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Background Internet-based Cognitive Behaviour Therapy (iCBT) for depression have been implemented in routine care across Europe in varying ways, at various scales and with varying success. This study aimed to advance our understanding of organisational implementation climate from the perspectives of implementers and mental health service deliverers. Methods Qualitative and quantitative methods were combined to study the concept of organisational implementation climate in mental health care settings. Based on concept mapping, a qualitative workshop with implementers was used to conceptualise organisational implementation climate for optimizing iCBT use in routine practice. Service deliverers involved in the provision of iCBT were invited to participate in an explorative cross-sectional survey assessing levels of satisfaction and usability of iCBT, and organisational implementation climate in implementing iCBT. The two methods were applied independently to study viewpoints of implementers as well as service deliverers. Corresponding to the explorative nature of the study, inductive reasoning was applied to identify patterns and develop a reasonable explanation of the observations made. Correlative associations between satisfaction, usability and implementation climate were explored. Results Sixteen implementers representing fourteen service delivery organisations across Europe participated in the workshop. The top-three characteristics of a supportive organisational implementation climate included: (1) clear roles and skills of implementers, (2) feasible implementation targets, and (3) a dedicated implementation team. The top-three tools for creating a supportive implementation climate included: (1) feedback on job performance, (2) progress monitoring in achieving implementation targets, and (3) guidelines for assessing the impact of iCBT. The survey (n=111) indicated that service providers generally regarded their organisational implementation climate as supportive in implementing iCBT services. Organisational implementation climate was weakly associated with perceived usability and moderately with satisfaction with iCBT services. Conclusions Organisational implementation climate is a relevant factor to implementers and service deliverers in implementing iCBT in routine care. It is not only an inherent characteristic of the context in which implementation takes place, it can also be shaped to improve implementation of iCBT services. Future research should further theorise organisational implementation climate and empirically validate the measurement instruments such as used in this study.

ispartof: Biofouling status: accepted

ispartof: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY vol:2020 issue:23 pages:3378-3389 status: published

ispartof: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY vol:2020 issue:11 pages:1695-1699 status: published

Bacteria commonly form dense biofilms encased in extracellular polymeric substances (EPS). Biofilms are often extremely tolerant to antimicrobials but their reliance on shared EPS may also be a weakness as social evolution theory predicts that inhibiting shared traits can select against resistance. Here we show that EPS of Salmonella biofilms is a cooperative trait whose benefit is shared among cells, and that EPS inhibition reduces both cell attachment and antimicrobial tolerance. We then compare an EPS inhibitor to conventional antimicrobials in an evolutionary experiment. While resistance against conventional antimicrobials rapidly evolves, we see no evolution of resistance to EPS inhibition. We further show that a resistant strain is outcompeted by a susceptible strain under EPS inhibitor treatment, explaining why resistance does not evolve. Our work suggests that targeting cooperative traits is a viable solution to the problem of antimicrobial resistance. ispartof: Nature Communications vol:11 issue:1 ispartof: location:England nrpages: 11 status: published

A post-Ugi gold-catalysed chemo- and diastereo-selective cascade dearomative spirocyclization/1,6-addition sequence is disclosed for the facile synthesis of diverse fused polyheterocyclic scaffolds bearing indole, pyrrole, benzothiophene, furan or electron-rich arene cores., A gold-catalysed post-Ugi chemo- and diastereoselective cascade dearomative spirocyclization/1,6-addition sequence is disclosed for the synthesis of diverse fused polyheterocyclic scaffolds bearing indole, pyrrole, benzothiophene, furan or electron-rich arene moieties from easily available building blocks. The effectiveness and efficiency of this diversity-oriented approach has been proved in the rapid construction of 28 fused polyheterocyclic scaffolds with a good building-block variability and structural complexity in two operational steps.

