From Bench to Browser: How Reddit Chemists Are Shaping AI, Flow Chemistry, ASOs, and Sustainability in Medicinal Chemistry.

Metal-organic frameworks (MOFs) and their composites have garnered significant attention in recent years due to their exceptional properties and diverse applications across various fields. The conventional batch synthesis methods for MOFs and their composites often suffer from challenges such as long reaction times, poor reproducibility, and limited scalability. Continuous flow synthesis has emerged as a promising alternative for overcoming these limitations. In this short review, we discuss the recent advancements, challenges, and future perspectives of continuous flow synthesis in the context of MOFs and their composites. The review delves into a brief overview of the fundamental principles of flow synthesis, highlighting its advantages over batch methods. Key benefits, including precise control over reaction parameters, improved scalability and efficiency, rapid optimization capabilities, enhanced reaction kinetics and mass transfer, and increased safety and environmental sustainability, are addressed. Additionally, the versatility and flexibility of flow synthesis techniques are discussed. The article then explores various flow synthesis methods applicable to MOF and MOF composite production. The techniques covered include continuous flow solvothermal synthesis, mechanochemical synthesis, microwave and ultrasound-assisted flow synthesis, microfluidic droplet synthesis, and aerosol synthesis. Notably, the combination of flow chemistry and aerosol synthesis with real-time characterization is also addressed. Furthermore, the impact of flow synthesis on the properties and performance of MOFs is explored. Finally, the review discusses current challenges and future perspectives in the field of continuous flow MOF synthesis, paving the way for further development and broader application of this promising technique.

Assessing the environmental impacts of flow and batch syntheses of hypercrosslinked polymers for low-pressure CO2 adsorption

BACKGROUNDThe work describes the synthesis of n‐amyl acetate from n‐amyl alcohol, a byproduct of the sugar industry. The synthesis was carried out using Burkholderia cepacia lipase immobilized on a hydrophobic polymer support containing hydroxypropyl methyl cellulose and polyvinyl alcohol. The reaction conditions were optimized and intrinsic kinetics were evaluated. An immobilized lipase‐coated film reactor was designed and evaluated for continuous flow synthesis. An attempt has been made to model the coated film reactor based on axial dispersion method.RESULTSThe reaction conditions were optimized using a central composite design‐based response surface method. The optimum conditions for a maximum conversion of 99.5% were an acyl donor : alcohol ratio of 2:1, temperature 50 °C and catalyst loading 40 mg in n‐hexane. The intrinsic kinetics of reaction were fitted using an order bi–bi model with alcohol inhibition. The continuous flow synthesis was carried out in a coated film reactor with residence times ranging from 12 min to 60 min with per pass conversions of 5.6% and 22%, respectively. The catalyst was successfully recycled for five cycles.CONCLUSIONThe activation energy of the reaction was found to be 15.48 kJ mol−1. The productivity from batch and continuous flow reactor were found to be 8.16 and 6.54 mmol g−1 h−1. © 2018 Society of Chemical Industry

Novel continuous flow synthesis, characterization and antibacterial studies of nanoscale zinc substituted hydroxyapatite bioceramics

Continuous microwave-assisted flow synthesis has been used as a simple, more efficient, and low-cost route to fabricate a range of nanosized (<100 nm) strontium-substituted calcium phosphates. In this study, fine nanopowder was synthesized via a continuous flow synthesis with microwave assistance from the solutions of calcium nitrate tetrahydrate (with strontium nitrate as Sr2+ ion source) and diammonium hydrogen phosphate at pH 10 with a time duration of 5 min. The morphological characterization of the obtained powder has been carried out by employing techniques such as transmission electron microscopy, X-ray diffraction, and Brunauer-Emmett-Teller surface area analysis. The chemical structural analysis to evaluate the surface properties was made by using X-ray photoelectron spectroscopy. Zeta potential analysis was performed to evaluate the colloidal stability of the particles. Antimicrobial studies were performed for all the compositions using four bacterial strains and an opportunistic human fungal pathogen Macrophomina phaseolina. It was found that the nanoproduct with high strontium content (15 wt% of strontium) showed pronounced antibacterial potential against M. luteus while it completely arrested the fungal growth after 48 h by all of its concentrations. Thus the synthesis strategy described herein facilitated the rapid production of nanosized Sr-substituted CaPs with excellent biological performance suitable for a bone replacement application.

