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We have recently reported a series of piano-stool ruthenium(II) complexes of the general formula [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] showing excellent cytotoxic activities (particularly when R2 = R3 = methyl). In the present study, new members of this family of compounds have been prepared with the objective to investigate the effect of the steric hindrance of a bulky phosphane ligand, namely diisopropyl(1-pyrenyl)phosphane (L), on exchange reactions involving the coordinated halides (X = Cl, I). Two η6-arene rings were used, i.e. η6-methyl benzoate (mba) and η6-p-cymene (p-cym), and four complexes were synthesized, namely [RuCl2(mba)(L)] (1Cl2iPr), [RuI2(mba)(L)] (1I2iPr), [RuCl2(p-cym)(L)] (2Cl2iPr), and [RuI2(p-cym)(L)] (2I2iPr). Unexpectedly, all of the complexes exhibited poor cytotoxic activities after 24 h of incubation with cells, in contrast to the related compounds previously reported. However, it was observed that aged DMSO solutions of 2I2iPr (from 2 to 7 days) exhibited better activities in comparison to freshly prepared solutions and that the activity improved over “aging” time. Thorough studies were therefore performed to uncover the origin of this lag time in the cytotoxicity efficiency. The data achieved clearly demonstrated that compounds 2I2iPr and 2Cl2iPr were undergoing a series of transformation reactions in DMSO (with higher rates for the iodido complex 2I2iPr), ultimately generating cyclometalated species through a mechanism involving DMSO as a coordinated proton abstractor. The cyclometalated complexes detected in solution were subsequently prepared; hence, pure [RuCl(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3CliPr), [RuI(p-cym)(κ2C-diisopropyl(1-pyrenyl)phosphane)] (3IiPr), and [Ru(p-cym)(κS-dmso)(κ2C-diisopropyl(1-pyrenyl)phosphane)]PF6 (3dmsoiPr) were synthesized and fully characterized. Remarkably, 3CliPr, 3IiPr, and 3dmsoiPr are all very efficient cytotoxic agents, exhibiting slightly better activities in comparison to the chlorido noncyclometalated complexes [RuCl2(η6-arene)(P(1-pyrenyl)R2R3)] described in an earlier report. For comparison purposes, the iodido compounds [RuI2(mba)(dimethyl(1-pyrenyl)phosphane)] (1I2Me) and [RuI2(p-cym)(dimethyl(1-pyrenyl)phosphane)] (2I2Me), bearing the less hindered dimethyl(1-pyrenyl)phosphane ligand, have also been prepared. The cytotoxic and chemical behaviors of 1I2Me and 1I2Me were comparable to those of their chlorido counterparts reported previously., Financial support from the Spanish Ministerio de Ciencia Innovación, y Universidades (Project Nos. CTQ2015-65040-P, RED2018-102471-T, PID2019-107006GB-C21, PGC2018-098630-B-I00, and CTQ2017-88446-R AEI/FEDER, UE) and from the Instituto de Salud Carlos III (ISCIIIFIS PI18/00441, FEDER) is acknowledged. A.G. thanks the Royal Society of Chemistry for financial support (RSC Research Fund grant RF19-7147). J.C. thanks the Spanish MICINN for a Ramoń y Cajal research contract (RYC2018-024692-I) and the Spanish Structures of Excellence María de Maeztu program (MDM-2017-0767). P.G. acknowledges the Institució Catalana de Recerca i Estudis Avançats (ICREA).

Reactions of optically pure P-stereogenic ortho-tolyl substituted phosphines with [RuCl2(p-cymene)]2 afforded the corresponding κP-coordinated ruthenium(II) dichlorides (C1′, C2’) even in the presence of sodium acetate. In contrast, the ruthenium cyclometallated (κ2-C,P) complexes (C3–C9) were obtained with phosphines containing a polycyclic aromatic substituent (L3-L9), namely 1-naphthyl, 9-phenanthryl or 1-pyrenyl. Some diastereoselectivity in the cyclometallation process has been observed for the most bulky ligands. The new compounds have been used as catalytic precursors in the reduction of acetophenone to 1-phenylethanol by transfer hydrogenation.

