Structural Characterization of Sm^III(EDTMP)

Abstract

Samarium-153 ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid) ((153)Sm-EDTMP, or samarium lexidronam), also known by its registered trademark name Quadramet, is an approved therapeutic radiopharmaceutical used in the palliative treatment of painful bone metastases. Typically, patients with prostate, breast, or lung cancer are most likely to go on to require bone pain palliation treatment due to bone metastases. Sm(EDTMP) is a bone-seeking drug which accumulates on rapidly growing bone, thereby delivering a highly region-specific dose of radiation, chiefly through β particle emission. Even with its widespread clinical use, the structure of Sm(EDTMP) has not yet been characterized at atomic resolution, despite attempts to crystallize the complex. Herein, we prepared a 1:1 complex of the cold (stable isotope) of Sm(EDTMP) under alkaline conditions and then isolated and characterized the complex using conventional spectroscopic techniques, as well as with extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional structure calculations, using natural abundance Sm. We present the atomic resolution structure of [Sm(III)(EDTMP)-8H](5-) for the first time, supported by the EXAFS data and complementary spectroscopic techniques, which demonstrate that the samarium coordination environment in solution is in agreement with the structure that has long been conjectured.

Harnessing the bone-seeking ability of Ca(ii)-like metal ions in the treatment of metastatic cancer and resorption disorders

“…It was only in 2015 that Yang, Pushie et al were able to use a variety of spectroscopic and computational methods, including extended X-ray absorption fine structure (EXAFS), DFT, FTIR, and NMR, to give the first characterization of Sm-EDTMP at atomic resolution. 23 The coordinating environment observed for Sm(III) was in good agreement with the atomic arrangement that has long been hypothesized (Fig. 3), and this refinement in structural resolution allows a better understanding of the drug's in vivo behaviour, and enables well-guided modifications that could lead to an improvement in efficacy.…”

“…In all cases, it is the metal ion's affinity for bone tissue -particularly in areas of augmented turnover -that enable site specific treatment to take place. [19][20][21][22][23][24][25][26]…”

Synthesis of Phosphonated Polymer Resins for the Extraction of Rare-Earth Elements

“…The IR spectrum of the polymer resin exhibited characteristic bands at 1349–1498 cm –1 (C–N) and 2906–3648 cm –1 (−OH) (Figure S1). These bands persisted in the functionalized resin; however, we observed additional absorption bands in the ranges of 852–954 cm –1 (P–O) and 1103–1263 cm –1 (PO) for the functionalized resin that were in agreement with previously published infrared (IR) spectra of similar phosphonate-containing molecules. , Furthermore, energy-dispersive X-ray spectroscopy (EDS) of the functionalized resin confirmed the presence of P and N on the functionalized resin surface (Figures S2 and S3). …”