@article {SOUTHCOTT2022111789,
	title = {Bis(amido)bis(oxinate)diamine Ligands for theranostic radiometals},
	journal = {J. Inorg. Biochem.},
	volume = {231},
	year = {2022},
	month = {03/2022},
	pages = {111789. Invited for Special Issue in Memory of Ademir Neves},
	abstract = {<p>With the interest in radiometal-containing diagnostic and therapeutic pharmaceuticals increasing rapidly, appropriate ligands to coordinate completely and stably said radiometals is essential. Reported here are two novel, bis(amido)bis(oxinate)diamine ligands, H2amidohox (2,2\&prime;-(ethane-1,2-diylbis(((8-hydroxyquinolin-2-yl)methyl)azanediyl))diacetamide) and H2amidoC3hox (2,2\&prime;-(propane-1,3-diylbis(((8-hydroxyquinolin-2-yl)methyl)azanediyl))diacetamide), that combine two 8-hydroxyquinoline and amide donor groups and differ by one carbon in their 1,2-ethylenediamine vs. 1,3-diaminopropane backbones, respectively. Both ligands have been thoroughly studied via metal complexation, solution thermodynamics and radiolabeling with three radiometal ions: [nat/64Cu]Cu2+, [nat/111In]In3+, and [nat/203Pb]Pb2+. X-ray crystallography determined the structures of the hexacoordinated Cu2+-ligand complexes, indicating a better fit of Cu2+ to the H2amidohox binding pocket. Concentration dependent radiolabeling with [64Cu]Cu2+ was successfully quantitative as low as 1\&nbsp;μM with H2amidohox and 10\&nbsp;μM with H2amidoC3hox within 5\&nbsp;min at room temperature. However, [64Cu][Cu(amidohox)] maintained higher kinetic inertness against a superoxide dismutase enzyme-challenge assay and ligand challenges compared to the [64Cu][Cu(amidoC3hox)] counterpart. Similarly, H2amidohox had significantly higher radiochemical conversion with both [111In]In3+ (97\% at 1\&nbsp;μM) and [203Pb]Pb2+ (97\% at 100\&nbsp;μM) under mild conditions compared to H2amidoC3hox (76\% with [111In]In3+ at 1\&nbsp;μM and 0\% with [203Pb]Pb2+). By studying non-radioactive and radioactive complexation with both ligands, a comprehensive understanding of the coordination differences between two- and three-carbon diamine backbones is discussed. Overall, the ethylenediamine backbone of H2amidohox proves to be superior in rapid, mild radiolabeling and kinetic inertness towards competing ligands and proteins.</p>},
	keywords = {COORDINATION CHEMISTRY, Theranostics, [In]In [Cu]Cu [Pb]Pb solution thermodynamic studies},
	issn = {0162-0134},
	doi = {https://doi.org/10.1016/j.jinorgbio.2022.111789},
	url = {https://www.sciencedirect.com/science/article/pii/S0162013422000782},
	author = {Lily Southcott and Jennifer N. Whetter and Luke Wharton and Brian O. Patrick and Kristof Zarschler and Manja Kubeil and Holger Stephan and Mar{\'\i}a de Guadalupe Jaraquemada-Pel{\'a}ez and Chris Orvig}
}
