THERMODYNAMIC STABILITY OF SEMIQUINONES AS A FUNCTION OF THEIR ENVIRONMENT

半醌的热力学稳定性随环境的变化

• 批准号: 6107316
• 负责人: ANTONIO E ALEGRIA
• 金额: $ 17万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107316
• 关键词: calorimetry; cations; chemical stability; chemical structure; cytotoxicity; electron spin resonance spectroscopy; electron transport; free radicals; high performance liquid chromatography; hydroquinones; ionic bond; ionic strengths; membrane potentials; nitric oxide; oxygen consumption; peroxidation; phospholipids; physical property; reducing agents; semiquinone; thermodynamics

Semiquinones are important intermediates in the cytotoxic action of quinone-containing drugs utilized in the treatment of several human illnesses. Our major aim is to understand the interrelated roles of environment and structure of semiquinones in determining the thermodynamic stability (or kinetic reactivity) of semiquinones since, by knowing these, an understanding of the cytotoxic action of quinones may be obtained and more efficient quinone-based drugs could be designed. This major aim can be subdivided in two types of specific aims, i.e., those where physical properties which measure semiquinone physical properties and association constants with their biologically relevant environment (metal cations and membranes) are determined, and those aimed at measuring the effectiveness of potential cytotoxic reactions as a function of changes in these physical properties. According to their nature, semiquinones can undergo ion-pairing with metal cations, disproportionation, electron transfer reactions, partition into phospholipid membranes and others. In addition, quinone- containing anti-tumor drugs are known to enhance their anti-tumor activity in the presence of ultrasound irradiation. Two potential cytotoxic reactions in which semiquinones play their role as mediators are electron donating reactions and lipid peroxidation. In particular, electron transfer to oxygen and nitric oxide to produce cytotoxic intermediates are biomedically relevant processes. This subproject will measure the rates of semiquinone/hydroquinone-mediated reduction of oxygen and nitric oxide, rates of quinone-induced lipid peroxidation and rates of ultrasound-induced oxygen reduction in the presence of quinones. Correlations will be sought between quinone-semiquinones physical properties and these rates. Undergraduate students will participate in this subproject. They will be trained in different laboratory, spectroscopic and computational techniques as applied to free radicals biomedical research. It is expected that the involvement of students in this subproject will serve as a means to obtain one of the desired goals, i.e. students entering and graduation from graduate, medical or odontology schools and pursuing biomedical research careers.

半喹酮类化合物是细胞毒作用的重要中间体。 含醌类药物用于治疗几种人类疾病 疾病。我们的主要目标是了解 半喹酮类化合物测定中的环境和结构 半喹酮的热力学稳定性(或动力学反应性)， 通过了解这些，理解了苯二酚的细胞毒性作用 可能会获得更有效的基于苯醌的药物 都是设计好的。这一主要目标可以细分为两种类型的具体目标 目标，即那些测量半喹酮的物理性质 物理性质和缔合常数与它们的生物学特性 确定了相关环境(金属阳离子和膜)，以及 旨在测量潜在的细胞毒性的有效性 作为这些物理性质变化的函数的反应。 根据其性质，半喹酮可以与离子配对 金属阳离子，歧化，电子转移反应， 分成磷脂膜和其他。此外，苯二酚- 已知含有抗肿瘤药物可增强其抗肿瘤作用 在超声波照射下的活性。两种潜力 半喹酮类化合物作为介体的细胞毒性反应 是电子供体反应和脂质过氧化。特别是， 电子转移到氧和一氧化氮产生细胞毒作用 中间体是与生物医学相关的过程。此子项目将 测定半对苯二酚/对苯二酚介导的还原速率 氧和一氧化氮，苯醌诱导的脂质过氧化和 超声波作用下的氧还原速率 奎诺内斯。将寻找对苯二酚和半对苯二酮之间的相关性 物理属性和这些比率。 本科生将参与这一子项目。他们将会是 在不同的实验室接受培训，光谱和计算 应用于自由基生物医学研究的技术。它是 希望学生参与这个子项目将有助于 作为实现预期目标之一的手段，即学生进入 并从研究生、医学或牙科学校毕业并追求 生物医学研究职业。