Chemical and biological evaluation of 153Sm and 166Ho complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid monoethylester) (H4dotpOEt)

Lanthanide(III) Complexes of 4,10‐Bis(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid (trans‐H6do2a2p) in Solution and in the Solid State: Structural Studies Along the Series

“…To correlate ligand protonation sites found in the solid state with a protonation sequence in aqueous solution, the dependence of 31 P and 1 H chemical shifts of the N-CH 2 -PO(OH) 2 moiety on the pH in the range 1.9 < pH < 13.8 was followed ( Figure S1 in the Supporting Information). From this dependence, values of six stepwise protonation constants (log K 1 to log K 6 : 13.17, 12.22, 6.47, 6.44, 3.17, 2.75, respectively) were reliably determined and they are in a good agreement with those determined by potentiometry (see below).…”

“…Similar thermodynamically stable species protonated on the ring nitrogen atoms have been suggested for analogous complexes of H 5 do3ap. [33,36] The stepwise protonation constants of the preformed [Ln(L)] 3À complexes (Ln = Ce, Pr, Nd, Sm, Eu, Tb, Dy, Er and Yb) were independently determined from the depen-A C H T U N G T R E N N U N G dence of the 31 P NMR spectroscopic shift of the complexes on pH (pH range 1.2-13.5). Such determination is possible, as all the lanthanideA C H T U N G T R E N N U N G (III) complexes are stable in a very acidic solution (pH < 2) for up to one week (evidenced by the absence of the free ligand signal in the 31 P NMR spectra).…”

“…[33,36] The stepwise protonation constants of the preformed [Ln(L)] 3À complexes (Ln = Ce, Pr, Nd, Sm, Eu, Tb, Dy, Er and Yb) were independently determined from the depen-A C H T U N G T R E N N U N G dence of the 31 P NMR spectroscopic shift of the complexes on pH (pH range 1.2-13.5). Such determination is possible, as all the lanthanideA C H T U N G T R E N N U N G (III) complexes are stable in a very acidic solution (pH < 2) for up to one week (evidenced by the absence of the free ligand signal in the 31 P NMR spectra). For all the complexes studied, only a single 31 P NMR spectroscopic resonance was observed over the entire pH range, thereby indicating that the protonated and deprotonated species were in a fast exchange.…”

“…The dota complexes have no significant preference for any organ, but the dotp complexes and other poly(phosphonic acid) ligands exhibit a high affinity for calcified tissues. [29,30] However, the bone affinity is specific to the complexes of polyphosphonic acids, as complexes of other phosphorus-containing ligands, such as phosphinic acids [26] or phosphonic monoesters, [28,31] have no bone localisation. The complexes of monophosphorus acid dota derivatives again show biodistributions similar to those of dota complexes.…”

“…The complexes of monophosphorus acid dota derivatives again show biodistributions similar to those of dota complexes. [32,33] Following our previous work on tetraazamacrocycles that bear phosphonate and/or acetate pendant arms, [13][14][15]25,29,[30][31][32][33][34] we have recently reported on the synthesis and characterisation of 1,4,7,10-tetraazacyclododecane-1,7-bis(acetic acid)-4,10-bis(methylenephosphonic acid) (trans-H 6 do2a2p, H 6 L; Scheme 1), on its interaction with 153 …”