Replacement of chlorides with dicarboxylate ligands in anticancer active Ru(II)-DMSO compounds: a new strategy that might lead to improved activity

A series of new Ru(II)-DMSO complexes containing dicarboxylate ligands (dicarb), namely, oxalate (ox), malonate (mal), methylmalonate (mmal), dimethylmalonate (dmmal), and succinate (suc), have been synthesized and structurally characterized. These compounds were prepared from the known Ru(II)-Cl-DMSO anticancer complexes cis,fac-[RuCl2(DMSO-S)3(DMSO-O)] (1) and trans-[RuCl2(DMSO-S)4] (2) and from the chloride-free precursor fac-[Ru(DMSO-S)3(DMSO-O)3][CF3SO3]2 (3), with the aim of assessing how the nature of the anionic ligands influences the biological activity of these species. Basically, the investigated ligands can be divided into two groups. The reaction of either 1 or 2 with K2(dicarb) (dicarb = ox, mal, mmal) yielded preferentially the mononuclear species [K]fac-[RuCl(DMSO-S)3(eta2-dicarb)] (dicarb = mal, 6; mmal, 9; ox, 14) that contains a chelating dicarboxylate unit and a residual chloride. Likewise, when 3 was used as a precursor, the neutral mononuclear species fac-[Ru(DMSO-O)(DMSO-S)3(eta2-dicarb)] (dicarb = mal, 7; mmal, 10; ox, 16), which contains a DMSO-O ligand in the place of Cl-, was obtained. On the contrary, K2(suc) and K2(dmmal) yielded preferentially the dinuclear species [fac-Ru(DMSO-S)3(H2O)(mu-dicarb)]2 (dicarb = dmmal, 11; suc, 13), with two bridging dicarboxylate moieties. The two water molecules in anti geometry have strong intramolecular H-bonding with the non-coordinated oxygen atoms of the carboxylate groups. The solid-state X-ray structural data showed that the preferential binding mode of the investigated dicarboxylates, either bridging (mu) or chelating (eta2), is dictated mainly by steric reasons. Oxalate, unlike the other dicarboxylates, has also the bridging bis-chelate (eta4,mu) coordination mode available: this was found in the dinuclear species [{fac-RuCl(DMSO-S)3}2(eta4,mu-ox)] (15) and [{fac-Ru(DMSO-O)(DMSO-S)3}2(eta4,mu-ox)][CF3SO3]2 (17). We also isolated the unprecedented neutral metallacycle, [fac-Ru(DMSO-S)3(eta3,mu-ox)]4 (18), in which each oxalate unit has one unbound oxygen atom. The new complexes were thoroughly characterized by 1-D (1H and 13C) and 2-D (H-H- COSY and HMQC) NMR spectroscopy in solution and by IR spectroscopy in the solid state. The molecular structures of 10 compounds, 6-11, 13, 15, 17, and 18, were determined by X-ray crystallography. The behavior of selected complexes in aqueous solution was investigated by 1H NMR spectroscopy.     

1-(2-Picolyl)-substituted 1,2,3-triazole as novel chelating ligand for the preparation of ruthenium complexes with potential anticancer activity

The 1,4-disubstituted 1,2,3-triazole ligand prepared by click chemistry 1-(2-picolyl)-4-phenyl-1H-1,2,3-triazole (ppt) was investigated as novel chelating ligand for Ru(II) complexes with potential antitumor activity. The preparation and structural characterization, mainly by NMR spectroscopy in solution and by X-ray crystallography in the solid state, of four new Ru(II) complexes is reported: two isomeric Ru-dmso compounds, trans,cis-[RuCl(2)(dmso-S)(2)(ppt)] (1) and cis,cis-[RuCl(2)(dmso-S)(2)(ppt)] (2), and two half-sandwich Ru-[9]aneS(3) coordination compounds, [Ru([9]aneS(3))(dmso-S)(ppt)][CF(3)SO(3)](2) (3) and [Ru([9]aneS(3))Cl(ppt)][CF(3)SO(3)] (4). In all compounds ppt firmly binds to ruthenium in a bidentate fashion through the pyridyl nitrogen atom and the triazole N2, thus forming a puckered six-membered ring. The chemical behavior in aqueous solution of the water-soluble complexes 3 and 4 was studied by UV-Vis and NMR spectroscopy and compared to that of the previously described organometallic analogue [Ru(η(6)-p-cymene)Cl(ppt)][Cl] (5) in view of their potential antitumor activity. Compounds 3-5 were tested also in vitro for cytotoxic activity against two human cancer cell lines, one sensitive and one resistant to cisplatin, in comparison with cisplatin. Compound 4, the one that aquates faster, was found to be more cytotoxic than cisplatin against human lung squamose carcinoma cell line (A-549).     

