Competition between glutathione and guanine for a ruthenium(II) arene anticancer complex: detection of a sulfenato intermediate

The organometallic anticancer complex [(eta6-bip)Ru(en)Cl]+ (1; bip = biphenyl, en = ethylenediamine) selectively binds to guanine (N7) bases of DNA (Novakova, O.; Chen, H.; Vrana, O.; Rodger, A.; Sadler, P. J.; Brabec, V. Biochemistry 2003, 42, 11544-11554). In this work, competition between the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly; GSH) and guanine (as guanosine 3',5'-cyclic monophosphate, cGMP) for complex 1 was investigated using HPLC, LC-MS and 1H,15N NMR spectroscopy. In unbuffered solution (pH ca. 3), the reaction of 1 with GSH gave rise to three intermediates: an S-bound thiolato adduct [(eta6-bip)Ru(en)(GS-S)] (4) and two carboxylate-bound glutathione products [(eta6-bip)Ru(en)(GSH-O)]+ (5, 6) during the early stages (<6 h), followed by en displacement and formation of a tri-GS-bridged dinuclear Ru(II) complex [((eta6-bip)Ru)2(GS-mu-S)3]2- (7). Under physiologically relevant conditions (micromolar Ru concentrations, pH 7, 22 mM NaCl, 310 K), the thiolato complex 4 was unexpectedly readily oxidized by dioxygen to the sulfenato complex [(eta6-bip)Ru(en)(GS(O)-S)] (8) instead of forming the dinuclear complex 7. Under these conditions, competitive reaction of complex 1 with GSH and cGMP gave rise to the cGMP adduct [(eta6-bip)Ru(en)(cGMP-N7)]+ (10) as the major product, accounting for ca. 62% of total Ru after 72 h, even in the presence of a 250-fold molar excess of GSH. The oxidation of coordinated glutathione in the thiolato complex 4 to the sulfenate in 8 appears to provide a facile route for displacement of S-bound glutathione by G N7. Redox reactions of cysteinyl adducts of these Ru(II) arene anticancer complexes could therefore play a significant role in their biological activity.     

Hydrolytic behaviour and chloride ion binding capability of [Ru(η6-p-cym)(H2O)3]2+: a solution equilibrium study

Hydrolysis of an organometallic cation, [Ru(η(6)-p-cym)(H(2)O)(3)](2+) (p-cym = 1-isopropyl-4-methylbenzene), in the presence of 0.20 M KNO(3) or KCl as supporting electrolyte was studied in detail with the combined use of pH-potentiometry, (1)H-NMR, UV-VIS and ESI-TOF-MS. Stoichiometry and stability constants of chlorido, hydroxido and mixed chlorido-hydroxido complexes formed in aqueous solution have been determined. At pH < 4.0 where hydrolysis of [Ru(η(6)-p-cym)(H(2)O)(3)](2+) is negligible with increasing chloride ion concentration two chlorido complexes, [Ru(η(6)-p-cym)(H(2)O)(2)Cl](+) and [{Ru(η(6)-p-cym)}(2)(μ(2)-Cl)(3)](+), are detectable. At pH > 5.0, in chloride ion free samples the exclusive formation of [{Ru(η(6)-p-cym)}(2)(μ(2)-OH)(3)](+) is found. However, if chloride ion is present (in the range 0-3.50 M) novel mixed chlorido-hydroxido species, [{Ru(η(6)-p-cym)}(2)(μ(2)-OH)(2)(μ(2)-Cl)](+) and [{Ru(η(6)-p-cym)}(2)(μ(2)-OH)(μ(2)-Cl)(2)](+) can also be identified at pH > 4.0. The results obtained in this study may help in rationalizing the solution behaviour of half-sandwich [Ru(η(6)-p-cym)(XY)Z] type complexes which, after dissociation of both the monodentate Z and the chelating XY, are capable of yielding the free aqua species [Ru(η(6)-p-cym)(H(2)O)(3)](2+). Our results demonstrate that different chloride ion concentrations can influence the speciation in the acidic pH range but at biologically relevant conditions (pH = 7.4, c(Cl(-)) = 0.16 M) and at c(M) = 1 μM [{Ru(η(6)-p-cym)}(2)(μ(2)-OH)(3)](+) is predominant in the absence of any coordinating ligands.     