The adoption of and opportunities in continuous flow synthesis ('flow chemistry') have increased significantly over the past several years. Continuous flow systems provide improved reaction safety and accelerated reaction kinetics, and have synthesised several active pharmaceutical ingredients in automated reconfigurable systems. Although continuous flow platforms are commercially available, systems constructed 'in-lab' provide researchers with a flexible, versatile, and cost-effective alternative. Herein, we describe the assembly and use of a modular continuous flow apparatus from readily available and affordable parts in as little as 30 min. Once assembled, the synthesis of a sulfonamide by reacting 4-chlorobenzenesulfonyl chloride with dibenzylamine in a single reactor coil with an in-line quench is presented. This example reaction offers the opportunity to learn several important skills including reactor construction, charging of a back-pressure regulator, assembly of stainless-steel syringes, assembly of a continuous flow system with multiple junctions, and yield determination. From our extensive experience of single-step and multistep continuous flow synthesis, we also describe solutions to commonly encountered technical problems such as precipitation of solids ('clogging') and reactor failure. Following this protocol, a nonspecialist can assemble a continuous flow system from reactor coils, syringes, pumps, in-line liquid-liquid separators, drying columns, back-pressure regulators, static mixers, and packed-bed reactors.

Continuous flow synthesis

Vitravene--another piece in the mosaic.

Microreactors have gained increasing attention in their application toward continuous micro flow synthesis. An unsolved problem of continuous flow synthesis is the lack of techniques for continuous product purification. Herein, we present a micro free-flow electrophoresis device and accompanying setup that enables the continuous separation and purification of unlabeled organic synthesis products. The system is applied to the separation and purification of triarylmethanes. For imaging of the unlabeled analytes on-chip a novel setup for large area (3.6 cm2) deep ultra violet excitation fluorescence detection was developed. Suitable separation conditions based on low conductivity electrophoresis buffers were devised to purify the product. With the optimized conditions, starting materials and product of the synthesis were well separated (R > 1.2). The separation was found to be very stable with relative standard deviations of the peak positions smaller than 3.5% over 15 min. The stable conditions enabled collection of the separated compounds, and purity of the product fraction was confirmed using capillary electrophoresis and mass spectrometry. This result demonstrates the great potential of free-flow electrophoresis as a technique for product purification or continuous clean-up in flow synthesis. Graphical Abstract Micro free-flow electrophoresis (μFFE) allows continuous separation and purification of small organic synthesis products. Enabled by a novel deep-UV imaging setup starting materials and product of a recently developed synthesis for triarylmethanes could be purified. Thereby demonstrating the potential of μFFE as continuous purification technique for micro flow synthesis.

This review comprehensively covers the translation from batch to continuous flow synthesis of metal nanowires (i.e., silver, copper, gold, and platinum nanowires) and their diverse applications across various sectors. Metal nanowires have attracted significant attention owing to their versatility and feasibility for large-scale synthesis. The efficacy of flow chemistry in nanomaterial synthesis has been extensively demonstrated over the past few decades. Continuous flow synthesis offers scalability, high throughput screening, and robust and reproducible synthesis procedures, making it a promising technology. Silver nanowires, widely used in flexible electronics, transparent conductive films, and sensors, have benefited from advancements in continuous flow synthesis aimed at achieving high aspect ratios and uniform diameters, though challenges in preventing agglomeration during large-scale production remain. Copper nanowires, considered as a cost-effective alternative to silver nanowires for conductive materials, have benefited from continuous flow synthesis methods that minimize oxidation and enhance stability, yet scaling up these processes requires precise control of reducing environments and copper ion concentration. A critical evaluation of various metal nanowire ink formulations is conducted, aiming to identify formulations that exhibit superior properties with lower metal solid content. This study delves into the intricacies of continuous flow synthesis methods for metal nanowires, emphasizing the exploration of engineering considerations essential for the design of continuous flow reactors. Furthermore, challenges associated with large-scale synthesis are addressed, highlighting the process-related issues.

In this Section of the journal, the literature on continuous flow synthesis (primarily organic synthesis and functional materials) from the period of July – September 2016 is presented. All the publications are listed ordered by journal name, with 8 Review articles appearing at the end. In this quarter the number of papers on continuous flow organic synthesis is relatively more and with a few special issues planned in the coming months this number will increase significantly. There are many ‘firsts’ achieved in flow synthesis in the last quarter, but the most noticeable ones include the synthesis of Water-Stable Covalent Organic Frameworks and flow synthesis using in-situ generated chlorine!

Peptide-mediated Cell and In Vivo Delivery of Antisense Oligonucleotides and siRNA

Synthesis of Lobeglitazone intermediates seeking for continuous drug production in flow capillary microreactor

Computational Medicinal Chemistry

Functional Rescue of Dystrophin-deficient mdx Mice by a Chimeric Peptide-PMO