Pyrazole and Pyrazolate as Ligands in the Synthesis and Stabilization of New Palladium(II) and (III) Compounds.

The versatility of pyrazole/pyrazolate as ligands has allowed the synthesis and the structural characterization of four different types of new orthometalated palladium compounds, for which DFT calculations have been performed in order to investigate their relative stabilities. [Pd2{µ-(C6H4)PPh2}2{µ-(R,R'2pz)}2] (R = R' = H, 2a; R = Br, R' = H, 2b; R = CH3, R' = H, 2c; R = H, R' = CH3, 2d; R = Br, R' = CH3, 2e) compounds with exo-bidentate pyrazolatos are the first paddlewheel dinuclear palladium(II) compounds with pyrazolato bridging ligands described and characterized in the literature. In the process of the synthesis of 2a, a new tetranuclear intermediate compound, [Pd4{µ-(C6H4)PPh2}4(µ-pz)2(µ-OH)2] (3a), has been isolated and structurally characterized. Compounds of the general formula [Pd2{µ-(C6H4)PPh2}2Br2(R,R'2pzH)2] (R = R' = H, 4a; R = Br; R' = H, 4b; R = CH3; R' = H, 4c; R = H; R' = CH3, 4d; R = Br; R' = CH3, 4e) with pyrazoles as monodentate ligands have also been obtained, in which, according to the QTAIM analysis, additional Br···HNpz weak interactions stabilize their structure. The tetranuclear Pd2Ag2 compounds, [Pd2{µ-(C6H4)PPh2}2{µ-(R,R'2pz-Ag-R,R'2pz)}2] (R = R' = H, 5a; R = Br; R' = H, 5b; R = CH3, R' = H, 5c), showed a distorted tetrahedron disposition of the metal atoms. The QTAIM analysis revealed an enhanced stability because of additional metal-metal interactions. New palladium(III) compounds, [Pd2{µ-(C6H4)PPh2}2{µ-(R,R'2pz)}2Cl2] (R = R' = H, 6a; R = Br, R' = H, 6b) were also synthesized by oxidation of compounds 2 with PhICl2. DFT calculations highlighted their greater stability compared to that of similar compounds with N,N-donor ligands, such as formamidinatos and triazenidos.

Tandem beta-boration/arylation of alpha,beta-unsaturated carbonyl compounds by using a single palladium complex to catalyse both steps.

Diphenyl(3-methyl-2-indolyl)phosphine (C(9)H(8)NPPh(2), 1) gives stable dimeric palladium(II) complexes that contain the phosphine in P,N-bridging coordination mode. On treating 1 with [Pd(O(2)CCH(3))(2)], the new complexes [Pd(mu-C(9)H(7)NPPh(2))(NCCH(3))](2) (2) or [Pd(mu-C(9)H(7)NPPh(2))(mu-O(2)CCH(3))](2) (3) were isolated, depending on the solvent used, acetonitrile or toluene, respectively. Further reaction of 3 with the ammonium salt of 1 led to the substitution of one carboxylate ligand to afford [Pd(mu-C(9)H(7)NPPh(2))(3)(mu-O(2)CCH(3))] (4), in which the bimetallic unit is bonded by three C(9)H(7)NPPh(2)(-) moieties and one carboxylate group. Using this methodology, [Pd(2)(mu-C(6)H(4)PPh(2))(2)(mu-C(9)H(7)NPPh(2))(mu-O(2)CCX(3))] (X=H (7); X=F (8)) were synthesised from the ortho-metalated compounds [Pd(C(6)H(4)PPh(2))(mu-O(2)CCX(3))](2) (X=H (5); X=F (6)). Complexes 3, 4, 7, and 8 have been found to be active in the catalytic beta-boration of alpha,beta-unsaturated esters and ketones under mild reaction conditions. Hindrance of the carbonyl moiety has an influence on the reaction rate, but quantitative conversion was achieved in many cases. More remarkably, when aryl bromides were added to the reaction media, complex 7 induced a highly successful consecutive beta-boration/cross-coupling reaction with dimethyl acrylamide as the substrate (99% conversion, 89% isolated yield).

Dirhodium(II) compounds with bridging thienylphosphines: studies on reversible P,C/P,S coordination.

