Atomically Precise Ni-Pd Alloy Carbonyl Nanoclusters: Synthesis, Total Structure, Electrochemistry, Spectroelectrochemistry, and Electrochemical Impedance Spectroscopy

The molecular nanocluster [Ni36-xPd5+x(CO)46]6- (x = 0.41) (16-) was obtained from the reaction of [NMe3(CH2Ph)]2[Ni6(CO)12] with 0.8 molar equivalent of [Pd(CH3CN)4][BF4]2 in tetrahydrofuran (thf). In contrast, [Ni37-xPd7+x(CO)48]6- (x = 0.69) (26-) and [HNi37-xPd7+x(CO)48]5- (x = 0.53) (35-) were obtained from the reactions of [NBu4]2[Ni6(CO)12] with 0.9-1.0 molar equivalent of [Pd(CH3CN)4][BF4]2 in thf. After workup, 35- was extracted in acetone, whereas 26- was soluble in CH3CN. The total structures of 16-, 26-, and 35- were determined with atomic precision by single-crystal X-ray diffraction. Their metal cores adopted cubic close packed structures and displayed both substitutional and compositional disorder, in light of the fact that some positions could be occupied by either Ni or Pd. The redox behavior of these new Ni-Pd molecular alloy nanoclusters was investigated by cyclic voltammetry and in situ infrared spectroelectrochemistry. All three compounds 16-, 26-, and 35- displayed several reversible redox processes and behaved as electron sinks and molecular nanocapacitors. Moreover, to gain insight into the factors that affect the current-potential profiles, cyclic voltammograms were recorded at both Pt and glassy carbon working electrodes and electrochemical impedance spectroscopy experiments performed for the first time on molecular carbonyl nanoclusters

An Italian multicenter retrospective real-life analysis of patients with brain metastases from renal cell carcinoma: the BMRCC study

Background: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC). Patients and methods: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS). Results: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59). Conclusions: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients

Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

Fascin, an actin-bundling protein involved in cell motility, has been shown to be upregulated in several types of carcinomas. In this study, we investigated the expression of fascin in 228 advanced colonic adenocarcinoma patients with a long follow-up. Fascin expression was compared with several clinicopathologic parameters and survival. Overall, fascin immunoreactivity was detected in 162 (71%) tumours with a prevalence for right-sided tumours (P<0.001). Fascin correlated significantly with sex, tumour grade and stage, mucinous differentiation, number of metastatic lymph nodes, extranodal tumour extension, and the occurrence of distant metastases. Patients with fascin-expressing tumours experienced a shorter disease-free and overall survival in comparison with those with negative tumours, and fascin immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Moreover, patients with the same tumour stages could be stratified in different risk categories for relapse and progression according to fascin expression. Our findings suggest that fascin is a useful prognostic marker for colonic adenocarcinomas

Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility : a Single-Institution Experience

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. OBJECTIVE: We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s). PATIENTS AND METHODS: From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36-86) and the median number of previous treatment lines was five (range 2-8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%). RESULTS: One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63-3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0-15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80-5.03] vs. 2.13 months [95% CI 1.77-2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17-9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33-10.80] vs. 7.18 months [95% CI 5.63-9.33], respectively, p = 0.06). CONCLUSIONS: This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment

Reductive Elimination of Dimethylcarbonate from (Dimethoxycarbonyl)tricarbonyl Cobaltates. Isolation and Crystal Structures of Cs[Co(COOCH3)2(CO)3] and K[(dibenzo-18-crown-6)][Co(COOCH3)2(CO)3]

Salts of the anion [Co(COOCH3)2(CO)3]- with Cs+ and K+ (with the latter cation complexed by dibenzo-18-crown-6 ether) have been isolated and structurally characterized. In the trigonal bipyramidal cobaltate two C-coordinated COOCH3 groups occupy trans-axial positions. There are ionic interactions between the cation and the terminal oxygen atoms of methoxycarbonyl involving both of the coordinated COOCH3 groups in the case of the Cs salt but only one of them in the case of the K salt. One methoxy group of the anion [Co(COOCH3)2(CO)3]- is strongly nucleophilic, as shown by the reactions with Co2(CO)8 or CO2. Under an inert atmosphere [Co(COOCH3)2(CO)3]- undergoes elimination of dimethylcarbonate

