Biological Potential of Halfsandwich Ruthenium(II) and Iridium (III) Complexes.

In vitro studies with the ruthenium(II) and analogous iridium(III) complexes [Ru(η6- p-cymene)Cl2{Ph2PCH2CH2CH2S(O)xPh-κP}], [Ru(η6-p-cymene)Cl{Ph2PCH2CH2CH2S(O)xPh- κP,κS}][PF6] (1-4), [Ir(η5-C5Me5)Cl2{Ph2PCH2CH2CH2S(O)xPh-κP}] and [Ir(η5-C5Me5)Cl{Ph2 PCH2CH2CH2S(O)xPh-κP,κS}][PF6] (5-8; x = 0, 1) revealed the high selectivity toward the 8505C, A253, MCF-7, SW480 and 518A2 cancer cell lines. Thus, the cationic ruthenium complex 4 proved to be the most selective one. In case of the neutral and cationic ruthenium complexes 1-4 the caspase-dependent apoptotic cell death was proven as the main cause of the drug's tumoricidal action on 8505C cell line.

The challenge of deciphering linkage isomers in mixtures of oligomeric complexes derived from 9-methyladenine and trans-(NH3)2Pt(II) units.

Metal coordination to N9-substituted adenines, such as the model nucleobase 9-methyladenine (9MeA), under neutral or weakly acidic pH conditions in water preferably occurs at N1 and/or N7. This leads, not only to mononuclear linkage isomers with N1 or N7 binding, but also to species that involve both N1 and N7 metal binding in the form of dinuclear or oligomeric species. Application of a trans-(NH3)2Pt(II) unit and restriction of metal coordination to the N1 and N7 sites and the size of the oligomer to four metal entities generates over 50 possible isomers, which display different feasible connectivities. Slowly interconverting rotamers are not included in this number. Based on (1)H NMR spectroscopic analysis, a qualitative assessment of the spectroscopic features of N1,N7-bridged species was attempted. By studying the solution behavior of selected isolated and structurally characterized compounds, such as trans-[PtCl(9MeA-N7)(NH3)2]ClO4⋅2H2O or trans,trans-[{PtCl(NH3)2}2(9MeA-N1,N7)][ClO4]2⋅H2O, and also by application of a 9MeA complex with an (NH3)3Pt(II) entity at N7, [Pt(9MeA-N7)(NH3)3][NO3]2, which blocks further cross-link formation at the N7 site, basic NMR spectroscopic signatures of N1,N7-bridged Pt(II) complexes were identified. Among others, the trinuclear complex trans-[Pt(NH3)2{µ-(N1-9MeA-N7)Pt(NH3)3}2][ClO4]6⋅2H2O was crystallized and its rotational isomerism in aqueous solution was studied by NMR spectroscopy and DFT calculations. Interestingly, simultaneous Pt(II) coordination to N1 and N7 acidifies the exocyclic amino group of the two 9MeA ligands sufficiently to permit replacement of one proton each by a bridging heterometal ion, Hg(II) or Cu(II), under mild conditions in water.

Lithiated sulfoxides: α-sulfinyl functionalized carbanions.

Reactions of alkyl aryl sulfoxides H-CRR'S(O)Ar with n-BuLi-TMEDA (TMEDA = N,N,N',N'-tetramethylethylenediamine) afforded α-sulfinyl functionalized alkyl aryl lithium compounds of the type [Li2{CRR'S(O)Ar}2(TMEDA)2] (1, R/R' = H/H, Ar = Ph; 2, R/R' = H/H, Ar = p-Tol; 3, R/R' = Me/Me, Ar = Ph; 4, R/R' = H/Ph, Ar = Ph; 5, R/R' = Me/Ph, Ar = Ph). The compounds were characterized by (1)H, (13)C and (7)Li NMR spectroscopy and, except for 5, by single-crystal X-ray diffraction analyses. In crystals of 1, 2, 3 and 4 ·Et2O dinuclear molecules with four-membered Li2O2 rings were found. There are no LiCα contacts, thus, "free" carbanions are the main structural feature. Reactions of 1-6 (6, R/R' = H/Me, Ar = Ph) with benzaldehyde and benzophenone afforded the corresponding sulfoxides of the type ArS(O)CRR'CHPhOH (1a-6a) and ArS(O)CRR'CPh2OH (1b-6b), respectively. The reactions yielding / and / proceeded with high diastereoselectivities. By X-ray diffractometry it has been shown that in the case of and the diastereomers consisting of the two enantiomers SSRC and RSSC were formed.

