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: 6437017
• 负责人: ANTONIO E ALEGRIA
• 金额: $ 25.93万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6437017
• 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.

半醌类化合物是化合物的细胞毒性作用的重要中间体， 含醌药物用于治疗几种人类 疾病。我们的主要目的是了解相互关联的作用， 测定半醌的环境和结构 半醌的热力学稳定性（或动力学反应性）， 通过了解这些，了解醌类的细胞毒性作用 可以获得更有效的醌类药物， 设计了这一主要目标可以细分为两类具体的 目的，即，那些测量半醌的物理性质 物理性质和缔合常数与其生物学特性 确定相关环境（金属阳离子和膜）， 那些旨在测量潜在细胞毒性药物的有效性的研究 这些物理性质变化的函数。 根据它们的性质，半醌可以与 金属阳离子，离子交换，电子转移反应， 分配到磷脂膜和其他。此外，醌- 已知含有抗肿瘤药物的化合物可增强其抗肿瘤活性， 在超声辐射的存在下的活性。两个潜在 半醌类作为介质发挥作用的细胞毒性反应 是供电子反应和脂质过氧化反应。特别是， 电子转移到氧和一氧化氮产生细胞毒性 中间体是生物医学相关过程。该分项目将 测量半醌/对苯二酚介导的 氧和一氧化氮，醌诱导的脂质过氧化反应速率， 超声诱导的氧还原率的存在下， 醌类。将寻求醌-半醌之间的相关性 物理性质和这些速率。 本科生将参与这个子项目。他们将 在不同的实验室，光谱和计算培训 技术应用于自由基生物医学研究。是 预计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 毕业于研究生院，医学或牙科学校， 生物医学研究职业。