Monocyclometalated compound [Rh(2){(C(8)H(4)S)P(C(8)H(5)S)(2)}(CH(3)CO(2)H)(2)(O(2)CCH(3))(3)] (1 a) and bis-cyclometalated compound [Rh(2){(C(8)H(4)S)P(C(8)H(5)S)(2)}(2)(CH(3)CO(2)H)(2)(O(2)CCH(3))(2)] (2 a) have been isolated from the reaction of dirhodium tetraacetate and tris(2-benzo[b]thienyl)phosphine (2 BTP) using low acidic solutions. By contrast, in pure acetic acid the reaction of Rh(2)(O(2)CCH(3))(4) with 2 BTP and tris(2-thienyl)phosphine (2 TP), followed by replacement of the axial acetate ligands by chlorides, led to [Rh(2){(2-C(8)H(5)S)P(2-C(8)H(5)S)(2)}(2)Cl(2)(O(2)CCH(3))(2)] (3 b) and [Rh(2){(2-C(4)H(3)S)P(C(4)H(3)S)(2)}(2)Cl(2)(O(2)CCH(3))(2)] (5 b), respectively. These new dirhodium(II) compounds possess equatorial bridging ligands in a phosphorous-sulfur (P,S) coordination mode. The reversible switching between the P,C and P,S bonding mode of the phosphine has been studied in the monocyclometalated [Rh(2){(C(4)H(2)S)P(C(4)H(3)S)(2)}(CH(3)CO(2)H)(2)(O(2)CCH(3))(3)] (6 a), which was selectively transformed into compound [Rh(2){(2-C(4)H(3)S)P(C(4)H(3)S)(2)}(CF(3)SO(3))(CH(3)CO(2)H)(O(2)CCH(3))(3)] (7 c) in triflic acid media. Remarkably, compound 7 c reverts to the starting compound 6 a upon treatment with sodium acetate. Theoretical DFT calculations for both the P,C/P,S rearrangement and the base-promoted reversion have been performed to explain the experimental findings. Data suggest the P,C/P,S rearrangement occurs by means of a "concerted protonation-demetalation mechanism" followed by eta(2) coordination of the thienyl ring and subsequent isomerization to the S-eta(1)-coordination mode. In the reversion reaction, the base coordinated at the axial position would promote a concerted metalation-deprotonation mechanism.

Synthesis of apoptosis-inducing iminophosphorane organogold(III) complexes and study of their interactions with biomolecular targets.

New stable cationic organogold(III) complexes containing the "pincer" iminophosphorane ligand (2-C(6)H(4)-PPh(2)=NPh) have been prepared by reaction of the previously described [Au{kappa(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}Cl(2)] 1 and a combination of sodium or silver salts and appropriate ligands. The presence of the P atom in the PR(3) fragment has been used as a "spectroscopic marker" to study the in vitro stability (and oxidation state) of the new organogold complexes in solvents like dimethyl sulfoxide and water. Compounds with dithiocarbamato ligands and water-soluble phosphines of the general type [Au{kappa(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(S(2)CN-R(2))]PF(6) (R = Me 2; Bz 3) and [Au{kappa(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(PR(3))(n)Cl]PF(6) (PR(3) = P{Cp(m-C(6)H(4)-SO(3)Na)(2)} n = 1 4, n = 2 TPA {1,3,5-triaza-7-phosphaadamantane} 5) have been synthesized and characterized in solution and in the solid state (the crystal structure of 2 has been determined by X-ray diffraction studies). Complexes 1-5 have been tested as potential anticancer agents, and their cytotoxicity properties were evaluated in vitro against HeLa human cervical carcinoma and Jurkat-T acute lymphoblastic leukemia cells. Compounds 2 and 3 are quite cytotoxic for these two cell lines. There is a preferential induction of apoptosis in HeLa cells after treatment with 1-5. However in the case of the more cytotoxic complex (2), cell death is activated because of both apoptosis and necrosis. The interactions of 1-5 with Calf Thymus DNA have been evaluated by Thermal Denaturation methods. All these complexes show no or little (electrostatic) interaction with DNA. The interaction of 2 with two model proteins (cytochrome c and thioredoxin reductase) has been analyzed by spectroscopic methods (vis-UV and fluorescence). Compound 2 manifests a high reactivity toward both proteins. The mechanistic implications of these results are discussed here.