Organotin(IV)-loaded mesoporous silica as a biocompatible strategy in cancer treatment.

The strong therapeutic potential of an organotin(IV) compound loaded in nanostructured silica (SBA-15pSn) is demonstrated: B16 melanoma tumor growth in syngeneic C57BL/6 mice is almost completely abolished. In contrast to apoptosis as the basic mechanism of the anticancer action of numerous chemotherapeutics, the important advantage of this SBA-15pSn mesoporous material is the induction of cell differentiation, an effect unknown for metal-based drugs and nanomaterials alone. This non-aggressive mode of drug action is highly efficient against cancer cells but is in the concentration range used nontoxic for normal tissue. JNK (Jun-amino-terminal kinase)-independent apoptosis accompanied by the development of the melanocyte-like nonproliferative phenotype of survived cells indicates the extraordinary potential of SBA-15pSn to suppress tumor growth without undesirable compensatory proliferation of malignant cells in response to neighboring cell death.

Anticancer potential of (pentamethylcyclopentadienyl)chloridoiridium(III) complexes bearing κP and κP,κS-coordinated Ph2 PCH2 CH2 CH2 S(O)x Ph (x=0-2) ligands.

Iridium(III) complexes of the type [Ir(η(5) -C5 Me5 )Cl2 {Ph2 PCH2 CH2 CH2 S(O)x Ph-κP}] (x=0-2; 1-3) and [Ir(η(5) -C5 Me5 )Cl{Ph2 PCH2 CH2 CH2 S(O)x Ph-κP,κS}][PF6 ] (x=0-1; 4 and 5) with 3-(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2 PCH2 CH2 CH2 S(O)x Ph were designed, synthesized, and characterized fully, including X-ray diffraction analyses for complexes 3 and 4. In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF-7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC50 values up to about 0.1 µM, representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal-based anticancer agents.

Biological activity of neutral and cationic iridium(III) complexes with κP and κP,κS coordinated Ph2PCH2S(O)xPh (x = 0-2) ligands.

Neutral iridium(III) complexes of the type [Ir(η(5)-C5Me5)Cl2{Ph2PCH2S(O)xPh-κP}] (1-3) with diphenylphosphino-functionalized methyl phenyl sulfides, sulfoxides, and sulfones Ph2PCH2S(O)xPh (x = 0, L1; 1, L2; 2, L3) and the cationic complex [Ir(η(5)-C5Me5)Cl{Ph2PCH2SPh-κP,κS}][PF6] (4) were synthesized and fully characterized analytically and spectroscopically. Furthermore, the structure of 2 was determined by X-ray diffraction analysis. The biological potential of the neutral and cationic iridium(III) complexes was tested in vitro against the cell lines 8505C, A253, MCF-7, SW480 and 518A2. Complex [Ir(η(5)-C5Me5)Cl2{Ph2PCH2S(O)Ph-κP}] (2), with ligand L2 κP coordinated containing a pendent sulfinyl group, is the most active one (IC50 values of about 3 µM), thus, with activities comparable to cisplatin. Complex 2 proved to have an even a higher antiproliferative activity than cisplatin against 8505C and SW480 cell lines, used as a model system of highly anaplastic cancers with low sensitivity to conventional chemotherapeutics such as cisplatin. Additional experiments demonstrated that apoptosis and autophagic cell death contribute to the drug's tumoricidal action.

