Synthesis, Characterization, and Cytotoxicity Studies of N-(4-Methoxybenzyl) Thiosemicarbazone Derivatives and Their Ruthenium(II)-p-cymene Complexes.

The reaction of [Ru2Cl2(µ-Cl)2(η6-p-cymene)2] with two thiosemicarbazones obtained by the condensation of N-(4-methoxybenzyl) thiosemicarbazide and 1,4-hydroxy-3-methoxyphenyl)ethan-1-one (HL1) or 2-fluoro-4-hydroxybenzaldehyde (HL2) was studied. The cationic complexes of formula [RuCl(η6-p-cymene)(HL)]+ were isolated as solid chloride and trifluoromethylsulfate (TfO) salts. A study of the solid state and NMR spectra suggests the presence in the material of two isomers that differ in the configuration in the iminic bond, C2=N3, of the coordinated thiosemicarbazone in the triflate salts and only the E isomer in the chloride. An X-ray study of single crystals of the complexes supports this hypothesis. The thiosemicarbazone ligand coordinates with the ruthenium center through the iminic and sulfur atoms to form a five-membered chelate ring. Furthermore, the isolation of single crystals containing the thiosemicarbazonate complex [Ru2(µ-L2)2(η6-p-cymene)2]2+ suggests the easy labilization of the coordinated chloride in the complex. The redox behavior of the ligands and complexes was evaluated by cyclic voltammetry. It seems to be more difficult to oxidize the complex derived from HL1 than HL2. The ability of the complexes to inhibit cell growth against the NCI-H460, A549 and MDA-MB-231 lines was evaluated. The complexes did not show greater potency than cisplatin, although they did have greater efficacy, especially for the complex derived from HL1.

Preparation of benzyl azide complexes of iridium(III).

Hydride complexes IrHCl(2)(PiPr(3))P(2) (1) and IrHCl(2)P(3) (2) [P = P(OEt)(3) and PPh(OEt)(2)] were prepared by allowing IrHCl(2)(PiPr(3))(2) to react with phosphite in refluxing benzene or toluene. Treatment of IrHCl(2)P(3), first with HBF(4).Et(2)O and then with an excess of ArCH(2)N(3), afforded benzyl azide complexes [IrCl(2)(eta(1)-N(3)CH(2)Ar)P(3)]BPh(4) (3, 4) [Ar = C(6)H(5), 4-CH(3)C(6)H(4); P = P(OEt)(3), PPh(OEt)(2)]. Azide complexes reacted in CH(2)Cl(2) solution, leading to the imine derivative [IrCl(2){eta(1)-NH=C(H)C(6)H(5)}P(3)]BPh(4) (5). The complexes were characterized by spectroscopy and X-ray crystal structure determination of [IrCl(2)(eta(1)-N(3)CH(2)C(6)H(5)){P(OEt)(3)}(3)]BPh(4) (3a) and [IrCl(2){eta(1)-NH=C(H)C(6)H(5)}{P(OEt)(3)}(3)]BPh(4) (5a). Both solid-state structure and (15)N NMR data indicate that the azide is coordinated through the substituted Ngamma [Ir]-Ngamma(CH(2)Ar)NNalpha nitrogen atom.

Preparation of stannyl complexes of ruthenium and osmium stabilised by polypyridine and phosphite ligands.

Trichlorostannyl complexes [M(SnCl3)(bpy)2P]BPh4 [M = Ru, P = P(OEt)(3), 1a PPh(OEt)2 1b; M = Os, P = P(OEt)3 2; bpy = 2,2'-bipyridine] were prepared by allowing chloro complexes [MCl(bpy)2P]BPh4 to react with SnCl2 in 1,2-dichloroethane. Bis(trichlorostannyl) compounds Ru(SnCl3)2(N-N)P2 [N-N = bpy, P = P(OEt)3 3a, PPh(OEt)2 3b; N-N = 1,10-phenanthroline (phen), P = P(OEt)3 4] were also prepared by reacting [RuCl(N-N)P3]BPh4 precursors with SnCl2.2H2O in ethanol. Treatment of both mono- 1a, 2 and bis 3a trichlorostannyl complexes with NaBH4 afforded mono- and bis(trihydridestannyl) derivatives [M(SnH3)(bpy)2P]BPh4 5, 6 and Ru(SnH3)2(bpy)P2 7[P = P(OEt)3], respectively. Treatment of 1a, 2 with MgBrMe gave the trimethylstannyl complexes [M(SnMe3)(bpy)2P]BPh4 8, 9 and treatment of 3a afforded the bis(stannyl) Ru(SnClMe2)2(bpy)P2 10 derivative. Alkynylstannyl complexes [M{Sn(C triple bond CR)3}(bpy)2P]BPh4 11-13 and Ru[Sn(C triple bond CR)3]2(N-N)P2 14-17(R = p-tolyl, Bu t; N-N = bpy, phen) were also prepared by allowing trichlorostannyl compounds 1-4 to react with Li+[RC triple bond C]* in thf. The complexes were characterised spectroscopically and by the X-ray crystal structure determination of [Ru(SnMe3)(bpy)2{P(OEt)3}]BPh4 derivative.

Synthesis and characterization of triazenide and triazene complexes of ruthenium and osmium.

