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Ramón Virasoro,1 Jessica M DeLong,1 Rafael E Estrella,2 Merycarla Pichardo,3 Ramón Rodriguez Lay,4 Gustavo Espino,5 Sean P Elliott6 1Urology of Virginia PLLC, Virginia Beach, VA, USA; 2Clinica Unión Medica, Santiago de los Caballeros, Dominican Republic; 3URUS, Santo Domingo, Dominican Republic; 4Cirujano Urologo Royal Center Panama City, Panama City, Panama; 5Centro Especializado San Fernando, Panama City, Panama; 6Department of Urology, University of Minnesota, Minneapolis, MN, USACorrespondence: Ramón Virasoro, Urology of Virginia PLLC, 225 Clearfield Ave, Virginia Beach, VA, 23462, USA, Tel +1 757-457-5100, Email viravira@yahoo.comIntroduction: Endoscopic management of male anterior urethral stricture disease is common; however, repeat treatment is associated with high recurrence rates. Here, we report the 3-year results of the ROBUST I trial, which evaluated the safety and efficacy of the Optilume® drug coated balloon (DCB) in men with recurrent urethral strictures.Methods: Adult men with recurrent bulbar urethral strictures ≤ 2 cm in length and 1– 4 prior endoscopic interventions were treated with the Optilume DCB. Functional success was defined as ≥ 50% reduction in International Prostate Symptom Score (IPSS) without need for retreatment. Other outcomes included quality of life, maximum flow rate, post-void residual urine volume, erectile function, and freedom from repeat intervention.Results: Of the 53 enrolled and treated men, 33 completed the 3-year visit, with 10 patients experiencing clinical failures at previous visits, giving a total of 43 subjects evaluable for the functional success endpoint. Functional success was achieved in 67% (29/43) and freedom from retreatment in 77% (33/43). Average IPSS improved from 25.2 at baseline to 5.5 at 3 years (p< 0.0001). Significant improvements were observed in quality of life, flow rate, and post-void residual urine volume. Erectile function was not affected by treatment. Device-related adverse events were mild or moderate in nature and resolved quickly after onset. There were no serious treatment-related adverse events.Conclusion: Symptomatic improvement after treatment with the Optilume DCB was maintained through 3 years in a population highly susceptible to recurrent urethral stricture disease. This minimally invasive therapy is safe with no negative impact on sexual function.Keywords: lower urinary tract symptoms, paclitaxel, urethral dilation, medical device, clinical trial

Photoredox catalysis constitutes a very powerful tool in organic synthesis, due to its versatility, efficiency, and the mild conditions required by photoinduced transformations. In this paper, we present an efficient and selective photocatalytic procedure for the aerobic oxidative dehydrogenation of partially saturated N-heterocycles to afford the respective N-heteroarenes (indoles, quinolines, acridines, and quinoxalines). The protocol involves the use of new Ir(III) biscyclometalated photocatalysts of the general formula [Ir(C^N)2(N^N′)]Cl, where the C^N ligand is 2- (2,4-difluorophenyl)pyridinate, and N^N′ are different ligands based on the 2-(2′-pyridyl)benzimidazole scaffold. In-depth electrochemical and photophysical studies as well as DFT calculations have allowed us to establish structure−activity relationships, which provide insights for the rational design of efficient metal-based dyes in photocatalytic oxidation reactions. In addition, we have formulated a dual mechanism, mediated by the radical anion superoxide, for the above-mentioned transformations., We acknowledge the financial support provided by the Spanish Ministerio de Ciencia, Innovación y Universidades (RTI2018- 100709-B-C21 and CTQ (QMC)-RED2018-102471-T), Consejería de Educación de la Junta de Castilla y León and FEDER (BU087G19 and BU067P20), and Junta de Comunidades de Castilla-La Mancha-FEDER (JCCM) (grant SBPLY/19/ 180501/000260). I.E. acknowledges his fellowship to both the European Social Fund and Consejería de Educación de la Junta de Castilla y León (EDU/1100/2017). We are also indebted to J. Delgado, P. Castroviejo, and M. Mansilla (PCT of the Universidad de Burgos) for technical support, G. GarcíaHerbosa for providing us access to CV equipment, and J. V. Cuevas-Vicario for support with Gaussian.

Photodynamic therapy is an alternative to classical chemotherapy due to its potential to reduce side effects by a controlled activation of a photosensitizer through local irradiation, which then interacts with oxygen and generates reactive oxygen species. Iridium biscyclometallated complexes are very promising photosensitizers due to their exceptional photophysical properties and their ability to target mitochondria. Four Ir(III) biscyclometallated complexes of formula [Ir(C^N)2(N^N’)]Cl, where N^N’ is a ligand containing a benzimidazolyl fragment, have been synthesized and characterized. The C^N ligands were 2-phenylpyridinate (ppy) and 2-(2,4-difluorophenyl)pyridinate (dfppy). The complexes exhibited high photostability. The electrochemical and photophysical properties were modulated by both the cyclometallating and the ancillary ligands. The dfppy derivatives yielded the highest emission energy values, quantum yields of phosphorescence and excited state lifetimes. All complexes generated 1O2 in aerated solutions upon irradiation. Biological studies revealed that these complexes have a moderate cytotoxicity in the dark against different human cancer cell lines: prostate (PC-3), colon (CACO-2) and melanoma (SK-MEL-28), and against non-malignant fibroblasts (CCD-18Co). However, derivatives with ppy ligands ([1a]Cl, [2a]Cl) yielded a relevant photodynamic activity upon light irradiation (450 nm, 24.1 J cm–2), with phototoxicity indexes (EC50,dark/EC50,light) of 20.8 and 17.3, respectively, achieved in PC-3 cells. Mechanistic studies showed that these complexes are taken up by the cells through endocytosis and preferentially accumulate in mitochondria. Upon photoactivation, the complexes induced mitochondrial membrane depolarization and DNA damage, thus triggering cell death, mainly by apoptosis. Complex [1a]Cl is also able to oxidize NADH. This mitochondria-targeted photodynamic mechanism greatly inhibited the reproductive capacity of cancer cells and provides a valuable alternative to traditional chemotherapy for the controlled treatment of cancer.