A kinetics and mechanistic study on the role of the structural rigidity of the linker on the substitution reactions of chelated dinuclear Pt(II) complexes

Substitution reactions of platinum complexes bearing cyclohexylamine/diamine moieties viz., [Pt(H(2)O)(N,N-bis(2-pyridylmethyl)cyclohexylamine)](CF(3)SO(3))(2), bpcHna; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-trans-1,4-cyclohexyldiamine)](CF(3)SO(3))(4), cHn and [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-4,4'-dicyclohexylmethanediamine)](CF(3)SO(3))(4), dcHnm and phenylamine/diamine moieties viz., ([Pt(H(2)O)N,N-bis(2-pyridylmethyl)phenylamine)](CF(3)SO(3))(2), bpPha; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-1,3-phenyldiamine)](CF(3)SO(3))(4), mPh; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-1,4-phenyldiamine)](CF(3)SO(3))(4), pPh and [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-4,4'-diphenylmethanediamine)](CF(3)SO(3))(4)), dPhm with thiourea nucleophiles were studied in acidified 0.01 M LiCF(3)SO(3) aqueous medium under pseudo-first-order conditions using stopped-flow and UV-visible spectrophotometric techniques. The rate of substitution follows a similar trend in the two sets of complexes and decreases in the order: bpcHna > dcHnm > cHn and bpPha > dPhm ≈ pPh ≈ mPh), respectively. The result of this study has shown that the rigidity and/or the planarity of a diamine bridge linking the two (2-pyridylmethyl)amine-chelated Pt(II) centres, influences the reactivity of the metal centres by protracting similar symmetry elements within the complexes, which determines the amount of steric influences felt on the coordination square-plane. Hence, the order of reactivity is controlled by both the steric hindrance and the magnitude of the trans σ-inductive effect originating from the linker towards the metal centre. These two factors also impact on the acidity of the complexes. The high negative entropies and low positive enthalpies support an associative mode of activation.     

Self-assembly of electroactive thiacrown ruthenium(II) complexes into hydrogen-bonded chain and tape networks

A family of coordination complexes has been synthesized, each comprising a ruthenium(II) center ligated by a thiacrown macrocycle, [9]aneS(3), [12]aneS(4), or [14]aneS(4), and a pair of cis-coordinated ligands, niotinamide (nic), isonicotinamide (isonic), or p-cyanobenzamide (cbza), that provide the complexes with peripherally situated amide groups capable of hydrogen bond formation. The complexes [Ru([9]aneS(3))(nic)(2)Cl]PF(6), 1(PF(6)); [Ru([9]aneS(3)) (isonic)(2)Cl]PF(6), 2(PF(6)); [Ru([12]aneS(4))(nic)(2)](PF(6))(2), 3(PF(6))(2); [Ru([12]aneS(4))(isonic)(2)](PF(6))(2), 4(PF(6))(2); [Ru([12]aneS(4)) (cbza)(2)](PF(6))(2), 5(PF(6))(2); [Ru([14]aneS(4))(nic)(2)](PF(6))(2), 6(PF(6))(2); [Ru([14]aneS(4))(isonic)(2)](PF(6))(2), 7(PF(6))(2); and [Ru([14]aneS(4))(cbza)(2)](PF(6))(2), 8(PF(6))(2) have been characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. UV/visible spectroscopy shows that each complex exhibits an intense high-energy band (230-255 nm) assigned to a pi-pi* transition and a lower energy band (297-355 nm) assigned to metal-to-ligand charge-transfer transitions. Electrochemical studies indicate good reversibility for the oxidations of complexes with nic and isonic ligands (|I(a)/I(c)| = 1; DeltaEp < 100 mV), In contrast, complexes 5 and 8, which incorporate cbza ligands, display oxidations that are not fully electrochemically reversible (|I(a)/I(c)| = 1, DeltaEp > or = 100 mV). Metal-based oxidation couples between 1.32 and 1.93 V versus Ag/AgCl can be rationalized in term of the acceptor capabilities of the thiacrown ligands and the amide-bearing ligands, as well as the pi-donor capacity of the chloride ligands in compounds 1 and 2. The potential to use these electroactive metal complexes as building blocks for hydrogen-bonded crystalline materials has been explored. Crystal structures of compounds 1(PF(6)).H(2)O, 1(BF(4)).2H(2)O, 2(PF(6)), 3(PF(6))(2), 6(PF(6))(2)CH(3)NO(2), and 8(PF(6))(2) are reported. Four of the six form amide-amide N-H...O hydrogen bonds leading to networks constructed from amide C(4) chains or tapes containing R(2)(2) (8) hydrogen-bonded rings. The other two, 2(PF(6)) and 8(PF(6)), form networks linked through amide-anion N-H...F hydrogen bonds. The role of counterions and solvent in interrupting or augmenting direct amide-amide network propagation is explored, and the systematic relationship between the hydrogen-bonded networks formed across the series of structures is presented, showing the relationship between chain and tape arrangements and the progression from 1D to 2D networks. The scope for future systematic development of electroactive tectons into network materials is discussed.     

New half sandwich Ru(II) coordination compounds for anticancer activity

With the aim of expanding the structure-activity relationship investigation, the series of Ru(II) half sandwich coordination compounds of the type [Ru([9]aneS3)(chel)(L)](n+) previously described by us (where [9]aneS3 is the neutral face-capping ligand 1,4,7-trithiacyclononane, chel is a neutral or anonic chelating ligand, L = Cl(-) or dmso-S, n = 0-2) was extended to 1,4,7-triazacyclononane ([9]aneN3). In addition, new neutral N-N, and anionic N-O and O-O chelating ligands, i.e. dach (trans-1,2-diaminocyclohexane), pic(-) (picolinate), and acac(-) (acetylacetonate), were investigated in combination with both [9]aneS3 and [9]aneN3. Overall, ten new half-sandwich complexes were prepared and fully characterized and their chemical behaviour in aqueous solution was established. The single-crystal X-ray structures of eight of them, including the versatile precursor [Ru([9]aneN3)(dmso-S)(2)Cl]Cl (9), were also determined. The results of in vitro antiproliferative tests performed on selected compounds against MDA-MB-231 human mammary carcinoma cells confirmed that, in this series, only compounds that hydrolyse the monodentate ligand at a reasonable rate show moderate activity, provided that the chelate ligand is a hydrogen bond donor.     

