Utilizing Baird's theory on triplet state aromaticity, we show that the singlet-triplet energy gaps (DeltaE(ST)) of pentafulvenes are easily varied through substitution by as much as 36 kcal mol(-1). This exploits the fact that fulvenes act as aromatic chameleons in which the dipoles reverse on going from the singlet ground state (S(0)) to the lowest pipi* triplet state (T1); thus, their electron distributions are adapted so as to achieve some aromaticity in both states. The results are based on quantum chemical calculations with the OLYP density functional theory method and the CASPT2 ab initio method, as well as spectroscopic determination of DeltaE(ST) by triplet sensitization. The findings can also be generalized to fulvenes other than the pentafulvenes, even though the effect is attenuated as the size of the fulvene increases. Our studies thus reveal that triplet-state aromaticity can greatly influence the properties of conjugated compounds in the T1 state.

Association of cellular influences and physical and chemical properties were examined for 24 kinds of industrial metal oxide nanoparticles: ZnO, CuO, NiO, Sb(2)O(3), CoO, MoO(3), Y(2)O(3), MgO, Gd(2)O(3), SnO(2), WO(3), ZrO(2), Fe(2)O(3), TiO(2), CeO(2), Al(2)O(3), Bi(2)O(3), La(2)O(3), ITO, and cobalt blue pigments. We prepared a stable medium dispersion for each nanoparticle and examined the influence on cell viability and oxidative stress together with physical and chemical characterizations. ZnO, CuO, NiO, MgO, and WO(3) showed a large amount of metal ion release in the culture medium. The cellular influences of these soluble nanoparticles were larger than insoluble nanoparticles. TiO(2), SnO(2), and CeO(2) nanoparticles showed strong protein adsorption ability; however, cellular influences of these nanoparticles were small. The primary particle size and the specific surface area seemed unrelated to cellular influences. Cellular influences of metal oxide nanoparticles depended on the kind and concentrations of released metals in the solution. For insoluble nanoparticles, the adsorption property was involved in cellular influences. The primary particle size and specific surface area of metal oxide nanoparticles did not affect directly cellular influences. In conclusion the most important cytotoxic factor of metal oxide nanoparticles was metal ion release.

"Nanoparticle" is defined as the particles whose diameter in at least one dimension is less than 100 nm. Compared with fine-particles, nanoparticles have large specific surface area. There is a dramatic increase over fine-particles in chemical and physical activities, such as ion release, adsorption ability, and ROS production. These properties are important for industrial use, and many nanoparticles are already used in products familiar to consumers as sunscreens and cosmetics. However, nanoparticle properties beneficial to the industry may also induce biological influences, including toxic activities. Recently, many investigations about the toxicology of nanoparticles have been reported. In the evaluation of nanoparticles toxicity, in vitro studies give us important information, especially in terms of toxic mechanisms. In vitro studies showed that some nanoparticles induce oxidative stress, apoptosis, production of cytokines, and cell death. There are reports that cellular influences of other nanoparticles are small. There are also reports of different results, some with low and some with high influences, for the same nanoparticle. One of the causes of this inconsistency might be a diremption of the living body influence study and the characterization study. Characterization of individual nanoparticles and their dispersions are essential for in vitro evaluation of their biological effects since each nanoparticle shows unique chemical and physical properties. Particularly, the aggregation state and metal ion release ability of nanoparticles affect its cellular influences. Reports concerning the characterization in the in vitro toxicity assessment are increasing. For an accurate risk assessment of nanoparticles, in this review, we outline recent studies of in vitro evaluation of cellular influences induced by nanoparticles. Moreover, we also introduce current studies about the characterization methods of nanoparticles and their dispersions for toxicological evaluation.

