Linear wave dynamics explains observations attributed to dark-solitons in a polariton quantum fluid

We investigate the propagation and scattering of polaritons in a planar GaAs microcavity in the linear regime under resonant excitation. The propagation of the coherent polariton wave across an extended defect creates phase and intensity patterns with identical qualitative features previously attributed to dark and half-dark solitons of polaritons. We demonstrate that these features are observed for negligible nonlinearity (i.e., polariton-polariton interaction) and are, therefore, not sufficient to identify dark and half-dark solitons. A linear model based on the Maxwell equations is shown to reproduce the experimental observations.Comment: Article + Supplementary Information (tot. 18 pages

PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes

Cyclic nucleotide phosphodiesterases 4 (PDE4) are a family of enzymes which specifically promote the hydrolysis and degradation of cAMP. The inhibition of PDE4 enzymes has been widely investigated as a possible alternative strategy for the treatment of a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma, as well as psoriasis and other autoimmune disorders. In this context, the identification of new molecules as PDE4 inhibitors continues to be an active field of investigation within drug discovery. This review summarizes the medicinal chemistry journey in the design and development of effective PDE4 inhibitors, analyzed through chemical classes and taking into consideration structural aspects and binding properties, as well as inhibitory efficacy, PDE4 selectivity and the potential as therapeutic agents

Solid-Phase Synthesis and In-Silico Analysis of Iron-Binding Catecholato Chelators

Siderophores are iron-complexing compounds synthesized by bacteria and fungi. They are low molecular weight compounds (500-1500 Daltons) possessing high affinity for iron(III). Since 1970 a large number of siderophores have been characterized, the majority using hydroxamate or catecholate as functional groups. The biosynthesis of siderophores is typically regulated by the iron levels of the environment where the organism is located. Because of their exclusive affinity and specificity for iron(III), natural siderophores and their synthetic derivatives have been exploited in the treatment of human iron-overload diseases, as both diagnostic and therapeutic agents. Here, solid-phase approach for the preparation of hexadentate, peptide-based tricatecholato containing peptides is described. The versatility of the synthetic method allows for the design of a common scaffolding structure whereby diverse ligands can be conjugated. With so many possibilities, a computational approach has been developed which will facilitate the identification of those peptides which are capable of providing a high affinity iron(III) binding site. This study reports an integrated computational/synthetic approach towards a rational development of peptide-based siderophores

Evaluating thermogravimetric analysis for the measurement of drug loading in mesoporous silica nanoparticles (MSNs)

In this study, a thermogravimetric analysis (TGA) method for measuring the drug loading in mesoporous silica nanoparticles (MSNs) has been developed and evaluated in comparison with the drug loading quantification by high-performance liquid chromatography (HPLC). Indapamide was loaded into two different types of MSNs, namely Mobile Crystalline Material (MCM-41, pore size = 1.2 nm) and Santa Barbara Amorphous (SBA-15, pore size = 4.1 nm). Physical mixtures of the drug and silica gave a linear correlation between the observed and expected drug content for both TGA and HPLC, which were used for calibration purposes. The limit of detection (LOD) for the TGA method obtained from the physical mixture calibration curve was 0.77 % (w/w) and the r² value was 0.9936, whereas the HPLC had a LOD of 0.06 % (w/w) and an r² value of 0.9933. The sensitivity of the TGA method was well established using the drug loading studies, as it can detect the low loading of MCM-41 at 2.2 ± 0.21 % (w/w), compared to 5.1 ± 0.12 % (w/w) with the SBA-15. In all samples applied, the multiple comparison analysis showed an insignificant difference between the two methods (p > 0.05). The TGA data presented good evidence for using this technique as a sensitive, cost-effective, and low-variable quantitative analysis in the drug loading determination of the MSNs. TGA is not a selective method of quantification, but optimising the method using the pure and blank samples of MSNs and drug can significantly improve the sensitivity. This work provides a unique approach to apply TGA as a selective and more favourable method to characterise MSNs to do early formulation developments

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series

The Non-linear Optical Spin Hall Effect and Long-Range Spin Transport in Polariton Lasers

We report on the experimental observation of the non-linear analogue of the optical spin Hall effect under highly non-resonant circularly polarized excitation of an exciton polariton condensate in a GaAs/AlGaAs microcavity. Initially circularly polarized polariton condensates propagate over macroscopic distances while the collective condensate spins coherently precess around an effective magnetic field in the sample plane performing up to four complete revolutions

Nonresonant optical control of a spinor polariton condensate

We investigate the spin dynamics of polariton condensates spatially separated from and effectively confined by the pumping exciton reservoir. We obtain a strong correlation between the ellipticity of the non-resonant optical pump and the degree of circular polarisation (DCP) of the condensate at the onset of condensation. With increasing excitation density we observe a reversal of the DCP. The spin dynamics of the trapped condensate are described within the framework of the spinor complex Ginzburg-Landau equations in the Josephson regime, where the dynamics of the system are reduced to a current-driven Josephson junction. We show that the observed spin reversal is due to the interplay between an internal Josephson coupling effect and the detuning of the two projections of the spinor condensate via transition from a synchronised to a desynchronised regime. These results suggest that spinor polariton condensates can be controlled by tuning the non-resonant excitation density offering applications in electrically pumped polariton spin switches.P.G.L acknowledges support by the Engineering and Physical Sciences Research Council of UK through the Hybrid Polaritonics Programme Grant (EP/M025330/1). P.G.S. acknowledges funding from the EU Social Fund and Greek National Resources (EPEAEK II, HRAKLEITOS II), N.G.B acknowledges the financial support by Ministry of Education and Science of Russian Federation 1425320 (Project DOI: RFMEFI58114X0006). The authors acknowledge fruitful discussions with Prof. Alexey Kavokin and Dr Hamid Ohadi. The data from this paper can be obtained from the University of Southampton e-Print research repository.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by APS