<div><div><div><p>The chemistry of the f-block is relatively unknown when compared to the rest of the periodic table. Transition metals and main group elements have enjoyed thorough study and development over the last 200 years, while many of the lanthanides and actinides weren’t even discovered until the 1940’s. This is troublesome, as knowledge of these elements is critical for environmental, industrial and technological advances. Understanding bonding motifs and reactivity pathways is fundamental to advancing the field of f-block chemistry. The use of redox- active ligands has aided in the construction of new bonding modes and discovery of new reaction pathways by providing electrons for these transformations. A particularly successful partnership is formed when redox-active ligands are combined with lanthanides, as these elements are usually considered redox-restricted. A series of lanthanide complexes featuring the iminoquinone ligand in three oxidation states will be discussed. The use of the ligands as a source of electrons for reactivity is also described, with new bonding motifs for lanthanides being realized. The iminoquinone ligand can also serve to break bonds. The uranyl (UO22+) ion is notoriously difficult to handle due to its strong U-O multiple bonds. To overcome this, we developed a series of uranyl complexes and studied the ability of the iminoquinone ligand to serve as an electron source for reduction of uranium, with concomitant U-O bond cleavage.</p></div></div></div>

NMR chemical shifts have an extremely high information content on the behaviour of macromolecules, owing to their non-trivial dependence on myriads of structural and environmental factors. Although such complex dependence creates an initial barrier for their use for the characterisation of the structures of protein and nucleic acids, recent developments in prediction methodologies and their successful implementation in resolving the structures of these molecules have clearly demonstrated that such barrier can be crossed. Furthermore, the significance of chemical shifts as useful observables in their own right has been substantially increased since the development of the NMR techniques to study low populated 'excited' states of biomolecules. This work is aimed at increasing our understanding of the multiple factors that affect chemical shifts in proteins and nucleic acids, and at developing high-quality chemical shift predictors for atom types that so far have largely escaped the attention in chemical shift restrained molecular dynamics simulations. A general approach is developed to optimise the models for structure-based chemical shift prediction, which is then used to construct CH3Shift and ArShift chemical shift predictors for the nuclei of protein side-chain methyl and aromatic moieties. These results have the potential of making a significant impact in structural biology, in particular when taking into account the advent of recent techniques for specific isotope labelling of protein side-chain atoms, which make large biomolecules accessible to NMR techniques. Through their incorporation as restraints in molecular dynamics simulations, the chemical shifts predicted by the approach described in this work create the opportunity of studying the structure and dynamics of proteins in a wide range of native and non-native states in order to characterise the mechanisms underlying the function and dysfunction of these molecules.

<p>Parkinson’s disease is a neurodegenerative disorder characterized by a loss of dopaminergic neurons, where mitochondrial dysfunction and neuroinflammation are implicated in this process. However, the exact mechanisms of mitochondrial dysfunction, oxidative stress and neuroinflammation leading to the onset and development of Parkinson’s disease are not well understood. There is a lack of tools necessary to dissect these mechanisms, therefore we engineered genetically encoded fluorescent biosensors to monitor redox status and an inflammatory signal peptide with high spatiotemporal resolution. To measure intracellular redox dynamics, we developed red-shifted redox sensors and demonstrated their application in dual compartment imaging to study cross compartmental redox dynamics in live cells. To monitor extracellular inflammatory events, we developed a family of spectrally diverse genetically encoded fluorescent biosensors for the inflammatory mediator peptide, bradykinin. At the organismal level, we characterized the locomotor effects of mitochondrial toxicant-induced dopaminergic disruption in a zebrafish animal model and evaluated a behavioral assay as a method to screen for dopaminergic dysfunction. Pairing our intracellular redox sensors and our extracellular bradykinin sensors in a Parkinson’s disease animal model, such as a zebrafish toxicant-induced model will prove useful for dissecting the role of mitochondrial dysfunction and inflammation in Parkinson’s disease. </p>

<div>Vibrational spectroscopic imaging has become an emerging platform for chemical visualization of biomolecules and materials in complex systems. For over a century, both Raman and infrared spectroscopy have demonstrated the capability to recognize molecules of interest by harnessing the characteristic features from molecular fingerprints. With the recent development of hyperspectral vibrational spectroscopy imaging, which records the chemical information without sacrificing the spatial-temporal resolution, numerous discoveries has been achieved in the field of molecular and cellular biology. Despite the ability to provide complimentary chemical information to Raman-based approaches, infrared spectroscopy has not been extensively applied in routine studies due to several fundamental limitations: 1). the poor spatial resolution; 2). inevitable strong water absorption; 3). lack of depth resolution.</div><div>Mid-infrared photothermal (MIP) microscopy overcame all the above mentioned problems and for the first time, enabled depth-resolved in vivo infrared imaging of live cells, microorganisms with submicrometer spatial resolution. The development of epi-detected MIP microscopy further extends its application in pharmaceutical and materials sciences. With the deployment of difference frequency generation and other nonlinear optical techniques, the spectral coverage of the MIP microscopy was significantly enhanced to enable chemical differentiation in complex systems across the broad mid-infrared region. In addition to the efforts to directly improve the performance of MIP microscopy, a novel quantitative phase imaging approach based on polarization wavefront shaping via custom-designed micro-retarder arrays was developed to take advantage of the highly sensitive phase measurement in combination with the photothermal effect. Besides, the extended depth-of-field and multifocus imaging enabled by polarization wavefront shaping could both improve the performance of MIP microscopy for volumetric imaging.</div>