No abstract

Nickel oxide (NiO) is one of the important industrial materials used in electronic substrates and for ceramic engineering. Advancements in industrial technology have enabled the manufacture of ultrafine NiO particles. On the other hand, it is well-known that nickel compounds exert toxic effects. The toxicity of nickel compounds is mainly caused by nickel ions (Ni(2+)). However, the ion release properties of ultrafine NiO particles are still unclear. In the present study, the influences of ultrafine NiO particles on cell viability were examined in vitro to obtain fundamental data for the biological effects of ultrafine green NiO and ultrafine black NiO. Ultrafine NiO particles showed higher cytotoxicities toward human keratinocyte HaCaT cells and human lung carcinoma A549 cells than fine NiO particles and also showed higher solubilities in culture medium (Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum) than fine NiO particles. In particular, the concentration of Ni(2+) released into the culture medium by ultrafine green NiO was 150-fold higher than that released by fine green NiO. The concentrations of Ni(2+) released by both types of NiO particles in an aqueous solution containing amino acids were remarkably higher than those released by NiO particles in water. Moreover, we prepared a uniform and stable dispersion of ultrafine black NiO in culture medium and examined its influence on cell viability in comparison with that of NiCl(2), a soluble nickel compound. A medium exchange after 6 h of exposure resulted in a loss of cytotoxicity in the cells exposed to NiCl(2), whereas cytotoxicity was retained in the cells exposed to NiO. Transmission electron microscope observations revealed uptake of both ultrafine and fine NiO particles into HaCaT cells. Taken together, the present results suggest that the intracellular Ni(2+) release could be an important factor that determines the cytotoxicity of NiO. Ultrafine NiO is more cytotoxic than fine NiO in vitro.

No abstract

Evaluation of Acute Oxidative Stress Induced by NiO Nanoparticles In Vivo and In Vitro:Masanori Horie, et al. Health Research Institute -Objectives: Nickel oxide (NiO) is an important industrial material, and it is also a harmful agent. The toxicity of NiO is size-related: nanoparticles are more toxic than fine-particles. The toxic mechanism induced by NiO nanoparticles remains unexplained, and the relationship between in vitro and in vivo NiO toxicity results is unclear. In the present study, we focused on the oxidative stress caused by NiO nanoparticles by examining and comparing in vitro and in vivo acute responses induced by NiO nanoparticles. Methods: Cellular responses induced by black NiO nanoparticles with a primary particle size of 20 nm, were examined in human lung carcinoma A549 cells. In vivo responses were examined by instillation of NiO nanoparticles into rat trachea. Bronchoalveolar lavage fluid (BALF) was collected after intratracheal instillation at different time points, and concentrations of lipid peroxide heme oxygenase-1 (HO-1), surfactant protein-D (SP-D) and lactate dehydrogenase (LDH) in BALF were measured. Results: The levels of intracellular reactive oxygen species and lipid peroxidation in A549 cells increased with increasing exposure to NiO nanoparticles, and increases in gene expressions of HO-1 and SP-D were observed in A549 cells. The lipid peroxide level in BALF significantly increased after 24 h instillation but decreased three days later. LDH leakage was also observed three days later. Conclusions: NiO nanoparticles induce oxidative stress-related lung injury. In vivo and in vitro oxidative stress was induced resulting in activation of antioxidant systems. Based on these responses, we conclude that the results of the in vivo and in vitro studies tend to correspond. (J Occup Health 2011; 53: 64-74)

Cerium oxide (CeO(2)) is an important metal oxide used for industrial products. Many investigations about the cellular influence of CeO(2) nanoparticles have been done, but results are contradictory. It has been reported that CeO(2) nanoparticles have an anti-oxidative effect in cells, but it has also been reported that CeO(2) nanoparticles induce oxidative stress. We investigated the potential influence on cells and the mechanisms induced by CeO(2) nanoparticles in vitro. We prepared a stable CeO(2) culture medium dispersion. Cellular responses in CeO(2) medium-exposed cells were examined. Cellular uptake of CeO(2) nanoparticles was observed. After 24-h exposure, a high concentration of CeO(2) nanoparticles (∼200 mg/ml) induced an increase in the intracellular level of reactive oxygen species (ROS); a low concentration of CeO(2) nanoparticles induced a decrease in the intracellular ROS level. On the other hand, exposure of CeO(2) nanoparticle for 24 h had little influence on the cell viability. Exposure of CeO(2) nanoparticles increased the intracellular Ca(2+) concentration and also Calpain was activated. These results suggest that CeO(2) nanoparticles have a potential to induce intracellular oxidative stress and increase the intracellular Ca(2+) level, but these influences are small.