On the need for multi-dimensional models for the safety analysis of (fast-spectrum) Molten Salt Reactors

This paper aims at characterizing the impact of adopting numerical models with different dimensionalities on the predicted behavior of fast-spectrum Molten Salt Reactors (MSRs). The study encompasses 1-D, 2-D, and 3-D representations of thermal-hydraulics and precursor transport/diffusion, along with spatial and point kinetics models for neutronics. We evaluate the accuracy of each model based on steady-state results and on the reactor response to 2 different transient initiators. The findings emphasize the significance of utilizing a 3-D representation with accurate thermal-hydraulics modeling, and with either spatial kinetics or carefully calibrated point kinetics incorporating a spatial description of precursors transport. 2-D and 1-D models can reproduce main trends and remain valuable tools for e.g. reactor design, control-oriented studies or uncertainty quantification. However, proper calibration of these models is needed and the user should be aware that alterations in flow patterns could jeopardize model calibration and hide first-order local effects

Different Coordination Modes of a Tripod Phosphine in Gold(I) and Silver(I) Complexes

The following gold(I) and silver(I) complexes of the tritertiary phosphine 1,1,1- tris(diphenylphosphinomethyl)ethane, tripod , have been synthesised: Au3(tripod)X3 [X = Cl(1), Br(2), I(3)]; [Au3(tripod)2Cl2]Cl (4); Au(tripod)X [X = Br(5), I(6)]; Ag3(tripod) (NO3)4 (7), Ag(tripod)NO3 (8). They were characterized by X-ray diffraction (complexes 2, 3 and 4), 31P NMR spectroscopy, electrospray and FAB mass spectrometry and infrared spectroscopy. Complexes 2 and 3 show a linear coordination geometry for Au(I), with relatively short Au-P bond distances. Complex 3 has a Au•••Au intramolecular distance of 3.326 A ° , while complex 2 had a short Au•••Au intermolecular interaction of 3.048 A ° . Complexes 4-6 were found by 31P NMR spectroscopy studies to contain a mixture of species in solution, one of which crystallised as [Au3(tripod|)2Cl2]Cl which was shown by X-ray diffraction to contain both tetrahedral and linear Au(I), the first example of a Au(I) complex containing such a mixture of geometries. The reaction of [Au3 (tripod)Cl3] (1) with tripod led successfully to the formation of [Au3(tripod|)2Cl2]+ and [Au3(tripod)2Cl3]+ and [Au3(tripod|)3Cl]2+. The silver(I) complexes, 7 and 8 appear to contain linear and tetrahedral Ag(I), respectively

Lessons learned from SARS-CoV and MERS-CoV : FDA-approved Abelson tyrosine-protein kinase 2 inhibitors may help us combat SARS-CoV-2

SARS-CoV-2 is a newly emerging infectious disease, which originated from Wuhan in the Hubei province of China in late December 2019 [1]. Since then, it has rapidly spread all over the world, and at the time of writing this letter, WHO statistics show more than 1,696,588 cases and 105,952 deaths confirmed across the world [2]. Although there is no specific therapy for SARS-CoV-2 infection [3], combination therapy with antiviral and anti-inflammatory drugs accompanied by supportive treatment have been used for SARS-CoV-2 patients [4]. The combination of well-known HIV protease inhibitors, such as ritonavir with lopinavir, has also been a common approach to treat SARS-CoV-2. Insufficient outcome in severe cases is, however, one of the main challenges associated with the current antiviral-based therapy for SARS-CoV-2 [5]. In view of the long period required for novel drug discovery and the desperate need for a prompt response to this pandemic infection, one must resort to repurposing FDA-approved drugs. In this direction, our experience with other close members of coronaviruses such as SARS and MERS has taught us that repurposing the current drugs is a reasonable strategy. Abelson tyrosine-protein kinase 2 (Abl2), the imatinib target, was required for efficient SARS-CoV and MERS-CoV replication in vitro [6]. Coleman et al. have shown that the imatinib target Abl2 is indispensable for efficient replication of SARS-CoV and MERS-CoV in vitro

Improved catalytic activity of ruthenium–arene complexes in the reduction of NAD+

