Search

The importance of bioconjugation reactions continues to grow for cell specific targeting and dual therapeutic plus diagnostic medical applications. This necessitates the development of new bioconjugation chemistries, in‐flow synthetic and analytical methods. With this goal, continuous flow bioconjugations were readily achieved with short residence times for strained alkyne substituted carbohydrate and therapeutic peptide biomolecules in reaction with azide and tetrazine substituted fluorophores. The strained alkyne substrates included substituted 2‐amino‐2‐deoxy‐α‐D‐glucopyranose, and the linear and cyclic peptide sequences QIRQQPRDPPTETLELEVSPDPAS‐OH and c(RGDfK) respectively. The catalyst and reagent‐free inverse electron demand tetrazine cycloadditions proved more favourable than the azide 1,3‐dipolar cycloadditions. Reaction completion was achieved with residence times of 5 min at 40 °C for tetrazine versus 10 min at 80 °C for azide cycloadditions. The use of a fluorogenic tetrazine fluorophore, in a glass channelled reactor chip, allowed for intra‐chip reaction monitoring by recording fluorescence intensities at various positions throughout the chip. As the Diels‐Alder reactions proceeded through the chip, the fluorescence intensity increased accordingly in real‐time. The application of continuous flow fluorogenic bioconjugations could offer an efficient translational access to theranostic agents. [ABSTRACT FROM AUTHOR]

A combined analytical, theoretical, and experimental study has shown that the vaping of vitamin E acetate has the potential to produce exceptionally toxic ketene gas, which may be a contributing factor to the upsurge in pulmonary injuries associated with using e-cigarette/vaping products. Additionally, the pyrolysis of vitamin E acetate also produces carcinogen alkenes and benzene for which the negative longterm medical effects are well recognized. As temperatures reached in vaping devices can be equivalent to a laboratory pyrolysis apparatus, the potential for unexpected chemistries to take place on individual components within a vape mixture is high. Educational programs to informof the danger are nowrequired, as public perception has grown that vaping is not harmful. [ABSTRACT FROM AUTHOR]

Tetrazine fluorogenic probes are of high value due to their ability to modulate emission intensity from low to high in response to inverse electron demand Diels-Alder cycloadditions with dienophiles. In this study, a tetrazine substituted BF 2 -azadipyrromethene probe and a related model tetrazine were investigated for their reactivity with strained alkyne and alkene dienophiles to identify the optimal probe for cellular use. Specifically, the reactivity of 2-deoxy- d -glucose substituted 1-methyl cyclopropene and bicyclononyne was tested, with the latter demonstrating superior reactivity with complete reactions observed within 15 min. Moreover, the tetrazine substituted BF 2 -azadipyrromethene showed a strong fluorogenic response at a λ max of 715 nm in aqueous solution as the cycloaddition proceeded. The high reaction efficiency and significant 43-fold fluorescence enhancement factor encouraged its translation to bioorthogonal cell imaging. Pre-incubating HeLa Kyoto cells with 2-deoxy-glucose-alkyne dienophile followed by treatment with the BF 2 -azadipyrromethene fluorogenic probe, allowed dynamic imaging of the bioorthogonal reaction in live cells. Pre-incubation of 2-deoxy-glucose alkyne for 24 h with subsequent fluorogenic cycloaddition indicated that bioorthogonal reaction occurred in subcellular regions such as the mitochondria. This study showed the potential for real-time observation of intra-cellular fluorogenic cycloadditions in the near-infrared spectral region. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of three inter-related synthetic routes to a water soluble alkyne substituted BF 2 -azadipyrromethene fluorochrome is described. Each route allows for the introduction of the required reactive alkynyl group and water solubilizing propane-sulfonic acid through either more advanced pyrrole intermediates or through their earlier synthetic precursors. The advantages and disadvantages of each route lie in the number of synthetic steps required versus the formation of undesired azadipyrromethene by-products. Upon its synthesis, the alkyne-bearing fluorochrome was shown to efficiently participate in CuACC reactions with a series of azido substrates in water at room temperature and 37 °C. NIR-photophysical properties of the fluorochrome and its conjugates were similar, showing strong potential for in vitro and in vivo imaging applications. [ABSTRACT FROM AUTHOR]

