The photoisomerization equilibrium between distal-and proximal- [Ru(tpy)

A new series of proximal,proximal-[Ru2(tpy)2(L)XY](n+) (p,p-Ru2XY, tpy = 2,2':6',2″-terpyridine, L = 5-phenyl-2,8-di(2-pyridyl)-1,9,10-anthyridine, X and Y = other coordination sites) were synthesized using photoisomerization of a mononuclear complex. The p,p-Ru2XY complexes undergo unusual reversible bridge-exchange reactions to generate p,p-Ru2(μ-Cl), p,p-Ru2(μ-OH), and p,p-Ru2(OH)(OH2) with μ-Cl, μ-OH, as well as hydroxo and aquo ligands at X and Y sites of p,p-Ru2XY, respectively. The geometric and electronic structures of these complexes were characterized based on UV-vis and (1)H NMR spectra, X-ray crystallography, and density functional theory (DFT) calculations. (1)H NMR data showed C2 symmetry of p,p-Ru2(OH)(OH2) with the distorted L chelate and nonequivalence of two tpy ligands, in contrast to the C2v symmetry of p,p-Ru2(μ-Cl) and p,p-Ru2(μ-OH). However, irrespective of the lower symmetry, p,p-Ru2(OH)(OH2) is predominantly formed in neutral and weakly basic conditions due to the specially stabilized core structure by multiple hydrogen-bond interactions among aquo, hydroxo, and backbone L ligands. The electrochemical data suggested that p,p-Ru2(OH)(OH2) (Ru(II)-OH:Ru(II)-OH2) is oxidized to the Ru(III)-OH:Ru(III)-OH state at 0.64 V vs saturated calomel electrode (SCE) and further to Ru(IV)═O:Ru(IV)-OH at 0.79 V by successive 1-proton-coupled 2-electron processes at pH 7.0. The cyclic voltammogram data exhibited that the p,p-Ru2(OH)(OH2) complex works more efficiently for electrocatalytic water oxidation, compared with a similar mononuclear complex distal-[Ru(tpy)(L)OH2](2+) (d-RuOH2) and p,p-Ru2(μ-Cl) and p,p-Ru2(μ-OH), showing that the p,p-Ru2 core structure with aquo and hydroxo ligands is important for efficient electrocatalytic water oxidation. Bulk electrolysis of the p,p-Ru2(OH)(OH2) solution corroborated the electrocatalytic cycle involving the Ru(III)-OH:Ru(III)-OH state species as a resting state. The mechanistic insight into O-O bond formation for O2 production was provided by the isotope effect on electrocatalytic water oxidation by p,p-Ru2(OH)(OH2) and d-RuOH2 in H2O and D2O media.

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes.

The authors present a case report of collecting duct carcinoma (CDC) that responded to nivolumab, a programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, following the failure of systemic treatment with chemotherapy and targeted therapy. The patient underwent right radical nephrectomy and segmentectomy of the lung following chemotherapy. Fifteen months following the first surgery, segmentectomy and subsequent second-line chemotherapy were performed for recurrence in the lung. Targeted therapy with temsirolimus for recurrence of the lung and lymph node metastases was ultimately used for 30 months. However, the temsirolimus treatment failed to suppress the growth of metastatic lesions. Nivolumab resulted in complete response of the lung metastasis, and it stabilized the lymph node metastasis. PD-L1 was highly expressed in both primary tumor and the metastatic regions. Therapy with nivolumab is ongoing. These findings suggest that treatment with nivolumab may be considered for metastatic and treatment-failure CDC.

We present a facile method for tungsten ion removal using lysine for the development of an environmentally friendly and sustainable recycling technique. Lysine addition to the tungsten solution achieved 100% tungsten removal within 5 min, as a white lysine–tungsten precipitate. Electrospray ionization mass spectrometry analyses of the tungsten and lysine mixed solutions showed that lysine promoted dehydration condensation reactions of anionic tungsten species such as HWO4 – and W6O19 2– through the electrostatic interactions between positively charged lysine and negatively charged tungsten ions. Calcination of the lysine–tungsten precipitate produced tungsten oxide powder of high purity (99.6%) because the lysine is completely decomposed. This facile and useful metal removal method can be used for polyoxometalates of other metals such as molybdenum, tantalum, and niobium.

