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.

Water-Soluble Polyoxometal Clusters of Molybdenum (V) with Pyrazole and Triazole: Synthesis and Study of Cytotoxicity and Antiviral Activity.

Among well-studied and actively developing compounds are polyoxometalates (POMs), which show application in many fields. Extending this class of compounds, we introduce a new subclass of polyoxometal clusters (POMCs) [Mo12O28(µ-L)8]4- (L = pyrazolate (pz) or triazolate (1,2,3-trz or 1,2,4-trz)), structurally similar to POM, but containing binuclear Mo2O4 clusters linked by bridging oxo- and organic ligands. The complexes obtained by ampoule synthesis from the binuclear cluster [Mo2O4(C2O4)2(H2O)2]2- in a melt of an organic ligand are soluble and stable in aqueous solutions. In addition to the detailed characterization in solid state and in aqueous solution, the biological properties of the compounds on normal and cancer cells were investigated, and antiviral activity against influenza A virus (subtype H5N1) was demonstrated.

Correction: Optical property trends in a family of {Mo6I8} aquahydroxo complexes.

Correction for 'Optical property trends in a family of {Mo6I8} aquahydroxo complexes' by Margarita V. Marchuk et al., Dalton Trans., 2021, 50, 8794-8802, https://doi.org/10.1039/D1DT01293B.

Silica-Based Materials Containing Inorganic Red/NIR Emitters and Their Application in Biomedicine.

The low absorption of biological substances and living tissues in the red/near-infrared region (therapeutic window) makes luminophores emitting in the range of ~650-1350 nm favorable for in vitro and in vivo imaging. In contrast to commonly used organic dyes, inorganic red/NIR emitters, including ruthenium complexes, quantum dots, lanthanide compounds, and octahedral cluster complexes of molybdenum and tungsten, not only exhibit excellent emission in the desired region but also possess additional functional properties, such as photosensitization of the singlet oxygen generation process, upconversion luminescence, photoactivated effects, and so on. However, despite their outstanding functional applicability, they share the same drawback-instability in aqueous media under physiological conditions, especially without additional modifications. One of the most effective and thus widely used types of modification is incorporation into silica, which is (1) easy to obtain, (2) biocompatible, and (3) non-toxic. In addition, the variety of morphological characteristics, along with simple surface modification, provides room for creativity in the development of various multifunctional diagnostic/therapeutic platforms. In this review, we have highlighted biomedical applications of silica-based materials containing red/NIR-emitting compounds.

Chemical Diversity of Mo5S5 Clusters with Pyrazole: Synthesis, Redox and UV-vis-NIR Absorption Properties.

The chemistry of transition metal clusters has been intensively developed in the last decades, leading to the preparation of a number of compounds with promising and practically useful properties. In this context, the present work demonstrates the preparation and study of the reactivity, i.e., the possibility of varying the ligand environment, of new square pyramidal molybdenum chalcogenide clusters [{Mo5(µ3-S)i4(µ4-S)i(µ-pz)i4}(pzH)t5]1+/2+ (pzH = pyrazole, i = inner, t = terminal). The one-step synthesis starting from the octahedral Mo6Br12 cluster as well as the substitution of the apical pyrazole ligand or the selective bromination of the inner pyrazolate ligands were demonstrated. All the obtained compounds were characterized in detail using a series of physicochemical methods both in solid state (X-ray diffraction analysis, etc.) and in solution (nuclear magnetic resonance spectroscopy, mass spectrometry, etc.). In this work, redox properties and absorption in the ultraviolet-visible and near-infrared region of the obtained compounds were studied.

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.

Improved Synthesis of (TBA)2[W6Br14] Paving the Way to Further Study of Bromide Cluster Complexes.