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerability, We acknowledge the “la Caixa” Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia Innovación y Universidades-FEDER (RTI2018-102040-B-100) and Junta de Castilla y León-FEDER (BU305P18) for financial support. Networking support by COST Action CA18202 (NECTAR) is also acknowledged.

Current societies demand sustainable synthetic procedures and accordingly the combination of two photocatalytic reactions in a one-pot process is a very appealing chemical tool. In the present work, we report on the development of new Ir(III) bis-cyclometallated photosensitizers with β-carboline ligands and disclose a simple and unprecedented photocatalytic one-pot two-step protocol for the chemoselective and C-3 regioselective oxidative thiocyanation of indolines to produce the corresponding 3-thiocyanato-indoles. The procedure is performed in THF at room temperature, in the presence of NH4SCN, O2 and the Ir(III) photocatalysts under blue light exposure. Moreover, this methodology combines important advantages such as an outstanding efficiency, based on good yields for low catalyst loadings, along with an excellent sustainability founded on the use of O2 as a green oxidant and light as the energy source. In addition, DFT studies have allowed a clear interpretation of the photophysical and electrochemical properties of the Ir(III) complexes and transient absorption experiments, along with other experimental proof, have demonstrated that the two photocatalytic processes are mediated by 1O2. Our results pave the way for future developments in the field of photocatalysis using Ir(III) biscyclometallated complexes as photosensitizers.

RTI2018-100709-B-C21 CTQ (QMC)-RED2018-102471-T) Junta de Castilla y Leon (BU087G19 FEDER (BU042U16-BU305P18). Five new RuII polypyridyl complexes bearing N-(arylsulfonyl)-8-amidoquinolate ligands and three of their biscyclometalated IrIII congeners have been prepared and employed as photocatalysts (PCs) in the photooxidation of benzylamines with O2. In particular, the new RuII complexes do not exhibit photoluminescence, rather they harvest visible light efficiently and are very stable in solution under irradiation with blue light. Their non-emissive behavior has been related to the low electrochemical energy gaps and rationalized on the basis of theoretical calculations (DFT analysis) that predict low S0←T1 energy values. Moreover, the RuII complexes, despite being non-emissive, display excellent activities in the selective photocatalytic transformation of benzylamines into the corresponding imines. The presence of an electron-withdrawing group (-CF3) on the arene ring of the N-(arylsulfonyl)-8-amidoquinolate ligand improves the photocatalytic activity of the corresponding photocatalyst. Furthermore, all the experimental evidence, including transient absorption spectroscopy measurements suggest that singlet oxygen is the actual oxidant. The IrIII analogues are considerably more photosensitive and consequently less efficient photosensitizers (PSs). authorsversion published

Three neutral Pt(II) complexes containing 1-Methylimidazole and the antifungal imidazolyl drugs Clotrimazole and Bifonazole have been prepared. The general formula of the new derivatives is [Pt(κ2-(C^N)Cl(L)], where C^N stands for ppy = 2-phenylpyridinate, and L = 1-Methylimidazole (MeIm) for [Pt-MeIm]; L = Clotrimazole (CTZ) for [Pt-CTZ] and L = Bifonazole (BFZ) for [Pt-BFZ]). The complexes have been completely characterized in solution and the crystal structures of [Pt-BFZ] and [Pt-CTZ] have been resolved. Complexes [Pt-MeIm] and [Pt-BFZ] present higher cytotoxicity than cisplatin in SW480 (colon adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian cancer) cell lines. [Pt-MeIm] shows the highest accumulation in A549 cells, in agreement with its inability to interact with serum albumin. By contrast, [Pt-CTZ] and [Pt-BFZ] interact with serum proteins, a fact that reduces their bioavailability. The strongest interaction with bovine serum albumin (BSA) is found for [Pt-BFZ], which is the least internalized inside the cells. All the complexes are able to covalently interact with DNA. The most cytotoxic complexes, [Pt-MeIm] and [Pt-BFZ] induce cellular accumulation in G0/G1 and apoptosis by a similar pathway, probably involving a reactive oxygen species (ROS) generation mechanism. [Pt-BFZ] turns out to be the most efficient complex regarding ROS generation and causes mitochondrial membrane depolarization, whereas [Pt-MeIm] induces the opposite effect, hyperpolarization of the mitochondrial membrane. On the contrary, the least cytotoxic complex, [Pt-CTZ] cannot block the cell cycle or generate ROS and the mechanism by which it induces apoptosis could be a different one., La Caixa Foundation (LCF/PR/PR12/11070003), Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100). M.V. is grateful for the financial support received from the Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18).

An important challenge in the field of anticancer chemotherapy is the search for new species to overcome the resistance of standard drugs. An interesting approach is to link bioactive ligands to metal fragments. In this work, we have synthesized a set of p-cymene-Ru or cyclopentadienyl-M (M = Rh, Ir) complexes with four chrysin-derived pro-ligands with different -OR substituents at position 7 of ring A. The introduction of a piperidine ring on chrysin led to the highly cytotoxic pro-ligand HL4 and its metal complexes L4-M (SW480 and A549 cell lines, cytotoxic order: L4-Ir > L4-Ru ≈ L4-Rh). HL4 and its complexes induce apoptosis and can overcome cis-platinum resistance. However, HL4 turns out to be more cytotoxic in healthy than in tumor cells in contrast to its metal complexes which displayed higher selectivity than cisplatin towards cancer cells. All L4-M complexes interact with double stranded DNA. Nonetheless, the influence of the metal is clear because only complex L4-Ir causes DNA cleavage, through the generation of highly reactive oxygen species (1O2 ). This result supports the hypothesis of a potential dual mechanism consisting of two different chemical pathways: DNA binding and ROS generation. This behavior provides this complex with a great effectivity in terms of cytotoxicity, Spanish Ministerio de Ciencia, Innovación y UniversidadesFEDER (RTI2018-100709-B-C21 and RTI2018-102040-B-100), Junta de Comunidades de CastillaLa Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260), Junta de Castilla y León-FEDER (BU087G19 and BU305P18), “la Caixa” Foundation (LCF/PR/PR12/11070003), as well as by UCLMFEDER (grants 2019-GRIN-27183 and 2019-GRIN-27209).