Side-on bound complexes of phenyl- and methyl-diazene

Treatment of trans-[FeCl(2)(dmpe)(2)] with phenylhydrazine and 1 equiv of base afforded the side-on bound phenylhydrazido complex cis-[Fe(η(2)-NH(2)NPh)(dmpe)(2)](+). Further deprotonation of the phenylhydrazido complex afforded the side-on bound phenyldiazene complex cis-[Fe(η(2)-HN═NPh)(dmpe)(2)] as a mixture of diastereomers. Treatment of cis-[RuCl(2)(dmpe)(2)] with phenylhydrazine or methylhydrazine afforded the end-on bound phenylhydrazine or methylhydrazine complexes cis-[RuCl(η(1)-NH(2)NHR)(dmpe)(2)](+) (R = Ph, Me). Treatment of the substituted hydrazine complexes with base afforded the side-on bound phenylhydrazido complex cis-[Ru(η(2)-NH(2)NPh)(dmpe)(2)](+) as well as the phenyldiazene and methyldiazene complexes cis-[Ru(η(2)-HN═NR)(dmpe)(2)] (R = Ph, Me). cis-[RuCl(η(1)-NH(2)NHR)(dmpe)(2)](+) (R = Ph, Me), cis-[M(η(2)-NH(2)NPh)(dmpe)(2)](+) (M = Fe, Ru) and cis-[Ru(η(2)-HN═NPh)(dmpe)(2)] were characterized structurally by X-ray crystallography. cis-[Ru(η(2)-HN═NPh)(dmpe)(2)] is the first side-on bound phenyldiazene complex to be structurally characterized. In the structure of cis-[Ru(η(2)-HN═NPh)(dmpe)(2)], the geometry of the coordinated diazene fragment is significantly nonplanar (CNNH angle 137°) suggesting that the complex is probably better described as a Ru(II) metallodiaziridine than a Ru(0) diazene π-complex.     

Indenyl ring slippage in crown thioether complexes [IndMo(CO)2L]+ and C-S activation of trithiacyclononane: experimental and theoretical studies

The macrocycle 1,4,7-trithiacyclononane (ttcn) reacts with [(η(5)-Ind)Mo(CO)(2)(NCMe)(2)](+) (or [(η(5)-Ind)Mo(CO)(2)(κ(2)-dme)](+)) to give [(η(3)-Ind)Mo(CO)(2)(κ(3)-ttcn)](+) as the BF(4)(-) salt (1), but its reaction with [(η(5)-Ind)Mo(CO)(2)(C(3)H(6))(FBF(3))] affords the C-S bond cleavage product [(η(5)-Ind)Mo(CO)(κ(3)-1,4,7-trithiaheptanate)]BF(4) (6), which has been characterised by X-ray crystallography (Ind = C(9)H(7), indenyl). In contrast to ttcn, the macrocycles 1,3,5-trithiane (tt) and 1,4,7,10-tetrathiacyclododecane (ttcd) fail to induce changes in the coordination mode of indenyl: tt and ttcd react with [(η(5)-Ind)Mo(CO)(2)(NCMe)(2)](+) (or [(η(5)-Ind)Mo(CO)(2)(κ(2)-dme)](+)) to give [(η(5)-Ind)Mo(CO)(2)(κ(2)-tt)](+) (2), characterised by X-ray crystallography, and [(η(5)-Ind)Mo(CO)(2)(κ(2)-ttcd)](+) (3), respectively. The cyclopentadienyl (Cp = C(5)H(5)) analogues [(η(5)-CpMo(CO)(2)(κ(2)-tt)](+) (4) and [(η(5)-CpMo(CO)(2)(κ(2)-ttcn)](+) (5) have also been synthesised and 5 characterised by X-ray crystallography. DFT calculations showed that the η(5)-Ind/Cp coordination mode is always the most stable. However, a molecular dynamics study of the macrocycles conformations revealed that the major conformer of ttcn was a chair, which favoured κ(3) coordination. As indenyl complexes undergo slippage with a small barrier (<10 kcal mol(-1)), the kinetically preferred species [(η(3)-Ind)Mo(CO)(2)(κ(3)-ttcn)](+) (1) is the observed one. The conversion to 6 proceeds stepwise, with loss of ethylene followed by loss of CO, as calculated by DFT, with a barrier of 38.7 kcal mol(-1), consistent with the slow uncatalysed reaction.     