Multifaceted palladium catalysts towards the tandem diboration-arylation reactions of alkenes.

Novel Pd(2) (6+) compounds have been synthesized in high yield. These compounds and their Pd(2) (4+) counterparts as synthetic precursors mediate the diboration of vinylarenes and aliphatic 1-alkenes, and under mild and basic reaction conditions they produce a variety of 1,2-diboronate esters with excellent conversions and chemoselectivities. The presence of bis(catecholato)diboron (B(2)cat(2)) favours the reduction of Pd(III) to Pd(II), while the catalytic precursor of Pd(II) is transformed into Pd(0)-nanoparticles. An "in situ" catalytic tandem reaction has been designed to transform the diboronate intermediates into the monoarylated product, which after oxidative workup, provides the carbohydroxylated adduct. Eventually, the same catalyst performs both sequences with total conversion from the alkene.

Versatile synthesis of cationic N-heterocyclic carbene-gold(i) complexes containing a second ancillary ligand. Design of heterobimetallic ruthenium-gold anticancer agents.

We describe a versatile and quick route to cationic gold(i) complexes containing N-heterocyclic carbenes and a second ancillary ligand (such as phosphanes, phosphites, arsines and amines) of interest for the synthesis of compounds with potential catalytic and medicinal applications. The general synthetic strategy has been applied in the preparation of novel cationic heterobimetallic ruthenium(ii)-gold(i) complexes that are highly cytotoxic to renal cancer Caki-1 and colon cancer HCT 116 cell lines while showing a synergistic effect and being more selective than their monometallic counterparts.

Titanocene-Gold Complexes Containing N-Heterocyclic Carbene Ligands Inhibit Growth of Prostate, Renal, and Colon Cancers in Vitro.

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = -OC(O)-p-C6H4-S-) bound to gold(I)-N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(µ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold-N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer cells was demonstrated for the selected compound 5a, indicating the robustness of the heterometallic compound in vitro. We describe here preliminary mechanistic data involving studies on the interaction of selected mono- and bimetallic compounds with plasmid (pBR322) used as a model nucleic acid and the inhibition of thioredoxin reductase in PC3 prostate cancer cells. The heterometallic compounds, which are highly apoptotic, exhibit strong antimigratory effects on the prostate cancer cell line PC3.

Unprecedented use of silver(I) N-heterocyclic carbene complexes for the catalytic preparation of 1,2-bis(boronate) esters.

Catalytic diboration of internal and terminal alkenes with Ag(I) N-heterocyclic carbene complexes leads to 1,2-bis(boronate) esters as single intermediates, that can be oxidised towards the corresponding diols.

Heterometallic titanium-gold complexes inhibit renal cancer cells in vitro and in vivo.

Following recent work on heterometallic titanocene-gold complexes as potential chemotherapeutics for renal cancer, we report here on the synthesis, characterization and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = S-C6H4-COO-) bound to gold(I)-phosphane fragments through a thiolate group ([(η-C5H5)2TiMe(µ-mba)Au(PR3)]. The compounds are more stable in physiological media than those previously reported and are highly cytotoxic against human cancer renal cell lines. We describe here preliminary mechanistic data involving studies on the interaction of selected compounds with plasmid (pBR322) DNA used as a model nucleic acid, and with selected protein kinases from a panel of 35 protein kinases having oncological interest. Preliminary mechanistic studies in Caki-1 renal cells indicate that the cytotoxic and anti-migration effects of the most active compound 5 ([(η-C5H5)2TiMe(µ-mba)Au(PPh3)] involve inhibition of thioredoxin reductase and loss of expression of protein kinases that drive cell migration (AKT, p90-RSK, and MAPKAPK3). The co-localization of both titanium and gold metals (1:1 ratio) in Caki-1 renal cells was demonstrated for 5 indicating the robustness of the heterometallic compound in vitro. Two compounds were selected for further in vivo studies on mice based on their selectivity in vitro against renal cancer cell lines when compared to non-tumorigenic human kidney cell lines (HEK-293T and RPTC) and the favourable preliminary toxicity profile in C57BL/6 mice. Evaluation of Caki-1 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (67%) after treatment for 28 days (3 mg/kg/every other day) with heterometallic compound 5 as compared with the previously described [(η-C5H5)2Ti{OC(O)-4-C6H4-P(Ph2)AuCI}2] 3 which was non-inhibitory. These findings indicate that structural modifications on the ligand scaffold affect the in vivo efficacy of this class of compounds.

