29 research outputs found

    Phosphorus-nitrogen compounds. Part 35. Syntheses, spectroscopic and electrochemical properties, and antituberculosis, antimicrobial and cytotoxic activities of mono-ferrocenyl-spirocyclotetraphosphazenes

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    Aydin, Betul/0000-0002-9092-1350; okumus, aytug/0000-0002-2169-5695; Hokelek, Tuncer/0000-0002-8602-4382; Simsek, Hulya/0000-0001-8636-9033The reactions of octachlorocyclotetraphosphazene, N4P4Cl8, with N-alkyl-N-mono-ferrocenyldiamines, FcCH(2)NH(CH2)(n)NHR1 [n = 2, Fc = ferrocene, R-1 = Me (1); n = 2, R-1 = Et (2) and n = 3, R-1 = Me (3)], led to the formation of monoferrocenyl-spirocyclotetraphosphazenes (4-6). When the reactions were carried out with excess pyrrolidine, morpholine and 1,4-dioxa-8-azaspiro[4,5] decane (DASD), the fully substituted products (4a-6c) were obtained in high yields. The structures of all the phosphazene derivatives were characterized by MS, FTIR, H-1, C-13 and P-31 NMR, HSQC and HMBC techniques. The crystal structures of 4a and 5a were determined by X-ray crystallography. The electrochemically reversible one-electron oxidation of Fc redox centers was observed for cyclotetraphosphazenes. The fully substituted phosphazenes (4a-6c) were evaluated for their antituberculosis activity against reference strain Mycobacterium tuberculosis H37Rv, and compounds 4a-6a and 5c were found to be active. The antibacterial activities of phosphazenes 4a-6c against G(+) and G(-) bacteria and their antifungal activities against yeast strains were carefully scrutinized. The results indicate that compounds 4a-6a, 6b, 4c and 5c are very effective against yeast strains. The anticandidal activities of 6a and 6b make them promising anticandidal agents. The interactions of these compounds with plasmid DNA and their cytotoxic activity against L929 fibroblast and DLD-1 colon cancer cell lines were also investigated.Turkish Academy of Sciences (TUBA)Turkish Academy of SciencesThe author Z. K. thanks Turkish Academy of Sciences (TUBA) for partial support of this work

    Randomised-controlled feasibility study evaluating the REgulate your SItting Time (RESIT) intervention for reducing sitting in individuals with type 2 diabetes: a process evaluation

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    Data availability statement: Data are available in a public, open access repository. The datasets supporting the conclusions of this article are available in Figshare, 10.17633/rd.brunel.25144490. The raw qualitative data (transcripts) are not publicly available due to privacy restrictions. Further details on the qualitative data and analysis that supports the findings of this study are available upon request to the corresponding author.Strengths and Limitations of This Study: ⇒ A comprehensive mixed- methods process evaluation was conducted that has strengthened the learnings from this feasibility trial. ⇒ Qualitative and quantitative data were integrated to provide an in- depth understanding of factors affecting trial and intervention implementation. ⇒ The quantitative data analysis was limited to the participants who responded to the process evaluation questionnaires, which could influence the findings.Objectives: The REgulate your SItting Time (RESIT) is a tailored intervention targeting reductions and breaks in sitting in adults with type 2 diabetes mellitus (T2DM). A feasibility trial of RESIT had been conducted and the purpose of this paper is to report findings from the process evaluation. Design: A mixed-methods process evaluation within a randomised controlled feasibility trial. Setting: The study was conducted remotely in the community. Participants: Ambulatory individuals with T2DM aged 18–85 years. Intervention: A tailored intervention comprising an online education session, regular health coaching and technology for self-monitoring behaviour and prompting breaks in sitting. Primary and secondary outcome measures: Questionnaires (intervention participants n=22 at both 3 and 6 months; control participants n=21 at 3 months, n=29 at 6 months) and interviews (n=30, with n=13 intervention participants, n=12 control participants, n=5 health coaches) to assess perceptions of the intervention components, strategies and barriers for sitting less, the role of the study evaluation measures, and reasons for taking part. Results: The trial operated a largely successful online education element for those in the intervention group (82% completion; ≥76% engagement in individual educational elements). There was good use of self-monitoring and prompt technology (apps and wearables) with 73% of participants reporting using these at 6 months. Health coaching had high engagement and was perceived as enjoyable and useful. Data revealed strategies used for behaviour change (eg, active functional tasks) alongside barriers to change (eg, restrictions at work). There were also potential behavioural influences from the study evaluation measures (eg, activity measures increasing awareness and execution of behaviours) for both intervention and control participants. Conclusions: A comprehensive process evaluation identified successful intervention elements (ie, online education, health coaching, wearables and smartphone apps) alongside strategies and barriers to behaviour change. These findings can inform future sedentary behaviour interventions for adults with T2DM and a definitive randomised controlled trial evaluating RESIT. Trial registration number: ISRCTN14832389.This work was supported by Diabetes UK grant number (19/0005972). This research is also supported by the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

