Protein-Based Platform for Purification, Chelation, and Study of Medical Radiometals: Yttrium and Actinium

Actinium-based therapies could revolutionize cancer medicine but remain tantalizing due to the difficulties in studying Ac chemistry. Current efforts focus on small synthetic chelators, limiting radioisotope complexation and purification efficiencies. Here we demonstrate how a recently discovered protein, lanmodulin, can be utilized to efficiently bind, recover, and purify medically-relevant radiometals, actinium(III) and yttrium(III), and probe their chemistry. The stoichiometry, solution behavior, and formation constant of the 228Ac-lanmodulin complex (Ac3LanM, Kd, 865 femtomolar) and its 90Y/natY/natLa analogues were experimentally determined, representing both the first actinium-protein and most stable actinide(III)-protein species to be characterized. Lanmodulin’s unparalleled properties enable the facile purification-recovery of radiometals, even in the presence of >10+10 equivalents of competing ions and at ultra-trace levels: down to 2 femtograms 90Y and 40 attograms 228Ac. The lanmodulin-based approach charts a new course to study elusive isotopes and develop versatile chelating platforms for medical radiometals, both for high-value separations and potentially in vivo applications.

Protein-Based Platform for Purification, Chelation, and Study of Medical Radiometals: Yttrium and Actinium

Actinium-based therapies could revolutionize cancer medicine but remain tantalizing due to the difficulties in studying Ac chemistry. Current efforts focus on small synthetic chelators, limiting radioisotope complexation and purification efficiencies. Here we demonstrate how a recently discovered protein, lanmodulin, can be utilized to efficiently bind, recover, and purify medically-relevant radiometals, actinium(III) and yttrium(III), and probe their chemistry. The stoichiometry, solution behavior, and formation constant of the 228Ac-lanmodulin complex (Ac3LanM, Kd, 865 femtomolar) and its 90Y/natY/natLa analogues were experimentally determined, representing both the first actinium-protein and most stable actinide(III)-protein species to be characterized. Lanmodulin’s unparalleled properties enable the facile purification-recovery of radiometals, even in the presence of >10+10 equivalents of competing ions and at ultra-trace levels: down to 2 femtograms 90Y and 40 attograms 228Ac. The lanmodulin-based approach charts a new course to study elusive isotopes and develop versatile chelating platforms for medical radiometals, both for high-value separations and potentially in vivo applications.

Competitive cocrystallization and its application in the separation of flavonoids

Recently, cocrystallization has been widely employed to tailor physicochemical properties of drugs in the pharmaceutical field. In this study, cocrystallization was applied to separate natural compounds with similar structures. Three flavonoids [baicalein (BAI), quercetin (QUE) and myricetin (MYR)] were used as model compounds. The coformer caffeine (CAF) could form cocrystals with all three flavonoids, namely BAI–CAF (cocrystal 1), QUE–CAF (cocrystal 2) and MYR–CAF (cocrystal 3). After adding CAF to methanol solution containing MYR and QUE (or QUE and BAI), cocrystal 3 (or cocrystal 2) preferentially formed rather than cocrystal 2 (or cocrystal 1), indicating that flavonoid separation could be achieved by competitive cocrystallization. After co-mixing the slurry of two flavonoids with CAF followed by centrifugation, the resolution ratio that could be achieved was 70–80% with purity >90%. Among the three cocrystals, cocrystal 3 showed the lowest formation constant with a negative Gibbs free energy of nucleation and the highest energy gap. Hirshfeld surface analysis and density of states analysis found that cocrystal 3 had the highest strong interaction contribution and the closest electronic density, respectively, followed by cocrystal 2 and cocrystal 1, suggesting CAF could competitively form a cocrystal with MYR much more easily than QUE and BAI. Cocrystallization is a promising approach for green and effective separation of natural products with similar chemical structures.

Extraction behavior of rutherfordium as a cationic fluoride complex with a TTA chelate extractant from HF/HNO3 acidic solutions

The aim of this study was to identify relevant Rf chemical species by using reversed-phase extraction chromatography with 2-thenoyltrifluoroacetone (TTA) resin as the stationary phase. Because TTA can be used to extract specific metal ions, the distribution ratios of the system enabled determination of the specific complex formation constant of Rf. We performed several experiments on chemical systems with Zr, Hf, No, and Rf, determined their adsorption coefficients, and deduced the Kd values for Rf.

Complex formation constant of ferric ion with Gly, Pro-Hyp and Gly-Pro-Hyp

Potentiometric titration to determine the complex formation constant of ferric ions with Gly, Pro-Hyp and Gly-Pro-Hyp.