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Background: Invadopodia facilitate cancer cell extravasation, but the molecular mechanism whereby invadopodia-specific proteases such as MT1-MMP are called to invadopodia is unclear. Methods: Mass spectrometry and immunoprecipitation were used to identify interactors of MT1-MMP in metastatic breast cancer cells. After identification, siRNA and small molecule inhibitors were used to assess the effect these interactors had on cellular invasiveness. The chicken embryo chorioallantoic membrane (CAM) model was used to assess extravasation and invadopodia formation in vivo. Results: In metastatic breast cancer cells, MT1-MMP was found to associate with plectin, a cytolinker and scaffolding protein. Complex formation between plectin and MT1-MMP launches invadopodia formation, a subtype we termed iplectin (i = invadopodial). iPlectin delivers MT1-MMP to invadopodia and is indispensable for regulating cell surface levels of the enzyme. Genetic depletion of plectin with siRNA reduced invadopodia formation and cell invasion in vitro. In vivo extravasation efficiency assays and intravital imaging revealed iplectin to be a key contributor to invadopodia ultrastructure and essential for extravasation. Pharmacologic inhibition of plectin using the small molecule Plecstatin-1 (PST-1) abrogated MT1-MMP delivery to invadopodia and extravasation efficiency. Conclusions: Anti-metastasis therapeutic approaches that target invadopodia are possible by disrupting interactions between MT1-MMP and iplectin. Clinical Trial Registration Number: NCT04608357 [ABSTRACT FROM AUTHOR]

Weak intermolecular forces are typically very difficult to observe in highly competitive polar protic solvents as they are overwhelmed by the quantity of competing solvent. This is even more challenging for three‐component ternary assemblies of pure organic compounds. In this work, we overcome these complications by leveraging the binding of fused aromatic N‐heterocycles in an open resorcinarene cavity to template the formation of a three‐component halogen‐bonded ternary assembly in a protic polar solvent system. [ABSTRACT FROM AUTHOR]

6-Alkoxy-2-aminopurine derivatives are potent inhibitors of Cyclin Dependent Kinases (CDKs), with some selectivity towards CDK2 and thus have potential as cancer therapeutics. Development of these inhibitors for targeting CDK2-cyclin A/E complexes has previously involved a thorough investigation of structure activity relationships of the C-2 amine moiety. However, the established synthesis of these compounds, which uses the alcohol reagent as solvent, limits the complexity of the O-6 functionality which is required for more selective targeting. Herein we report an improved and refocused synthesis of a model CDK2 inhibitor (NU6247), affording convenient access to inhibitors with O-6 substituents whose parent alcohol is not amenable for use as solvent. This revised synthesis allows for a meaningful exploration of the O-6 position in this class of CDK2 inhibitors. [ABSTRACT FROM AUTHOR]

Preparative thin-layer chromatography (prepTLC) is a commonly used method of purification suitable for small-scale reactions. However, descriptions of the preferred methodology to load, run, and recover samples from prepTLC are non-standard and varied, making it part of the 'hidden curriculum' of laboratory techniques. In this article we report on the simple, cost-effective methods we use to load and collect samples from a plate, which enhance the convenience, speed, and precision of this technique. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is highly overexpressed in most prostate cancers and is clinically visualized using PSMAspecific probes incorporating glutamate-ureido-lysine (GUL). PSMA is effectively absent from certain high-mortality, treatment-resistant subsets of prostate cancers, such as neuroendocrine prostate cancer (NEPC); however, GUL-based PSMA tracers are still reported to have the potential to identify NEPC metastatic tumors. These probes may bind unknown proteins associated with PSMA-suppressed cancers. We have identified the up-regulation of PSMA-like aminopeptidase NAALADaseL and the metabotropic glutamate receptors (mGluRs) in PSMA-suppressed prostate cancers and find that their expression levels inversely correlate with PSMA expression and are associated with GUL-based radiotracer uptake. Furthermore, we identify that NAALADaseL and mGluR expression correlates with a unique cell cycle signature. This provides an opportunity for the future study of the biology of NEPC and potential therapeutic directions. Computationally predicting that GUL-based probes bind well to these targets, we designed and synthesized a fluorescent PSMA tracer to investigate these proteins in vitro, where it shows excellent affinity for PSMA, NAALADaseL, and specific mGluRs associated with poor prognosis. [ABSTRACT FROM AUTHOR]