A series of 1,2,4,5-tetrazine integrated near infrared (NIR) fluorophores based on the BF2 azadipyrromethene (NIR-AZA) class has been synthesised and their ability to modulate emission from low to high in response to Diels–Alder cycloaditions has been assessed. Substituents on the tetrazine component of the probe (Cl, OMe, p-NO2C6H4O) were seen to strongly influence quantum yields, fluorescence enhancement factors, and rates of cycloadditions. Cycloadditions between tetrazine-NIR-AZA constructs and a strained alkyne substrate were seen to be highly efficient in organic or aqueous solutions and in gels with high fluorescence enhancements of up to 48-fold observed. Real-time demonstration of the cycloaddition mediated fluorogenic property was achieved by imaging the “turn-on” reaction within a continous flow micro-reactor. Preliminary evidence indicates that excited state quenching involves a photoinduced electron transfer. [ABSTRACT FROM AUTHOR]

Azadipyrromethenes were first described over 70 years ago as blue pigments, but now are rapidly emerging as a compound class with highly desirable near infrared photophysical properties. Since the turn of the century several routes to azadipyrromethenes have been developed and numerous post-synthesis derivatizations have allowed for their exploitation in both biological and material sciences. The relative ease of access to specifically designed derivatives is now allowing their use in multiple technological formats from real-time fluorescence imaging, to solar energy materials, to optoelectronic devices and many more. In this review we have highlighted the synthetic component of this story as it is the ability to generate the designer azadipyrromethene that opens the door to exciting applications. [ABSTRACT FROM AUTHOR]

Addition of organotrimethylsilane reagents to chiral N-tert-butanesulfinyl imines can be achieved in good yields and with excellent diastereoselectivities by employing TMSO-/Bu4N+ as a Lewis base activator in THF. A variety of aliphatic, aromatic, heteroaromatic and organometallic chiral imines were utilised as electrophiles for the synthesis of enantioenriched N-tert-butanesulfinyl amides. Remarkably, the same sets of reaction conditions could be used with a highly diverse range of bench-stable organotrimethylsilane reagents, which highlights the generality and robustness of this methodology. [ABSTRACT FROM AUTHOR]

The synthesis of the reagent 2,2-bis(trimethylsilyl)-1,3-dithiane was directly achieved in an excellent yield from 1,3-dithiane in one step. The bench-stable reagent can be utilized for Peterson olefinations using either TMSOK/Bu4NCl or fluoride ion as promoter of α-silyl carbanion formation, thereby generating ketene dithioacetals, which are versatile intermediates in organic synthesis. Olefination reactions were successfully achieved with aromatic, heteroaromatic, aliphatic aldehydes and ketones. [ABSTRACT FROM AUTHOR]

The addition of a broad variety of substituted aromatic and heterocyclic silanes to chiral N-tert-butanesulfinylimines has been achieved providing 1,1-diaryl and diheterocyclic substituted sulfinamides with excellent diastereoselectivity in all cases. Employing Me3SiO-/Bu4N+ as the Lewis base activator for silicon allowed a general procedure for all silane reagents, including the less reactive aromatic derivatives. Evidence that the diastereoselective additions occur via an open transition state is presented. [ABSTRACT FROM AUTHOR]

The use of Me3SiO-/Bu4N+ as a general activator of organotrimethylsilanes for addition reactions has been established. The broad scope of the method offers trimethylsilanes (including acetate, allyl, propargyl, benzyl, dithiane, heteroaryl, and aryl derivatives) as bench-stable organometallics that can be readily utilized as carbanion equivalents for synthesis. Reactions are achieved at rt without the requirement of specialized precautions that are commonplace for other organometallics. [ABSTRACT FROM AUTHOR]

The metalation of benzene by Schlosser's base ( nBuLi/ tBuOK) occurs smoothly in THF at low temperatures to afford a discrete mixed-metal Li2K4 cluster that contains phenyl anions and tert-butoxide. The aggregate itself exhibits superbasic behavior by metalating toluene. The delocalized benzyl anion obtained this way π bonds to potassium counterions, thereby creating a 2D coordination polymer. [ABSTRACT FROM AUTHOR]

Die Metallierung von Benzol durch die Schlosser ‐ Base (nBuLi/tBuOK) läuft in THF glatt bei niedrigen Temperaturen unter Bildung eines diskreten, gemischtmetallischen Li2K4 ‐ Clusters ab, der neben tert ‐ Butoxid auch Phenylanionen enthält (siehe Bild). Das Aggregat selbst weist mit der Metallierung von Toluol superbasische Reaktivität auf. Das auf diesem Weg erhaltene Benzylanion zeigt π ‐ Wechselwirkungen zum Kaliumgegenion, unter Bildung eines 2D ‐ Koordinationspolymers. Die Metallierung von Benzol durch die Schlosser ‐ Base (nBuLi/tBuOK) läuft in THF glatt bei niedrigen Temperaturen unter Bildung eines diskreten, gemischtmetallischen Li2K4 ‐ Clusters ab, der neben tert ‐ Butoxid auch Phenylanionen enthält (siehe Bild). Das Aggregat selbst weist mit der Metallierung von Toluol superbasische Reaktivität auf. Das auf diesem Weg erhaltene Benzylanion zeigt π ‐ Wechselwirkungen zum Kaliumgegenion unter Bildung eines 2D ‐ Koordinationspolymers. [ABSTRACT FROM AUTHOR]

Abstract: The regioselective benzylic metalation of toluenes using BuLi/KO t Bu/TMP(H) (LiNK metalation conditions) and subsequent transmetalation to Si by reaction with TMSCl provides a general one-pot procedure for the synthesis of substituted benzyltrimethylsilanes. ArCH2Si(Me)3 derivatives are bench stable reagents yet can serve as benzyl anion equivalents under mild reaction conditions. Following activation with fluoride they can successfully participate in a wide range of additions to both non-enolizable and enolizable carbonyls. In addition, their use in the synthesis of isochromanones and trifluoromethylated amines is illustrated. The broad synthetic scope and mild practical conditions of use for ArCH2Si(Me)3 reagents demonstrate their general potential as benzyl anion equivalents. [Copyright &y& Elsevier]

The first synthesis of both organic and aqueous soluble BF2chelated 3,3′-dimethyl-5,5′-diarylazadipyrromethenes has been achieved. The fluorophores are emissive in organic and aqueous solvents with high quantum yields in the key biological near-infrared (NIR) spectral region of 675–700 nm. Following efficient cellular uptake from aqueous media the fluorophore can be readily visualized with confocal microscopy. [ABSTRACT FROM AUTHOR]

A general method is described for benzylic metalation of o-, m-, and p-substituted toluenes using a mixed metal amide base generated from BuLi/KOtBu/TMP at -78 °C in THF. The excellent selectivity achieved can be rationalized by the ability of the mixed metal amide base to facilitate an anion migration from the kinetic (o-aryl) to the benzylic metalation site. Remarkably, this controlled anion migration is achievable with catalytic amounts of TMP at -78 °C. [ABSTRACT FROM AUTHOR]

The (-)-sparteine-mediated enantioselective intermolecular carbolithiation of (E)-2-propenylarylamines allows for the generation of chiral lithiated intermediates which have broad synthetic potential. These intermediates have been exploited in a series of further in situ reactions with electrophiles to generate a collection of products each containing a common stereogenic center. The stereogenic center, formed in high enantiomeric ratio in the first carbolithiation step, is carried through the cascade reaction sequence to the final products and is independent of electrophile used. The methodology is demonstrated by the synthesis of structurally diverse chiral anilines, indoles, and indolones all with an er of 92:8 (± I). The heterocyclic syntheses involve an enantioselective alkene carbolithiation and subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring closure and dehydration to generate the indole or indolone rings. [ABSTRACT FROM AUTHOR]

A regioselective carbolithiation of o-amino-(E)-stilbenes has been achieved with a series of alkyllithiums when THF is employed as the reaction solvent. The use of other solvents, such as diethyl ether or hydrocarbons, leads to a pronounced loss in regioselectivity, Moreover, high levels of diastereoselectivity have been obtained following reaction of the lithiated intermediate in THF with different electrophiles such as MeOD, COs, and Bu3SnCl. It was shown that diastereoselectivity was influenced by the ortho-amino substituent and the alkyllithium utilized for carbolithiation with N-Boc substituent and t-BuLi proving optimal. In the case of carbolithiated intermediate 3a, obtained from the reaction of N-Boc substituted stilbene with t-BuLi, 1H and 13C NMR analysis revealed predominantly one diastereoisomer which was stable at room temperature. Application of the carbolithiation/electrophile reaction methodology to the synthesis of six-membered quinoline ring systems is demonstrated with substituted 3,4- dihydroquinolin-2-ones, 1,2,3,4-tetrahydroquinolines, 1,4-dihydroquinolines, and quinolines all prepared by a common cascade route. [ABSTRACT FROM AUTHOR]

