The chalcogen bond is a nonclassical σ-hole-based noncovalent interaction with emerging applications in medicinal chemistry and material science. It is found in organic compounds, including 2D aromatics, but has so far never been observed in 3D aromatic inorganic boron hydrides. Thiaboranes, harboring a sulfur heteroatom in the icosahedral cage, are candidates for the formation of chalcogen bonds. The phenyl-substituted thiaborane, synthesized and crystalized in this study, forms sulfur⋅⋅⋅π type chalcogen bonds. Quantum chemical analysis revealed that these interactions are considerably stronger than both in their organic counterparts and in the known halogen bond. The reason is the existence of a highly positive σ-hole on the positively charged sulfur atom. This discovery expands the possibilities of applying substituted boron clusters in crystal engineering and drug design.

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme that regulates pH in hypoxic tumors and promotes tumor cell survival. Its expression is associated with the occurrence of metastases and poor prognosis. Here, we present nine derivatives of the cobalt bis­(dicarbollide)(1−) anion substituted at the boron or carbon sites by alkysulfamide group(s) as highly specific and selective inhibitors of CAIX. Interactions of these compounds with the active site of CAIX were explored on the atomic level using protein crystallography. Two selected derivatives display subnanomolar or picomolar inhibition constants and high selectivity for the tumor-specific CAIX over cytosolic isoform CAII. Both derivatives had a time-dependent effect on the growth of multicellular spheroids of HT-29 and HCT116 colorectal cancer cells, facilitated penetration and/or accumulation of doxorubicin into spheroids, and displayed low toxicity and showed promising pharmacokinetics and a significant inhibitory effect on tumor growth in syngenic breast 4T1 and colorectal HT-29 cancer xenotransplants.

The conditions for a reaction between nido‐B10H14 (1) and aqueous formaldehyde in an alkaline solution have been optimized, which resulted in the isolation of the [arachno‐6‐CB9H14]− anion (2) in 52% yield. Anion 2 was used as a convenient source for the synthesis of a series of basic monocarbaborane compounds. Thus, oxidation of 2 (Et4N+ salt) with I2 in CH2Cl2 in the presence of Et3N at room temperature afforded the [nido‐6‐CB9H12]− anion (3). Acidification of anion 2 (generated in situ from borane 1) with hydrochloric acid, in the presence of both FeCl3·6H2O and CH2O, led to the formation of arachno‐4‐CB8H14 (4), from which nido‐1‐CB8H12 (5) was obtained by dehydrogenation at 200 °C in quantitative yield. Compound 4 can easily be converted into the [closo‐1‐CB7H8]− anion (6) in 71% yield via reaction with Et3N and I2 in THF at −78 °C. Anion 6 is also formed in 75% yield by treatment of carborane 5 with Et3N in refluxing toluene. The [closo‐1‐CB8H9]− anion (7) was isolated by iodination of carborane 5 in the presence of Et3N (yield 81%) or by the heating of the PPh4+ salt of anion 2 at 220 °C (yield 95%). The structure of anion 2 was determined by an X‐ray diffraction study and the structures of compounds 2, 4, 5, and 7 were geometry optimized at the RMP2(fc)/6‐31G* level. The NMR spectroscopic measurements are in some cases complemented by unpublished 13C NMR spectroscopic data. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)