This review intends to provide the reader with a clear and concise overview of how preparative continuous flow organic chemistry could potentially impact on current important societal challenges. These societal challenges include health/well‐being and sustainable development. Continuous flow chemistry has enabled significant advances for the manufacturing of pharmaceuticals, as well as for biomass valorization toward a biosourced chemical industry. Examples related to pharmaceutical production are herein focused on (a) the implementation of flow chemistry to reduce the occurrence of drug shortages, (b) continuous flow manufacturing of orphan drugs, (c) continuous flow preparation of active pharmaceuticals listed on the WHO list of essential medicines and (d) perspectives for the manufacturing of peptide‐based pharmaceuticals. Examples related to sustainable development are focused on the valorization of biosourced platform molecules. Besides positive impacts on societal challenges, this review also illustrates some of the potentially most threatening perspectives of continuous flow technology within the actual context of terrorism and drug abuse.
Highly
efficient and chemoselective singlet oxygen oxidation of
unprotected methionine was performed in water using a continuous mesofluidic
reactor. Sustainable process engineering and conditions were combined
to maximize process efficiency and atom economy, with virtually no
waste generation and safe operating conditions. Three water-soluble
metal-free photosensitizers [Rose Bengal, Methylene Blue, and tetrakis(4-carboxyphenyl)porphyrin]
were assessed. The best results were obtained with Rose Bengal (0.1
mol %) at room temperature under white light irradiation and a slight
excess of oxygen. Process and reaction parameters were monitored in
real-time with in-line NMR. Other classical organic substrates (α-terpinene
and citronellol) were oxidized under similar conditions with excellent
performances.
Continuous flow photochemistry relying on photosensitizers faces two main challenges: 1) Photodegradation (bleaching) and 2) the downstream removal of the photosensitizer. Rose bengal (RB) is a common photosensitizer utilized for photooxygenation reactions with singlet oxygen (1O2), but is notoriously sensitive to photobleaching and difficult to remove from reactor effluents. The heterogenization of photosensitizers on mesoporous silica nanoparticles (MSNs) is arguably a viable option for such applications. Herein, we report on the use of RB covalently incorporated into MSNs (RB@MSNs) for photooxygenation reactions under continuous flow conditions. RB@MSNs enable the 1O2 photooxygenation of various organic substrates upon irradiation with 540 nm LEDs. A series of organic substrates were evaluated including methionine, α‐terpinene, 2‐furoic acid, triphenylphosphine, citronellol and cyclopentadiene. These results emphasize an improved resistance to photobleaching, and the possibility to use RB@MSNs as an easily recoverable catalyst, which could be removed from the reactor effluent either a) by centrifugation or b) by in‐line membrane filtration.
ConclusionsThese results confirm the limitations of batch technologies in terms of light penetration and mass transfer when working with 1 O 2 -photosensitized oxygenations.RB concentration, light intensity and O 2 flow have been evaluated in batch reactor.Pseudo-first order kinetics and space-time yields have been also calculated in both technologies obtaining an enhancement of 12 and 3 fold for r 0 and STY, respectively when using when using continuous-flow microreactor.
Multidisciplinary lab experiments
combining microfluidics, nanoparticle
synthesis, and characterization are presented. These experiments rely
on the implementation of affordable yet efficient microfluidic setups
based on perfluoroalkoxyalkane (PFA) capillary coils and standard
HPLC connectors in upper undergraduate chemistry laboratories. Fundamental
principles and concepts as well as practical tips for the rapid deployment
of microfluidics are presented. In-line membrane separation, the segmented-flow
regime, high-temperature experiments, and in-line analytical techniques
are illustrated by the preparation of inorganic nanoparticles (silver,
gold, and cadmium selenide or telluride) in microreactors. Besides
microfluidics, analytical techniques for nanoparticle analysis are
also illustrated.
Modafinil is an anti-narcoleptic drug used to treat excessive daytime sleepiness associated with sleep apnea and shift-work disorder. It is unique in its lack of significant side-effects or addiction-inducing properties...
PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [68Ga]Ga-DOTA-TATE. Al[18F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [68Ga]Ga-DOTA-TATE and Al[18F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [68Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[18F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[18F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [68Ga]Ga-DOTA-TATE but not by Al[18F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[18F]F-NOTA-Octreotide but not by [68Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[18F]F-NOTA-Octreotide is comparable to [68Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[18F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE.
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