Abstract: The sequential reactions of a pyridine vinylation and alkene carbolithiation constitutes a new route to substituted 7-azaindoles. The methodology involves a reaction sequence of controlled carbolithiation of the vinyl double bond, subsequent trapping of the formal di-anion intermediate with a suitable electrophile, followed by an in situ ring closure and dehydration. The reaction sequence allows for aryl, heteroaryl, alkyl and keto substituents to be included at different positions around the heterocycle. [Copyright &y& Elsevier]

Carbolithiation of diphenylacetylene can be exploited to generate (K)-1-lithio-1,2-diphenylalkyl-1-enes which can be reacted in Situ with triisopropylborate to stereoselectively provide (E)-1,2-diphenyl-1-alkylene boronic acids. These tetrasubstituted vinylboronic acids served as versatile intermediates for the generation of tetrasubstituted olefins with retention of stereochemistry. The application of this method for the stereoselective synthesis of (Z)-tamoxifen and related analogues is described. [ABSTRACT FROM AUTHOR]

Abstract: An effective synthesis of the 7-azaindole ring system has been developed from substituted 2-amino-3-vinyl pyridines. The methodology involves a novel cascade reaction sequence of controlled carbolithiation of the vinyl double bond, subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by ring closure and dehydration. [Copyright &y& Elsevier]

The synthesis of functionalized aryl vinyl ether derivatives can be readily achieved utilizing a room temperature copper(II) acetate mediated coupling of substituted phenols with 2,4,6-trivinylcyclotriboroxane-pyridine complex in the presence of a suitable base. The scope of the procedure was demonstrated by the generation of an array of substituted aryl vinyl ethers. The reaction was seen to be tolerant of a diverse range of functional groups yielding products in high isolated yields. We have shown that one role of an amine base in the reaction sequence is the in situ generation of an amine coordinated boroxine ring. An X-ray crystal structure and low temperature 11B NMR study of 2,4,6-trivinylcyclotriboroxane-pyridine complex demonstrated the nature of the tetracoordinate boron species, which may have a key role to play within the reaction sequence. [ABSTRACT FROM AUTHOR]

Examines the utilization of Suzuki cross-coupling protocol in the synthesis of functionalized styrene derivatives. Importance of styrenes in the synthesis of benzo-fused ring systems; Reaction of aryl halides with reagents; Mechanism of styrene polymerization.

Examines the rational biosynthesis of meso-substituted chlorin building blocks. Combination of 3,3-dimethyl-2,3-dihydrodipyrrin (Western half) and bromodipyrromethane carbinol (Eastern half); Preparation of Eastern half by sequential acylation and bromination of 5-substituted dipyrromethane; Synthesis of Western half in pyrrole-2-carboxaldehyde.

Molecular probes with the ability to differentiate between subcellular variations in acidity levels remain important for the investigation of dynamic cellular processes and functions. In this context, a series of cyclic peptide and PEG bio-conjugated dual near-infrared emissive BF2-azadipyrromethene fluorophores with maxima emissions at 720 nm (at pH > 6) and 790 nm (at pH < 5) have been developed and their aqueous solution photophysical properties determined. Their inter-converting emissions and fluorescence lifetime characteristics were exploited to track their spatial and temporal progression from first contact with the plasma membrane to subcellular locales to their release within extracellular vesicles. A pH-dependent reversible phenolate/phenol interconversion on the fluorophore controlled the dynamic changes in dual emission responses and corresponding lifetime changes. Live-cell confocal microscopy experiments in the metastatic breast cancer cell line MDA-MB-231 confirmed the usability of the dual emissive properties for imaging over prolonged periods. All three derivatives performed as probes capable of real-time continuous imaging of fundamental cellular processes such as plasma membrane interaction, tracking endocytosis, lysosomal/large acidic vesicle accumulation, and efflux within extracellular vesicles without perturbing cellular function. Furthermore, fluorescence lifetime imaging microscopy provided valuable insights regarding fluorophore progression through intracellular microenvironments over time. Overall, the unique photophysical properties of these fluorophores show excellent potential for their use as information-rich probes. [ABSTRACT FROM AUTHOR]

Discusses the development of procedures for metalation of porphyric compounds under homogeneous and heterogeneous conditions. Use of chlorophylls and bacteriochlorophylls in analysis; Reaction on heterogeneous magnesium insertion; Comparison between homogeneous and heterogeneous method; Size of magnesium cores.