Octahedral cluster complexes of molybdenum and tungsten, [M6X8Y6]n- (M = Mo, W; X, Y = Cl, Br, I), are promising active components in various fields, including biomedicine and solar energy. Cluster complexes draw considerable attention due to their X-ray opacity, red/near-IR luminescence, and ability to convert triplet molecular oxygen to active singlet oxygen under UV and visible irradiation. Among the octahedral cluster complexes of molybdenum and tungsten, compounds with a {W6Br8}4+ core are the least studied. There are only a few examples of compounds with substituted terminal ligands, and their properties are not well understood. Among other things, this is due to more labor-intensive and expensive methods for obtaining the starting compounds in comparison with molybdenum counterparts. In this paper, we describe the synthesis of an octahedral cluster complex, (TBA)2[W6Br14] (TBA+ = tetrabutylammonium), in gram quantities, starting from simple substances─W, Br2, and Bi─in 70% yield. The formation of pentanuclear tungsten cluster complexes was recorded as a byproduct. Compounds with substituted terminal ligands (TBA)2[W6Br8Y6] (Y = NO3, Cl, I) were obtained. We also discuss the instability of (TBA)2[W6Br8(NO3)6] under light exposure, the optical properties of a series of compounds (TBA)2[W6Br8Y6] (Y = Cl, Br, I), and the effect of terminal ligands on the chemical shifts in 183W NMR spectra in dimethyl sulfoxide-d6. The presented approach to the synthesis of one of the main precursors of various bromide cluster complexes on a gram scale can stimulate the study of their properties and development of new functional materials based on them.

Unusual Square Pyramidal Chalcogenide Mo5 Cluster with Bridging Pyrazolate-Ligands.

The family of chalcogenide molybdenum clusters is well presented in the literature by a series of compounds of nuclearity ranging from binuclear to multinuclear articulating octahedral fragments. Clusters actively studied in the last decades were shown to be promising as components of superconducting, magnetic, and catalytic systems. Here, we report the synthesis and detailed characterization of new and unusual representatives of chalcogenide clusters: square pyramidal complexes [{Mo5(µ3-Se)i4(µ4-Se)i(µ-pz)i4}(pzH)t5]1+/2+ (pzH = pyrazole, i = inner, t = terminal). Individually obtained oxidized (2+) and reduced (1+) forms have very close geometry (proven by single-crystal X-ray diffraction analysis) and are able to reversibly transform into each other, which was confirmed by cyclic voltammetry. Comprehensive characterization of the complexes, both in solid and in solution, confirms the different charge state of molybdenum in clusters (XPS), magnetic properties (EPR), and so on. DFT calculations complement the diverse study of new complexes, expanding the chemistry of molybdenum chalcogenide clusters.

Nano TiO2 and Molybdenum/Tungsten Iodide Octahedral Clusters: Synergism in UV/Visible-Light Driven Degradation of Organic Pollutants.

Emissions of various organic pollutants in the environment becomes a more and more acute problem in the modern world as they can lead to an ecological disaster in foreseeable future. The current situation forces scientists to develop numerous methods for the treatment of polluted water. Among these methods, advanced photocatalytic oxidation is a promising approach for removing organic pollutants from wastewater. In this work, one of the most common photocatalysts-titanium dioxide-was obtained by direct aqueous hydrolysis of titanium (IV) isopropoxide and impregnated with aqueous solutions of octahedral cluster complexes [{M6I8}(DMSO)6](NO3)4 (M = Mo, W) to overcome visible light absorption issues and increase overall photocatalytic activity. XRPD analysis showed that the titania is formed as anatase-brookite mixed-phase nanoparticles and cluster impregnation does not affect the morphology of the particles. Complex deposition resulted in the expansion of the absorption up to ~500 nm and in the appearance of an additional cluster-related band gap value of 1.8 eV. Both types of materials showed high activity in the photocatalytic decomposition of RhB under UV- and sunlight irradiation with effective rate constants 4-5 times higher than those of pure TiO2. The stability of the catalysts is preserved for up to 5 cycles of photodegradation. Scavengers' experiments revealed high impact of all of the active species in photocatalytic process indicating the formation of an S-scheme heterojunction photocatalyst.

Oxygen-Sensitive Photo- and Radioluminescent Polyurethane Nanoparticles Modified with Octahedral Iodide Tungsten Clusters.

The development of cancer treatment techniques able to cure tumors located deep in the body is an urgent task for scientists and physicians. One of the most promising methods is X-ray-induced photodynamic therapy (X-PDT), since X-rays have unlimited penetration through tissues. In this work, octahedral iodide tungsten clusters, combining the properties of a scintillator and photosensitizer, are considered as a key component of nanosized polyurethane (pU) particles in the production of materials promising for X-PDT. Cluster-containing pU nanoparticles obtained here demonstrate bright photo- and X-ray-induced emission in both solid and water dispersion, great efficiency in the generation of singlet oxygen, and high sensitivity regarding photoluminescence intensity in relation to oxygen concentration. Additionally, incorporation of the cluster complex into the pU matrix greatly increases its stability against hydrolysis in water and under X-rays.

Water-Soluble Chalcogenide W6-Clusters: On the Way to Biomedical Applications.

