Kinetics and Mechanism of Azole n-π*-Catalyzed Amine Acylation.

Azole anions are highly competent in the activation of weak acyl donors, but, unlike neutral (aprotic) Lewis bases, are not yet widely applied as acylation catalysts. Using a combination of in situ and stopped-flow 1H/19F NMR spectroscopy, kinetics, isotopic labeling, 1H DOSY, and electronic structure calculations, we have investigated azole-catalyzed aminolysis of p-fluorophenyl acetate. The global kinetics have been elucidated under four sets of conditions, and the key elementary steps underpinning catalysis deconvoluted using a range of intermediates and transition state probes. While all evidence points to an overarching mechanism involving n-π* catalysis via N-acylated azole intermediates, a diverse array of kinetic regimes emerges from this framework. Even seemingly minor changes to the solvent, auxiliary base, or azole catalyst can elicit profound changes in the temporal evolution, thermal sensitivity, and progressive inhibition of catalysis. These observations can only be rationalized by taking a holistic view of the mechanism and a set of limiting regimes for the kinetics. Overall, the analysis of 18 azole catalysts spanning nearly 10 orders of magnitude in acidity highlights the pitfall of pursuing ever more nucleophilic catalysts without regard for catalyst speciation.

Mechanistic analysis by NMR spectroscopy: A users guide.

A 'principles and practice' tutorial-style review of the application of solution-phase NMR in the analysis of the mechanisms of homogeneous organic and organometallic reactions and processes. This review of 345 references summarises why solution-phase NMR spectroscopy is uniquely effective in such studies, allowing non-destructive, quantitative analysis of a wide range of nuclei common to organic and organometallic reactions, providing exquisite structural detail, and using instrumentation that is routinely available in most chemistry research facilities. The review is in two parts. The first comprises an introduction to general techniques and equipment, and guidelines for their selection and application. Topics include practical aspects of the reaction itself, reaction monitoring techniques, NMR data acquisition and processing, analysis of temporal concentration data, NMR titrations, DOSY, and the use of isotopes. The second part comprises a series of 15 Case Studies, each selected to illustrate specific techniques and approaches discussed in the first part, including in situ NMR (1/2H, 10/11B, 13C, 15N, 19F, 29Si, 31P), kinetic and equilibrium isotope effects, isotope entrainment, isotope shifts, isotopes at natural abundance, scalar coupling, kinetic analysis (VTNA, RPKA, simulation, steady-state), stopped-flow NMR, flow NMR, rapid injection NMR, pure shift NMR, dynamic nuclear polarisation, 1H/19F DOSY NMR, and in situ illumination NMR.

Heavy-Atom Kinetic Isotope Effects: Primary Interest or Zero Point?

Chemists have many options for elucidating reaction mechanisms. Global kinetic analysis and classic transition-state probes (e.g., LFERs, Eyring) inevitably form the cornerstone of any strategy, yet their application to increasingly sophisticated synthetic methodologies often leads to a wide range of indistinguishable mechanistic proposals. Computational chemistry provides powerful tools for narrowing the field in such cases, yet wholly simulated mechanisms must be interpreted with great caution. Heavy-atom kinetic isotope effects (KIEs) offer an exquisite but underutilized method for reconciling the two approaches, anchoring the theoretician in the world of calculable observables and providing the experimentalist with atomistic insights. This Perspective provides a personal outlook on this synergy. It surveys the computation of heavy-atom KIEs and their measurement by NMR spectroscopy, discusses recent case studies, highlights the intellectual reward that lies in alignment of experiment and theory, and reflects on the changes required in chemical education in the area.

Within-patch and edge microclimates vary over a growing season and are amplified during a heatwave: Consequences for ectothermic insects.