Photocatalysis is an expanding tool designed to synthesize organic molecules in a very efficient and selective way, using mild and environmentally friendly conditions. Thus, the development of new photosensitizers and photocatalytic protocols can further boost the applicability of photocatalysis in preparative chemistry. In this paper, we have conceived a family of Ru(II) polypyridyl complexes of general formula [Ru(bpy)2(N^N)]Cl2 (bpy = 2,2′-bipyridine) bearing the 2-pyridylbenzimidazole (Hpybim) scaffold in the ancillary ligands (N^N = R-pybim). Moreover, using these Ru(II) derivatives as photosensitizers we have described a protocol for the synthesis of imines from primary and secondary amines and also a simple, efficient and selective methodology for the one-pot preparation of α-amino nitriles from primary and secondary amines involving the consecutive photooxidation of the amine substrate and the cyanation of the imine intermediate. In addition, we have formulated a mechanism for the afore-mentioned transformations based on the participation of singlet oxygen.

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19) resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%) which associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19, demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney., Graphical abstract

Background This is the first report of the 1-year outcomes of the EVEREST-I study evaluating the safety and efficacy of the Optilume® BPH Catheter System, a prostatic paclitaxel-coated balloon catheter system, for the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). Methods Subjects were men >50 years old with moderate-to-severe LUTS secondary to BPH, peak urinary flow rate of 5–15 ml/s, prostatic urethra length 30–55 mm, and prostate volume 20–80 g. All were treated with the Optilume BPH Catheter System and followed at Foley removal, 2 weeks, 30 days, 3, 6, and 12 months after treatment. The primary endpoint was the proportion of subjects with ≥40% improvement in International Prostate Symptom Score (IPSS). The rate of post-procedural complications was evaluated. Results Eighty subjects were treated at six sites in Latin America and 75 completed the 1-year follow-up. The percent of subjects with an improvement ≥40% in IPSS from baseline was 81% at 3 months and 1 year. IPSS improved from 22.3 at baseline to 7.9 at 1 year, Qmax improved from 10.9 to 18.4 ml/s, and IPSS QoL improved from 4.6 to 1.3. Post-procedural complications included common urologic events and the rate of complications was significantly impacted by device diameter. Conclusions Treatment with the minimally invasive Optilume BPH Catheter System is safe and showed subjective and objective improvements in LUTS. Benefits were rapid and persisted through 1 year. The initial results warrant further evaluation of this therapy as a treatment option for patients with LUTS related to BPH.

The development of efficient and eco-friendly methods for the synthesis of elaborate amines is highly desired as they are valuable chemicals. The catalytic alkylation of amines using alcohols as alkylating agents, through the so-called borrowing hydrogen process, satisfies several of the principles of green chemistry. In this paper, four neutral half-sandwich complexes of Ru(II), Rh(III), and Ir(III) have been synthesized and tested as catalysts in the N-benzylation of amines with benzyl alcohol. The new derivatives contain a N^N′ anionic ligand derived from 5-(pyridin-2-ylmethylene)hydantoin (Hpyhy) that has never been tested in metal complexes with catalytic applications. In particular, the Ir derivatives, [(Cp*)IrX(pyhy)] (X = Cl or H), exhibit high activity along with good selectivity in the process. Indeed, the scope of the optimized protocol has been proved in the benzylation of several primary and secondary amines. The selectivity towards monoalkylated or dialkylated amines has been tuned by adjusting the amine:alcohol ratio and the reaction time. Experimental results support a mechanism consisting of three consecutive steps, two of which are Ir catalyzed, and a favorable condensation step without the assistance of the catalyst. Moreover, an unproductive competitive pathway can operate when the reaction is performed in open-air vessels, due to the irreversible release of H2. This route is hampered when the reaction is carried out in close vessels, likely because the release of H2 is reversed through metal-based heterolytic cleavage. From our viewpoint, these results show the potential of the new catalysts in a very attractive and promising methodology for the synthesis of amines., El desarrollo de métodos eficientes y ecológicos para la síntesis de aminas elaboradas es muy deseable, ya que son sustancias químicas valiosas. La alquilación catalítica de aminas utilizando alcoholes como agentes alquilantes, mediante el llamado proceso de préstamo de hidrógeno, satisface varios de los principios de la química verde. En este artículo, se sintetizaron y probaron cuatro complejos semisándwich neutros de Ru(II), Rh(III) e Ir(III) como catalizadores en la N -bencilación de aminas con alcohol bencílico. Las nuevas derivadas contienen un N ^ N′ ligando aniónico derivado de 5-(piridin-2-ilmetileno)hidantoína (Hpyhy) que nunca se ha probado en complejos metálicos con aplicaciones catalíticas. En particular, los derivados de Ir, [(Cp*)IrX(pyhy)] (X = Cl o H), muestran una alta actividad junto con una buena selectividad en el proceso. De hecho, el alcance del protocolo optimizado ha sido probado en la bencilación de varias aminas primarias y secundarias. La selectividad hacia las aminas monoalquiladas o dialquiladas se ha ajustado ajustando la relación amina:alcohol y el tiempo de reacción. Los resultados experimentales respaldan un mecanismo que consta de tres pasos consecutivos, dos de los cuales son catalizados por Ir y un paso de condensación favorable sin la ayuda del catalizador. Además, una vía competitiva improductiva puede operar cuando la reacción se realiza en recipientes al aire libre,2 . Esta ruta se ve obstaculizada cuando la reacción se lleva a cabo en recipientes cerrados, probablemente porque la liberación de H 2 se invierte a través de la escisión heterolítica basada en metales. Desde nuestro punto de vista, estos resultados muestran el potencial de los nuevos catalizadores en una metodología muy atractiva y prometedora para la síntesis de aminas.

