Combining Different Docking Engines and Consensus Strategies to Design and Validate Optimized Virtual Screening Protocols for the SARS-CoV-2 3CL Protease

The 3CL-Protease appears to be a very promising medicinal target to develop anti-SARS-CoV-2 agents. The availability of resolved structures allows structure-based computational approaches to be carried out even though the lack of known inhibitors prevents a proper validation of the performed simulations. The innovative idea of the study is to exploit known inhibitors of SARS-CoV 3CL-Pro as a training set to perform and validate multiple virtual screening campaigns. Docking simulations using four different programs (Fred, Glide, LiGen, and PLANTS) were performed investigating the role of both multiple binding modes (by binding space) and multiple isomers/states (by developing the corresponding isomeric space). The computed docking scores were used to develop consensus models, which allow an in-depth comparison of the resulting performances. On average, the reached performances revealed the different sensitivity to isomeric differences and multiple binding modes between the four docking engines. In detail, Glide and LiGen are the tools that best benefit from isomeric and binding space, respectively, while Fred is the most insensitive program. The obtained results emphasize the fruitful role of combining various docking tools to optimize the predictive performances. Taken together, the performed simulations allowed the rational development of highly performing virtual screening workflows, which could be further optimized by considering different 3CL-Pro structures and, more importantly, by including true SARS-CoV-2 3CL-Pro inhibitors (as learning set) when available.     

Towards a parameter-free characterization of charge transfer via hopping: the case of tris(8-hydroxyquinolato) aluminum

By using calculations based on density functional theory, we investigate the physical factors determining the elemental charge transfer in Alq3, taken as a prototype of molecular systems in condensed phase. The effect of the environment on the hopping of the charge carrier is evaluated self-consistently in a model in which an Alq3 dimer is embedded in an ensemble of permanent and polarizable dipoles, including orientational disorder and the presence of impurities. The results indicate that the origin of the activation barrier is mainly extrinsic and that the local orientation of the dipole moments plays a major role. The influence of nonadiabaticity is also studied and found to be more important for a hole than for an electron.     

Pharmacological modulation of functional connectivity: the correlation structure underlying the phMRI response to d-amphetamine modified by selective dopamine D3 receptor antagonist SB277011A

Pharmacological MRI (phMRI) experiments utilise fMRI time series methods to map the central effect of pharmaceutical compounds. The typical univariate maps may, however, integrate the effects of several different neurotransmitter systems or underlying mechanisms. The results may thus be spatially and/or mechanistically nonspecific. Intersubject correlation analysis based on the phMRI response amplitude can more directly identify patterns of functional connectivity underlying the central effects of an acutely administered compound. In this article, we extend this approach to experiments where the effects of one compound in modulating the response to another are of interest. Specifically, we show a modulation of the correlation structure of a probe compound (d-amphetamine) by pretreatment with the selective dopamine D3 receptor antagonist SB277011A in the rat. The strongest modifications in the correlation patterns occurred in connection with the ventral tegmental area, the source of mesolimbic dopamine projections and a key substrate in the reward system.     

Effect of lithium intercalation on the photovoltaic performances of photovoltachromic cells

In the last few years, a new class of smart multifunctional photoelectrochemical devices has been attracting the interest of several academic institutions and industrial companies: photovoltachromic cells, combining the features of photoelectrochromic cells with those of dye‐sensitized solar cells. Here, we report the results of a detailed electrochemical analysis aiming at investigating the electrochemical behavior of these complex photoelectrochemical devices. In particular, we have been focused on the effect of Li⁺ ions displacement during the coloration of the electrochromic tungsten oxide on the performances of the photovoltaic unit. As we had previously observed striking differences between the performances of the barely photovoltaic mode (with the tungsten oxide in the bleached state) and the photovoltachromic mode (with the tungsten oxide in the colored state), we thus attempted to provide a reasonable physical interpretation to the observed phenomena. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparative analysis of the outdoor performance of a dye solar cell mini‐panel for building integrated photovoltaics applications

