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The 16-electron complex CpCoS2C2B10H10 (1) is found to react with the alkynes HC≡CC(O)R [R = methyl (Me), phenyl (Ph), styryl (St), ferrocenyl (Fc)] at ambient temperature to give two types of 17-electron cobalt complexes 2a-d and 3a-d containing unique B(3)/B(6)-norbornyl carborane moieties. A formation mechanism via a tandem sequence of metal-induced B-H activation, B-Cp formation, Cp delivery and Diels-Alder addition is proposed on the basis of DFT calculations. The reactivity of these paramagnetic 17-electron complexes has been studied: Exposed to a combination of air, moisture and silica, complexes 2a-d undergo alkyl C-S cleavage to give 16-electron complexes 4a-c containing a boron-norbornadienyl moiety, and simultaneous carboranyl C-S cleavage to afford cobalt-free carborane derivatives 5a-d containing a boron-norbornyl unit. Both 2a-d and 3a-d allow further alkyne insertion into the Co-S bond to generate cobalt-free boron-norbornyl carborane derivatives (Z/E)-7a-d and (Z/E)-8a-d, both containing a vinyl sulfido group. Addition of AlCl3 not only promotes the conversion of 2a-d, but also leads predominantly to (E)-9a-d as retro-Diels-Alder products. Upon heating, the isomerization from E to Z-configuration of the vinyl group and reorganization of the norbornyl moiety of (Z/E)-7a-d occur to lead to (Z)-9a-d as well as the unexpected [1,2]-H shifted products (Z)-10b,c. Thus, the 17-electron complexes 2a-d and 3a-d serve as intermediates for synthesis of variety of boron-functionalized carborane derivatives. In this study, efficient routes have been developed through cobalt-mediated B-H activation to prepare boron-functionalized carborane derivatives that are unavailable by conventional routes.

The 16e half-sandwich complex Cp*Co(S(2)C(2)B(10)H(10))(1, Cp* = pentamethylcyclopentadienyl) reacts with N-1-naphthylpropargylamide to afford two 18e complexes (2) and (3). 2 is a 1 : 1 adduct containing a four-membered metallacycle. In 3 the alkyne is twofold inserted into one Co-S bond in a head-head mode. Reactions of 1 with 1-(2-furyl)-2-propyn-1-one and 1-ferrocenyl-2-propyn-1-one lead to two types of alkyne twofold inserted products (4)/(5) and (6)/(7), respectively. The reaction of 1 with phenylacetylene gives rise to the sole complex (8) of the same structural type as 3, 4 and 6, whereas the reaction of 1 with dimethyl acetylene dicarboxylate affords the sole 1 : 1 adduct (9). Complexes 2-9 have been characterized by IR, NMR, elemental analysis and mass spectrometry, and 3-9 have also been determined by single-crystal X-ray diffraction analysis.

The large diversity of structures and unique bonding modes of organometallic complexes make them possible to act as promising candidate therapeutic agents. In this study, the new type of ferrocene-substituted dithio-o-carborane conjugates (FcSB1, FcSB2, and FcSBCO) has been synthesized, and their in vitro antineoplastic activities have been explored by means of the electrochemical study, the real time cell electronic sensing (RT-CES) system, and biological assays. The conjugate-cell interactions were first monitored by electrochemistry, and the results show different cell uptake efficiency for FcSB1, FcSB2, and FcSBCO toward target cells. Both the highly hydrophobic ferrocenyl and carboranyl groups render the conjugates able to rapidly enter cells and exert acute cytotoxicity after 4 h incubation in serum-free media. However, FcSB1, FcSB2, and FcSBCO display different inhibition efficiencies toward SMMC-7721 and HepG2 cancer cells via the G(0)/G(1) arrest mechanism in a physiological environment. The anticancer activity is in the order FcSB2 > FcSB1 > FcSBCO, which is parallel to the order of the redox potentials of the ferrocenyl groups in the three complexes. In particular, FcSB1 and FcSB2 display a potent selective inhibition effect on the proliferation of the cancer cell lines SMMC-7721 and HepG2, but almost no effect on the normal cell line, the human embryonic lung fibroblast (HELF) cells. Thus, these results may provide some clues for use of the ferrocene-carborane conjugates in developing anticancer drugs.