The importance of ion pairing in different fields of chemistry is widely recognized. In this work, we have synthesized a set of cationic

Introduction: Mechanical balloon dilation and direct visualization internal urethrotomy (DVIU) are the most widely used treatments for urethral stricture disease in the U.S., but recurrence rates are high, especially after re-treatment. This study investigates the safety and efficacy of the Optilume™ paclitaxel-coated balloon for the treatment of recurrent strictures. Methods: Men with recurrent bulbar strictures ≤2 cm with 1–4 prior endoscopic treatments were treated with the Optilume™ drug-coated balloon. Patients were evaluated within 14 days, three, six, 12, and 24 months post-treatment. The primary safety endpoint was serious urinary adverse events. The primary efficacy endpoint was ≥50% improvement in International Prostate Symptom Score (IPSS) at 24 months. Secondary outcomes included quality of life, erectile function, flow rate, and post-void residual urine volume. Results: A total of 53 subjects were enrolled and treated; 46 completed the 24-month followup. Forty-three percent of men had undergone >1 previous dilations, with a mean of 1.7 prior dilations. There were no serious adverse events related to treatment at two years. Success was achieved in 32/46 (70%), and baseline IPSS improved from a mean of 25.2 to 6.9 at 24 months (p

INTRODUCTION AND OBJECTIVE:Data includes the initial 1 year EVEREST– I Study experience with the Optilume BPH Catheter System, with minimally invasive urethral prostatic balloon dilation, anterior ...

INTRODUCTION AND OBJECTIVE:We report 2-year outcomes of ROBUST I, a multi-center, single-arm, open-label study of the safety and efficacy of a paclitaxel drug-coated balloon (DCB) for treatment of ...

Five new Ru

A new family of neutral chiral cyclometalated platinum(II) complexes with formula [Pt(κ2-(C^N))Cl(κ1-(L))], where (C^N) = 2-phenylpyridinate and (L) = 2-(2-pyridyl)benzimidazole (L1) or (N-(CH2)-Ar-(2-(2-pyridyl)benzimidazole) ligands; (Ar = phenyl (L2), naphthyl (L3), pyrenyl (L4)), have been synthesized and completely characterized. The unexpected κ1 coordination mode of the 2-(2-pyridyl)benzimidazole-derived ligands has been confirmed by spectroscopic techniques and X-ray diffraction. The aromatic moieties on the ligands in the new platinum(II) complexes have a remarkable influence on the cytotoxicity and in the binding mode to DNA. [Pt-L1]-[Pt-L4] complexes internalized more than cisplatin in the SW480 cancer cells even though only [Pt-L1] and [Pt-L2] display high cytotoxicity. 1H NMR and 13P{1H}NMR pointed out that [Pt-L1] and [Pt-L2] complexes bind covalently to dGMP, while the electrophoresis assays and CD experiments indicate that only [Pt-L2] is able to covalently interact with DNA, inducing the same conformational changes in the plasmid DNA as cisplatin. Although the complex [Pt-L4] intercalates into DNA, probably through the pyrenyl moiety, no biological activity is observed.

Considering the interest in processes related to hydrogen storage such as CO2 hydrogenation and formic acid (FA) decomposition, we have synthesized a set of Ir, Rh, or Ru complexes to be tested as versatile precatalysts in these reactions. In relation with the formation of H2 from FA, the possible applicability of these complexes in the transfer hydrogenation (TH) of challenging substrates as quinoline derivatives using FA/formate as hydrogen donor has also been addressed. Bearing in mind the importance of secondary coordination sphere interactions, N,N' ligands containing NH2 groups, coordinated or not to the metal center, were used. The general formula of the new complexes are [( p-cymene)RuCl(N,N')]X, X = Cl-, BF4- and [Cp*MCl(N,N')]Cl, M = Rh, Ir, where the N,N' ligands are 8-aminoquinoline (HL1), 6-pyridyl-2,4-diamine-1,3,5-triazine (L2) and 5-amino-1,10-phenanthroline (L3). Some complexes are not active or catalyze only one process. However, the complexes [Cp*MCl(HL1)]Cl with M = Rh, Ir are versatile catalysts that are active in hydrogenation of quinolines, FA decomposition, and also in CO2 hydrogenation with the iridium derivative being more active and robust. The CO2 hydrogenation takes place in mild conditions using only 5 bar of pressure of each gas (CO2 and H2). The behavior of some precatalysts in D2O and after the addition of 9 equiv of HCO2Na (pseudocatalytic conditions) has been studied in detail and mechanisms for the FA decomposition and the hydrogenation of CO2 have been proposed. For the Ru, Ir, or Rh complexes with ligand HL1, the amido species with the deprotonated ligand are observed. In the case of ruthenium, the formate complex is also detected. For the iridium derivative, both the amido intermediate and the hydrido species have been observed. This hydrido complex undergoes a process of umpolung D+↔ Ir-D. All in all, the results of this work reflect the active role of -NH2 in the transfer of H+.

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral IrIII biscyclometalated complexes of general formula [Ir(C^N)2(N^O)], where the N^O ligands are 2‐(benzimidazolyl)phenolate‐N,O (L1, series a) and 2‐(benzothiazolyl)phenolate‐N,O (L2, series b), and the C^N ligands are 2‐(phenyl)pyridinate or its derivatives, are described,. Complexes of types a and b exhibit dissimilar photophysical and biological properties. In vitro cytotoxicity tests conclusively prove that derivatives of series a are harmless in the dark against SW480 cancer cells (colon adenocarcinoma), but express enhanced cytotoxicity versus the same cells after stimulation with UV or blue light. In contrast, complexes of type b show a very high cytotoxic activity in the dark, but low photosensitizing ability. Thus, the ancillary N^O ligand is the main factor in terms of cytotoxic activity both in the dark and upon irradiation. However, the C^N ligands play a key role regarding cellular uptake. In particular, the complex of formula [Ir(dfppy)2(L1)] (dfppy=2‐(4,6‐difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for 1O2 generation and a potential agent for photodynamic therapy. These capabilities are probably related to a combination of its notable cellular internalization, remarkable photostability, high photoluminescence quantum yield, and long triplet excited‐state lifetime. Both types of complexes exhibit notable catalytic activity in the photooxidation of thioanisole and S‐containing aminoacids with full selectivity., SpanishMinisteriode Econom&ayCompetitividad-FEDER(CTQ2014-58812-C2-1-Rand CTQ2014-58812-C2-2-R,CTQ2015-70371-REDT,CTQ2015-71353-R,CTQ2015-71154-P,and Unidadde Excelencia Mar&adeMaeztuMDM-2015-0538),the Conseje-r&adeEducacijn-Juntade CastillayLejn-FEDER(BU299A12-1,BU042U16and BU051U16).The Generalitat Valenciana(Prome-teo2016/135),andthe “la Caixa”Foundation(LCF/PR/PR12/11070003)