Cationic arene ruthenium(II) complexes with chelating P-functionalized alkyl phenyl sulfide and sulfoxide ligands as potent anticancer agents.

The synthesis and characterization of cationic ruthenium(II) complexes of the type [Ru(η(6)-p-cym)Cl{Ph(2)P(CH(2))(n)S(O)(x)Ph-κP,κS}][PF(6)] (n = 1-3; x = 0, 1; p-cym = p-cymene) are presented. Furthermore, their high biological potential even against cisplatin-resistant tumor cell lines and their structure-activity relationships are discussed.

Platinum(II/IV) complexes containing ethylenediamine-N,N'-di-2/3-propionate ester ligands induced caspase-dependent apoptosis in cisplatin-resistant colon cancer cells.

Several new R(2)eddp (R = i-Pr, i-Bu; eddp = ethylenediamine-N,N'-di-3-propionate) esters and corresponding platinum(ii) and platinum(iv) complexes of the general formula [PtCl(n)(R(2)edda-type)] (n = 2, 4) were synthesized and characterized by spectroscopic methods (IR, (1)H and (13)C NMR) and elemental analysis. The crystal structure of platinum(iv) complex [PtCl(4){(c-Pe)(2)eddip}] (3a) was resolved and is given herein. Ligand precursors, platinum(ii), and platinum(iv) complexes were tested against eight tumor cell lines (CT26CL25, HTC116, SW620, PC3, LNCaP, U251, A375, and B16). Selectivity in the action of those compounds between tumor and two normal primary cells (fibroblasts and keratinocytes) are discussed. A structure-activity relationship of these compounds is discussed. Furthermore, cell cycle distribution, induction of necrosis, apoptosis, autophagy, anoikis, caspase activation, ROS, and RNS are presented on the cisplatin-resistant colon carcinoma HCT116 cell line.

Highly active neutral ruthenium(II) arene complexes: synthesis, characterization, and investigation of their anticancer properties.

Reactions of ω-diphenylphosphino-functionalized alkyl phenyl sulfides Ph(2)P(CH(2))(n)SPh (n=1, L1; 2, L2; 3, L3), sulfoxides Ph(2)P(CH(2))(n)S(O)Ph (n=1, L4; 2, L5; 3, L6) and sulfones Ph(2)P(CH(2))(n)S(O)(2)Ph (n=1, L7; 2, L8; 3, L9) with the dinuclear chlorido bridged ruthenium(II) complex [{Ru(η(6)-p-cymene)Cl(2)}(2)] afforded mononuclear ruthenium(II) complexes of the type [Ru(η(6)-p-cymene)Cl(2){Ph(2)P(CH(2))(n)S(O)(x)Ph-κP}] (n/x=1/0, 1; 2/0, 2; 3/0, 3; 1/1, 4; 2/1, 5; 3/1, 6; 1/2, 7; 2/2, 8; 3/2, 9) having the P(∩)S(O)(x) ligands κP coordinated. The complexes were characterized by (1)H, (13)C and (31)P NMR spectroscopy. The crystal structures of complexes 2, 7·CH(2)Cl(2) and 8 were determined by X-ray diffraction analysis. All complexes have been screened for cytostatic activity against cell lines 518A2, 8505C, A253, MCF-7, and SW480. In vitro biological experiments demonstrate that these compounds are active toward the used cell lines. The ruthenium(II) complex [Ru(η(6)-p-cymene)Cl(2){Ph(2)P(CH(2))(2)SPh-κP}] (2) is the most active compound in the human cancer cell line MCF-7 with the IC(50) value 1.4 µM lower than cisplatin (2.0 µM).

Chlorido[1-diphenyl-phosphanyl-3-(phenyl-sulfan-yl)propane-κ(2)P,S](η(5)-penta-methyl-cyclo-penta-dien-yl)iridium(III) chloride monohydrate.