The preparation of a series of 4,4′,5,5′-substituted benzo-fused 1,2,5,6-tetrathiocins X2C6H2S4C6H2X2 (1a–1g) were prepared from the reaction of S2Cl2 with 1,2-C6H4X2 (X = OMe, OEt; X2 = OCH2O, OCH2CH2O, OCH2CH2CH2O, MeNC(＝O)NMe, O(CH2CH2O)4). The oxidative addition of 1a–1g to zero-valent Pd2dba3 or Pt2dba3 (dba = dibenzylideneacetone) in the presence of bis (diphenylphosphino)ethane (dppe) resulted in formation of the substituted mononuclear benzenedithiolate complexes M(L)(dppe) [L = dithiolate ligand; 2a–2g (M = Pd) and 3a–3g (M = Pt)] in 37–89% yield based on recrystallized material. Representative examples of M(L)(dppf) [dppf = bis-diphenylphosphinoferrocene; 4a, 4g (M = Pd) and 5g (M = Pt)] were prepared in a similar fashion. The structures of all derivatives were determined by X-ray diffraction, multinuclear NMR and elemental analysis. The reactivity of the two crown ether dithiolate complexes, 2g and 4g, with 1 equivalent of NaBPh4 led to isolation of the 1 : 1 complexes in which the Na+ cation is bound in the macrocyclic crown, [Na(2g)(MeOH)2][BPh4] and [Na(4g)][BPh4] whose structures were determined by X-ray diffraction. Electrochemical studies supported through DFT calculations on the crown ether derivatives revealed a series of ligand-based oxidation waves corresponding to the dithiolate ligand (and dppf for 4g and 5g) whose redox potentials were shifted by ca. +0.1 V on binding to Na+. [ABSTRACT FROM AUTHOR]

Archaeal threonyl-tRNA synthetase (ThrRS) possesses an editing active site wherein tRNAThr that has been misaminoacylated with serine (i.e., Ser-tRNAThr) is hydrolytically cleaved to serine and tRNAThr. It has been suggested that the free ribose sugar hydroxyl of Ado76 of the tRNAThr (Ado762'OH) is the mechanistic base, promoting hydrolysis by orienting a nucleophilic water near the scissile Ser-tRNAThr ester bond. We have performed a computational study, involving molecular dynamics (MD) and hybrid ONIOM quantum mechanics/molecular mechanics (QM/MM) methods, considering all possible editing mechanisms to gain an understanding of the role played by Ado762'OH group. More specifically, a range of concerted or stepwise mechanisms involving four-, six-, or eight-membered transition structures (total of seven mechanisms) were considered. In addition, these seven mechanisms were fully optimized using three different DFT functionals, namely, B3LYP, M06-2X, and M06-HF. The M06-HF functional gave the most feasible energy barriers followed by the M06-2X functional. The most favorable mechanism proceeds stepwise through two six-membered ring transition states in which the Ado762'OH group participates, overall, as a shuttle for the proton transfer from the nucleophilic H2O to the bridging oxygen (Ado763'O) of the substrate. More specifically, in the first step, which has a barrier of 25.9 kcal/mol, the Ado762'-OH group accepts a proton from the attacking nucleophilic water while concomitantly transferring its proton onto the substrates C-Ocarb center. Then, in the second step, which also proceeds with a barrier of 25.9 kcal/mol, the Ado762'-OH group transfers its proton on the adjacent Ado763'-oxygen, cleaving the scissile Ccarb-O3'Ado76 bond, while concomitantly accepting a proton from the previously formed C-OcarbH group. [ABSTRACT FROM AUTHOR]

Glutaminyl-tRNA synthetase (GlnRS) catalyzes the aminoacylation of glutamine to the corresponding tRNAGln. However, most bacteria and all archaea lack GlnRS and thus an indirect noncanonical aminoacylation is required. With the assistance of a non-discriminating version of Glutamyl-tRNA synthetases (ND-GluRS) the tRNAGln is misaminoacylated by glutamate. In this study, we have computationally investigated the aminoacylation mechanism in GlnRS and ND-GluRS employing Molecular Dynamics (MD) simulations, Quantum Mechanics (QM) cluster and Quantum Mechanics/Molecular Mechanics (QM/MM) calculations. Our investigations demonstrated the feasibility of a water-mediated, substrate-assisted catalysis pathway with rate limiting steps occurring at energy barriers of 25.0 and 25.4 kcal mol−1 for GlnRS and ND-GluRS, respectively. A conserved lysine residue participates in a second proton transfer to facilitate the departure of the adenosine monophosphate (AMP) group. Thermodynamically stable (−29.9 and −9.3 kcal mol−1 for GlnRS and ND-GluRS) product complexes are obtained only when the AMP group is neutral. [ABSTRACT FROM AUTHOR]

