Gold(I) chloride adducts of 1,3-bis(di-2-pyridylphosphino)propane: synthesis, structural studies and antitumour activity

The novel water soluble bidentate phosphine ligand 1,3-bis(di-2-pyridylphosphino)propane (d2pypp) has been synthesized by a convenient route involving treatment of 2-pyridyllithium with Cl(2)P(CH(2))(3)PCl(2) and isolation in crystalline form as the hydrochloride salt. The synthesis of the precursor Cl(2)P(CH(2))(3)PCl(2) has been optimized by the use of triphosgene as the chlorinating agent. The 2 : 1 and 1 : 2 AuCl : d2pypp adducts have been synthesized and characterized by NMR spectroscopy and single crystal X-ray studies, and shown to be of the form (AuCl)(2)(mu-d2pypp-P,P') and [Au(d2pypp-P,P')(2)]Cl(.3.75H(2)O), respectively. The latter is more lipophilic than analogous 1 : 2 adducts of gold(I) chloride with the diphosphine ligands 1,2-bis(di-n-pyridylphosphino)ethane (dnpype) for n = 2, 3 and 4, based on measurement of the n-octanol-water partition coefficient (log P = -0.46). A single crystal structure determination of the 1 : 2 Au(I) complex of the 3-pyridyl ethane ligand shows it to be of the form [Au(d3pype-P,P')(2)]Cl.5H(2)O. The in vitro cytotoxic activity of [Au(d2pypp)(2)]Cl was assessed in human normal and cancer breast cells and selective toxicity to the cancer cells found. The significance of these results to the antitumour properties of chelated 1 : 2 Au(I) diphosphine complexes is discussed.     

Solution equilibria between aluminum(III) ion and some fluoroquinolone family members. Spectroscopic and potentiometric study

Complex formation between aluminum(III) ion and fluoroquinolone antibacterials-either moxifloxacin (4th generation antibiotic) or fleroxacin (2nd generation antibiotic) were studied in aqueous solutions without and in the presence of sodium dodecylsulfate (SDS). The investigations were performed by glass electrode potentiometric (ionic medium: 0.1 mol/dm(3) LiCl, 298 K), UV spectrophotometric, multinuclear (1H and 13C) magnetic resonance and ESI-MS measurements. The experimental data were consistent with the formation of Al(HL)L2+, Al(HL)3+ AlL2+, Al(OH)L+ and Al(OH)2L complexes in the pH interval ca. 3-8 and up to 5 : 1 ligand to metal mole ratio with range of Al3+ concentrations between ca. 0.025 to 1.0 mmol/dm3. The binary complex, AlL2+ is fairly stable (log beta(1,0,1) ca. 11.0) and its stability increases in the presence of SDS. At higher concentration ratios of ligands to aluminum, up to 5 : 1, the complex Al(HL)L2+ is formed with rather high overall stability constant (log beta(1,1,2) ca. 24.0). The ESI-MS data generally, confirmed the derived model, and the formation of the complex with ligand to metal ratio 2 : 1. NMR measurements indicate that both ligands utilize 4-carbonyl and carboxyl oxygens as donor atoms. The presence of surface active substance, SDS, favors the formation of the complex in which the ligand is protonated, i.e. Al(HL) and its maximum formation is shifted toward milder acidic region (pH ca. 4). The aluminum-quinolone complexes may affect the bio-distribution of both, quinolone and/or aluminum ion upon concomitant ingestion of aluminum-based antacids or phosphate binders and fluoroquinolones.     

Modified interfacial statistical associating fluid theory: a perturbation density functional theory for inhomogeneous complex fluids

A density functional theory based on Wertheim's first order perturbation theory is developed for inhomogeneous complex fluids. The theory is derived along similar lines as interfacial statistical associating fluid theory [S. Tripathi and W. G. Chapman, J. Chem. Phys. 122, 094506 (2005)]. However, the derivation is more general and applies broadly to a range of systems, retaining the simplicity of a segment density based theory. Furthermore, the theory gives the exact density profile for ideal chains in an external field. The general avail of the theory has been demonstrated by applying the theory to lipids near surfaces, lipid bilayers, and copolymer thin films. The theoretical results show excellent agreement with the results from molecular simulations.     

Effects of a static magnetic field on water and electrolyte solutions

Water and electrolyte solutions were exposed for 5 min to a weak static magnetic field (B = 15 mT). Their conductivity and the amount of evaporated water were then measured as a function of time. Simultaneously, these quantities were determined for magnetically untreated samples, as reference systems. It was found that a magnetic field influences these two parameters and their changes depend on the thermodynamic functions of hydration of these ions. A roughly linear change in conductivity versus 'scaled' functions was obtained. On this basis it was concluded that the magnetic field causes changes in the hydration shells of the ions.     

