Biodegradable Nanohybrid Materials as Candidates for Self-Sanitizing Filters Aimed at Protection from SARS-CoV-2 in Public Areas

The COVID-19 pandemic has raised the problem of efficient, low-cost materials enabling the effective protection of people from viruses transmitted through the air or via surfaces. Nanofibers can be a great candidate for efficient air filtration due to their structure, although they cannot protect from viruses. In this work, we prepared a wide range of nanofibrous biodegradable samples containing Ag (up to 0.6 at.%) and Cu (up to 20.4 at.%) exhibiting various wettability. By adjusting the magnetron current (0.3 A) and implanter voltage (5 kV), the deposition of TiO₂ and Ag⁺ implantation into PCL/PEO nanofibers was optimized in order to achieve implantation of Ag⁺ without damaging the nanofibrous structure of the PCL/PEO. The optimal conditions to implant silver were achieved for the PCL-Ti0.3-Ag-5kV sample. The coating of PCL nanofibers by a Cu layer was successfully realized by magnetron sputtering. The antiviral activity evaluated by widely used methodology involving the cultivation of VeroE6 cells was the highest for PCL-Cu and PCL-COOH, where the VeroE6 viability was 73.1 and 68.1%, respectively, which is significantly higher compared to SARS-CoV-2 samples without self-sanitizing (42.8%). Interestingly, the samples with implanted silver and TiO₂ exhibited no antiviral effect. This difference between Cu and Ag containing nanofibers might be related to the different concentrations of ions released from the samples: 80 μg/L/day for Cu²⁺ versus 15 µg/L/day for Ag⁺. The high antiviral activity of PCL-Cu opens up an exciting opportunity to prepare low-cost self-sanitizing surfaces for anti-SARS-CoV-2 protection and can be essential for air filtration application and facemasks. The rough cost estimation for the production of a biodegradable nanohybrid PCL-Cu facemask revealed ~$0.28/piece, and the business case for the production of these facemasks would be highly positive, with an Internal Rate of Return of 34%.     

Identification of Small Molecule Inhibitors against Mycobacteria in Activated Macrophages

Mycobacterial pathogens are intrinsically resistant to many available antibiotics, making treatment extremely challenging, especially in immunocompromised individuals and patients with underlying and chronic lung conditions. Even with lengthy therapy and the use of a combination of antibiotics, clinical success for non-tuberculous mycobacteria (NTM) is achieved in fewer than half of the cases. The need for novel antibiotics that are effective against NTM is urgent. To identify such new compounds, a whole cell high-throughput screen (HTS) was performed in this study. Compounds from the Chembridge DIVERSet library were tested for their ability to inhibit intracellular survival of M. avium subsp. hominissuis (MAH) expressing dtTomato protein, using fluorescence as a readout. Fifty-eight compounds were identified to significantly inhibit fluorescent readings of MAH. In subsequent assays, it was found that treatment of MAH-infected THP-1 macrophages with 27 of 58 hit compounds led to a significant reduction in intracellular viable bacteria, while 19 compounds decreased M. abscessus subsp. abscessus (Mab) survival rates within phagocytic cells. In addition, the hit compounds were tested in M. tuberculosis H37Ra (Mtb) and 14 compounds were found to exhibit activity in activated THP-1 cells. While the majority of compounds displayed inhibitory activity against both replicating (extracellular) and non-replicating (intracellular) forms of bacteria, a set of compounds appeared to be effective exclusively against intracellular bacteria. The efficacy of these compounds was examined in combination with current antibiotics and survival of both NTM and Mtb were evaluated within phagocytic cells. In time-kill dynamic studies, it was found that co-treatment promoted increased bacterial clearance when compared with the antibiotic or compound group alone. This study describes promising anti-NTM and anti-Mtb compounds with potential novel mechanisms of action that target intracellular bacteria in activated macrophages.     

Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Short Peptide-Based Drugs in Human Blood Plasma

A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1% v/v formic acid (aqueous solution) and 0.1% v/v formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5–20 ng/mL, with correlation coefficients between 0.998–0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.     

X-ray absorption spectroscopic studies of chromium(V/IV/III)- 2-ethyl-2-hydroxybutanoato(2-/1-) complexes

