Osmium Nitrosyl Complexes Research Articles

Biological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles.

Since the discovery that nitric oxide (NO) is a physiologically relevant molecule, there has been great interest in the use of metal nitrosyl compounds as antitumor pharmaceuticals. Particularly interesting are those complexes which can deliver NO to biological targets. Ruthenium- and osmium-based compounds offer lower toxicity compared to other metals and show different mechanisms of action as well as different spectra of activity compared to platinum-based drugs. Novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles were studied to elucidate their cytotoxicity and possible interactions with DNA. Apoptosis induction, changes of mitochondrial transmembrane potential and possible formation of reactive oxygen species were investigated as indicators of NO-mediated damage by flow cytometry. Results suggest that ruthenium- and osmium-nitrosyl complexes with the general formula (indazolium)[cis/trans-MCl4(NO)(1H-indazole)] have pronounced cytotoxic potency in cancer cell lines. Especially the more potent ruthenium complexes strongly induce apoptosis associated with depolarization of mitochondrial membranes, and elevated reactive oxygen species levels. Furthermore, a slight yet not unequivocal trend to accumulation of intracellular cyclic guanosine monophosphate attributable to NO-mediated effects was observed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00775-016-1345-z) contains supplementary material, which is available to authorized users.

Striking difference in antiproliferative activity of ruthenium- and osmium-nitrosyl complexes with azole heterocycles.

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.

523 Biological Effects of Ruthenium and Osmium Nitrosyl Complexes with Azole Heterocycles

523 Biological Effects of Ruthenium and Osmium Nitrosyl Complexes with Azole Heterocycles

Protonation and H/D exchange reactions promoted by a sulfur-rich osmium hydride complex: identification of a labile dihydrogen complex

The sulfur-rich osmium nitrosyl complexes Bu(4)N[Os(NO)((bu)S(2))(2)] (1) [(bu)S(2)(2-) = 3,5-tert-butyl-1,2-benzenedithiolate(2-)] and [Os(NO)(py(bu)S(4))]Br ()[py(bu)S(4)(2-) = 2,6-bis(2-sulfanyl-3,5-di-tert-butylphenylthio)dimethylpyridine(2-)] have been synthesized. The molecular structure of 1 exhibits a square-pyramidal geometry with the NO group at the apical position. A pseudo-octahedral geometry with two thiolate and two thioether donors in trans configuration is found for 2. Compound 2 shows two quasi-reversible one-electron redox waves at E(1/2) = 0.51 and -0.46 V vs. NHE for the redox couples [Os(NO)(py(bu)S(4))](+1/0) and [Os(NO)(py(bu)S(4))](0/-1), respectively. 2 reacts with NaAlH(4) to produce Na[Os(H)(py(bu)S(4))] (3), which exhibits a typical hydride resonance in the (1)H NMR spectrum at delta =-15.03 ppm. Protonation of 3 with HBF(4)/CD(3)OD at 20 degrees C rapidly releases H(2)/HD to afford the dinuclear complex [Os(py(bu)S(4))](2) (4). Low temperature (1)H and (2)H NMR spectra of in [D(8)]THF with CH(3)OH or CD(3)OD at -80 degree C allow the observation of the formation of [Os(H(2)/HD)(py(bu)S(4))]. A 1 : 1 : 1 triplet at delta = -7.84 ppm [J(HD) = 31.2 Hz] and a relaxation time of T(1)(min) = 6 ms (-65 degrees C, 270 MHz) firmly establish the presence of eta(2)-H(2)/HD ligand. At room temperature, 3 interacts with D(2) (1 atm) and undergoes heterolytic D(2) cleavage followed by H/D exchange to form Na[Os(D)(py(bu)S(4))] (3a). A plausible cyclic mechanism has been proposed.

Synthesis, characterization, and protonation of octaethylporphyrin osmium nitrosyl complexes containing axial thiolate ligands - X-ray structures of an alkyl thionitrite (RSNO) and its (OEP)Os(NO)(SR) addition product