• New access to planar chiral [2.2]metacyclophane derivatives starting from inexpensive starting materials. • (−)-Menthyl chloroformate shown to be an efficient chiral auxiliary to access both enantiomeric planar chiral forms. • Negates the need for the use of (−)-sparteine. The synthesis of planar chiral [2.2]metacyclophanes has been readily accomplished in a single synthetic step via the directed ortho metalation of a pro-chiral substituted metacyclophane. The use of (−)-menthyl chloroformate as a chiral auxiliary allows the introduction of the useful carbonyl functional group into the aryl ring, giving access to carboxy-substituted diastereomeric mixture of planar chiral [2.2]metacyclophanes. The separation of diastereoisomers has been easily accomplished by semipreparative HPLC, allowing the structural analysis of a single diastereoisomer by X-ray crystallography and NMR spectroscopy. The structural features of the planar chiral metacyclophanes and their high inversion barriers, determined at 473 K, encourage future investigations as chiral catalysts and ligands. This synthetic route complements our previously reported enantioselective synthesis avoiding the restrictive use of (−)-sparteine as the chiral inducer. [ABSTRACT FROM AUTHOR]

Time analysis of the course of an infectious disease epidemic is a critical way to understand the dynamics of pathogen transmission and the effect of population scale interventions. Computational methods have been applied to the progression of the COVID-19 outbreak in five different countries (Ireland, Germany, UK, South Korea and Iceland) using their reported daily infection data. A Gaussian convolution smoothing function constructed a continuous epidemic line profile that was segmented into longitudinal time series of mathematically fitted individual logistic curves. The time series of fitted curves allowed comparison of disease progression with differences in decreasing daily infection numbers following the epidemic peak being of specific interest. A positive relationship between the rate of declining infections and countries with comprehensive COVID-19 testing regimes existed. Insight into different rates of decline infection numbers following the wave peak was also possible which could be a useful tool to guide the reopening of societies. In contrast, extended epidemic timeframes were recorded for those least prepared for large-scale testing and contact tracing. As many countries continue to struggle to implement population wide testing it is prudent to explore additional measures that could be employed. Comparative analysis of healthcare worker (HCW) infection data from Ireland shows it closely related to that of the entire population with respect to trends of daily infection numbers and growth rates over a 57-day period. With 31.6% of all test-confirmed infections in healthcare workers (all employees of healthcare facilities), they represent a concentrated 3% subset of the national population which if exhaustively tested (regardless of symptom status) could provide valuable information on disease progression in the entire population (or set). Mathematically, national population and HCWs can be viewed as a set and subset with significant influences on each other, with solidarity between both an essential ingredient for ending this crisis. [ABSTRACT FROM AUTHOR]

Review: 169 refs. [ABSTRACT FROM AUTHOR]

Various aryl substituted bis(trimethylsilane) reagents react with aryl substituted N-tert-butylsulfinyl imines to form olefins in high yields and with very high (Z)-selectivity. [ABSTRACT FROM AUTHOR]

An abstract of the article "Highly Selective Addition of a Broad Spectrum of Trimethylsilane Pro-Nucleophiles to N-tert-Butanesulfinyl Imines" is presented.

The required title reagent (III) is readily available in one pot and excellent yield and can be applied with success to the olefination of a variety of aliphatic and aromatic aldehydes under either conditions A) or B). [ABSTRACT FROM AUTHOR]

A diagram is presented showing the diastereoselective addition of aryl and heterocyclic trimethylsilanes on N-tert-butanesulfinylimines.

The article examines the generality of enantioselective carbolithiation initiated cascade reactions. The method involved a cascade reaction sequence of alkyllithium addition to the styrene double bond, subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring closure and dehydration to generate the substituted indole ring. The goal is to advance the method for 2-propenylarylamines which could form an asymmetric route to the indole scaffold.

Presents a new organolithium addition methodology to diversely functionalized indoles. Biochemical roles played by the indole ring; Anionic polymerization of styrene using organolithium; Generation of the required starting materials; Viability of the reaction sequence; Deprotection of indoles.