Factors that influence the antiproliferative activity of half sandwich Ru(II)-[9]aneS3 coordination compounds: activation kinetics and interaction with guanine derivatives

Half sandwich Ru(ii)-[9]aneS3 complexes ([9]aneS3 = 1,4,7-trithiacyclononane) are being studied for their antiproliferative activity. We investigated here the activation kinetics of three such complexes, namely [Ru([9]aneS3)(en)Cl](PF(6)) (1), [Ru([9]aneS3)(bpy)Cl](PF(6)) (2) and [Ru([9]aneS3)(pic)Cl] (3) (en = 1,2-diaminoethane, pic = picolinate), and their interaction with DNA model bases. The aim of the study was to assess how they are affected by the nature and charge of the chelating ligand. The model reactions of 1-3 with the guanine derivatives 9-methylguanine (9MeG), guanosine (Guo), and guanosine 5'-monophosphate (5'-GMP) were studied by NMR spectroscopy. All reactions lead, although with different rates and to different extents, to the formation of monofunctional adducts with the guanine derivatives N7-bonded to the Ru center. Two products, the complexes [Ru([9]aneS3)(en)(9MeG-N7)](PF(6))(2) (4) and [Ru([9]aneS3)(pic)(9MeG-N7)](PF(6)) (10), were structurally characterized also by X-ray crystallography. The structure of 4 is stabilized by strong intramolecular H-bonding between an NH of en and the carbonyl O6 of 9MeG. The kinetics of aquation and anation of complexes 2 and 3, as well as the kinetics and the mechanism of the reaction of complexes 1-3 with the biologically more relevant 5'-GMP ligand were studied by UV-Vis spectroscopy. The rate of the reaction of 1-3 with 5'-GMP depends on the nature of the chelating ligand rather than on the charge of the complex, decreasing in the order 3≈2 > 1. The measured enthalpies and entropies of activation (ΔH(≠) > 0, ΔS(≠) < 0) support an associative mechanism for the substitution process.     

New star-shaped trinuclear Ru(II) polypyridine complexes of imidazo[4,5-f][1,10]phenanthroline derivatives: syntheses, characterization, photophysical and electrochemical properties

A series of new star-shaped trinuclear Ru(II) complexes of imidazo[4,5-f][1,10]phenanthroline derivatives, [{Ru(bpy)(2)}(3){μ-mes(1,4-phO-Izphen)(3)}](ClO(4))(6)·4H(2)O (6), [{Ru(phen)(2)}(3){μ-mes(1,4-phO-Izphen)(3)}](ClO(4))(6)·3H(2)O (7), [{Ru(bpy)(2)}(3){μ-mes(1,2-phO-Izphen)(3)}](ClO(4))(6)·4H(2)O (8), and [{Ru(phen)(2)}(3){μ-mes(1,2-phO-Izphen)(3)}](ClO(4))(6)·3H(2)O (9) [mes(1,4-phO-Izphen)(3) (4) = 2,4,6-tri methyl-1,3,5-tris(4-oxymethyl-1-yl(1H-imidazo-2-yl-[4,5-f][1,10]phenanthroline)phenyl)benzene and (mes(1,2-phO-Izphen)(3) (5) = 2,4,6-trimethyl-1,3,5-tris(2-oxymethyl-1-yl(1H-imidazo-2-yl[4,5-f][1,10]phenanthroline)phenyl)benzene] have been synthesized and characterized. Their photophysical and electrochemical properties have also been studied. The core molecule, 1,3,5-tris(bromomethyl)-2,4,6-trimethylbenzene (1) and the trialdehyde intermediate, 2,4,6-trimethyl-1,3,5-tris(4-oxymethyl-1-formylphenyl)benzene (2) are characterized by single crystal X-ray diffraction: triclinic, P1[combining macron]. The complexes 6-9 exhibit Ru(II) metal centered emission at 618, 601, 615, and 605 nm, respectively, in fluid solution at room temperature. The emission profile and emission maxima are similar and independent of the excitation wavelength for each complex. The complexes 6-9 undergo metal centered oxidation and the E(1/2) values for the Ru(II)/Ru(III) redox couples are 1.33, 1.34, 1.35, and 1.35 V versus Ag/Ag(+), respectively, which are cathodically shifted with respect to that of the mononuclear complex [Ru(bpy)(2)(PIP)](2+) (PIP = 2-phenylimidazo[4,5-f][1,10]phenanthroline). The study demonstrates the versatility of the highly symmetric trinucleating imidazo[4,5-f][1,10]phenanthroline-based core ligands 4 and 5 in forming trinuclear Ru(II) complexes.     