A second-generation approach to the synthesis of hydromorphone by oxidative dearomatization/Diels-Alder cycloaddition was investigated. Detailed analysis of the stereochemical outcome of the [4 + 2] cycloaddition was performed first on a truncated model system as well as on the material leading to ent-hydromorphone. The stereochemical assignments were made by NMR and X-ray methods. The second-generation synthesis of hydromorphone was completed in both enantiomeric series. Improvements in the dearomatization conditions were attained using hypervalent iodine reagents instead of Pb(OAc)4. Electrochemical methods of oxidative dearomatization were also investigated. New conditions enabling the rearomatization of ring A from the methoxyketal were developed, and a formal synthesis of the natural enantiomer of hydromorphone was completed. Experimental and spectral data are provided for all new compounds. [ABSTRACT FROM AUTHOR]

Treatment of the imine PhC(=NSiMe3)py with Et2BOMe or BF3·Et2O afforded bicyclic ketiminoboranes 4a and 4bvia intramolecular N-coordination. The basicity of the imine N is evidenced by their reactivity towards Brønsted and Lewis acids and the structures of 4a·HCl and 4b·BF3 are reported as well as the dipyridyl imine derivative 4c·HCl. [ABSTRACT FROM AUTHOR]

CuII-promoted aerial oxidation of a series of benzothiadiazines (1) under ambient conditions affords the first structurally characterised examples of thiadiazine S-oxides (2). The isolation of the homoleptic CuII 3-(2′-pyridyl)benzothiadiazide-S-oxide complex provides insight into the reaction mechanism. [ABSTRACT FROM AUTHOR]

The reactivity of a Schiff-base bis-imine ligand 3 is probed by X-ray diffraction studies. Its susceptibility to hydrolysis, oxidation and nucleophilic addition reactions is demonstrated by the isolation of the methanol adduct 4 and two diazapene heterocycles 5 and 6. This reactivity is also reflected in the molecular structures of two coordination complexes isolated by the reaction of 3 with M(hfac)2 salts, to afford [Cu(5)(hfac)(tfa)] (8) and [Zn(6)(hfac)2] (9). [ABSTRACT FROM AUTHOR]

Reaction of the novel ligand 3-(2'-pyridyl)-benzo-1,2,4-thiadiazine (L) with the transition metal chloride salts MCl2·xH2O (MII = Mn, Fe, Co, Cu and Zn) in a 2 : 1 mole ratio afforded the mononuclear octahedral (high spin) complexes L2MCl2 (1a-1e respectively) in which L binds in a chelate fashion via N(2) and the pyridyl N atoms. In the case of CuCl2 the intermediate 1 : 1 four-coordinate complex LCuCl2 (2) was also isolated which adopts a polymeric structure with pseudo-square planar molecules linked via long CuS contacts (dCu...S = 2.938(1) Å) in the apical position. In the presence of non-interacting ions, 3 : 1 complexes are isolated, exemplified by the reaction of L with Fe(CF3SO3)2 in a 3 : 1 ratio which affords the low spin complex [L3Fe][CF3SO3]2 (3). Reaction of L with VCl3 in a 2 : 1 mole ratio under aerobic conditions afforded the vanadyl complex [L2V(vO)Cl][Cl] (4). [ABSTRACT FROM AUTHOR]

The syntheses, structures, and magnetic properties of three new coordination complexes, tetranuclear [Zn2L³(OAc)(OMe)]2⋅3MeOH⋅H2O (3), trinuclear [Ni3(L³)3]⋅6H2O (4), and a 1-D chain {[Cu2L³(OAc)2]2⋅H2O}n (6), of a polydentate, doubly deprotonated, 3,3'-disubstituted bipyridine ligand [L³]2- are reported. The X-ray crystal structures demonstrate that the ditopic ligand provides a flexible N3 donor set for transition metal ions where each binding pocket shifts from fac to intermediate fac/mer to the mer isomer affording a Ni3 triangle, a Zn4 tetramer, and a 1-D Cu(II) polymer, respectively. This variation in coordination preference is rationalized with the aim of designing future ligands with controlled coordination modes. Magnetic susceptibility studies on 4 reveal it belongs to the rare family of ferromagnetically coupled [Ni3] clusters. In contrast, magnetic studies of the 1-D chain 6 reveal weak antiferromagnetic interactions due to the poor orbital overlap of the singly occupied Cu(II) ... orbitals with the one-atom bridge that connects them along the Jahn-Teller distortion axis. [ABSTRACT FROM AUTHOR]