Aqueous Organometallic Chemistry of Ruthenium(II). Aquo Carbonyl Derivatives and Related Ethene Hydrocarboxylation in Fully Aqueous Solvent

A series of new water soluble and stable organometallic compounds is reported, and the peculiar role of water in their formation and stabilization is documented together with their catalytic properties in aqueous solution. The complex fac-Ru(OCOCF3)2(CO)3(H2O) (1) constitutes the entry to a new type of aqueous organometallic chemistry. The substitution of trifluoroacetato ligands by H2O yields [fac-Ru(CO)3(H2O)3]2+ (2), isolated as the tetrafluoroborate derivative, the first structurally characterized complex bearing CO and H2O ligands only. In water, 2 undergoes nucleophilic attack by the solvent yielding [fac-Ru(COOH)(CO)2(H2O)3]+ (3), followed by CO2 elimination to give [fac-RuH(CO)2(H2O)3]+ (4), a ruthenium(II) hydride devoid of group-15-donor coligands and stable toward strong acids. 4 inserts ethene in water to give [fac-Ru(C2H5)(CO)2(H2O) 3]+ (5), an exceptionally inert alkyl complex which inserts CO yielding [fac-Ru(C(O)C2H5)(CO)2(H2O) 3]+ (6). Attempts to isolate the mononuclear cationic acyl complex gave the tetranuclear Ru4(C(O)C2H5)4(OH) 2(CF3SO3)2(CO)8 (7). At 140°C the mononuclear organometallic complexes become labile intermediates of a Reppe hydrocarboxylation of ethene in fully aqueous solvent

Hydrocarboxylation and stepwise alternating oligomerization of carbon monoxide and ethylene catalyzed by cis-[Rh(CO)2(amine)2](PF6) complexes in a wet liquid tetrabutylammonium hydrogensulfate

In aqueous solution with tetrabutylammonium hydrogensulfate cocatalyst, rhodium complexes like cis-[Rh(CO)2(amine)2](PF6) (amine¼4-picoline, 3-picoline, 2-picoline, pyridine, or 2,6-lutidine) promote the oligomerization and, to a lesser extent, the hydrocarboxylation of CO/ethylene. Higher rates for both the production of alternating polyketones and propionic acid are observed in wet tetrabutylammonium hydrogensulfate medium. An in situ FT-IR spectroscopy study confirms that five coordinated rhodium species of the type trans-[Rh(CO)3(amine)2]þ are formed under catalytic conditions. The data are discussed in terms of a potential catalytic cycle, and the formation of propionic acid and ketones is determined to come from the hydrolysis and hydrogenolysis of the Rh-acyl intermediates formed under the catalytic conditions

AQUIVION® perfluorosulfonic acid resin for butyl levulinate production from furfuryl alcohol

This study reports the sustainable production of butyl levulinate (BL) from furfuryl alcohol (FA), a highly abundant biomass derived platform obtained from C5 sugars in hemicellulose. FA upgrading is performed adopting a robust and easily recyclable commercial perfluorosulfonic acid resin, Aquivion® P87S, used as cylinder shaped pellets. This approach avoids the use of corrosive and harmful mineral acids allowing a simple separation of the catalyst from the reaction mixture, reducing the cost of equipment materials and disposal or neutralization issues, also resulting in reduced solvent dehydration. Moreover, FA alcoholysis to BL involves butanol as a sustainable reaction medium, also readily obtained from biomass. The catalyst remains stable up to 6 recycles. Furthermore, the absence of heavy by-products and the stability of the catalyst allowed us to perform successive additions of the substrate to the reaction medium to increase the BL concentrations up to 0.66 M (13 wt%)