PEGylation of Terminal Ligands as a Route to Decrease the Toxicity of Radiocontrast Re6-Clusters.

The development of novel radiocontrast agents, mainly used for the visualization of blood vessels, is still an emerging task due to the variety of side effects of conventional X-ray contrast media. Recently, we have shown that octahedral chalcogenide rhenium clusters with phosphine ligands-Na2H14[{Re6Q8}(P(C2H4COO)3)6] (Q = S, Se)-can be considered as promising X-ray contrast agents if their relatively high toxicity related to the high charge of the complexes can be overcome. To address this issue, we propose one of the most widely used methods for tuning the properties of proteins and peptides-PEGylation (PEG is polyethylene glycol). The reaction between the clusters and PEG-400 was carried out in acidic aqueous media and resulted in the binding of up to five carboxylate groups with PEG. The study of cytotoxicity against Hep-2 cells and acute toxicity in mice showed a twofold reduction in toxicity after PEGylation, demonstrating the success of the strategy chosen. Finally, the compound obtained has been used for the visualization of blood vessels of laboratory rats by angiography and computed tomography.

Multifunctional Oxidized Dextran as a Matrix for Stabilization of Octahedral Molybdenum and Tungsten Iodide Clusters in Aqueous Media.

Due to their high abundance, polymeric character, and chemical tunability, polysaccharides are perfect candidates for the stabilization of photoactive nanoscale objects, which are of great interest in modern science but can be unstable in aqueous media. In this work, we have demonstrated the relevance of oxidized dextran polysaccharide, obtained via a simple reaction with H2O2, towards the stabilization of photoactive octahedral molybdenum and tungsten iodide cluster complexes [M6I8}(DMSO)6](NO3)4 in aqueous and culture media. The cluster-containing materials were obtained by co-precipitation of the starting reagents in DMSO solution. According to the data obtained, the amount and ratio of functional carbonyl and carboxylic groups as well as the molecular weight of oxidized dextran strongly affect the extent of stabilization, i.e., high loading of aldehyde groups and high molecular weight increase the stability, while acidic groups have some negative impact on the stability. The most stable material based on the tungsten cluster complex exhibited low dark and moderate photoinduced cytotoxicity, which together with high cellular uptake makes these polymers promising for the fields of bioimaging and PDT.

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%.

Electrospun Biodegradable Nanofibers Coated Homogenously by Cu Magnetron Sputtering Exhibit Fast Ion Release. Computational and Experimental Study.

Copper-coated nanofibrous materials are desirable for catalysis, electrochemistry, sensing, and biomedical use. The preparation of copper or copper-coated nanofibers can be pretty challenging, requiring many chemical steps that we eliminated in our robust approach, where for the first time, Cu was deposited by magnetron sputtering onto temperature-sensitive polymer nanofibers. For the first time, the large-scale modeling of PCL films irradiation by molecular dynamics simulation was performed and allowed to predict the ions penetration depth and tune the deposition conditions. The Cu-coated polycaprolactone (PCL) nanofibers were thoroughly characterized and tested as antibacterial agents for various Gram-positive and Gram-negative bacteria. Fast release of Cu2+ ions (concentration up to 3.4 µg/mL) led to significant suppression of E. coli and S. aureus colonies but was insufficient against S. typhimurium and Ps. aeruginosa. The effect of Cu layer oxidation upon contact with liquid media was investigated by X-ray photoelectron spectroscopy revealing that, after two hours, 55% of Cu atoms are in form of CuO or Cu(OH)2. The Cu-coated nanofibers will be great candidates for wound dressings thanks to an interesting synergistic effect: on the one hand, the rapid release of copper ions kills bacteria, while on the other hand, it stimulates the regeneration with the activation of immune cells. Indeed, copper ions are necessary for the bacteriostatic action of cells of the immune system. The reactive CO2/C2H4 plasma polymers deposited onto PCL-Cu nanofibers can be applied to grafting of viable proteins, peptides, or drugs, and it further explores the versatility of developed nanofibers for biomedical applications use.

Noble Metals for Modern Implant Materials: MOCVD of Film Structures and Cytotoxical, Antibacterial, and Histological Studies.

This work is aimed at developing the modification of the surface of medical implants with film materials based on noble metals in order to improve their biological characteristics. Gas-phase transportation methods were proposed to obtain such materials. To determine the effect of the material of the bottom layer of heterometallic structures, Ir, Pt, and PtIr coatings with a thickness of 1.4-1.5 µm were deposited by metal-organic chemical vapor deposition (MOCVD) on Ti6Al4V alloy discs. Two types of antibacterial components, namely, gold nanoparticles (AuNPs) and discontinuous Ag coatings, were deposited on the surface of these coatings. AuNPs (11-14 nm) were deposited by a pulsed MOCVD method, while Ag films (35-40 nm in thickness) were obtained by physical vapor deposition (PVD). The cytotoxic (24 h and 48 h, toward peripheral blood mononuclear cells (PBMCs)) and antibacterial (24 h) properties of monophase (Ag, Ir, Pt, and PtIr) and heterophase (Ag/Pt, Ag/Ir, Ag/PtIr, Au/Pt, Au/Ir, and Au/PtIr) film materials deposited on Ti-alloy samples were studied in vitro and compared with those of uncoated Ti-alloy samples. Studies of the cytokine production by PBMCs in response to incubation of the samples for 24 and 48 h and histological studies at 1 and 3 months after subcutaneous implantation in rats were also performed. Despite the comparable thickness of the fibrous capsule after 3 months, a faster completion of the active phase of encapsulation was observed for the coated implants compared to the Ti alloy analogs. For the Ag-containing samples, growth inhibition of S. epidermidis, S. aureus, Str. pyogenes, P. aeruginosa, and Ent. faecium was observed.

The role of gold nanoparticles' aspect ratio in plasmon-enhanced luminescence and the singlet oxygen generation rate of Mo6 clusters.

Here we present a study on the effect of the aspect ratio (AR) of gold nanoparticles on the emission intensity and singlet oxygen production rate of hexamolybdenum cluster-doped silica particles. It was shown that these parameters can be enhanced gradually up to 6.7- and 13-fold with the AR.

Biodistribution of 10B in Glioma Orthotopic Xenograft Mouse Model after Injection of L-para-Boronophenylalanine and Sodium Borocaptate.

Boron neutron capture therapy (BNCT) is based on the ability of the boron-10 (10B) isotope to capture epithermal neutrons, as a result of which the isotope becomes unstable and decays into kinetically active elements that destroy cells where the nuclear reaction has occurred. The boron-carrying compounds-L-para-boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH)-have low toxicity and, today, are the only representatives of such compounds approved for clinical trials. For the effectiveness and safety of BNCT, a low boron content in normal tissues and substantially higher content in tumor tissue are required. This study evaluated the boron concentration in intracranial grafts of human glioma U87MG cells and normal tissues of the brain and other organs of mice at 1, 2.5 and 5 h after administration of the boron-carrying compounds. A detailed statistical analysis of the boron biodistribution dynamics was performed to find a 'window of opportunity' for BNCT. The data demonstrate variations in boron accumulation in different tissues depending on the compound used, as well as significant inter-animal variation. The protocol of administration of BPA and BSH compounds used did not allow achieving the parameters necessary for the successful course of BNCT in a glioma orthotopic xenograft mouse model.

Synergetic Effect of Mo6 Clusters and Gold Nanoparticles on the Photophysical Properties of Both Components.

Photodynamic and photothermal therapies (PDT, and PTT, respectively) are promising candidates for multimodal anticancer therapies (i.e., combinations of therapies), since their action is based on mechanisms that generally cannot be resisted by cancer cells, that is, generation of highly oxidizing oxygen species and high temperature, respectively. Herein, hybrid materials that combine octahedral molybdenum clusters as potential PDT agents and plasmonic spherical gold nanoparticles (AuNPs) as PTT agents are reported. Partial overlap of the photoemission spectrum of the cluster and the surface plasmon resonance band of the AuNPs facilitates energy transfer between the photoactive components, which resulted in synergetic enhancement of their photophysical properties. Specifically, by careful selection of the spacing between the cluster and the gold nanoparticle, a significant increase in luminescence and photosensitizing properties of the cluster was achieved in comparison with similar, but gold-free, particles. On the other hand, the cluster complex facilitated energy conversion to heat by gold particles and hence increased the heating rate under laser irradiation.

Single-domain antibody C7b for address delivery of nanoparticles to HER2-positive cancers.

