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

Deconstruction of the Corso Grosseto viaduct and setup of a testing site for full scale load tests

BRIDGE|50 is a research project recently launched in Italy in the context of the Torino-Ceres construction works jointly with Politecnico di Milano, Politecnico di Torino, public authorities and private companies. The aim of the BRIDGE|50 research project is to investigate the residual structural performance of the Corso Grosseto 50-year-old prestressed concrete bridge through an experimental campaign. The dismantling and demolition procedures of Corso Grosseto viaduct are presented in this paper, including the setup of the field laboratory where several deck beams and pier caps will be tested up to collapse

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

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

Value of long-term streamflow forecasts to reservoir operations for water supply in snow-dominated river catchments

We present a forecast-based adaptive management framework for water supply reservoirs and evaluate the contribution of long-term inflow forecasts to reservoir operations. Our framework is developed for snow-dominated river basins that demonstrate large gaps in forecast skill between seasonal and inter-annual time horizons. We quantify and bound the contribution of seasonal and inter-annual forecast components to optimal, adaptive reservoir operation. The framework uses an Ensemble Streamflow Prediction (ESP) approach to generate retrospective, one-year-long streamflow forecasts based on the Variable Infiltration Capacity (VIC) hydrology model. We determine the optimal sequence of daily release decisions using the Model Predictive Control (MPC) optimization scheme. We then assess the forecast value by comparing system performance based on the ESP forecasts with the performances based on climatology and perfect forecasts. We distinguish among the relative contributions of the seasonal component of the forecast versus the inter-annual component by evaluating system performance based on hybrid forecasts, which are designed to isolate the two contributions. As an illustration, we first apply the forecast-based adaptive management framework to a specific case study, i.e., Oroville Reservoir in California, and we then modify the characteristics of the reservoir and the demand to demonstrate the transferability of the findings to other reservoir systems. Results from numerical experiments show that, on average, the overall ESP value in informing reservoir operation is 35% less than the perfect forecast value and the inter-annual component of the ESP forecast contributes 20–60% of the total forecast value.</p

Intraligand Charge Transfer Enables Visible Light Mediated Nickel Catalyzed Cross Coupling Reactions

We demonstrate that several visible light mediated carbon heteroatom cross coupling reactions can be carriedout using a photoactive Ni II 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 coupling reactions follows a hitherto undisclosed mechanism that is different from previously reported light responsive nickel complexes that undergo metal to ligand charge transfer. Theoretical 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 coupling reactions. The heterogeneous catalyst shows stable performance in a packed bed flow reactor during a week of continuous operatio