The (OEP)Os(NO)(SR) compounds (R = Me, Et, i-Pr, t-Bu) have been prepared in 33-48% isolated yields by the formal trans-addition of the precursor alkyl thionitrites (RSNO) across the metal center in (OEP)Os(CO). The nitrosyl thiolate compounds have been characterized by IR,1H NMR, and UV-vis spectroscopy, and by FAB mass spectrometry. Their IR spectra display bands in the 1751-1755 cm-1(KBr) range, which is indicative of terminal N-bound NO ligands in this class of compounds. The thiolate-thiol (OEP)Os(NO)(SCH2CH2SH) complex has been prepared in 70% isolated yield from the reaction of (OEP)Os(NO)(O-i-C5H11) with ethane-1,2-dithiol. Nitrosation of the free -SH group in (OEP)Os(NO)(SCH2CH2SH) with t-BuONO, followed by reaction with (TTP)Ru(CO) gave [(OEP)Os(NO)](µ-SCH2CH2S-S,S')[Ru(NO)(TTP)] in 70% yield by1H NMR spectroscopy. The (OEP)Os(NO)(SCR'2CH2NHC(O)Me) compounds have also been prepared either by an alkoxide-thiolate exchange reaction (for R' = H) or by RSNO addition to (OEP)Os(CO) (for R' = Me). The solid-state molecular structures of the precursor RSNO thionitrite (for R' = Me) and the metalloderivative have been determined by single-crystal X-ray crystallography. Protonation of these (OEP)Os(NO)(SCR'2CH2NHC(O)Me) complexes gave the amide-bound [(OEP)Os(NO)(O=C(Me)NHCH2CR'2SH)]BF4derivatives. The latter cationic compounds were also obtained by the sequential reaction of (OEP)Os(CO) with nitrosonium tetrafluoroborate, followed by addition of the amide-thiol reagent. Key words: thionitrite, nitrosothiol, porphyrin, X-ray structure, nitric oxide, osmium.

Synthesis, characterization, and protonation of octaethylporphyrin osmium nitrosyl complexes containing axial thiolate ligands - X-ray structures of an alkyl thionitrite (RSNO) and its (OEP)Os(NO)(SR) addition product

Synthesis, characterization, and protonation of octaethylporphyrin osmium nitrosyl complexes containing axial thiolate ligands - X-ray structures of an alkyl thionitrite (RSNO) and its (OEP)Os(NO)(SR) addition product

The structural chemistry of some osmium nitrosyl complexes

The two complexes tribromo(nitrosyl)(diethylsulfide)(diethylsulfoxide)osmium(II), Os(NO)Br 3(Et 2S)- (Et 2SO) and dichloro(nitrosyl)bis(diethylphenylphosphine)(2-methoxyethanoate)osmium(II), Os(NO)- Cl 2(Et 2PPh) 2(CH 3OCH 2CH 2O), have been isolated during studies of photochemical reactions of platinum metal nitrosyl compounds. The molecular structures of these compounds have been determined by single crystal X-ray diffraction. The bright red crystals of Os(NO)Br 3(Et 2S)(Et 2SO) are monoclinic P2 1/ c; a=13.398(3), b=8.501(2), c=16.199(3) Å, β=105.69(5)°, V=1776.41(55) Å 3, Z=4. The structure was refined to a R factor of 0.0617 and a R w, of 0.0599. The complex is isostructural with the ruthenium analogue whose structure has been reported previously. The nitric oxide is coordinated in the linear manner (OsNO=174.3(29)°) and the diethylsulfoxide ligand is oxygen bound (OsO=2.074(17) Å) trans to the NO as suggested from its infrared spectrum ( v(SO)=940 cm −1). The pale orange crystals of Os(NO)Cl 2(Et 2PPh) 2(CH 3OCH 2CH 2O) are also monoclinic P2 1/ c; a=10.869(1), b=11.381(1), c=22.673(2) Å, β=102.17(10)°, V=2741.5(10) Å 3, z=4. The structure was refined to an R of 0.0482 and a R w of 0.0464. The diethylphenylphosphine ligands are coordinated in the trans-arrangement, and the OsP bond lengths are identical; 2.427(3), 2.428(3) Å. The nitric oxide is coordinated in the linear manner (OsNO=1.837(10) Å) and the 2-methoxyethanoate is coordinated trans to the nitrosyl (OsO=1.949(7) Å).

The coordination chemistry of iminooxosulphuranes VIII. The coupling of tosyliminooxosulphurane with ethylene, allene, and alkynes coordinated to osmium