Raman multivariate curve resolution (Raman-MCR) spectroscopy is used to study water-mediated interactions by decomposing Raman spectra of aqueous solutions into bulk water and solute-correlated (SC) spectral components. The SC spectra are minimum-area difference spectra that reveal solute-induced perturbations of water structure, including changes in water hydrogen-bonding strength, tetrahedral structure, and formation of dangling (non-hydrogen-bonded) OH defects in a solute's hydration shell. Additionally, Raman-active intramolecular vibrational modes of the solute may be used to uncover complementary information regarding solute--solute interactions. Herein, Raman-MCR is applied to address fundamental questions related to: (1) confined cavity water and its connection to host-guest binding, (2) hydrophobic hydration of fluorinated solutes, (3) specific ion effects on nonionic micelle formation, and (4) ion pairing in aqueous solutions.

In the area of forensic chemistry, improved or new analysis methods are continually being investigated. One common and powerful technique used in forensic chemistry is wall-coated open-tubular column (WCOT) gas chromatography with electron ionization single quadrupole mass spectrometry (GC-MS). Improvements to and effectiveness of alternatives to this instrumental platform were explored in an array of parallel inquiries. The areas studied included the column for the chromatographic separation, the universal detection method employed, and the fragmentation method used to enhance molecular identification. <br><br>Superfine-micropacked capillary (SFµPC) columns may provide an alternative to commercial packed GC columns and WCOT GC columns that combines the benefits of the larger sample capacity of packed columns and the benefits of the excellent separation capabilities and mass spectrometry (MS) flow rate compatibility of WCOT columns. SFµPC columns suffer from high inlet pressure requirements and prior reported work has required specialized instrumentation for their use. Fabrication of and chromatography with SFµPC GC columns was successfully achieved with typical GC-MS instrumentation and within the flow rate limit of a MS. Additionally, the use of higher viscosity carrier gasses was demonstrated to reduce the required inlet pressure for SFµPC GC columns.<br><br>Recently, a new vacuum ultraviolet spectrometer (VUV) universal detector has been commercialized for GC. The ability of VUV detectors to acquire absorbance spectra from 125 nm to 430 nm poses a potential alternative to MS. As such, GC-VUV provides an exciting potential alternative approach to achieving excellent quantitative and qualitative analysis across a wide range of analytes. The performance of VUV and MS detectors for forensic analysis in terms of quantitative and qualitative analysis was compared. Analysis of alkylbenzenes in ignitable liquids was explored, which can be important evidence from suspected arson fires and are difficult to differentiate with MS. The VUV detector was found to have superior specificity and comparable sensitivity to the MS detector in scan mode.<br><br>Addition of thermolysis (Th) as an orthogonal fragmentation pathway provides the opportunity to increase the differences between MS fragmentation patterns. Fragmentation has been widely established to aid in identification of molecules with MS by providing characteristic fragments at characteristic relative abundances. However, molecules with very similar structures do not result in sizable spectral differences in all cases with typical MS fragmentation techniques. A series of Th units were fabricated and integrated into GC-Th-MS instruments. Th-MS was conducted with the thermally labile nitrate esters across a range of instrumentation and thermal conditions.<br>

<p>  </p> <p>Experimental and computational techniques are used to study physico-chemical phenomena occurring in water on which hydrophobic interactions play a role. In particular, hydrophobic self-aggregation, including host-guest binding, and the affinity of ions to oil/water interfaces are investigated. Raman multivariate curve resolution (Raman-MCR) spectroscopy was the experimental technique used to unveil intermolecular interactions through the analysis of solute-correlated (SC) vibrational spectra. Molecular simulations, including molecular dynamics (MD) simulations, quantum-mechanical calculations, or a combination of both, were carried out to assist with the molecular-level interpretation of the experimental SC spectra.</p>

The development of solution-processable semiconducting polymers has brought mankind’s long-sought dream of plastic electronics to fruition. Their potential in the manufacturing of lightweight, flexible yet robust, and biocompatible electronics has spurred their use in organic transistors, photovoltaics, electrochromic devices, batteries, and sensors for wearable electronics. Yet, despite the successful engineering of semiconducting polymers, we do not fully understand their molecular behavior and how it influences their doping (oxidation/reduction) properties. This is especially true for donor-acceptor (D-A) p-systems which have proven to be very efficient at tuning the electronic properties of organic semiconductors. Historically, chain-length dependent studies have been essential in uncovering the relationship between the molecular structure and polymer properties. Discussed here is the systematic investigation of a complete D-A molecular series composed of monodispersed and well-defined conjugated molecules ranging from oligomer (n=3-21) to polymer scale lengths. Structure-property relationships are established between the molecular structure, chain conformation, and redox-active opto-electronic properties for the molecular series in solution. This research reveals a rod-to-coil transition at the 15 unit chain length, or 4500 Da, in solution. The redox-active optical and electronic properties are investigated as a function of increasing chain-length, giving insight into the nature of charge carriers in a D-A conjugated system. This research aids in understanding the solution behavior of conjugated organic materials. <br>