Monoclonal antibodies (mAb) demonstrate great potential as immunotherapy agents for the treatment of diseases such as cancer as well as tagging for the targeted delivery of multicomponent therapeutic or diagnostic systems. Nevertheless, the large physical size, poor stability of mAbs and abnormal allergic reactions still remain the main issues affecting their generalised use. Single-domain antibodies (sdAb) are seen as the next generation of antibody derived therapeutics and diagnostics. This work presents the optimised production method for HER2-specific sdAb C7b, which led to an ∼11-fold increase in protein yield. In addition, the in vitro and in vivo efficiencies of the targeted delivery of a model nanoparticle cargo (50 nm silica particles doped with Mo6 phosphorescent clusters) conjugated to C7b against those conjugated to HER2-specific trastuzumab is benchmarked. Specifically, this paper demonstrates the significantly higher rate of accumulation in and excretion from xenograft cancer tissue of nanoparticles with C7b, which is of particular importance for diagnostics, i.e. delivery of imaging agents.

Hexamolybdenum Clusters Supported on Exfoliated h-BN Nanosheets for Photocatalytic Water Purification.

Nowadays, the development of new effective photocatalytic materials for the purification of real wastewaters and model systems containing organic molecules constitutes an important challenge. Here we present a preparation strategy for composite materials based on hexamolybdenum cluster complexes and exfoliated hexagonal boron nitride (h-BN) nanosheets. Cluster deposition on the nanosheet surface was achieved by impregnation of the matrix by a (Bu4N)2[{Mo6I8}(NO3)6]/acetone solution. Successful cluster immobilization and chemical composition of the samples were verified by inductively coupled plasma atomic emission spectroscopy, transmission electron microscopy with elemental mapping (TEM/EDS), X-ray photoelectron spectroscopy (XPS), and optical diffuse-reflectance spectroscopy. A small amount of water in acetone initiates the hydrolysis of a molybdenum cluster precursor with labile NO3- ligands, which are absent in the final composite, according to the XPS data. Intermediate hydrolyzed cluster forms anchor to the surface of h-BN nanosheets and promote growth of the insoluble compound [{Mo6I8}(H2O)2(OH)4]·yH2O as the final hydrolysis product. TEM/EDS proves that the cluster exists at the nanosheet surface in the form of an X-ray diffraction amorphous thin film. The samples obtained show high photocatalytic activity in the degradation of a model pollutant rhodamine B under UV- and visible-light irradiation. The materials retain their initial photocatalytic efficacy during at least six cycles without the need for recovery.

From Specific γ-CD/[Nb6 Cl12 (H2 O)6 ]2+ Recognition to Biological Activity Tuning.

Specific molecular recognition of γ-cyclodextrin (γ-CD) by the cationic hexanuclear niobium [Nb6 Cl12 (H2 O)6 ]2+ cluster complex in aqueous solutions results in a 1:1 supramolecular assembly {[Nb6 Cl12 (H2 O)6 ]@γ-CD}2+ . NMR spectroscopy, isothermal titration calorimetry (ITC), and ESI-MS were used to study the interaction between the inorganic cluster and the organic macrocycle. Such molecular association affects the biological activity of [Nb6 Cl12 (H2 O)6 ]2+ , decreasing its cytotoxicity despite enhanced cellular uptake. The 1:1 stoichiometry is maintained in solution over a large window of the reagents' ratio, but crystallization by slow evaporation produces a 1:2 host-guest complex [Nb6 Cl12 (H2 O)6 @(γ-CD)2 ]Cl2 ⋅20 H2 O featuring the cluster encapsulated between two molecules of γ-CD. The 1:2 complex was characterized by XRD, elemental analysis, IR spectroscopy, and thermogravimetric analysis (TGA). Quantum chemical calculations were performed to model host-guest interaction.

Residue coevolution reveals functionally important intramolecular interactions in formamidopyrimidine-DNA glycosylase.

