Synthesis of conjugated polyrotaxanes

A series of conjugated polyrotaxane insulated molecular wires are synthesised by aqueous Suzuki polymerisation, using hydrophobic binding to promote threading of the cyclodextrin units. These polyrotaxanes have conjugated polymer cores based on poly(para-phenylene), polyfluorene, and poly(diphenylene-vinylene), threaded through 0.9-1.6 cyclodextrins per repeat unit. Bulky naphthalene-3,6-disulfonate endgroups prevent the macrocycles from slipping off the conjugated polymer chains. Dialysis experiments show that the cyclodextrins become unthreaded only if smaller stoppers are used. MALDI TOF mass spectra detect oligomers with up to ten threaded cyclodextrins, and reveal the presence of some defects that result for oxidative homo-coupling of boronic acids. Weight-average molecular weights were determined by analytical ultracentrifugation, demonstrating that step-growth polymerisation is efficient enough to achieve degrees of polymerisation up to approximately 20 repeat units (84 para-phenylenes). The fluorescence spectra of these polyrotaxanes indicate that the presence of the threaded cyclodextrin macrocycles reduces the flexibility of the conjugated polymer pi-systems. Both the solution and the solid-state photoluminescence quantum yields are enhanced upon threading of the conjugated polyaromatic cores through alpha- or beta-cyclodextrins, and the emission spectra of the polyrotaxanes are blue-shifted compared to the corresponding unthreaded polymers. The greater weight of the 0-0 transition in the emission spectra, as well as the smaller Stokes shift, indicate that the polyrotaxanes are more rigid than the unthreaded polymers.     

Stabilization of carbon dioxide-in-water emulsions with silica nanoparticles

Stable carbon dioxide-in-water emulsions were formed with silica nanoparticles adsorbed at the interface. The emulsion stability and droplet size were characterized with optical microscopy, turbidimetry, and measurements of creaming rates. The increase in the emulsion stability as the silica particle hydrophilicity was decreased from 100% SiOH to 76% SiOH is described in terms of the contact angles and the resulting energies of attachment for the silica particles at the water-CO(2) interface. The emulsion stability also increased with an increase in the particle concentration, CO(2) density, and shear rate. The dominant destabilization mechanism was creaming, whereas flocculation, coalescence, and Ostwald ripening played only a minor role over the CO(2) densities investigated. The ability to stabilize these emulsions with solid particles at CO(2) densities as low as 0.739 g/mL is particularly relevant in practical applications, given the difficulty in stabilizing these emulsions with surfactants, because of the unusually weak solvation of the surfactant tails by CO(2).     

Signatures of beta-sheet secondary structures in linear and two-dimensional infrared spectroscopy

Using idealized models for parallel and antiparallel beta sheets, we calculate the linear and two-dimensional infrared spectra of the amide I vibration as a function of size and secondary structure. The model assumes transition-dipole coupling between the amide I oscillators in the sheet and accounts for the anharmonic nature of these oscillators. Using analytical and numerical methods, we show that the nature of the one-quantum vibrational eigenstates, which govern the linear spectrum, is, to a large extent, determined by the symmetry of the system and the relative magnitude of interstrand interactions. We also find that the eigenstates, in particular their trends with system size, depend sensitively on the secondary structure of the sheet. While in practice these differences may be difficult to distinguish in congested linear spectra, we demonstrate that they give rise to promising markers for secondary structure in the two-dimensional spectra. In particular, distinct differences occur between the spectra of parallel and antiparallel beta sheets and between beta hairpins and extended beta sheets.     

Surface forces,supramolecular polymers,and inversion symmetry

The effects of supramolecular equilibrium polymers on surface forces are studied by both a phenomenological Landau type analysis and a molecular model based on a Bethe-Guggenheim approximation. We point out that surface forces brought about by equilibrium polymers may be completely different from what can be found with "ordinary" polymers. The new feature is the role of inversion (a)symmetry or "directionality" of the associating unit molecules ("monomers"). Symmetric B-B monomers (where B denotes a self-complementary binding group) give rise to nondirectional chains and lead to attractive forces between similar surfaces. Asymmetric A-D monomers (where A and D denote complementary acceptor and donor groups, respectively) produce directional chains and can cause strong repulsion. The range of the attractive force has a maximum at intermediate concentration, while the range of the repulsive force increases over the whole concentration range.     