Two Schiff bases derived from o-vanillin (o-HVA), a well-known antioxidant hydroxo aldehyde, have been obtained from condensation with 2-thiophenecarboxilic acid hydrazide (TPNNH) and 2- thiophenemethylamine (TPNH2), respectively. The inclusion of thiophene is based on its significance in the development of effective therapeutic agents. The study of the compounds oVATPNNH and oVATPNH2 includes solid state structural and spectroscopic analysis by single-crystal X-ray diffraction and vibrational spectroscopy (FTIR and Raman). The crystal structure of oVATPNH2 shows a peculiar rotational disorder in the heterocycle. Tautomeric equilibria in solution, which depends on the molecule structure and the nature of the solvent, were analysed by means of 1H and 13C{1H} NMR along with electronic spectroscopy. Tautomerism plays an important role not only in the molecular interactions but also in the behaviour of the Schiff base when acting as a ligand in coordination compounds. Results obtained from DFT calculations were used in the interpretation of the experimental data and in the spectral assignments., Centro de Química Inorgánica

The synthesis and characterization of Pt(II) (1 and 2) and Ru(II) arene (3 and 4) or polypyridine (5 and 6) complexes is described. With the aim of having a functional group to form bioconjugates, one uncoordinated carboxyl group has been introduced in all complexes. Some of the complexes were selected for their potential in photodynamic therapy (PDT). The molecular structures of complexes 2 and 5, as well as that of the sodium salt of the 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine ligand (cptpy), were determined by X-ray diffraction. Different techniques were used to evaluate the binding capacity to model DNA molecules, and MTT cytotoxicity assays were performed against four cell lines. Compounds 3, 4, and 5 showed little tendency to bind to DNA and exhibited poor biological activity. Compound 2 behaves as bonded to DNA probably through a covalent interaction, although its cytotoxicity was very low. Compound 1 and possibly 6, both of which contain a cptpy ligand, were able to intercalate with DNA, but toxicity was not observed for 6. However, compound 1 was active in all cell lines tested. Clonogenic assays and apoptosis induction studies were also performed on the PC-3 line for 1. The photodynamic behavior for complexes 1, 5, and 6 indicated that their nuclease activity was enhanced after irradiation at λ = 447 nm. The cell viability was significantly reduced only in the case of 5. The different behavior in the absence or presence of light makes complex 5 a potential prodrug of interest in PDT. Molecular docking studies followed by molecular dynamics simulations for 1 and the counterpart without the carboxyl group confirmed the experimental data that pointed to an intercalation mechanism. The cytotoxicity of 1 and the potential of 5 in PDT make them good candidates for subsequent conjugation, through the carboxyl group, to "selected peptides" which could facilitate the selective vectorization of the complex toward receptors that are overexpressed in neoplastic cell lines.

Introduction: We aimed to investigate the safety and preliminary efficacy of the OptilumeTM paclitaxel-coated balloon for the treatment of recurrent urethral stricture. Methods: Men with bulbar urethral strictures ≤2 cm with 1–4 prior endoscopic treatments were enrolled at four study sites after Ethics Committee approvals. All subjects were treated with mechanical balloon dilation or direct visualization internal urethrotomy prior to drug-coated balloon treatment. Patients were evaluated at 2–5 days, 14 days, three, six, and 12-months post-treatment. The primary safety endpoint was serious complications through 90 days post-procedure. The preliminary efficacy endpoint was anatomic success, defined as urethral lumen ≥14 Fr at 12 months. Results: A total of 53 subjects were enrolled and treated; 46 completed the 12-month followup. Forty-three percent of men had undergone >1 previous dilation; the mean for the overall study population was 1.7 prior dilations. There were no serious adverse events related to the treatment within 90 days. Anatomic success was achieved in 32/46 (70%; 95% confidence interval [CI] 54–82%) at 12 months. The 14 failures included seven cystoscopic recurrences, five retreatments, and two patients who exited the study early due to symptom recurrence. Conclusions: One-year data indicates the OptilumeTM paclitaxel-coated balloon is safe for the treatment of recurrent bulbar urethral strictures. Early efficacy results are encouraging and support further followup of these men through five years, as well as further investigation with a randomized trial.

The synthesis and characterization of two half-sandwich complexes of Ru(II) and Ir(III) with thiabendazole as ancillary ligand and their DNA binding ability were investigated using experimental and computational methods. 1H NMR and acid–base studies have shown that aquo-complexes are the reactive species. Kinetic studies show that both complexes bind covalently to DNA through the metal site and non covalently through the ancillary ligand. Thermal stability studies, viscosity, circular dichroism measurements and quantum chemical calculations have shown that the covalent binding causes breaking of the H-bonding between base pairs, bringing about DNA denaturation and compaction. Additionally, molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations shed light into the binding features of the Ru(II) and Ir(III) complexes and their respective enantiomers toward double-helical DNA, highlighting the important role played by the NˆN ancillary ligand once the complexes are covalently linked to DNA. Moreover, metal quantification in the nucleus of SW480 colon adenocarcinoma cells were carried out by inductively coupled plasma–mass spectrometry (ICP–MS), both complexes are more internalized than cisplatin after 4h of exposition. However, in spite of the dramatic changes in the helicity of the DNA secondary structure induced by these complexes and their nuclear localization, antiproliferative studies have revealed that both, Ru(II) and Ir(III) complexes, cannot be considered cytotoxic. This unexpected behavior can be justified by the fast formation of aquo-complexes, which may react with components of the cell culture medium or the cytoplasm compartment in such a way that they may become deactivated before reaching DNA. Graphic abstract: [Figure not available: see fulltext.].