The crystal structure of the title compound, [Ir(C(10)H(15))Cl(C(21)H(21)PS)]Cl·H(2)O, consists of discrete [Ir(η(5)-C(5)Me(5))Cl{Ph(2)P(CH(2))(3)SPh-κP,κS}](+) cations, chloride anions and water mol-ecules. The Ir(III) atom is coordinated by an η(5)-C(5)Me(5) ligand, a chloride and a Ph(2)P(CH(2))(3)SPh-κP,κS ligand, leading to a three-legged piano-stool geometry. In the crystal, two water molecules and two chloride anions are linked by weak O-H⋯Cl hydrogen bonding into tetra-mers that are located on centers of inversion. The H atoms of one of the methyl groups are disordered and were refined using a split model.

On the isomerization of cyclooctyne into cycloocta-1,3-diene: synthesis, characterization and structure of a dinuclear platinum(II) complex with a µ-η2:η2-1,3-COD ligand.

The Zeise's salt type cyclooctyne compound [K(18C6)][PtCl(3)(COC)] (1; COC = cyclooctyne; 18C6 = 18-crown-6) was found to react in chloroform solution at room temperature within several weeks yielding the dinuclear cyclooctadiene compound [K(18C6)](2)[(PtCl(3))(2)(µ-η(2):η(2)-1,3-COD)] (2; 1,3-COD = cycloocta-1,3-diene) and non-coordinated cycloocta-1,3-diene. The identity of 2 was confirmed by microanalysis, NMR spectroscopy ((1)H, (13)C) and electrospray ionization mass spectrometry (ESI-MS). A single-crystal X-ray diffraction analysis of 2 exhibited a bridging µ-η(2):η(2)-cycloocta-1,3-diene ligand with non-conjugated double bonds each coordinated to a PtCl(3) fragment. On the basis of DFT calculations as well as energy decomposition analyses (EDA), charge decomposition analyses (CDA) and natural bond orbital (NBO) analyses the peculiarities of the nature of the Pt-C bonds in the dinuclear complex anion [(PtCl(3))(2)(µ-η(2):η(2)-1,3-COD)](2-) (2a') compared with those in mononuclear olefin complexes of Zeise's salt type [PtCl(3)L](-) (L = η(2)-1,3-COD, 3a'; cis-but-2-ene, 4a'; COE, 5a'; COE = cyclooctene) are discussed. Furthermore, the driving force for the strongly exergonic reaction with formation of the cyclooctadiene complex 2a' was found to be a significant release of ring strain of the cyclooctyne ligand in the starting compound 1.

[3-Meth-oxy-1-(phenyl-sulfan-yl)prop-yl]triphenyl-tin(IV) benzene 0.17-solvate.

In the title compound, [Sn(C(6)H(5))(3)(C(10)H(13)OS)]·0.17C(6)H(6), the Sn(IV) atom exhibits a slightly distorted tetra-hedral coordination geometry built up by four C atoms, which are the three ipso-C atoms of the phenyl rings and the α-C atom of the deprotonated γ-O-functionalized propyl phenyl sulfide. The benzene mol-ecule lies about a threefold rotoinversion axis.

Synthesis, characterization and reactivity of carbohydrate platinum(IV) complexes with thioglycoside ligands.