Embedded in longer term warming are extreme climatic events such as heatwaves and droughts that are increasing in frequency, duration and intensity. Changes in climate attributes such as temperature are often measured over larger spatial scales, whereas environmental conditions to which many small ectothermic arthropods are exposed are largely determined by small-scale local conditions. Exposed edges of plant patches often exhibit significant short-term (daily) variation to abiotic factors due to wind exposure and sun radiation. By contrast, within plant patches, abiotic conditions are generally much more stable and thus less variable. Over an eight-week period in the summer of 2020, including an actual heatwave, we measured small-scale (1 m2) temperature variation in patches of forbs in experimental mesocosms. We found that soil surface temperatures at the edge of the mesocosms were more variable than those within mesocosms. Drought treatment two years earlier, amplified this effect but only at the edges of the mesocosms. Within a plant patch both at the soil surface and within the canopy, the temperature was always lower than the ambient air temperature. The temperature of the soil surface at the edge of a patch may exceed the ambient air temperature when ambient air temperatures rise above 23 °C. This effect progressively increased with ambient temperature. We discuss how microscale-variation in temperature may affect small ectotherms such as insects that have limited ability to thermoregulate, in particular under conditions of extreme heat.

Systematic Evaluation of 1,2-Migratory Aptitude in Alkylidene Carbenes.

Alkylidene carbenes undergo rapid inter- and intramolecular reactions and rearrangements, including 1,2-migrations of ß-substituents to generate alkynes. Their propensity for substituent migration exerts profound influence over the broader utility of alkylidene carbene intermediates, yet prior efforts to categorize 1,2-migratory aptitude in these elusive species have been hampered by disparate modes of carbene generation, ultrashort carbene lifetimes, mechanistic ambiguities, and the need to individually prepare a series of 13C-labeled precursors. Herein we report on the rearrangement of 13C-alkylidene carbenes generated in situ by the homologation of carbonyl compounds with [13C]-Li-TMS-diazomethane, an approach that obviates the need for isotopically labeled substrates and has expedited a systematic investigation (13C{1H} NMR, DLPNO-CCSD(T)) of migratory aptitudes in an unprecedented range of more than 30 alkylidene carbenes. Hammett analyses of the reactions of 26 differentially substituted benzophenones reveal several counterintuitive features of 1,2-migration in alkylidene carbenes that may prove of utility in the study and synthetic application of unsaturated carbenes more generally.

Serum triamcinolone levels during intensive, inpatient wet-dressing therapy.

BACKGROUND: Wet dressings combined with topical corticosteroids are beneficial for patients with generalized and refractory dermatosis; however, to our knowledge, serum levels after topical corticosteroid absorption during intensive therapy have not been reported previously. AIM: To examine serum levels of triamcinolone acetonide (TAC) after topical corticosteroid application during intensive wet-dressing therapy. METHODS: We performed a retrospective study of adult patients admitted for inpatient wet-dressing therapy from 7 November 2015 to 24 June 2016. Data were collected on sex, age, body surface area, TAC serum levels, number of wet-dressing changes after 24 and 48 h, and type of wet dressing. RESULTS: In total, 29 patients (14 men, 15 women) were assessed. Median [interquartile range (IQR)] age was 57 years (51.5-67.0 years) and involved body surface area was 1.98 m2 (1.88-2.15) m2 . Before the 24-hour blood draw, patients had received 1-3 dressing changes. Median (IQR) TAC level at 24 h was 0.33 µg/dL (0.20-0.58 µg/dL), with no significant difference noted between the number of dressing changes and TAC serum level. At 48 h, results of a serum TAC test were available for 22 patients with 2-6 dressing changes. Mean (IQR) serum level was 0.30 µg/dL (0.30-0.87 µg/dL). For each additional dressing change, there was an estimated 0.21 µg/dL increase in TAC serum level (95% CI 0.11-0.31; P < 0.001). TAC serum level was not significantly associated with sex, age, body surface area or dressing type. CONCLUSIONS: Intensive, inpatient wet-dressing therapy is associated with detectable TAC serum levels. However, we suspect that topical TAC has a primarily local therapeutic effect on the skin.

Taming Ambident Triazole Anions: Regioselective Ion Pairing Catalyzes Direct N-Alkylation with Atypical Regioselectivity.