4-([2,2'-Bi(1,3-dithiolylidene)]-4-yl)benzonitrile undergoes a [2 + 2] photocycloaddition reaction upon irradiation with polychromatic light, an unusual single-crystal-to-single-crystal transformation for a TTF derivative. In contrast, the closely related pyridylnitrile derivative adopts a different packing motif and is stable to light under the same conditions. [ABSTRACT FROM AUTHOR]

The syntheses of nine benzo-fused-1,2,4-thiadizines are reported. The use of microwave synthesis has been shown to afford high yields and short reaction times in several key reaction steps. The molecular geometries of these heterocycles are discussed and their solid state packing motifs reveal a strong tendency for the N-H group to form hydrogen bonded chains. [ABSTRACT FROM AUTHOR]

A unique octanuclear copper(II) cluster with a saddle-shaped structural topology has been prepared from a large, flexible polydentate ligand comprising a 4,4'-bipyridine linker bearing four pendant pyrazolate heterocycles. [ABSTRACT FROM AUTHOR]

Oxidative addition of the electron-rich tetra-methoxy-dibenzo-1,2,5,6-tetrathiocine [(MeO)2C6H2S2]2 to zero-valent group 10 transition metal complexes in the presence of diphenylphosphinoethane (dppe) affords the corresponding dithiolate complexes, [(DMOBD)M(dppe)] (DMOBD = dimethoxybenzenedithiolato, (MeO)2C6H2S2 2-; M = Ni, Pd, Pt) in high yield which were characterized by single crystal X-ray diffraction. Whereas the Pd and Pt complexes exhibit two quasi-reversible 1e- oxidation processes, the nickel species undergoes a quasi-reversible 1e- reduction. [ABSTRACT FROM AUTHOR]

High loading of the radical PhCNSSN. (1) into faujasite has been achieved via gas phase diffusion. Whilst the large 12 Å pores can accommodate the enthalpically preferred dimer, the smaller pores dictate inclusion as a paramagnetic monomer. Powder X-ray diffraction studies reveal the host framework is unchanged whilst TGA reveal that the void space has high radical loadings. SQUID magnetometry coupled with EPR spectroscopy indicate that the majority of radicals adopt diamagnetic π*-π* dimers consistent with predominant location of 1 as dimers within the large cavities. [ABSTRACT FROM AUTHOR]

The bisoxazole containing natural product O-methyl siphonazole was assembled using a suite of microreactors via a flowbased approach in concert with traditional batch methods. The use of a toolbox of solid-supported scavengers and reagents to aid purification afforded the natural product in a total of nine steps. [ABSTRACT FROM AUTHOR]

The outcome of the oxidative addition reactions of bis(4′,5′-dimethoxybenzo)-1,2,5,6-tetrathiocin to Pd2dba3 under microwave conditions is sensitive to the nature of the phosphine coreagent; the bidentate phosphines dppm, dppe, and dppf afford the mononuclear dithiolates (dmobdt)Pd(dppm) (4), (dmobdt)Pd(dppe) (2), and (dmobdt)Pd(dppf) (5), whereas more labile monodentate phosphines lead to aggregation; Ph3P afforded the dinuclear dithiolate (dmobdt)2Pd2(PPh3)2 (6), whereas tBu3P generated the phosphine-free hexanuclear edge-capped octahedral complex Pd6(dmobdt)6 (7) [dmobdt = 4,5-dimethoxybenzenedithiolate, (MeO)2C6H2S22–]. [ABSTRACT FROM AUTHOR]

