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.     

Room Temperature Ionic Liquids in Asymmetric Hetero-Ene Type Reactions: Improving Organocatalyst Performance at Lower Temperatures

Room temperature ionic liquids (RTILs) have been widely used as (co)solvents in several catalytic processes modifying, in most of the cases, the catalyst activity and/or the selectivity for the studied reactions. However, there are just a few examples of their use in hydrogen bonding organocatalysis. In this paper, we show the positive effect of a set of imidazole-based ionic liquids ([bmim]BF₄ and [hmim]PF₆) in the enantioselective addition of formaldehyde tert-butylhydrazone to prochiral α-keto esters catalyzed by a sugar-based chiral thiourea. Reactions performed in the presence of low percentages of RTILs led to an increase of the catalyst activity, thereby making possible to work at lower temperatures. Thus, the chiral tert-butyl azomethyl tertiary alcohols could be obtained with moderate to good conversions and higher enantioselectivities for most of the studied substrates when using up to 30 vol% of [hmim]PF₆ as a cosolvent in processes performed in toluene.     

Memory Effects in High-Dimensional Systems Faithfully Identified by Hilbert–Schmidt Speed-Based Witness

A witness of non-Markovianity based on the Hilbert–Schmidt speed (HSS), a special type of quantum statistical speed, has been recently introduced for low-dimensional quantum systems. Such a non-Markovianity witness is particularly useful, being easily computable since no diagonalization of the system density matrix is required. We investigate the sensitivity of this HSS-based witness to detect non-Markovianity in various high-dimensional and multipartite open quantum systems with finite Hilbert spaces. We find that the time behaviors of the HSS-based witness are always in agreement with those of quantum negativity or quantum correlation measure. These results show that the HSS-based witness is a faithful identifier of the memory effects appearing in the quantum evolution of a high-dimensional system with a finite Hilbert space.     

Production and Digestibility Studies of β-Galactosyl Xylitol Derivatives Using Heterogeneous Catalysts of LacA β-Galactosidase from Lactobacillus Plantarum WCFS1

The synthesis of β-galactosyl xylitol derivatives using immobilized LacA β-galactosidase from Lactobacillus plantarum WCFS1 is presented. These compounds have the potential to replace traditional sugars by their properties as sweetener and taking the advantages of a low digestibility. The enzyme was immobilized on different supports, obtaining immobilized preparations with different activity and stability. The immobilization on agarose-IDA-Zn-CHO in the presence of galactose allowed for the conserving of 78% of the offered activity. This preparation was 3.8 times more stable than soluble. Since the enzyme has polyhistidine tags, this support allowed the immobilization, purification and stabilization in one step. The immobilized preparation was used in synthesis obtaining two main products and a total of around 68 g/L of β-galactosyl xylitol derivatives and improving the synthesis/hydrolysis ratio by around 30% compared to that of the soluble enzyme. The catalyst was recycled 10 times, preserving an activity higher than 50%. The in vitro intestinal digestibility of the main β-galactosyl xylitol derivatives was lower than that of lactose, being around 6 and 15% for the galacto-xylitol derivatives compared to 55% of lactose after 120 min of digestion. The optimal amount immobilized constitutes a very useful tool to synthetize β-galactosyl xylitol derivatives since it can be used as a catalyst with high yield and being recycled for at least 10 more cycles.     

Development of Magnesium Anode-Based Transient Primary Batteries

Biodegradable primary batteries, also known as transient batteries, are essential to realize autonomous biodegradable electronic devices with high performance and advanced functionality. In this work, magnesium, copper, iron, and zinc – metals that exist as trace elements in the human body – were tested as materials for biomedical transient electronic devices. Different full cell combinations of Mg and X (where X = Cu, Fe, and Zn and the anodized form of the metals) with phosphate buffered saline (PBS) as electrolyte were studied. To form the cathodes, metal foils were anodized galvanostatically at a current density of 2.0 mA cm⁻² for 30 mins. Electrochemical measurements were then conducted for each electrode combination to evaluate full cell battery performance. Results showed that the Mg−Cu_anodized chemistry has the highest power density at 0.99 mW/cm². Nominal operating voltages of 1.26 V for the first 0.50 h and 0.63 V for the next 3.7 h were observed for Mg−Cu_anodized which was discharged at a current density of 0.70 mA cm⁻². Among the materials tested, Mg−Cu_anodized exhibited the best discharge performance with an average specific capacity of 2.94 mAh cm⁻², which is comparable to previous reports on transient batteries.     

Determination of strain and stress distribution on shearwalls by using the speckle photography technique

Speckle photography (SP) is a powerful tool that is adequate to determine small displacements in micrometer range. This information shows other characteristics of structure deformation under loads and can be determined as stress and strain distribution. In this paper we present the results of the application of the SP technique used to study the behaviour of discontinuities in a shearwall model. These structural elements are very important to the stability of buildings. The displacement whole field around the discontinuities and loading points was determined using the pointwise method. This allows us to determine stress distribution at the point of interest by means of the suitable equations. We also present the stress distribution obtained through the finite element method in order to compare the results obtained by means of these two techniques. Good correspondence was found between the displacements determined by both techniques (r=0.982) and also between the stress values we obtained.     

CS2 Reductive Coupling to Acetylenedithiolate by a Dinuclear Ytterbium(II) Complex

The activation of CS₂ is of interest in a broad range of fields and, more particularly, in the context of creating new C−C bonds. The reaction of the dinuclear ytterbium(II) complex [Yb₂L₄], 1 , [L=(OtBu)₃SiO⁻] with carbon disulfide led to the isolation of unprecedented reduction products. In particular, the crystallographic characterization of complex [Yb₂L₄(μ-C₂S₂)], 2 , provided the first example of an acetylenedithiolate ligand formed from metal reduction of CS₂. Computational studies indicated that this unprecedented reactivity can be ascribed to the unusual binding mode of CS₂²⁻ in the isolated “key intermediate” [Yb₂L₄(μ-CS₂)], 3 , which results from the dinuclear nature of 1 .     

Multivariate calibration for the improvement of the quantification of cadmium in the presence of potassium as interferent by total reflection X-ray fluorescence

A multivariate calibration method was applied to improve the accuracy of the determination of cadmium in the presence of potassium by total reflection X-ray fluorescence (TXRF). Due to TXRF's relatively low resolution, a particular interference caused by potassium at line Kα 3.31 keV as interference can compromise the cadmium determination at line Lα 3.13 keV, respectively. The method is based on the hypothesis that the application of a multivariate calibration method, for example, partial least squares, could reduce variations due to interference and, consequently, improve the selectivity and accuracy in Cd determination. In this work, this strategy was evaluated on the X-ray fluorescence emission signals between 2.50 and 3.90 keV for a set of 26 different synthetic calibration mixtures and eight different mixtures for external calibration. Based on a certified reference material (Clay 2—CRM051) with high potassium levels, a significant improvement of accuracy for cadmium determination was observed, overcoming the problems associated with spectral interferences by potassium.