    A randomised-controlled feasibility study of the REgulate your SItting Time (RESIT) intervention for reducing sitting time in individuals with Type 2 diabetes: study protocol

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    © The Author(s) 2021. Background People with type 2 diabetes mellitus (T2DM) generally spend a large amount of time sitting. This increases their risk of cardiovascular disease, premature mortality, diabetes-related complications and mental health problems. There is a paucity of research that has evaluated interventions aimed at reducing and breaking up sitting in people with T2DM. The primary aim of this study is to assess the feasibility of delivering and evaluating a tailored intervention to reduce and break up sitting in ambulatory adults with T2DM. Methods This is a mixed-methods randomised controlled feasibility trial. Participants (n=70) with T2DM aged 18-85 years who sit ≥7 h/day and are able to ambulate independently will be randomly allocated to receive the REgulate your SItting Time (RESIT) intervention or usual care (control group) for 24 weeks. RESIT is a person-focused intervention that delivers a standardised set of behaviour change techniques to the participants, but the mode through which they are delivered can vary depending on the tools selected by each participant. The intervention includes an online education programme, health coach support, and a range of self-selected tools (smartphone apps, computer-prompt software, and wearable devices) that deliver behaviour change techniques such as self-monitoring of sitting and providing prompts to break up sitting. Measures will be taken at baseline, 12 and 24 weeks. Eligibility, recruitment, retention and data completion rates will be used to assess trial feasibility. Sitting, standing and stepping will be measured using a thigh-worn activity monitor. Cardiometabolic health, physical function, psychological well-being, sleep and musculoskeletal symptoms will also be assessed. A process evaluation will be conducted including evaluation of intervention acceptability and fidelity. Discussion This study will identify the feasibility of delivering a tailored intervention to reduce and break up sitting in ambulatory adults with T2DM and evaluating it through a randomised controlled trial (RCT) design. The findings will inform a fully powered RCT to evaluate the effectiveness of the intervention. Trial registration ISRCTN, ISRCTN14832389; Registered 6 August 2020.Diabetes UK grant number [19/0005972

    Phosphorus-nitrogen compounds: part 71. Novel unsymmetrically-substituted dispiro-cyclotriphosphazenes: synthesis, characterization, antituberculosis activity, and phototunable charge storage studies

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    The aim of this research is to synthesize and characterize new organic-inorganic hybrid multi-heterocyclic dichlorodispiro(N/N)cyclotriphosphazenes and to elucidate their antituberculosis activities. To achieve this aim, primarily, trans (6a-11a) and cis (6b-11b) unsymmetrical dichlorodispiro(N/N)cyclotriphosphazenes were obtained from ferrocenyldiamines (4 and 5) and benzyl-pendant armed tetrachloromonospirophosphazenes as starting materials. Several spectroscopic techniques (mass spectrometry, FTIR, and 1H, 13C, and 31P NMR), as well as elemental analysis, were employed to characterize the new phosphazenes. All unsymmetrically substituted phosphazenes are expected to be racemic mixtures (RR '/SS ' and RS '/SR ') due to two different stereogenic P-centers. In addition, the molecular and crystal structures of cis-6b, cis-10b, and cis-11b isomers were elucidated via single-crystal X-ray crystallography. They belong to centrosymmetric C2/c, P21/c, and P1 space groups, respectively; thus, their crystal lattices must contain both the enantiomers, RR '/SS ' or SR '/RS '. Moreover, only one oxidation-reduction wave was observed for the ferrocenyl-dispirophosphazenes in the reversible cyclic voltammograms. The HOMO and LUMO energy values of the phosphazenes were calculated using the oxidation potential (Eox) and the optical band gap values using Tauc plots, respectively. To determine the phototunable charge storage properties of the four dispirophosphazenes, their memory functions were investigated under UV illumination. The antituberculosis activities of the dichlorodispiro(N/N)cyclotriphosphazenes trans-6a, cis-6b, trans-10a, and cis-10b against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain were evaluated. The results showed that among these compounds, trans-6a (MIC value 18 mu g mL-1) was much more effective than the other phosphazenes. Unsymmetrical cis/trans dispirocyclotriphosphazenes were prepared. The electrochemical behaviors and phototunable charge storage properties of the compounds were determined. The antituberculosis activities were examined against M. tuberculosis H37Rv.Z. K. thanks the Turkish Academy of Sciences (TBA) for partial support of this work. T. H. is grateful to the Hacettepe University Scientific Research Project Unit (Grant No. 013 D04 602 004).Z. K. thanks the Turkish Academy of Sciences (TUBA) for partial support of this work. T. H. is grateful to the Hacettepe University Scientific Research Project Unit (Grant No. 013 D04 602 004)

