Metal-Dependent Cytotoxic and Kinesin Spindle Protein Inhibitory Activity of Ru, Os, Rh, and Ir Half-Sandwich Complexes of Ispinesib-Derived Ligands

Ispinesib is a potent inhibitor of kinesin spindle protein (KSP), which has been identified as a promising target for antimitotic anticancer drugs. Herein, we report the synthesis of half-sandwich complexes of Ru, Os, Rh, and Ir bearing the ispinesib-derived N,N-bidentate ligands (R)- and (S)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one and studies on their chemical and biological properties. Using the enantiomerically pure (R)- and (S)-forms of the ligand, depending on the organometallic moiety, either the SM,R or RM,S diastereomers, respectively, were observed in the molecular structures of the Ru- and Os(cym) (cym = η6-p-cymene) compounds, whereas the RM,R or SM,S diastereomers were found for the Rh- and Ir(Cp*) (Cp* = η5-pentamethylcyclopentadienyl) derivatives. However, density functional theory (DFT) calculations suggest that the energy difference between the diastereomers is very small, and therefore a mixture of both will be present in solution. The organometallics exhibited varying antiproliferative activity in a series of human cancer cell lines, with the complexes featuring the (R)-enantiomer of the ligand being more potent than the (S)-configured counterparts. Notably, the Rh and Ir complexes demonstrated high KSP inhibitory activity, even at 1 nM concentration, which was independent of the chirality of the ligand, whereas the Ru and especially the Os derivatives were much less active

Methanol Adsorption on Vanadium Oxide Surfaces Observed by Ambient Pressure X-ray Photoelectron Spectroscopy

Ambient pressure X-ray photoelectron spectroscopy (APXPS) has been used to study the initial stages of methanol adsorption on vanadium oxide surfaces. V 2p, O 1s, C 1s, and K 2p XPS spectra were collected as a function of relative methanol pressure in a series of isotherm and isobar experiments on two VO2/TiO2 (100) films with different surface vanadium oxidation states. The binding energies and O 1s/C 1s peak area ratios for adsorbates were consistent with a mixture of molecular methanol, methoxide, hydroxide, and water, indicating that both molecular and dissociative methanol adsorption occur. In contrast to water adsorption experiments on similar films, an adsorption onset was observed at a consistent temperature, rather than a consistent relative pressure, indicating that a more complex reaction mechanism is at play. Vanadium oxidation state, C 1s peak position, and the area of carbon and oxygen adsorbate peaks were correlated, suggesting that reduced surface sites play a critical role in enhancing both the dissociative and molecular adsorption of methanol. The two fairly similar VO2/TiO2 (100) films showed quite different behavior, with the more reduced surface showing greater reactivity toward methanol. The difference in reactivity could be linked to different levels of potassium in the two films, which appears to play an important role in determining the vanadium oxidation state and has important practical consequences for the design of catalytic systems