[en] The discriminate bonding of metal ions is a challenge to the synthetic chemist and a phenomenon of considerable practical importance.1 An important feature of many technical applications is the specific or preferential binding of a single metal ion in the presence of many metals. Examples range from large-volume uses (e.g. ferric EDTA as a plant food, calcium complexing agents as water softeners or anticaking formulations) to very high technology applications (technetium complexation in radiopharmaceuticals, synthetic metalloenzymes). We are interested in efficient and discriminate binding of actinides for waste stream remediation. Actinides represent a major and long-lived contaminant in nuclear waste. While the separation of actinides from other radioactive components of waste, such as Sr and Cs, is relatively well established, the separation of actinides from each other and in complex solutions (e.g. those found in tank wastes) is not as well resolved. The challenge of designing metal-specific (actinide) ligands is facilitated by examples from nature. Bacteria synthesize Fe(III)-specific ligands, called siderophores, to sequester Fe(III) from the environment and return it to the cell. The similarities between Fe(III) and Pu(IV) (their charge-to-size ratios and acidity), make the siderophores prototypical for designing actinide-specific ligands. The chelating groups present in siderophores are usually hydroxamic acids and catecholamides. We have developed derivatives of these natural products which have improved properties. The catechol derivatives are the 2,3-dihydroxyterephthalamides (TAMs), and 3,4-dihydroxysulfonamides (SFAMs), and the hydroxamic acid derivatives are three isomers of hydroxypyridinones, 1,2- HOPO, 3,2-HOPO, and 3,4-HOPO. All of these ligands are attached to molecular backbones by amides and a very important feature of HOPO and CAM ligands is a strong hydrogen bonds formed between the amide proton and the adjacent phenolic oxygen in the metal complex, thereby enhancing the stability (Figure 1)

[en] Seven water-soluble, tetradentate bis(3-hydroxy-N-methyl-pyridin-2-one) (bis-Me-3,2-HOPO) ligands were synthesized that vary only in linker geometry and rigidity. Solution phase thermodynamic measurements were conducted between pH 1.6 and pH 9.0 to determine the effects of these variations on proton and uranyl cation affinity. Proton affinity decreases by introduction of the solubilizing triethylene glycol group as compared to un-substituted reference ligands. Uranyl affinity was found to follow no discernable trends with incremental geometric modification. The butyl-linked 4Li-Me-3,2-HOPO ligand exhibited the highest uranyl affinity, consistent with prior in vivo decorporation results. Of the rigidly-linked ligands, the o-phenylene linker imparted the best uranyl affinity to the bis-Me-3,2-HOPO ligand platform.

[en] Synthetic supramolecular host assemblies can impart unique reactivity to encapsulated guest molecules. Synthetic host molecules have been developed to carry out complex reactions within their cavities, despite the fact that they lack the type of specifically tailored functional groups normally located in the analogous active sites of enzymes. Over the past decade, the Raymond group has developed a series of self-assembled supramolecules and the Bergman group has developed and studied a number of catalytic transformations. In this Account, we detail recent collaborative work between these two groups, focusing on chemical catalysis stemming from the encapsulation of protonated guests and expanding to acid catalysis in basic solution. We initially investigated the ability of a water-soluble, self-assembled supramolecular host molecule to encapsulate protonated guests in its hydrophobic core. Our study of encapsulated protonated amines revealed rich host-guest chemistry. We established that self-exchange (that is, in-out guest movement) rates of protonated amines were dependent on the steric bulk of the amine rather than its basicity. The host molecule has purely rotational tetrahedral (T) symmetry, so guests with geminal N-methyl groups (and their attendant mirror plane) were effectively desymmetrized; this allowed for the observation and quantification of the barriers for nitrogen inversion followed by bond rotation. Furthermore, small nitrogen heterocycles, such as N-alkylaziridines, N-alkylazetidines, and N-alkylpyrrolidines, were found to be encapsulated as proton-bound homodimers or homotrimers. We further investigated the thermodynamic stabilization of protonated amines, showing that encapsulation makes the amines more basic in the cavity. Encapsulation raises the effective basicity of protonated amines by up to 4.5 pK_a units, a difference almost as large as that between the moderate and strong bases carbonate and hydroxide. The thermodynamic stabilization of protonated guests was translated into chemical catalysis by taking advantage of the potential for accelerating reactions that take place via positively charged transition states, which could be potentially stabilized by encapsulation. Orthoformates, generally stable in neutral or basic solution, were found to be suitable substrates for catalytic hydrolysis by the assembly. Orthoformates small enough to undergo encapsulation were readily hydrolyzed by the assembly in basic solution, with rate acceleration factors up to 3900 compared with those of the corresponding uncatalyzed reactions. Furthering the analogy to enzymes that obey Michaelis-Menten kinetics, we observed competitive inhibition with the inhibitor NPr₄⁺, thereby confirming that the interior cavity of the assembly was the active site for catalysis. Mechanistic studies revealed that the assembly is required for catalysis and that the rate-limiting step of the reaction involves proton transfer from hydronium to the encapsulated substrate. Encapsulation in the assembly changes the orthoformate hydrolysis from an A-1 mechanism (in which decomposition of the protonated substrate is the rate-limiting step) to an A-S_E2 mechanism (in which proton transfer is the rate-limiting step). The study of hydrolysis in the assembly was next extended to acetals, which were also catalytically hydrolyzed by the assembly in basic solution. Acetal hydrolysis changed from the A-1 mechanism in solution to an A-2 mechanism inside the assembly, where attack of water on the protonated substrate is rate limiting. This work provides rare examples of assembly-catalyzed reactions that proceed with substantial rate accelerations despite the absence of functional groups in the cavity and with mechanisms fully elucidated by quantitative kinetic studies.