Enantio- and diastereocontrol in intermolecular cyclopropanation reaction of styrene catalyzed by dirhodium(II) complexes with bulky ortho-metalated aryl phosphines.

Enantiomerically pure dirhodium(II) complexes with ortho-metalated p-substituted aryl phosphines have been shown to be enantio- and diastereoselective in the cyclopropanation of styrene by ethyl diazoacetate. Enantioselectivities up to 91% and diastereoselectivities up to 90% are observed for ethyl cis-2-phenylcyclopropanecarboxylate.

Further orthometalated dinuclear palladium(III) compounds with bridging N,S-donor ligands.

New dinuclear palladium(III) compounds of general formula Pd2[(C6H4)PPh2]2[N-S]2Cl2, N-S being 2-mercaptopyridinate, 3a; 2-mercapto-6-methylpyridinate, 3b; 2-quinolinethiolate, 3c; 2-mercaptopyrimidinate, 3d; 1-methyl-1H-imidazole-2-thiolate, 3e; 1-methyl-1H-benzimidazole-2-thiolate, 3f; 2-mercaptobenzothiazolate, 3g and 5-mercapto-1-methyltetrazolate, 3h have been obtained by oxidation with PhICl2 of the corresponding palladium(II) counterparts. The stability of the new compounds has been studied by (31)P NMR spectroscopy from 200 to 298 K. Compounds 3f-h were relatively stable until room temperature and they have been synthesized and characterized by (31)P, (1)H and (13)C NMR spectroscopy at 223 K. Compound 3h was also structurally characterized by single X-ray diffraction methods at 150 K showing a Pd-Pd distance of 2.6334(6) Å. A topological charge density analysis has also been performed in order to obtain information on the nature of the bonding in these new palladium(II) and (III) compounds. The contribution of the sulphur p orbitals to the HOMO orbitals in the oxidized compounds allows greater stabilization.

Auranofin and related heterometallic gold(I)-thiolates as potent inhibitors of methicillin-resistant Staphylococcus aureus bacterial strains.

A series of new heterometallic gold(I) thiolates containing ferrocenyl-phoshines were synthesized. Their antimicrobial properties were studied and compared to that of FDA-approved drug, auranofin (Ridaura), prescribed for the treatment of rheumatoid arthritis. MIC in the order of one digit micromolar were found for most of the compounds against Gram-positive bacteria Staphylococcus aureus and CA MRSA strains US300 and US400. Remarkably, auranofin inhibited S. aureus, US300 and US400 in the order of 150-300 nM. This is the first time that the potent inhibitory effect of auranofin on MRSA strains has been described. The effects of a selected heterometallic compound and auranofin were also studied in a non-tumorigenic human embryonic kidney cell line (HEK-293).

Organometallic Titanocene-Gold Compounds as Potential Chemotherapeutics in Renal Cancer. Study of their Protein Kinase Inhibitory Properties.

Early-late transition metal TiAu2 compounds [(η-C5H5)2Ti{OC(O)CH2PPh2AuCl}2] (3) and new [(η-C5H5)2Ti{OC(O)-4-C6H4PPh2AuCl}2] (5) were evaluated as potential anticancer agents in vitro against renal and prostate cancer cell lines. The compounds were significantly more effective than monometallic titanocene dichloride and gold(I) [{HOC(O)RPPh2}AuCl] (R = -CH2- 6, -4-C6H4- 7) derivatives in renal cancer cell lines, indicating a synergistic effect of the resulting heterometallic species. The activity on renal cancer cell lines (for 5 in the nanomolar range) was considerably higher than that of cisplatin and highly active titanocene Y. Initial mechanistic studies in Caki-1 cells in vitro coupled with studies of their inhibitory properties on a panel of 35 kinases of oncological interest indicate that these compounds inhibit protein kinases of the AKT and MAPKAPK families with a higher selectivity toward MAPKAPK3 (IC503 = 91 nM, IC505 = 117 nM). The selectivity of the compounds in vitro against renal cancer cell lines when compared to a nontumorigenic human embryonic kidney cell line (HEK-293T) and the favorable preliminary toxicity profile on C57black6 mice indicate that these compounds (especially 5) are excellent candidates for further development as potential renal cancer chemotherapeutics.

