(2026-02-05) Kline, Jessica; Ginger, David
Perovskite quantum dots are one of the most promising colloidal single photon sources with high single photon purity, narrow linewidths and fast radiative recombination at all temperatures. However, these materials still suffer from non-ideal behavior in the form of blinking and spectral diffusion. Both blinking and spectral diffusion are correlated to quantum dot surface quality and as such improving the surface of perovskite quantum dots is key to their long-term success as a single photon source. Here we explore the surface chemistry of perovskite quantum dots through tailoring ligand passivation and morphology. We find that CsPbBr3 quantum dots passivated with zwitterionic lecithin exhibit significantly less blinking than their oleylammonium/oleate passivated counterparts because lecithin binds to the surface ten times more strongly resulting in less ligand desorption during sample preparation. We also find that, in contrast to cubic CsPbBr3 quantum dots, spheroidal CsPbBr3 quantum dots have an asymmetric photoluminescence with a red tail due to emissive traps. Finally, we benchmark silane-based passivation for formamidinium lead bromide (FAPbBr3) quantum dots against phosphoethylammonium-based passivation for FAPbBr3 quantum dots. We find that, while silane-based passivation works extremely well at room temperature, the performance of these materials at 4K is hampered by increased trion formation which results in irreversible photodegradation.
Advances in Open Microfluidics from Fundamental Flow Dynamics to Environmental and Translational Science Applications
(2026-02-05) Tokihiro, Jodie C; Theberge, Ashleigh B.
This dissertation will demonstrate and discuss advances in open-channel microfluidics at the fundamental and translational levels. Chapter 1 outlines new fundamental open-microfluidic tools through via analytical models and comparisons with open channel fluid flow experiments. Chapter 2 will demonstrate enhanced capillary flow through the coupling of homothetic, bifurcating capillary trees and semi-circular paper pads at the extremities to maintain high fluid velocities throughout the channel over an extended period of time. Chapter 3 will discuss and demonstrate the need for a dynamic contact angle (DCA) at high fluid velocities through a survey of current theoretical approaches including multiple hydrodynamic models and the molecular kinetic theory with a comparison to in-lab flow experiments in U-shaped open microfluidic channels. Chapter 4 will present the implementation of trigger valves in open channel configurations allowing for the formation of lateral flow of multiple liquids in parallel for precise fluid addition. Chapter 5 will focus on the use of an open-channel droplet generator that can encapsulate human sperm samples for the use in cryopreservation steps in assisted reproductive technology (ART) workflows.
Analysis of Test Mixture and Water Contaminants Using Advanced Chromatographic Techniques
(2026-02-05) Abdigali, Perizat; Synovec, Robert RS
This thesis work highlights Solid Phase Extraction (SPE) coupled with Intuvo 9000 Gas Chromatography (GC), comprehensive two-dimensional (2D) gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS), and one-dimensional gas chromatography-mass spectrometry (GC-qMS) to study the chemical components of a Test Mixture and contaminated by a diesel water sample. Diesel compounds were found during the first step of the analysis on one- dimensional GC-qMS. However, due to significant peak overlap, the compound resolution and identification were limited. GC×GC-TOFMS was used to analyze samples and its SPE extracts to overcome those limitations. During the analysis of the Test Mixture, a consistent temperature program and other conditions were adjusted on GC-qMS developed method. Nonadecane peak intensities were used as an example compound to find the limit of detection (LOD), which produces detection ability at low concentrations, and gave an instrumental practical value of 4 ppm. To analyze changes and determine which compounds were most reduced or eluted during the extraction, chemometric techniques such as Principal Analysis (PCA) and tile-based F statistic ratio (F-ratio) analysis were used. A significant change in analytes was shown by the separation of the extracts and original neat sample by PCA. To reduce noise and correct retention time shifts, the chromatograms with more than 2500 differential areas were reduced to around 1216 significant features using F-ratio analysis. A detailed analysis of a typical peak at mass-to-charge ratio 120 discovered that the Extracts had a weaker signal intensity than the Original Neat Diesel Sample, which shows partial compound loss after extraction. When comparing the real laboratory data with the NIST library mass spectrum, it has strong match across significant fragment ions, confirming the identification of 1-ethyl-2methylbenzene.
Chemistry-Driven Dissection of Malaria Immunity and Resistance: Multiplex Antibody Analysis and Mechanistic Inhibition Studies
(2026-02-05) Momoh, Elizabeth; Rathod, Pradipsinh K; Theberge, Ashleigh B
This dissertation discusses the dissection of antimalarial immunity and resistance, with an emphasis on chemistry-driven tools for antibody analysis and parasite inhibition. Malaria remains a major global health burden, and despite the availability of frontline therapeutics, widespread resistance and incomplete immune protection underscore the urgent need for new strategies. To address these challenges, this work integrates chemical biology approaches to interrogate antibody responses, evaluate drug efficacy, and characterize host-parasite interactions during the erythrocytic life cycle.First, bead-based multiplexing assays were developed and optimized as a platform for the simultaneous analysis of antibody responses against multiple malaria antigens. By applying advanced coupling chemistries and addressing limitations in antigen production and orientation, this platform enabled high-throughput, sensitive, and reproducible profiling of naturally acquired immunity. These innovations provide an improved chemical framework for antigen prioritization and vaccine candidate evaluation. Second, mechanistic growth inhibition assays (GIAs) were employed to investigate parasite susceptibility to small molecules, monoclonal antibodies, and patient sera. Using well-characterized compounds such as Tartrolon E, DSM265, and artemisinin as pharmacological benchmarks, these assays established a robust comparative system for evaluating inhibitory potency. Parallel studies with monoclonal antibodies targeting key invasion ligands (MSP1, AMA1, EBA175) highlighted distinct inhibitory profiles and stage-specific vulnerabilities, while patient sera from a malaria-endemic region revealed protective capacity that complements drug and antibody-mediated mechanisms. Finally, resistance studies focused on dihydroorotate dehydrogenase (DHODH) inhibitors, a promising class of antimalarials. Cross-resistance analyses of DSM265-resistant P. falciparum mutant lines against a panel of novel DHODH inhibitors revealed susceptibility patterns. These findings provide critical insights into drug-target interactions and resistance evolution, informing future drug design strategies. Together, this dissertation demonstrates how chemical tools and mechanistic assays can be harnessed to dissect the molecular basis of antimalarial immunity and drug resistance. The integration of multiplex immunoassays, pharmacological profiling, and resistance mapping establishes a versatile framework for advancing vaccine development, drug discovery, and malaria research.

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