<h3>Title</h3>
<h3>Design and Development of Non-macrocyclic Chelators for Mn-based MRI Contrast Agents</h3>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p>Contrast-enhanced magnetic resonance imaging (MRI) has become an indispensable non-invasive diagnostic tool since the FDA approval of Gd-DTPA in 1988.1 However, lately, physicians have reported nephrogenic systemic fibrosis in patients with poor kidney function and a history of Gd-based contrast agent use for MRI scans.2 This has led to safety concerns that limit the use of Gd-based contrast agents and ultimately have sparked the search for alternative contrast agents. Mn2+ being an essential divalent metal ion makes an attractive alternative to Gd3+ as it offers ideal properties for efficient T1-weighted MR imaging probes such as 5/2 spin quantum number, rapid water-exchange rates, and long electronic relaxation time.3 In addition to that, the positron emitter manganese-52g is of increasing clinical relevance for its use for PET imaging3 as well as for manganese-52g/55 based bimodal PET/MRI agents. To harness the potential of Mn2+ ion for MRI and PET applications, we are working on developing a library of acyclic chelators using fundamental principles of coordination chemistry. Here, I will talk about the design and development of new heptadentate chelators with N5O2 donor set consisting of three pyridine rings and ethanolamine/carboxylate arms. The ligand, H2PyMEA has been characterized by 1H NMR and 13C NMR and its coordination chemistry has been investigated with 3d transition metal ions (Mn2+, Cu2+, Fe2+, and Zn2+) by employing UV-Vis absorbance spectroscopy, 1H NMR, and mass spectroscopy. Ligand synthesis, characterization and preliminary relaxometry studies of the Mn2+-H2PyMEA complex will be discussed along with ongoing synthesis of another ligand, H2PyGly.</p>
<p><br />References<br />(1) Caravan, P.; J. Ellison, J.; J. McMurry, T.; B. Lauffer, R. Chem. Rev. 1999, 99, 2293–2352. (2) Le Fur, M.; Caravan, P. Metallomics, 2019,11, 240–254.<br />(3) Wahsner, J.; Gale, E. M.; Rodríguez-Rodríguez, A.; Caravan, P. Chem. Rev. 2019, 119, 957–1057.</p>