A rhodium(III)-catalyzed intramolecular oxidative annulation of O-substituted N-hydroxyacrylamides for the construction of indolizinones via sequential C(sp2)-H activation and C(sp3)-H amination has been developed. This approach shows excellent functional-group tolerance. The synthesized scaffold forms the core of many natural products with pharmacological relevance. ispartof: Beilstein Journal of Organic Chemistry vol:15 pages:571-576 ispartof: location:Germany status: Published online

ispartof: Ampere Newsletter issue:96 pages:24-29 status: published

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim A copper-catalyzed two-step one-pot procedure for the synthesis of thiazolidine-2-thiones has been developed. The process involves a three-component coupling of an alkyne, an aldehyde, and an amine (A3-coupling) followed by trapping the resulting propargylamine with carbon disulfide and subsequent cyclization. ispartof: European Journal of Organic Chemistry vol:2017 issue:6 pages:1063-1069 status: published

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim A one-pot procedure involving a four-component Ugi reaction followed by an intramolecular Diels–Alder reaction/HCl elimination cascade has been developed to provide rapid access to the isoindolinone framework in a diversity-oriented fashion. The scope of the process has been investigated with respect to all four components, and a comparison between the one-pot and sequential approaches is given. The possibility of a late-stage one-pot functionalization through Suzuki coupling has been explored. ispartof: European Journal of Organic Chemistry vol:30 issue:30 pages:4379-4388 status: published

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim We describe our results on the synthesis of fused 1,2,3-triazolo-1,3,6-triazonines through a copper-catalyzed multicomponent reaction. The products were obtained in moderate to excellent yields by the reaction of 2-azidobenzaldehydes, substituted diaminobenzenes and a range of terminal alkynes in the presence of a catalytic amount of copper iodide, with Et3N as base, in DMSO at 100 °C. This method proved to be efficient for the combinatorial synthesis of new medium-sized N-heterocyclic rings with potential applications in biological studies. ispartof: European Journal of Organic Chemistry vol:2017 issue:18 pages:2579-2586 status: published

Most of the human bacterial infections are associated with the biofilm formation and the natural tolerance of biofilms to antibiotics challenges treatment. Because of their low immunity, cancer patients are especially susceptible to bacterial infections. Compounds with anti-biofilm activity could therefore become a useful adjunct to chemotherapy, in particular if they also show antiproliferative activities. Taking this into consideration and as a result of our continuous interest in 2-aminoimidazole derivatives, we have designed and synthesized a series of novel polysubstituted 2-aminoimidazoles (20a-x). The compounds were evaluated against a panel of three bacterial strains for their biofilm and planktonic growth inhibitory activity and most of them show promising results. Furthermore, the synthesized compounds were evaluated against various cancer cell lines and almost all the compounds were found to possess potent antiproliferative activity. The substitution pattern at the C-4 position and the aryl carboxamide ring at the N-1 position have major effects on the biofilm inhibitory and antiproliferative activity. Especially, the introduction of a p-methyl group at the carboxamide ring remarkably enhances both the anti-biofilm and antiproliferative activity. The two most potent compounds (20i &20r) were further studied for their antiproliferative activity and a flow cytometer-based cell cycle experiment was performed, which revealed their capability to induce G2/M phase cell cycle arrest. Based on these results, these two new compounds having potential to target both cancer proliferation and microbial biofilms might be used in single drug monotherapy. ispartof: European Journal of Medicinal Chemistry vol:138 pages:152-169 ispartof: location:France status: published

A new protocol for the one-pot synthesis of pyrrolones and butenolides involving an isocyanide-based multicomponent reaction (Ugi or Passerini) followed by a triethylamine-promoted cycloisomerization is described. ispartof: Synthesis vol:48 issue:14 pages:2280-2286 status: published

A one-pot sequential A3-coupling-azidation-cyclisation approach leading to potentially biologically active diazepine analogues has been developed. The implementation of the A3-coupling reaction ensures diversity. Attention is given to this so far rarely studied structural motif of fused heterocyclic diazepines. ispartof: European Journal of Organic Chemistry vol:2015 issue:21 pages:4726-4731 status: published

Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. A comprehensive study on gold- and silver-catalyzed cycloisomerizations of hydroxypropargylamides into oxazepines is described. Three different types of hydroxypropargylamide substrates derived from either amide coupling or Ugi reactions have been validated resulting in establishment of selective and general access to a medium-ring oxazepine core. A comprehensive study on gold- and silver-catalyzed cycloisomerizations of hydroxypropargylamides into oxazepines is described. ispartof: European Journal of Organic Chemistry vol:19 issue:19 pages:4190-4197 status: published

Heterocyclic fused α-methylene β-lactams were successfully synthesized by a post-Ugi InIII-catalyzed intramolecular addition reaction. Switching from InCl3 to AlCl3 led to the regioselective synthesis of α,β-unsaturated γ-lactams. Moreover, replacing terminal alkynes by substituted alkynes in the Ugi adducts resulted in the exclusive formation of γ-lactams with both catalytic systems. ispartof: European Journal of Organic Chemistry vol:2015 issue:18 pages:3957-3962 status: published

In this work, the application of heterogeneous catalysis, i.e. polymer-supported phosphine, metal nanoparticles and metal nanoclusters, was investigated to construct a diverse range of heterocyclic molecules through the activation of triple bonds. The work aimed to render the activation of triple bonds more environmentally friendly and cost-efficient by applying reusable heterogeneous catalysts under batch as well as in continuous flow. An "umpolung Michael addition" was reported to synthesize three-dimensional polyheterocyclic structures employing a nucleophilic phosphine catalyst. Next, silver nanoparticles and nanocluster were used to mainly generate 5-membered heterocycles. Silver nanoclusters (Ag NCs) were used to construct C-N, C-O and C-C bonds. The activity of silver clusters was higher for the hydroamination (C-N bond) of the propargylguanidines and for the synthesis of 2-phenylbenzofuran (C-O bond) as compared to previously reported nano-based catalysts. The Ag NCs were also reactivated by hydrogen peroxide to regain their catalytic activity. The stability of metal nanoclusters was investigated under different reaction conditions. Metal nanoparticles and nanoclusters were characterized by HRTEM, XPS, and MP-AES to understand the effect of reaction conditions on the morphology of the catalysts. Interestingly, no appreciable leaching was detected by MP-AES under the applied reaction conditions. status: published

status: published

Aromatic heterocycles are omnipresent motifs in pharmaceutical and agrochemical structures. Functionalization of these ring systems is an important part of many synthetic procedures. In this chapter, an overview is given of how microflow technology has been employed as a powerful tool for the diversification of heteroarenes. An emphasis is put on fine chemical synthesis, although reactor design and problem solving will be discussed when relevant, as it comprises an important part of the research field. Pragmatic translations to microflow are reviewed for existing functionalization protocols, and a few elusive reactions are highlighted that cannot be performed satisfyingly in batch mode.

The research described in this thesis centers on the application of 3-substituted propiolic acids in a four-component Ugi reaction. The triple bond of propiolic acid in combination with other functionalities produces an important type of Ugi adducts which could be then readily applied in a large variety of post transformations providing a diversity-oriented access towards a large number of heterocyclic scaffolds. Chapter 1 serves as an introduction into the post-Ugi chemistry in general, and into the reactivity of Ugi-adducts bearing C-C triple bond in particular. The objectives and targets of the current research are also formulated in this chapter. Chapter 2 is dedicated to the elaboration of a novel cascade transformation involving Ugi reaction followed by enolization-triggered 5-endo-dig carbocyclization and retro-Claisen fragmentation providing an efficient and fast access to 1H-pyrrol-2(5H)-one core. Chapter 3 describes a comprehensive study on gold- and silver-catalyzed cyclisomerizations of hydroxypropargylamides into oxazepines. Three different types of hydroxypropargylamide substrates derived from either amide coupling or Ugi reaction have been validated providing selective and general access to a medium-ring oxazepine core. Chapter 4 deals with a two-step sequence involving Ugi reaction followed by reductive Heck cyclization leading to a 3-benzazepine framework. Several aspects related to the substrate scope and the optimal distribution of the required functional groups have been addressed, resulting in a diversity-oriented synthesis of a small library of title compounds, featuring four distinct types of substitution pattern. status: published

Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Обычная таблица"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0pt 5.4pt 0pt 5.4pt; mso-para-margin:0pt; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;}This thesis is devoted to the exploration of synthetic strategies for the generation of secondary N-alkylpropargylamines, aswell as to the study of their synthetic utility for the construction of smallheterocycles. A substantial part of this work deals with additions of secondary propargylamines tovarious heteroallennes, followed by transition metal-catalyzedcycloisomerizations. Also special attention is given to the regio- andchemoselectivity of these processes in the context of existing methodologies.The elaborated protocols rely on modern transition metal catalysis and utilizereadily available starting materials.Chapter1 serves as anintroduction to the chemistry of propargylamines in general, and secondary N-alkylpropargylamines inparticular, highlighting the A3-coupling reaction as a modernmethod for their synthesis. Several processes which are relevant to the presentstudy and which utilize secondary N-alkylpropargylaminesas starting materials, are also briefly outlined. The objectives of thecurrent research are summarized in this chapter.Chapter2 is dedicated to theelaboration of microwave-assisted Cu(I)-catalyzed coupling of a ketone, analkyne and a primary amine (KA2-coupling), providing a generalaccess to quaternary carbon-containing secondary N-alkylpropargylamines.Chapter3 describes theapplication of the above propargylamines in the Ag(I)-mediated tandem guanylation/cycloisomerizationreaction previously developed in our group, in order to access a structurallyinteresting class of heterocycles featuring a spiro-cyclic guanidine unit.Chapter4 deals with acomparative study on transition metal-catalyzed cycloisomerizations of propargylicureas derived in situ from secondarypropargylamines and tosyl isocyanate. The influence of the catalytic system onthe reaction outcome was thoroughly studied with two model examples, resultingin the establishment of two selective protocols for both O- and N-cyclizations,leading to oxazolidin-2-imines and imidazolidin-2-ones, respectively. Anattempt to rationalize the observed chemoselectivity is given.Chapter5 is dedicated to theunexpected regio- and chemoselectivity of cationic gold-catalyzedcycloisomerizations of propargylic ureas derived in situ from secondary propargylamines and aryl or alkylisocyanates, providing an efficient access to the 3,4-dihydropyrimidin-2(1H)-one core.Finally,General conclusions and perspectives are highlighted. status: published

Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Обычная таблица"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0pt 5.4pt 0pt 5.4pt; mso-para-margin:0pt; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;}Thisthesis is devoted to the exploration of the strategies for the synthesis ofnitrogen-containing medium-sized rings fused with benzene or indole. Theimplemented approaches are based on several carbocyclization reactionsdeveloped previously in our laboratory which involve the construction of thekey C-C bond with the simultaneous assembly of the medium-sized ring. The elaboratedprotocols rely on modern transition metal catalysis and utilize readilyavailable starting materials.Chapter 1 serves as anintroduction into the chemistry of the title heterocycles, highlighting theiroccurrence in nature, biological properties and existing methodologies fortheir synthesis. The goals of the current research are also summarized in thischapter.Chapter 2 is dedicatedto the diversification of the 3-benzazepine scaffold using A3-couplingas a tool for the generation of propargylamine precursors for furtherPd-catalyzed intramolecular alkyne hydroarylation (reductive Heck reaction).Chapter 3 describesthe development of a novel protocol for a tandem Heck-Suzuki reaction and itsfurther application for diversification of the 3-benzazepine scaffold. A broadoptimization survey as well as detailed studies on the scope and limitations ofthis procedure are included.Chapter 4 deals withthe application of the Pd-catalyzed intramolecular alkyne hydroarylationreaction for the construction of the azocino[4,5,6-cd]indole framework. Some interesting structural features of thetitle heterocycles are commented.Chapter 5 discussesthe elaboration of the AuPPh3Cl/AgOTf-catalyzed protocol for the intramolecular alkyne hydroarylation processleading to azocino[5,4-b]indoles. A close look on thereactions with terminal propargylic amides resulted in the isolation and characterizationof hitherto unknown cyclized products interesting for the mechanisticunderstanding of such processes.Finally, General conclusions and perspectives arehighlighted. status: published