NN型双齿半夹心Ru(Ⅱ)化合物:无受体脱氢环化合成喹啉和吡咯衍生物的催化剂

四个含NN型双齿配体的半夹心(η^6-p-cymene)Ru(II)化合物被成功制备.这四个化合物分别为(η^6-p-cymene)-Ru(C5H4N-C5H3N-OH)(1),(η^6-p-cymene)Ru(C5H4N-CH2-C5H4N)(2),(η^6-p-cymene)Ru(C5H4N-CH2-C5H3N-OH)(3)和(η^6-p-cymene)Ru(C5H4N-CH2-C5H3N-OCH3)(4).这些化合物通过核磁氢谱、碳谱和元素分析等手段表征,化合物2的结构被X射线单晶衍射证实.将这些化合物应用于催化氨醇与酮的环化反应,其中3的催化效率最高.在0.5mol%化合物3的存在下,制备了一系列喹啉和吡啶衍生物.     

Cationic diiron and diruthenium μ-allenyl complexes: synthesis, X-ray structures and cyclization reactions with ethyldiazoacetate/amine affording unprecedented butenolide- and furaniminium-substituted bridging carbene ligands

The novel cationic diiron μ-allenyl complexes [Fe(2)Cp(2)(CO)(2)(μ-CO){μ-η(1):η(2)(α,β)-C(α)(H)=C(β)=C(γ)(R)(2)}](+) (R = Me, 4a; R = Ph, 4b) have been obtained in good yields by a two-step reaction starting from [Fe(2)Cp(2)(CO)(4)]. The solid state structures of [4a][CF(3)SO(3)] and of the diruthenium analogues [Ru(2)Cp(2)(CO)(2)(μ-CO){μ-η(1):η(2)(α,β)-C(α)(H)=C(β)=C(γ)(R)(2)}][BPh(4)] (R = Me, [2a][BPh(4)]; R = Ph, [2c][BPh(4)]) have been ascertained by X-ray diffraction studies. The reactions of 2c and 4a with Br?nsted bases result in formation of the μ-allenylidene compound [Ru(2)Cp(2)(CO)(2)(μ-CO){μ-η(1):η(1)-C(α)=C(β)=C(γ)(Ph)(2)}] (5) and of the dimetallacyclopentenone [Fe(2)Cp(2)(CO)(μ-CO){μ-η(1):η(3)-C(α)(H)=C(β)(C(γ)(Me)CH(2))C(=O)}] (6), respectively. The nitrile adducts [Ru(2)Cp(2)(CO)(NCMe)(μ-CO){μ-η(1):η(2)-C(α)(H)=C(β)=C(γ)(R)(2)}](+) (R = Me, 7a; R = Ph, 7b), prepared by treatment of 2a,c with MeCN/Me(3)NO, react with N(2)CHCO(2)Et/NEt(3) at room temperature, affording the butenolide-substituted carbene complexes [Ru(2)Cp(2)(CO)(μ-CO){μ-η(1):η(3)-C(α)(H)[upper bond 1 start]C(β)C(γ)(R)(2)OC(=O)C[upper bond 1 end](H)] (R = Me, 10a; R = Ph, 10b). The intermediate cationic compound [Ru(2)Cp(2)(CO)(μ-CO){μ-η(1):η(3)-C(α)(H)[upper bond 1 start]C(β)C(γ)(Me)(2)OC(OEt)C[upper bond 1 end](H)](+) (9) has been detected in the course of the reaction leading to 10a. The addition of N(2)CHCO(2)Et/NHEt(2) to 7a gives the 2-furaniminium-carbene [Ru(2)Cp(2)(CO)(μ-CO){μ-η(1):η(3)-C(α)(H)[upper bond 1 start]C(β)C(γ)(Me)(2)OC(OEt)C[upper bond 1 end](H)](+) (11). The X-ray structures of 10a, 10b and [11][BF(4)] have been determined. The reactions of 4a,b with MeCN/Me(3)NO result in prevalent decomposition to mononuclear iron species.     

