@article { ISI:000414243600021,
	title = {H(4)octapa: synthesis, solution equilibria and complexes with useful radiopharmaceutical metal ions},
	journal = {Dalton Trans.},
	volume = {46},
	number = {42},
	year = {2017},
	month = {NOV 14},
	pages = {14647-14658},
	abstract = {<p>H(4)octapa is an extremely versatile acyclic chelator for a wide variety of medicinally relevant metal ions, forming complexes of both high thermodynamic and kinetic stability. This work reports a significantly simplified 3 step high yield straightforward synthesis of H(4)octapa directly from EDDA. Crystals of the octa-protonated form of the ligand {[}H(8)octapa](4+) as its tetrachloride salt, and of the mixed lanthanumsodium salt of {[}La(octapa)]-were isolated and characterized by X-ray diffraction. All eight protonation constants for the ligand were determined through combined potentiometric-spectrophotometric titrations and in batch experiments using UV spectrophotometry and H-1 NMR spectroscopy. Synthesis, characterisation and solution equilibria studies are presented for complexes {[}Ln(octapa)]-(Ln = lanthanide element) with Sm(III), Dy(III), and Yb(III) (each of which have radiopharmaceutical applications). Complex formation equilibria studies provided evidence of Ln(Hoctapa), {[}Ln(octapa)]-and {[}Ln(octapa)(OH)](2-)species in solution, and their stability constants were evaluated by pH-potentiometric competition titrations using {[}ttha](6-) as a competing ligand, and by UV-vis spectrophotometric measurements. The high stability constants of the {[}Ln(octapa)]-complexes with Sm(III), Dy(III), and Yb(III) (log K-SmL = 20.10(2), log K-DyL = 20.14(3) and log K-YbL = 19.90(1)) are similar to the published values for other lanthanides and consequently these initial investigations confirm H(4)octapa as a valuable ligand for Sm(III), Dy(III), Yb(III) and other Ln for application in diagnostic and therapeutic nuclear medicine.</p>},
	issn = {1477-9226},
	doi = {10.1039/c7dt02343j},
	author = {Jaraquemada-Pelaez, Maria de Guadalupe and Wang, Xiaozhu and Clough, Thomas J. and Cao, Yang and Choudhary, Neha and Emler, Kirsten and Patrick, Brian O. and Orvig, Chris}
}