C-H cleavage and double alkyl additions to the disulfido ligand in dicyanido-bridged Ru2S2 complexes

Novel dicyanido-bridged dicationic RuIIISSRuIII complexes [{Ru(P(OCH3)3)2}2(mu-S2)(mu-X)2{mu-m-C6H4(CH2CN)2}](CF3SO3)2 (4, X=Cl, Br) were synthesized by the abstraction of the two terminal halide ions of [{RuX(P(OCH3)3)2}2(mu-S2)(mu-X)2] (1, X=Cl, Br) followed by treatment with m-xylylenedicyanide. 4 reacted with 2,3-dimethylbutadiene to give the C4S2 ring-bridged complex [{Ru(P(OCH3)3)2}2{mu-SCH2C(CH3)=C(CH3)CH2S}(mu-X)2{mu-m-C6H4(CH2CN)2}](CF3SO3)2 (6, X=Cl, Br). In addition, 4 reacted with 1-alkenes in CH3OH to give alkenyl disulfide complexes [{Ru(P(OCH3)3)2}2{mu-SS(CH2C=CHR)}(mu-Cl)2{mu-m-C6H4(CH2CN)2}](CF3SO3) (7: R=CH2CH3, 9: R=CH2CH2CH3) and alkenyl methyl disulfide complexes [{Ru(P(OCH3)3)2}2{mu-S(CH3)S(CH2C=HR)}(mu-Cl)2{mu-m-C6H4(CH2CN)2}](CF3SO3)2 (8: R=CH2CH3, 10: R=CH2CH2CH3) via the activation of an allylic C-H bond followed by the elimination of H+ or condensation with CH3OH. Additionally, the reaction of 4 with 3-penten-1-ol gave [{Ru(P(OCH3)3)2}2{mu-SS(CH2C=CHCH2OH)}(mu-Cl)2{mu-m-C6H4(CH2CN)2}](CF3SO3) (11) via the elimination of H+ and [{Ru(P(OCH3)3)2}2(mu-SCH2CH=CHCH2S)(mu-Cl)2{mu-m-C6H4(CH2CN)2}](CF3SO3)2 (12) via the intramolecular elimination of a H2O molecule. 12 was exclusively obtained from the reaction of 4 with 4-bromo-1-butene.     

Hydrolysis of dinuclear ruthenium complexes [{CpRu(PPh3)2}2(micro,eta(1:1)-L)][CF3SO3]2 (L=P4, P4S3): simple access to metal complexes of P2H4 and PH2SH

The reaction of [CpRu(PPh(3))(2)Cl] (1) with half an equivalent of P(4) or P(4)S(3) in the presence of AgCF(3)SO(3) as chloride scavenger affords the stable dimetal complexes [{CpRu(PPh(3))(2)}(2)(micro,eta(1:1)-P(4))][CF(3)SO(3)](2).3 CH(2)Cl(2) (2) and [{CpRu(PPh(3))(2)}(2)(micro,eta(1:1)-P(apical)-P(basal)-P(4)S(3))][CF(3)SO(3)](2).0.5 C(7)H(8) (3), in which the tetrahedral P(4) and mixed-cage P(4)S(3) molecules are respectively bound to two CpRu(PPh(3))(2) fragments through two phosphorus atoms. The coordinated cage molecules, at variance with the free ligands, readily react with an excess of water in THF under mild conditions. Among the hydrolysis products, the new, remarkably stable complexes [{CpRu(PPh(3))(2)}(2)(micro,eta(1:1)-P(2)H(4))][CF(3)SO(3)](2) (4) and [CpRu(PPh(3))(2)(eta(1)-PH(2)SH)]CF(3)SO(3) (8) were isolated. In the former, diphosphane, P(2)H(4), is coordinated to two CpRu(PPh(3))(2) fragments, and in the latter thiophosphinous acid, H(2)PSH, is coordinated to the metal centre through the phosphorus atom. All compounds were characterised by elemental analyses and IR and NMR spectroscopy. The crystal structures of 2, 3, 4 and 8 were determined by X-ray diffraction.     

Titanium(IV) and zirconium(IV) sulfato complexes containing the Kläui tripodal ligand: molecular models of sulfated metal oxide surfaces

Treatment of titanyl sulfate in about 60 mM sulfuric acid with NaL(OEt) (L(OEt) (-)=[(eta(5)-C(5)H(5))Co{P(O)(OEt)(2)}(3)](-)) afforded the mu-sulfato complex [(L(OEt)Ti)(2)(mu-O)(2)(mu-SO(4))] (2). In more concentrated sulfuric acid (>1 M), the same reaction yielded the di-mu-sulfato complex [(L(OEt)Ti)(2)(mu-O)(mu-SO(4))(2)] (3). Reaction of 2 with HOTf (OTf=triflate, CF(3)SO(3)) gave the tris(triflato) complex [L(OEt)Ti(OTf)(3)] (4), whereas treatment of 2 with Ag(OTf) in CH(2)Cl(2) afforded the sulfato-capped trinuclear complex [{(L(OEt))(3)Ti(3)(mu-O)(3)}(mu(3)-SO(4)){Ag(OTf)}][OTf] (5), in which the Ag(OTf) moiety binds to a mu-oxo group in the Ti(3)(mu-O)(3) core. Reaction of 2 in H(2)O with Ba(NO(3))(2) afforded the tetranuclear complex (L(OEt))(4)Ti(4)(mu-O)(6) (6). Treatment of 2 with [{Rh(cod)Cl}(2)] (cod=1,5-cyclooctadiene), [Re(CO)(5)Cl], and [Ru(tBu(2)bpy)(PPh(3))(2)Cl(2)] (tBu(2)bpy=4,4'-di-tert-butyl-2,2'-dipyridyl) in the presence of Ag(OTf) afforded the heterometallic complexes [(L(OEt))(2)Ti(2)(O)(2)(SO(4)){Rh(cod)}(2)][OTf](2) (7), [(L(OEt))(2)Ti(O)(2)(SO(4)){Re(CO)(3)}][OTf] (8), and [{(L(OEt))(2)Ti(2)(mu-O)}(mu(3)-SO(4))(mu-O)(2){Ru(PPh(3))(tBu(2)bpy)}][OTf](2) (9), respectively. Complex 9 is paramagnetic with a measured magnetic moment of about 2.4 mu(B). Treatment of zirconyl nitrate with NaL(OEt) in 3.5 M sulfuric acid afforded [(L(OEt))(2)Zr(NO(3))][L(OEt)Zr(SO(4))(NO(3))] (10). Reaction of ZrCl(4) in 1.8 M sulfuric acid with NaL(OEt) in the presence Na(2)SO(4) gave the mu-sulfato-bridged complex [L(OEt)Zr(SO(4))(H(2)O)](2)(mu-SO(4)) (11). Treatment of 11 with triflic acid afforded [(L(OEt))(2)Zr][OTf](2) (12), whereas reaction of 11 with Ag(OTf) afforded a mixture of 12 and trinuclear [{L(OEt)Zr(SO(4))(H(2)O)}(3)(mu(3)-SO(4))][OTf] (13). The Zr(IV) triflato complex [L(OEt)Zr(OTf)(3)] (14) was prepared by reaction of L(OEt)ZrF(3) with Me(3)SiOTf. Complexes 4 and 14 can catalyze the Diels-Alder reaction of 1,3-cyclohexadiene with acrolein in good selectivity. Complexes 2-5, 9-11, and 13 have been characterized by X-ray crystallography.     

