Acknowledgments
3.3 Rare Earth Complexes with Polyaminopolycarboxylic Acids
3.3.2 Structural Chemistry of Rare Earth Complexes with Polyaminopolycarboxylic Acids
The synthesis is normally carried out by refluxing an aqueous mixture of polyaminopolycar- boxylic acid and a selected rare earth oxide in a molar ratio of RE : L=1 : 1. The resulting solution can be neutralized to pH 5–6 by adding a dilute solution of NaOH, KOH, NH3·H2O, NaHCO3, or NaHCO3. After filtration, the complex can be crystallized by evaporation or with the addition of EtOH. The rare earth oxide can be replaced by a rare earth carbonate or other soluble salts, such as chlorides, nitrates, perchlorates, or acetates [104]. The synthesis can also be done under hydrothermal conditions [105], which leads to complexes of polymeric structure, while most of the complexes obtained under ambient conditions are monomeric (see Section 3.3.2 for examples).
3.3.2 Structural Chemistry of Rare Earth Complexes with Polyaminopolycarboxylic Acids
Polyaminopolycarboxylic acids, with EDTA, DTPA, and DOTA as the representatives, are among the ligands capable of forming the most stables complexes with RE(III), due to the affinity of RE(III) for N and O donors and the chelating ability of the ligands. In the structures, the RE(III) ions are coordinated by ligands through monodentate carboxylate (η1) groups and the nitrogen atoms, and the coordination numbers are usually nine for light rare earth, and eight for the heavy ones.
3.3.2.1 Structures of Rare Earth Complexes with EDTA, DTPA, and TTHA
As a hexadentate ligand, H4EDTAcoordinates to RE(III) through its two nitrogen atoms, and the four oxygen atoms from its four carboxylates, that is, (N2O4). Most of the RE–H4EDTA com- plexes are mononuclear with a formula M[RE(H2O)n(EDTA)]·mH2O (M=Na+, K+, Cs+, NH+4, and [C(NH2)3]+;n=2 or 3;m=0–5), CN=8 or 9. The structures and the coordination modes of the complexes seem to be dominated by two factors, that is, the size of the RE(III) and the property of the counter cation [104]. Complexes (I) Na[RE(H2O)3(EDTA)]·5H2O (RE=La–Er, Y) and (II) K[RE(H2O)3(EDTA)]·5H2O (RE=La–Ho) are isostructural and isomorphous with an orthorhombic space groupFdd2, where the RE(III) ion is coordinated by the hexadentate EDTA and three water molecules, CN=9 (Figure 3.23). With Cs+ as the counter cation, two series complexes were obtained: (III) Cs[RE(H2O)3(EDTA)]·4H2O (RE=Sm and Gd) and (IV) Cs[RE(H2O)2(EDTA)]·3H2O (RE=Dy and Ho). The coordina- tion modes of (III) and (IV) are very similar to (I) and (II) with EDTA in a hexadentate mode (N2O4), except that (IV) has only two aqua ligands, CN=8.
Er1
Figure 3.23 The structure of monomeric complex [Er(H2O)3(EDTA)]−[Er, black (large ball); O, grey;
N, black (small balls); C, white; H, omitted)]. (Redrawn from the CIF file of N. Sakagamiet al., “Crystal structures and stereochemical properties of lanthanide(III) complexes with ethylenediamine-N, N, N,N- tetraacetate,’’Inorganica Chimica Acta,288(1), 7–16, 1999 [104].)
La1
Figure 3.24 The structure polymeric [La(H2O)(EDTA)]n−n [Nd, black (large balls); O, grey; N, black (small balls); C, white; H, omitted)]. (Redrawn from the CIF file of N. Sakagami et al., “Crystal structures and stereochemical properties of lanthanide(III) complexes with ethylenediamine-N, N, N,N- tetraacetate,’’Inorganica Chimica Acta,288(1), 7–16, 1999 [104].)
While the mononuclear complexes (I)–(IV) were crystallized under ambient conditions, two polymeric complexes, [RE(H2O)(HEDTA)]n (RE=La and Nd) were obtained by hydro(solvo)thermal synthesis. In the structure, the HEDTA3+ligand is octadentate with its two nitrogen atoms and four carboxylato oxygen atoms coordinating the central RE(III), and the remaining oxygen atom of theµ2-η1η1carboxylate coordinating its neighboring RE(III) along theadirection to form a 1D-chain. The chain is then linked to another chain through the oxygen atoms of theµ2-η1η1(O, O) carboxylate groups, affording a double-chained structure (Figure 3.24) [105].