Reactions of fac-[PtMe3(4,4'-R2bpy)(Me2CO)][BF4] (R = H, 1a; tBu, 1b) and fac-[PtMe3(OAc-kappa2O,O')(Me2CO)] (2), respectively, with thioglycosides containing thioethyl (ch-SEt) and thioimidate (ch-STaz, Taz = thiazoline-2-yl) anomeric groups led to the formation of the carbohydrate platinum(IV) complexes fac-[PtMe3(4,4-R2bpy)(ch*)][BF4] (ch* = ch-SEt, 8-14; ch-STaz, 15-23) and fac-[PtMe3(OAc-kappa2O,O')(ch*)] (ch* = ch-SEt, 24-28; ch-STaz = 29-35), respectively. NMR (1H, 13C, 195Pt) spectroscopic investigations and a single-crystal X-ray diffraction analysis of 19 (ch-STaz = 2-thiazolinyl 2,3,4,6-tetra-O-benzoyl-1-thio-beta-D-galactopyranose) revealed the S coordination of the ch-SEt glycosides and the N coordination of the ch-STaz glycosides. Furthermore, X-ray structure analyses of the two decomposition products fac-[PtMe3(bpy)(STazH-kappaS)][BF4] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-beta-D-glucopyranose (23a), where a cleavage of the anomeric C-S bond had occurred in both cases, gave rise to the assumption that this decomposition was mediated due to coordination of the thioglycosides to the high electrophilic platinum(IV) atom, in non-strictly dried solutions. Reactions of fac-[PtMe3(Me2CO)3][BF4] (3) with ch-SEt as well as with ch-SPT and ch-Sbpy thioglycosides (PT = 4-(pyridine-2-yl)-thiazole-2-yl; bpy = 2,2'-bipyridine-6-yl), having N,S and N,N heteroaryl anomeric groups, respectively, led to the formation of platinum(IV) complexes of the type fac-[PtMe3(ch*)][BF4] (ch* = ch-SEt, 36-40, ch-SPT 42-44, ch-Sbpy 45, 46). The thioglycosides were found to be coordinated in a tridentate kappaS,kappa2O,O, kappaS,kappaN,kappaO and kappaS,kappa2N,N coordination mode, respectively. Analogous reactions with ch-STaz ligands succeeded for 2-thiazolinyl 2,3,4-tri-O-benzyl-6-O-(2,2'-bipyridine-6-yl)-1-thio-beta-D-glucopyranoside (5h) resulting in fac-[PtMe3(ch-STaz)][BF4] (41, ch-STaz = 5h), having a kappa3N,N',N''coordinated thioglycoside ligand.

Synthesis, characterization and structures of cyclic organorhodium complexes of the type [Rh{CH(SO2Ph)CH2CH2YR2-κC,κY}L2] (YR2 = PPh2, NMe2; L2 = diphosphine, cyclooctadiene).

Reactions of dinuclear chloridorhodium(I) complexes [(RhL2)2(µ-Cl)2] (L2 = P[symbol: see text]P: Me2P(CH2)2PMe2, dmpe, 7a; Ph2PCH2PPh2, dppm, 7b; Ph2P(CH2)2PPh2, dppe, 7c; Ph2P(CH2)3PPh2, dppp, 7d; L2 = cycloocta-1,5-diene, cod, 5) with lithiated γ-phosphino- and γ-aminofunctionalized propyl phenyl sulfones (Li[CH(SO2Ph)CH2CH2PPh2], 2; Li[CH(SO2Ph)CH2CH2NMe2], 4) led to the formation of organorhodium inner complexes of the type [Rh{CH(SO2Ph)CH2CH2PPh2-κC,κP}(P[symbol: see text]P)] (8a-d), [Rh{CH(SO2Ph)CH2CH2NMe2-κC,κN}(P[symbol: see text]P)] (9a-d), [Rh{CH(SO2Ph)CH2CH2PPh2-κC,κP}(cod)]·LiCl (11·LiCl) and [Rh{CH(SO2Ph)CH2CH2NMe2-κC,κN}(cod)]·LiCl (12·LiCl), respectively. Single-crystal X-ray diffraction analysis of 9c·THF, 11 and 12 exhibited in all three compounds a distorted square planar coordination of the rhodium atoms having bidentately coordinated neutral co-ligands (cod, 11, 12; dppe, 9c) and anionic α-phenylsulfonyl γ-phosphinopropyl (κC,κP; 11) and γ-aminopropyl ligands (κC,κN; 12, 9c), thus being typical organorhodium inner complexes. Furthermore, organorhodium inner complexes of type 8 were obtained in reactions of the dinuclear chloridobridged rhodium complexes [(RhL2)2(µ-Cl)2] (L2 = P[symbol: see text]P, 7a-d; cod, 5; (C2H4)2, 6) with the (non-lithiated) γ-phosphinofunctionalized propyl phenyl sulfone PhSO2CH2CH2CH2PPh2 (1) resulting in the formation of complexes having the sulfone κP coordinated ([RhClL2-(Ph2PCH2CH2CH2SO2Ph-κP)] (L2 = P[symbol: see text]P, 10a-d; cod, 13; (C2H4)2, 14) which were deprotonated (10a-d, 13) at the α-C atom with lithium diisopropyl amide (LDA) in a subsequent reaction. Single-crystal X-ray diffraction analysis of 10c (P[symbol: see text]P = dppe) revealed the expected square-planar coordination geometry of Rh. The identities of all rhodium complexes have been unambiguously proved by microanalyses and NMR spectroscopy (¹H, ¹³C, ³¹P).