    Synthesis and spectroscopic properties of (N/O) mono- and dispirocyclotriphosphazene derivatives with benzyl pendant arms: study of biological activity

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    The Cl replacement reactions of hexachlorocyclotriphosphazene (trimer; N3P3Cl6) with sodium (N-benzyl)aminopropanoxides (1 and 2) produced monospiro- (3 and 4), cis-, and trans-dispirocyclotriphosphazenes (13-16). The monospiro tetrakis-aminocyclotriphosphazenes (5-12) were obtained by the Cl substitutions of 3 and 4 with different secondary amines. The cis- (13 and 14) and trans-dispirophosphazenes (15 and 16) possessed 2 chiral P centers, and they were able to present meso and racemic forms, respectively. Moreover, the structures of compounds 5 and 14 were designated using X-ray data. The absolute configuration of compound 14 was found as SR in the solid state. Analytical and spectroscopic data of the phosphazenes were consistent with their suggested structures. Antimicrobial activities of the benzyl-pendant-armed cyclotriphosphazenes were scrutinized against G(+) and G(-) bacteria and yeast strains. The bacterium most affected by the synthesized compounds was Pseudomonas aeruginosa. Minimum inhibitory concentrations and minimal bacterial concentrations were in the range of 125-500 mu M. Interactions between the phosphazenes (3-12 and 15) and plasmid DNA were studied with agarose gel electrophoresis. The phosphazeneDNA interaction studies of the cyclotriphosphazenes revealed that phosphazenes 3, 4, and 15 had a substantial effect on supercoiled DNA by cleavage of the double helix

    Mono- and dispirocyclotriphosphazenes containing 4-bromobenzyl pendant arm(s): Synthesis, spectroscopy, crystallography and biological activity studies

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    The N/N donor-type bromobenzyldiamines (1-3) were successively prepared by reduction of Schiff bases formed as a result of condensation reactions of 4-bromobenzaldehyde with aliphatic diamines. The Cl exchange reactions of hexachlorocyclotriphosphazene (HCCP; trimer; N3P3Cl6; 4) with the bidentate ligands (1-3) produced the new monospiro- (5-7) and dispirocyclotriphosphazenes (8-13) containing 4-bromo-benzyl pendant arm(s). The tetrachloro phosphazenes (5-7) were reacted with pyrrolidine, tetra-1,4-dioxa-8-azaspiro [4.5]decane (DASD) and piperidine to give the tetraamino substituted mono-spirophosphazenes (5a-7c). The spectral analyses of all the phosphazenes were made using appropriate spectroscopic methods; such as FTIR, H-1, C-13, P-31 NMR and ESI-MS. The molecular and crystal structures of 5, 6, 7 and 12 were also determined by X-ray crystallography. On the other hand, the antimicrobial activities of the phosphazenes were evaluated against G (-) and G (+) bacteria and fungi. Some of the tetraaminophosphazenes were found to be very active against several bacteria and fungi. Besides, the interactions of the cyclotriphosphazenes with plasmid DNA were investigated using agarose gel electrophoresis. (C) 2020 Elsevier B.V. All rights reserved

    Phosphorus-nitrogen compounds: part 53-synthesis, characterization, cytotoxic and antimicrobial activity, DNA interaction and molecular docking studies of new mono- and dispirocyclotriphosphazenes with pendant arm(s)

