Iodothyronine deiodinases (Dios) are important selenoproteins that control the concentration of the active thyroid hormone (TH) triiodothyronine through regioselective deiodination. The X-ray structure of a truncated monomer of Type III Dio (Dio3), which deiodinates TH inner rings through a selenocysteine (Sec) residue, revealed a thioredoxin-fold catalytic domain supplemented with an unstructured Ω-loop. Loop dynamics are driven by interactions of the conserved Trp207 with solvent in multi-microsecond molecular dynamics simulations of the Dio3 thioredoxin(Trx)-fold domain. Hydrogen bonding interactions of Glu200 with residues conserved across the Dio family anchor the loop’s N-terminus to the active site Ser-Cys-Thr-Sec sequence. A key long-lived loop conformation coincides with the opening of a cryptic pocket that accommodates thyroxine (T4) through an I⋯Se halogen bond to Sec170 and the amino acid group with a polar cleft. The Dio3-T4 complex is stabilized by an I⋯O halogen bond between an outer ring iodine and Asp211, consistent with Dio3 selectivity for inner ring deiodination. Non-conservation of residues, such as Asp211, in other Dio types in the flexible portion of the loop sequence suggests a mechanism for regioselectivity through Dio type-specific loop conformations. Cys168 is proposed to attack the selenenyl iodide intermediate to regenerate Dio3 based upon structural comparison with related Trx-fold proteins.

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Azo‐based energetic materials may initiate explosive decomposition by extruding molecular nitrogen to produce radical fragments. Density functional theory and Wiberg bond index analysis were used to determine trends in bond strength for a series of aromatic azo compounds. Interactions between ortho ring hydrogens and an azo nitrogen lone pair favor a planar molecule with a strengthened azo linkage. Steric groups substituted ortho to the azo linkage cause the molecule to twist, which disrupts delocalization of the π density and weakens the CNazo bond. The results of this study are generally consistent with the low sensitivity of various aromatic azo‐based energetic materials. Discrepancies between calculated bond strengths and the experimental impact sensitivities could be attributed to packing forces that affect molecular planarity in the solid state.