Tms-OK/Bu4NCl is used as a general activator of organotrimethylsilanes for addition reaction. [ABSTRACT FROM AUTHOR]

A general one-pot procedure for the synthesis of benzyltrimethylsilanes (III) is developed. [ABSTRACT FROM AUTHOR]

A series of mono- and bis-polyethylene glycol (PEG)-substituted BF2-azadipyrromethene fluorophores have been synthesized with emissions in the near-infrared region (700–800 nm) for the purpose of fluorescence guided intraoperative imaging; chiefly ureter imaging. The Bis-PEGylation of fluorophores resulted in higher aqueous fluorescence quantum yields, with PEG chain lengths of 2.9 to 4.6 kDa being optimal. Fluorescence ureter identification was possible in a rodent model with the preference for renal excretion notable through comparative fluorescence intensities from the ureters, kidneys and liver. Ureteral identification was also successfully performed in a larger animal porcine model under abdominal surgical conditions. Three tested doses of 0.5, 0.25 and 0.1 mg/kg all successfully identified fluorescent ureters within 20 min of administration which was sustained up to 120 min. 3-D emission heat map imaging allowed the spatial and temporal changes in intensity due to the distinctive peristaltic waves of urine being transferred from the kidneys to the bladder to be identified. As the emission of these fluorophores could be spectrally distinguished from the clinically-used perfusion dye indocyanine green, it is envisaged that their combined use could be a step towards intraoperative colour coding of different tissues. [ABSTRACT FROM AUTHOR]

Sequential azide/diyne cycloadditions proved highly effective for the macrocyclization of a bis-azido aza-dipyrrin. Macrocyclic aza-dipyrrin could be produced in 30 min at rt in water with changes in fluorescence intensity and lifetimes measurable upon reaction. Live cell microscopy showed that aza-dipyrrins were suitable for confocal and STED super-resolution imaging and a bioorthogonal response to macrocyclization could be detected in cellular compartments. These results will encourage a broader examination of the sensing and imaging uses of aza-dipyrrins. [ABSTRACT FROM AUTHOR]

BF2-azadipyrromethenes are highly versatile fluorophores used for cellular and in vivo imaging in the near-infrared and far-red regions of the spectrum. As of yet, their use in conjunction with super-resolution imaging methodologies has not been explored. In this report, a series of structurally related BF2-azadipyrromethenes has been examined for their suitability for use with stimulated emission depletion (STED) nanoscopy. The potential for STED imaging was initially evaluated using aqueous solutions of fluorophores as an effective predictor of fluorophore suitability. For live cell STED imaging in both 2D and 3D, several far-red emitting BF2-azadipyrromethenes were successfully employed. Image resolution below the diffraction limit of a confocal microscope was demonstrated through measurement of distinct intracellular features including the nuclear membrane, nuclear lamina invaginations, the endoplasmic reticulum, and vacuoles. As the STED ability of BF2-azadipyrromethene fluorophores has now been established, their use with this super-resolution method may be expected to increase in the future. [ABSTRACT FROM AUTHOR]