In protein evolution, functionally important intramolecular interactions, such as polar bridges or hydrophobic interfaces, tend to be conserved. We have analyzed coevolution of physicochemical properties in pairs of amino acid residues in the formamidopyrimidine-DNA glycosylase (Fpg) protein family, identified three conserved polar bridges (Arg54-Glu131, Gln234-Arg244, and Tyr170-Ser208 in the E. coli protein) located in known functional regions of the protein, and analyzed their roles by site-directed mutagenesis. The structure and molecular dynamic modeling showed that the coevolving pairs do not form isolated bridges but rather participate in tight local clusters of hydrogen bonds. The Arg54-Glu131 bridge, connecting the N- and C-terminal domains, was important for DNA binding, as its abolishment or even ion pair reversal inactivated Fpg and greatly decreased the enzyme's affinity for DNA. Mutations of the Gln234-Arg244 bridge, located at the base of the single Fpg ß-hairpin zinc finger, did not affect the activity but sharply decreased the melting temperature of the protein, with the bridge reversal partially restoring the thermal stability. Finally, Tyr170 mutation to Phe decreased Fpg binding but did not fully inactivate the protein, whereas Ser208 replacement with Ala had no effect; molecular dynamics showed that in both wild-type and S208 A Fpg, Tyr170 quickly re-orients to form an alternative set of hydrogen bonds. Thus, the coevolution analysis approach, combined with biochemical and computational studies, provides a powerful tool for understanding intramolecular interactions important for the function of DNA repair enzymes.

Comprehensive study of hexarhenium cluster complex Na4[{Re6Te8}(CN)6] - In terms of a new promising luminescent and X-ray contrast agent.

Octahedral rhenium cluster complexes may have considerable potential as therapeutic and diagnostic drugs due to their luminescent and X-ray contrast properties, as well as their ability to generate singlet oxygen upon photoirradiation. However, their potential biological effects and toxicity in vitro and in vivo are rather far from being understood. Thus, the aim of our research was to study cytotoxicity, intracellular localization and cellular uptake/elimination kinetics in vitro, biodistribution and acute intravenous toxicity in vivo of a complex Na4[{Re6Te8}(CN)6] as the promising compound for biomedical application. The results have demonstrated that the complex penetrates through cell membranes with the maximum accumulation in cells in 24h of incubation and have low toxic effects in vitro and in vivo. The median lethal dose (LD50) of intravenously administrated Na4[{Re6Te8}(CN)6] is equal to 1082±83mg/kg. These findings will be useful for future development of cluster-based agents for different biomedical applications.

Analysis of high-purity germanium dioxide by ETV-ICP-AES with preliminary concentration of trace elements.

The paper presents a combined technique of germanium dioxide analysis by inductively coupled plasma atomic emission spectrometry (ICP-AES) with preconcentration of trace elements by distilling off matrix and electrothermal (ETV) introduction of the trace elements concentrate into the ICP. Evaluation of metrological characteristics of the developed technique of high-purity germanium dioxide analysis was performed. The limits of detection (LODs) for 25 trace elements ranged from 0.05 to 20ng/g. The accuracy of proposed technique is confirmed by "added-found" («or spiking¼) experiment and comparing the results of ETV-ICP-AES and ICP-AES analysis of high purity germanium dioxide samples.

Selenate as a novel ligand for keplerate chemistry. New {W72Mo60} keplerates with selenates inside the cavity.

The synthesis and characterization of three novel keplerate-type compounds containing the {W72Mo60} mixed-metal core are reported. Complexes (NH4)72[{W6O21(H2O)6}12{Mo2O4(SeO4)}30]·150H2O·6(NH4)2SeO4 (1a) and (NH4)25(NH2Me2)47[{W6O21(H2O)6}12{Mo2O4(SeO4)}30]·130H2O·3(NH4)2SeO4 (1b) were prepared by ligand substitution from the acetate anionic complex [{W6O21(H2O)5(CH3COO)0.5}12{Mo2O4(CH3COO)}30](48-) and selenate. The selenate anions in keplerate ions [{W6O21(H2O)6}12{Mo2O4(SeO4)}30](72-) are very labile and easily aquate with the formation of [{W6O21(H2O)6}12{Mo2O4}30(SeO4)20(H2O)20](52-), which was isolated as (NH4)20(NH2Me2)32[{W6O21(H2O)6}12{Mo2O4}30(SeO4)20(H2O)20]·150H2O (2) and structurally characterized. In the crystal structure of 2 selenate has several coordination modes, preferentially bonding to the {Mo2O4}(2+) units, and, additionally, to the {(W)W5} pentagonal blocks. The compounds have been characterized by elemental analysis, Raman, IR and (77)Se NMR spectroscopy, and by ESI mass spectrometry. Capillary electrophoresis was used for characterization of keplerates in solution for the first time.