Lectures & Events

A hydrogen-bonded framework toolkit for molecular structure determination

Single crystal X-ray diffraction is arguably the most definitive method for molecular structure determination, but the inability to grow suitable single crystals can frustrate conventional X-ray diffraction analysis. Building on a prolonged examination of hydrogen-bonded frameworks and inclusion compounds derived from guanidinium organosulfonates, we have devised an approach to molecular structure determination that relies on a versatile toolkit of these host frameworks, which form crystalline inclusion compounds with target guest molecules in a single-step crystallization. This approach complements the so-called crystalline sponge method that relies on diffusion of the target into the cages of a metal-organic framework, while circumventing many of its challenges. The peculiar properties of the host frameworks enable rapid stoichiometric inclusion of a wide range of target molecules with full occupancy, typically without disorder and accompanying solvent, affording well-refined structures. Moreover, anomalous scattering by the framework sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. An ever-expanding library of organosulfonates provides a toolkit of frameworks for capturing specific target molecules for their structure determination. This presentation will describe examples of this approach to structure determination, preceded by an account of the unusual properties and resilience of these hydrogen-bonded frameworks, their substantial diversity of framework architectures, and their utility in other applications. Department of Chemistry and Molecular Design Institute, New York University

New Approaches for Structure Determination of Protein Complexes by Mass Spectrometry

Characterization of the overall topology and inter-subunit contacts of protein complexes, and their assembly/disassembly and unfolding pathways, is critical because protein complexes regulate key biological processes, including processes important in understanding and controlling disease. Tools to address structural biology problems continue to improve. Native mass spectrometry (nMS) and associated technologies such as ion mobility are becoming an increasingly important component of the structural biology toolbox. When the mass spectrometry approach is used early or mid-course in a structural characterization project, it can provide answers quickly using small sample amounts and samples that are not fully purified. Integration of sample preparation/purification with effective dissociation methods (e.g., surface-induced dissociation), ion mobility, and computational approaches provide a MS workflow that can be enabling in biochemical, synthetic biology, and systems biology approaches. Native MS can determine whether the complex of interest exists in a single or in multiple oligomeric states and can provide characterization of topology/intersubunit connectivity, and other structural features. Beyond its strengths as a stand-alone tool, nMS can also guide and/or be integrated with other structural biology approaches such as NMR, X-ray crystallography, and cryoEM. Department of Chemistry and Biochemistry, Ohio State University Columbus, OH

Chemical and Biological Physics Dept Seminar

Biomolecular imaging at the preclinical stage is an essential tool in various biomedical research areas such as immunology, oncology or neurology. Among all modalities available to date, optical imaging techniques play a central role, while fluorescence, in particular in the NIR region of the spectrum, provides high sensitivity and high specificity with relatively cheap instrumentation. Several whole-body optical pre-clinical NIR imaging systems are commercially available. Instruments using continuous wave (CW or time-independent) illumination allow basic small animal imaging at low cost. However, CW techniques cannot provide fluorescence lifetime contrast, which allows to probe the microenvironment and affords an increased multiplexing power. In the first part of my talk I will introduce our single photon, time-gated, phasor-based fluorescence lifetime Imaging method which circumvents limitations of conventional techniques in speed, specificity and ease of use, using fluorescent lifetime as the main contrast mechanism. In the second part of my talk I will present the tracking and multiplexing of two different cell populations, based on their different lifetimes (following their fluorescent dyes-loading). Despite major advantages of optical based NIR imaging, the reason that NIR imagers are not clinically used, is that only very few such fluorescent molecules absorb and emit in the NIR (or in the shortwave infrared, SWIR region), and even fewer have favorable biological properties (and FDA approval). I will introduce small lung cancer and dendritic cells tracking using small polyethylene glycol/phosphatidylethanolamine (PEG–PE) micelles loaded with NIR dyes (using commercial dyes as well as dyes synthesized in Prof. Sletten’s lab, UCLA Chemistry Dept.). Micelles’ endocytosis into cells affords efficient loading and exhibits strong bio stability, enabling to track the loaded cells for several days using these formulations, even though dyes were diluted by cells division (leading to reduced dye concentration within the dividing cells). Moreover, fluorescent lifetime contrast (achieved through our time-gated imaging method), significantly improved these cells detection. These advances in NIR fluorescence based imaging open up new avenues toward NIR and SWIR imaging for biomedical applications, such as tracking and monitoring cells during immunotherapy and/or drug delivery (treatment monitoring) for various types of disease. Postdoctoral Fellow, UCLA, CA

Chemistry colloquium

University of Maine

Chemistry colloquium

Institut Catalana d'Investigacio Quimica