Novel Boronate Probe Based on 3-Benzothiazol-2-yl-7-hydroxy-chromen-2-one for the Detection of Peroxynitrite and Hypochlorite

Derivatives of coumarin, containing oxidant-sensitive boronate group, were recently developed for fluorescent detection of inflammatory oxidants. Here, we report the synthesis and the characterization of 3-(2-benzothiazolyl)-7-coumarin boronic acid pinacol ester (BC-BE) as a fluorescent probe for the detection of peroxynitrite (ONOO^–), with high stability and a fast response time. The BC-BE probe hydrolyzes in phosphate buffer to 3-(2-benzothiazolyl)-7-coumarin boronic acid (BC-BA) which is stable in the solution even after a prolonged incubation time (24 h). BC-BA is slowly oxidized by H₂O₂ to form the phenolic product, 3-benzothiazol-2-yl-7-hydroxy-chromen-2-one (BC-OH). On the other hand, the BC-BA probe reacts rapidly with ONOO⁻. The ability of the BC-BA probe to detect ONOO^– was measured using both authentic ONOO^– and the system co-generating steady-state fluxes of O₂^•– and ^•NO. BC-BA is oxidized by ONOO^– to BC-OH. However, in this reaction 3-benzothiazol-2-yl-chromen-2-one (BC-H) is formed in the minor pathway, as a peroxynitrite-specific product. BC-OH is also formed in the reaction of BC-BA with HOCl, and subsequent reaction of BC-OH with HOCl leads to the formation of a chlorinated phenolic product, which could be used as a specific product for HOCl. We conclude that BC-BA shows potential as an improved fluorescent probe for the detection of peroxynitrite and hypochlorite in biological settings. Complementation of the fluorescence measurements by HPLC-based identification of oxidant-specific products will help to identify the oxidants detected.     

l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.     

A Phage Display-Identified Short Peptide Capable of Hydrolyzing Calcium Pyrophosphate Crystals—The Etiological Factor of Chondrocalcinosis

Chondrocalcinosis is a metabolic disease caused by the presence of calcium pyrophosphate dihydrate crystals in the synovial fluid. The goal of our endeavor was to find out whether short peptides could be used as a dissolving factor for such crystals. In order to identify peptides able to dissolve crystals of calcium pyrophosphate, we screened through a random library of peptides using a phage display. The first screening was designed to select phages able to bind the acidic part of alendronic acid (pyrophosphate analog). The second was a catalytic assay in the presence of crystals. The best-performing peptides were subsequently chemically synthesized and rechecked for catalytic properties. One peptide, named R25, turned out to possess some hydrolytic activity toward crystals. Its catalysis is Mg²⁺-dependent and also works against soluble species of pyrophosphate.     

Is Bitcoin Still a King? Relationships between Prices,Volatility and Liquidity of Cryptocurrencies during the Pandemic

We try to establish the commonalities and leadership in the cryptocurrency markets by examining the mutual information and lead-lag relationships between Bitcoin and other cryptocurrencies from January 2019 to June 2021. We examine the transfer entropy between volatility and liquidity of seven highly capitalized cryptocurrencies in order to determine the potential direction of information flow. We find that cryptocurrencies are strongly interrelated in returns and volatility but less in liquidity. We show that smaller and younger cryptocurrencies (such as Ripple’s XRP or Litecoin) have started to affect the returns of Bitcoin since the beginning of the pandemic. Regarding liquidity, the results of the dynamic time warping algorithm also suggest that the position of Monero has increased. Those outcomes suggest the gradual increase in the role of privacy-oriented cryptocurrencies.     

Whether the Support Region of Three-Bit Uniform Quantizer Has a Strong Impact on Post-Training Quantization for MNIST Dataset?

Driven by the need for the compression of weights in neural networks (NNs), which is especially beneficial for edge devices with a constrained resource, and by the need to utilize the simplest possible quantization model, in this paper, we study the performance of three-bit post-training uniform quantization. The goal is to put various choices of the key parameter of the quantizer in question (support region threshold) in one place and provide a detailed overview of this choice’s impact on the performance of post-training quantization for the MNIST dataset. Specifically, we analyze whether it is possible to preserve the accuracy of the two NN models (MLP and CNN) to a great extent with the very simple three-bit uniform quantizer, regardless of the choice of the key parameter. Moreover, our goal is to answer the question of whether it is of the utmost importance in post-training three-bit uniform quantization, as it is in quantization, to determine the optimal support region threshold value of the quantizer to achieve some predefined accuracy of the quantized neural network (QNN). The results show that the choice of the support region threshold value of the three-bit uniform quantizer does not have such a strong impact on the accuracy of the QNNs, which is not the case with two-bit uniform post-training quantization, when applied in MLP for the same classification task. Accordingly, one can anticipate that due to this special property, the post-training quantization model in question can be greatly exploited.     

Can Eucalyptol Replace Antibiotics?

One of the primary reasons for the search for new antimicrobial agents is the increasing and spreading resistance of microorganisms to previously used drugs. This is particularly important in the case of rapidly progressing infections that require the rapid administration of an appropriately selected antibiotic. However, along with the administration of antibiotics, complications in the disease-weakened body may arise in the form of systemic mycoses, viral infections, and protozoan infections. Therefore, there is an increasing interest among researchers focusing on the use of naturally occurring terpenic compounds in stand-alone or combined therapies with antibiotics. In this publication, the aim of our work is to present the results of a literature review on the antimicrobial activity of eucalyptol.