Triazenide [M(eta2-1,3-ArNNNAr)P4]BPh4 [M = Ru, Os; Ar = Ph, p-tolyl; P = P(OMe)3, P(OEt)3, PPh(OEt)2] complexes were prepared by allowing triflate [M(kappa2-OTf)P4]OTf species to react first with 1,3-ArN=NN(H)Ar triazene and then with an excess of triethylamine. Alternatively, ruthenium triazenide [Ru(eta2-1,3-ArNNNAr)P4]BPh4 derivatives were obtained by reacting hydride [RuH(eta2-H2)P4]+ and RuH(kappa1-OTf)P4 compounds with 1,3-diaryltriazene. The complexes were characterized by spectroscopy and X-ray crystallography of the [Ru(eta2-1,3-PhNNNPh){P(OEt)3}4]BPh4 derivative. Hydride triazene [OsH(eta1-1,3-ArN=NN(H)Ar)P4]BPh4 [P = P(OEt)3, PPh(OEt)2; Ar = Ph, p-tolyl] and [RuH{eta1-1,3-p-tolyl-N=NN(H)-p-tolyl}{PPh(OEt)2}4]BPh4 derivatives were prepared by allowing kappa1-triflate MH(kappa1-OTf)P4 to react with 1,3-diaryltriazene. The [Os(kappa1-OTf){eta1-1,3-PhN=NN(H)Ph}{P(OEt)3}4]BPh4 intermediate was also obtained. Variable-temperature NMR studies were carried out using 15N-labeled triazene complexes prepared from the 1,3-Ph15N=N15N(H)Ph ligand. Osmium dihydrogen [OsH(eta2-H2)P4]BPh4 complexes [P = P(OEt)3, PPh(OEt)2] react with 1,3-ArN=NN(H)Ar triazene to give the hydride-diazene [OsH(ArN=NH)P4]BPh4 derivatives. The X-ray crystal structure determination of the [OsH(PhN=NH){PPh(OEt)2}4]BPh4 complex is reported. A reaction path to explain the formation of the diazene complexes is also reported.

Preparation and reactivity of penta- and tetracoordinate platinum(II) hydride complexes with P(OEt)3 and PPh(OEt)2 phosphite ligands.

The pentacoordinate [PtH{P(OEt)3}4]BF4 (1) hydride complex was prepared by allowing the tetrakis(phosphite) Pt{P(OEt)3}4 to react with HBF4.Et2O at -80 degrees C. Depending on the nature of the acid used, however, the protonation of the related Pt{PPh(OEt)2}4 complex yielded the pentacoordinate [PtH{PPh(OEt)2}4]BF4 (3) or the tetracoordinate [PtH{PPh(OEt)2}3]Y (4) [Y = BF4- (a), CF3SO3- (b), Cl- (c)] derivatives. Neutral PtHClP2 (7,8) [P = P(OEt)3, PPh(OEt)2] hydride complexes were prepared by allowing PtCl2P2 to react with NaBH4 in CH3CN. The tetrakis(phosphite)[Pt{P(OEt)3}4](BF4)2 (2) derivative was also synthesised and then characterised spectroscopically and by an X-ray crystal structure determination. Reactivity with aryldiazonium cations of all the hydrides was investigated and found to proceed only with the PtHClP2 complex to yield the aryldiazene [PtCl(ArN=NH)P2]BF4[P = PPh(OEt)2] derivative. The hydrazine [PtCl(NH2NH2){PPh(OEt)2}2]BPh4 complex was also prepared by allowing PtHClP2 to react first with AgCF3SO3 and then with hydrazine.

Ruthenium tris(pyrazolyl)borate diazo complexes: preparation of aryldiazenido, aryldiazene, and hydrazine derivatives.

Tris(pyrazolyl)borate aryldiazenido complexes [RuTpLL'(ArN(2))](BF(4))(2) (1-3) [Ar = C(6)H(5), 4-CH(3)C(6)H(4); Tp = hydridotris(pyrazolyl)borate; L = P(OEt)(3) or PPh(OEt)(2), L' = PPh(3); L = L' = P(OEt)(3)] were prepared by allowing dihydrogen [RuTp(eta(2)-H(2))LL'](+) derivatives to react with aryldiazonium cations. Spectroscopic characterization (IR, (15)N NMR) using the (15)N-labeled derivatives strongly supports the presence of a linear [Ru]-NN-Ar aryldiazenido group. Hydrazine complexes [RuTp(RNHNH(2))LL']BPh(4) (4-6) [R = H, CH(3), C(6)H(5), 4-NO(2)C(6)H(4); L = P(OEt)(3) or PPh(OEt)(2), L' = PPh(3); L = L' = P(OEt)(3)] were also prepared by reacting the [RuTp(eta(2)-H(2))LL'](+) cation with an excess of hydrazine. The complexes were characterized spectroscopically (IR and NMR) and by X-ray crystal structure determination of the [RuTp(CH(3)NHNH(2))[P(OEt)(3)](PPh(3))]BPh(4) (4d) derivative. Tris(pyrazolyl)borate aryldiazene complexes [RuTp(ArN=NH)LL']BPh(4) (7-9) (Ar = C(6)H(5), 4-CH(3)C(6)H(4)) were prepared following three different methods: (i). by allowing hydride species RuHTpLL' to react with aryldiazonium cations in CH(2)Cl(2); (ii). by treating aryldiazenido [RuTpLL'(ArN(2))](BF(4))(2) with LiBHEt(3) in CH(2)Cl(2); (iii). by oxidizing arylhydrazine [RuTp(ArNHNH(2))LL']BPh(4) complexes with Pb(OAc)(4) in CH(2)Cl(2) at -30 degrees C. Methyldiazene complexes [RuTp(CH(3)N=NH)LL']BPh(4) were also prepared by the oxidation of the corresponding methylhydrazine [RuTp(CH(3)NHNH(2))LL']BPh(4) with Pb(OAc)(4).