New half sandwich-type Ru(II) coordination compounds characterized by the fac-Ru(dmso-S)3 fragment: influence of the face-capping group on the chemical behavior and in vitro anticancer activity

The Ru(II) complex fac-[RuCl(dmso-S)(3)(dmso-O)(2)][PF(6)] (P2) was found to be an excellent precursor for the facile preparation in high yield of half sandwich-type compounds of the general formula fac-[RuCl(dmso-S)(3)(N)(2)][PF(6)] (e.g. (N)(2) = 1,2-diaminoethane (en, 4), trans-1,2-diaminocyclohexane (dach, 5), or 2 NH(3) (6)). Neutral half sandwich-type compounds of the general formula fac-[RuCl(dmso-S)(3)(N-O)] where N-O is an anionic chelating ligand (e.g. N-O = picolinate (pic, 7)) are best prepared from the universal Ru(II)-dmso precursor cis-[RuCl(2)(dmso)(4)] (P1). These complexes, that were fully characterized in solution and in the solid state, are structurally similar to the anticancer organometallic compounds [Ru(η(6)-arene)(chel)Cl][PF(6)](n) but, in place of a face-capping arene, have the fac-Ru(dmso-S)(3) fragment. In contrast to what observed for the corresponding arene compounds, that rapidly hydrolyze the Cl ligand upon dissolution in water, compounds 4-6 are very stable and inert in aqueous solution. Probably their inertness is the reason why they showed no significant cytotoxicity against the MDA-MB-231 cancer cell line.     

Molecular wheels of ruthenium and osmium with bridging chalcogenolate ligands: edge-shared-octahedron structures and metal-ion binding

Inventing new wheels: reaction of [M(3)(CO)(12) ] (M=Ru, Os) with 4-RC(6)H(4)SH afforded [{M(S-4-RC(6)H(4))(2)(CO)(2)}(8)] (R=H; I) or [{M(S-4-RC(6)H(4))(2)(CO)(2)}(6)] (R=Me, iPr; II; see scheme), all of which have been structurally characterized. The octamers I are unique metal molecular wheels featuring skew-edge-shared octahedra with a central planar M(8) octagon. [{Ru(S-4-iPrC(6)H(4))(2)(CO)(2)}(6)] selectively binds a Cu(+) or Ag(+) ion to form [M'{Ru(S(4-iPr-C(6)H(4)))(2)(CO)(2)}(6)](+) (III).     

Synthesis and structural,spectroscopic, and electrochemical characterization of new ruthenium dimethyl sulfoxide nitrosyls

The reactivity of ruthenium(II)- and ruthenium(III)-chloride-dimethyl sulfoxide precursors and of the antimetastatic drug [ImH][trans-RuCl(4)(dmso-S)(Im)] (NAMI-A, Im = imidazole, dmso = dimethyl sulfoxide) toward NO was investigated. Treatment of [(dmso)(2)H][trans-RuCl(4)(dmso-S)(2)] and mer-RuCl(3)(dmso)(3) with gaseous NO yielded [(dmso)(2)H][trans-RuCl(4)(dmso-O)(NO)] (1) and mer,cis-RuCl(3)(dmso-O)(2)(NO) (2), respectively. Thus, coordination of the strong pi-acceptor NO induces a S to O linkage isomerization of the dmso trans to it to avoid competition for pi-electrons. In light-protected nitromethane solutions, complex 2 equilibrates slowly with the two isomers mer-RuCl(3)(dmso-S)(dmso-O)(NO) (3), with NO trans to Cl, and mer-RuCl(3)(dmso-S)(dmso-O)(NO) (4), with NO trans to dmso-O; the equilibrium mixture consists of ca. 64% 2, 3% 3, and 33% 4. Treatment of the Ru(II) precursor trans-RuCl(2)(dmso-S)(4) with gaseous NO in CH(2)Cl(2) solution yielded the nitrosyl-nitro derivative trans,cis,cis-RuCl(2)(dmso-O)(2)(NO)(NO(2)) (5). Finally, [(Im)(2)H][trans-RuCl(4)(Im)(NO)] (6) was prepared by treatment of [ImH][trans-RuCl(4)(dmso-O)(NO)] (1Im) with an excess of imidazole in refluxing acetone. The spectroscopic features are consistent with the [Ru(NO)](6) formulation for all complexes, that is, a diamagnetic Ru(II) nucleus bound to NO(+). Compounds 1, 2, 5, and 6 were characterized also by X-ray crystallography; they all show a linear nitrosyl group, with short Ru-NO bond distances consistent with a strong d(pi) --> pi NO back-bonding. An unusual inertness of O-bonded dmso was observed in compound 1. Complexes 1, 2, 3, 5, and 6 are all redox active in DMF solutions showing irreversible reductions whose peak potentials depend on the other ligands attached to the Ru metal center. The site of reduction is the NO(+) moiety. The reduced complexes are not stable and release a Cl(-) or NO(2)(-) ligand followed by the NO(*) radical. The chemical reactions following electron transfer are all fast (rate constant >100 s(-1) at 293 K). The Ru product species are not redox active within the DMF window.     