Solving ozone depletion and climate change problems require the development of effective methods for sustainably curbing them. With this aim, Milstein and coworkers developed a PNP pincer ruthenium catalyst for the homogeneous hydrogenation of nitrous oxide (N2O), an ozone-depleting substance and the third most important greenhouse gas, to generate dinitrogen and water as resultant products. The mechanism of this promising transformation was unveiled by means of experiments together with Density Functional Theory (DFT) calculations, which inspired Milstein and coworkers to use similar (PNN)Ru-H pincer catalysts for the reduction of N2O by CO to produce N2 and CO2. The use of the latter type of catalysts resulted in the proposition of a new reaction protocol and allowed to work under milder conditions. Here we describe the detailed mechanism of the last transformation catalyzed by a (PNN)Ru−H catalyst by means of DFT calculations, and not only this, but we also discover the way to block undesired parasitic reactions. Apart from that, we have explored a new evolution of this family of catalysts to go beyond previous experimental outcomes. The mechanism consists in a cascade of easy steps, starting from an insertion of the N2O oxygen into the Ru-H bond generating a hydroxo intermediate and releasing N2, and ending with a β-hydride elimination to form CO2 and regenerate the catalyst. The whole process occurs in a facile way with the exception of two steps: the formation of the hydroxyl ligand and the final β-hydride elimination to form CO2. However, the energy barriers of these two steps are not the bottleneck of the catalysis, but rather the easiness of the pyridyl group bonded to Ru to isomerize by C-H activation. We propose to solve this drawback by tuning the PNN ligand to block the pyridyl free rotation S.E. thanks Universitat de Girona and Donostia International Physics Center (DIPC) for an IFUdG2019 PhD fellowship. A.P. is a Serra Húnter Fellow. A.P. and M.S. thank the Ministerio de Economía y Competitividad (MINECO) of Spain for projects PGC2018-097722-B-I00 and CTQ2017-85341-P and the Generalitat de Catalunya for project 2017SGR39 and the ICREA Academia prize 2019 awarded to A.P. We thank Prof. David Milstein for helpful discussion

A new bis-facial dinuclear ruthenium complex, {[RuII(bpy)]2(μ-bimp)(μ-Cl)}2+, 22+, containing a hexadentate pyrazolate- bridging ligand (Hbimp) and bpy as auxiliary ligands has been synthesized and fully characterized in solution by spectrometric, spectroscopic, and electrochemical techniques. The new compound has been tested with regard to its capacity to oxidize water and alkenes. The in situ generated bis-aqua complex, {[RuII(bpy)(H2O)]2(μ-bimp)}3+, 33+, is an excellent catalyst for the epoxidation of a wide range of alkenes. High turnover numbers (TN), up to 1900, and turnover frequencies (TOF), up to 73 min−1, are achieved using PhIO as oxidant. Moreover, 33+ presents an outstanding stereospecificity for both cis and trans olefins toward the formation of their corresponding epoxides due to specific interactions transmitted by its ligand scaffold. A mechanistic analysis of the epoxidation process has been performed based on density functional theory (DFT) calculations in order to better understand the putative cooperative effects within this dinuclear catalyst Support form MINECO (Grants CTQ2011-26440, CTQ-2013-49075-R and CTQ2010-21532-C02-02) and the DFG (Grant Me1313/9-1) is gratefully acknowledged. J.A. is grateful for the award of a PIF doctoral grant from UAB. A.P. thanks the Spanish MINECO for the project CTQ2014-59832-JIN and the European Commission for a Career Integration Grant (No.CIG09-GA-2011-293900)

Density functional theory (DFT) calculations have been used to describe the first turnover of an olefin metathesis reaction calling for a new in silico family of homogenous Ru-based catalysts bearing a phosphine–phosphonium ylide ligand, with ethylene as a substrate. Equal to conventional Ru-based catalysts bearing an N-heterocyclic carbene (NHC) ligand, the activation of these congeners occurs through a dissociative mechanism, with a more exothermic first phosphine dissociation step. In spite of a stronger electron-donating ability of a phosphonium ylide C-ligand with respect to a diaminocarbene analogue, upper energy barriers were calculated to be on average ca. 5 kcal/mol higher than those of Ru–NHC standards. Overall, the study also highlights advantages of bidentate ligands over classical monodentate NHC and phosphine ligands, with a particular preference for the cis attack of the olefin. The new generation of catalysts is constituted by cationic complexes potentially soluble in water, to be compared with the typical neutral Ru–NHC ones Albert Poater thanks the Spanish Ministry of Economy and Competitiveness (MINECO) for a project CTQ2014-59832-JIN and Xarxa de Química Teòrica i Computacional for a VALCHEM2016 project