The synthesized 2-(hydroxy-1-naphtyl)imidazo-[4,5-f][1,10]phenanthroline (HNAIP) ligand and its new iridium ([Ir(ppy)2(HNAIP)]Cl) and rhodium ([Rh(ppy)2(HNAIP)]Cl) complexes, being ppy = 2-phenylpiridinate, show cytotoxic effects in SW480 (colon adenocarcinoma) and A549 (epithelial lung adenocarcinoma) cells. They all are cytotoxic in the tested cell lines. HNAIP and [Rh(ppy)2(HNAIP)]+ are the most cytotoxic, whereas [Ir(ppy)2(HNAIP)]+ displays negligible cytotoxicity towards A549 cells and moderate activity towards SW480. The interaction of all three compounds with Bovine Serum Albumin (BSA), l-glutathione reduced (GSH), nicotinamide adenine dinucleotide (NADH) and DNA was studied to explain the differences found in terms of cytotoxicity. None of them are able to interact with BSA, thus excluding bioavailability due to plasma protein interaction as the possible differentiating factor in their biological activity. By contrast, small differences have been observed regarding DNA interaction. In addition, taking advantage of the emission properties of these molecules, they have been visualized in the cytoplasmic region of A549 cells. Inductively coupled plasma mass spectrometry (ICP-MS) experiments show, in turn, that the internalization ability follow the sequence [Rh(ppy)2(HNAIP)]+ > [Ir(ppy)2(HNAIP)]+ > cisplatin. Therefore, it seems clear that the cellular uptake by tumour cells is the key factor affecting the different cytotoxicity of the metal complexes and that this cellular uptake is influenced by the hydrophobicity of the studied complexes. On the other hand, preliminary catalytic experiments performed on the photo-oxidation of GSH and some amino acids such as l-methionine (Met), l-cysteine (Cys) and l-tryptophan (Trp) provide evidence for the photocatalytic activity of the Ir(III) complex in this type of reactions., “la Caixa” Banking Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100 and RTI2018-100709-B-C21), Junta de Castilla y León (BU305P18, FEDER Funds)

The importance of ion pairing in different fields of chemistry is widely recognized. In this work, we have synthesized a set of cationic p-cymene ruthenium complexes of general formula [(p-cym)Ru(L′)(κ2-O^N–L)]X (p-cym = p-cymene; L′ = N-methylimidazole (MeIm), N-ethylpiperidylimidazole (EpipIm), 1,3,5-triaza-7-phosphaadamantane (PTA); L = 2-(1H-benzimidazol-2-yl)phenolato (L1), 2-(1,3-benzothiazol-2-yl)phenolato (L2); X = Cl–, BF4–, OTf–, BPh4–). X-ray diffraction studies on selected complexes revealed relatively strong anion–cation interactions in the solid state mainly based on N–H···X (X = Cl, F, O) and C–H···π interactions, also observed in the DFT-modeled complexes in the gas phase. Moreover, NMR studies showed that they exist as intimate ion pairs in solution and, remarkably, as head-to-tail quadruples in the particular case of the cation [(p-cym)Ru(MeIm)(κ2- O^N–L1)]+ ([1]+) with Cl– and BPh4– as counteranions. Furthermore, a value of ΔG = −2.9 kcal mol–1 at 299 K has been estimated for the equilibrium {[1]BPh4···[1]BPh4} ⇆ 2{[1]+···BPh4–} in concentrated CDCl3 solutions. In addition, preliminary studies concerning the cytotoxic properties against HeLa cell lines of the derivatives suggested a positive effect derived from the presence of the lipophilic BPh4– anion and also from the NH group of the benzimidazolyl fragment., This work has been funded by the Spanish Ministerio de Ciencia, Innovación y Universidades (RTI2018-100709-B-C21) and MINECO/FEDER/AGE (CTQ2017-83421-P, C.T.), Junta de Castilla y León (BU087G19) and Gobierno de Aragón/FEDER (GA/FEDER, Inorganic Molecular Architecture Group E08_17R; C.T.), as well as by UCLM (grants 2019-GRIN-27183 and 2019-GRIN-27209) and Junta de Comunidades de Castilla-La Mancha (JCCM; grants SBPLY/19/180501/000260 and SBPLY/19/180501/000251), both cofinanced with the European Union FEDER.

The synthesized 2-(hydroxy-1-naphtyl)imidazo-[4,5-f][1,10]phenanthroline (HNAIP) ligand and its new iridium ([Ir(ppy)

INTRODUCTION AND OBJECTIVES:Introduction & Objective: Urethral strictures are most commonly treated via minimally invasive techniques such as dilation or direct vision internal urethrotomy (DVIU); ...

We have synthesized a set of bombesin derivatives with the aim of exploring their tumor targeting properties to deliver metal-based chemotherapeutics into cancer cells. Peptide QRLGNQWAVGHLL-NH2 (BN3) was selected based on its high internalization in gastrin-releasing peptide receptor (GRPR)-overexpressing PC-3 cells. Three metallopeptides were prepared by incorporating the terpyridine Pt(II) complex [PtCl(cptpy)]Cl (1) (cptpy = 4′-(4-carboxyphenyl)-2,2′:6,2″-terpyridine) at the N-terminus of BN3 or at the NƐ- or Nα-amino group of an additional Lys residue (1-BN3, Lys-1-BN3 and 1-Lys-BN3, respectively). 1-Lys-BN3 displayed the best cytotoxic activity (IC50: 19.2 ± 1.7 μM) and similar ability to intercalate into DNA than complex 1. Moreover, the polypyridine Ru(II) complex [Ru(bpy)2)(cmbpy)](PF6)2 (2) (bpy = 2,2′-bipyridine; cmbpy = 4-methyl-2,2′-bipyridine-4′-carboxylic acid), with proven activity as photosensitizer, was coupled to BN3 leading to metallopeptide 2-Lys-BN3. Upon photoactivation, 2-Lys-BN3 displayed 2.5-fold higher cytotoxicity against PC-3 cells (IC50: 7.6 ± 1.0 μM) than complex 2. To enhance the accumulation of the drugs into the cell nucleus, the nuclear localization signal (NLS) PKKKRKV was incorporated at the N-terminus of BN3. NLS-BN3 displayed higher cellular internalization along with nuclear biodistribution. Accordingly, metallopeptides 1-NLS-BN3 and 2-NLS-BN3 showed increased cytotoxicity (IC50: 12.0 ± 1.1 μM and 2.3 ± 1.1 μM). Interestingly, the phototoxic index of 2-NLS-BN3 was 8-fold higher than that of complex 2. Next, the selectivity towards cancer cells was explored using 1BR3.G fibroblasts. Higher selectivity indexes were obtained for 1-NLS-BN3 and 2-NLS-BN3 than for the unconjugated complexes. These results prove NLS-BN3 effective for targeted delivery of metallodrugs to GRPR-overexpressing cells and for enhancing the cytotoxic efficacy of metal-based photosensitizers.