Highly regioselective benzylic metalations in hydrocarbon solvent have been achieved at rt and 0 °C using a mixed-metal Li/K-TMP amide comprised of KOtBu, BuLi, and 2,2,6,6,-tetramethylpiperidine (TMP(H)). Mixing of KOtBu, BuLi, and TMP(H) in heptane gave a solution of the base mixture which when used in deuterium labeling experiments confirmed the requirement of the three reagent components for both reactivity and selectivity. The reaction protocol is operationally straightforward and found to be applicable to a broad range of substrates. Upon generation of the metalated products, they are reacted in heptane at ambient temperature in a variety of synthetically useful ways. Illustrated examples include generation of the benzyltrimethylsilanes and α,α-bis(trimethylsilyl)toluenes reagents, which are bench-stable surrogates of benzyl anions and α-silyl carbanions utilized for nucleophilic addition and Peterson olefination reactions. Direct C-C couplings mediated by 1,2-dibromoethane provided entries into bibenzyls and [2.2]metacyclophanes. Comparison of reaction outcomes with the same reactions carried out in THF at -78 °C showed no negative effects for conducting the reactions under these milder more user-friendly conditions. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most aggressive adult brain tumour with a dismal 2-year survival rate of 26–33%. Maximal safe resection plays a crucial role in improving patient progression-free survival (PFS). Neurosurgeons have the significant challenge of delineating normal tissue from brain tumour to achieve the optimal extent of resection (EOR), with 5-Aminolevulinic Acid (5-ALA) the only clinically approved intra-operative fluorophore for GBM. This review aims to highlight the requirement for improved intra-operative imaging techniques, focusing on fluorescence-guided imaging (FGS) and the use of novel dyes with the potential to overcome the limitations of current FGS. The review was performed based on articles found in PubMed an.d Google Scholar, as well as articles identified in searched bibliographies between 2001 and 2022. Key words for searches included 'Glioblastoma' + 'Fluorophore'+ 'Novel' + 'Fluorescence Guided Surgery'. Current literature has favoured the approach of using targeted fluorophores to achieve specific accumulation in the tumour microenvironment, with biological conjugates leading the way. These conjugates target specific parts overexpressed in the tumour. The positive results in breast, ovarian and colorectal tissue are promising and may, therefore, be applied to intracranial neoplasms. Therefore, this design has the potential to produce favourable results in GBM by reducing the residual tumour, which translates to decreased tumour recurrence, morbidity and ultimately, mortality in GBM patients. Several preclinical studies have shown positive results with targeted dyes in distinguishing GBM cells from normal brain parenchyma, and targeted dyes in the Near-Infrared (NIR) emission range offer promising results, which may be valuable future alternatives. [ABSTRACT FROM AUTHOR]

The use of an inorganic oxidant with an acetic acid/acetonitrile solvent combination has been identified as optimal for direct arene/1,2-disubstituted alkene oxidative couplings, providing an efficient route to trisubstituted alkenes. The acetonitrile cosolvent dramatically accelerates the rate of reaction, and an insoluble inorganic oxidant limits unwanted oxidation of substrates. The scope of this procedure is illustrated with arenes and alkenes containing electron-donating and -withdrawing substituents resulting in a general synthetic strategy to trisubstituted alkenes. In situ ESI-MS analysis of the reaction components has identified the key Pd intermediates in the Fujiwara--Moritani catalytic cycle. [ABSTRACT FROM AUTHOR]

As the aryl acetate moieties found in both THC-O-acetate and VEA are structurally similar, it could be anticipated that their thermally induced chemical reactivity would also be alike (Fig. THC-O-acetate, also called "THC-O", is a synthetic cannabinoid that is purported to be more potent than SP 9 sp -tetrahydrocannabinol, the primary psychoactive constituent of marijuana. This brief report is to alert the public health community to the confirmed presence of SP 8 sp -THC-O acetate in commercially available vaping products and the potential risk of pulmonary toxicity from vaping THC-O. The impetus for this study was the presence of the aryl acetate moiety in THC-O. Mass spectrometry (MS) evidence and activation energy (AE) calculations indicating that vaping of THC-O is likely to generate ketene, a suspected cause of lung injury, are provided. [Extracted from the article]

Abstract: A two-step synthesis of carboxy-functionalized planar chiral [2.2]metacyclophanes from m-xylenes is described. Both transformative steps utilize LiNK metalation conditions (BuLi, KOt-Bu, TMP(H)) for m-xylene benzylic deprotonation with subsequent in situ oxidative C–C coupling. Inclusion of the carboxy substituents at either C4, or C4 and C14, renders the [2.2]metacyclophanes planar chiral and the structural analysis of both substitution patterns has been achieved with X-ray crystallography and NMR spectroscopy. The C4 mono- and C4/14 di-substituted carboxylic acid methyl ester racemates were readily separated by analytical and preparative chiral HPLC and their inversion barriers measured in heptanes at 373 K at 125.3 kJ/mol and 130.9 kJ/mol, respectively. The facile synthesis, separation, and high inversion barriers of planar chiral [2.2]metacyclophanes present an opportunity for their investigation as chiral catalysts and ligands, which to date has yet to be explored. [Copyright &y& Elsevier]

