Einfluss elektronischer Faktoren auf die katalytische Aktivität von chiral-at-metal Ruthenium Komplexen

Transition metal complexes with metal centered chirality, also called chiral-at-metal complexes, provide a useful and expandable toolbox for asymmetric catalysis. This thesis focuses on the synthesis of chiralat- metal ruthenium complexes with previously unused substituents to explore the electronic influence concerning reactivity and enantioselectivity. Within the first part of the thesis (Chapter 3.1) the synthesis of bis(pyridinyl-NHC) ruthenium complexes with 5-bromo and 4-dimethyl amino substitution at the pyridine moiety is presented. During the investigation of structural isomers, the formation of a mixed normal/abnormal NHC complex was observed and further investigated. By lowering the temperature and extending the reaction time, a ratio of 9.8:1 in favor of the mixed nNHC/aNHC complex was achieved. Formation of this mixed coordination was only observed for 5-CF3 (62%) and 5-bromo (53%) substituted complexes, while trimethylsilyl as well as 4-dimethyl amino substitution showed selective formation of the nNHC complex. The separation of diastereomeric complexes was realized by application of (tolylsulfonyl)benzamides as chiral auxiliaries. Due to the non–C2–symmetry of the mixed complexes, four diastereomers can be formed. Two of the resulting complexes were stable against silica gel and were found to consist of the same metal-centered chirality. Brùnsted acid induced labilization of the auxiliary ligand under retention of configuration created the corresponding complexes with up to ] 99% ee. The same protocol was applied to di-isopropylphenyl substituted complexes, providing access to sterically more demanding complexes. The second part of this thesis (Chapter 3.2) focuses on the application of the obtained complexes in asymmetric catalysis. In detail, the ring contraction of isoxazoles to 2H-azirines was investigated. Here, the 5-bromo substituted complex allowed a faster conversion at lower temperatures compared to the previously reported rhodium complexes. After a broad screening of reaction conditions, a maximum of 67% ee was obtained. During the investigation, non-linear effects were observed as well as a light induced racemisation of the product catalyzed by the applied ruthenium complexes. For the asymmetric C(sp3)-H amination reaction, the newly obtained mixed nNHC/aNHC complex was found to provide an 160-fold increased turnover frequency compared to the analogus nNHC complex. This allowed a reduction of the reaction time down to 10 min. For the alkynylation of trifluoroacetophenone, the differences between the nNHC and mixed nNHC/aNHC complexes were negligible. For a propargylic substitution, the di-isopropylphenyl substituted complexes showed higher enantioselectivity (up to 55% ee), the mixed nNHC/aNHC complex provided low enantioselectivity (11% ee) while the bis-nNHC complex induced no enantioselectivity. Initial UV-Vis studies with acyl imidazoles indicated a broad absorption around 550 nm. Among the tested complexes, the 4-dimethyl amino substitution showed a maximum at 640 nm, followed by the mixed nNHC/aNHC complexes, while the bis-nNHC complexes showed maxima at 520 nm. This could be used in further studies concerning the potential application of ruthenium complexes in asymmetric photocatalysis

Psychotherapies for borderline personality disorder : a focused systematic review and meta-analysis

Background: A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD). Aims: To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely. Method: We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition. Results: Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD) −0.54, P = 0.006; psychosocial functioning: SMD −0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P < 0.0007; suicide-related outcomes: risk ratio 0.10, P < 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD −0.66, P = 0.002; psychosocial functioning: SMD −0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference −8.49, P < 0.00001), manual-assisted cognitive therapy (self-harm: mean difference −3.03, P = 0.03; suicide-related outcomes: SMD −0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD −0.48, P = 0.002). Conclusions: There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings

Pharmacological interventions for people with borderline personality disorder

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of pharmacological treatment for adolescents and adults with borderline personality disorder (BPD)

Psychological therapies for people with borderline personality disorder

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of psychological therapies for people with borderline personality disorder (BPD)