Reactions of a ruthenium(II) arene antitumor complex with cysteine and methionine

The Ru(II) organometallic antitumor complex [(eta(6)-biphenyl)RuCl(en)][PF(6)] (1) reacts slowly with the amino acid L-cysteine (L-CysH(2)) in aqueous solution at 310 K. Reactions were followed over periods of up to 48 h using HPLC, electronic absorption spectroscopy, LC-ESI-MS, and 1D or 2D (1)H and (15)N NMR spectroscopy. Reactions at a 1 mM/2 mM (Ru/L-CysH(2)) ratio were multiphasic in acidic solutions (pH 5.1) and appeared to involve aquation as the first step. Initially, 1:1 adducts involving substitution of Cl by S-bound or O-bound L-CysH(2), [(eta(6)-biphenyl)Ru(S-L-CysH)(en)](+) (4a) and [(eta(6)-biphenyl)Ru(O-L-CysH(2))(en)](2+) (4b) formed, followed by the cystine adduct [(eta(6)-biphenyl)Ru(O-Cys(2)H(2))(en)](2+) (3), and two dinuclear complexes from which half or all of the chelated ethylenediamine had been displaced, [(eta(6)-biphenyl)Ru(H(2)O)(microS,N-L-Cys)Ru(eta(6)-biphenyl)(en)](2+) (5) containing one bridging cysteine, and [(eta(6)-biphenyl)Ru(O,N-L-Cys-S)(S-L-Cys-N)Ru(eta(6)-biphenyl)(H(2)O)] (6) containing two bridging cysteines. The unusual cluster species [(biphenyl)Ru](8) (7a) was also detected by MS and was more prevalent in reactions at higher L-CysH(2) concentrations. Complex 5 was the dominant product at pH 2-5, but overall, only ca. 50% of 1 reacted with L-CysH(2) in these conditions. The reaction between 1 and L-CysH(2) was suppressed in 50 mM triethylammonium acetate solution at pH > 5 or in 100 mM NaCl. Only 27% of complex 1 reacted with L-methionine (L-MetH) at an initial pH of 5.7 after 48 h at 310 K and gave rise to only one adduct [(eta(6)-biphenyl)Ru(S-L-MetH)(en)](2+) (8).     

Synthesis of the phosphino-fullerene PPh2(o-C6H4)(CH2NMeCH)C60 and its function as an η1-P or η3-P,C2 ligand

Following the method of Prato et al., reaction of C(60), N-methylglycine and o-(diphenylphosphino)benzaldehyde affords PPh(2)(o-C(6)H(4))(CH(2)NMeCH)C(60) (1) in moderate yield. Compound 1 reacts with W(CO)(4)(NCMe)(2) to produce W(CO)(4)(η(3)-PPh(2)(o-C(6)H(4))(CH(2)NMeCH)C(60)) (2), through coordination of the phosphine group and one 6 : 6-ring junction of fullerene. Reaction of 1 and Os(3)(CO)(11)(NCMe) affords Os(3)(CO)(11)(PPh(2)(o-C(6)H(4))(CH(2)NMeCH)C(60)) (3), which undergoes a cluster fragmentation reaction in refluxing toluene to produce Os(CO)(3)(η(3)-PPh(2)(o-C(6)H(4))(CH(2)NMeCH)C(60)) (4). Thermal reaction of 1 and Os(3)(CO)(12) affords 3 and 4. On the other hand, reaction of 1 and Ru(3)(CO)(12) yields only the mononuclear complex Ru(CO)(3)(η(3)-PPh(2)(o-C(6)H(4))(CH(2)NMeCH)C(60)) (5). The structures of 1-3 and 5 were determined by an X-ray diffraction study.     