The regioselective benzylic metalation of substituted toluenes using BuLi/KO-t-Bu/TMP(H) (LiNK metalation conditions) with subsequent in situ oxidative C-C coupling has been developed for the facile generation of 1,2-diarylethanes. A range of oxidants can be used for the oxidative coupling step, with 1,2-dibromoethane proving optimal. Heterocouplings can be achieved starting from a mixture of two different toluenes with a bias toward cross coupling achievable by using a 2-fold excess of one toluene starting material. The utility of this approach is illustrated by the synthesis of several biologically active natural products. A distinct advantage is that the synthetic steps typically required to preactivate the coupling substrates are eliminated and no transition metal is required to facilitate the C-C bond formation. [ABSTRACT FROM AUTHOR]

As indocyanine green (ICG) with near-infrared (NIR) endoscopy enhances real-time intraoperative tissue microperfusion appreciation, it may also dynamically reveal neoplasia distinctively from normal tissue especially with video software fluorescence analysis. Colorectal tumours of patients were imaged mucosally following ICG administration (0.25 mg/kg i.v.) using an endo-laparoscopic NIR system (PINPOINT Endoscopic Fluorescence System, Stryker) including immediate, continuous in situ visualization of rectal lesions transanally for up to 20 min. Spot and dynamic temporal fluorescence intensities (FI) were quantified using ImageJ (including videos at one frame/second, fps) and by a bespoke MATLAB® application that provided digitalized video tracking and signal logging at 30fps (Fluorescence Tracker App downloadable via MATLAB® file exchange). Statistical analysis of FI-time plots compared tumours (benign and malignant) against control during FI curve rise, peak and decline from apex. Early kinetic FI signal measurement delineated discriminative temporal signatures from tumours (n = 20, 9 cancers) offering rich data for analysis versus delayed spot measurement (n = 10 cancers). Malignant lesion dynamic curves peaked significantly later with a shallower gradient than normal tissue while benign lesions showed significantly greater and faster intensity drop from apex versus cancer. Automated tracker quantification efficiently expanded manual results and provided algorithmic KNN clustering. Photobleaching appeared clinically irrelevant. Analysis of a continuous stream of intraoperatively acquired early ICG fluorescence data can act as an in situ tumour-identifier with greater detail than later snapshot observation alone. Software quantification of such kinetic signatures may distinguish invasive from non-invasive neoplasia with potential for real-time in silico diagnosis. [ABSTRACT FROM AUTHOR]

Insights gained from a comparison of aminometalation reactions with lithium amides, potassium amides and mixed lithium/potassium amides are presented. A combination of structural characterization, DFT calculations and electrophile reactions of aminometalated intermediates has shown the advantages of using a mixed metal strategy. While potassium amides fail to add, the lithium amides are uncontrollable and eliminated, yet the mixed K/Li amides deliver the best of both systems. Aminopotassiation proceeds to form the alkylpotassium species which has enhanced stability over its lithium counterpart allowing for its isolation and thereby its further characterization. [ABSTRACT FROM AUTHOR]

Im Folgenden werden Erkenntnisse aus dem Vergleich von Aminometallierungs‐Reaktionen mit Lithiumamiden, Kaliumamiden und gemischten Lithium/Kaliumamiden vorgestellt. Durch eine Kombination von Einkristallröntgenstrukturanalysen, DFT‐Berechnungen und Abfangreaktionen von aminometallierten Zwischenprodukten werden die Vorteile einer hetero‐metallischen Strategie deutlich. Während Kaliumamide keine Reaktivität zeigen, ist die der Lithiumamide unkontrollierbar und eine Eliminierung kann nicht verhindert werden. Durch die synergistische Kombination beider Metalle wird jedoch eine ausreichend kontrollierbare Reaktivität erreicht. Die Aminometallierung mit Kalium führt zur Bildung von Alkylkalium‐Spezies, die im Vergleich zu ihren Lithium‐Kongeneren eine höhere Stabilität aufweisen und dadurch eine Isolierung sowie eine weitere Charakterisierung ermöglichen. [ABSTRACT FROM AUTHOR]

A general three step asymmetric synthesis of planar chiral [2.2]metacyclophanes utilizing selective benzylic and aryl metalations is described. The final enantioselective step is achieved using a (−)-sparteine mediated aryl metalation, following which electrophile reaction gives planar chiral cyclophanes with enantiomeric ratios (er) above 90 : 10. [ABSTRACT FROM AUTHOR]

Describes the crystal structure of the organic compound, tert-butyl 5-methoxy-3-pentylindole-1-carboxylate. Eta-eta stacking; Intermolecular interactions; Alternating indole rings; Separation of aromatic ring cetroids.