The reactions of the zerovalent osmium nitrosyl complexes [OsCl(NO)(PPh3)2(L)] (L  CH2CH2, CH2CCH2, PhCCPh, PhCCH, CH3CCCH3 and CF3CCCF3) with toluene sulphonyliminooxo-λ4-sulphurane, OSNSO2C6H4Me-4 (OSNSO2R) have been investigated. The ethylene complex reacts either by ethylene substitution to provide [OsCl(NO)(PPh3)2(OSNSO2R)] or by formation of the metallacyclic complex [Os{CH2CH2S(NSO2R)O}Cl(NO)(PPh3)2], which has been crystallographically characterised. The allene complex reacts in a similar manner, also forming a metallacycle [Os{C(CH2)CH2S(NSO2R)O}Cl(NO)(PPh3)2]. The reactivity of the alkyne complexes depends upon the nature of the alkyne substituents: the strongly bound hexafluorobut-2-yne complex is unreactive, the but-2-yne complex reacts by alkyne substitution (i.e., formation of [OsCl(NO)(PPh3)2(OSNSO2R)]), and the aryl alkyne complexes react by metallacycle formation to give [Os{CPhCR′S(NSO2R)O}Cl(NO)(PPh3)2] (R′  H, Ph). The metallacyclic derivatives are readily and reversibly protonated (HBF4) at the exocyclic sulphimine substituent.

Comparison of the electronic structures of osmium-thionitrosyl and osmium-nitrosyl complexes

The electronic structure of the isoelectronic complexes [Os(NX)Cl 5] 2− (X=S or O) and [Os(NS)- Cl 4(H 2O)] 1− has been investigated within a CNDO/2 formalism in order to investigate the nature and energetics of the interaction between osmium and isoelectronic NS and NO ligands. The computed trends for OsN, NS and NO bond strengths in the complexes, as measured by Wiberg indices, charge distribution and orbital population suggest that the strength of the OsNS bond is greater than that of the OsNO bond and the NS ligand is a better electron remover from the central metal atom than the NO ligand. The strength of the OsCl bond trans to the NS ligand is weaker than the OsCl bond trans to the NO ligand. The calculations confirm the experimental observations that the chlorine atom positioned trans to a NS ligand is more labile and, hence, more susceptible to replacement.

Synthesis and reactions of osmium nitrosyl complexes

Nitrosyl halides NOX (X = Cl, Br) reacted with osmium carbonyl complexes [OsH(CO)CIL 3], [Os(CO)Cl 2L 3] and [OsH 2(CO)L 3] (L = PPh 3, AsPh 3) to give osmium nitrosyl complexes [Os(NO)X 3L 2], [Os(NO)CIBr 2L 2] and [Os(NO)C1 2BrL 2] and osmium carbonyl complexes [Os(CO) 2X 2L 2] (X = Cl, Br; L = PPh 3, AsPh 3). Low valent osmium nitrosyl complexes [Os(NO)X(AsPh 3) 3] (X = Cl, Br) were prepared by refluxing [Os(NO)X 3 (AsPh 3) 2] with excess AsPh 3. Reaction of sulphur with [Os(NO)X 3(PPh 3) 2] resulted in the formation of novel thionitro complexes [Os(NSO)X 2(PPh 3) 2]. [Os(NO)C1 3(PPh 3) 2] reacted with [Na(S 2CNR 2) · xH 2O] (R = Et. Me) under different reaction conditions to produce the complexes [Os(NO)Cl 2(S 2CNR 2)(PPh 3)] and [Os(S 2CNR 2) 3]. The products have been characterized by elemental analyses, magnetic measurements, IR and electronic spectral studies.

Mononuclear, low-valent osmium nitrosyl complexes

Mononuclear, low-valent osmium nitrosyl complexes

Electrochemistry of coordination compounds Part XVIII. Electrochemical behaviour of d8 iron and osmium nitrosyl complexes a comparison with their ruthenium analogue

A detailed study of the electrochemical behaviour of the d 8 complexes [Fe(NO)(Ph 2 PCH 2 CH 2 PPh 2 ) 2 ] + and [Os(NO)(Ph 2 PCH 2 CH 2 PPh 2 ) 2 ] + , with emphasis on the properties of the reduced species, has been made and the results compared with those obtained in the reduction of the corresponding ruthenium derivative. the reduction proceeds in two reversible one-electron steps leading to d 10 anionic complexes through an intermediate which, in the case of iron, is labile towards the loss of one phosphorus ligand. A tentative interpretation of this behaviour is suggested.

Electrochemistry of coordination compounds: Part XVIII. Electrochemical behaviour of d8 iron and osmium nitrosyl complexes a comparison with their ruthenium analogue

A detailed study of the electrochemical behaviour of the d 8 complexes [Fe(NO)(Ph 2PCH 2CH 2PPh 2) 2] + and [Os(NO)(Ph 2PCH 2CH 2PPh 2) 2] +, with emphasis on the properties of the reduced species, has been made and the results compared with those obtained in the reduction of the corresponding ruthenium derivative. the reduction proceeds in two reversible one-electron steps leading to d 10 anionic complexes through an intermediate which, in the case of iron, is labile towards the loss of one phosphorus ligand. A tentative interpretation of this behaviour is suggested.