(Acetato-κO)(2,2'-bipyridine-κN,N')trimethyl-platinum(IV) monohydrate.

In the title hydrate, [Pt(CH(3))(3)(CH(3)COO)(C(10)H(8)N(2))]·H(2)O, the Pt(IV) atom exhibits a distorted octa-hedral coordination geometry built up by three methyl ligands in a facial arrangement, a bipyridine ligand and a monodentately bound acetate ligand. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds are observed between the water mol-ecule and the platinum complex, which link the mol-ecules into chains along the c axis.

(OC-6-33)-(2,2'-Bipyridine-κN,N')trimeth-yl(2-methyl-sulfanyl-2-thia-zoline-κN)platinum(IV) tetra-fluoridoborate.

The asymmetric unit of the title complex, [Pt(CH(3))(3)(C(10)H(8)N(2))(C(4)H(7)NS(2))]BF(4), contains two crystallographically independent mol-ecules. The Pt(IV) atom in each complex cation exhibits a distorted octa-hedral coordination geometry, built up by three methyl ligands in a facial binding fashion, a bipyridine ligand and a monodentately N-bound 2-methyl-sulfanyl-2-thia-zoline ligand (configuration index: OC-6-33). In the crystal structure, weak inter-molecular C-H⋯F hydrogen bonds are found between the complex cations and BF(4) (-) anions.

Synthesis, characterization, in vitro antitumoral investigations and interaction with plasmid pBR322 DNA of R2eddp-platinum(IV) complexes (R = Et, n-Pr).

The studies on synthetic, spectroscopic and biological properties of platinum(IV) complexes, [PtCl(4)(R(2)eddp)] (R = Et, 1; n-Pr, 2), containing kappa(2)N,N' bidentate ligands, esters of ethylenediamine-N,N'-di-3-propionic acid (HOOCCH(2)CH(2)NHCH(2)CH(2)NHCH(2)CH(2)COOH, H(2)eddp), are reported. Complexes have been characterized by infrared, (1)H and (13)C NMR spectroscopy and elemental analysis and it was concluded that the coordination of the ligands occurs via nitrogen donor atoms of the ester ligands (R(2)eddp). Cytotoxicity studies were performed for ligand precursors and corresponding platinum(IV) complexes. Although the n-Pr(2)eddp.2HCl itself showed no activity (IC(50) values > 125 microM) in selected cell lines, the activity of complex 2, via apoptotic mode of cell death, has increased significantly for a broad range of cancer cell lines tested in vitro (IC(50) = 8.6-49 microM). As it was found that complexes 1 and 2 are able to interact with pBR322 plasmid DNA, platinum(IV) complexes of this type may act as drugs and pro-drugs.

Coordination chemistry approach to the long-standing challenge of stereocontrolled chemical glycosylation.

This study clearly demonstrates that a multi-dentate metal coordination to the leaving group, along with O-5 and/or a protecting group at O-6, has a strong effect on the stereoselectivity of chemical glycosylation.

Synthesis of trimethylplatinum(IV) complexes with N,N- and N,O-heterocyclic carbene ligands and their reductive C-C elimination reactions.

