The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry, and the construction of electronic devices. This Review discusses the mechanism, scope, and applications of the RuAAC reaction, covering the literature from the last 10 years.

https://research.chalmers.se/publication/246752/file/246752_Fulltext.pdf

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications.

https://orbit.dtu.dk/files/129911346/PT_Revised_Main_Manuscript_with_embedded_figures.pdf

Allosteric small-molecule kinase inhibitors

Light-based therapeutic and imaging modalities, which emerge in clinical applications, rely on molecular tools, such as photocleavable protecting groups and photoswitches that respond to photonic stimulus and translate it into a biological effect. However, optimisation of their key parameters (activation wavelength, band separation, fatigue resistance and half-life) is necessary to enable application in the medical field. In this perspective, we describe the applications scenarios that can be envisioned in clinical practice and then we use those scenarios to explain the necessary properties that the photoresponsive tools used to control biological function should possess, highlighted by examples from medical imaging, drug delivery and photopharmacology. We then present how the (photo)chemical parameters are currently being optimized and an outlook is given on pharmacological aspects (toxicity, solubility, and stability) of light-responsive molecules. With these interdisciplinary insights, we aim to inspire the future directions for the development of photocontrolled tools that will empower clinical applications of light.

/pdf/photoresponsive-molecular-tools-for-emerging-applications-of-g63a475g55.pdf

Photoresponsive molecular tools for emerging applications of light in medicine.

There has been an increasing body of evidence that flow hydrogenation enhances reduction outcomes across a wide range of synthetic transformations. Moreover flow reactors enhance laboratory safety with pyrophoric catalysts contained in sealed cartridges and hydrogen generated in situ from water. This mini-review focuses on recent applications of flow chemistry to mediate nitro, imine, nitrile, amide, azide, and azo reductions. Methodologies to effect de-aromatisation, hydrodehalogenation, in addition to olefin, alkyne, carbonyl, and benzyl reductions are also examined. Further, protocols to effect chemoselective reductions and enantioselective reductions are highlighted. Together these applications demonstrate the numerous advantages of performing hydrogenation under flow conditions which include enhanced reaction throughput, yields, simplified workup, and the potential applicability to multistep and cascade synthetic protocols.

The expanding utility of continuous flow hydrogenation.

Introducing novel strategies, concepts, and technologies that speed up drug discovery and the drug development cycle is of great importance both in the highly competitive pharmaceutical industry as well as in academia. This Perspective aims to present a "big-picture" overview of recent strategic innovations in medicinal chemistry and drug discovery.

/pdf/overview-of-recent-strategic-advances-in-medicinal-chemistry-1aan70s3zl.pdf

Overview of Recent Strategic Advances in Medicinal Chemistry

Future brain-machine interfaces, prosthetics, and intelligent soft robotics will require integrating artificial neuromorphic devices with biological systems. Due to their poor biocompatibility, circuit complexity, low energy efficiency, and operating principles fundamentally different from the ion signal modulation of biology, traditional Silicon-based neuromorphic implementations have limited bio-integration potential. Here, we report the first organic electrochemical neurons (OECNs) with ion-modulated spiking, based on all-printed complementary organic electrochemical transistors. We demonstrate facile bio-integration of OECNs with Venus Flytrap (Dionaea muscipula) to induce lobe closure upon input stimuli. The OECNs can also be integrated with all-printed organic electrochemical synapses (OECSs), exhibiting short-term plasticity with paired-pulse facilitation and long-term plasticity with retention >1000 s, facilitating Hebbian learning. These soft and flexible OECNs operate below 0.6 V and respond to multiple stimuli, defining a new vista for localized artificial neuronal systems possible to integrate with bio-signaling systems of plants, invertebrates, and vertebrates. 

/pdf/organic-electrochemical-neurons-and-synapses-with-ion-2d8q8ac4.pdf

Organic electrochemical neurons and synapses with ion mediated spiking

Biomimicry at the hardware level is expected to overcome at least some of the challenges, including high power consumption, large footprint, two-dimensionality, and limited functionality, which arise as the field of artificial intelligence matures. One of the main attributes that allow biological systems to thrive is the successful interpretation of and response to environmental signals. Taking inspiration from these systems, the first demonstration of using multiple environmental inputs to trigger the formation and control the growth of an evolvable synaptic transistor is reported here. The resulting transistor exhibits long-term changes in the channel conductance at a fixed gate voltage. Biomimetic logic circuits are investigated based on this evolvable transistor that implement temperature and pressure inputs to achieve higher order processes like self-regulation of synaptic strength and coincidence detection.

A Biomimetic Evolvable Organic Electrochemical Transistor

Proto-oncogene tyrosine-protein kinase receptor RET is implicated in the development and maintenance of neurons of the central and peripheral nervous systems. Attaching activity-compromising photocleavable groups (caging) to inhibitors could allow for external spatiotemporally controlled inhibition using light, potentially providing novel information on how these kinase receptors are involved in cellular processes. Here, caged RET inhibitors were obtained from 3-substituted pyrazolopyrimidine-based compounds by attaching photolabile groups to the exocyclic amino function. The most promising compound displayed excellent inhibitory effect in cell-free, as well as live-cell assays upon decaging. Furthermore, inhibition could be efficiently activated with light in vivo in zebrafish embryos and was shown to effect motoneuron development.

/pdf/a-caged-ret-kinase-inhibitor-and-its-effect-on-motoneuron-3idbr8p62b.pdf

David Bliman

Papers

Organic electrochemical neurons and synapses with ion mediated spiking

A Biomimetic Evolvable Organic Electrochemical Transistor

A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos

8-Bromination of 2,6,9-trisubstituted purines with pyridinium tribromide

Synthesis and photophysical characterization of 1- and 4-(purinyl)triazoles