Lanthanide complexes kinetic inertness

For the application of lanthanide complexes in medical diagnosis and therapy, a general requirement is that the ion Ln3+ and the ligand should remain associated while the complex is in the body, i. e. their dissociation should be minimal, since the free ligand and Ln3+ are toxic. For the dissociation to be negligible, the complexes must be kinetically inert under physiological conditions. Since the complexation properties of the lanthanide ions and Y3+ are quite similar, it is of interest to compare the results obtained as concerns the kinetic behavior of Gd3+ complexes with those known for the complexes of other lanthanides and Y3+. 

DOTA is of particular interest as a BFC for radiolabeling of small BMs with yttrium and lanthanide isotopes. The macrocyclic framework is well organized so that it forms yttrium and indium complexes with high thermodynamic stability and kinetic inertness. The pXa values of the carboxylic groups are in the range 2-5. Lower pKa values result in less competition from protons, high stability of the metal complex, and minimum acid-assisted demetallation, even... 

The most thermodynamically stable and kinetically inert complexes of the trivalent lanthanides are those of the ligand DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) (42, 43). Our search for lanthanide macrocyclic complexes that would remain intact for longer time periods led us to examine derivatives of DOTA. There are two potential difficulties with the use of DOTA complexes of the trivalent lanthanides for RNA cleavage. First, the overall negative charge on the complex is not conducive to anion binding for example, Gd(DOTA)-does not bind hydroxide well (44). Second, DOTA complexes of the middle lanthanides Eu(III) and Gd(III) have only one available coordination site for catalysis. The previous lanthanide complexes that we used, e.g., Eu(L1)3+, were good catalysts and had at least two available coordination sites. 

In this chapter, we deal with Gd " " complexes applied as Ti agents in MRI. In the first part of the chapter, we discuss the different relaxation mechanisms and how supramolecular approaches can be used to optimize the efficacy of Gd " "-based contrast agents. Nontoxicity is of prime importance for in vivo nse of metal chelates therefore, we also shortly assess some aspects related to their thermodynamic stability and kinetic inertness. We include a short infioduction to CEST (chemical exchange saturation transfer) agents, a new class of lanthanide-based MRI probes, and discnss how supramolecular systems, particularly liposomes, can be beneficial to decrease the sensitivity limit of CEST detection. In the second part of the chapter. 

Because of ligand-field factors, certain transition metal ions, notably Cr + and Co +, almost exclusively exhibit a coordination number of six in their complexes. The kinetically inert nature of Cr and Co complexes, dramatically different from that of the extremely labile lanthanide solvento ions, facilitates the isolation of isomeric species and was crucial in enabling Alfred Werner to formulate the fundamental tenets of coordination chemistry. For simple lanthanide ion complexes, their lability and the lack of a marked sensitivity of their visually observed colors to the nature of the coordination sphere renders Wernerian procedures inapplicable, such that the establishment of high and variable coordination numbers as a characteristic of lanthanide ions has depended largely on modem spectroscopic and crystallographic measurements. 

The competition titrations presented in the previous paragraph are interesting to establish the stability of a given complex compared to another. They are also useful tools to ensure the kinetic inertness of the complex over time. Any decrease of intensity would iudicate a modificatiou of the coordination sphere. On release of any ligand, the lanthanide ion would be exposed to water molecules in its vicinity, thus causing a decay of its luminescence intensity. Nevertheless, in snch long experiments, one has to ensure that the lamp is stable over time, that no evaporation of the solution or precipitation takes place over time, etc. 

Among the lanthanide macrocyclic complexes [1], the (2.2.1) cryptates (where (2.2.1) stands for pentaoxa-4,7,13,16,21-diaza-l,10-bicyclo[8.8.5]tricosane) are of special interest because they display several unusual properties such as high thermodynamic stability [2-3], kinetic inertness in water [4] and stabilization of the +2 oxidation state [4]. Up to the present, studies of the lanthanide (2.2.1) cryptates have been restricted to solution studies and no crystallographic investigation has yet been reported. The present paper is part of our efforts directed at elucidating the solid-state and solution conformation of these complexes. We report herein the... 

Following some detailed studies of kinetically inert complexes of yttrium - for targeted radiotherapy - and of gadolinium, for use as contrast agents in magnetic resonance imaging, we were attracted by the chemical versatility of single component, luminescent lanthanide complexes. The monoanionic tetracarboxylate and... 

Rare earth cryptates (table 5) are more stable than coronates and are highly kinetically inert towards dissociation in aqueous solutions. They can therefore be studied in water, but hydrolysis hinders their synthesis in this solvent. On the contrary, the preparation of unsolvated 1 1 complexes requires anhydrous conditions (Gansow and Triplett, 1981). The hydrated lanthanide salt solutions in... 

Given the kinetic inertness of low spin tf transition metal complexes, especially with low spin metal ions, our focus wiU be mainly on the kinetic stability of lanthanide chelates and their derivatives described in this chapter. 

The solid phase lends itself to the preparation of lanthanide containing heterometallic materials. In this case the choice of lanthanide complexes is ample since it is not only limited to kinetically inert complexes. The solid state acts as kinetic trap so that building blocks formed by p-diketonates are widely applied for designing multimetallic architectures such as the one represented in Fig. 9.3 [17—19]. 

All of the kinetic studies of substitution and related reactions of inert metal complexes with co-ordination numbers greater than six reported in the present volume are concerned with eight-co-ordinate complexes. The relevant references are collected together in Table 29. It is likely that the co-ordination numbers of the lanthanide and actinide cations whose complexes are mentioned in Sections 7 and 8 of this chapter are greater than six, but as knowledge of the precise co-ordination number in each case is lacking, these are not included in Table 29. 

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