A new family of ruthenium complexes based on the N-pentadentate ligand Py2Metacn (N-methyl-N′,N′′-bis(2-picolyl)-1,4,7-triazacyclononane) has been synthesised and its catalytic activity has been studied in the water-oxidation (WO) reaction. We have used chemical oxidants (ceric ammonium nitrate and NaIO4) to generate the WO intermediates [RuII(OH2)(Py2Metacn)]2+, [RuIII(OH2)(Py2Metacn)]3+, [RuIII(OH)(Py2Metacn)]2+ and [RuIV(O)(Py2Metacn)]2+, which have been characterised spectroscopically. Their relative redox and pH stability in water has been studied by using UV/Vis and NMR spectroscopies, HRMS and spectroelectrochemistry. [RuIV(O)(Py2Metacn)]2+ has a long half-life (>48 h) in water. The catalytic cycle of WO has been elucidated by using kinetic, spectroscopic, 18O-labelling and theoretical studies, and the conclusion is that the rate-determining step is a single-site water nucleophilic attack on a metal-oxo species. Moreover, [RuIV(O)(Py2Metacn)]2+ is proposed to be the resting state under catalytic conditions. By monitoring CeIV consumption, we found that the O2 evolution rate is redox-controlled and independent of the initial concentration of CeIV. Based on these facts, we propose herein that [RuIV(O)(Py2Metacn)]2+ is oxidised to [RuV(O)(Py2Metacn)]2+ prior to attack by a water molecule to give [RuIII(OOH)(Py2Metacn)]2+. Finally, it is shown that the difference in WO reactivity between the homologous iron and ruthenium [M(OH2)(Py2Metacn)]2+ (M=Ru, Fe) complexes is due to the difference in the redox stability of the key MV(O) intermediate. These results contribute to a better understanding of the WO mechanism and the differences between iron and ruthenium complexes in WO reactions We thank the ICIQ Foundation, MEC for a FPU PhD grant FPU14/02550 (C.C.), the European Research Foundation for projects FP7-PEOPLE-2010-ERG-268445 (J.L.F.) and ERC-2009- StG-239910 (M.C.), the MICINN for project CTQ2009-08464 (M.C.) and for a Ramon y Cajal contract, the Generalitat de Catalunya for an ICREA Academia Award (M.C.) and the CELLEX Foundation through the CELLEX-ICIQ high-throughput experimentation platform for financial support. We also thank MINECO for support through Severo Ochoa Excellence Accreditation 2014–2018 (SEV-2013-0319). We acknowledge Catexcel for a generous gift of Ts3tacn

The synthesis via phosphine-boranes of 13 new optically pure P-stereogenic diarylphosphines P(Het)PhR (Het = 4-dibenzofuranyl (DBF), 4-dibenzothiophenyl (DBT), 4-dibenzothiophenyl-S,S-dioxide (DBTO2) and 1-thianthrenyl (TA); R = OMe, Me, i-Pr, Fc (ferrocenyl)) following the Jugé-Stephan method is described. The ligands were designed with the aim of having a heteroatom in a position capable of interacting with a metal upon coordination. The ligands and their precursors have been fully characterised, including the determination of two crystal structures of phosphine-boranes. Ru neutral complexes of the type [RuCl2(η(6)-arene)(κP-P)] (arene = p-cymene and methyl benzoate) have been prepared and characterised, including three crystal structure determinations. Treatment of solutions of the complexes with TlPF6 allowed the preparation of well-defined cationic complexes [RuCl(η(6)-arene)(κ(2)P,S-P)]PF6 for DBT- and TA-based phosphines. The complexes possess a stereogenic Ru atom and in most of the cases they are present as a single isomer in solution. All the Ru complexes have been used in the asymmetric transfer hydrogenation of acetophenone in refluxing 2-propanol, with good activities and up to 70% ee.

