2-Pyridylmethylimidazolium salts and IrH5(PPh3)2 give an [(N-C)IrH2(PPh3)2]+ species with the imidazole ring bound in the 'wrong way': at C-5, not at the expected C-2.

Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions.

We show that imidazolium salts do not always give normal or even aromatic carbenes on metalation, and the chemistry of these ligands can be much more complicated than previously thought. N,N'-disubstituted imidazolium salts of type [(2-py)(CH(2))(n)(C(3)H(3)N(2))R]BF(4) react with IrH(5)(PPh(3))(2) to give N,C-chelated products (n = 0, 1; 2-py = 2-pyridyl; C(3)H(3)N(2) = imidazolium; R = mesityl, n-butyl, i-propyl, methyl). Depending on the circumstances, three types of kinetic products can be formed: in one, the imidazole metalation site is the normal C2 as expected; in another, the metalation occurs at the abnormal C4 site; and in the third, C4 metalation is accompanied by hydrogenation of the imidazolium ring. The bonding mode is confirmed by structural studies, and spectroscopic criteria can also distinguish the cases. Initial hydrogen transfer can take place from the metal to the carbene to give the imidazolium ring hydrogenation product, as shown by isotope labeling; this hydrogen transfer proves reversible on reflux when the abnormal aromatic carbene is obtained as final product. Care may therefore be needed in the future in verifying the structure(s) formed in cases where a catalyst is generated in situ from imidazolium salt and metal precursor.

Air and thermally stable palladium(II) complexes of CNC and CCC bis-carbene pincer ligands have a twisted conformation and catalyze Heck olefination of activated aryl chlorides.

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The bond-valence bond-length concept has been applied to derive a correlation between the hydrogen−hydrogen and the metal−hydrogen distances in the nonclassical dihydrogen complexes and classical transition metal dihydrides. The parameters of this correlation are similar to those for strong hydrogen-bonded systems. The predicted correlation is supported by 18 neutron structures of transition metal dihydrides or dihydrogen complexes and 2 neutron structures of transition metal trihydride complexes. It is also shown that the bond-valence bond-length concept can also be used to establish a correlation between the dihydrogen distance r HH in dihydrogen/dihydride complexes and the scalar coupling constants J HH/J HD/J HT in the different isotopomers of these complexes.

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In this paper a unified description of the effects of the coherent and incoherent dihydrogen exchange on the NMR and INS spectra of transition metal hydrides based on the quantum-mechanical density matrix formalism of Alexander-Binsch is proposed. The dynamic parameters of the line shape analyses are the exchange couplings or rotational tunnel splittings J of the coherent exchange and the rate constants k of the incoherent exchange. As experimental examples, we report the temperature dependent values J and k for 1 ≡ Cp*RuH 3 (PCy 3 ) (Cp* ≡ C 5 (CH 3 ) 5 and Cy ≡ cyclohexyl) including the kinetic HH/HD/DD isotope effects on the incoherent exchange, determined by NMR, and for the tungsten dihydrogen complex 2 ≡ W(PCy 3 ) 2 (CO) 3 -(η-H 2 ), determined by INS. The temperature dependence of J and k is interpreted qualitatively in terms of a simple reaction scheme involving at each temperature a ground state and a dominant ro-vibrationally excited state. Using formal kinetics it is shown that a coherent exchange in the excited state contributes to J only if this exchange presents the rate limiting reaction step, i.e., if vibrational deactivation is fast. This is the case for levels located substantially below the top of the barrier. A very fast coherent exchange of levels located close to the top of the barrier contributes only to k. This result reproduces in a simple way the quantummechanical results of Szymanski, S.