Benzylic fluorination induced by N–F bond activation of Selectfluor^® with a solvent-dependent selectivity switch

We present a divergent radical strategy for the fluorination of phenylacetic acid derivatives through N–F bond activation of Selectfluor® with 4-(dimethylamino)pyridine. Comprehensive reaction investigation revealed the critical role of reaction media on selectivity. In presence of water, decarboxylative fluorination through a single electron oxidation is dominant. Non-aqueous conditions result in the clean formation of α-fluoro-α-arylcarboxylic acids through hydrogen atom transfer

Benzylic fluorination induced by a charge-transfer complex with a solvent-dependent selectivity switch

We present a divergent strategy for the fluorination of phenylacetic acid derivatives that is induced by a charge-transfer complex between Selectfluor and 4-(dimethylamino)pyridine. A comprehensive investigation of the conditions revealed a critical role of the solvent on the reaction outcome. In the presence of water, decarboxylative fluorination through a single-electron oxidation is dominant. Non-aqueous conditions result in the clean formation of α-fluoro-α-arylcarboxylic acids

Combining radial and continuous flow synthesis to optimize and scale-up the production of medicines

Current drug production in batch cannot adapt rapidly to market demands,} evidenced by recent shortages in many markets globally of essential medicines. Flow chemistry is a valuable tool for on-demand production of active pharmaceutical ingredients (APIs). Here{,} we reveal a new concept to develop and produce APIs{,} where an automated synthesizer that works with discrete volumes of solutions is employed at the discovery stage to identify the optimal synthetic route and conditions before a commercially available continuous flow system is used for scale-up. This concept is illustrated by the synthesis of nifedipine and paracetamol{,} in short supply in Germany during the COVID-19 pandemic{, and the local anesthetic lidocaine

Lanthanides: Applications in Cancer Diagnosis and Therapy

Lanthanide complexes are of increasing importance in cancer diagnosis and therapy, owing to the versatile chemical and magnetic properties of the lanthanide-ion 4f electronic configuration. Following the first implementation of gadolinium(III)-based contrast agents in magnetic resonance imaging in the 1980s, lanthanide-based small molecules and nanomaterials have been investigated as cytotoxic agents and inhibitors, in photodynamic therapy, radiation therapy, drug/gene delivery, biosensing, and bioimaging. As the potential utility of lanthanides in these areas continues to increase, this timely review of current applications will be useful to medicinal chemists and other investigators interested in the latest developments and trends in this emerging field

SVILUPPO DI UNA MACCHINA PER PROVE DI TRAZIONE VELOCE

I materiali metallici sottoposti a carichi di natura dinamica vanno soggetti ad un fenomeno noto anche comeincrudimento dinamico.L’incrudimento dinamico ha un’enorme rilevanza nell’ambito della sicurezza passiva. Procedure di prova chepermettano di valutare l’influenza della velocità di deformazione sulle proprietà meccaniche di un materialesono fondamentali per una corretta progettazione di strutture sicure ad impatto.In questo articolo viene presentata una procedura per prove di trazione veloce che prevede l’utilizzo di unaslitta verticale e di una macchina ad inversione.In fase di sviluppo, per verificarne il funzionamento, sono state condotte prove usando provini ottenuti dapiastre di due diversi materiali: un acciaio dolce d’uso comune e una lega leggera di alluminio tipica dellecostruzioni aeronautiche. I dati ottenuti per i due materiali sono ripetibili e confrontati coi dati presenti inbibliografia hanno mostrato che la procedura di prova sviluppata è in grado di fornire dati accurati

Triptans and troponin: a case report

This case report describes for the first time acute coronary syndrome in a 67-year old patient after oral intake of naratriptan for migraine. So far in the literature, only sumatriptan, zolmitriptan and frovatriptan have been described to cause acute coronary syndromes

Intraligand charge transfer enables visible-light-mediated nickel-catalyzed cross-coupling reactions

We demonstrate that several visible-light mediated carbon–heteroatom cross-couplings can be carried out using a photoactive NiII precatalyst that forms in situ from a nickel salt and a bipyridine ligand decorated with two carbazole groups (Ni(Czbpy)Cl2). The activation of this precatalyst towards cross-couplings follows a hitherto undisclosed mechanism that is different from previously reported light-responsive nickel complexes that were reported to undergo metal-to-ligand charge transfer. Theoretic and spectroscopic investigations revealed that irradiation of Ni(Czbpy)Cl2 with visible-light causes an initial intraligand charge transfer event that triggers productive catalysis. Ligand polymerization affords a porous, recyclable organic polymer for heterogeneous nickel catalysis of cross-couplings. The heterogeneous catalyst shows stable performance in a packed-bed flow reactor during a week of continuous operation

Utility of percutaneous lung biopsy for diagnosing filamentous fungal infections in hematologic malignancies

Background and Objectives. The incidence of invasive filamentous fungal infections in hematologic patients is increasing as a consequence of high dose chemotherapy and bone marrow transplant procedures. Mortality is usually very high. The diagnosis is often difficult and yet a fast, accurate diagnosis is of fundamental importance for treating the infection and planning subsequent management of the hematologic disease. We evaluated the sensitivity of computed tomography (CT)-guided percutaneous biopsy in diagnosing pulmonary fungal infections. Design and Methods. Between 1997 and 2002 we performed 17 CT-guided percutaneous transthoracic lung biopsies in 17 hematologic patients with suspected filamentous fungi infection with negative BAL, to obtain a certain diagnosis and to know what species of fungi was responsible for infection. In all cases suspected mycosis began during the post-chemotherapy aplastic period. Patients were receiving antifungal therapy at the time of all biopsies. When the platelet count rose above 50 7109/L, CT-guided percutaneous lung biopsy with fine-needle aspiration for cytology was performed. Results. Twelve of 17 patients had histologic confirmation of the fungal infection (70.5%), 8 with Aspergillus spp. 4 with Mucorales spp. Biopsies provided non-specific results in 4 cases; in 2 of these cases, clinical course and response to therapy confirmed the diagnosis of mycosis; in the last case bronchoalveolar carcinoma was found as a new diagnosis. Cultures were positive in only 6 cases, all for Aspergillus spp. The sensitivity of CT-guided percutaneous lung biopsy was 70.6% and its positive predictive value (PPV) was 100%. This procedure provided an immediate diagnosis and only one side-effect (1 pneumothorax, without complications). Interpretation and Conclusions. Histologic discrimination between aspergillosis and mucormycosis is very important for deciding secondary prophylaxis during transplant procedures, because Mucor is usually resistant to azoles

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

OBJECT: Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. METHODS: The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. RESULTS: The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. CONCLUSIONS: Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT)