Roberto A. Sánchez-Delgado

Breaking CS bonds with transition metal complexes. A review of molecular approaches to the study of the mechanisms of the hydrodesulfurization reaction

Abstract In spite of the large scale industrial applications of the hydrodesulfurization (HDS) process, and of the considerable number of studies of this reaction on heterogeneous catalysts, the mechanisms involved are not yet clearly understood. In this article we first summarize the main mechanistic pathways that have been proposed to occur on surfaces for HDS of thiophenes, and then review those aspects of coordination and organometallic chemistry that are most pertinent to the activation, desulfurization and hydrogenation of thiophenes on metal complexes. The examples described constitute excellent molecular analogues of the species and reactions that are thought to intervene in heterogeneous catalysis, and thus complement surface studies and contribute to the understanding of this important reaction.

The chemistry and catalytic properties of ruthenium and osmium complexes. Part 5. Synthesis of new compounds containing arsine ligands and catalytic activity in the homogeneous hydrogenation of aldehydes

SummaryThe complexes MHCl(CO)(AsPh3)3 (1: M=Ru and2: M=Os) readily react with Ph2PCH2CH2AsPh2 (Arphos) to yield MHCl(CO) (AsPh3) (Arphos) (3: M=Ru and4: M=Os) and with acetic acid to produce MCl(CO) (OCOMe) (AsPh3)2 (5: M=Ru and6: M=Os); the new compounds were characterized by elemental analysis, i.r. and1H n.m.r. spectroscopy. Complexes (1−6) are efficient catalyst precursors for the homogeneous hydrogenation of the C=O bond of propionaldehyde under moderate reaction conditions; some relations between structures and catalytic activities are described, as well as comparisons with analogous systems containing phosphine ligands.

Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine.

The new Ru(II) chloroquine complexes [Ru(eta(6)-arene)(CQ)Cl2] (CQ = chloroquine; arene = p-cymene 1, benzene 2), [Ru(eta(6)-p-cymene)(CQ)(H2O)2][BF4]2 (3), [Ru(eta(6)-p-cymene)(CQ)(en)][PF6]2 (en = ethylenediamine) (4), and [Ru(eta(6)-p-cymene)(eta(6)-CQDP)][BF4]2 (5, CQDP = chloroquine diphosphate) have been synthesized and characterized by use of a combination of NMR and FTIR spectroscopy with DFT calculations. Each complex is formed as a single coordination isomer: In 1-4, chloroquine binds to ruthenium in the eta(1)-N mode through the quinoline nitrogen atom, whereas in 5 an unprecedented eta(6) bonding through the carbocyclic ring is observed. 1, 2, 3, and 5 are active against CQ-resistant (Dd2, K1, and W2) and CQ-sensitive (FcB1, PFB, F32, and 3D7) malaria parasites (Plasmodium falciparum); importantly, the potency of these complexes against resistant parasites is consistently higher than that of the standard drug chloroquine diphosphate. 1 and 5 also inhibit the growth of colon cancer cells, independently of the p53 status and of liposarcoma tumor cell lines with the latter showing increased sensitivity, especially to 1 (IC50 8 microM); this is significant because this type of tumor does not respond to currently employed chemotherapies.

Toward a novel metal-based chemotherapy against tropical diseases. 6. Synthesis and characterization of new copper(II) and gold(I) clotrimazole and ketoconazole complexes and evaluation of their activity against Trypanosoma cruzi.

The complexes [Cu(CTZ)(4)]Cl(2).2H(2)O (1), [Cu(CTZ)Cl(2)](2) (2), [Cu(KTZ)(3)Cl(2)] (3), and [Cu(KTZ)Cl(2)](2).2H(2)O (4) were prepared by reaction of CuCl(2) with CTZ and KTZ (where CTZ = 1-[[(2-chlorophenyl)diphenyl]methyl]-1H-imidazole and KTZ = cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine), respectively, in acetonitrile at different ligand to metal molar ratios. Gold complexes [Au(PPh(3))(CTZ)]PF(6) (5) and [Au(PPh(3))(KTZ)]PF(6).H(2)O (6) were synthesized by reaction of AuClPPh(3), with KPF(6) and CTZ or KTZ in acetonitrile. All the new compounds were characterized by NMR spectroscopy and microanalytical methods, and for the paramagnetic species EPR spectroscopy and DC magnetic susceptibility measurements were also employed. The solid-state structure of 1 has been determined by X-ray crystallography. 1 crystallizes in the triclinic space group P(-)1, with a = 12.773(2) A, b = 15.326(4) A, c = 11.641(2) A, V = 1957.4(7) A(3), Z = 1, and D(calcd) = 1.284 g/cm(3). The structure refinement converged at R1 = 0.0731 and wR2 = 0.1962. Complex 1 displayed a square-planar structure typical for tetrakis(imidazole)copper(II) complexes. The new compounds were tested for in vitro activity against cultures of epimastigotes of Trypanosoma cruzi, the causative agent of Chagas disease. At concentrations equivalent to 10(-6) M of total CTZ or KTZ (in DMSO) all the complexes exhibited significantly higher growth inhibitory activity than their respective parental compounds.

Searching for New Chemotherapies for Tropical Diseases: Ruthenium-Clotrimazole Complexes Display High in vitro Activity Against Leishmania major and Trypanosoma cruzi and Low Toxicity Toward Normal Mammalian Cells

Eight new ruthenium complexes of clotrimazole (CTZ) with high antiparasitic activity have been synthesized, cis,fac-[Ru(II)Cl(2)(DMSO)(3)(CTZ)] (1), cis,cis,trans-[Ru(II)Cl(2)(DMSO)(2)(CTZ)(2)] (2), Na[Ru(III)Cl(4)(DMSO)(CTZ)] (3), Na[trans-Ru(III)Cl(4)(CTZ)(2)] (4), [Ru(II)(η(6)-p-cymene)Cl(2)(CTZ)] (5), [Ru(II)(η(6)-p-cymene)(bipy)(CTZ)][BF(4)](2) (6), [Ru(II)(η(6)-p-cymene)(en)(CTZ)][BF(4)](2) (7), and [Ru(II)(η(6)-p-cymene)(acac)(CTZ)][BF(4)] (8) (bipy = bipyridine; en = ethlylenediamine; acac = acetylacetonate). The crystal structures of compounds 4-8 are described. Complexes 1-8 are active against promastigotes of Leishmania major and epimastigotes of Trypanosoma cruzi. Most notably, complex 5 increases the activity of CTZ by factors of 110 and 58 against L. major and T. cruzi, with no appreciable toxicity to human osteoblasts, resulting in nanomolar and low micromolar lethal doses and therapeutic indexes of 500 and 75, respectively. In a high-content imaging assay on L. major-infected intraperitoneal mice macrophages, complex 5 showed significant inhibition on the proliferation of intracellular amastigotes (IC(70) = 29 nM), while complex 8 displayed some effect at a higher concentration (IC(40) = 1 μM).

Hydrogenation of arenes and N-heteroaromatic compounds over ruthenium nanoparticles on poly(4-vinylpyridine): a versatile catalyst operating by a substrate-dependent dual site mechanism

A nanostructured catalyst composed of Ru nanoparticles immobilized on poly(4-vinylpyridine) (PVPy) has been synthesized by NaBH(4) reduction of RuCl(3)·3H(2)O in the presence of the polymer in methanol at room temperature. TEM measurements show well-dispersed Ru nanoparticles with an average diameter of 3.1 nm. Both powder XRD patterns and XPS data indicate that the Ru particles are predominantly in the zerovalent state. The new catalyst is efficient for the hydrogenation of a wide variety of aromatic hydrocarbons and N-heteroaromatic compounds representative of components of petroleum-derived fuels. The experimental data indicate the existence of two distinct active sites in the nanostructure that lead to two parallel hydrogenation pathways, one for simple aromatics involving conventional homolytic hydrogen splitting on Ru and a second one for N-heteroaromatics taking place via a novel heterolytic hydrogen activation on the catalyst surface, assisted by the basic pyridine groups of the support.