Reactions of the platinum(IV) complexes [PtMe(3)(OCMe(2))(3)](BF(4)) (1(BF(4))), [(PtMe(3)I)(4)] (2), and [PtMe(3)I(py)(2)] (3) with the N,N-heterocyclic carbene 1,3-dimethylimidazol-2-ylidene (N,N-hc, 4) resulted in a rapid reductive elimination of ethane, yielding platinum(II) complexes [PtMe(N,N-hc)(3)](+) (7), trans-[PtMeI(N,N-hc)(2)] (8), and cis-[PtMe(py)(N,N-hc)(2)](+) (10), respectively. Subsequent substitution of the iodo ligand in 8 by pyridine resulted in the formation of trans-[PtMe(py)(N,N-hc)(2)](CF(3)COO) (9(CF(3)COO)). 9 and 10 are stereoisomers. In contrast to this, the analogous reaction of [PtMe(3)(OCMe(2))(3)](BF(4)) (1(BF(4))) with the N,O-heterocyclic carbene 3-methyloxazol-2-ylidene (N,O-hc, 5) was found to yield the tris(carbene)trimethylplatinum(IV) compound [PtMe(3)(N,O-hc)(3)](BF(4)) (12(BF(4))), which is thermally stable up to 218 degrees C in the solid state. Furthermore, reactions of [{PtMe(3)(acac)}(2)] (15) with the N,X-heterocyclic carbenes (X = N, O, S; N,S-hc = 3-methylthiazol-2-ylidene, 6) resulted in the formation of monocarbenetrimethylplatinum(IV) complexes [PtMe(3)(acac)(N,X-hc)] (X = N, 16; X = O, 17; X = S, 18), which were found to be stable against reductive C-C elimination at ambient temperature. Reactions of 16 and 17 with 2,2'-bipyridine (bpy) in the presence of stoichiometric amounts of H(BF(4)) yielded cationic monocarbeneplatinum(IV) complexes, which were isolated as tetrafluoroborate salts [PtMe(3)(bpy)(N,X-hc)](BF(4)) (X = N, 19(BF(4)); X = O, 20(BF(4))). The compounds have been fully characterized analytically and NMR spectroscopically, and for the bis(carbene)platinum(II) compound 9(CF(3)COO) as well as the monocarbeneplatinum(IV) compounds 16 and 20(BF(4)) by single-crystal X-ray diffraction analyses. DFT calculations of mono-, bis-, and tris(carbene)trimethylplatinum(IV) complexes and their propensity to reductive eliminate ethane were performed. In accordance with the experimental findings, a much higher stability of the tris(N,O-hc)- compared with the tris(N,N-hc)trimethylplatinum(IV) complexes against reductive ethane elimination was found, which could be ascribed mainly to a higher steric demand of the N,N-hc ligand.

Palladium(II) complexes with R2edda-derived ligands. Part II. Synthesis, characterization and in vitro antitumoral studies of R2eddip esters and palladium(II) complexes.

New R(2)eddip-type esters (R = cyclopentyl, L3 x 2 HCl 1.5 H(2)O; cyclohexyl, L4 x 2 HCl x H(2)O) and corresponding palladium(II) complexes, [PdCl(2)L3] (3) and [PdCl(2)L4] x H(2)O (4), as well as [PdCl(2)L2] (2; L2 diisobutyl ester of eddip) were synthesized and characterized by IR, (1)H and (13)C NMR spectroscopies and elemental analysis. The crystal structure of L3 x 2 HCl x 2 CHCl(3) was resolved and is given herein. The NMR spectroscopy confirmed the presence of two isomers (from three possible) for each palladium(II) complex. DFT calculations support the formation of two diastereoisomers. In addition, antitumoral investigations were performed and these investigations also included the diisopropyl ester of eddip (L1) and corresponding palladium(II) complex, [PdCl(2)L1] (1). In vitro antiproliferative activity was determined against several tumor cell lines HeLa, Fem-x, K562 and rested and stimulated normal immunocompetent cells (human peripheral blood mononuclear cells--PBMCs) using MTT test.