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We report here two novel "extended-arms" porphyrins, TetbpyPP and TedabpyPP, in which four peripheral bpy fragments are connected to the meso positions of the macrocycle through flexible linkers of different length and hydrophilicity. We describe also the new, water-soluble, tetracationic conjugate [TedabpyPP{Ru([9]aneS3)Cl}(4)][Cl](4) (6). Compound 6 belongs to the series of cationic Ru-porphyrin conjugates 1-5, each bearing four peripheral Ru(II) half-sandwich coordination compounds, that we recently prepared as potential photosensitizing chemotherapeutic agents. The in vitro cell growth inhibition of conjugates 1-6 toward MDA-MB-231 human breast cancer cells and HBL-100 human nontumorigenic epithelial cells are reported, together with the phototoxic effects of 1, 4, and 6 on MDA-MB-231 cells. All conjugates have IC(50) values in the low micromolar range that decrease by 1 order of magnitude upon irradiation of cell cultures with visible light. The most promising compounds 1 and 6 are phototoxic at low light and drug doses.

Ten complexes of general formula [Ru(η6-arene)Cl2(L)], [Ru(η6-arene)Cl(L)2][X], and [Ru(η6-arene)(L)3][X]2 (η6-arene = benzene, p-cymene; L = imidazole, benzimidazole, N-methylimidazole, N-butylimidazole, N-vinylimidazole, N-benzoylimidazole; X = Cl, BF4, BPh4) have been prepd. and characterized by spectroscopy. The structures of five representative compds. have been established in the solid state by single-crystal X-ray diffraction. All the new compds. were assessed by the same in vitro screening assays applied to [imidazole-H][trans-RuCl4(DMSO)(imidazole)] (NAMI-A) and [Ru(η6-arene)Cl2(1,3,5-triaza-7-phosphaadamantane)] (RAPTA) compds. It was found that the new compds. show essentially the same order of cytotoxicity as the RAPTA compds. toward cancer cells. Several of the compds. were selective toward cancer cells in that they were less (or not) cytotoxic toward nontumorigenic cells that are used to model healthy human cells. Thus, two of the compds., [Ru(η6-p-cymene)Cl(vinylimid)2][Cl] (vinylimid = N-vinylimidazole) and [Ru(η6-benzene)(mimid)3][BF4]2 (mimid = N-methylimidazole), have been selected for a more detailed in vivo evaluation.

Ruthenium compounds have gained large interest for their potential application as chemotherapeutic agents, and in particular the complexes of the type (X)[trans-RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole) are under investigation for their antimetastatic properties. The NAMI(-A)-like compounds are prodrugs that hydrolyze in vivo, and the investigation of their hydrolytic properties is therefore important for determining the nature of the potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso-S)(dmtp)]·H2O (3), was isolated and characterized. The molecular structures of 1 and 3 were determined by single-crystal X-ray diffraction analyses and prove the ...

The chemistry of halogen-dimethyl sulfoxide-ruthenium(II) complexes with the general formula RuX/sub 2/(DMSO)/sub 4/ (X = Cl, Br) is reported. In particular the synthesis and x-ray structure of trans-RuCl/sub 2/(DMSO)/sub 4/ are described and compared with those of the already known cis-RuCl/sub 2/(DMSO)/sub 4/ and trans-RuBr/sub 2/(DMSO)/sub 4/. The structure op a new crystal form of cis-RuCl/sub 2/(DMSO)/sub 4/ is also reported. While the cis isomers are thermodynamically more stable and form from the trans species a photochemically driven cis to trans isomerization reaction is observed in dimethyl sulfoxide solution. Kinetic parameters for the thermal trans to cis isomerization reactions for trans-RuCl/sub 2/(DMSO)/sub 4/ and trans-RuBr/sub 2/(DMSO)/sub 4/ are reported. In chloroform solution the complexes, and in particular the trans isomers, tend to release a dimethyl sulfoxide molecule to give pentacoordinated Ru(II) complexes. However, in aqueous solution, while the cis complexes immediately release one DMSO, the trans ones release two. In both cases, this step is followed by the slow dissociation of a halide ion. For the chloro derivatives the dissociation is completely inhibited at physiological chloride concentrations. Preliminary results from pharmacological tests show that trans-RuCl/sub 2/(CMSO)/sub 4/ is more active than the cis isomer against Lewis lung carcinoma, a metastasizingmore » murine tumor. A remarkable dependence of activity on the halogen nature (Cl > Br) is also observed. 33 refs., 4 figs., 9 tabs.« less