The chemistry and catalytic properties of ruthenium and osmium compounds. Part 7. Regioselective hydrogenation of cinnamaldehyde (3-phenyl-2-propenal) catalyzed by Ru and Os triphenylphosphine complexes in homogeneous solution and by meta-sulfonatophenyl-diphenyldiphosphine (TPPMS) and tris-meta-sulfonato-phenylphosphine (TPPTS) derivatives in an aqueous biphasic system

Abstract NMR data for two Ru-TPPMS complexes previously described as unsaturated monomeric species have led to their reformulation as the chloro-bridged dimers [RuCl(TPPMS)2(μ-Cl)]2(1) and [RuH(TPPMS)2(μ-Cl)]2(2); three new water-soluble complexes OsH4(TPPMS)3(3), OsHCl(CO)(TPPMS)2(4), and [OsCl(TPPMS)2(μ-Cl)]2(5) have been synthesized and characterized. Complexes 1–5, as well as mixtures of Ru and Os salts with TPPMS and TPPTS catalyze the hydrogenation of cinnamaldehyde under mild reaction conditions in aqueous biphasic systems; the activities and selectivities of these catalysts have been compared with those of homogeneous PPh3 analogues. In general there is a clear advantage in using the aqueous biphasic mixtures over their analogous homogeneous solutions, since catalyst recovery and recycling are easy and because the regioselectivity towards the production of the α, β-unsaturated alcohol is considerably enhanced on going from the homogeneous PPh3 to the biphasic TPPMS and TPPTS systems, particularly in the case of Ru.

Interactions of arene-Ru(II)-chloroquine complexes of known antimalarial and antitumor activity with human serum albumin (HSA) and transferrin.

The interactions of π-arene-Ru(II)-chloroquine complexes with human serum albumin (HSA), apotransferrin and holotransferrin have been studied by circular dichroism (CD) and UV-Visible spectroscopies, together with isothermal titration calorimetry (ITC). The data for [Ru(η(6)-p-cymene)(CQ)(H(2)O)Cl]PF(6) (1), [Ru(η(6)-benzene)(CQ)(H(2)O)Cl]PF(6) (2), [Ru(η(6)-p-cymene)(CQ)(H(2)O)(2)][PF(6)](2) (3), [Ru(η(6)-p-cymene)(CQ)(en)][PF(6)](2) (4), [Ru(η(6)-p-cymene)(η(6)-CQDP)][BF(4)](2) (5) (CQ: chloroquine; DP: diphosphate; en: ethylenediamine), in comparison with CQDP and [Ru(η(6)-p-cymene)(en)Cl][PF(6)] (6) as controls demonstrate that 1, 2, 3, and 5, which contain exchangeable ligands, bind to HSA and to apotransferrin in a covalent manner. The interaction did not affect the α-helical content in apotransferrin but resulted in a loss of this type of structure in HSA. The binding was reversed in both cases by a decrease in pH and in the case of the Ru-HSA adducts, also by addition of chelating agents. A weaker interaction between complexes 4 and 6 and HSA was measured by ITC but was not detectable spectroscopically. No interactions were observed for complexes 4 and 6 with apotransferrin or for CQDP with either protein. The combined results suggest that the arene-Ru(II)-chloroquine complexes, known to be active against resistant malaria and several lines of cancer cells, also display a good transport behavior that makes them good candidates for drug development.

Selective homogeneous hydrogenation of benzothiophene and quinoline catalysed by ruthenium, osmium, rhodium and iridium complexes

Abstract The homogeneous selective hydrogenation of benzothiophene to 1,2-dihydrobenzothiophene and of quinoline to 1,2,3,4-tetrahydroquinoline is efficiently achieved by the use of RuCl2(PPh3)3, [RuHCl(CO)(PPh3)3], [OsHCl(CO)(PPh3)3], RhCl(PPh3)3, [Rh(cod)(PPh3)2]PF6, and [Ir(cod)(PPh3)2]PF6 (cod = cyclooctadiene) at 170°C and 115 bar and 150°C and 30 bar H2, respectively.

New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents

In the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(II) complexes with the formula [Ru(2)(p-cymene)(2)(L)(2)]X(2), where X = Cl or PF(6), were synthesized and the crystal structures of two of them were solved by X-ray diffraction methods. Two of the complexes show significant in vitro growth inhibition activity against Trypanosoma brucei brucei and are highly selective towards trypanosomal cells with respect to mammalian cells (J774 murine macrophages). These promising results make the title organoruthenium compounds good lead candidates for further developments towards potential antitrypanosomal organometallic drugs.