Past Seminars & Events

Porous framework materials, including metal- organic frameworks (MOFs), are highly tunable materials with myriad potential applications ranging from chemical separations to gas storage to catalysis. This is due to the unusual local environment offered by their pores. Herein we will discuss how this tunability can be used to unlock new reactive species relevant to organic synthesis and catalysis, focusing on fluorination chemistry, which is critical to the pharmaceutical, polymer, and agrochemical industries. We will also draw inspiration from organic chemistry for the design of new chemical separations and electrocatalytically active materials.

Our multidisciplinary research group focuses on molecular inorganic synthesis, thin film materials via atomic layer deposition (ALD), and heterogeneous catalysis for fine chemical transformations. Our goal is the convergence of these subdisciplines of inorganic chemistry towards the synthesis of complex hierarchical catalyst systems that are active, selective, and highly reusable. Specifically, we are seeking to discover and develop sustainable synthetic methodologies enroute to our desired end products – often these alternative routes enable the synthesis of previously inaccessible, or difficult to access products. To that end, the presentation will focus on three of our current areas of interest:

1. Mechanochemical synthesis: by leveraging mechanochemical forces via vibratory ball milling or ultrasonic irradiation, we can expedite the synthesis of Schiff base coordination complexes. These reactions can be performed solvent-free or solvent-minimal and facilitate the formation of target compounds in one-pot and one- step from multiple starting materials in minutes-to-hours compared to conventional multi-day, multi-step processes.
2. Silane-based reductions: using stoichiometric silanes, high- valent, mid d-block metal halides can be stoichiometrically reduced to highly reactive mid-valent synthons (e.g. MoCl 3 from MoCl 5 ). The reactions are facile and produce only H 2 and recoverable and reusable chlorosilanes as byproduct. The resulting mid-valent metal chlorides form ideal starting points towards new precursors for ALD and chemical vapor deposition (CVD); enabling technologies for coatings, electronic materials, and heterogeneous catalysis.
3. Monolith-based nanocatalysts: controlled growth of nanocatalysts on contiguous Ni foams; porous, contiguous membranes that enable facile handling, reuse, and direct applicability to flow reactions. The application of these materials towards the catalytic hydrogenation of nitro, alkene, and alkyne moieties, in batch and flow, under mild conditions will be discussed.

Comprehensive characterization of all signaling molecules in a biological system with chemical, spatial and temporal information is often critical to deciphering their functional roles, yet it poses a daunting challenge. In this presentation, I will present our recent progress on the development of a multi-faceted mass spectrometry (MS)-based analytical platform to probe neuronal signaling with enhanced sensitivity and selectivity. By combining chemical labeling, micro-scale separation, and tandem MS sequencing techniques, we discovered more than 300 novel neuropeptides in several model organisms. Moreover, both mass spectrometric imaging (MSI) technology and in vivo microdialysis sampling tools have been developed and implemented to follow neuropeptide distribution and secretion with unprecedented details. Additionally, several in situ chemical derivatization strategies have been developed to enable spatial mapping of various biomolecules including lipids and glycans in complex biological samples, such as human cell lines and cancer tissue samples. Recent progress towards single- cell lipidomics enabled by dual-polarity ionization and ion mobility MS imaging will be highlighted as well.

Furthermore, we are developing multiplexed isobaric and isotopic tagging strategies to discover, identify and evaluate candidate biomarkers of Alzheimer’s disease (AD) in cerebrospinal fluids (CSFs) obtained from asymptomatic cognitively-healthy middle- aged adults, older cognitively-normal adults, and patients with mild cognitive impairment (MCI) and AD. A large-scale comparative glycoproteomic analysis via the 12-plex DiLeu (N,N-dimethyl leucine) tagging strategy revealed distinct glycosylation patterns and dynamic changes of certain glycoforms in CSF samples collected from the control, MCI, and AD patients. Additionally, we report on a multiplexed quantitation method for simultaneous proteomics and amine metabolomics analyses via nanoflow reversed phase LC-MS/MS, exploiting mass defect-based DiLeu (mdDiLeu) labeling. Several on-going efforts and future perspectives provided by these enabling technologies will be highlighted and discussed.