(b) (a)
Dy1 Dy1
Figure 3.25 The structure of (a) [Dy(H2O)(DTPA)]− and (b) [Dy2(DTPA)2]4− [Dy, black (large balls); O, grey; N, black (small balls); C, white; H, omitted)]. (Redrawn from the CIF files of J. Wang et al., “Syntheses and structural determinations of the nine-coordinate rare earth metal:
Na4[DyIII(dtpa)(H2O)]2·16H2O, Na[DyIII(edta)(H2O)3]·3.25H2O and Na3[DyIII(nta)2(H2O)]·5.5H2O,’’
Journal of Coordination Chemistry, 60(20), 2221–2241, 2007 [106]; and Y. Inomata, T. Sunakawa and F.S. Howell, “The syntheses of lanthanide metal complexes with diethylenetriamine-N, N, N, N, N-pentaacetic acid and the comparison of their crystal structures,’’Journal of Molecular Structure,648 (1–2), 81–88, 2007 [107].)
H5DTPA, diethylenetriaminepentacarboxylic acid, is an octadentate ligand (N3O5), and can form mononuclear and dinuclear complexes with RE(III). Similar to their EDTA analogs, the structures of the RE–DTPA complexes also vary on changing the counter cations. For example, M2[Dy(H2O)(DTPA)]·nH2O (M=Na+, n=8; M=K+, n=5) are mononuclear with the Dy(III) coordinated by three nitrogen atoms and five monodentate carboxylates, and one aqua ligand, CN=9 (Figure 3.25a) [106], while M4[Dy2(DTPA)2]·nH2O (M=Cs+, n=13; M=NH+4, n=8) are dinuclear with the two Dy(DTPA)2− joined through the two µ2-η1η1carboxylate groups, CN=9 (Figure 3.25b) [107].
H6TTHA, triethylenetetraaminehexaacetic acid, is a decadentate ligand with four nitro- gen and six oxygen donors (N4O6). In its complexes with RE(III), the ten donor atoms can coordinate one central atom collectively or partially, which keeps water or other solvent molecules from entering the coordination sphere. The structures of the complexes reported so far are of four types, that is, (a) [RE(TTHA)]3+or [RE(HTTHA)]2+(RE=La–Nd, CN=10);
(b) [RE(TTHA)]3+ or [RE(HTTHA)]2+ (RE=Eu–Yb, CN=9); (c) [RE2(HTTHA)2]4+ (RE=Sm–Tb, Y, CN=9); and (d) [RE2(H2O)5(TTHA)]n(RE=Tm). Here the complexes of TTHA6− and HTTHA5− are placed in the same groups because they have very simi- lar coordination modes, as exemplified by the ten-coordination(N4O6) in [Nd(TTHA)]3+ and [Nd(HTTHA)]2+ [108], and the nine-coordination (N4O5) in [Er(TTHA)]3+ or [Er(HTTHA)]2+[109, 110].
Apparently, both large and small RE(III) can form 1 : 1 mononuclear anionic complexes, [RE(TTHA)]3−or [RE(HTTHA)]2−, however with different coordination modes. The struc- tures of [Nd(TTHA)]3+and [Er(TTHA)]3+are shown in Figure 3.26a and b, respectively. The larger Nd(III) is coordinated by N4O6, CN=10, whereas the smaller Er(III) is coordinated by N4O5, CN=9. The structure of a dinuclear complex, [Gd2(HTTHA)2]4+, is shown in Figure 3.26c, wherein each of the Gd(III) is coordinated by N3O4O2(O=the oxygen atom
(a) Nd1
Eu1
Eu2
Er1
(b) (c)
Figure 3.26 The structure of (a) [Nd(TTHA)]3+; (b) [Er(TTHA)]3+; and (c) polymer [Gd2(DTPA)2]4−
[RE, black (large balls); O, grey; N, black (small balls); C, white; H, omitted]. (Redrawn from the CIF files of J. Wanget al., “Syntheses and structural determinations of the nine-coordinate rare earth metal:
Na4[DyIII(dtpa)(H2O)]2·16H2O, Na[DyIII(edta)(H2O)3]·3.25H2O and Na3[DyIII(nta)2(H2O)]·5.5H2O,’’
Journal of Coordination Chemistry, 60(20), 2221–2241, 2007 [106]; and Y. Inomata, T. Sunakawa and F.S. Howell, “The syntheses of lanthanide metal complexes with diethylenetriamine-N, N, N, N, N-pentaacetic acid and the comparison of their crystal structures,’’Journal of Molecular Structure,648 (1–2), 81–88, 2007 [107].)