Hybrid dibismuthines and distibines as ligands towards transition metal carbonyls

The hybrid dibismuthines O(CH(2)CH(2)BiPh(2))(2) and MeN(CH(2)-2-C(6)H(4)BiPh(2))(2) react with [M(CO)(5)(thf)] (M = Cr or W) to form [{M(CO)(5)}(2){O(CH(2)CH(2)BiPh(2))(2)}] and [{Cr(CO)(5)}(2){MeN(CH(2)-2-C(6)H(4)BiPh(2))(2)}] containing bridging bidentate (Bi(2)) coordination. The unsymmetrical tertiary bismuthine complexes [M(CO)(5){BiPh(2)(o-C(6)H(4)OMe)}] are also described. Depending upon the molar ratio, the hybrid distibines O(CH(2)CH(2)SbMe(2))(2) and MeN(CH(2)-2-C(6)H(4)SbMe(2))(2) react with [M(CO)(5)(thf)] to give the pentacarbonyl complexes [{M(CO)(5)}(2){O(CH(2)CH(2)SbMe(2))(2)}] and [{Cr(CO)(5)}(2){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] or tetracarbonyls cis-[M(CO)(4){O(CH(2)CH(2)SbMe(2))(2)}] and cis-[M(CO)(4){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}]. The latter can also be obtained from [Cr(CO)(4)(nbd)] or [W(CO)(4)(pip)(2)], and contain chelating bidentates (Sb(2)-coordinated) as determined crystallographically. S(CH(2)-2-C(6)H(4)SbMe(2))(2) coordinates as a tridentate (SSb(2)) in fac-[M(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}] (M = Cr or Mo) and fac-[Mn(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)]. Fac-[Mn(CO)(3){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)] contains NSb(2)-coordinated ligand in the solid state, but in solution a second species, Sb(2)-coordinated and with a κ(1)-CF(3)SO(3) replacing the coordinated amine is also evident. X-ray crystal structures were also determined for fac-[Cr(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}], fac-[Mn(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)] and fac-[Mn(CO)(3){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] [CF(3)SO(3)]. Hypervalent N···Sb interactions are present in cis-[M(CO)(4){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] (M = Mo or W), but absent for M = Cr.     

Bis[tetraruthenium(IV)]-containing polyoxometalates: [{Ru(IV)4O6(H2O)9}2Sb2W20O68(OH)2]4- and [{Ru(IV)4O6(H2O)9}2{Fe(H2O)2}2{β-TeW9O33}2H]-

The reaction of [Sb(2)W(22)O(74)(OH)(2)](12-) and [Fe(4)(H(2)O)(10)(β-TeW(9)O(33))(2)](4-) with (NH(4))(2)[RuCl(6)] in aqueous solution resulted in the novel ruthenium(IV)-containing polyanions [{Ru(IV)(4)O(6)(H(2)O)(9)}(2)Sb(2)W(20)O(68)(OH)(2)](4-) and [{Ru(IV)(4)O(6)(H(2)O)(9)}(2){Fe(H(2)O)(2)}(2){β-TeW(9)O(33)}(2)H](-), exhibiting two cationic, adamantane-like, tetraruthenium(IV) units {Ru(4)O(6)(H(2)O)(9)}(4+) bound to the respective polyanion in an external, highly accessible fashion.     

Ruthenium nitrosyl complexes with 1,4,7-trithiacyclononane and 2,2'-bipyridine (bpy) or 2-phenylazopyridine (pap) coligands. Electronic structure and reactivity aspects