Highly electrophilic, 16-electron [Ru(P(OMe)(OH)(2))(dppe)(2)](2+) complex turns H(2)(g) into a strong acid and splits a Si-H bond heterolytically. Synthesis and structure of the novel phosphorous acid complex [Ru(P(OH)(3))(dppe)(2)](2+)

The highly electrophilic, 16-electron, coordinatively unsaturated [Ru(P(OMe)(OH)(2))(dppe)(2)][OTf](2) complex brings about the heterolytic activation of H(2)(g) and spontaneously generates HOTf. In addition, trans-[Ru(H)(P(OMe)(OH)(2))(dppe)(2)](+) and an unprecedented example of a phosphorous acid complex, [Ru(P(OH)(3))(dppe)(2)](2+), are formed. The [Ru(P(OMe)(OH)(2))(dppe)(2)][OTf](2) complex also cleaves the Si-H bond in EtMe(2)SiH in a heterolytic fashion, resulting in the trans-[Ru(H)(P(OMe)(OH)(2))(dppe)(2)](+) derivative.     

Highly efficient redox isomerisation of allylic alcohols catalysed by pyrazole-based ruthenium(IV) complexes in water: mechanisms of bifunctional catalysis in water

The catalytic activity of ruthenium(IV) ([Ru(η(3):η(3)-C(10)H(16))Cl(2)L]; C(10)H(16) = 2,7-dimethylocta-2,6-diene-1,8-diyl, L = pyrazole, 3-methylpyrazole, 3,5-dimethylpyrazole, 3-methyl-5-phenylpyrazole, 2-(1H-pyrazol-3-yl)phenol or indazole) and ruthenium(II) complexes ([Ru(η(6)-arene)Cl(2)(3,5-dimethylpyrazole)]; arene = C(6)H(6), p-cymene or C(6)Me(6)) in the redox isomerisation of allylic alcohols into carbonyl compounds in water is reported. The former show much higher catalytic activity than ruthenium(II) complexes. In particular, a variety of allylic alcohols have been quantitatively isomerised by using [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)] as a catalyst; the reactions proceeded faster in water than in THF, and in the absence of base. The isomerisations of monosubstituted alcohols take place rapidly (10-60?min, turn-over frequency = 750-3000?h(-1)) and, in some cases, at 35?°C in 60?min. The nature of the aqueous species formed in water by this complex has been analysed by ESI-MS. To analyse how an aqueous medium can influence the mechanism of the bifunctional catalytic process, DFT calculations (B3LYP) including one or two explicit water molecules and using the polarisable continuum model have been carried out and provide a valuable insight into the role of water on the activity of the bifunctional catalyst. Several mechanisms have been considered and imply the formation of aqua complexes and their deprotonated species generated from [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)]. Different competitive pathways based on outer-sphere mechanisms, which imply hydrogen-transfer processes, have been analysed. The overall isomerisation implies two hydrogen-transfer steps from the substrate to the catalyst and subsequent transfer back to the substrate. In addition to the conventional Noyori outer-sphere mechanism, which involves the pyrazolide ligand, a new mechanism with a hydroxopyrazole complex as the active species can be at work in water. The possibility of formation of an enol, which isomerises easily to the keto form in water, also contributes to the efficiency in water.     

Dithiocarboxylate complexes of ruthenium(II) and osmium(II)