from a different ligand), CN=9. [Tm2(H2O)5(TTHA)]n is a coordination polymer. There are two independent metals in the structure, Tm1 and Tm2. Tm1 is coordinated by N2O3O1 and two aqua ligands, CN=8, while Tm2 is coordinated by N2O3and three aqua ligands, CN=8 [111].
3.3.2.2 Structures of Rare Earth Complexes with DOTA, HP-DO3A, and BT-DO3A The high magnetic moment (7.9 BM) and the long electron-spin relaxation time (10−8−10−9s) makes Gd(III) an ideal candidate for producing MRI contrast agents [102]. However, owing to the toxicity of free Gd3+, the metal ions have to be encapsulated in the form of kinetically and thermodynamically stable complexes if they are to be applied in living diagnoses. The 1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (H4DOTA) was the first ligand, in addition to DTPA and its derivatives, to form complexes with RE(III) with high stability (about 10 orders of magnitude larger than the corresponding stability constant of EDTA) with slow dissociation kinetics [112]. Since then, extensive research has been done to develop better macrocyclic polyaminopolycarboxylic acid ligands. So far, at least three Gd(III) complexes of this family have been approved for clinical uses. They are (meglumine) [Gd(DOTA)(H2O)] (Dotarem®, gadoterate meglumine), [Gd(HP-DO3A)(H2O)] (ProHance®), and [Gd(BT-DO3A)(H2O)]
(Gadovist®), where HP-DO3A=10-(2-hydroxypropy1)-1,4,7,10-tetraazacyclododecane- 1,4,7-triacetate, BT-DO3A=10-(1-(hydroxymethyl)-2,3-dihydroxypropyl)-1,4,7,10-tetraaza- cyclododecane-1,4,7-triacetate.
The structures of [Gd(DOTA)(H2O)]−and [Gd2(BT-DO3A)2] are shown in Figure 3.27. In [Gd(DOTA)(H2O)]−, the nine-coordinated Gd(III) in theC4symmetric anion is coordinated by the four nitrogen atoms of the aza crown, four oxygen atoms from the carboxylates, and the ninth coordination site is occupied by an aqua ligand. The coordination geometry can be best described as a distorted monocapped square antiprism, with the four nitrogens forming the basal plane and four oxygens as the upper plane, with the water molecule located in
(a) Gd1
Gd1
(b)
Figure 3.27 The structure of (a) [Gd(DOTA)]− and (b) [Gd2(BT-DO3A)2] [RE, black (large balls);
O, grey; N, black (small balls); C, white; H, omitted)]. (Redrawn from the CIF files of C.A. Chang et al., “Synthesis, characterization, and crystal structures of M(DO3A) (M=iron, gadolinium) and Na[M(DOTA)] (M=Fe, Y, Gd),’’Inorganic Chemistry,32(16), 3501–3508, 1993 [113]; and J. Platzek et al., “Synthesis and structure of a new macrocyclic polyhydroxylated gadolinium chelate used as a contrast agent for magnetic resonance imaging,’’Inorganic Chemistry,36(26), 6086–6093, 1997 [115].)
the capping position [113]. The structure of [Gd(HP-DO3A)(H2O)] is very similar to that of [Gd(DOTA)(H2O)]−, where the four vertex oxygens are from the three carboxylates and the hydroxyl group [114].
The dinuclear complex, [Gd2(BT-DO3A)2], is centrosymmetrical, and only half of the molecule is unique. Each of the two Gd(III) ions is thus coordinated by N4O4of one ligand, and then bridged to the other half of the molecule through twoµ2-η1η1carboxylate groups. The two Gd(III) ions each keep the distorted monocapped square antiprism coordination geometry, but with the carboxylato oxygen from the other ligand sitting in the capping position. It remains unclear why [Gd2(BT-DO3A)2] is dimeric while the other two complexes are mononuclear in the solid state, when experiments have shown that Gd-(BT-DO3A) is a monomer in aqueous solution [115].