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Schistosomiasis, caused by a parasitic blood fluke of the genus Schistosoma, is a global health problem for which new chemotherapeutic options are needed. We explored the scaffold of gallinamide A, a natural peptidic metabolite of marine cyanobacteria that has previously been shown to inhibit cathepsin L-type proteases. We screened a library of 19 synthetic gallinamide A analogs and identified nanomolar inhibitors of the cathepsin B-type protease SmCB1, which is a drug target for the treatment of schistosomiasis mansoni. Against cultured S. mansoni schistosomula and adult worms, many of the gallinamides generated a range of deleterious phenotypic responses. Imaging with a fluorescent-activity-based probe derived from gallinamide A demonstrated that SmCB1 is the primary target for gallinamides in the parasite. Furthermore, we solved the high-resolution crystal structures of SmCB1 in complex with gallinamide A and its two analogs and describe the acrylamide covalent warhead and binding mode in the active site. Quantum chemical calculations evaluated the contribution of individual positions in the peptidomimetic scaffold to the inhibition of the target and demonstrated the importance of the P1 and P2 positions. Our study introduces gallinamides as a powerful chemotype that can be exploited for the development of novel antischistosomal chemotherapeutics.

Co-pyrolysis reactions of B2Br4 with S2Br2 at 350 °C in vacuo yielded the brominated thiaboranes closo-SB5Br5 (1), closo-1-SB9Br9 (2) and closo-SB11Br11 (3), confirmed by high-resolution mass spectrometry, experimental and computational 11B NMR spectroscopy. The strong Brδ+(σ-hole)⋯Brδ−(ring) attraction has been the decisive energy contribution in the crystal of 1. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the effectiveness of various computational methods in reproducing the experimental heats of formation of boron hydrides using the atomization energy approach. The results have demonstrated that the empirical dispersion combined with the BJ damping function provided too large intramolecular dispersion energies, thereby compromising the accuracy of the outcomes produced by the DFT-D3 methods. Additionally, the CCSD(T) method has reproduced the experimental values only when combined with a basis set optimized for an accurate description of the core-valence correlation effect. Furthermore, the number of multicenter bonds present in the molecules under examination has also reflected their stability, as indicated by the heats of formation. Finally, a five-center two electron (5c–2e) bond has emerged in B5H9, by applying the intrinsic bond orbital (IBO) method. [ABSTRACT FROM AUTHOR]

Herein, we report on the synthesis and stereochemistry of mono- and isomeric dinitrile derivatives of [(1,2-C2B9H11)2-3,3′-Co]− ions. The shape and electronic properties of CN groups can apparently surmount the strain associated with the substitution of two vicinal carbon positions. Owing to electron donation to the cage, this results in a substituent-induced rearrangement of one of the carbon atoms to the upper pentagonal ring. The molecular structure of this isomer was confirmed using sc-XRD and DFT chemical computations. [ABSTRACT FROM AUTHOR]

Six‐vertex closo‐SB5Cl5 (1) and ten‐vertex closo‐1‐SB9Cl9 (2) thiaboranes have been prepared, besides the already known 12‐vertex closo‐SB11Cl11 (3), from the co‐pyrolysis reaction of B2Cl4 with S2Cl2 at 280 °C in vacuo. The compounds are sublimable, off‐white solids. Their elemental composition has been determined by high‐resolution mass spectrometry. They were further characterized by one‐ and two‐dimensional 11B NMR spectroscopy and X‐ray structure determination for 1 and 3. Ab initio/GIAO/NMR computations support octahedral, bicapped square‐antiprismatic, and icosahedral geometries for 1, 2 and 3, respectively, as expected based on their closo‐electron counts. 1 is the first isolated example of a neutral polyhedral closo‐thiaborane with a cluster size smaller than ten vertices. The solid‐state structure of 3 is one of the rare examples of a single‐crystal X‐ray structure determination of an icosahedral heteroborane reported. The corresponding crystal‐packing forces show the different role of chalcogen bonding in these octahedral and icosahedral crystals. In addition, there is a mass‐spectrometry evidence for the recurrent formation of further thiaborane homologs of closo‐SBnCln with n=4, 6, 10, and supra‐icosahedral 12. [ABSTRACT FROM AUTHOR]

The recent success in the formation of chlorinated telluraboranes and the reactivities of pnictogenaboranes prompted us to re-examine the vacuum co-pyrolysis of B2Cl4 with Se2Cl2 at various molar ratios and temperatures in order to search for the generation of other polyhedral selenaboranes than closo-SeB5Cl5 (1a) and closo-SeB11Cl11 (1b), the latter being observed earlier. Interestingly, a new compound with the elemental composition SeB9Cl9 (2) was detected, this time by high- and low-resolution mass spectrometry. Further characterization by 1- and 2-D 11B-NMR spectroscopy suggests that 2 should adopt a closed bicapped square-antiprismatic geometry with selenium at the apical position. Moreover, vacuum sublimation gave suitable crystals of 1b, which were subjected to single-crystal X-ray structure determination. Crystallographic data analysis confirmed that 1b, consistent with its 26 skeletal electron count, adopts a distorted icosahedral structure close to the symmetry of C5v. Computations at the DFT-D3 level have revealed that 33% of the total computed binding motifs in the grown 1b crystals are due to the very strong chalcogen bonding. Moreover, SAPT decomposition has shown that the bonding motifs in the crystals are stabilized mainly by dispersion and electrostatic terms. Homodecoupling and high resolution 11B NMR and 77Se NMR experiments have resolved both coupling constants ¹J(11B11B) and ¹J(77Se11B) as well as the 77Se chemical shift of 1a and 1b, which are in reasonable agreement with the corresponding computed values. The computed 11B chemical shifts of 2 were determined by the well-established DFT/GIAO/NMR structural tool based on its B3LYP/6-311+G** internal coordinates. They agree well with the experimental values and provide a good representation of the molecular structure of 2 in solution. The extraordinary downfield 11B NMR chemical shift of B(10) in 2 has been ascribed to the intensive paramagnetic contribution to the shielding tensor in this bicapped square-antiprismatic motif. Calculations of the synproportionation free energies of smaller (n – 1) closo-selenaboranes with larger-sized (n + 1) ones support the extraordinary stability of octahedral, bicapped square-antiprismatic and icosahedral closo motifs in the SeBnCln family (n = 4–12). [ABSTRACT FROM AUTHOR]

Six‐vertex closo‐TeB5Cl5 (1) and twelve‐vertex closo‐TeB11Cl11 (2) telluraboranes have been prepared via co‐pyrolysis of B2Cl4 with TeCl4 in vacuo at temperatures between 360 °C and 400 °C. Both compounds are sublimable, off‐white solids, and they have been characterized by one‐ and two‐dimensional 11B NMR and high‐resolution mass spectroscopy. Both ab initio/GIAO/NMR and DFT/ZORA/NMR computations support octahedral and icosahedral geometries for 1 and 2, respectively, as expected due to their closo‐electron counts. The octahedral structure of 1 has been confirmed by single‐crystal X‐ray diffraction on an incommensurately modulated crystal. The corresponding bonding properties have been analyzed in terms of the intrinsic bond orbital (IBO) approach. 1 is the first example of a polyhedral telluraborane with a cluster size smaller than 10 vertices. [ABSTRACT FROM AUTHOR]

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