Lanthanide Complexes Formed with the Tri‐ and Tetraacetate Derivatives of Bis(aminomethyl)phosphinic Acid: Equilibrium, Kinetic and NMR Spectroscopic Studies

Abstract

The lanthanide(III) complexes formed with the tri‐ and tetraacetate derivatives of bis(aminomethyl)phosphinic acid, L1 and L2, respectively, have been studied by pH potentiometry, spectrophotometry and 1H and 17O NMR spectroscopy. L1 forms [Ln(L1)]–, [Ln(L1)2]4–, protonated [Ln(HL1)] and Ln(H2L1)]+, and [Ln(L1)(OH)]2– hydroxido complexes. Heptadentate L2 forms [Ln(L2)]2– and protonated [Ln(HL2)]– and [Ln(H2L2)] complexes in solution and it shows a strong propensity to form [Ln2(L2)]+ dinuclear complexes, which has not been observed previously. The stability constants (log KLnL) of the complexes increase in the order [Ln(L1)]– < [Ln(L2)]2– following the order of increasing number of acetate pendants attached to the bis(aminomethyl)phosphinic acid (BAP) backbone. Within the LnIII series, the log KLnL values increase from La3+ to Gd3+ and remain practically constant for the heavier lanthanides. Despite the lower basicity, the ligands that contain a phosphinate group generally form similar (L1) or more stable (L2) Ln3+ complexes than the structurally similar N‐benzylethylenediamine‐N,N′,N′‐triacetic acid (L3) and propylenediamine‐N,N,N′,N′‐tetraacetic acid (L4), respectively. This indicates that the hard phosphinate group may be coordinated to the Ln3+ ions in the complexes, whereas the larger negative charge of the BAP derivatives may also have an extra stabilizing effect. The kinetic inertness of [Ln(L1)] and [Ln(L2)] is lower than that of similar [Ln(EDTA)]– (EDTA = ethylenediamine‐N,N,N′,N′‐tetraacetic acid), but the rate constants that characterize the dissociation of [Ln(L2)]2– are at least two orders of magnitude lower than those obtained for [Ln(L4)]–. Variable‐temperature 17O transverse and longitudinal relaxation rates and NMR spectroscopic chemical shifts have been measured to assess the water exchange and rotational dynamics of [Gd(L2)]. The chemical shifts evidenced monohydration of the complex. The water exchange rate, kex298 = (2.7 ± 0.4) × 107 s–1 is about ten times higher than that of [Ln(DTPA)]2– (DTPA = diethylenetriamine‐N,N,N′,N″,N″‐pentaacetic acid). The rotational correlation time, τRO298 = 270 ± 30 ps, is long considering the small size of the chelate, which points to aggregation in aqueous solution, in accordance with the high value of the proton relaxivity measured.

Nyíltláncú és makrociklusos aminokarboxilát ligandumok szintézise és fémkomplexeik vizsgálata: koordinációs kémia az orvosi képalkotás szolgálatában

“…foszfinátcsoport (BIMP), metilhidrazin-csoportokat tartalmazó piridin egység (HYD), éteres oxigén (OBETA), geminális helyzetû metilcsoportok (DMPDTA), cisz-izoforon-diamin (cisz-IPDTA)). [17][18][19][20][21] Ezáltal rálátásunk van az említett csoportok és a képzõdõ komplexek fizikai-kémiai sajátságai közötti összefüggésekre, amik igen hasznosak új komplexképzõk (akár makrociklusos ligandumok) tervezésekor és elõállításakor.…”

“…a megfelelõ [Ln(EDTA)] --komplexhez képest kisebb stabilitás a jellemzõ, és megjelennek a kis stabilitású (log K=3, [0][1][2][3]5) kétmagvú komplexek is). 19 Az [Ln(BIMP)] 2--komplex savkatalizált bomlására jellemzõ sebességi állandó kisebb, ugyanakkor a fémion közvetlen támadásával lejátszódó reakcióra jellemzõ sebességi együttható nagyobb, mint azt a megfelelõ [Ln(EDTA)] --komplex esetében tapasztalták, de összességében a Cu 2+ -ionnal lejátszódó cserereakciók nagyon gyorsan játszódnak le, és csak a "stopped-flow" technikával követhetõk. 19 Hasonló következtetésekre jutottunk a DO3A-PIC komplexképzõ két vegyértékû és Ln 3+ -ionokkal képzõdõ komplexei vizsgálata során is: a képzõdõ komplexek stabilitása meghaladta az DO3A ligandum Ln 3+ -komplexei esetében tapasztaltat, ami a pikolinátcsoport koordinációjára utal.…”

17o NMR

“…The solution structure, stability and dynamics of several lanthanide complexes have been extensively studied using high resolution 17 O relaxation. [190][191][192] Complexes with other metal ions such as Mn(II) have also been proposed and characterized. 193,194 The design of new complexes has relied also on DFT calculations of chemical shifts and of hyperfine coupling constants, which are responsible for the scalar contribution to the oxygen relaxation rates.…”

Strategies for Optimizing Water-Exchange Rates of Lanthanide-Based Contrast Agents for Magnetic Resonance Imaging

“…Representative Gd III -containing complexes that undergo water exchange via dissociative ( 1 and 2 ), dissociative interchange ( 9 ), associative ( 3 , 4 , 7 , 8 , 10 , and 11 ), and associative interchange ( 5 and 6 ) processes [28,29,30,31,32,33,34,35,36,37]. …”

“…The water-exchange rates of hydroxypyridonate (HOPO)-based complexes 3 – 5 , reported by Raymond and co-workers, are closer to the optimum water-exchange rate (10 8 s −1 ) of T 1 -shortening agents at 1.5 T than those of clinically approved polyaminopolycarboxylate-based complexes 1 and 2 [28,29,30,31]. Similar to HOPO-based complexes, the fast water-exchange rates observed for polyaminopolycarboxylate-based complexes 6 and 7 and phosphonate-containing complex 8 can be attributed in part to an associative exchange mechanism [32,33,34].…”