1. Iodide Binding in Sodium-Coupled Cotransporters
Ariela Vergara-Jaque, Peying Fong, Jeffrey Comer J Chem Inf Model. 2017 Dec 26;57(12):3043-3055.doi: 10.1021/acs.jcim.7b00521.Epub 2017 Dec 4.
Several apical iodide translocation pathways have been proposed for iodide efflux out of thyroid follicular cells, including a pathway mediated by the sodium-coupled monocarboxylate transporter 1 (SMCT1), which remains controversial. Herein, we evaluate structural and functional similarities between SMCT1 and the well-studied sodium-iodide symporter (NIS) that mediates the first step of iodide entry into the thyroid. Free-energy calculations using a force field with electronic polarizability verify the presence of a conserved iodide-binding pocket between the TM2, TM3, and TM7 segments in hNIS, where iodide is coordinated by Phe67, Gln72, Cys91, and Gln94. We demonstrate the mutation of residue Gly93 of hNIS to a larger amino acid expels the side chain of a critical tryptophan residue (Trp255) into the interior of the binding pocket, partially occluding the iodide binding site and reducing iodide affinity, which is consistent with previous reports associating mutation of this residue with iodide uptake deficiency and hypothyroidism. Furthermore, we find that the position of Trp255 in this hNIS mutant mirrors that of Trp253 in wild-type hSMCT1, where a threonine (Thr91) occupies the position homologous to that occupied by glycine in wild-type hNIS (Gly93). Correspondingly, mutation of Thr91 to glycine in hSMCT1 makes the pocket structure more like that of wild-type hNIS, increasing its iodide affinity. These results suggest that wild-type hSMCT1 in the inward-facing conformation may bind iodide only very weakly, which may have implications for its ability to transport iodide.
2. Cathodic stripping voltammetric determination of iodide using disposable sensors
Hugo Cunha-Silva, M Julia Arcos-Martinez Talanta. 2019 Jul 1;199:262-269.doi: 10.1016/j.talanta.2019.02.061.Epub 2019 Feb 16.
The World Health Organization considers iodide deficiency diseases (IDD) to be a public health problem. The main indicator to access IDD is urinary iodide, since approximately 90% of the ingested iodide uses this clearance path, with urine being a preferable target for the analysis. In this work, two screen-printed carbon electrode (SPCE) based sensors were developed to determine iodide by using only a single drop of sample. A first approach based on a SPCE proves to selectively determine iodide through the control of the cathodic stripping voltammetric (CSV) parameters. However, this strategy exhibits a gap in determining trace iodide concentrations, which is improved by modifying the working electrode surface with a chitosan coating. The performance of this new CS/SPCE-based sensor was compared with that of the previous SPCE-based sensor, showing improved iodide determination sensitivity. A limit of detection of 1.0 × 10-8 M and a linear analysis range of 0.15-500 µM were achieved with this sensor. The application of both sensors to real-life samples found values close to those determined by the standard Sandell-Kolthoff spectrophotometric method, proving them to be powerful analytical tools for iodide determination in different kinds of samples, including biological matrices.
3. Catalytic, Enantioselective 1,2-Difluorination of Cinnamamides
Moriana K Haj, Steven M Banik, Eric N Jacobsen Org Lett. 2019 Jul 5;21(13):4919-4923.doi: 10.1021/acs.orglett.9b00938.Epub 2019 Apr 9.
The enantio- and diastereoselective synthesis of 1,2-difluorides via chiral aryl iodide-catalyzed difluorination of cinnamamides is reported. The method uses HF-pyridine as a fluoride source and mCPBA as a stoichiometric oxidant to turn over catalyst, and affords compounds containing vicinal, fluoride-bearing stereocenters. Selectivity for 1,2-difluorination versus a rearrangement pathway resulting in 1,1-difluorination is enforced through anchimeric assistance from a N- tert-butyl amide substituent.
CAS No.: 1835705-72-0
Purity: ≥98%