The precise placement of functional groups along a polymer chain plays a key role in encoding specific intra- and intermolecular interactions that direct self-assembly into discrete architectures. Biopolymers known to associate with specific geometries and stoichiometries have been exploited for the assembly of synthetic building blocks. However, such systems are neither scalable nor amenable to the relatively harsh conditions required by various materials science applications, particularly those involving non-aqueous environments. To overcome these limitations, I will discuss our work on sequence-defined oligocarbamates (SeDOCs) and data highlighting the effect of sequence on network topology, mechanical and optical properties. I will then discuss SeDOC ligands that assemble into duplexes through complementary hydrogen bonds between thymine (T) and diaminotriazine (D) pendant groups. We’ve successfully synthesized monovalent, divalent, and trivalent SeDOCs and characterized their hybridization via a variety of techniques, including diffusion ordered spectroscopy, 1 H-NMR titration, and isothermal titration calorimetry. Our findings reveal that the binding strength of monovalent oligomers with complementary pendant groups is entropically driven and independent of monomer sequence, that hybridization of multivalent oligomers is cooperative, and that SeDOCs ligands bearing D and T groups exhibit signatures of enthalpy- entropy compensation.

Christopher A. Alabi

Macrophages regulate how the immune system recognizes self. When a foreign/exhausted cell or pathogen is detected, macrophages engulf and destroy it in a process called phagocytosis. Anti-phagocytic signaling axes, also referred to as ‘don’t eat me’ (DEM) signals, exist between macrophages and other cells. To evade macrophages, healthy cells express DEM signal ligands on their surface. When a DEM ligand engages a DEM receptor on a macrophage, downstream signaling blocks phagocytosis. Four DEM signal ligand- receptor pairs have been discovered, and it is hypothesized that there are others. Dysregulation of DEM signaling has been implicated in cancer, infectious disease, neurodegeneration, and atherosclerosis. In addition to DEM signal ligands, mammalian cells also present ‘eat me’ (EM) ligands, which engage macrophage EM receptors, and are required for phagocytosis. Despite the fundamental role these signals play in basic and disease biology, relatively little is known about the biological mechanisms and consequences of these pathways. Learning to harness and exploit DEM and EM signaling would result in a wave of new biologic discovery in human health and disease. However, highly-selective chemical probes and new specialized chemical proteomic approaches are required. To this end, my lab has developed selective chemical tools and novel proteomic techniques to study macrophage function and host-pathogen interactions. Our new toolkit has lead to discoveries in macrophage function that reveal how we combat disease and may change the way we design immunotherapeutics.

The Williams lab has been investigating the utility of highly Lewis acidic boron centers for the activation and cleavage of alkyl ethers and in halogen exchange reactions of trifluoromethylarenes. Such strategies have enabled the targeting of strong C–O bonds and C–F bonds for cleavage in the presence of weaker bonds. These practical methods have important applications in medicinal and agricultural chemistry, as well as in sustainable chemistry development, such as the mild separation of cellulose from lignocellulose – a biopolymer that can provide a renewable source of aromatic chemicals such as vanillin. This talk will examine the development of such boron-mediated methodologies, applications to different modern challenges, and the differential reactivity and behavior of boron trihalide species.

For several decades, chemists have designed new approaches to valuable materials that are economically efficient and environmentally benign. To this end, synthetic chemists have developed new synthetic strategies to access complex molecules from simple, inexpensive, and abundant feedstock chemicals. Our research group explores. new methods in this area. We present recent examples from our laboratory of stereoselective reactions with feedstock chemicals as starting materials. First, we discuss our approach to the stereoselective functionalization of unsaturated hydrocarbons through catalytic pericyclic reactions with chalcogen-based reagents. For example, we have developed enantioselective allylic functionalizations of terminal and internal alkenes. Second, we describe our approach to the enantioselective α-alkylation of aldehydes with amino acid derived alkylating reagents. We have devised a strategy for the activation of pyridinium salts derived from amino acids through the formation of light-activated charge transfer complexes with catalytically generated electron rich chiral enamines derived from aldehyde substrates and a chiral amine catalyst.