The nicotinamide coenzyme NADH, consumed in enantioselective reduction of ketones catalysed by alcohol dehydrogenases, needs to be regenerated in order to maintain enzymatic activity. We therefore studied the catalytic potential of

The ferrocene derivative (η5-C5H4PPh2)Fe(η5-C5H4COOH) (3), a potential hybrid phosphine ligand with heteroannular soft and hard donor groups, was synthesized in 71% yield from 1-phenyl-1-phospha[1]ferrocenophane by ring opening with phenyllithium, followed by reaction with carbon dioxide and acidification. Oxidation of 3 with hydrogen peroxide and its esterification with diazomethane provided the derivatives, phosphine oxide 4 and methyl ester 5, respectively. The new compounds were characterized by IR, UV/vis, MS, and NMR spectroscopy, the degenerate 1H NMR spectra being assigned with the aid of selective 1H{1H} decoupling, 1H,1H-COSY, 13C HMQC, and n J(P,C) from APT. The solid-state structures of 3−5 were determined by single-crystal X-ray diffraction. Voltammetric measurements of 3−5 and related monosubstituted derivatives in acetonitrile revealed that the phosphines are first oxidized to the corresponding ferrocenium derivatives which are then the subject of the intramolecular electron transfer from the phosphine group to iron, the resulting species being immediately stabilized by further electrochemical and/or chemical oxidation to give phosphine oxides. The second independent electrochemical process is the reversible oxidation of these ferrocene/phosphine oxides to ferrocenium/phosphine oxides. There are further electrochemical processes associated with the irreversible oxidation of the carboxyl group.

A series of cationic dinuclear p-cymene ruthenium trithiophenolato complexes of the type [(g 6-p-MeC 6 H 4 Pr i) 2 Ru 2 (SC 6 H 4-p-X) 3 ] ? (1 X is H, 2 X is Me, 3 X is Ph, 4 X is Br, 5 X is OH, 6 X is NO 2 , 7 X is OMe, 8 X is CF 3 , 9 X is F, 10 X is Pr i , 11 X is Bu t) have been synthesized from the reaction of [(g 6-p-MeC 6 H 4 Pr i)-RuCl 2 ] 2 with the corresponding thiol, isolated as the chloride salts, and further studied for their electrochemical properties, cytotoxicity towards human ovarian cancer cells, and catalytic activity for glutathione (GSH) oxidation. Complex 1 was also compared with the benzene and hexamethylbenzene analogues [(g 6-C 6 H 6) 2 Ru 2 (SC 6 H 5) 3 ] ? (12) and [(g 6-C 6 Me 6) 2 Ru 2 (SC 6 H 5) 3 ] ? (13). The most active compound [11]Cl was structurally studied by single-crystal X-ray diffraction analysis. The concentrations corresponding to 50 % inhibition of cancer cell growth (IC 50 values) in the A2780 and A2780cisR cell lines of these complexes except for 6 were in the submicromolar range, complex 11 showing an IC 50 value of 0.03 lM in both cell lines. The high in vitro anticancer activity of these complexes may be at least partially due to their catalytic potential for the oxidation of GSH, although there is no clear correlation between the IC 50 values and the turnover frequencies at about 50 % conversion. However, the cytotoxicity is tentatively correlated to the physicochemical properties of the compounds determined by the electronic influence of the substituents X (Hammett constants r p) and the lipophilicity of the thiols p-XC 6 H 4 SH (calculated log P parameters).

Cationic arene ruthenium-based tetranuclear complexes comprising rectangular structures have been obtained from the dinuclear arene ruthenium complexes [Ru 2 (arene) 2 (OO∩OO) 2 Cl 2 ](arene= p-cymene, hexamethylbenzene; OO∩OO=2,5-dihydroxy-1,4-benzoquinonato, 2,5-dichloro-1,4-benzo-quinonato) by reaction with pyrazine or bipyridine linkers (N∩N=pyrazine, 4,4 0 -bipyridine, 1,2-bis(4-pyridyl)ethylene) in methanol in the presence of AgO 3 SCF 3 , forming tetranuclear cations of general for-mula [Ru 4 (arene) 4 (N∩N) 2 (OO∩OO) 2 ] 4þ . All complexes were isolated in good yield as triflate salts and were characterized by NMR and IR spectroscopy and studied by cyclic voltammetry. The cytotoxicities of the water-soluble compounds of the 4,4 0 -bipyridine and 1,2-bis(4-pyridyl)ethylene series have been established using ovarian A2780 cancer cells. The large rectangles incorporating 1,2-bis(4-pyridyl)-ethylene linkers are ca. 5 times more cytotoxic (IC 50 e 6 μM) than the 4,4 0 -bipyridine-containing cations (IC 50 g 30 μM). Structural characterization by X-ray diffraction of two representative compounds, i.e., the triflate salts of [Ru 4 (hexamethylbenzene) 4 (4,4 0 -bipyridine) 2 (2,5-dihydroxy-1,4-benzoquinonato) 2 ] 4þ and [Ru 4 (hexamethylbenzene) 4 (1,2-bis(4-pyridyl)ethylene) 2 (2,5-dichloro-1,4-benzoquinonato) 2 ] 4þ ,re-veals differently sized cavities, different flexibilities, and different packing arrangements, suggesting a correlation between these structural properties and the observed cytotoxicities.

Organometallic ruthenium(II) complexes of general formula [Ru(eta(6)-arene)Cl(2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(5))], where arene = C(6)H(6) (1), C(6)H(5)Me (2), p-iPrC(6)H(4)Me (3), and C(6)Me(6) (4), and of general formula [Ru(eta(6)-arene)Cl(2)](2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(4)-COOC(5)H(4)N), where arene = p-iPrC(6)H(4)Me (5) and C(6)Me(6) (6), have been synthesized and characterized, the molecular structures of these complexes being confirmed by single-crystal X-ray structure analysis of complex 4 as a representative example. The redox properties and in vitro anticancer activities of complexes 1-6 have been studied. All the compounds are moderately cytotoxic toward the A2780 and A2780cisR (cisplatin-resistant) human ovarian carcinoma cell lines. The diruthenium arene complexes 5 and 6 are about twice as active as their mononuclear analogues 3 and 4. Cyclic voltammetry revealed a good correlation of the RuII/RuIII redox potentials of 1-4 and the number of alkyl substituents in the arene ligand.