Benzobisoxazole Cruciforms and Guanosine Derivatives: Syntheses, Structural Analyses, and Optical Properties

This dissertation presents two studies in supramolecular chemistry; one is the chemistry of benzobisoxazole cruciforms in which two linearly conjugated π systems meet at the unsaturated center, and the other is that of guanosine derivatives. Chapter One. This chapter summarizes the previous work on molecular cruciforms: tetrakis(arylethynyl)benzenes, distyrylbis(arylethynyl)benzenes, tetrakis(aryl-vinyl)benzenes, and tetraethynylethenes. Chapter Two. The synthesis, optical properties, and computational calculation of benzobisoxazole-based molecular cruciforms are presented. The potential use of donor/acceptor substituted cruciforms as sensors is also discussed, and optical response of cruciform compounds to different concentration of trifluoroacetic acid in the liquid state is presented. Chapter Three. A method for the identification method of carboxylic acids, organoboronic acids, phenols, amines, ureas, and tetrabutylammonium salts is described using one of donor/acceptor substituted benzobisoxazole-cruciforms as the sensor. Chapter Four. Structural study of benzobisoxazole cruciforms is presented: their solid state structures, obtained by X-ray crystallography, are presented. Chapter Five. The synthesis and structural analysis of 8-arylethynyl substituted guanosine derivatives is presented. The structural effects of this substitution, in comparison to the previous work in guanosine chemistry, is also discussed.Chemistry, Department o

Selective and Sensitive Fluoride Detection through Alkyne Cruciform Desilylation

Desilylation of silylethynyl-substituted benzobisoxazole cruciforms can be achieved using stoichiometric amounts of fluoride, leading to a significant change in their UV–vis absorption and fluorescence. This response is observable at micromolar concentrations of fluoride, and, in the case of a triisopropylsilyl-substituted cruciform fluorophore, extraordinarily selective for fluoride over other small inorganic anions, including hydroxide, acetate, and phosphate

Synthesis and Structural Analyses of Phenylethynyl-Substituted Tris(2-Pyridylmethyl)Amines and their Copper(II) Complexes

Three new tris(2-pyridylmethyl) amine-based ligands possessing phenylethynyl units have been prepared using Sonogashira couplings and substitution reactions. Copper(II) complexes of those tetradentate ligands have also been synthesized. Solid-state structures of the six new compounds have been determined by single-crystal X-ray diffraction analyses. Examination of the molecular structures of the ligands revealed the expected triangular geometries with virtually undeformed carbon-carbon triple bonds. While the tertiary nitrogen of the free ligands seem to be prevented from participation in supramolecular non-covalent interactions by the pyridyl hydrogen at the 3-position, the pyridyl nitrogens play a crucial role in the packing mode of the crystal structure. The nitrogens form weak hydrogen bonds, varied in length between 2.32 and 2.66 angstrom, with the pyridyl hydrogen of its neighbouring molecule. The [N center dot center dot center dot H-C] contacts enforce one-dimensional columnar assemblies on ligands that organize into wall-like structures, which in turn assemble into three-dimensional structures through CH-pi interactions. Structural analyses of Cu(II) complexes of the ligands revealed propeller-like structures caused by steric crowding of three pyridine ligands. The copper complexes of the ligands having three phenylethynyl substituents showed a remarkably deformed carbon-carbon triple bond enforced by a steric effect of the three phenyl groups. Most significantly, a total of seventy non-covalent interactions, classified into twelve types of hydrogen-involving short contacts, were identified in this study. The phenylethynyl substituent participated in forty-two interactions as a hydrogen bond acceptor, and its role was more distinctive in the crystal structures of the Cu(II) complexes.National Science Foundation CHE-1212971Welch Foundation F-0046Chemistr

Benzobisoxazole Cruciforms: Heterocyclic Fluorophores with Spatially Separated Frontier Molecular Orbitals

We report the synthesis of nine conjugated cruciform-shaped molecules based on the central benzo­[1,2-<i>d</i>:4,5-<i>d</i>′]­bisoxazole nucleus, at which two conjugated currents intersect at a ∼90° angle. Cruciforms’ substituents were varied pairwise among the electron-neutral phenyl groups, electron-rich 4-(<i>N</i>,<i>N</i>-dimethylamino)­phenyl substituents, and electron-poor pyridines. Hybrid density functional theory calculations revealed that the highest occupied molecular orbitals (HOMOs) are localized (24–99%) in all cruciforms, in contrast to the lowest unoccupied molecular orbitals (LUMOs) which are strongly dependent on the substitution and less localized (6–64%). Localization of frontier molecular orbitals (FMOs) along different axes of these cruciforms makes them promising as sensing platforms, since analyte binding to the cruciform should mandate a change in the HOMO–LUMO gap and the resultant optical properties. This prediction was verified using UV/vis absorption and emission spectroscopy: cruciforms’ protonation results in hypsochromic and bathochromic shifts consistent with the preferential stabilization of HOMO and LUMO, respectively. In donor–acceptor-substituted systems, a two-step optical response to protonation was observed, wherein an initial bathochromic shift is followed by a hypsochromic one with continued acidification. X-ray diffraction studies of three selected cruciforms revealed the expected ∼90° angle between the cruciform’s substituents, and crystal packing patterns dominated by [π···π] stacking and edge-to-face [C–H···π] contacts

The Effectiveness of the Use of Regdanvimab (CT-P59) in Addition to Remdesivir in Patients with Severe COVID-19: A Single Center Retrospective Study

Introduction: Coronavirus disease 2019 (COVID-19) still has a high mortality rate when it is severe. Regdanvimab (CT-P59), a neutralizing monoclonal antibody that has been proven effective against mild to moderate COVID-19, may be effective against severe COVID-19. This study was conducted to determine the effectiveness of the combined use of remdesivir and regdanvimab in patients with severe COVID-19. Methods: From March to early May 2021, 124 patients with severe COVID-19 were admitted to Ulsan University Hospital (Ulsan, Korea) and received oxygen therapy and remdesivir. Among them, 25 were also administered regdanvimab before remdesivir. We retrospectively compared the clinical outcomes between the remdesivir alone group [n = 99 (79.8%)] and the regdanvimab/remdesivir group [n = 25 (20.2%)]. Results: The oxygen-free days on day 28 (primary outcome) were significantly higher in the regdanvimab/remdesivir group [mean ± SD: 19.36 ± 7.87 vs. 22.72 ± 3.66, p = 0.003]. The oxygen-free days was also independently associated with use of regdanvimab in the multivariate analysis, after adjusting for initial pulse oximetric saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio (severity index). Further, in the regdanvimab/remdesivir group, the lowest SpO2/FiO2 ratio during treatment was significantly higher (mean ± SD: 237.05 ± 89.68 vs. 295.63 ± 72.74, p = 0.003), and the Kaplan-Meier estimates of oxygen supplementation days in surviving patients (on day 28) were significantly shorter [mean ± SD: 8.24 ± 7.43 vs. 5.28 ± 3.66, p = 0.024]. Conclusions: In patients with severe COVID-19, clinical outcomes can be improved by administering regdanvimab, in addition to remdesivir