Synthesis of charged and uncharged complexes of gadolinium and yttrium with cyclic polyazaphosphinic acid ligands for in vivo applications

Abstract
The synthesis of 18 new macrocyclic complexing agents incorporating phosphinic acid (and carboxylic acid) groups is reported, based on the 1,4,7,10-tetraazacyclododecane ring. Through selective functionalisation of one ring nitrogen or by changing the nature of the P-substituent, anionic, neutral and cationic complexes of yttrium and gadolinium may be prepared of varying lipophilicity. Diamagnetic complexes have been characterised by 1H, 31P and 89Y NMR spectroscopy, and the rate of uptake of 90Y of selected ligands compared. The kinetics of dissociation of nine gadolinium complexes has been measured in the pH range 1–2 using 153Gd-labelled complexes. Charge-neutral complexes dissociate more slowly than their anionic analogues, and the phosphinate complexes, although slightly less stable than their carboxylate analogues, are nevertheless sufficiently kinetically inert for in vivo applications.

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