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We synthesize and characterize As(Cys)₃, Sb(Cys)₃, and Bi(Cys)₃, describe their crystal structures, analyze structural trends across Pn(SR)₃compounds, and compare their features to the structures of proteins with these centers bound to Cys₃motifs. 

The synthetic strategies employed to isolate monomeric stibinidene chalcogenides (RSbCh) and monomeric stibine chalcogenides (R₃SbCh) are discussed, and a perspective on the outcomes and future directions of this exciting area is provided. 

Abstract Structure elucidation plays a critical role across the landscape of medicinal chemistry, including medicinal inorganic chemistry. Herein, we discuss the importance of structure elucidation in drug development and then provide three vignettes that capture key instances of its relevance in the development of biologically active inorganic compounds. In the first, we describe the exploration of the biological activity of the trinuclear Ru compound called ruthenium red and the realization that this activity derived from a dinuclear impurity. We next explore the development of Au‐based antitubercular and antiarthritic drugs, which features a key step whereby ligands were discovered to bind to Au through S atoms. The third exposition traces the development of As‐based antiparasitic drugs, a key step of which was the realization that the reaction of arsenic acid and aniline does not produce an anilide of arsenic acid, as originally thought, but rather an amino arsonic acid. These case studies provide the motivation for an outlook in which the development of Sb‐based antiparasitic drugs is described. Although antileishmanial pentavalent antimonial drugs remain in widespread use to this day, their chemical structures remain unknown. 

Phosphine oxides and arsine oxides feature highly polarized pnictoryl groups (Pn + –O − /Pn = O; Pn = P, As) and react as Brønsted bases through O-centered lone pairs. We recently reported the first example of a monomeric stibine oxide, Dipp 3 SbO (Dipp = diisopropylphenyl), allowing periodic trends in pnictoryl bonding to be extended to antimony for the first time. Computational studies suggest that, as the pnictogen atom becomes heavier, delocalization of electron density from the O-centered lone pairs to the Pn–C σ* orbitals is attenuated, destabilizing the lone pairs and increasing the donor capacity of the pnictine oxide. Herein, we assess the Brønsted basicity of a series of monomeric pnictine oxides (Dipp 3 PnO; Pn = P, As, and Sb). Stoichiometric reactivity between Dipp 3 PnO and a series of acids demonstrates the greatly enhanced ability of Dipp 3 SbO to accept protons relative to the lighter congeners, consistent with theoretical isodesmic reaction enthalpies and proton affinities. 1 H NMR spectrometric titrations allow for the p K aH,MeCN determination of Dipp 3 AsO and Dipp 3 SbO, revealing a 10 6 -fold increase in Brønsted basicity from Dipp 3 AsO to Dipp 3 SbO. The increased basicity can be exploited in catalysis; Dipp 3 SbO exhibits dramatically increased catalytic efficiency in the Brønsted base-catalyzed transesterification between p -nitrophenyl acetate and 2,2,2-trifluoroethanol. Our results unambiguously confirm the drastic increase in Brønsted basicity from Dipp 3 PO < Dipp 3 AsO < Dipp 3 SbO, a direct consequence of the variation in the electronic structure of the pnictoryl bond as the pnictogen atom increases in atomic number. 

The structures of the pentavalent antimonials, small-molecule Sb-containing drugs used to treat the neglected tropical disease leishmaniasis, remain unknown despite their widespread use for over half a century. These drugs are prepared by combination of an Sb( v ) precursor and a sugar derivative and proposed structures frequently invoke a cyclic stiborane motif in which a vicinal diolate ligand chelates an Sb( v ) center. As a step towards better understanding the structures of the pentavalent antimonial drugs, a series of cyclic organostiboranes spanning the stereochemical space afforded by a vicinal diolate motif has been synthesized and characterized. X-ray crystallography and NMR spectroscopy provide unambiguous characterization of the structures of these model compounds and of the interaction of the diolate with the Sb( v ) center. Particularly notable are the systematic trends observed in the NMR spectroscopic signals as a function of the stereochemistry of the diolate. The spectroscopic signatures identified with these model compounds will provide a framework for elucidating the structures of the pentavalent antimonial drugs. 

Abstract In contrast to phosphine oxides and arsine oxides, which are common and exist as stable monomeric species featuring the corresponding pnictoryl functional group (Pn=O/Pn⁺–O⁻; Pn = P, As), stibine oxides are generally polymeric, and the properties of the unperturbed stiboryl group (Sb=O/Sb⁺–O⁻) remain unexplored. We now report the isolation of the monomeric stibine oxide, Dipp₃SbO (where Dipp = 2,6-diisopropylphenyl). Spectroscopic, crystallographic and computational studies provide insight into the nature of the Sb=O/Sb⁺–O⁻bond. Moreover, isolation of Dipp₃SbO allows the chemistry of the stiboryl group to be explored. Here we show that Dipp₃SbO can act as a Brønsted base, a hydrogen-bond acceptor and a transition-metal ligand, in addition engaging in 1,2-addition, O-for-F₂exchange and O-atom transfer. In all cases, the reactivity of Dipp₃SbO differed from that of the lighter congeners Dipp₃AsO and Dipp₃PO.