Controlling the regioselectivity of ambident nucleophiles toward alkylating agents is a fundamental problem in heterocyclic chemistry. Unsubstituted triazoles are particularly challenging, often requiring inefficient stepwise protection-deprotection strategies and prefunctionalization protocols. Herein we report on the alkylation of archetypal ambident 1,2,4-triazole, 1,2,3-triazole, and their anions, analyzed by in situ 1H/19F NMR, kinetic modeling, diffusion-ordered NMR spectroscopy, X-ray crystallography, highly correlated coupled-cluster computations [CCSD(T)-F12, DF-LCCSD(T)-F12, DLPNO-CCSD(T)], and Marcus theory. The resulting mechanistic insights allow design of an organocatalytic methodology for ambident control in the direct N-alkylation of unsubstituted triazole anions. Amidinium and guanidinium receptors are shown to act as strongly coordinating phase-transfer organocatalysts, shuttling triazolate anions into solution. The intimate ion pairs formed in solution retain the reactivity of liberated triazole anions but, by virtue of highly regioselective ion pairing, exhibit alkylation selectivities that are completely inverted (1,2,4-triazole) or substantially enhanced (1,2,3-triazole) compared to the parent anions. The methodology allows direct access to 4-alkyl-1,2,4-triazoles ( rr up to 94:6) and 1-alkyl-1,2,3-triazoles ( rr up to 99:1) in one step. Regioselective ion pairing acts in effect as a noncovalent in situ protection mechanism, a concept that may have broader application in the control of ambident systems.

Adventures in boron chemistry - the prediction of novel ultra-flexible boron oxide frameworks.

Recent periodic density functional calculations have predicted the existence of ultra-flexible low-energy forms of boron oxides in which rigid boron-oxygen heterocycles are linked by flexible B-O-B bridges. The minima in the energy landscapes of these frameworks are remarkably broad, with widths in excess of those of many hybrid metal-organic frameworks. Enormous changes in cell volume, which can exceed a factor of two, are accompanied by negligible changes in energy. Here we explore the underlying reasons for this behaviour using molecular electronic-structure calculations, periodic density functional theory and template-based geometric simulations. The angular flexibility of the B-O-B bridge depends only upon the geometry of the local B2O5 unit, independent of the configuration of neighbouring bridges. Unique cooperativity between the bending and twisting motions of the bridges leads to considerable anisotropy in framework flexibility. Exceptional flexibility is conferred not only by the intrinsic bending flexibility of the bridges but by topological factors, crucially the relaxation of torsional constraints when B3O3 rings are present. We test these conclusions by showing how the flexibility of the frameworks can be tuned by decoration with isoelectronic rings. The new nanoporous boron oxides presented in this work are predicted to be potential novel guest-host materials because of their flat energy landscapes. Furthermore, such structures can be generated systematically from silicates by the substitution of B2O54- for SiO44-. A borate analogue of ß-cristobalite is shown to be isoenergetic with the known B2O3-I polymorph. We raise the possibility of new families of frameworks and zeolite analogues.

Ultrafast Observation of a Photoredox Reaction Mechanism: Photoinitiation in Organocatalyzed Atom-Transfer Radical Polymerization.

Photoredox catalysis has driven a revolution in the field of organic chemistry, but direct mechanistic insights into reactions of genuine synthetic utility remain relatively scarce. Herein we report ultrafast time-resolved spectroscopic observation of a bimolecular organocatalyzed photoredox reaction, from catalyst photoexcitation through to photoinduced electron transfer (PET) and intermediate formation, using transient vibrational and electronic absorption spectroscopy with sub-picosecond time resolution. Specifically, the photochemical dynamics of initiation in organocatalyzed atom-transfer radical polymerization (O-ATRP) are elucidated for two complementary photoredox organocatalysts (N,N-diaryl-5,10-dihydrophenazines). Following photoexcitation, a dissociative bimolecular electron transfer is observed from the first excited singlet state of both photocatalysts to methyl 2-bromopropionate in dichloromethane, toluene, and dimethylformamide. The photocatalyst excited donor state, ground state, and radical cation are tracked in real time alongside the debrominated radical fragment. Our work challenges previously proposed mechanisms of initiation in O-ATRP and indicates that PET from short-lived excited singlet states can exert control of polymer molecular weight and dispersity by suppressing the steady-state concentration of the reactive debrominated radical. More broadly, we aim to demonstrate the potential of ultrafast absorption spectroscopy to observe directly transient, open-shell intermediates in mechanistic studies of photoredox catalysis.