Anions are important hydrogen bond acceptors in a range of biological, chemical, environmental and medical molecular recognition processes. These interactions have been exploited for the design and synthesis of ditopic resorcinarenes as the hydrogen bond strength can be tuned through the modification of the substituent at the 2-position. However, many potentially useful compounds, especially those incorporating electron-withdrawing functionalities, have not been prepared due to the challenge of their synthesis: their incorporation slows resorcinarene formation that is accessed by electrophilic aromatic substitution. As part of our broader campaign to employ resorcinarenes as selective recognition elements, we need access to these specialized materials. In this article, we report a straightforward synthetic pathway for obtaining a 2-(carboxymethyl)-resorcinarene, and resorcinarene esters in general. We discuss the unusual conformation it adopts and propose that this arises from the electron-withdrawing nature of the ester substituents that renders them better hydrogen bond acceptors than the phenols, ensuring that each of them acts as a donor only. Density Functional Theory (DFT) calculations show that this conformation arises as a consequence of the unusual configurational isomerism of this compound and interruption of the archetypal hydrogen bonding by the ester functionality. [ABSTRACT FROM AUTHOR]

The heavier chalcogens sulfur and selenium are important in organic and inorganic chemistry, and the role of such chalcogens in biological systems has recently gained more attention. Sulfur and, to a lesser extent selenium, are involved in diverse reactions from redox signaling to antioxidant activity and are considered essential nutrients. We investigated the ability of the DFT functionals (B3LYP, B3PW91, ωB97XD, M06-2X, and M08-HX) relative to electron correlation methods MP2 and QCISD to produce reliable and accurate structures as well as thermochemical data for sulfur/selenium-containing systems. Bond lengths, proton affinities (PA), gas phase basicities (GPB), chalcogen–chalcogen bond dissociation enthalpies (BDE), and the hydrogen affinities (HA) of thiyl/selenyl radicals were evaluated for a range of small polysulfur/selenium compounds and cysteine per/polysulfide. The S–S bond length was found to be the most sensitive to basis set choice, while the geometry of selenium-containing compounds was less sensitive to basis set. In mixed chalcogens species of sulfur and selenium, the location of the sulfur atom affects the S–Se bond length as it can hold more negative charge. PA, GPB, BDE, and HA of selenium systems were all lower, indicating more acidity and more stability of radicals. Extending the sulfur chain in cysteine results in a decrease of BDE and HA, but these plateau at a certain point (199 kJ mol−1 and 295 kJ mol−1), and PA and GPB are also decreased relative to the thiol, indicating that the polysulfur species exist as thiolates in a biological system. In general, it was found that ωB97XD/6-311G(2d,p) gave the most reasonable structures and thermochemistry relative to benchmark calculations. However, nuances in performance are observed and discussed. [ABSTRACT FROM AUTHOR]

Weak intermolecular forces are typically very difficult to observe in highly competitive polar protic solvents as they are overwhelmed by the quantity of competing solvent. This is even more challenging for three-component ternary assemblies of pure organic compounds. In this work, we overcome these complications by leveraging the binding of fused aromatic N-heterocycles in an open resorcinarene cavity to template the formation of a three-component halogen-bonded ternary assembly in a protic polar solvent system., (© 2023 Wiley-VCH GmbH.)

The preparation of a series of 4,4',5,5'-substituted benzo-fused 1,2,5,6-tetrathiocins X2C6H2S4C6H2X2 (1a-1g) were prepared from the reaction of S2Cl2 with 1,2-C6H4X2 (X = OMe, OEt; X2 = OCH2O, OCH2CH2O, OCH2CH2CH2O, MeNC([double bond, length as m-dash]O)NMe, O(CH2CH2O)4). The oxidative addition of 1a-1g to zero-valent Pd2dba3 or Pt2dba3 (dba = dibenzylideneacetone) in the presence of bis (diphenylphosphino)ethane (dppe) resulted in formation of the substituted mononuclear benzenedithiolate complexes M(L)(dppe) [L = dithiolate ligand; 2a-2g (M = Pd) and 3a-3g (M = Pt)] in 37-89% yield based on recrystallized material. Representative examples of M(L)(dppf) [dppf = bis-diphenylphosphinoferrocene; 4a, 4g (M = Pd) and 5g (M = Pt)] were prepared in a similar fashion. The structures of all derivatives were determined by X-ray diffraction, multinuclear NMR and elemental analysis. The reactivity of the two crown ether dithiolate complexes, 2g and 4g, with 1 equivalent of NaBPh4 led to isolation of the 1 : 1 complexes in which the Na+ cation is bound in the macrocyclic crown, [Na(2g)(MeOH)2][BPh4] and [Na(4g)][BPh4] whose structures were determined by X-ray diffraction. Electrochemical studies supported through DFT calculations on the crown ether derivatives revealed a series of ligand-based oxidation waves corresponding to the dithiolate ligand (and dppf for 4g and 5g) whose redox potentials were shifted by ca. +0.1 V on binding to Na+.