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

proximal,proximal-(p,p)-[Ru(tpy)LXY] (tpy = 2,2';6',2″-terpyridine, L = 5-phenyl-2,8-di-2-pyridyl-1,9,10-anthyridine, and X and Y = other coordination sites) yields the structurally and functionally unusual Ru(μ-OH)Ru core, which is capable of catalyzing water oxidation with key water insertion to the core (Inorg. Chem. 2015, 54, 7627). Herein, we studied a sequence of bridging-ligand substitution among p,p-[Ru(tpy)L(μ-Cl)] (Ru(μ-Cl)), p,p-[Ru(tpy)L(μ-OH)] (Ru(μ-OH)), p,p-[Ru(tpy)L(OH)(OH)] (Ru(OH)(OH)), and p,p-[Ru(tpy)L(OH)] (Ru(OH)) in aqueous solution. Ru(μ-Cl) converted slowly (10 s) to Ru(μ-OH), and further Ru(μ-OH) converted very slowly (10 s) to Ru(OH)(OH) by the insertion of water to reach equilibrium at pH 8.5-12.3. On the basis of density functional theory (DFT) calculations, Ru(OH)(OH) was predicted to be thermodynamically stable by 13.3 kJ mol in water compared to Ru(μ-OH) because of the specially stabilized core structure by multiple hydrogen-bonding interactions involving aquo, hydroxo, and L backbone ligands. The observed rate from Ru(μ-OH) to Ru(OH) by the insertion of an OH ion increased linearly with an increase in the OH concentration from 10 to 100 mM. The water insertion to the core is very slow (∼10 s) in aqueous solution at pH 8.5-12.3, whereas the insertion of OH ions is accelerated (10-10 s) above pH 13.4 by 2 orders of magnitude. The kinetic data including activation parameters suggest that the associative mechanism for the insertion of water to the Ru(μ-OH)Ru core of Ru(μ-OH) at pH 8.5-12.3 alters the interchange mechanism for the insertion of an OH ion to the core above pH 13.4 because of relatively stronger nucleophilic attack of OH ions. The hypothesized p,p-[Ru(tpy)L(μ-OH)] and p,p-[Ru(tpy)L(OH)] formed by protonation from Ru(μ-OH) and Ru(OH)(OH) were predicted to be unstable by 71.3 and 112.4 kJ mol compared to Ru(μ-OH) and Ru(OH)(OH), respectively. The reverse reactions of Ru(μ-OH), Ru(OH)(OH), and Ru(OH) to Ru(μ-Cl) below pH 5 could be caused by lowering the core charge by protonation of the μ-OH or OH ligand.

Dinuclear ruthenium­(II) complexes, proximal,proximal-[Ru2(Hcptpy)2L­(μ-Cl)]3+ (Ru 2 (μ-Cl), Hcptpy = 4′-(4-carboxyphenyl)-2,2′;6′,2″-terpyridine and L = 5-phenyl-2,8-di­(2-pyridyl)-1,9,10-anthyridine) and proximal,proximal-[Ru2(cptpy)2L­(OH)­(OH2)]+ (Ru 2 (OH)­(OH 2 )), were synthesized with the aid of quantitative photoisomerization of a mononuclear ruthenium­(II) complex, distal-[Ru­(Hcptpy)­L­(OH2)]2+ (d-RuOH 2 ). Ru 2 (μ-Cl) and Ru 2 (OH)­(OH 2 ) were chemically adsorbed on a nanoporous TiO2 electrode via 4-carboxyphenyl linker moieties on the complexes, and the stability of these complexes adsorbed on the electrode was considerably improved by addition of 0.1 M KPF6 in a phosphate buffer solution due to the low solubility of PF6 salts of these complexes in water. Ru 2 (OH)­(OH 2 ) worked efficiently for electrocatalytic water oxidation on the electrode with an overpotential (ηO2 ) of 530 mV at a pH of 7.0 and a high catalytic current of 5.1 mA cm–2 at 1.6 V versus saturated calomel electrode (SCE) compared with Ru 2 (μ-Cl). This suggests that the dinuclear structure with vicinal OH2 and OH– ligands on each Ru center in Ru 2 (OH)­(OH 2 ) is important for efficient water oxidation catalysis. In bulk electrolysis at 1.16 V versus SCE using the Ru 2 (OH)­(OH 2 )/TiO2 electrode, O2 was evolved with 87% of Faraday efficiency. After the electrocatalysis, 75% of Ru 2 (OH)­(OH 2 ) remained on the electrode in Ru2 II(OH)­(OH2) (or Ru2 II(OH)2) and Ru2 III(OH)2 states, and 21% was eluted to the electrolyte solution in the higher oxidation states of Ru2 III(OH)2 and/or Ru2 IV(O)­(OH), even with the suppression effect on the complex elusion by addition of KPF6 maintained. The mechanistic investigation revealed the important catalytic aspect involving the active Ru2 IV(O)­(OH) state, which could be responsible for the O–O bond formation by intramolecular coupling of their oxos on the electrode surface.