The ruthenium(II) complexes [Ru(R)(κ(2)-S(2)C·IPr)(CO)(PPh(3))(2)](+) (R = CH=CHBu(t), CH=CHC(6)H(4)Me-4, C(C≡CPh)=CHPh) are formed on reaction of IPr·CS(2) with [Ru(R)Cl(CO)(BTD)(PPh(3))(2)] (BTD = 2,1,3-benzothiadiazole) or [Ru(C(C≡CPh)=CHPh)Cl(CO)(PPh(3))(2)] in the presence of ammonium hexafluorophosphate. Similarly, the complexes [Ru(CH=CHC(6)H(4)Me-4)(κ(2)-S(2)C·ICy)(CO)(PPh(3))(2)](+) and [Ru(C(C≡CPh)=CHPh)(κ(2)-S(2)C·ICy)(CO)(PPh(3))(2)](+) are formed in the same manner when ICy·CS(2) is employed. The ligand IMes·CS(2) reacts with [Ru(R)Cl(CO)(BTD)(PPh(3))(2)] to form the compounds [Ru(R)(κ(2)-S(2)C·IMes)(CO)(PPh(3))(2)](+) (R = CH=CHBu(t), CH=CHC(6)H(4)Me-4, C(C≡CPh)=CHPh). Two osmium analogues, [Os(CH=CHC(6)H(4)Me-4)(κ(2)-S(2)C·IMes)(CO)(PPh(3))(2)](+) and [Os(C(C≡CPh)=CHPh)(κ(2)-S(2)C·IMes)(CO)(PPh(3))(2)](+) were also prepared. When the more bulky diisopropylphenyl derivative IDip·CS(2) is used, an unusual product, [Ru(κ(2)-SC(H)S(CH=CHC(6)H(4)Me-4)·IDip)Cl(CO)(PPh(3))(2)](+), with a migrated vinyl group, is obtained. Over extended reaction times, [Ru(CH=CHC(6)H(4)Me-4)Cl(BTD)(CO)(PPh(3))(2)] also reacts with IMes·CS(2) and NH(4)PF(6) to yield the analogous product [Ru{κ(2)-SC(H)S(CH=CHC(6)H(4)Me-4)·IMes}Cl(CO)(PPh(3))(2)](+)via the intermediate [Ru(CH=CHC(6)H(4)Me-4)(κ(2)-S(2)C·IMes)(CO)(PPh(3))(2)](+). Structural studies are reported for [Ru(CH=CHC(6)H(4)Me-4)(κ(2)-S(2)C·IPr)(CO)(PPh(3))(2)]PF(6) and [Ru(C(C≡CPh)=CHPh)(κ(2)-S(2)C·ICy)(CO)(PPh(3))(2)]PF(6).     

Controlled assembly of ruthenium complexes through ortho-carborane dithiolate and polysulfide ligands

Treatment of ortho-carborane, n-butyl lithium, sulfur, and [(p-cymene)RuCl(2)](2) in varying ratio led to four new compounds (p-cymene)Ru[S(3)(C(2)B(10)H(10))(2)] (3), [(p-cymene)Ru(2)(μ(2)-S(2)C(2)B(10)H(9))(μ(3)-S(2)C(2)B(10)H(10))](2) (4), [(p-cymene)Ru](2)Ru(μ(2)-η(2):η(2)-S(2)) (μ(2)-η(2):η(1)-S(2)Cl)(μ(2)-S(2)C(2)B(10)H(10))(2) (5), and [(p-cymene)Ru](2)Ru(μ(2)-η(1):η(1)-S(2))(μ(3)-η(2):η(2)-S(4)) (μ(2)-S(2)C(2)B(10)H(10))(2) (6), respectively. In 3, the ruthenium atom is coordinated by three S atoms from a in situ generated tridentate [S(3)(C(2)B(10)H(10))(2)](2-) ligand. 4 consists of two identical dinuclear (p-cymene)Ru(2)(μ(2)-S(2)C(2)B(10)H(9))(μ(3)-S(2)C(2)B(10)H(10)) subunits which connect to each other via the Ru-Ru bond and two bridging o-carborane-1,2-dithiolate ligands. In 4, a Ru-B bond is present. 5 contains a Ru(3)(μ(2)-S)(2)(μ(2)-S(2))(μ(2)-S(2)Cl) core, and the central ruthenium atom is coordinated by seven S atoms in a distorted pentagonal bipyramidal geometry. In 5, a S-Cl bond is generated. 6 has a novel Ru(3)(μ(2)-S)(2)(μ(2)-S(2))(μ(3)-S(4)) core, and the three ruthenium atoms are connected through the two terminal sulfur atoms of the S-S-S-S chain in a μ(3) binding fashion. All the four complexes have been characterized by elemental analysis, mass, NMR, and X-ray crystallography.     

