Local interactions of the quantised electromagnetic field

Photons, i.e. the basic energy quanta of monochromatic waves, are highly non-localised and occupy all available space in one dimension. This non-local property can complicate the modelling of the quantised electromagnetic field in the presence of optical elements that are local objects. Therefore, this thesis takes an alternative approach and shows that a local second quantisation of the electromagnetic (EM) field is possible but requires an extension of conventional quantum theory. For light propagating in one dimension, we obtain highly localised bosonic Fock operators, which we do by doubling the usual photon Hilbert space with some photonic modes evolving according to the standard Schrodinger equation and others evolving according to the complex conjugated Schrodinger equation. We also view the quantised EM field as a biorthogonal system. However, we view it as a biorthogonal system where the intersection of the Hilbert space and its dual Hilbert space is non-zero. To the best of our knowledge, this is the first time such a construction of the EM field has been made. These highly localised bosonic Fock operators provide natural building blocks of wave packets of light and enable us to construct locally acting interaction Hamiltonians for two-sided semi-transparent mirrors. Using these Hamiltonians, we produce appropriate classical dynamics of the electric field near a mirror. The question of how to model local transformations of the EM field is a hot topic, as physicists often measure interactions between the EM field and local optical devices in experiments. Therefore, we expect our results to find large appeal across both the quantum optics and non-Hermitian communities. We finish by discussing possible future avenues of research

Quantising the electromagnetic field in position space

In a recent paper [Southall et al., Locally-acting mirror Hamiltonians, arXiv:1908.07597 (2021)], we showed that it is possible to design locally-acting mirror Hamiltonians which only affect incoming but do not change the dynamics of outgoing wave packets. To better justify our approach, this paper presents a systematic quantisation of the electromagnetic field in position space. Starting from the assumption that the basic building blocks of the electromagnetic field in one dimension are localised bosonic wave packets with a clear direction of propagation -- so-called bosons localised in position (BLiPs) -- we identify the relevant Schroedinger equation and construct Lorentz covariant electric and magnetic field observables. Our description contains the standard description of the quantised electromagnetic field which is shown to apply to a subspace of states.Comment: 15 pages, no figure

Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle

Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure– activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of 7ii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis

High-Throughput Screening, Discovery, and Optimization to Develop a Benzofuran Class of Hepatitis C Virus Inhibitors

Using a high-throughput, cell-based HCV luciferase reporter assay to screen a diverse small-molecule compound collection (~300 000 compounds), we identified a benzofuran compound class of HCV inhibitors. The optimization of the benzofuran scaffold led to the identification of several exemplars with potent inhibition (EC50 25 µM), and excellent selectivity (selective index = CC50/EC50, > 371-fold). The structure–activity studies culminated in the design and synthesis of a 45-compound library to comprehensively explore the anti-HCV activity. The identification, design, synthesis, and biological characterization for this benzofuran series is discussed

Novel Cell-Based Hepatitis C Virus Infection Assay for Quantitative High-Throughput Screening of Anti-Hepatitis C Virus Compounds

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Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection

Recently, we reported that chlorcyclizine (CCZ, <b>Rac-2</b>), an over-the-counter antihistamine piperazine drug, possesses <i>in vitro</i> and <i>in vivo</i> activity against hepatitis C virus. Here, we describe structure–activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC₅₀ values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved <i>in vivo</i> pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host–virus interaction

Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection

Recently, we reported that chlorcyclizine (CCZ, <b>Rac-2</b>), an over-the-counter antihistamine piperazine drug, possesses <i>in vitro</i> and <i>in vivo</i> activity against hepatitis C virus. Here, we describe structure–activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC₅₀ values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved <i>in vivo</i> pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host–virus interaction

High-Throughput Screening, Discovery, and Optimization To Develop a Benzofuran Class of Hepatitis C Virus Inhibitors

Using a high-throughput, cell-based HCV luciferase reporter assay to screen a diverse small-molecule compound collection (∼300 000 compounds), we identified a benzofuran compound class of HCV inhibitors. The optimization of the benzofuran scaffold led to the identification of several exemplars with potent inhibition (EC₅₀ < 100 nM) of HCV, low cytotoxicity (CC₅₀ > 25 μM), and excellent selectivity (selective index = CC₅₀/EC₅₀, > 371-fold). The structure–activity studies culminated in the design and synthesis of a 45-compound library to comprehensively explore the anti-HCV activity. The identification, design, synthesis, and biological characterization for this benzofuran series is discussed