KGaA, Weinheim.Density functional theory calculations have been used to explore the potential of Ru-based complexes with 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene (SIMes) ligand backbone (A) being modified in silico by the insertion of a C60 molecule (B and C), as olefin metathesis catalysts. To this end, we investigated the olefin metathesis reaction catalyzed by complexes A, B, and C using ethylene as the substrate, focusing mainly on the thermodynamic stability of all possible reaction intermediates. Our results suggest that complex B bearing an electron-withdrawing N-heterocyclic carbene improves the performance of unannulated complex A. The efficiency of complex B is only surpassed by complex A when the backbone of the N-heterocyclic carbene of complex A is substituted by two amino groups. The particular performance of complexes B and C has to be attributed to electronic factors, that is, the electronic-donating capacity of modified SIMes ligand rather than steric effects, because the latter are predicted to be almost identical for complexes B and C when compared to those of A. Overall, this study indicates that such Ru-based complexes B and C might have the potential to be effective olefin metathesis catalysts A.P. thanks the Spanish MINECO for a project CTQ2014-59832-JIN, and the European Commission for a Career Integration Grant (CIG09-GA-2011-293900)

SPN thanks the European Research Council(227817) (Advanced Investigator Award ‘FUNCAT’), the EU(CP-FP 211468) (Seventh Framework Programme Project ‘EUMET’), and the Engineering and Physical Sciences Research Council for funding. SPN is a Royal Society Wolfson Merit Award holder. AP thanks the Spanish MINECO for a Ramón y Cajal contract (RYC-2009-05226) and European Commission for a Career Integration Grant (CIG09-GA-2011-293900). The commercially-available metathesis pre-catalyst M23 has been evaluated alongside new complex [RuCl2((3-phenyl)indenylidene)(PPh3)(SIPrOMe)] (1), which bears a para-methoxy-substituted N-heterocyclic carbene ligand. Several model metathesis reactions could be conducted using only parts-per-million levels of ruthenium catalyst. The effects of the different NHC ligands on reactivity have been explored. Postprint

DFT calculations have been used to determine the thermodynamic and kinetic preference for ruthenacyclobutanes resulting from the experimentally proposed interconversion pathways (olefin and alkylidene rotations) through the investigation of cross-metathesis reaction mechanism for neutral Grubbs catalyst, RuCl2(=CHEt)NHC (A), with ethylene and 1-butene as the substrates. Our results show that although the proposed interconversions are feasible due to the predicted low energy barriers (2-6 kcal/mol), the formation of ruthenacyclobutane is kinetically favored over the competitive reactions involving alkylidene rotations. In comparison with catalyst A, the reaction energy profile for cationic Piers catalyst [RuCl2(=CHPCy3)NHC+] (B) is more endothermic in nature with both ethylene and 1-butene substrates A.P. thanks the Spanish MINECO for a Ramón y Cajal contract (RYC-2009-05226) and a José Castillejo fellowship (CAS14/00165), and European Commission for a Career Integration Grant (CIG09-GA-2011-293900)

Ru-aqua complex {[RuII(trpy)(H2O)] 2(μ-pyr-dc)}+ is a powerful epoxidation catalyst for a wide range of linear and cyclic alkenes. High turnover numbers (TNs), up to 17000, and turnover frequencies (TOF), up to 24120 h-1 (6.7 s -1), have been obtained using PhIO as oxidant. This species presents an outstanding stereospecificity for both cis and trans olefins towards the formation of their corresponding cis and trans epoxides. In addition, it shows different reactivity to cis and trans olefins due to a substrate orientation supramolecular effect transmitted by its ligand scaffold. This effect together with the impressive reaction rates are rationalized using electrochemical techniques and DFT calculations. A new Ru-aqua complex that behaves as a powerful epoxidation catalyst for a wide range of linear and cyclic alkenes is reported. High turnover numbers and frequencies are obtained by using PhIO as oxidant. The complex shows an outstanding stereospecificity for both cis and trans olefins towards the formation of their corresponding cis and trans epoxides This research was supported financially by MINECO (CTQ2011-23156/BQU, CTQ2010-21497 and PRI-PIBIN-2011-1278), ICIQ, FEDER fund (UNGI08-4E-003), ICREA Academia, Generalitat de Catalunya (2009SGR637); Ramon y Cajal contract (RYC-2009-05226) of MINECO, and Career Integration Grant (CIG09-GA-2011-293900) of the European Commission. COST Actions CM1205 and CM1202 are also gratefully acknowledged

