Trapping of Gd(III) Ions by Keplerate Polyanionic Nanocapsules in Water: A ¹H Fast Field Cycling NMR Relaxometry Study

Abstract

Polyoxomolybdates of the type [{MoVI­MoVI 5­O21­(H2O)6}12{MoV 2­O4(L)}30](12+30n)–, also referred to as keplerates (Kps), are polyanionic nanocapsules bearing 20 {Mo9O9} pores connected to a central cavity by 20 channels. In solution, they can entrap cations in different sites of their porous structure (in the internal cavity, in the pores, or on the capsule surface) in equilibrium with cations free in solution. The porosity of Kps was previously exploited to prepare nanostructured potential contrast agents through the self-assembly of KpOAc or KpHPO4 (i.e., Kp with L = acetate or hydrogen phosphate) macroanions and Gd­(III) cations in water, accompanied by stabilization with F-127 Pluronics. The strongly enhanced water proton relaxivity observed at 20 MHz was postulated to derive from the trapping of Gd­(III) aqua ions by the nanocapsules. In the present work, 1H fast field cycling NMR relaxometry allowed this hypothesis to be verified on aqueous suspensions containing either KpOAc or KpHPO4 and Gd­(III) in different proportions. The analysis of 1H longitudinal relaxivity versus the Larmor frequency on the basis of the theory for paramagnetic relaxation enhancement gave a detailed description of the state of [Gd­(H2O)8]3+ ions in these systems in dependence on the different capsule charge and Gd to Kp molar ratios. [Gd­(H2O)8]3+ ions were found to be trapped in the KpOAc capsules, most probably located in up to 11 pores, with no evidence for free ions. On the other hand, equilibria between trapped and free [Gd­(H2O)8]3+ ions established in the suspensions containing KpHPO4 and a maximum of 3 to 4 ions per capsule were found. A major role of the NH4 + counterion was considered to rationalize the different behavior of the studied Kps.

Physicochemical and biochemical properties of the Keplerate-type nanocluster polyoxomolybdates as promising components for biomedical use

“…In addition, it was shown that simpler molybdenum-containing POMs can be used in chemotherapy [115,116]. On the other hand, the initially predicted possibility of the formation of POM conjugates with bioactive substances, drugs, and metal cations using intra-and extrasphere interactions, the possibility of their transport (including iontophoretic) in the body, adds relevance to the studies of POM in the field of targeted drug delivery and diagnostics [117][118][119][120][121][122][123][124][125][126][127][128][129][130][131]. These prospects may relate, inter alia, to immunomodulatory and antiviral agents.…”

“…The hydrophobized POMs acquire an ability to more actively interact with molecules of nonpolar substances and adsorb them [110]. There appears a possibility of formation of ionic associates based on POM and cations of metals (alkaline earths, rare earths, transition metals, including luminescent labels and magnetic resonance imaging (MRI) tags [19,[121][122][123]), and of cationic surfactants. Weaker, e.g., hydrogen, bonds also actively participate in the interaction of organic compounds with POMs [182].…”

NMR Relaxivities of Paramagnetic Lanthanide-Containing Polyoxometalates

“…In this quest, one of the approaches we took was to synthesize and analyze the NMR relaxometry of ultrahigh-spin polyoxometalates (POM)-based heterometallic clusters in aqueous solutions [22]. The usage of Ln-POM nanocomposites as host/guest assemblies for contrast agents has also been reported by other groups [26][27][28]. POMs, as anionic metal oxide clusters, bear many properties that make them attractive for applications in various fields such as catalysis, magnetism, imaging, optics, medicine and also have interesting electrochemical properties [29][30][31][32][33][34].…”

NMR Relaxivities of Paramagnetic, Ultra‐High Spin Heterometallic Clusters within Polyoxometalate Matrix as a Function of Solvent and Metal Ion

“…[5,6,20,21] Polyoxometalate (POM) clusters were used as host assemblies for contrast agents. [22,23] We explored [Ln 30 Co 8 Ge 12 W 108 O 408 (OH) 42 (OH 2 ) 30 ] 56À abbreviated as {Ln 30 Co 8 }, these POMs were also studied with Ln2[Gd III , Dy III , Eu III , Y III ]. [24] The main solvent was water as a 10 : 90 H 2 O : D 2 O mix.…”

“…Other examples are the heterometallic high‐spin coordination clusters [Fe 10 Ln 10 (Me‐tea) 10 (Me‐teaH) 10 (NO 3 ) 10 ] with the lanthanides (Ln) Y III , Gd III , Tb III , Dy III , Er III , and Tm III , abbreviated as {Fe 10 Ln 10 } [5,6,20,21] . Polyoxometalate (POM) clusters were used as host assemblies for contrast agents [22,23] . We explored [Ln 30 Co 8 Ge 12 W 108 O 408 (OH) 42 (OH 2 ) 30 ] 56− abbreviated as {Ln 30 Co 8 }, these POMs were also studied with Ln∈[Gd III , Dy III , Eu III , Y III ] [24] .…”