A reactive Ru-binaphtholate building block with self-tuning hapticity

A versatile Ru-BINO building block is reported, which offers a straightforward entry point into the chemistry of atropisomeric binaphtholate complexes of ruthenium. Reaction of RuCl(2)(PPh(3))(3)6a with Tl(2)((S)-BINO) affords Ru((S)-BINO)(PPh(3))(2)7 as a mixture of isomers: in 7', the BINO ligand is bound via η(3)-CCO,η(1)-O' donors, and in symmetrical 7″, via η(3)-CCO,η(3)-O'C'C' interactions. The bis(enolate) BINO bonding mode in the latter, not previously observed for any metal, underscores the remarkable geometric and electronic flexibility of the binaphtholate moiety. The BINO ligand proves able to stabilize complexes containing as few as two, and as many as four, additional ligands in 7 and its derivatives, enabling a synthetic versatility that contrasts with that of the superficially similar o-catecholate complex Ru(o-cat)(PPh(3))(3). As with the important achiral Ru precursor 6a, complex 7 undergoes facile transformation into a range of products under mild conditions, including acetonitrile, pyridine, and vinylidene derivatives. Single-crystal X-ray structures are reported for three of these complexes: Ru(η(3),η(3)-(S)-BINO)(PPh(3))(2)7″, Ru(η(3),η(1)-(S)-BINO)(PPh(3))(2)(MeCN) 9, and Ru(η(3),η(1)-(S)-BINO)(PPh(3))(py)(2)11. (13)C{(1)H} NMR signatures are proposed for new and known BINO coordination modes (η(1)-O,η(1)-O'; η(1)-C1,η(1)-O'; η(3)-CCO,η(3)-O'C'C'; η(3)-CCO,η(1)-O'; η(6)-C(6),η(1)-O'), as a potential aid to further developments in late-metal BINO chemistry.     

Ruthenium(II) arene complexes with chelating chloroquine analogue ligands: synthesis, characterization and in vitro antimalarial activity

Three new ruthenium complexes with bidentate chloroquine analogue ligands, [Ru(η(6)-cym)(L(1))Cl]Cl (1, cym = p-cymene, L(1) = N-(2-((pyridin-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine), [Ru(η(6)-cym)(L(2))Cl]Cl (2, L(2) = N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) and [Ru(η(6)-cym)(L(3))Cl] (3, L(3) = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine) have been synthesized and characterized. In addition, the X-ray crystal structure of 2 is reported. The antimalarial activity of complexes 1-3 and ligands L(1), L(2) and L(3), as well as the compound N-(2-(bis((pyridin-2-yl)methyl)amino)ethyl)-7-chloroquinolin-4-amine (L(4)), against chloroquine sensitive and chloroquine resistant Plasmodium falciparum malaria strains was evaluated. While 1 and 2 are less active than the corresponding ligands, 3 exhibits high antimalarial activity. The chloroquine analogue L(2) also shows good activity against both the chloroquine sensitive and the chloroquine resistant strains. Heme aggregation inhibition activity (HAIA) at an aqueous buffer/n-octanol interface (HAIR(50)) and lipophilicity (D, as measured by water/n-octanol distribution coefficients) have been measured for all ligands and metal complexes. A direct correlation between the D and HAIR(50) properties cannot be made because of the relative structural diversity of the complexes, but it may be noted that these properties are enhanced upon complexation of the inactive ligand L(3) to ruthenium, to give a metal complex (3) with promising antimalarial activity.     

Strong agostic-type interactions in ruthenium benzylidene complexes containing 7-azaindole based scorpionate ligands

The complexes [Ru(Tai)Cl{=C(H)Ph}(PCy(3))] (4) and [Ru((Ph)Bai)Cl{=C(H)Ph}(PCy(3))] (5) [where Tai = HB(7-azaindolyl)(3) and (Ph)Bai = Ph(H)B(7-azaindolyl)(2)] have been prepared and structurally characterised. The borohydride unit is located in the coordination site trans to the chloride ligand in both complexes. The degree of interaction between the borohydride group and the metal centre was found to be significantly large in both cases. Thermolysis reactions involving complex 4 led to a dehydrogenation reaction forming [Ru(Tai)Cl{PCy(2)(η(2)-C(6)H(9))}] (6) where the benzylidene group acts as a hydrogen acceptor.     

