Singlet Oxygen Production and Biological Activity of Hexanuclear Chalcocyanide Rhenium Cluster Complexes [{Re6Q8}(CN)6]4- (Q = S, Se, Te).

Octahedral rhenium cluster complexes have recently emerged as relevant building blocks for the design of singlet oxygen photosensitizing materials toward biological applications such as blue-light photodynamic therapy. However, their singlet oxygen generation ability as well as biological properties have been studied only superficially. Herein we investigate in detail the singlet oxygen photogeneration, dark and photoinduced cytotoxicity, cellular uptake kinetics, cellular localization and in vitro photoinduced oxidative stress, and photodynamic cytotoxicity of the series of octahedral rhenium cluster complexes [{Re6Q8}(CN)6]4-, where Q = S, Se, Te. Our results demonstrate that the selenium-containing complex possesses optimal properties in terms of absorption and singlet oxygen productivity. These features coupled with the cellular internalization and low dark toxicity lead to the first photoinduced cytotoxic effect observed for a molecular [{M6Q8}L6] complex, making it a promising object for further study in terms of blue-light PDT.

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.

A comparative study of hydrophilic phosphine hexanuclear rhenium cluster complexes' toxicity.

The octahedral rhenium cluster compound Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] has recently emerged as a very promising X-ray contrast agent for biomedical applications. However, the synthesis of this compound is rather challenging due to the difficulty in controlling the hydrolysis of the initial P(C2H4CN)3 ligand during the reaction process. Therefore, in this report we compare the in vitro and in vivo toxicity of Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] with those of related compounds featuring the fully hydrolysed form of the phosphine ligand, namely Na2H14[{Re6Q8}(P(C2H4COO)3)6] (Q = S or Se). Our results demonstrate that the cytotoxicity and acute in vivo toxicity of the complex Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] solutions were considerably lower than those of compounds with the fully hydrolysed ligand P(C2H4COOH)3. Such behavior can be explained by the higher osmolality of Na2H14[{Re6Q8}(P(C2H4COO)3)6] versus Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6].

Nanosized mesoporous metal-organic framework MIL-101 as a nanocarrier for photoactive hexamolybdenum cluster compounds.

Inclusion compounds of photoluminescent hexamolybdenum cluster complexes in the chromium terephthalate metal-organic framework, MIL-101 (MIL, Matérial Institut Lavoisier) were successfully synthesized in two different ways and characterized by means of powder X-Ray diffraction, chemical analysis and nitrogen sorption. Some important functional properties of hexamolybdenum cluster complexes for biological and medical applications, in particular singlet oxygen generation ability, luminescence properties, cellular uptake behavior and cytotoxicity were studied. It was revealed that the inclusion compounds possessed significant singlet oxygen generation activity. The materials obtained showed a low cytotoxicity, thus allowing them to be used in living cells. Confocal microscopy of human larynx carcinoma (Hep-2) cells incubated with the inclusion compounds showed that MIL-101 performed as a nanocarrier adhering to the external cell membrane surface and releasing the cluster complexes which that penetrated into the cells. Moreover, photoinduced generation of reactive oxygen species (ROS) in Hep-2 cells incubated with inclusion compounds was demonstrated. The cluster supported on MIL-101 was shown to possess in vivo phototoxicity.

Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex - a new promising X-ray contrast agent.

The octahedral cluster compound Na2 H8 [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6 ] has been shown to be highly radio dense, thus becoming a promising X-ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD50 ) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex Hn [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6 ]n-10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd.

Cellular internalisation, bioimaging and dark and photodynamic cytotoxicity of silica nanoparticles doped by {Mo6I8}4+ metal clusters.

Silica nanoparticles (SNPs) doped by hexanuclear molybdenum cluster complexes [{Mo6X8}L6]n (X = Cl, Br, or I; L = various inorganic or organic ligands) have been recently suggested as materials with high potential for biomedical applications due to both their outstanding photoluminescence properties and their ability to efficiently generate singlet oxygen upon photoirradiation. However, no studies were undertaken so far to prove this concept. Therefore, here we examined the potential of photoluminescent SNPs doped by {Mo6I8}4+ for applications such as bioimaging and photodynamic therapy using the human epidermoid larynx carcinoma (Hep-2) cell line as a model. Our results demonstrated both: (i) significant luminescence from cells with internalised molybdenum cluster-doped SNPs combined with the low cytotoxicity of particles in the darkness and (ii) significant cytotoxicity of the particles upon photoirradiation. Thus, this research provides strong experimental evidence for high potential of molybdenum-cluster-doped materials in biomedical applications such as optical bioimaging, biolabeling and photodynamic therapy.

The Interdependence of Behavior and Immunity: Possible Mechanisms and Significance.

Mechanisms and significance of interdependence of immunity and behavior are very important line of investigations. The aim of this work was to present an analytical survey of own and literature data accumulated worldwide on this problems. The continuation of such investigations will favor not only to the accumulation of fundamental data in this field, but to application of the results obtained for immuno- and psychoregulation as well.