The possibility of semiconductor–metal transition in a spherical quantum dot

We observe an abrupt change in diamagnetic susceptibility at critical donor concentration for an $\text{ Al }_\mathrm{x}\text{ Ga }_\mathrm{1-x}\text{ As/GaAs }$ Al x Ga 1 ? x As/GaAs quantum dot system in the effective mass approximation indicating a possible semiconductor metal transition. The effect of confining potential and the laser intensity on the abrupt change in diamagnetic susceptibility has also been studied. The effect of nonparabolicity of the conduction band has been included in our calculations. Results are presented and discussed.     

Multiplex metal-detection based assay (MMDA) for COVID-19 diagnosis and identification of disease severity biomarkers

The ongoing COVID-19 pandemic caused by SARS-CoV-2 highlights the urgent need to develop sensitive methods for diagnosis and prognosis. To achieve this, multidimensional detection of SARS-CoV-2 related parameters including virus loads, immune response, and inflammation factors is crucial. Herein, by using metal-tagged antibodies as reporting probes, we developed a multiplex metal-detection based assay (MMDA) method as a general multiplex assay strategy for biofluids. This strategy provides extremely high multiplexing capability (theoretically over 100) compared with other reported biofluid assay methods. As a proof-of-concept, MMDA was used for serologic profiling of anti-SARS-CoV-2 antibodies. The MMDA exhibits significantly higher sensitivity and specificity than ELISA for the detection of anti-SARS-CoV-2 antibodies. By integrating the high dimensional data exploration/visualization tool (tSNE) and machine learning algorithms with in-depth analysis of multiplex data, we classified COVID-19 patients into different subgroups based on their distinct antibody landscape. We unbiasedly identified anti-SARS-CoV-2-nucleocapsid IgG and IgA as the most potently induced types of antibodies for COVID-19 diagnosis, and anti-SARS-CoV-2-spike IgA as a biomarker for disease severity stratification. MMDA represents a more accurate method for the diagnosis and disease severity stratification of the ongoing COVID-19 pandemic, as well as for biomarker discovery of other diseases.

A MMDA platform is developed by using metal-tagged antibodies as reporting probes combined with machine learning algorithms, as a general strategy for highly multiplexed biofluid assay.     

Orally administered bismuth drug together with N-acetyl cysteine as a broad-spectrum anti-coronavirus cocktail therapy

The emergence of SARS-CoV-2 variants of concern compromises vaccine efficacy and emphasizes the need for further development of anti-SARS-CoV-2 therapeutics, in particular orally administered take-home therapies. Cocktail therapy has shown great promise in the treatment of viral infection. Herein, we reported the potent preclinical anti-SARS-CoV-2 efficacy of a cocktail therapy consisting of clinically used drugs, e.g. colloidal bismuth subcitrate (CBS) or bismuth subsalicylate (BSS), and N-acetyl-l-cysteine (NAC). Oral administration of the cocktail reduced viral loads in the lung and ameliorated virus-induced pneumonia in a hamster infection model. The mechanistic studies showed that NAC prevented the hydrolysis of bismuth drugs at gastric pH via the formation of the stable component [Bi(NAC)₃], and optimized the pharmacokinetics profile of CBS in vivo. Combination of bismuth drugs with NAC suppressed the replication of a panel of medically important coronaviruses including Middle East respiratory syndrome-related coronavirus (MERS-CoV), Human coronavirus 229E (HCoV-229E) and SARS-CoV-2 Alpha variant (B.1.1.7) with broad-spectrum inhibitory activities towards key viral cysteine enzymes/proteases including papain-like protease (PL^pro), main protease (M^pro), helicase (Hel) and angiotensin-converting enzyme 2 (ACE2). Importantly, our study offered a potential at-home treatment for combating SARS-CoV-2 and future coronavirus infections.

A cocktail therapy comprising bismuth drugs and N-acetyl-l-cysteine is reported to suppress the replication of SARS-CoV-2 via the oral route. The broad-spectrum inhibitory activities of the combination upon key viral cysteine enzymes are verified.