Hydride ion transfer from ruthenium(II) complexes in water: kinetics and mechanism

Reactions of hydride complexes of ruthenium(II) with hydride acceptors have been examined for Ru(terpy)(bpy)H(+), Ru(terpy)(dmb)H(+), and Ru(η(6)-C(6)Me(6))(bpy)(H)(+) in aqueous media at 25 °C (terpy = 2,2';6',2'-terpyridine, bpy = 2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine). The acceptors include CO(2), CO, CH(2)O, and H(3)O(+). CO reacts with Ru(terpy)(dmb)H(+) with a rate constant of 1.2 (0.2) × 10(1) M(-1) s(-1), but for Ru(η(6)-C(6)Me(6))(bpy)(H)(+), the reaction was very slow, k ≤ 0.1 M(-1) s(-1). Ru(terpy)(bpy)H(+) and Ru(η(6)-C(6)Me(6))(bpy)(H)(+) react with CH(2)O with rate constants of (6 ± 4) × 10(6) and 1.1 × 10(3) M(-1) s(-1), respectively. The reaction of Ru(η(6)-C(6)Me(6))(bpy)(H)(+) with acid exhibits straightforward, second-order kinetics, with the rate proportional to [Ru(η(6)-C(6)Me(6))(bpy)(H)(+)] and [H(3)O(+)] and k = 2.2 × 10(1) M(-1) s(-1) (μ = 0.1 M, Na(2)SO(4) medium). However, for the case of Ru(terpy)(bpy)H(+), the protonation step is very rapid, and only the formation of the product Ru(terpy)(bpy)(H(2)O)(2+) (presumably via a dihydrogen or dihydride complex) is observed with a k(obs) of ca. 4 s(-1). The hydricities of HCO(2)(-), HCO(-), and H(3)CO(-) in water are estimated as +1.48, -0.76, and +1.57 eV/molecule (+34, -17.5, +36 kcal/mol), respectively. Theoretical studies of the reactions with CO(2) reveal a "product-like" transition state with short C-H and long M-H distances. (Reactant) Ru-H stretched 0.68 ?; (product) C-H stretched only 0.04 ?. The role of water solvent was explored by including one, two, or three water molecules in the calculation.     

1-Borabenzonitrile (B-cyanoboratabenzene)

The reaction of 1-chloro-2-(trimethylsilyl)-1-boracyclohexa-2,5-diene with [(n)Bu(4)N]C≡N provides the 1-borabenzonitrile salt [(n)Bu(4)N][C(5)H(5)BC≡N] which in turn reacts with [Ru(4)(μ-Cl)(4)(η-C(5)Me(5))(4)] to afford the sandwich complex [Ru(η(6)-C(5)H(5)BC≡N)(η-C(5)Me(5))]. The bonding of 1-borabenzonitrile is discussed with recourse to crystallographic data for [(n)Bu(4)N][C(5)H(5)BC≡N] and [Ru(η(6)-C(5)H(5)BC≡N)(η-C(5)Me(5))].     

Peroxydisulfate activation by [RuII(tpy)(pic)(H2O)]+. Kinetic, mechanistic and anti-microbial activity studies

The oxidation of [Ru(II)(tpy)(pic)H(2)O](+) (tpy = 2,2',6',2'-terpyridine; pic(-) = picolinate) by peroxidisulfate (S(2)O(8)(2-)) as precursor oxidant has been investigated kinetically by UV-VIS, IR and EPR spectroscopy. The overall oxidation of Ru(II)- to Ru(IV)-species takes place in a consecutive manner involving oxidation of [Ru(II)(tpy)(pic)H(2)O](+) to [Ru(III)(tpy)(pic)(OH)](+), and its further oxidation of to the ultimate product [Ru(IV)(tpy)(pic)(O)](+) complex. The time course of the reaction was followed as a function of [S(2)O(8)(2-)], ionic strength (I) and temperature. Kinetic data and activation parameters are interpreted in terms of an outer-sphere electron transfer mechanism. Anti-microbial activity of Ru(II)(tpy)(pic)H(2)O](+) complex by inhibiting the growth of Escherichia coli DH5α in presence of peroxydisulfate has been explored, and the results of the biological studies have been discussed in terms of the [Ru(IV)(tpy)(pic)(O)](+) mediated cleavage of chromosomal DNA of the bacteria.     

Efficient oxidation of cysteine and glutathione catalyzed by a dinuclear areneruthenium trithiolato anticancer complex

The highly cytotoxic diruthenium complex [(p-MeC(6)H(4)Pr(i))(2)Ru(2)(SC(6)H(4)-p-Me)(3)](+) (1), water-soluble as the chloride salt, is shown to efficiently catalyze oxidation of the thiols cysteine and glutathione to give the corresponding disulfides, which may explain its high in vitro anticancer activity.