Jesse D. Carrick

Separation of Americium from Europium using Camphor-BisTriazinyl Pyridine: A Fundamental Study

ABSTRACT Among the different components present in spent nuclear fuel, long-lived trivalent actinides are particularly difficult to separate from the shorter-lived lanthanide fission products due to their similar chemical properties. Selective extraction of americium from acidic solution (up to 2M HNO3) containing tenth molar quantities of lanthanides has been achieved using neutral pyridine-based ligands dissolved in polar diluents. Nitrogen-based Bis Triazinyl Pyridine (BTP) ligands are desirable for both their excellent An/Ln selectivity and incinerability. Results pertaining to ligand solubility, kinetics, hydrolytic stability, and extraction performance in various nitric acid environments are presented.

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

A ligand-targeted compound may alleviate hypophosphatemia-associated metabolic deficiencies in patients with excess production of FGF-23. Ligand-targeted therapy for hypophosphatemia Patients with excess fibroblast growth factor–23 (FGF-23) in their circulation have metabolic deficiencies that contribute to chronic kidney disease and the bone-softening disorder rickets. The pharmacokinetics of the available molecules that target the FGF-23 receptor complex limit clinical applicability. Xiao et al. used computationally based screening to identify a compound predicted to bind the ligand, not the receptor. When tested experimentally, the compound was selective for FGF-23 compared to other FGF family ligands and prevented FGF signaling in cultured kidney cells and isolated renal tubules. The compound reduced the serum concentration of FGF-23 and raised the serum concentration of phosphorus, vitamin D, and parathyroid hormone in a mouse model of excess FGF-23. Thus, this approach of targeting the ligand, rather than the receptor, may be a new therapeutic option for hypophosphatemic patients. Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. These chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.

Modular Approaches to Diversified Soft Lewis Basic Complexants through Suzuki-Miyaura Cross-Coupling of Bromoheteroarenes with Organotrifluoroborates.

Remediation or transmutation of spent nuclear fuel obtained as a function of energy production and legacy waste remains a significant environmental concern. Substantive efforts over the last three decades have focused on the potential of soft-Lewis basic complexants for the chemoselective separation of trivalent actinides from lanthanides in biphasic solvent systems. Recent efforts in this laboratory have focused on the concept of modularity to rapidly prepare complexants and complexant scaffolds not easily accessible via traditional linear methods in a convergent manner to better understand solubility and complexation structure/activity function in process-relevant solvents. The current work describes an efficient method for the construction of diversified complexants through multi-Suzuki-Miyaura cross-coupling of bromoheteroarenes with organotrifluoroborates affording efficient access to 22 novel materials in 43-99% yield over two, three, or four cross-couplings on the same scaffold. Optimization of the catalyst/ligand system, application, and limitations are reported herein.

Separation of americium from europium using 3,3'-dimethoxy-phenyl-bis-1,2,4-triazinyl-2,6-pyridine

ABSTRACT The development of liquid–liquid separation processes for the effective removal of minor actinide Am(III) from used nuclear fuel (UNF) using ligand-based strategies continues to be an area of significant research focus. The current investigation demonstrates the efficacy of a nitrogen-based bis-triazinyl pyridine (BTP) derivative to selectively extract Am(III) from nitric acid solutions containing light lanthanides. The performance of 3,3ʹ-dimethoxy-phenyl-bis-1,2,4-triazinyl-2,6-pyridine (MOB-BTP) was compared to that of a camphor-substituted BTP (CA-BTP). The results of this investigation demonstrate the novel 3,3ʹ-methoxy-BTP extractant dissolved in a polar diluent was a more efficient extractant for Am(III) at a lower concentration than CA-BTP under comparable conditions.

Determination of Extractant Solubility in Ionic Liquids by Thermogravimetric Analysis

ABSTRACT The high thermal stability typical of many room temperature ionic liquids (RTILs) is exploited as the basis of a method employing thermogravimetric analysis (TGA) for the determination of the solubility of various metal ion extractants in these solvents. The approach is simple, applicable to extractants lacking functional groups that would permit their ready quantification by other methods, and requires only small (mg) quantities of sample. These features of the method, along with its limitations, are illustrated by the determination of the solubility of representative examples of several common extractant families, including bis(2-ethylhexyl)phosphoric acid (HDEHP) and di-tert-butylcyclohexano-18-crown-6 (DtBuCH18C6), in a series of 1,3-dialkylimidazolium (Cnmim+)-based ionic liquids.

Synthetic Access to Functionalized Dipolarophiles of Lewis Basic Complexant Scaffolds through Sonogashira Cross-Coupling

Soft Lewis basic complexants that facilitate selective removal of discrete ions resident in spent nuclear fuel can decrease repository volume and radiotoxicity and are of significant interest. Optimization of chelation efficacy is predicated on modular access to synthons to rapidly evaluate structure-activity relationships. The following work highlights efficient access to functionalized synthons for use as potential dipolarophiles in subsequent cycloaddition processes via Sonogashira coupling of 3-(6-bromo-pyridin-2-yl)-[1,2,4]triazine scaffolds. The 41 examples explored during method development evaluated electrophile and nucleophile diversity affording the desired coupled products in 31-96% isolated yield. Method optimization, substrate scope, a scale-up reaction, and downstream product functionalization are reported herein.