An olefin metathesis catalyst featuring a SIPr NHC and an ester chelating carbene ligand is introduced. In contrast to its previously published SIMes analogue, only the trans dichloro configurated isomer was obtained. The two counterparts are tested in various olefin metathesis reactions, revealing a striking superiority of the new complex in the cross metathesis of olefins with methyl vinyl ketone allowing for full conversion with only 500 ppm catalyst loading Financial support of this work from the Higher Education Commission of Pakistan (for M. A.) and the European Community (CP-FP 211468-2 EUMET) is gratefully acknowledged. A. P. thanks the Spanish MINECO for a Ramon y Cajal contract (ref. RYC-2009-05226) and the European Commission for a Career Integration Grant (CIG09-GA-2011-293900)

A photoactivated ruthenium(II) arene complex has been conjugated to two receptor-binding peptides, a dicarba analogue of octreotide and the Arg-Gly-Asp (RGD) tripeptide. These peptides can act as "tumor-targeting devices" since their receptors are overexpressed on the membranes of tumor cells. Both ruthenium-peptide conjugates are stable in aqueous solution in the dark, but upon irradiation with visible light, the pyridyl-derivatized peptides were selectively photodissociated from the ruthenium complex, as inferred by UV-vis and NMR spectroscopy. Importantly, the reactive aqua species generated from the conjugates, [(η(6)-p-cym)Ru(bpm)(H(2)O)](2+), reacted with the model DNA nucleobase 9-ethylguanine as well as with guanines of two DNA sequences, (5')dCATGGCT and (5')dAGCCATG. Interestingly, when irradiation was performed in the presence of the oligonucleotides, a new ruthenium adduct involving both guanines was formed as a consequence of the photodriven loss of p-cymene from the two monofunctional adducts. The release of the arene ligand and the formation of a ruthenated product with a multidentate binding mode might have important implications for the biological activity of such photoactivated ruthenium(II) arene complexes. Finally, photoreactions with the peptide-oligonucleotide hybrid, Phac-His-Gly-Met-linker-p(5')dCATGGCT, also led to arene release and to guanine adducts, including a GG chelate. The lack of interaction with the peptide fragment confirms the preference of such organometallic ruthenium(II) complexes for guanine over other potential biological ligands, such as histidine or methionine amino acids.

The development of photoactivatable metal complexes with potential anticancer properties is a topical area of current investigation. Photoactivated chemotherapy using coordination compounds is typically based on photochemical processes occurring at the metal center. In the present study, an innovative approach is applied that takes advantage of the remarkable photochemical properties of diarylethenes. Following a proof-of-concept study with two complexes, namely, C1 and C2, a series of additional platinum(II) complexes from dithienylcyclopentene-based ligands was designed and prepared. Like C1 and C2, these new coordination compounds exhibit two thermally stable, interconvertible photoisomers that display distinct properties. The photochemical behavior of ligands L3-L7 has been analyzed by 1H NMR and UV-vis spectroscopies. Subsequently, the corresponding platinum(II) complexes C3-C7 were synthesized and fully characterized, including by single-crystal X-ray diffraction for some of them. Next, the interaction of each photoisomer (i.e., containing the open or closed ligand) of the metal complexes with DNA was examined thoroughly using various techniques, revealing their distinct DNA-binding modes and affinities, as observed for the earlier compounds C1 and C2. The antiproliferative activity of the two forms of the complexes was then assessed with five cancer cell lines and compared with that of C1 and C2, which supported the use of such diarylethene-based systems for the generation of a new class of potential photochemotherapeutic metallodrugs., Financial support from the Spanish Ministerio de Economía y Competitividad/FEDER (Project Nos. CTQ2015-70371-REDT, CTQ2014-55293-P, and CTQ2017-88446-R) is acknowledged. P.G. thanks the Institució Catalana de Recerca i Estudis Avançats (ICREA). This work was partially supported by a grant from the Spanish government and the EU (FIS PI13/00089), a grant from La Marató de TV3 Foundation (20132730). Also, an individual contract to L.K.G. supported by a program from the Barcelona Univ. in collaboration with Obra Social de la Fundació Bancaria “La Caixa” is acknowledged. This research used resources of the Advanced Light Source, which is a Department of Energy Office of Science User Facility under Contract No. DE-AC02-05CH11231.