Archaeal threonyl-tRNA synthetase (ThrRS) possesses an editing active site wherein tRNA Thr that has been misaminoacylated with serine (i.e., Ser-tRNA Thr ) is hydrolytically cleaved to serine and tRNA Thr . It has been suggested that the free ribose sugar hydroxyl of Ado76 of the tRNA Thr ( Ado76 2'OH) is the mechanistic base, promoting hydrolysis by orienting a nucleophilic water near the scissile Ser-tRNA Thr ester bond. We have performed a computational study, involving molecular dynamics (MD) and hybrid ONIOM quantum mechanics/molecular mechanics (QM/MM) methods, considering all possible editing mechanisms to gain an understanding of the role played by Ado76 2'OH group. More specifically, a range of concerted or stepwise mechanisms involving four-, six-, or eight-membered transition structures (total of seven mechanisms) were considered. In addition, these seven mechanisms were fully optimized using three different DFT functionals, namely, B3LYP, M06-2X, and M06-HF. The M06-HF functional gave the most feasible energy barriers followed by the M06-2X functional. The most favorable mechanism proceeds stepwise through two six-membered ring transition states in which the Ado76 2'OH group participates, overall, as a shuttle for the proton transfer from the nucleophilic H 2 O to the bridging oxygen ( Ado76 3'O) of the substrate. More specifically, in the first step, which has a barrier of 25.9 kcal/mol, the Ado76 2'-OH group accepts a proton from the attacking nucleophilic water while concomitantly transferring its proton onto the substrates C-O carb center. Then, in the second step, which also proceeds with a barrier of 25.9 kcal/mol, the Ado76 2'-OH group transfers its proton on the adjacent Ado76 3'-oxygen, cleaving the scissile C carb -O3' Ado76 bond, while concomitantly accepting a proton from the previously formed C-O carb H group.

Treatment of the imine PhC(=NSiMe3)py with Et2BOMe or BF3·Et2O afforded bicyclic ketiminoboranes and via intramolecular N-coordination. The basicity of the imine N is evidenced by their reactivity towards Brønsted and Lewis acids and the structures of ·HCl and ·BF3 are reported as well as the dipyridyl imine derivative ·HCl.

Reaction of the novel ligand 3-(2'-pyridyl)-benzo-1,2,4-thiadiazine (L) with the transition metal chloride salts MCl2·xH2O (M(II) = Mn, Fe, Co, Cu and Zn) in a 2 : 1 mole ratio afforded the mononuclear octahedral (high spin) complexes L2MCl2 (1a-1e respectively) in which L binds in a chelate fashion via N(2) and the pyridyl N atoms. In the case of CuCl2 the intermediate 1 : 1 four-coordinate complex LCuCl2 (2) was also isolated which adopts a polymeric structure with pseudo-square planar molecules linked via long Cu···S contacts (d(Cu···S) = 2.938(1) Å) in the apical position. In the presence of non-interacting ions, 3 : 1 complexes are isolated, exemplified by the reaction of L with Fe(CF3SO3)2 in a 3 : 1 ratio which affords the low spin complex [L3Fe][CF3SO3]2 (3). Reaction of L with VCl3 in a 2 : 1 mole ratio under aerobic conditions afforded the vanadyl complex [L2V(=O)Cl][Cl] (4).

Microwave chemistry has already impacted significantly on the everyday synthesis of organic molecules. The adoption and integration of this liberating technology has permitted a resurrection of many synthetic transformations that were previously considered too extreme in their conditions (temperatures, pressures, reaction times) to be synthetically useful. Furthermore, whole arrays of additional chemical transformations have been devised under microwave heating that allow access to more diverse chemical architectures via more expedient routes. Continuous flow processing of chemical intermediates taking advantage of the unique heating mechanism and characteristics of microwave irradiation will certainly be the next evolutionary step forward in this area. The synergistic combination afforded by the simultaneous application of these two core processing tools will enhance still further the synthetic capabilities of tomorrow's chemists. This short review aims to highlight the current developments and future potential offered by continuous flow microwave mediated synthesis.

The cycloaddition of acetylenes with azides to give the corresponding 1,4-disubstituted 1,2,3-triazoles is reported using immobilised reagents and scavengers in pre-packed glass tubes in a modular flow reactor.