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

铁 (II)/铁 (III) 和钴 (II) 配合物作为磁共振成像 (MRI) 氧化还原可调探针

• 批准号: 2004135
• 负责人: Janet Morrow
• 金额: $ 42万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2004135&HistoricalAwards=false
• 关键词: Iron; II; III; Cobalt; Complexes

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.

炎症是包括动脉硬化、多发性硬化和癌症在内的许多疾病的特征性特征。 开发追踪炎症的探针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，其与MRI探针结合，可以实现疾病状态中炎症的映射。 在这个项目中，Morrow博士正在开发新的MRI探针，这些探针在炎症期间由身体的免疫防御系统产生的某些分子存在的情况下显示信号的变化。这些MRI探针含有钴或铁开关，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铁分子的制备及其在溶液和炎症动物模型中的研究。 纽约州立大学布法罗大学的莫罗博士积极参与外联活动，以她的研究为基础，促进学生参与科学、技术、工程和数学（STEM）学科。这些活动包括在Morrow博士实验室为初中和高中教师提供暑期研究实习，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Morrow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MRI造影剂，对炎症引起的细胞氧化还原失衡作出反应。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、多发性硬化和癌症。 例如，动脉粥样硬化病变含有高水平的过氧化物酶活性。 Morrow博士正在合成新的Co（II）和Fe（II）/Fe（III）复合物，作为对炎症有反应的MRI造影剂。 Fe（II）的小分子配位络合物在这些氧化条件下通过形成高自旋Fe（III）络合物而被活化，所述高自旋Fe（III）络合物是弛豫对比剂。 负载有Co（II）或Fe（II）的脂质体系统在氧化还原环境改变时显示信号位置的偏移。 MRI研究在溶液和小鼠中进行。 Morrow博士积极参与STEM外展计划，重点是针对初中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，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

Co( ii ) complexes of tetraazamacrocycles appended with amide or hydroxypropyl groups as paraCEST agents

带有酰胺或羟丙基的四氮杂大环Co(ii)配合物作为对位CEST试剂

• DOI: 10.1039/d3dt01572f
• 发表时间: 2023
• 期刊: Dalton Transactions
• 影响因子: 4
• 作者: Raymond, Jaclyn J.;Abozeid, Samira M.;Sokolow, Gregory E.;Bond, Christopher J.;Yap, Constance E.;Nazarenko, Alexander Y.;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.

Redox-Responsive MRI Probes Based on First-Row Transition-Metal Complexes

• DOI: 10.1021/acs.inorgchem.2c02197
• 发表时间: 2022-09-06
• 期刊: INORGANIC CHEMISTRY
• 影响因子: 4.6
• 作者: Morrow, Janet R.;Raymond, Jaclyn J.;Sahoo, Priya Ranjan
• 通讯作者: Sahoo, Priya Ranjan

Liposomal Fe(III) Macrocyclic Complexes with Hydroxypropyl Pendants as MRI Probes.

• DOI: 10.1021/acsabm.1c00879
• 发表时间: 2021-11-15
• 期刊: ACS APPLIED BIO MATERIALS
• 影响因子: 4.7
• 作者: Abozeid, Samira M;Chowdhury, Md Saiful I;Asik, Didar;Spernyak, Joseph A;Morrow, Janet R
• 通讯作者: Morrow, Janet R

Liposomal MRI probes containing encapsulated or amphiphilic Fe(III) coordination complexes

含有封装或两亲性 Fe(III) 配位络合物的脂质体 MRI 探针

• DOI: 10.1039/d3bm00029j
• 发表时间: 2023
• 期刊: Biomaterials Science
• 影响因子: 6.6
• 作者: Chowdhury, Md Saiful;Kras, Elizabeth A.;Turowski, Steven G.;Spernyak, Joseph A.;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.

Magnetization of Yeast by Labeling with Iron Complexes: An Undergraduate Laboratory Experiment

通过铁络合物标记磁化酵母：本科生实验室实验

• DOI: 10.1021/acs.jchemed.2c00791
• 发表时间: 2022
• 期刊: Journal of Chemical Education
• 影响因子: 3
• 作者: Pinti, John C.;Kras, Elizabeth A.;Patel, Akanksha;Schrier, Chloe L.;Stoj, Christopher S.;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.