Heavily Substituted Atropisomeric Diarylamines by Unactivated Smiles Rearrangement of N-Aryl Anthranilamides.

Diarylamines find use as metal ligands and as structural components of drug molecules, and are commonly made by metal-catalyzed C-N coupling. However, the limited tolerance to steric hindrance of these couplings restricts the synthetic availability of more substituted diarylamines. Here we report a remarkable variant of the Smiles rearrangement that employs readily accessible N-aryl anthranilamides as precursors to diarylamines. Conformational predisposition of the anthranilamide starting material brings the aryl rings into proximity and allows the rearrangement to take place despite the absence of electron-withdrawing substituents, and even with sterically encumbered doubly ortho-substituted substrates. Some of the diarylamine products are resolvable into atropisomeric enantiomers, and are the first simple diarylamines to display atropisomerism.

Habitat complexity reduces parasitoid foraging efficiency, but does not prevent orientation towards learned host plant odours.

It is well known that many parasitic wasps use herbivore-induced plant odours (HIPVs) to locate their inconspicuous host insects, and are often able to distinguish between slight differences in plant odour composition. However, few studies have examined parasitoid foraging behaviour under (semi-)field conditions. In nature, food plants of parasitoid hosts are often embedded in non-host-plant assemblages that confer both structural and chemical complexity. By releasing both naïve and experienced Cotesia glomerata females in outdoor tents, we studied how natural vegetation surrounding Pieris brassicae-infested Sinapis arvensis and Barbarea vulgaris plants influences their foraging efficiency as well as their ability to specifically orient towards the HIPVs of the host plant species on which they previously had a positive oviposition experience. Natural background vegetation reduced the host-encounter rate of naïve C. glomerata females by 47 %. While associative learning of host plant HIPVs 1 day prior to foraging caused a 28 % increase in the overall foraging efficiency of C. glomerata, it did not reduce the negative influence of natural background vegetation. At the same time, however, females foraging in natural vegetation attacked more host patches on host-plant species on which they previously had a positive oviposition experience. We conclude that, even though the presence of natural vegetation reduces the foraging efficiency of C. glomerata, it does not prevent experienced female wasps from specifically orienting towards the host-plant species from which they had learned the HIPVs.

Children with autism spectrum disorders show abnormal conditioned response timing on delay, but not trace, eyeblink conditioning.

Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes the subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ASD children performed normally during trace EBC, exhibiting no differences from TD subjects with regard to the learning rate or the timing of the conditioned response. However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of the cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals.

The roles of ecological fitting, phylogeny and physiological equivalence in understanding realized and fundamental host ranges in endoparasitoid wasps.

Co-evolutionary theory underpins our understanding of interactions in nature involving plant-herbivore and host-parasite interactions. However, many studies that are published in the empirical literature that have explored life history and development strategies between endoparasitoid wasps and their hosts are based on species that have no evolutionary history with one another. Here, we investigated novel associations involving two closely related solitary endoparasitoids that originate from Europe and North America and several of their natural and factitious hosts from both continents. The natural hosts of both species are also closely related, all being members of the same family. We compared development and survival of both parasitoids on the four host species and predicted that parasitoid performance is better on their own natural hosts. In contrast with this expectation, survival, adult size and development time of both parasitoids were similar on all (with one exception) hosts, irrespective as to their geographic origin. Our results show that phylogenetic affinity among the natural and factitious hosts plays an important role in their nutritional suitability for related parasitoids. Evolved traits in parasitoids, such as immune suppression and development, thus enable them to successfully develop in novel host species with which they have no evolutionary history. Our results show that host suitability for specialized organisms like endoparasitoids is closely linked with phylogenetic history and macro-evolution as well as local adaptation and micro-evolution. We argue that the importance of novel interactions and 'ecological fitting' based on phylogeny is a greatly underappreciated concept in many resource-consumer studies.

