Determining the Crystal Structures of Peptide Analogs of Boronic Acid in the Absence of Single Crystals: Intricate Motifs of Ixazomib Citrate Revealed by XRPD Guided by ss-NMR

Uncertainties in the structure determination of peptide analogs of boronic acid, exacerbated by the many coordination modes of boron, represent an obstacle in understanding their role in living organisms and thus also in developing the next generation of anticancer drugs. For that reason, we present here a general experimental-computational strategy allowing structure determination of complex boronic acid derivatives with extensive conformational variability. We demonstrate successful solution of the crystal structures of two nonsolvated polymorphs of ixazomib citrate directly from synchrotron powder diffraction data, which is challenging because the two molecules in the asymmetric unit cell that exhibit 32 degrees of conformational freedom push the limits of current solution procedures. We used a novel two-step Rietveld refinement based on DFT-D restraints to improve information quality derived from powder diffraction data to be comparable with that of single-crystal solutions. NMR crystallography was applied to verify the crystal structures, and the high potential value of using ¹¹B NMR parameters toward the solution of unknown structures was demonstrated. Evolution of ¹¹B–¹¹B double-quantum coherences allows probing of interatomic distances up to 7 Å. Overall, we present an integrated approach that applies several techniques in conjunction to provide otherwise unavailable structural information

Oxidative Additions of Homoleptic Tin(II) Amidinate

Seven tin­(IV) amidinates were prepared and isolated from the reactions of tin­(II) bisamidinate [Cy–NC­(<i>n</i>Bu)­N–Cy]₂Sn with a series of various 1,2-diones ((4 + 1) oxidative cycloaddition mechanism) and chlorine/oxygen molecules, respectively. The ligand substitution effect of (non)­symmetric 1,3-diones to starting stannylene as well as intermolecular CO₂ activation via prepared dimeric stannoxane is also reported. All the prepared tin containing compounds as well as ligand substitution reactions were investigated by the multinuclear NMR (¹H, ¹³C, and ¹¹⁹Sn) spectroscopic techniques. Molecular structures of one tin­(II) and seven tin­(IV) amidinates investigated were determined by X-ray diffractions and also evaluated by DFT methods. The UV–vis absorption spectra of all desired colored tin­(IV) diolates and its diketo precursors were recorded and simulated by TD-DFT methods