Publications

Deconvolution of the protein targets of hit compounds from phenotypic screens, often conducted in live cells, is critical for understanding mechanism of action and identifying potentially hazardous off-target interactions. While photoaffinity labeling and chemoproteomics are long-established approaches for discovering small-molecule-protein interactions in live cells, there are a relatively small number of photoaffinity labeling strategies that can be applied for chemoproteomic target identification studies. Recently, we reported a novel chemical framework for photoaffinity labeling based on the photo-Brook rearrangement of acyl silanes and demonstrated its ability, when appended to protein-targeting ligands, to label recombinant proteins. Here, we report the application of these probes to live cell photoaffinity workflows, demonstrate their complementarity to current state-of-the-art minimalist diazirine-based photoaffinity probes, and introduce a modular synthetic route to access acyl silane scaffolds with improved labeling properties.

Herein, we combine Density Functional Theory (DFT) with ab initio molecular dynamics at ambient conditions to calculate surface properties of and CO binding trends to the electrocatalytically relevant Pt(111), Cu(111), Ag(111), and Au(111) metals. By accounting for thermal effects both the RPBE GGA and the B97M-rV meta-GGA functionals show better metal surface strain trends, CO binding energetics, and the correct low-coordination site preference for the Cu(111) and Pt(111) surfaces. The importance of dispersion is evident at finite temperatures, with only B97M-rV exhibiting binding energetics in agreement with experiment for the Ag(111) and Au(111) surfaces, and is found to consist of a mixture of chemisorbed and physisorbed CO species. Overall this work begins to address a longstanding theoretical discrepancy with experimental observations on these important metals relevant to the electrochemical CO2 reduction reaction through the full accounting of thermal fluctuations.

Physisorption in porous materials is a promising route to meet mol. hydrogen (H_2) storage and delivery requirements for
\ntransportation because it is both fast and fully reversible at mild conditions. However, most current candidates have binding
\nenthalpies to H_2 that are too small, which lead to volumetric capacity at 298 K of less than 10 g/L compared to the system
\ntarget of 40 g/L. Using accurate quantum mech. (QM) methods, we det. the H_2 binding enthalpy of 48 compds. (5 linkers and
\n11 different transition metals) used for porous covalent org. frameworks (COF) which we metalated with different transition
\nmetals (TM) , including first row TM (Sc though Cu) and precious TM (Pd and Pt) . We showed that first row TM give similar and
\nsometimes superior van der Waals interactions with H_2 than precious TMs. Based on these results, we constructed 26 new
\nCOFs based on these linkers and we det. the uptake using force fields (FF) based on QM and grand canonical Monte Carlo
\nsimulations. We detd. new COFs that reach the DOE 2017 target of 40 g/L. This work highlights the designing principles for
\nthe optimal interaction enthalpy in the next generation of H_2 storage materials.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Combinatorial approaches together with high-throughput screening have been used to develop highly selective stationary phases for chiral recognition. Libraries of potential chiral selectors have been prepared by the Ugi multicomponent condensation reactions and screened for their enantioselectivity using the reciprocal approach involving a chiral stationary phase with immobilized model target compound N-(3,5-dinitrobenzoyl)-alpha-l-leucine. The best candidates were identified from the library of phenyl amides of 2-oxo-azetidineacetic acid derivatives. This screening also enabled specification of the functionalities of the selector desired to achieve the highest level of chiral recognition. The substituents of the phenyl ring adjacent to the chiral center of the selector candidates exhibited the most profound effect on the chiral recognition. The best candidate was then synthesized on a larger scale, resolved into single enantiomers using preparative enantioselective HPLC, and attached to porous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) beads via an ester linkage to afford the desired stationary phase. Selectivities alpha as high as 3.2 were found for the separation of a variety of amino acid derivatives.

Copper boryl species have been widely invoked as reactive intermediates in Cu-catalysed C−H borylation reactions, but their isolation and study have been challenging. Use of the robust dinucleating ligand DPFN (2,7-bis(fluoro-di(2-pyridyl)methyl)-1,8-naphthyridine) allowed for the isolation of two very thermally stable dicopper(I) boryl complexes, [(DPFN)Cu2(µ-Bpin)][NTf2] (2) and [(DPFN)Cu2(µ-Bcat)][NTf2] (4) (pin = 2,3-dimethylbutane-2,3-diol; cat = benzene-1,2-diol). These complexes were prepared by cleavage of the corresponding diborane via reaction with the alkoxide [(DPFN)Cu2(µ-OtBu)][NTf2] (3). Reactivity studies illustrated the exceptional stability of these boryl complexes (thermal stability in solution up to 100 °C) and their role in the activation of C(sp)−H bonds. X-ray diffraction and computational studies provide a detailed description of the bonding and electronic structures in these species, and suggest that the dinucleating character of the naphthyridine-based ligand is largely responsible for their remarkable stability.

The impedance behavior of pre-oxidized iron in liquid lead-bismuth eutectic (LBE) at 200 oC is studied using electrochemical impedance spectroscopy. The structures and resistance of oxide grown on iron oxidized in air at different temperatures and durations are compared. The results show that the resistance of the oxide film increases with increasing oxidizing temperature, due to the formation of a thicker scale and fewer defects. At the same temperature (600 oC), increasing the oxidation time can also reduce the defect concentration in the oxide film and improve the impedance of the oxide scale in LBE.