The present article describes ruthenium nitrosyl complexes with the {RuNO}(6) and {RuNO}(7) notations in the selective molecular frameworks of [Ru(II)([9]aneS(3))(bpy)(NO(+))](3+) (4(3+)), [Ru(II)([9]aneS(3))(pap) (NO(+))](3+) (8(3+)) and [Ru(II)([9]aneS(3))(bpy)(NO˙)](2+) (4(2+)), [Ru(II)([9]aneS(3))(pap)(NO˙)](2+) (8(2+)) ([9]aneS(3) = 1,4,7-trithiacyclononane, bpy = 2,2'-bipyridine, pap = 2-phenylazopyridine), respectively. The nitrosyl complexes have been synthesized by following a stepwise synthetic procedure: {Ru(II)-Cl} → {Ru(II)-CH(3)CN} → {Ru(II)-NO(2)} → {Ru(II)-NO(+)} → {Ru(II)-NO˙}. The single-crystal X-ray structure of 4(3+) and DFT optimised structures of 4(3+), 8(3+) and 4(2+), 8(2+) establish the localised linear and bent geometries for {Ru-NO(+)} and {Ru-NO˙} complexes, respectively. The crystal structures and (1)H/(13)C NMR suggest the [333] conformation of the coordinated macrocyclic ligand ([9]aneS(3)) in the complexes. The difference in π-accepting strength of the co-ligands, bpy in 4(3+) and pap in 8(3+) (bpy < pap) has been reflected in the ν(NO) frequencies of 1945 cm(-1) (DFT: 1943 cm(-1)) and 1964 cm(-1) (DFT: 1966 cm(-1)) and E°({Ru(II)-NO(+)}/{Ru(II)-NO˙}) of 0.49 and 0.67 V versus SCE, respectively. The ν(NO) frequency of the reduced {Ru-NO˙} state in 4(2+) or 8(2+) however decreases to 1632 cm(-1) (DFT: 1637 cm(-1)) or 1634 cm(-1) (DFT: 1632 cm(-1)), respectively, with the change of the linear {Ru(II)-NO(+)} geometry in 4(3+), 8(3+) to bent {Ru(II)-NO˙} geometry in 4(2+), 8(2+). The preferential stabilisation of the eclipsed conformation of the bent NO in 4(2+) and 8(2+) has been supported by the DFT calculations. The reduced {Ru(II)-NO˙} exhibits free-radical EPR with partial metal contribution revealing the resonance formulation of {Ru(II)-NO˙}(major)?{Ru(I)-NO(+)}(minor). The electronic transitions of the complexes have been assigned based on the TD-DFT calculations on their DFT optimised structures. The estimated second-order rate constant (k, M(-1) s(-1)) of the reaction of the nucleophile, OH(-) with the electrophilic {Ru(II)-NO(+)} for the bpy derivative (4(3+)) of 1.39 × 10(-1) is half of that determined for the pap derivative (8(3+)), 2.84 × 10(-1) in CH(3)CN at 298 K. The Ru-NO bond in 4(3+) or 8(3+) undergoes facile photolytic cleavage to form the corresponding solvent species {Ru(II)-CH(3)CN}, 2(2+) or 6(2+) with widely varying rate constant values, (k(NO), s(-1)) of 1.12 × 10(-1) (t(1/2) = 6.2 s) and 7.67 × 10(-3) (t(1/2) = 90.3 s), respectively. The photo-released NO can bind to the reduced myoglobin to yield the Mb-NO adduct.     

Redox non-innocence of thioether crowns: elucidation of the electronic structure of the mononuclear Pd(III) complexes [Pd([9]aneS3)2]3+ and [Pd([18]aneS6)]3+

The Pd(II) complexes [Pd([9]aneS(3))(2)](PF(6))(2)·2MeCN (1) ([9]aneS(3) = 1,4,7-trithiacyclononane) and [Pd([18]aneS(6))](PF(6))(2) (2) ([18]aneS(6) = 1,4,7,10,13,16-hexathiacyclooctadecane) can be oxidized electrochemically or chemically oxidized with 70% HClO(4) to [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+), respectively. These centers have been characterized by single crystal X-ray diffraction, and by UV/vis and multifrequency electron paramagnetic resonance (EPR) spectroscopies. The single crystal X-ray structures of [Pd(III)([9]aneS(3))(2)](ClO(4))(6)·(H(3)O)(3)·(H(2)O)(4) (3) at 150 K and [Pd([18]aneS(6))](ClO(4))(6)·(H(5)O(2))(3) (4) at 90 K reveal distorted octahedral geometries with Pd-S distances of 2.3695(8), 2.3692(8), 2.5356(9) and 2.3490(6), 2.3454(5), 2.5474(6) ?, respectively, consistent with Jahn-Teller distortion at a low-spin d(7) Pd(III) center. The Pd(II) compound [Pd([9]aneS(3))(2)](PF(6))(2) shows a one-electron oxidation process in MeCN (0.2 M NBu(4)PF(6), 293 K) at E(1/2) = +0.57 V vs. Fc(+)/Fc assigned to a formal Pd(III)/Pd(II) couple. Multifrequency (Q-, X-, S-, and L-band) EPR spectroscopic analysis of [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+) gives g(iso) = 2.024, |A(iso(Pd))| = 18.9 × 10(-4) cm(-1); g(xx) = 2.046, g(yy) = 2.041, g(zz) = 2.004;?|A(xx(Pd))| = 24 × 10(-4) cm(-1), |A(yy(Pd))| = 22 × 10(-4) cm(-1), |A(zz(Pd))| = 14 × 10(-4) cm(-1), |a(xx(H))| = 4 × 10(-4) cm(-1), |a(yy(H))| = 5 × 10(-4) cm(-1), |a(zz(H))| = 5.5 × 10(-4) cm(-1) for [Pd([9]aneS(3))(2)](3+), and g(iso) = 2.015, |A(iso(Pd))| = 18.8× 10(-4) cm(-1); g(xx) = 2.048 g(yy) = 2.036, g(zz) = 1.998; |a(xx(H))| = 5, |a(yy(H))| = 5, |a(zz(H))| = 6 × 10(-4) cm(-1); |A(xx(Pd))| = 23× 10(-4) cm(-1), |A(yy(Pd))| = 22 × 10(-4) cm(-1), |A(zz(Pd))| = 4 × 10(-4) cm(-1) for [Pd([18]aneS(6))](3+). Both [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+) exhibit five-line superhyperfine splitting in the g(zz) region in their frozen solution EPR spectra. Double resonance spectroscopic measurements, supported by density functional theory (DFT) calculations, permit assignment of this superhyperfine to through-bond coupling involving four (1)H centers of the macrocyclic ring. Analysis of the spin Hamiltonian parameters for the singly occupied molecular orbital (SOMO) in these complexes gives about 20.4% and 25% Pd character in [Pd([9]aneS(3))(2)](3+) and [Pd([18]aneS(6))](3+), respectively, consistent with the compositions calculated from scalar relativistic DFT calculations.     

