Photochemical Delivery and Metal Mediated Reactions of Nitrogen Oxides and other Bioactive Small Molecules

氮氧化物和其他生物活性小分子的光化学传递和金属介导的反应

• 批准号: 1058794
• 负责人: Peter Ford
• 金额: $ 51.5万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1058794&HistoricalAwards=false
• 关键词: Photochemical; Delivery; Metal; Mediated; Reactions

This award in the Chemistry of Life Processes (CLP) program supports continuing fundamental research by Professor Peter C. Ford at the University of California, Santa Barbara into how transition metal centers define the biological chemistry of nitric oxide (NO) and other small molecules that play key regulatory roles in mammalian physiology. These studies will also explore photochemical strategies using new nanomaterials for delivering such species to specific targets. It is now broadly known that NO, nitrogen oxide derivatives such as nitrite ion, carbon monoxide (CO) and several other simple molecular species have profound roles in controlling certain physiological functions including the cardiovascular system, wound healing, immune response to pathogens, etc. In nearly all such cases, the chemical reactions with metal centers, such as hemoglobin and other iron and copper containing proteins, is essential to the physiological effects. One goal of the current research is to define and to understand the relevant biochemistry of these metal--small molecule interactions. The techniques employed are reaction kinetics and modern analytical methods as well as theoretical computations. Another goal is to design, prepare and test new molecular and nano-scaled assemblies that that can be used with light to deliver such bioregulators to targeted tissues for the purpose of affecting the viability of the target. By using light as the triggering mechanism one can control the location, timing, and dosages of bioregulator release. Along this line, the UCSB group has developed new systems where nano-sized semiconductor quantum dots (QDs) serve as templates for carrying the small molecule precursors while simultaneously acting as the antennas for light absorption for triggering. On-going studies will refine these assemblies and study their effectivity. From a broader perspective, the UCSB studies will develop fundamental chemical understanding of these bioregulatory molecules that must underlie potential development of new therapeutic applications. The research performed under this award also serves as a template for training undergraduate, graduate and postdoctoral students in the nuances of creative scholarship. This also extends to local K-12 schools, since members of the Ford group have participated actively in scientific outreach programs. Undergraduates leaving the group have entered graduate and medical school programs and Ph.D. and postdoctoral graduates have assumed responsible roles in industry, government and academia, thereby contributing to the US scientific manpower pool.

生命过程化学（CLP）计划中的这一奖项支持Peter C.圣巴巴拉的加州大学的福特教授研究了过渡金属中心如何定义一氧化氮（NO）和其他在哺乳动物生理学中起关键调节作用的小分子的生物化学。这些研究还将探索使用新的纳米材料将这些物种运送到特定目标的光化学战略。现在广泛地知道，NO、氮氧化物衍生物如亚硝酸根离子、一氧化碳（CO）和几种其它简单的分子种类在控制某些生理功能中具有深远的作用，包括心血管系统、伤口愈合、对病原体的免疫应答等。在几乎所有这样的情况下，与金属中心如血红蛋白和其它含铁和铜的蛋白质的化学反应，对生理效应至关重要 目前研究的一个目标是定义和理解这些金属-小分子相互作用的相关生物化学。 所采用的技术是反应动力学和现代分析方法以及理论计算。 另一个目标是设计，制备和测试新的分子和纳米级组件，其可以与光一起使用以将这种生物调节剂递送到靶组织，以影响靶的活力。 通过使用光作为触发机制，可以控制生物调节剂释放的位置、定时和剂量。 沿着这条路线，UCSB小组开发了新的系统，其中纳米尺寸的半导体量子点（QD）作为模板，用于携带小分子前体，同时作为天线，用于光吸收触发。 正在进行的研究将完善这些组合并研究其有效性。 从更广泛的角度来看，UCSB的研究将发展对这些生物调节分子的基本化学理解，这些分子必须成为新治疗应用的潜在开发的基础。在这个奖项下进行的研究也作为一个模板，培养本科生，研究生和博士后学生在创造性奖学金的细微差别。 这也延伸到当地的K-12学校，因为福特集团的成员积极参与科学推广计划。 离开该集团的本科生进入了研究生和医学院课程，并获得了博士学位。博士和博士后毕业生在工业界、政府和学术界担任重要角色，从而为美国的科学人才库做出了贡献。