[en] The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using ⁵⁹Fe, ²³⁸Pu, and ²⁴¹Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents (deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides) and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

[en] This project addresses the fundamental issues and requirements for developing hazardous metal ion separation technologies applicable to the treatment and disposal of radioactive waste. Our research encompasses the following areas: the design and synthesis of metal ion specific sequestering ligands, structural and thermodynamic investigations of these ligand and the complexes formed with targeted metal ions, and the development and incorporation of these ligands into applied separation technologies as highly effective materials for hazardous metal ion decontamination

[en] This fundamental research on combined cesium, strontium, and actinide separation from alkaline media by solvent extraction addresses the EM need for more efficient processes for the combined separation of these elements

No abstract available

[en] The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd^III chelates

[en] The efficiency of Eu3+ luminescence by energy transfer from an antenna ligand can be strongly dependent on the metal ion coordination geometry. The geometric component of the Eu(III) sensitization has been probed using series of tetradentate 1,2-HOPO derivatives that are connected by bridges of varying length and geometry. The ligands are N,N'-(1,2-phenylene)bis(1-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxamide) for the ligand (L¹), 1-hydroxy-N-(2-(1-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxamido)benzyl) -6-oxo-1,6-dihydropyridine-2-carboxamide (L²) and N,N'-(1,2-phenylenebis(methylene))bis (1-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxamide) (L³). Spectroscopic characterization of both the Gd(III) and Eu(III) metal complexes, TD-DFT analysis of model compounds and evaluation of the kinetic parameters for the europium emission were completed. Some striking differences were observed in the luminescence quantum yield by altering the bridging unit. The [Eu(L²)₂]^- derivative shows efficient sensitization coupled with good metal centered emission. For [Eu(L³)₂]^-, the large quenching of the luminescence quantum yield compared to [Eu(L²)₂]^- is primarily a result of one inner sphere water molecule bound to the europium cation while for [Eu(L¹)₂]^-, the low luminescence quantum yield can be attributed to inefficient sensitization of the europium ion.

[en] 1,2-Hydroxypyridinone (1,2-HOPO) ligands were installed as self-assembled monolayers on nanoporous silica (MCM-41) to create a superior class of sorbent materials for lanthanide cations. Lanthanides were used as a model system for the radioactive, expensive and highly hazardous actinides in the preliminary screening studies. The ligand properties of the 1,2-HOPO ligand field and the extremely large surface area of the MCM-41, coupled with the dense monolayer coating contribute to extremely high lanthanide binding capacity of the 1,2-HOPO nanoporous sorbent. At pH 4-5.9, the mass-weighted partition coefficients (Kd) for La, Nd, Eu, Lu were 354,000, 344,000, 210,800, 419,800, respectively. The rigid, open pore structure of the silica also allows for very rapid sorption. Being silica-based, the sorbent is compatible with vitrification processing into a final glasseous waste form, for subsequent disposition in a deep geological repository