Molecular chemical study of Neutrotoxicity and Molecular structure of Industrial chemical compounds

工业化合物中性毒性和分子结构的分子化学研究

• 批准号: 62570232
• 负责人: MISUMI Junichi
• 金额: $ 0.83万
• 依托单位: Medical College of Oita
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570232/
• 关键词: 2,5-hexanedione; 3,4-dimethyl 2,5-hexanedione; neurotoxicity; molecular orbital energy; structure-activity relationship; HOMO; LUMO; 2,5-ヘキサンジオン; 分子軌道エネルギー; 構造毒性相関; 量子化学的研究

It is well known that 2,5-hexanedione, a major metabolite of n-hexane is responsible for the development of neurotoxicity. The mechanism of the neurotoxicity of this compound is related to pyrol-formation by binding with amine groups of body protein.Present study is aimed to reveal the relationships between neurotoxicity and chemical properties.Highest occupied molecular orbital, lowest unoccupied molecular orbital, electric density and length between carbonyl groups were used as the parameters of reactivity of chemical substances.As the results, LUMO of 3,4-dimethyl 2,5-hexanedione, the most active neurotoxin was lowest and secondarily that of 2,5-hexanedione was low. The relations between neurotoxic activity and chemical properties was strongly suggested. It was also suggested that the acceptability of electrons in these gamma-diketones was closely related to develop neuropathy. These gamma-diketones were considered to combine with anion groups of protein in neurofilaments of axon. This shows that gamma-diketones, neurotoxins are able to combine with amine, sulfur or hydroxy groups of amino acid of protein in neurons.

众所周知，2，5-己二酮是正己烷的主要代谢物，与神经毒性的发生有关。该化合物的神经毒性作用机制与其与人体蛋白质的胺基结合生成焦酚有关，本研究旨在揭示神经毒性与化学性质的关系，以最高占据分子轨道、最低未占据分子轨道、电子密度和羰基间长度作为化学物质反应活性的参数。结果表明，3，4-二甲基2，5-己二酮的LUMO活性最低，2，5-己二酮的LUMO活性次之。神经毒活性与化学性质之间存在明显的相关性。研究还表明，这些伽玛二酮中电子的可接受性与神经病的发生密切相关。这些伽马二酮被认为与轴突神经丝中的蛋白质阴离子基团结合。这说明伽玛二酮、神经毒素都能与神经元中的胺、硫或羟基氨基酸结合。