Quantification of various factors influencing the precision of thermoluminescent detector calibrations for new and used chip sets.

Factors affecting the random and systematic error in calibrating three sets of 100 LiF:Mg,Ti thermoluminescent detector chips were investigated. The chips were held in a polymethyl methacrylate plate with 0.3 cm deep wells covered with a thin top plate, affixed to a polymethyl methacrylate phantom 150 cm from a 3.2 × 10(10) GBq 137Cs source, used to irradiate the chips to 4.52 mGy. Three sets of chips were used: one new, one heavily used, and one having relatively high degrees of visible physical damage. Variations in the exposure rate across the plate were measured with an ion chamber. Experimental drift was judged by performing successive calibrations on subsequent days, while always reading the chips in the same order. The chips were subject to manual examination to determine variations in mass and physical quality. This study indicates that more accurate calibrations can be obtained by accounting for the error caused by nonuniformity in the delivered dose, which was in this study as high as 4.4% from the center to the edges of the target. Making use of more than three calibrations only reduces the standard deviation as a percentage of the mean of a set by less than 1%. Desirable dosimeters in commercially rejected sets were identified by comparing each dosimeter's standard deviation of response across all calibrations to a commercially acceptable control set. Up to 50% variations in mass and visual quality, including opacity, fracture, and surface scratches to chips, showed little to no correlation with their response.

Divergent composition but similar function of soil food webs of individual plants: plant species and community effects.

Soils are extremely rich in biodiversity, and soil organisms play pivotal roles in supporting terrestrial life, but the role that individual plants and plant communities play in influencing the diversity and functioning of soil food webs remains highly debated. Plants, as primary producers and providers of resources to the soil food web, are of vital importance for the composition, structure, and functioning of soil communities. However, whether natural soil food webs that are completely open to immigration and emigration differ underneath individual plants remains unknown. In a biodiversity restoration experiment we first compared the soil nematode communities of 228 individual plants belonging to eight herbaceous species. We included grass, leguminous, and non-leguminous species. Each individual plant grew intermingled with other species, but all plant species had a different nematode community. Moreover, nematode communities were more similar when plant individuals were growing in the same as compared to different plant communities, and these effects were most apparent for the groups of bacterivorous, carnivorous, and omnivorous nematodes. Subsequently, we analyzed the composition, structure, and functioning of the complete soil food webs of 58 individual plants, belonging to two of the plant species, Lotus corniculatus (Fabaceae) and Plantago lanceolata (Plantaginaceae). We isolated and identified more than 150 taxa/groups of soil organisms. The soil community composition and structure of the entire food webs were influenced both by the species identity of the plant individual and the surrounding plant community. Unexpectedly, plant identity had the strongest effects on decomposing soil organisms, widely believed to be generalist feeders. In contrast, quantitative food web modeling showed that the composition of the plant community influenced nitrogen mineralization under individual plants, but that plant species identity did not affect nitrogen or carbon mineralization or food web stability. Hence, the composition and structure of entire soil food webs vary at the scale of individual plants and are strongly influenced by the species identity of the plant. However, the ecosystem functions these food webs provide are determined by the identity of the entire plant community.

Anomalous fluctuations of s-wave reduced neutron widths of 192,194Pt resonances.

We obtained an unprecedentedly large number of s-wave neutron widths through R-matrix analysis of neutron cross-section measurements on enriched Pt samples. Careful analysis of these data rejects the validity of the Porter-Thomas distribution with a statistical significance of at least 99.997%.

Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors.