Despite the great potential of octahedral tungsten cluster complexes in fields of biomedical applications such as X-ray computed tomography or angiography, there is only one example of a water-soluble W6Q8-cluster that has been reported in the literature. Herein we present the synthesis and a detailed characterization including X-ray structural analysis, NMR, IR, UV-Vis spectroscopies, HR-MS spectrometry, and the electrochemical behavior of two new cluster complexes of the general formula W6Q8L6 with phosphine ligands containing a hydrophilic carboxylic group, which makes the complexes soluble in an aqueous medium. The hydrolytic stability of the clusters' aqueous solutions allows us to investigate for the first time the influence of W6-clusters on cell viability. The results obtained clearly demonstrate their very low cytotoxicity, comparable to the least-toxic clusters presented in the literature.

Stabilization of Octahedral Metal Halide Clusters by Host-Guest Complexation with γ-Cyclodextrin: Toward Nontoxic Luminescent Compounds.

γ-Cyclodextrin (γ-CD) interacts in aqueous solution with octahedral halide clusters Na2[{M6X8}Cl6] (M = Mo, W; X = Br, I) to form robust inclusion supramolecular complexes [{M6X8}Cl6@2γ-CD]2-. Single-crystal X-ray diffraction analyses revealed two conformational organizations within the adduct depending on the nature of the inner halide X within the {M6X8} core. Using 35Cl NMR and UV-vis as complementary techniques, the kinetics of the hydrolysis process were shown to increase with the following order: {W6I8} < {W6Br8} ≈ {Mo6I8} < {Mo6Br8}. The complexation with γ-CD drastically enhances the hydrolytic stability of luminescent [{M6X8}Cl6]2- cluster-based units, which was quantitatively proved by the same techniques. The resulting host-guest complexation provides a protective shell against contact with water and offers promising horizons for octahedral clusters in biology as revealed by the low dark cytotoxicity and cellular uptake.

The role of hydrolysis in biological effects of molybdenum cluster with DMSO ligands.

Biological applications of octahedral molybdenum cluster complexes are complicated by their hydrolytic instability, since hydrolysis leads to irreversible changes in the structure and properties of these compounds. On the other hand, if such changes are thoroughly investigated and understood, the hydrolysis process can become an important tool for regulating specific biological effects of the clusters. In this work, we demonstrate how the luminescence and biological properties (cellular uptake, cytotoxicity in the dark and photodynamic effect) of highly unstable cluster complex [{Mo6I8}(DMSO)6](NO3)4 change along with the degree of hydrolysis. Particularly, cluster solution preliminarily aged in water demonstrated lower dark and higher photoinduced cytotoxicity and higher cellular uptake in comparison with fresh solution.

Self-Assembled Microporous M-HOFs Based on an Octahedral Rhenium Cluster with Benzimidazole.

Substitution of apical halide ligands in [{Re6Sei8}Xa6]3- (X = Cl, Br) by benzimidazole (bimzH) accompanied by a self-assembly process leads to the formation of microporous Re6-based hydrogen-bonded organic frameworks (Re6-HOFs) constructed on N-H···X hydrogen bonds and π-π-stacking interactions between bimzH ligands. Re6-HOFs demonstrate sorption properties with a Brunauer-Emmett-Teller surface area of up to 443 m2 g-1 and luminescence with a quantum yield and an emission lifetime of up to 0.16 and 16 µs, respectively. The compounds obtained complement small groups of transition-metal cluster-based HOFs, which are a perspective for the development of multifunctional frameworks.

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.

Optical property trends in a family of {Mo6I8} aquahydroxo complexes.

Luminescence is one of the key properties of octahedral molybdenum cluster complexes and the basis for most areas of their possible practical applications. Nevertheless, the factors affecting the optical properties of the clusters are insufficiently studied and establishing them will allow us to tune both absorption and emission more precisely. In this work, we obtained two new cationic [{Mo6I8}(H2O)4(OH)2](An)2·nH2O (An = NO3-, n = 3; An = OTs-, n = 2, OTs- - p-toluenesulfonate), and two neutral [{Mo6I8}(H2O)2(OH)4]·nH2O (n = 2, 12) aquahydroxo complexes. Due to the similar compositions of the clusters obtained, we determined the influence of crystal packing and ligand environment on the absorption and photo- and radioluminescence properties. Thus, the four-component nature of the cluster emission was established using Gaussian deconvolution of the photoluminescence spectra. It was shown that the influence of both ligand type and crystal density decreases when moving to the red (lower-energy) part of the spectra, with only the first two components located in the blue (higher-energy) part of the spectra being strongly affected. Also, it was found that protonation of two hydroxo ligands leads to a significant decrease in absorption in the visible spectral region.