New generation photovoltaic (PV) devices such as polymer and dye sensitized solar cells (DSC) have now reached a more mature stage of development, and among their various applications, building integrated PVs seems to have the most promising future, especially for DSC devices. This new generation technology has attracted an increasing interest because of its low cost due to the use of cheap printable materials and simple manufacturing techniques, easy production, and relatively high efficiency. As for the more consolidated PV technologies, DSCs need to be tested in real operating conditions and their performance compared with other PV technologies to put into evidence the real potential. This work presents the results of a 3 months outdoor monitoring activity performed on a DSC mini‐panel made by the Dyepower Consortium, positioned on a south oriented vertical plane together with a double junction amorphous silicon (a‐Si) device and a multi‐crystalline silicon (m‐Si) device at the ESTER station of the University of Rome Tor Vergata. Good performance of the DSC mini‐panel has been observed for this particular configuration, where the DSC energy production compares favorably with that of a‐Si and m‐Si especially at high solar angles of incidence confirming the suitability of this technology for the integration into building facades. This assumption is confirmed by the energy produced per nominal watt‐peak for the duration of the measurement campaign by the DSC that is 12% higher than that by a‐Si and only 3% lower than that by m‐Si for these operating conditions. Copyright © 2013 John Wiley & Sons, Ltd.     

Quantification of Intact and Truncated Stromal Cell-Derived Factor-1α in Circulation by Immunoaffinity Enrichment and Tandem Mass Spectrometry

Stromal cell-derived factor 1α (SDF-1α) or CXCL12 is a small pro-inflammatory chemoattractant cytokine and a substrate of dipeptidyl peptidase IV (DPP-IV). Proteolytic cleavage by DPP-IV inactivates SDF-1α and attenuates its interaction with CXCR4, its cell surface receptor. To enable investigation of suppression of such inactivation with pharmacologic inhibition of DPP-IV, we developed quantitative mass spectrometric methods that differentiate intact SDF-1α from its inactive form. Using top-down strategy in quantification, we demonstrated the unique advantage of keeping SDF-1α’s two disulfide bridges intact in the analysis. To achieve the optimal sensitivity required for quantification of intact and truncated SDF-1α at endogenous levels in blood, we coupled nano-flow tandem mass spectrometry with antibody-based affinity enrichment. The assay has a quantitative range of 20 pmol/L to 20 nmol/L in human plasma as well as in rhesus monkey plasma. With only slight modification, the same assay can be used to quantify SDF-1α in mice. Using two in vivo animal studies as examples, we demonstrated that it was critical to differentiate intact SDF-1α from its truncated form in the analysis of biomarkers for pharmacologic inhibition of DPP-IV activity. These novel methods enable translational research on suppression of SDF-1 inactivation with DPP-IV inhibition and can be applied to relevant clinical samples in the future to yield new insights on change of SDF-1α levels in disease settings and in response to therapeutic interventions.

An Aluminophosphate Molecular Sieve with 36 Crystallographically Distinct Tetrahedral Sites

The structure of the new medium‐pore aluminophosphate molecular sieve PST‐6 is determined by the combined use of rotation electron diffraction tomography, synchrotron X‐ray powder diffraction, and computer modeling. PST‐6 was prepared by calcination of another new aluminophosphate material with an unknown structure synthesized using diethylamine as a structure‐directing agent, which is thought to contain bridging hydroxy groups. PST‐6 has 36 crystallographically distinct tetrahedral sites in the asymmetric unit and is thus crystallographically the most complex zeolitic structure ever solved.     

A Cationic Zinc Hydride Cluster Stabilized by an N‐Heterocyclic Carbene: Synthesis,Reactivity, and Hydrosilylation Catalysis

The trinuclear cationic zinc hydride cluster [(IMes)₃Zn₃H₄(THF)](BPh₄)₂ ( 1 ) was obtained either by protonation of the neutral zinc dihydride [(IMes)ZnH₂]₂ with a Brønsted acid or by addition of the putative zinc dication [(IMes)Zn(THF)]²⁺. A triply bridged thiophenolato complex 2 was formed upon oxidation of 1 with PhS? SPh. Protonolysis of 1 by methanol or water gave the corresponding trinuclear dicationic derivatives. At ambient temperature, 1 catalyzed the hydrosilylation of aldehydes, ketones, and nitriles. Carbon dioxide was also hydrosilylated under forcing conditions when using (EtO)₃SiH, giving silylformate as the main product.     

Work function and negative electron affinity of ultrathin barium fluoride films

Thin films of barium fluorides with different thicknesses were deposited on GaAs substrate by electron beam evaporation. The aim of the work was to identify the best growth conditions for the production of coatings with a low work function suitable for the anode of hybrid thermionic-photovoltaic (TIPV) devices. The chemical composition and work function φ of the films with different thicknesses were investigated by X-ray photoelectron spectroscopy (XPS) and ultraviolet photoelectron spectroscopy (UPS). The lowest value of φ = 2.1 eV was obtained for the film with a thickness of ~2 nm. In the valence band spectra of the films at low kinetic energy, near the cutoff, a characteristic peak of negative electron affinity was present. This effect contributed to a further reduction of the film's work function.