Project Summary/Abstract The focus of the Zadrozny laboratory is the design of metal complexes for noninvasive sensing of physiological chemistry. The broader goal of the effort is to make molecular probes that overcome inherent challenges in electron paramagnetic resonance imaging (EPRI), the unpaired electron analog to conventional 1H MRI. EPRI can sense local chemistry and could produce comprehensive chemical and anatomical maps of the body if merged with 1H MRI. Modern EPRI molecular imaging probes are organic radicals which require dangerous high-energy microwaves for use in the large magnetic field of an MRI scanner. Hence, the two techniques remain disconnected. For EPRI to enable imaging of physiological chemistry by integration with MRI, new probes must be developed to avoid high frequency microwaves at high magnetic fields. The next five years of the Zadrozny lab’s work involve exploring high-spin metal complexes as an alternative platform to radicals for molecular probes in EPRI. A key inherent advantage of metal ions is that the unique electronic feature of large zero-field splitting enables the possibility of safe, low-frequency microwave use at high magnetic field. Hence, metal complexes with this feature could provide a completely new set of EPRI molecular imaging probes with capabilities unmatched by organic radicals. However, all of the basic EPR spectral properties of metal complexes with low frequency microwaves are unmapped. The Zadrozny lab will amend this knowledge gap. The work will use synthetic inorganic chemistry and spectroscopic analyses to (1) understand how to target the frequency/field of the resonance to match the magnetic fields of MRI scanners with low-frequency microwaves (2) understand how to control the linewidth of the low-frequency EPR resonances to enhance resolution, and (3) how to merge radical/metal chemistry in hybrid molecules to gain the advantages of both metals and radicals for a single molecular probe system. Meeting these objectives will provide a new class of imaging probe capable of mapping physiological chemistry in a conventional MRI scanner.