Structures of the complexes [Cr(V)O(ehba)(2)](-), [Cr(IV)O(ehbaH)(2)](0), and [Cr(III)(ehbaH)(2)(OH(2))(2)](+) (ehbaH(2) = 2-ethyl-2-hydroxybutanoic acid) in frozen aqueous solutions (10 K, [Cr] = 10 mM, 1.0 M ehbaH(2)/ehbaH, pH 3.5) have been determined by single- and multiple-scattering fitting of X-ray absorption fine structure (XAFS) data. An optimal set of fitting parameters has been determined from the XAFS calculations for a compound with known crystal structure, Na[Cr(V)O(ehba)(2)] (solid, 10 K). The structure of the Cr(V) complex [Cr(V)O(ehba)(2)](-) does not change in solution in the presence of excess ligand. Contrary to the earlier suggestions made from the kinetic data (Ghosh, M. C.; Gould, E. S. J. Chem. Soc., Chem. Commun. 1992, 195-196), the structure of the Cr(IV) complex (generated by the Cr(VI) + As(III) + ehbaH(2) reaction) is close to that of the Cr(V) complex (five-coordinate, distorted trigonal bipyramidal) and different from that of the Cr(III) complex (six-coordinate, octahedral). For both Cr(V) and Cr(IV) complexes, some disorder in the position of the oxo group is observed, which is consistent with but not definitive for the presence of geometric isomers. The structure of the Cr(IV) complex differs from that of Cr(V) by protonation of alcoholato groups of the ligands, which leads to significant elongation of the corresponding Cr-O bonds (2.0 vs 1.8 A). This is reflected in the different chemical properties reported previously for the Cr(IV) and Cr(V) complexes, including their reactivities toward DNA and other biomolecules in relation to Cr-induced carcinogenicity.     

The features of the synthesis and chemical behavior of some β-cyclodextrin silyl derivatives

Conditions are found for the regioselective silylation of the β-cyclodextrin primary hydroxy groups by diphenylmethylsilyl chloride and trimethylsilyl chloride. It is shown that the position of silyl substituents at the primary or secondary hydroxyl can be determined using ²⁹Si NMR spectroscopy. In the case of acetic and phosphorous acid chlorides, the subsequent functionalization of the secondary hydroxyls occurs with a significant removal of the protective silyl groups.     

Coverings of random ellipsoids,and invertibility of matrices with i.i.d. heavy-tailed entries

Let A = (a_ij) be an n × n random matrix with i.i.d. entries such that Ea₁₁ = 0 and Ea ₁₁ ² = 1. We prove that for any δ > 0 there is L > 0 depending only on δ, and a subset N of B ₂ ⁿ of cardinality at most exp(δn) such that with probability very close to one we have

$$A\left( {B_2^n} \right)\subset\mathop \cup \limits_{y \in A\left( \mathcal{N} \right)} \left( {y + L\sqrt n B_2^n} \right)$$

. In fact, a stronger statement holds true. As an application, we show that for some L' > 0 and u ∈ [0, 1) depending only on the distribution law of a11, the smallest singular value sn of the matrix A satisfies

$$\mathbb{P}\left\{ {{s_n}\left( A \right) \leq \varepsilon {n^{ - 1/2}}} \right\} \leq L'\varepsilon + {u^n}$$

for all ε > 0. The latter result generalizes a theorem of Rudelson and Vershynin which was proved for random matrices with subgaussian entries.

     

Mechanical Unfolding of a Homopolymer Globule: Applied Force versus Applied Deformation

We propose the quantitative mean-field theory of mechanical unfolding of a globule formed by long flexible homopolymer chain collapsed in poor solvent and subjected to an extensional force We show that with an increase in the applied force the globule unfolds as a whole without formation of an intermediate state. The value of the threshold force and the corresponding jump in the distance between chain ends increase with a deterioration of the solvent quality and / or with an increase in the degree of polymerization. This way of globule unfolding is compared with that in the D-ensemble, when the distance between chain ends is imposed.     

Regularities of the formation of iron(III) nanocrystalline particles during the oxidation of iron(II) compounds in a neutral medium

The regularities of the formation of iron(III) oxide hydroxides as nanocrystalline particles via oxidation of iron(II) compounds in a near-neutral pH region were studied by potentiometric titration, electron microscopy, chemical analysis, and X-ray diffraction. The oxidation process comprises two steps. The first step produces Fe(II)-Fe(III) hydroxo salts having a “green rust” structure in the form of nanocrystalline particles shaped as hexagons. The second step produces anisotropic nanocrystalline particles of iron(III) oxide hydroxides via the dissolution-oxidation-precipitation mechanism and via solid-phase oxidation. The oxidation of chlorine-containing suspensions helps the formation of single-phase nanocrystalline lepidocrocite, while oxidation in the presence of sulfate ions yields nanocrystalline goethite.     

A new method for pyrrole peri-annulation: synthesis of 1H-1,5,7-triazacyclopenta[c,d]phenalenes from 1H-perimidines

New methods for the synthesis of 1H-1,5,7-triazacyclopenta[c,d]phenalenes have been developed based on a sequence involving Schmidt reaction of keto-perimidines and acylation of the intermediate amides with 1,3,5-triazines or carboxylic acids. The same synthetic sequence starting from the corresponding alkylperimidine includes acylation with acetic acid as the first step.