Luminescent iminophosphorane gold, palladium and platinum complexes as potential anticancer agents.

A series of coordination gold(III), palladium(II), and platinum(II) complexes with a luminescent iminophosphorane ligand derived from 8-aminoquinoline [Ph3P=N-C9H6N] (1), have been synthesized and structurally characterized. The coordination palladium(II) and platinum(II) compounds can evolve further, under appropriate conditions, to give stable cyclometalated endo species [M{κ3-C,N,N-C6H4(PPh2=N-8-C9H6N}Cl] (M = Pd, Pt) by C-H activation of the phenyl group of the PPh 3 fragment. Iminophosphorane 1 and the new metallic complexes are luminescent in DMSO or DMSO:H2O (1:1 mixture) solutions at RT. The compounds have been evaluated for their antiproliferative properties in a human ovarian cancer cell line (A2780S), in human lung cancer cells (A-549) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). Most compounds have been more toxic to the ovarian cancer cell line than to the non-tumorigenic cell line. The new complexes interact with human serum albumin (HSA) faster than cisplatin. Studies of the interactions of the compounds with DNA indicate that, in some cases, they exert anticancer effects in vitro based on different mechanisms of action with respect to cisplatin.

In vitro and in vivo evaluation of water-soluble iminophosphorane ruthenium(II) compounds. A potential chemotherapeutic agent for triple negative breast cancer.

A series of organometallic ruthenium(II) complexes containing iminophosphorane ligands have been synthesized and characterized. Cationic compounds with chloride as counterion are soluble in water (70-100 mg/mL). Most compounds (especially highly water-soluble 2) are more cytotoxic to a number of human cancer cell lines than cisplatin. Initial mechanistic studies indicate that the cell death type for these compounds is mainly through canonical or caspase-dependent apoptosis, nondependent on p53, and that the compounds do not interact with DNA or inhibit protease cathepsin B. In vivo experiments of 2 on MDA-MB-231 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (shrinkage) of 56% after 28 days of treatment (14 doses of 5 mg/kg every other day) with low systemic toxicity. Pharmacokinetic studies showed a quick absorption of 2 in plasma with preferential accumulation in the breast tumor tissues when compared to kidney and liver, which may explain its high efficacy in vivo.

Potential anticancer heterometallic Fe-Au and Fe-Pd agents: initial mechanistic insights.

A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligands derived from ferrocenylphosphanes [{Cp-P(Ph2)═N-Ph}2Fe] (1), [{Cp-P(Ph2)═N-CH2-2-NC5H4}2Fe] (2), and [{Cp-P(Ph2)═N-CH2-2-NC5H4}Fe(Cp)] (3) have been synthesized and structurally characterized. Ligands 2 and 3 afford stable coordination complexes [AuCl2(3)]ClO4, [{AuCl2}2(2)](ClO4)2, [PdCl2(3)], and [{PdCl2}2(2)]. The complexes have been evaluated for their antiproliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), in human breast cancer cells (MCF7) and in a nontumorigenic human embryonic kidney cell line (HEK-293T). The highly cytotoxic trimetallic derivatives M2Fe (M = Au, Pd) are more cytotoxic to cancer cells than their corresponding monometallic fragments. Moreover, these complexes were significantly more cytotoxic than cisplatin in the resistant A2780R and the MCF7 cell lines. Studies of the interactions of the trimetallic compounds with DNA and the zinc-finger protein PARP-1 indicate that they exert anticancer effects in vitro based on different mechanisms of actions with respect to cisplatin.

Organometallic Palladium Complexes with a Water-Soluble Iminophosphorane Ligand as Potential Anticancer Agents.