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    Mono-/dispirocyclotriphosphazenes with pendant arm(s) are robust, but they are less investigated inorganic ring systems. In this study, a series of mono (3 and 4)- and dispirocyclotriphosphazenes with 4-chloro-benzyl pendant arm(s) (13-16) was obtained from the Cl exchange reactions of hexachlorocyclotriphosphazene with sodium (N-benzyl)aminopropanoxides (1 and 2). When compound (3) reacted with excess pyrrolidine, morpholine, tetra-1,4-dioxa-8-azaspiro[4,5]decane (DASD) and piperidine, the fully substituted monospirocyclotriphosphazenes (7, 9, 10 and 12) occurred. But, the reactions of 4 with excess piperidine and morpholine produced the gem-piperidino (5)- and morpholino (6)-substituted monospirocyclotriphosphazenes, whereas the reactions of 4 with excess pyrrolidine and DASD gave the fully substituted monospirocyclotriphosphazenes (8) and (11). However, it should be indicated that these derivatives were obtained to be used for the investigation of their spectral, stereogenic and biological properties. The structures of 5, 7 and 14 were determined crystallographically. X-ray data of 5 and 14 displayed that both of compounds were chiral in solid state, and their absolute configurations were assigned as R and RR. Additionally, the antimicrobial activities of phosphazenes were investigated. Minimum inhibitory concentrations, minimal bacterial concentrations and minimum fungicidal concentrations of phosphazenes were determined. The interactions of phosphazenes with plasmid DNA were evaluated by agarose gel electrophoresis. The cytotoxic activities of compounds were studied against L929 fibroblast and DLD-1 colon cancer cells. In addition, density functional theory calculations of 5, 7 and 14 were reported, and their molecular docking studies with DNA, E. coli DNA gyrase and topoisomerase IV were presented

    Art and the artist in the literary works of Elsa Triolet

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    This thesis takes a representative selection of Triolet's works to study the themes of writing and creativity as they are presented in the novels. These are all portraits of artists and the accounts of the search for a synthesis of aesthetic freedom and ethical responsibility. It considers Triolet's importance as a foreign writer, adopting a new creative language to be adopted by a different cultural environment, to be essential in understanding her importance to the French literary tradition. By emphasising her formative years in the avant-garde circles of prerevolutionary Russia, my study demonstrates her considerable contribution to the meeting of Russian and French aesthetic theories. I extend this with close textual readings of certain works to demonstrate her techniques in novelistic construction which reveal many Formalist practices before Formalist works in translation made their official influence on creative methods. The introduction considers the reasons for Triolet's neglect as a writer. It then considers various contemporary and recent critical appraisals which indicate the interest she has received until present and which allow me to define my own critical approach. Part One traces Triolet's literary evolution from her formative years in Russia, through exile to her first publications in Russian. It then considers her insertion into French literary activity, and her association with the schools of socialist realism and the "nouveau roman". Part Two examines two traditional novels which portray the creative and metaphorical roles of the artist and his work, showing the constant conflict between private and public lives. In Part Three, I show how aspects of novelistic traditionalism are gradually foregrounded so that the work develops a dual-sided character where it both narrates and examines the processes of its own narration. In Part Four, this move to highly self-conscious aesthetics demonstrates an idiosyncratic exploration of new paths for the novel that bring visual, auditive and cinematographic media into the traditional domain of written art. Accompanying the very post-modernist experimentation, I show how this research within the novel into the novel's own future has an ethical and redemptive purpose whose final conclusion is that creativity and human freedom are inexorably interwoven

    Phosphorus-nitrogen compounds. Part 35. Syntheses, spectroscopic and electrochemical properties, and antituberculosis, antimicrobial and cytotoxic activities of mono-ferrocenyl-spirocyclotetraphosphazenes

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    The reactions of octachlorocyclotetraphosphazene, N4P4Cl8, with N-alkyl-N-mono-ferrocenyldiamines, FcCH(2)NH(CH2)(n)NHR1 [n = 2, Fc = ferrocene, R-1 = Me (1); n = 2, R-1 = Et (2) and n = 3, R-1 = Me (3)], led to the formation of monoferrocenyl-spirocyclotetraphosphazenes (4-6). When the reactions were carried out with excess pyrrolidine, morpholine and 1,4-dioxa-8-azaspiro[4,5] decane (DASD), the fully substituted products (4a-6c) were obtained in high yields. The structures of all the phosphazene derivatives were characterized by MS, FTIR, H-1, C-13 and P-31 NMR, HSQC and HMBC techniques. The crystal structures of 4a and 5a were determined by X-ray crystallography. The electrochemically reversible one-electron oxidation of Fc redox centers was observed for cyclotetraphosphazenes. The fully substituted phosphazenes (4a-6c) were evaluated for their antituberculosis activity against reference strain Mycobacterium tuberculosis H37Rv, and compounds 4a-6a and 5c were found to be active. The antibacterial activities of phosphazenes 4a-6c against G(+) and G(-) bacteria and their antifungal activities against yeast strains were carefully scrutinized. The results indicate that compounds 4a-6a, 6b, 4c and 5c are very effective against yeast strains. The anticandidal activities of 6a and 6b make them promising anticandidal agents. The interactions of these compounds with plasmid DNA and their cytotoxic activity against L929 fibroblast and DLD-1 colon cancer cell lines were also investigated
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