BackgroundThe new ruthenium(II)-arene complex, which bearing a carborane unit, ruthenium and ferrocenyl functional groups, has a novel versatile synthetic chemistry and unique properties of the respective material at the nanoscale level. The ruthenium(II)-arene complex shows significant cytotoxicity to cancer cells and tumor-inhibiting properties. However, ruthenium(II)-arene complex of mechanism of anticancer activity are scarcely explored. Therefore, it is necessary to explore ruthenium(II)-arene complex mechanism of anticancer activity for application in this area.ResultsIn this study, the ruthenium(II)-arene complex could significantly induce apoptosis in human lung cancer HCC827 cell line. At the concentration range of 5 μM-100 μM, ruthenium(II)-arene complex had obvious cell cytotoxicity effect on HCC827 cells with IC50 values ranging 19.6 ± 5.3 μM. Additionally, our observations demonstrate that the ruthenium(II)-arene complex can readily induce apoptosis in HCC827 cells, as evidenced by Annexin-V-FITC, nuclear fragmentation as well as DNA fragmentation. Treatment of HCC827 cells with the ruthenium(II)-arene complex resulted in dose-dependent cell apoptosis as indicated by high cleaved Caspase-8,9 ratio. Besides ruthenium(II)-arene complex caused a rapid induction of cleaved Caspase-3 activity and stimulated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP) in vitro and in vivo.ConclusionIn this study, the ruthenium(II)-arene complex could significantly induce apoptosis in human lung cancer HCC827 cell line. Treatment of HCC827 cells with the ruthenium(II)-arene complex resulted in dose-dependent cell apoptosis as indicated by high cleaved Caspase-8,9 ratio. Besides ruthenium(II)-arene complex caused a rapid induction of cleaved Caspase-3 activity and stimulated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP) in vitro and in vivo. Our results suggest that ruthenium(II)-arene complex could be a candidate for further evaluation as a chemotherapeutic agent for human cancers, especially lung cancer.

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The reaction of the dinuclear cobalt compound [(CpCoS(2)C(2)B(10)H(10))(CpCoSC(2)B(10)H(11))(n-C(4)H(9)S)] (1) with HC≡CC(O)Fc leads to the cobalt-free products (C(2)B(10)H(10))(SCH=CHCOFc)(2) (4-6), (S(2)C(2)B(10)H(10))(HC=CCOFc) (7), and (C(2)B(10)H(11))(SCH=CHCOFc) (8, 9). 4-6 are produced by hydrosulfuration of the alkyne at the 1,2-dicarba-closo-dodecaborane-dithiolate ligand with the generated vinyl groups in Z/Z, Z/E and E/E configurations, respectively. In 7, the alkyne is added to 1,2-dicarba-closo-dodecaborane-dithiolate at the two sulfur sites. 8 and 9 are the products of alkyne hydrosulfuration at the 1,2-dicarba-closo-dodecaborane-1-monothiolate ligand with the generated vinyl group in either Z or E configuration. The treatment of 1 with HC≡CCO(2)Me gives rise to the parallel products (C(2)B(10)H(10))(SCH=CHCO(2)Me)(2) (10-12) and (C(2)B(10)H(11))(SCH=CHCO(2)Me) (13, 14). All of the new compounds have been characterized by IR, NMR, elemental analysis and mass spectroscopy. The structures of compounds 4, 7, and 8 have also been determined by single-crystal X-ray diffraction analysis.

Ag(I)-Catalyzed C-H Borylation of Terminal Alkynes. -This efficient method can afford the target products on gram scale. The obtained borylated alkynes can be converted to a wide range of desirable synthons in good yield. The Ag-catalyst can be recovered conveniently after the reaction. -(HU*, J.-R.; LIU, L.-H.; HU, X.; YE, H.-D.; Tetrahedron 70 (2014) 35, 5815-5819, http://dx.