The synthesis and characterization of a new water-soluble iminophosphorane ligand TPA=N-C(O)-2BrC(6)H(4) (C,N-IM; TPA = 1,3,5-triaza-7-phosphaadamantane) 1 is reported. Oxidative addition of 1 to Pd(2)(dba)(3) affords the orthopalladated dimer [Pd(µ-Br){C(6)H(4)(C(O)N=TPA-kC,N)-2}](2) (2) as a mixture of cis and trans isomers (1:1 molar ratio) where the iminophosphorane moeity behaves as a C,N-pincer ligand. By addition of different neutral or monoanionic ligands to 2, the bridging bromide can be cleaved and a variety of hydrophilic or water-soluble mononuclear organometallic palladium(II) complexes of the type [Pd{C(6)H(4)(C(O)N=TPA-kC,N)-2}(L-L)] (L-L = acac (3); S(2)CNMe(2) (4); 4,7-Diphenyl-1,10-phenanthrolinedisulfonic acid disodium salt C(12)H(6)N(2)(C(6)H(4)SO(3)Na)(2) (5)); [Pd{C(6)H(4)(C(O)N=TPA-kC,N)-2}(L)Br] (L = P(mC(6)H(4)SO(3)Na)(3) (6); P(3-Pyridyl)(3) (7)) and, [Pd(C(6)H(4)(C(O)N=TPA)-2}(TPA)(2)Br] (8) are obtained as single isomers. All new complexes were tested as potential anticancer agents and their cytotoxicity properties were evaluated in vitro against human Jurkat-T acute lymphoblastic leukemia cells, normal T-lymphocytes (PBMC) and DU-145 human prostate cancer cells. Compounds [Pd(µ-Br){C(6)H(4)(C(O)N=TPA-kC,N)-2}](2) (2) and [Pd{C(6)H(4)(C(O)N=TPA-kC,N)-2}(acac)] 3 (which has been crystallographically characterized) display the higher cytotoxicity against the above mentioned cancer cell lines while being less toxic to normal T-lymphocytes (peripheral blood mononuclear cells: PBMC). In addition, 3 is very toxic to cisplatin resistant Jurkat shBak indicating a cell death pathway that may be different to that of cisplatin. The interaction of 2 and 3 with plasmid (pBR322) DNA is much weaker than that of cisplatin pointing to an alternative biomolecular target for these cytotoxic compounds. All the compounds show an interaction with human serum albumin (HSA) faster than that of cisplatin.

Cytotoxic hydrophilic iminophosphorane coordination compounds of d8 metals. Studies of their interactions with DNA and HSA.

The synthesis and characterization of a new water-soluble N,N-chelating iminophosphorane ligand TPAN-C(O)-2-NC(5)H(4) (N,N-IM) (1) and its d(8) (Au(III), Pd(II) and Pt(II)) coordination complexes are reported. The structures of cationic [AuCl(2)(N,N-IM)]ClO(4) (2) and neutral [MCl(2)(N,N-IM)] M=Pd (3), Pt(4) complexes were determined by X-ray diffraction studies or by means of density-functional calculations. While the Pd and Pt compounds are stable in mixtures of DMSO/H(2)O over 4 days, the gold derivative (2) decomposes quickly to TPAO and previously reported neutral gold(III) compound [AuCl(2)(N,N-H)] 5 (containing the chelating N,N-fragment HN-C(O)-2-NC(5)H(4)). The cytotoxicities of complexes 2-5 were evaluated in vitro against human Jurkat-T acute lymphoblastic leukemia cells and DU-145 human prostate cancer cells. Pt (4) and Au compounds (2 and 5) are more cytotoxic than cisplatin to these cell lines and to cisplatin-resistant Jurkat sh-Bak cell lines and their cell death mechanism is different from that of cisplatin. All the compounds show higher toxicity against leukemia cells when compared to normal human T-lymphocytes (PBMC). The interaction of the Pd and Pt compounds with calf thymus and plasmid (pBR322) DNA is different from that of cisplatin. All compounds bind to human serum albumin (HSA) faster than cisplatin (measured by fluorescence spectroscopy). Weak and stronger binding interactions were found for the Pd (3) and Pt (4) derivatives by isothermal titration calorimetry. Importantly, for the Pt (4) compounds the binding to HSA was reversed by addition of a chelating agent (citric acid) and by a decrease in pH.