Considering the interest in processes related to hydrogen storage such as CO

A new family of neutral ruthenium(II) arene complexes of the type [Ru(η6-arene)X(κ2-O,N-L)] (η6-arene = p-cym, bz; X = Cl–, SCN–; HL1 = 2-(2′-hydroxyphenyl)benzimidazole, HL2 = 2-(2′-hydroxyphenyl)benzothiazole) has been synthesized and characterized. The cytotoxic activity of the Ru(II) complexes was evaluated in several tumor cell lines (A549, HepG2 and SW480) both in the dark and after soft irradiation with UV and blue light. None of the complexes bearing benzimidazole (HL1) as a ligand displayed phototoxicity, whereas the complexes with a benzothiazole ligand (HL2) exhibited photoactivation; the sensitivity observed for UV was higher than for blue light irradiation. The interesting results displayed by HL2 and [Ru(η6-p-cym)(NCS)(κ2-O,N-L2)], [3a], in terms of photo cytotoxicity prompted us to analyze their interaction with DNA, both in the dark and under irradiation conditions, in an effort to shed some light on their mechanism of action. The results of this study revealed that HL2 interacts with DNA ...

Two pairs of Rh(III) and Ir(III) biscyclometallated complexes with thiabendazole (L1), named [Ir-a]Cl and [Rh-a]Cl, and N-benzyl-thiabendazole (L2), named [Ir-b]Cl and [Rh-b]Cl, have been designed and synthesized to explore the photophysical and biological effects that arise from changing both the metal center and the ancillary ligand. In the dark, the four metal complexes exhibit greater cytotoxicity than cisplatin against human colon (SW480) and human lung (A549) adenocarcinoma cell lines. Moreover, the pair of complexes bearing the ligand L2 is markedly more cytotoxic and present higher uptake values than complexes with L1, thereby their biological properties were studied further to determine their mechanism of action. Interestingly, in spite of the different metal center both the [Ir-b]Cl and [Rh-b]Cl complexes are responsible for the loss of mitochondrial functionality and the activation of apoptotic cell death pathways. Moreover, the photodynamic activity of the four complexes, [Ir-a,b]Cl and [Rh-a,b]Cl, was tested using visible blue light (460 nm) under soft irradiation conditions (20 min, 5.5 mW cm−2). While the Rh complexes are not photopotentiated, the phototoxicity index (IC50 non-irradiated/IC50 irradiated) of [Ir-a]Cl and [Ir-b]Cl complexes was 15.8 and 3.6, respectively. We also demonstrate that only the Ir derivatives are capable of photocatalyzing the oxidation of S-containing l -amino acids under blue light irradiation, [Ir-a]Cl being more active than [Ir-b]Cl, which provides a reasonable mechanism for their biological action (oxidative stress could be selectively promoted through a photocatalytic action) upon irradiation. This different PDT behaviour depending on the metal center and the ancillary substituent may be useful for future rational design of metal-based photosensitizers.

A new family of heteroleptic bis-cyclometalated Ir

A new family of heteroleptic bis-cyclometalated IrIII complexes with formula [Ir(C _ N)2(N _ N)]Cl (C _ N=2-phenylpyridinate and N _ N=2,2’-dipyridylamine or N-benzylated 2,2’-dipyridylamines, were synthesized, characterized, and successfully used as photosensitizers in the catalytic photooxidation of an array of dialkyl, dibenzyl, alkyl aryl, and diaryl sulfides, as well as sulfur-containing amino acids. Furthermore, the reactions proceeded with optimal chemoselectivity, and atom economy under mild conditions. Experimental observations support a dual mechanism in which singlet oxygen and superoxide are the actual oxidants., Consejer &a de Educacijn-Junta de Castilla y Lejn (BU042U16). Financial support by the Spanish Ministry of Economy and Competitiveness (MINECO) (projects CTQ2014-58812-C2@1-R, (CTQ2014-58812-C2-2-R, CTQ2015-70371-REDT, FEDER funds), Obra Social “la Caixa” (OSLC-2012-007), Junta de Castilla y Lejn (BU-042U16)

The complex [(η6-p-cymene)Ru(OH2)(κ2-N,N-HL1)](OTf)2 (HL1 = 2-pyridin-2-yl-1H-benzimidazole), [2c](OTf)2, undergoes easy deprotonation of the N-H group at physiological pH, producing [(η6-p-cymene)Ru(OH2)(κ2-N,N-L1)]+, [2c′]+, prone to dimerization both in solution and in the solid state. X-ray measurements on [2c′]BF4 have shown that dimer units are formed in the solid state by a combination of π-π stacking contacts between the aromatic rings of [L1]- and hydrogen bonding involving the water molecules coordinated to the metal center and the deprotonated imidazolyl N atom. The T-jump kinetic curves of the 2D → D2 equilibrium recorded in the microsecond time scale have allowed us to determine the parameters of the dimerization process. The dimer content diminishes as the ionic strength drops. The different kinetic and thermodynamic techniques have all shown that the monomer reacts with DNA, producing the bifunctional intercalated (through the benzimidazole ligand)-covalent (Ru/N7G) [(η6-p-cymene)Ru(κ2-N,N-L1)]/DNA complex. The cytotoxic activity of [2c′]+ was evaluated against human lung carcinoma cells (A549) by the MTT cell viability assay. Interestingly, the percentage of surviving cells as a function of the [2c′]+ content displayed biphasic behavior, interpreted as a result of the rise in the dimer content of [2c′]+. As only the monomer can react with DNA, a reasonable correlation between cytotoxic activity and formation of the [(η6-p-cymene)Ru(κ2-N,N-L1)]/DNA complex is established.

