Cereblon (CRBN) is a substrate receptor of the CRL4 E3 ubiquitin ligase complex and a key component in the mechanism of action of immunomodulatory drugs (IMiDs) such as pomalidomide. In this study, we investigated the molecular interaction between pomalidomide and the C-terminal thalidomide-binding domain of CRBN (CdCRBN) using solution NMR spectroscopy, isothermal titration calorimetry (ITC), and fluorescence-based competition assays. Two glycine residues, G354 and G383, located near the ligand-binding site, were employed as markers to monitor binding-induced chemical shift perturbations. The ¹H, ¹⁵N-HSQC titration revealed concentration-dependent chemical shift changes, indicating fast exchange kinetics. The dissociation constant (Kd) calculated by NMR was 55 ± 1.8 µM, while ITC analysis showed a stronger binding affinity (Kd = 12.5 µM), suggesting an enthalpy-driven interaction. A fluorescence resonance energy transfer (FRET)-based competition assay using MANT-uracil further supported the interaction, yielding a Ki of 2.1 µM. These results confirm that pomalidomide binds to the canonical thalidomide-binding pocket of CdCRBN, providing a structural and thermodynamic basis for its function as a molecular glue.

𝛽-Ga₂O₃ single crystals co-doped with Fe³⁺ and Mn²⁺ impurity ions were grown using the floating zone method. By employing an X-band electron magnetic resonance (EMR) spectrometer, electron magnetic resonance spectra of Fe³⁺ impurity ions in the host crystals were recorded at room temperature. The rotation patterns of Fe³⁺ resonance lines in the crystallographic planes clearly show that the real local site symmetry of Fe³⁺ ion within the crystal is monoclinic. It turns out that the Fe³⁺ impurity ions substitute for Ga³⁺ ions (Ga³⁺_I sites) in the oxygen octahedron in 𝛽-Ga₂O₃ single crystal doped with Fe and Mn ions. The substitutional sites of Fe³⁺ ions are discussed and compared with Mn²⁺, Cr³⁺, and Gd³⁺ impurity ions in the host 𝛽-Ga₂O₃ crystals.

The key intermediate 5 of the AB-CHMINACA metabolite M2 was synthesized through a sequence of alkylation, hydrolysis, and amide coupling reactions, affording a moderate yield. In particular, the compound 2 and its regioisomer 3 were distingushed by Nuclear Overhouse Effect (NOE) experiments. In the NOE analysis, compound 3 show no NOE correlation between the methylene (CH2) and the aromatic proton, whereas compound 2 exhibited a pronounced NOE effect. The unambiguous identification of compound 2 was crucial for the synthesis of the AB-CHMINACA metabolite M2. The resulting sy nthetic metabolite will serve as a reference standard compound for the detection of illicit drugs.