Relevance of philosophy of life and optimism for psychological distress among individuals in a stage where death is approaching

The purpose was to investigate the relevance of philosophy of life as well as optimism for the psychological distress among Swedish individuals in a stage where death is approaching. Sixty-nine persons were included; of these were 42 patients newly diagnosed with advanced gastrointestinal cancer and 26 were partners to these patients. The participants' philosophy of life was studied through a semi-structured interview. The interview statements were subjected to content analysis. Optimism was measured by the Life Orientation Test and psychological distress by the Hospitality and Depression Scale. The results showed that optimistic respondents had less psychological distress. Two aspects of philosophy of life had relevance for such distress. These were wondering about why the cancer had occurred and having a feeling of being able to live a good life having or living near a person with advanced cancer. In conclusion, the above-mentioned aspects of philosophy of life as well as optimism have relevance for psychological distress among these individuals, which stress the importance that health-care staff address both patients' and their partners' concerns about their philosophy of life

Psychological therapies for adolescents with borderline personality disorder (BPD) or BPD features-A systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis.

ObjectivesTo review the effectiveness of psychological therapies for adolescents with borderline personality disorder (BPD) or BPD features.MethodsWe included randomized clinical trials on psychological therapies for adolescents with BPD and BPD features. Data were extracted and assessed for quality according to Cochrane guidelines, and summarized as mean difference (MD) with 95% confidence intervals (CI) for continuous data and as Odds ratios (OR) with 95% CI for dichotomous data. Risk of bias was assessed using Cochrane's risk of bias tool for each domain. When possible, we pooled trials into meta-analyses, and used Trial Sequential Analysis (TSA) to control for random errors. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).Results10 trials on adolescents with BPD or BPD features were included. All trials were considered at high risk of bias, and the quality of the evidence was rated as "very low". We did TSA on the primary outcome and found that the required information size was reached. The risk of random error was thus discarded.ConclusionOnly 10 trials have been conducted on adolescents with BPD or BPD features. Of these only few showed superior outcomes of the experimental intervention compared to the control intervention. No adverse effects of the interventions were mentioned. Attrition rates varied from 15-75% in experimental interventions. The overall quality was very low due to high risk of bias, imprecision and inconsistency, which limits the confidence in effect estimates. Due to the high risk of bias, high attrition rates and underpowered studies in this area, it is difficult to derive any conclusions on the efficacy of psychological therapies for BPD in adolescence. There is a need for more high quality trials with larger samples to identify effective psychological therapies for this specific age group with BPD or BPD features

Individual participant data systematic reviews with meta-analyses of psychotherapies for borderline personality disorder

Introduction The heterogeneity in people with borderline personality disorder (BPD) and the range of specialised psychotherapies means that people with certain BPD characteristics might benefit more or less from different types of psychotherapy. Identifying moderating characteristics of individuals is a key to refine and tailor standard treatments so they match the specificities of the individual participant. The objective of this is to improve the quality of care and the individual outcomes. We will do so by performing three systematic reviews with meta-analyses of individual participant data (IPD). The aim of these reviews is to investigate potential predictors and moderating patient characteristics on treatment outcomes for patients with BPD.Methods and analysis We performed comprehensive searches in 22 databases and trial registries up to October 6th 2020. These will be updated with a top-up search up until June 2021. Our primary meta-analytic method will be the one-stage random-effects approach. To identify predictors, we will use the one-stage model that accounts for interaction between covariates and treatment allocation. Heterogeneity in case-mix will be assessed with a membership model based on a multinomial logistic regression where study membership is the outcome. A random-effects meta-analysis is chosen to account for expected levels of heterogeneity.Ethics and dissemination The statistical analyses will be conducted on anonymised data that have already been approved by the respective ethical committees that originally assessed the included trials. The three IPD reviews will be published in high-impact factor journals and their results will be presented at international conferences and national seminars.PROSPERO registration number CRD42021210688