Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

Abstract

Bio-organometallics is a research strategy of biology that uses organic-inorganic hybrid molecules. The molecules are expected to exhibit useful bioactivities based on the unique structure formed by interaction between the organic structure and intramolecular metal(s). However, studies on both biology and toxicology of organic-inorganic hybrid molecules have been incompletely performed. There can be two types of toxicological studies of bio-organometallics; one is evaluation of organic-inorganic hybrid molecules and the other is analysis of biological systems from the viewpoint of toxicology using organic-inorganic hybrid molecules. Our recent studies indicate that cytotoxicity of hybrid molecules containing a metal that is nontoxic in inorganic forms can be more toxic than that of hybrid molecules containing a metal that is toxic in inorganic forms when the structure of the ligand is the same. Additionally, it was revealed that organic-inorganic hybrid molecules are useful for analysis of biological systems important for understanding the toxicity of chemical compounds including heavy metals.

Synergistic cytotoxicity caused by forming a complex of copper and 2,9-dimethyl-1,10-phenanthroline in cultured vascular endothelial cells

“…However, as yet, such hybrid molecules have made scant contributions to biology, and there has been no clear strategy for using them in biological research fields. From the viewpoint of toxicology, we have proposed two types of researches using hybrid molecules: one is to evaluate hybrid molecules as toxic substances, and the other is to use hybrid molecules to analyze biological systems (Fujie et al, 2016a).…”

Copper diethyldithiocarbamate as an inhibitor of tissue plasminogen activator synthesis in cultured human coronary endothelial cells

“…Although organic-inorganic compounds have contributed little to the life science fields to date, the application of such molecules as part of a bio-organometallics strategy has recently begun (Fujie et al, 2016a). In this new strategy, organicinorganic hybrid molecules are not only evaluated as toxic compounds (Murakami et al, 2015;Kohri et al, 2015;Hara et al, 2016) they are also used as tools for analyzing biological systems.…”

Bis(1,4-dihydro-2-methyl-1-phenyl-4-thioxo-3-pyridiolato)zinc(II) exhibits strong cytotoxicity and a high intracellular accumulation in cultured vascular endothelial cells

“…It is believed that zinc complexes are in general non-toxic or only slightly toxic because inorganic zinc is non-toxic. However, organic-inorganic hybrid molecules, including zinc complexes, can exhibit distinct biological activities from that of the intramolecular metal in inorganic forms (Fujie et al, 2016a). The biological activities, including cytotoxicity, of either the molecular structures or that of the metals that make up the hybrid molecules cannot be used to predict the biological activities of such hybrid molecules (Kohri et al, 2015;Murakami et al, 2015;Hara et al, 2016;Nakamura et al, 2017).…”

“…The present data suggest that a part of the structure, especially the binding site of the metal atom, was responsible for accumulation of zinc complexes, and the entire structure is responsible for their cytotoxicity in vascular endothelial cells. Recently, we have proposed bio-organometallics, a research strategy in biology that uses organic-inorganic hybrid molecules, as a tool to analyze biological systems (Fujie et al, 2016a). This research strategy succeeded in revealing the intracellular signal transduction of metallothionein induction (Fujie et al, 2016b) and that of syndecan-4 expression (Hara et al,…”