The new complex [(η6-p-cym)RuCl(κ2-N,N-dmbpy)](BF4) (p-cym = p-cymene; dmbpy = 4,4′-dimethyl-2,2′-bipyridine) is water-soluble and active in the catalytic transfer hydrogenation (TH) of different ketones (cyclohexanone, 2-cyclohexenone, and 3-pentanone) to the corresponding alcohols using aqueous HCOONa/HCOOH as the hydrogen source at pH 4.4. A higher activity was found for the TH of the imine N-benzylideneaniline under the same conditions. Excellent results have been obtained for catalyst recycling. Aqua, formato, and hydrido species were detected by 1H NMR experiments in D2O. Importantly, when the catalytic reaction was carried out in D2O, selective deuteration at the Cα of the alcohols was observed due to a rapid Ru–H/D+ exchange, which was also deduced theoretically. This process involves a reversal of polarity of the D+ ion, which is transformed into a Ru–D function (“umpolung”). Negligible deuterium labeling was observed for the imine, possibly due to the high activity in the TH process and also to ...

Aminophosphines 2-(diphenylphosphino)-1-methylimidazole (dpim) and diphenyl-2-pyridylphosphine (PPh(2)py) have been used to prepare two series of Ru(II) arene complexes of formulae [(η(6)-p-cymene)Ru(κ(2)-O,O'-X)(κ(1)-P-dpim)]Y (series a: 1a·Y-3a·Y) and [(η(6)-p-cymene)Ru(κ(2)-O,O'-X)(κ(1)-P-PPh(2)py)]Y (series b: 1b·Y-3b·Y) (where X=acac, acetylacetonate; bzac, benzoyl acetonate; dbzm, dibenzoyl methanoate; Y=BF(4), BPh(4)). The structures of 1a·BF(4), 1a·BPh(4), 3a·BF(4), 1b·BPh(4) and 3b·BPh(4) were determined by X-ray diffraction. The tetrafluoroborate derivatives are more soluble in organic solvents than their tetraphenylborate counterparts. Five BF(4)(-) derivatives (all except the unstable 1b·BF(4)) were selected to evaluate the cytotoxic behavior in vitro against the human cancer cell lines MCF-7 (breast cancer) and CAPAN-1 (pancreatic cancer). 2b·BF(4) and 3b·BF(4) exhibited IC(50) values similar to those of cisplatin. Electrophoresis and AFM studies showed good correspondence between the biological activity levels of 2b·BF(4) and 3b·BF(4) and their ability to modify the DNA structure. Hydrolytic studies indicate that aquation could be involved in the activation mechanism of these complexes and confirm that the hydrolysis rate of 3b·BF(4) is higher than that of 3a·BF(4). Thus, the cytotoxic activity trends are explained in terms of the higher reactivity of derivatives from series b, which in turn is rationalized as being the result of the electronic features of dpim and PPh(2)py established by cyclic voltammetry measurements.

The reaction of [RuCl2(cod)(bpzm)] [cod = 1,5-cyclooctadiene, bpzm = bis(pyrazol-1-yl)methane] with 2-diphenylphosphino-1-methylimidazole (dpim) and crystallisation from CHCl3 yielded crystals of cis-[RuCl(κ2-N,N-bpzm)(κ1-P-dpim)(κ2-P,N-dpim)][Cl(CHCl3)4]·CHCl3, (1√(CHCl3)5), in which the Cl− counteranion was solvated by four CHCl3 molecules and interacted with the most positive region of the cation. The structure of the anionic entity and the presence of non-covalent interactions were studied. Theoretical calculations allowed the evaluation of the stability of [Cl(CHCl3) n ]− aggregates. A pronounced stability was found for aggregates with n = 6 with an increasing charge transfer from the chloride ion to the CHCl3 molecules from n = 1 to 6. A literature survey on the occurrence of anionic species [Cl(CXCl3) n (HB) m ]− (X = H or D; HB = hydrogen bonds with the cation) in solid state structures was carried out and the findings correlated with the results of computational studies. A stabilisation effect...

The preparation of three series of arene Ru(II) half-sandwich compounds with the functional ligand 4,4′-dimethoxy-2,2′-bipyridine (dmobpy) is described. The new cationic derivatives have the general formula [(η6-arene)RuCl(κ2-N,N-dmobpy)]X (arene = benzene, X = Cl– ([1]Cl), BF4– ([1][BF4]), TsO– ([1]TsO), PF6– ([1][PF6]); arene = p-cymene (p-cym), X = Cl– ([2]Cl), BF4– ([2][BF4]), TsO– ([2]TsO), PF6– ([2][PF6]); arene = 2-phenoxy-1-ethanol (phoxet), X = Cl– ([3]Cl), BF4– ([3][BF4]), TsO– ([3]TsO), PF6– ([3][PF6])). The structures of [1]Cl, [1]TsO, [2]TsO, [2][BF4], and [2][PF6] were determined by X-ray crystallography. All of the complexes except the PF6– salts were water-soluble, and they behaved as active catalysts in two different processes: the transfer hydrogenation of water-soluble and -insoluble ketones to the corresponding alcohols, using HCOONa as the hydrogen source at pH 4, and the oxidation of rac-1-phenylethanol to acetophenone with tBuOOH at pH 7, both in aqueous solution. For the transfer h...

The protonation with Bronsted acids HB (HBF4 and CF3CO2H) of [RuH2(arene)(PPh2Het)] derivatives (PPh2Het = dpim, Het = 2-N-methylimidazolyl; PPh2Het = PPh2py, Het = 2-pyridyl) that contain uncoordinated N atoms has been analyzed experimentally by NMR spectroscopy and through computational studies. Initially, at low temperature, the uncoordinated N atoms of the phosphine are protonated and a proton–hydride exchange is observed by 1H NMR spectroscopy. The proton transfer leads to the corresponding cationic trihydride intermediates, which exhibit a dual character of classical and nonclassical hydrides, with the nonclassical species being more stable, especially when Het = 2-pyridyl. In fact, the release of H2 and the formation of the respective monohydride complexes [RuH(arene)(κ2-N,P-PPh2Het)]B was observed at room temperature. The participation of the uncoordinated N center in the proton transfer process in the stabilization of RuH(H2)+ with respect to RuH3+ species and in the hydride–dihydrogen exchange (...