Heterogeneous photoactive antimicrobial coatings based on a fluoroplastic doped with an octahedral molybdenum cluster compound.

Despite the wide variety of strategies developed to combat pathogenic microorganisms, the infectious diseases they cause remain a worldwide health issue. Hence, the search for new disinfectants, which prevent infection spread, constitutes an extremely urgent task. One of the most promising methods is the use of photoactive compounds - photosensitizers, capable of generating reactive oxygen species, in particular, singlet oxygen (O2(1Δg)), which causes rapid and effective death of microorganisms of all types. In this work, we propose the utilization of the powdered cluster complex (Bu4N)2[{Mo6I8}(OTs)6] as a photoactive additive to commercially available fluoroplastic lacquer F-32L to create heterogeneous self-sterilizing coatings. We show that soaking of the prepared films in water for 60 days did not lead to a decrease in their photosensitization properties indicating their excellent stability. Moreover, the use of the cluster complex in the solid state allowed significant expansion of the operating wavelength range, which covers the UV region and a large part of the visible region (250-650 nm). The films displayed high photoantimicrobial activity against five common pathogens (bacteria and fungi) under white-light irradiation. Overall, the properties demonstrated make these materials promising for practical use in everyday outdoor and indoor disinfection since they are active under both sunlight and artificial lighting.

"Host in Host" Supramolecular Core-Shell Type Systems Based on Giant Ring-Shaped Polyoxometalates.

Herein, we show how the chaotropic effect arising from reduced molybdate ions in acidified aqueous solution is able to amplify drastically weak supramolecular interactions. Time-resolved Small Angle X-ray Scattering (SAXS) analysis suggests that molybdenum-blue oligomeric species form huge aggregates in the presence of γ-cyclodextrin (γ-CD) which results in the fast formation of nanoscopic {Mo154 }-based host-guest species, while X-ray diffraction analysis reveals that the ending-point of the scenario results in an unprecedented three-component well-ordered core-shell-like motif. A similar arrangement was found by using preformed hexarhenium chalcogenide-type cluster [Re6 Te8 (CN)6 ]4- as exogenous guest. This seminal work brings better understanding of the self-assembly processes in general and gives new opportunities for practical applications in the design of complex multicomponent materials via the simplicity of the non-covalent chemistry.

A water-soluble octahedral molybdenum cluster complex as a potential agent for X-ray induced photodynamic therapy.

X-ray-induced photodynamic therapy (X-PDT) has recently evolved into a suitable modality to fight cancer. This technique, which exploits radiosensitizers producing reactive oxygen species, allows for a reduction of the radiation dose needed to eradicate cancer in the frame of the radiotherapy treatment of deep tumors. The use of transition metal complexes able to directly produce singlet oxygen, O2(1Δg), upon X-ray irradiation constitutes a promising route towards the optimization of the radiosensitizer's architecture. In our endeavour to conceive pertinent agents for X-PDT, we designed an octahedral molybdenum cluster complex (Mo6) with iodine inner ligands, and carboxylated apical ligands bearing ethylene oxide organic functions. The sodium salt of this complex is highly soluble in aqueous media and displays red luminescence which is efficiently quenched by oxygen to produce O2(1Δg) in a high quantum yield. Furthermore, due to its high radiodensity, the complex exhibits radioluminescence in aqueous media, with the same spectral features as for photoluminescence, indicating the production of O2(1Δg) upon X-ray irradiation. The uptake of the complex by Hep-2 and MRC-5 cells is negligible during the first hours of incubation, then considerably increases in connection with the hydrolysis of the apical ligands. The complex exhibits low toxicity in vitro and induces a radiotoxic effect, noticeable against cancerous Hep-2 cells but negligible against normal MRC-5 cells, at X-ray doses that do not affect cell viability otherwise. The first evaluation of in vivo toxicity of an Mo6 complex on a mouse model evidences a moderate and delayed toxic effect on kidneys, with an intravenous LD50 value of 390 ± 30 mg kg-1, possibly connected with hydrolysis-induced aggregation of the complex. Overall, this complex displays attractive features as a singlet oxygen radiosensitizer for X-PDT, highlighting the potential of transition metal cluster complexes towards this modality.

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.