fac-[Re(CO)3(dmso-O)3](CF3SO3): a new versatile and efficient Re(I) precursor for the preparation of mono and polynuclear compounds containing fac-[Re(CO)3]+ fragments

We show here that the new complex fac-[Re(CO)3(dmso-O)3](CF3SO3) (1), efficiently prepared in one step from [ReBr(CO)5] and featuring a broad range of solubility, is, in general, a better precursor for the one-step synthesis of mono- and polynuclear inorganic compounds containing fac-[Re(CO)3]+ fragments compared to the commonly used (NEt4)2fac-[ReBr3(CO)3] and fac-[Re(CO)3(CH3CN)3](Y) (Y = PF6, BF4, ClO4) species. Compound 1 is the first example of a Re(I)-dmso complex structurally characterized and confirms the rule that dmso is always O-bonded when trans to CO. The reactivity of 1 was tested in the one-step preparation of several new and known complexes. The O-bonded sulfoxides of 1 are replaced under mild conditions by tri- (L3) and bidentate ligands (L2) to produce fac-[Re(CO)3(L3)]+ and fac-[Re(CO)3(L2)(dmso-O)]+ compounds, respectively. An excess of monodentate ligands (L) and more forcing conditions are needed to prepare fac-[Re(CO)3(L)3]+ compounds. The new compounds include fac-[Re(CO)3(bipy)(dmso-O)](CF3SO3) (4), that turned out to be an excellent precursor for binding the luminescent fac-[Re(CO)3(bipy)]+ fragment to polytopic ligands for the construction of more elaborate assemblies. One example reported here is the two-step preparation of fac-[{Re(CO)3(bipy)}(mu-4,4'-bipy){Ru(TPP)(CO)}](CF3SO3) (8) (TPP = tetraphenylporphyrin). The X-ray structures of the new compounds 1, 4, of the bis-porphyrin complex fac-[Re(CO)3Cl(4'MPyP)2] (13) (4'MPyP = 5-(4'pyridyl)-10,15,20-triphenylporphyrin), and of the rhenium-cyclophane [{(CO)3Re(mu-OH)2Re(CO)3}2(micro-4,4'-bipy)2] (15), among others, are described. Compound 1 might find useful applications in supramolecular chemistry (metal-mediated assembly of large architectures), in the in situ preparation of stable Re compounds to be used in nuclear medicine, and for the labeling of biomolecules.     

The acylation of an acyl complex resulting in a labile OCO tridentate ligand

The reaction of propionic anhydride with [fac-Ru(C(O)Et)-(CO)2(H2O)3][CF3SO3] produces a new propylidin dipropionato group, which behaves as a tridentate ligand giving the neutral complex Ru(CEt(OC(O)Et)2)(CO)2(CF3SO3).     

Synthesis of mononuclear and dinuclear ruthenium(II) tris(heteroleptic) complexes via photosubstitution in bis(carbonyl) precursors

A novel, and quite general, approach for the preparation of tris(heteroleptic) ruthenium(II) complexes is reported. Using this method, which is based on photosubstitution of carbonyl ligands in precursors such as [Ru(bpy)(CO)(2)Cl(2)] and [Ru(bpy)(Me(2)bpy)(CO)(2)](PF(6))(2), mononuclear and dinuclear Ru(II) tris(heteroleptic) polypyridyl complexes containing the bridging ligands 3,5-bis(pyridin-2-yl)-1,2,4-triazole (Hbpt) and 3,5-bis(pyrazin-2-yl)-1,2,4-triazole (Hbpzt) have been prepared. The complexes obtained were purified by column chromatography and characterized by HPLC, mass spectrometry, 1H NMR, absorption and emission spectroscopy and by electrochemical methods. The X-ray structures of the compounds [Ru(bpy)(Me(2)bpy)(bpt)](PF(6))x0.5C(4)H(10)O [1x0.5C(4)H(10)O], [Ru(bpy)(Me(2)bpy)(bpzt)](PF(6))xH(2)O (2xH(2)O) and [Ru(bpy)(Me(2)bpy)(CH(3)CN)(2)](PF(6))(2)xC(4)H(10)O (6xC(4)H(10)O) are reported. The synthesis and characterisation of the dinuclear analogues of 1 and 2, [{Ru(bpy)(Me(2)bpy)}(2)bpt](PF(6))(3)x2H(2)O (3) and [{Ru(bpy)(Me(2)bpy)}(2)bpzt](PF(6))(3) (4), are also described.