Iron(II)/Iron(III) and Cobalt(II) Complexes as Redox-tunable Probes for Magnetic Resonance Imaging (MRI)

炎症是许多疾病的特征，包括动脉硬化、多发性硬化症和癌症。追踪炎症的探针的发展可以为这些疾病的诊断和治疗提供信息。磁共振成像(MRI)提供高分辨率和深层组织图像，与MRI探针相结合，可以绘制疾病状态下的炎症图谱。在这个项目中，莫罗博士正在开发新的MRI探测器，这种探测器可以显示在炎症过程中人体免疫防御系统产生的某些分子存在时，信号会发生变化。这些核磁共振探针包含钴或铁开关，这些开关是小分子或脂质纳米颗粒的一部分。该项目涉及几种新的含钴或含铁分子的制备，以及它们在溶液中的研究和在炎症动物模型中的研究。纽约州立大学布法罗分校的莫罗博士在她的研究的基础上，积极参与外联活动，以促进学生对科学、技术、工程和数学(STEM)学科的参与。这些活动包括在莫罗博士的实验室为中学和高中教师进行暑期研究实习，旨在改善K-12学生的教育，并鼓励他们对STEM职业的兴趣。纽约州立大学布法罗分校的莫罗博士在化学系化学结构、动力学和机制-B项目的资助下，正在开发过渡金属络合物作为核磁共振造影剂，对炎症引起的细胞氧化还原失衡做出反应。与防御性免疫反应相关的炎症是许多疾病和损伤的特征，包括动脉硬化、多发性硬化症和癌症。例如，动脉粥样硬化性病变含有高水平的过氧化物酶活性。莫罗博士正在合成新的钴(II)和铁(II)/铁(III)络合物，作为对炎症反应的核磁共振造影剂。在这些氧化条件下，Fe(II)的小分子配位络合物通过形成高自旋的Fe(III)络合物作为弛豫度造影剂而被激活。当氧化还原环境改变时，负载Co(II)或Fe(II)的脂质体系统显示信号的位置发生变化。磁共振研究既在溶液中进行，也在小鼠身上进行。莫罗博士积极参与STEM外展计划，重点关注中学和高中教师以及本科生的暑期研究经验和合作项目，以改善STEM领域的教育，以支持该项目的更广泛影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Inflammation is a characteristic feature of many diseases including arteriosclerosis, multiple sclerosis, and cancer. The development of probes to track inflammation could provide information towards the diagnosis and treatment of these diseases. Magnetic resonance imaging (MRI) provides high resolution and deep tissue images, which in conjunction with MRI probes, may enable mapping of inflammation in disease states. In this project, Dr. Morrow is developing new MRI probes that demonstrate a change in signal in the presence of certain molecules that are produced by the immune defense system of the body during inflammation. These MRI probes contain cobalt or iron switches that are part of small molecules or lipid nanoparticles. This project involves the preparation of several new cobalt or iron containing molecules and their study in solution and in animal models of inflammation. Dr. Morrow of the University at Buffalo, the State University of New York is actively engaged in outreach activities that build upon her research to promote engagement of students in science, technology, engineering and mathematics (STEM) disciplines. These activities, which include summer research internships for middle school and high school teachers in Dr. Morrow’s laboratory, are directed at improving education of K-12 students and encouraging their interest in STEM careers. With funding from the Chemical Structure, Dynamics and Mechanisms-B program of the Chemistry Division, Dr. Morrow of the University at Buffalo, the State University of New York is developing transition metal complexes as MRI contrast agents that respond to cellular redox imbalances attributed to inflammation. Inflammation that is associated with the defensive immune response is a characteristic of many diseases and injuries including arteriosclerosis, multiple sclerosis, and cancer. For example, atherosclerotic lesions contain high levels of perioxidase activity. Dr. Morrow is synthesizing new Co(II) and Fe(II)/Fe(III) complexes as MRI contrast agents that are responsive to inflammation. Small molecule coordination complexes of Fe(II) are activated under these oxidizing conditions through the formation of high spin Fe(III) complexes that are relaxivity contrast agents. Liposome systems loaded with Co(II) or Fe(II) show a shift in the position of the signal upon change in redox environment. MRI studies are carried out both in solution and in mice. Dr. Morrow is actively engaged in STEM outreach programs focused on summer research experiences and collaborative projects for middle and high school teachers and for undergraduates to improve education in the STEM fields, in support of broader impacts of the project.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.