A series of neutral Ru-II half-sandwich complexes of the type [(eta(6)-arene)Ru(N,N')Cl] where the arene is para-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), or benzene (bn) and N,N' is N-(2-aminoethyl) -4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-4-toluenesulfonamide (TsEn), or N-(2-aminoethyl)-methylenesulfonamide (MsEn) were synthesized and characterized. X-ray crystal structures of [(p-cym)Ru(MsEn)Cl] (1), [(hmb)Ru(TsEn)Cl] (5), [(hmb)Ru(TfEn)Cl] (6), [(bip)Ru(MsEn)Cl] (7), and [(bip)Ru(TsEn)Cl] (8) have been determined. The complexes can regioselectively catalyze the transfer hydrogenation of NAD(+) to give 1,4-NADH in the presence of formate. The turnover frequencies (TOF) when the arene is varied decrease in the order bn > bip > p-cym > hmb for complexes with the same N,N' chelating ligand. The TOF decreased with variation in the N,N' chelating ligand in the order TfEn > TsEn > MsEn for a given arene. [(bn)Ru(TfEn)Cl] (12) was the most active, with a TOP of 10.4 h(-1). The effects of NAD(+) and formate concentration on the reaction rates were determined for [(p-cym)Ru(TsEn)Cl] (2). Isotope studies implicated the formation of [(arene)Ru(N,N')(H)] as the rate-limiting step. The coordination of formate and subsequent CO2 elimination to generate the hydride were modeled computationally by density functional theory (DFT). CO2 elimination occurs via a two-step process with the coordinated formate first twisting to present its hydrogen toward the metal center. The computed barriers for CO2 release for arene = benzene follow the order MsEn > TsEn > TfEn, and for the Ms En system the barrier followed bn < hmb, both consistent with the observed rates. The effect of methanol on transfer hydrogenation rates in aqueous solution was investigated. A study of pH dependence of the reaction in D2O gave the optimum pH* as 7.2 with a TOF of 1.58 h(-1) for 2. The series of compounds reported here show an improvement in the catalytic activity by an order of magnitude compared to the ethylenediamine analogues

Platinum(IV)-azido monocarboxylato complexes are photocytotoxic under irradiation with visible light

Complexes trans,trans,trans-[Pt(N-3)(2)(OH)(OCOR)(py)(2)] where py = pyridine and where OCOR = succinate (1); 4-oxo-4-propoxybutanoate (2) and N-methylisatoate (3) have been synthesized by derivation of trans, trans,trans-[Pt(OH)(2)(N-3)(2)(py)(2)] (4) and characterised by NMR and EPR spectroscopy, ESI-MS and X-ray crystallography. Irradiation of 1-3 with green (517 nm) light initiated photoreduction to Pt(II) and release of the axial ligands at a 3-fold faster rate than for 4. TD-DFT calculations showed dissociative transitions at longer wavelengths for 1 compared to 4. Complexes 1 and 2 showed greater photocytotoxicity than 4 when irradiated with 420 nm light (A2780 cell line IC50 values: 2.7 and 3.7 mu M) and complex 2 was particularly active towards the cisplatin-resistant cell line A2780cis (IC50 3.7 mu M). Unlike 4, complexes 1-3 were phototoxic under green light irradiation (517 nm), with minimal toxicity in the dark. A pK(a)(H2O) of 5.13 for the free carboxylate group was determined for 1, corresponding to an overall negative charge during biological experiments, which crucially, did not appear to impede cellular accumulation and photocytotoxicity.NF thanks the Wellcome Trust (201406/Z/16/Z); Cancer Research UK (CR-UK) grant number C5255/A18085 through the Cancer Research UK Oxford Centre and the John Fell Fund for funding. NF thanks Profs. Stephen Faulkner for support. PJS and NF thank the EPSRC (for grant EP/P030572/1 and studentship for ES), PJS also thanks the ERC (grant 247450). L. S. performed this work under the Severo Ochoa Centres of Excellence Programme run by the Spanish State Research Agency, grant no. CEX2018-000867-S (DIPC). L. S. also thanks the Spanish Multi-MetDrugs network (RED2018-102471-T) for fruitful discussio

Molecular simplification of natural products: Synthesis, antibacterial activity, and molecular docking studies of berberine open models

Berberine, the main bioactive component of many medicinal plants belonging to various genera such as Berberis, Coptis, and Hydrastis is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species. Rewardingly, the berberine simplified analogues displayed 2–20-fold higher potency with respect to berberine. Since our berberine simplified analogues may be easily synthesized and are characterized by lower molecular weight than the parent compound, they are further functionalizable and should be more suitable for oral administration. Molecular docking simulations suggested FtsZ, a well-known protein involved in bacterial cell division, as a possible target

Pharmacological treatments of COVID-19

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies. © 2020, Maj Institute of Pharmacology Polish Academy of Sciences