Ruthenium nitrosyl complexes of the general formulas (cation)+[cis-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (Hind) (1c), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (Hpz) (2c), (cation)+ = (H2bzim)+, Hazole = 1H-benzimidazole (Hbzim) (3c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (Him) (4c) and (cation)+[trans-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (1t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (2t), as well as osmium analogues of the general formulas (cation)+[cis-OsCl4(NO)(Hazole)]−, where (cation)+ = (n-Bu4N)+, Hazole =1H-indazole (5c), 1H-pyrazole (6c), 1H-benzimidazole (7c), 1H-imidazole (8c), (cation)+ = Na+; Hazole =1H-indazole (9c), 1H-benzimidazole (10c), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11c), (cation)+ = H2pz+, Hazole = 1H-pyrazole (12c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (13c), and (cation)+[trans-OsCl4(NO)(Hazole)]−, where (cation)+ = n-Bu4N+, Hazole = 1H-indazole (5t), 1H-pyrazole (6t), (cation)+ = Na+, Hazole = 1H-indazole (9t), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (12t), have been synthesized. The compounds have been comprehensively characterized by elemental analysis, ESI mass spectrometry, spectroscopic techniques (IR, UV–vis, 1D and 2D NMR) and X-ray crystallography (1c·CHCl3, 1t·CHCl3, 2t, 3c, 6c, 6t, 8c). The antiproliferative activity of water-soluble compounds (1c, 1t, 3c, 4c and 9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c) in the human cancer cell lines A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma) has been assayed. The effects of metal (Ru vs Os), cis/trans isomerism, and azole heterocycle identity on cytotoxic potency and cell line selectivity have been elucidated. Ruthenium complexes (1c, 1t, 3c, and 4c) yielded IC50 values in the low micromolar concentration range. In contrast to most pairs of analogous ruthenium and osmium complexes known, they turned out to be considerably more cytotoxic than chemically related osmium complexes (9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c). The IC50 values of Os/Ru homologs differ by factors (Os/Ru) of up to ∼110 and ∼410 in CH1 and SW480 cells, respectively. ESI-MS studies revealed that ascorbic acid may activate the ruthenium complexes leading to hydrolysis of one M–Cl bond, whereas the osmium analogues tend to be inert. The interaction with myoglobin suggests nonselective adduct formation; i.e., proteins may act as carriers for these compounds.

The study reported herein focused on the electronic structure of the {Ru(NO)} 6 fragment and characterization of the oxidation state of ruthenium in mer,trans- [RuCl 3 (Hind) (3) were experimentally and theoretically investigated as reference compounds. A complete active space SCF calculation was performed to estimate the extent of antiferromagnetic spin-spin coupling in 1. We found that the closed-shell structure {Ru III (NO) 0 } 6 fits better to the physical/ spectroscopic properties of 1, although {Ru II (NO) + } 6 is formally still suitable for describing the oxidation state of Ru in this entity.

The title mol­ecule, C14H18Cl2N2O2, lies on a crystallographic inversion center and the each 4-chloro­butanamide group adopts an anti-staggered conformation. In the crystal, adjacent mol­ecules are linked through N—H⋯O contacts, forming infinite ribbons extending parallel to the a axis.