Contemporary receptor theory was developed to account for the existence of constitutive activity, as defined by the presence of receptor signaling in the absence of any ligand. Thus, ligands acting at a constitutively active receptor, can act as agonists, antagonists, and inverse agonists. In vitro studies have also revealed the complexity of ligand/receptor interactions including agonist-directed stimulus trafficking, a finding that has led to multi-active state models of receptor function. Studies with a variety of cell types have established that the serotonin 5-HT(2A) and 5-HT(2C) receptors also demonstrate constitutive activity and inverse agonism. However, until recently, there has been no evidence to suggest that these receptors also demonstrate constitutive activity and hence reveal inverse agonist properties of ligands in vivo. This paper describes our current knowledge of constitutive activity in vitro and then examines the evidence for constitutive activity in vivo. Both the serotonin 5-HT(2A) and 5-HT(2C) receptors are involved in a number of physiological and behavioral functions and are the targets for treatment of schizophrenia, anxiety, weight control, Parkinsonism, and other disorders. The existence of constitutive activity at these receptors in vivo, along with the possibility of inverse agonism, provides new avenues for drug development.

Oviposition cues for a specialist butterfly--plant chemistry and size.

The oviposition choice of an insect herbivore is based on a complex set of stimuli and responses. In this study, we examined the effect of plant secondary chemistry (the iridoid glycosides aucubin and catalpol) and aspects of size of the plant Plantago lanceolata, on the oviposition behavior of the specialist butterfly Melitaea cinxia. Iridoid glycosides are known to deter feeding or decrease the growth rate of generalist insect herbivores, but can act as oviposition cues and feeding stimulants for specialized herbivores. In a previous observational study of M. cinxia in the field, oviposition was associated with high levels of aucubin. However, this association could have been the cause (butterfly choice) or consequence (plant induction) of oviposition. We conducted a set of dual- and multiple-choice experiments in cages and in the field. In the cages, we found a positive association between the pre-oviposition level of aucubin and the number of ovipositions. The association reflects the butterfly oviposition selection rather than plant induction that follows oviposition. Our results also suggest a threshold concentration below which females do not distinguish between levels of iridoid glycosides. In the field, the size of the plant appeared to be a more important stimulus than iridoid glycoside content, with bigger plants receiving more oviposition than smaller plants, regardless of their secondary chemistry. Our results illustrate that the rank of a cue used for oviposition may be dependent on environmental context.

Positron emission tomography and pathological evidence of response to neoadjuvant therapy in adenocarcinoma of the esophagus.

Our aim was to determine if fluorodeoxyglucose positron emission tomography (FDG-PET) could be correlated with a pathological response in patients with esophageal adenocarcinoma receiving neoadjuvant chemotherapy and/or chemoradiation therapy. Patients with resectable, histologically proven adenocarcinoma of the esophagus were entered in the study. Preoperative chemotherapy comprised two cycles of cisplatin and 5-fluorouracil. Radiation therapy commenced with the second cycle on day 22. FDG-PET images were obtained pre-treatment and on completion of intended neo-adjuvant treatment. Quantification was achieved by the calculation of both standardized uptake values (SUV) and tumor/liver ratios (TLR). Evidence of histopathological response was identified according to the Mandard tumor regression scoring system. There were 45 patients, 22 receiving neoadjuvant chemotherapy and 23 chemoradiation therapy. Forty patients underwent surgical resection. Seven patients (16%) had a histopathological response. The mean percentage change in SUV in the histological responders group was -56.8% (SD 29) and in the non-responders -27.8% (SD 32.1) (P = 0.035). The mean percentage change in TLR was -49.1% (SD 44.8) in the responders and in the non-responders -27.3% (SD 31.3) (P = 0.128). There was no difference between the two methods of assessment, however there was less variation with SUV. There was no correlation between the FDG-PET response and the histopathological response. Presently an FDG-PET scan performed 3-6 weeks after neoadjuvant therapy for adenocarcinoma of the esophagus should not be used as a marker of the potential result of the treatment. The optimal timing of a second FDG-PET remains unclear.

Salvage definitive chemo-radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: retrospective review.

To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo-radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo-radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo-radiotherapy was 16 months and the 2-year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo-radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival.