Synthesis of InP/ZnS Nanocrystals and Phase Transfer by Hydrolysis of Ester

The synthesis of highly luminescent non-toxic nanocrystals (NCs) and the subsequent phase transfer to aqueous solution by hydrolysis of the crystal-bound ester are presented. Therefore, the synthesis of the spherical semiconductor system InP/ZnS was modified by changing the sulfur precursor in the synthesis from 1-dodecanethiol to dodecyl 3-mercaptopropionate (D3MP). By employing D3MP both as sulfur precursor for the ZnS shell growth and as stabilizing ligand, the phase transfer from organic to aqueous solution can be performed easily. Instead of the usually employed ligand exchange with mercaptopropionic acid, the NCs are only shaken with a sodium borate buffer in order to obtain aqueous soluble NCs by hydrolysis of the ester. In future work, the NCs must be protected against aggregation and the long term stability has to be increased. The optical properties of the samples are investigated by UV/Vis and photoluminescence spectroscopy, and the morphology of the nanoparticles (NPs) before and after phase transfer is determined by transmission electron microscopy

Temperature-Sensitive Localized Surface Plasmon Resonance of α-NiS Nanoparticles

The presented work shows a synthesis route to obtain nanoparticles of the hexagonal α-NiS phase and core-shell particles where the same material is grown onto previously prepared Au seeds. In the bulk, this nickel sulfide phase is known to exhibit a metal-insulator type phase transition (MIT) at 265 K which drastically alters its electrical conductivity. Since the produced nanoparticles show a localized surface plasmon resonance (LSPR) in the visible range of the electromagnetic spectrum, the development of their optical properties depending on the temperature is investigated. This is the first time an LSPR of colloidal nanoparticles is monitored regarding such a transition. The results of UV-vis absorbance measurements show that the LSPR of the particles can be strongly and reversibly tuned by varying the temperature. It can be switched off by cooling the nanoparticles and switched on again by reheating them above the transition temperature. Additional to the phase transition, the temperature-dependent magnetic susceptibility of α-NiS and Au-NiS nanoparticles suggests the presence of different amounts of uncompensated magnetic moments in these compounds that possibly affect the optical properties and may cause the observed quantitative differences in the LSPR response of these materials

Halide ion influence on the formation of nickel nanoparticles and their conversion into hollow nickel phosphide and sulphide nanocrystals

A dependence of the formation of tri-n-octylphosphine-capped Ni nanocrystals on the presence of halide ions during their synthesis is shown. For the application-oriented synthesis of Ni particles, this information can be crucial. Furthermore, Ni nanoparticles can be converted to nickel phosphide or sulphide by heating them up in the presence of a phosphorus or sulphur source, resulting in either solid or hollow nanocrystals, formed via the nanoscale Kirkendall effect, depending on the synthesis route. By adjusting the Ni crystallite size in the initial nanoparticles via the halide ion concentration the cavity size of the resulting hollow nanocrystals can be tuned, which is otherwise impossible to realise for particles of a similar total diameter by using this process. The synthesised hollow Ni3S2 nanocrystals exhibit a much sharper localised surface plasmon resonance (LSPR) band than all previously presented particles of this material, which is known to show molar extinction coefficients at the LSPR maximum similar to Au. This narrow linewidth could be explained by the nanoparticles’ high crystallinity resulting from the Kirkendall process and is interesting for various possible optical applications such as surface-enhanced Raman spectroscopy owing to the low cost of the involved materials compared to the widely used noble metals

Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M^(pro)), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M^(pro). In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Schlüssel-Schloss-Wechselwirkung konkav und konvex geformter Nanopartikel mit maßgeschneiderter Partikelmorphologie

Trotz aller bisherigen Forschungsresultate und Erfahrungen bleibt die Synthese von Hybridnanopartikeln ein herausforderndes Arbeitsgebiet und ist weiterhin Gegenstand aktueller Forschung. In diesem Forschungsbereich sind die Kapitel 3 bis 4 einzuordnen. Vorab wird in Kapitel 2 die Synthese monodisperser, quasi-sphärischer Goldnanopartikel mit definiertem Durchmesser beschrieben. Diese Nanopartikel sind als Kristallkeime für nachgeschaltete Aufwachssynthesen anderer Materialien geeignet, da ihre Partikelgrößenverteilung schmal, die Partikelkonzentration verhältnismäßig hoch und die Partikelmorphologie einheitlich ist. In Kapitel 3 wird eine Syntheseprozedur vorgestellt, durch welche das Aufwachsen des Halbleitermaterials Cadmiumsulfid auf Goldnanopartikel möglich ist. Hierbei hat sich der Einfluss von Chloridionen auf das Aufwachsverhalten als signifikant herausgestellt. Im Wesentlichen ist für eine erfolgreiche Synthese von Au-CdS Hybridnanopartikeln die Zugabe gewisser Mengen Chloridionen zur Syntheselösung erforderlich. Die Ergebnisse lassen sich im gewissen Rahmen auf weitere Metall-Cadmiumchalkogenid-Systeme übertragen. Im anschließenden Kapitel 4 wird gezeigt, dass Chloridionen auch beim Aufwachsen von Metalloxiden auf Goldnanopartikel einen starken Einfluss ausüben können. Zur Herstellung von Gold-Eisenoxid Hybridnanopartikel ist ebenfalls der gezielte Einsatz von Chloridionen ein äußerst wichtiger Schlüsselaspekt zum Syntheseerfolg. In Kapitel 5 werden gezielt Nanopartikel mit konkaver Partikelmorphologie hergestellt, indem die Golddomäne aus Gold-Manganoxid Hybridnanopartikeln selektiv entfernt wird. Die so erzeugten konkaven Manganoxidnanopartikel zeigen eine größen- und formspezifische Wechselwirkung mit konvexen Nanopartikeln in komplementärer Form und Größe. Hierbei wird der erste experimentelle Beweis für eine größenspezifische, reversible, interpartikuläre Wechselwirkung in kolloidaler Lösung erbracht. Diese Wechselwirkung ist weitestgehend unabhängig vom Material der Nanopartikel. So können die selben konkaven Manganoxidnanopartikel mit Nanopartikeln aus unterschiedlichen Materialien wie Gold, Silber, Eisenoxid und sogar Gold-Nickelsulfid Kern-Schale Nanopartikeln in gleicher Weise wechselwirken

Growth of Cu_2–<i>x</i>Se–CuPt and Cu_1.1S–Pt Hybrid Nanoparticles

Copper chalcogenides are the focus of research due to their abundant elements and their low toxicity. In particular, plasmonic Cu_2–<i>x</i>Se and Cu_1.1S NPs represent a main topic of recent research efforts due to the postsynthetic tunability of their localized surface plasmon resonance (LSPR). In this paper, we describe the growth of Cu_2–<i>x</i>Se–CuPt and Cu_1.1S–Pt hybrid nanoparticles. In both systems we investigate the quenching of the LSPR in relation to the Pt ratios. The resulting Cu_2–<i>x</i>Se–CuPt hybrid particles form a cubic CuPt domain during the growth process. On the Cu_1.1S platelets, several, 2–3 nm sized Pt domains are formed. The changes for both systems finally result in a nearly complete damping of the LSPRs. The structural changes of the chalcogenide domain as well as of the metal domain are analyzed in depth and are related to the changes in the LSPRs of the hybrid systems