Project Grant 2400128

RESPONSIVE IRON MRI PROBES WITH ENHANCED RELAXIVITY -WITH THE SUPPORT OF THE CHEMICAL STRUCTURE, DYNAMICS & MECHANISMS-B (CSDM-B) PROGRAM AND THE CHEMICAL MEASUREMENT AND IMAGING (CMI) PROGRAM OF THE CHEMISTRY DIVISION, PROFESSOR JANET MORROW AND HER TEAM IN THE DEPARTMENT OF CHEMISTRY AT THE UNIVERSITY OF BUFFALO, THE STATE UNIVERSITY OF NEW YORK IS DEVELOPING NEW CLASSES OF MAGNETIC RESONANCE IMAGING (MRI) CONTRAST AGENTS OR PROBES BASED ON IRON COORDINATION COMPLEXES. THE GOAL OF THIS RESEARCH IS TO DESIGN CONTRAST AGENTS THAT PRODUCE A STRONG MRI SIGNAL BY USING THE BIOLOGICALLY RELEVANT METAL, IRON. THESE IRON-BASED AGENTS WILL BE IN THE FORM OF SMALL MOLECULE COMPLEXES OR LIPOSOMAL NANOPARTICLES. ONE CLASS OF IRON-BASED AGENTS WILL BE STABILIZED IN THE SIGNAL PRODUCING FORM AND THE OTHER CLASS WILL PRODUCE SIGNAL ONLY UNDER OXIDIZING CONDITIONS OF INFLAMMATION. THE PROJECT LIES AT THE NEXUS OF ORGANIC, INORGANIC, BIOLOGICAL CHEMISTRY AND IMAGING SCIENCE. PROFESSOR JANET MORROW'S GROUP IS WELL-POSITIONED TO EDUCATE AND TRAIN GRADUATE AND UNDERGRADUATE STUDENTS INCLUDING THOSE UNDERREPRESENTED IN SCIENCE. OUTREACH ACTIVITIES INVOLVING HIGH SCHOOL STUDENTS AND THEIR TEACHERS WILL BE PART OF THE FUNDED PROJECT WITH THE GOAL OF DEVELOPING LABORATORY AND LECTURE MATERIALS ON THE PREPARATION AND MAGNETIC PROPERTIES OF IRON NANOPARTICLES. FE(III)-BASED MRI PROBES ARE OF INTEREST AS ALTERNATIVES FOR GD(III) COMPLEXES USED IN THE CLINIC AND ALSO FOR THE DEVELOPMENT OF RESPONSIVE CONTRAST AGENTS FOR THE REGISTRATION OF INFLAMMATION FOUND IN DISEASE STATES. THE PROPOSED RESEARCH WILL EXPLORE THE SYNTHESIS OF IRON-BASED MRI PROBES AS SMALL MOLECULES OR INCORPORATED INTO LIPOSOMAL AGENTS AND WILL INCLUDE STUDIES IN SOLUTION AND IN MICE. OVERALL GOALS INCLUDE THE OPTIMIZATION OF FE(III) COORDINATION COMPLEXES AS RELAXATION AGENTS THROUGH THE STUDY OF THE MAGNETIC FIELD STRENGTH DEPENDENCE OF THE LONGITUDINAL RELAXIVITY (T1) BY USING NUCLEAR MAGNETIC RELAXATION DISPERSION (NMRD) TO GAIN INFORMATION ON WATER INTERACTIONS AND ELECTRONIC RELAXATION PROCESSES. SECOND, THE EXPERTISE OF PROFESSOR JANET MORROW'S GROUP IN THE COORDINATION CHEMISTRY OF BOTH FE(II) AND FE(III) PLACES THEM IN A STRONG POSITION TO ADDRESS THE CHALLENGES OF DEVELOPING MRI CONTRAST AGENTS THAT ARE RESPONSIVE TO OXIDATION PROCESSES CORRESPONDING TO INFLAMMATION. COORDINATION COMPLEXES AND LIPOSOMAL AGENTS WILL BE STUDIED AS RESPONSIVE MRI PROBES IN SOLUTION IN THE PRESENCE OF ENZYMES THAT GENERATE OXIDANTS FOUND IN INFLAMMATORY PROCESSES. FINALLY, MRI STUDIES IN MICE WILL ENABLE THE EXPLORATION OF BIODISTRIBUTION OF THE PROBE AND PROVIDE OPPORTUNITIES FOR STUDYING INFLAMMATION-IMPACTED TISSUE AS A LONG-TERM GOAL. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.