Synthesis and characterization of palladacyclopentadiene complexes with N-heterocyclic carbene ligands

New palladacyclopentadiene compounds containing different chelate NHC-thioether and NHC-pyridine ligands have been prepared by transfer of the functionalized carbenes from the respective silver complexes to the polymeric precursors [PdC-COOR)4]n (R = Me, t-Bu). Their dynamic behaviour in solution was discussed and the solid-structure of 2c was determined by X-ray crystallography. The treatment of [Pd(C-COOCH3)4]n with two equivalents of the carbene silver complexes led to the (NHC)2Pd(C4-COOCH3)4 derivatives (3cei), a new class of compounds with only PdeC bonds. A serious limitation to this synthetic procedure is an excessive steric crowding around the metal centre. The complexes 3 are present in solution as a mixture of two atropoisomers, due to restricted rotation around the CarbeneePd bond. The kinetics of equilibration between the two configurational isomers was studied for complex 3c, which was also structurally defined by X-ray crystallography (anti isomer). Finally a synthetic protocol was set up for the synthesis of mixed NHC-Phosphine and NHC-Isocyanide palladacyclopentadiene complexes. In this procedure the order of addition of the reactants is of great importanc

Examining childhood trauma and comorbid mental disorders among people with opioid use disorder

Opioid use disorder (OUD) is characterised by persistent opioid use despite the experience of harm. Current literature suggests that childhood trauma and mental disorders are risk factors for illicit OUD. However, little is known about the effects of childhood trauma and mental disorders on OUD-related harm. Our understanding of this relationship is also limited by imprecise childhood trauma and mental disorder prevalence data; few studies on people prescribed opioids for chronic non-cancer pain (CNCP); and a lack of research on interventions that reduce harm related to childhood trauma and mental disorders among people with OUD. This thesis uses multiple study methods on data from several different opioid-using populations to broaden our understanding of the relationship between childhood trauma, mental disorders, and OUD. The studies in this thesis aimed to 1) estimate the prevalence of specific childhood trauma types and mental disorders among people with OUD; 2) investigate childhood trauma as an independent risk factor for OUD among a large sample of people prescribed opioids for CNCP; 3) explore the effects of childhood trauma and mental disorders on OAT engagement, crime, and mortality among people with illicit OUD; and 4) examine the associations between OAT and causes of mortality, including suicide, among people with OUD. Multiple key findings emerged from this thesis. The first two studies confirmed that people with OUD experience childhood trauma and mental disorders at far higher rates than the general population. The third study of people prescribed opioids for CNCP found that childhood trauma independently increased the risk of OUD after controlling for mental disorders and other known OUD risk factors. The fourth study found that childhood trauma and most mental disorders were related to poorer OAT engagement and higher criminal offending rates among people with OUD. The fifth study, a systematic review and meta-analysis, found that OAT was associated with reduced risk of multiple causes of mortality, including suicide, among people with OUD. Findings from these studies highlight the importance of addressing childhood trauma and mental disorders in both the treatment of OUD and the management of CNCP with pharmaceutical opioids. The results can inform clinical guidelines, policy, and future research that impact people with OUD and those prescribed opioids for CNCP

Computational investigations on the unexpected extrusion of molecular iodine in Pd(II) σ-butadienyl complexes

4reservedmixedSCATTOLIN, THOMAS; VISENTIN, Fabiano; CANOVESE, Luciano; SANTO, ClaudioScattolin, Thomas; Visentin, Fabiano; Canovese, Luciano; Santo, Claudi

Reactions of palladium(0) olefin complexes stabilized by some different hetero- and homo-ditopic spectator ligands with propargyl halides

Several new allenyl and propargyl complexes have been obtained by oxidative addition with propargyl chlorides of palladium (0) olefin complexes stabilized by N−N, P−P, N−P, N−S. and N−C homo− and hetero−ditopic spectator ligands. The oxidative addition of some of the isolated palladium(0) olefin derivatives with 3−chloro−1−propyne and 3−chloro−1− phenyl−propyne has been investigated and the ensuing tautomeric mixtures bearing propargyl and allenyl fragmenst η1− coordinated isolated. As a consequence of a detailed kinetic study, we have analyzed the influence of the electronic and steric parameters of the involved reactants and hypothesized the mechanism of reaction. The tautomeric rearrangement of one allenyl isomer into its propargyl counterpart was also investigated and in this case the complete determination of all the rate constants involved has been obtained. Beside these studies, two very rare η3−propargyl palladium derivatives have been isolated and characterized

Halogen metathesis in Pd(II) σ-butadienyl complexes

4reservedmixedSCATTOLIN, THOMAS; VISENTIN, Fabiano; CANOVESE, Luciano; SANTO, ClaudioScattolin, Thomas; Visentin, Fabiano; Canovese, Luciano; Santo, Claudi

All-cause and cause-specific mortality among people with regular or problematic cocaine use:A systematic review and meta-analysis

Aims: To estimate pooled all-cause and cause-specific mortality risk for people with regular or problematic cocaine use.Methods: Systematic review and meta-analysis of prospective or retrospective cohort studies or clinical trials (n ≥30) of people with regular or problematic cocaine use with data on all-cause or cause-specific mortality. Of 2808 papers, 28 were eligible and reported on 21 cohorts, with a total 170 019 individuals. Cohorts identified based on acute care for drug poisoning or other severe health presentation were excluded. Title/abstract screening was conducted by one reviewer; a second reviewer independently checked 10% of excluded studies. Two reviewers conducted full-text screening. Data were extracted by one reviewer and checked by a second. A customized review-specific study reporting quality/risk of bias tool was used. Data on crude mortality rates (CMR) and standardized mortality ratios were extracted for both all-cause and cause-specific mortality. Standardized mortality ratios were imputed where not provided by the author using extracted data and information from the Global Burden of Disease Study 2017. Data were pooled using a random-effects model.Results: The pooled all-cause crude mortality rate was 1.24 per 100 person-years [95% confidence interval (CI) = 0.86, 1.78; n = 16 cohorts], but with considerable heterogeneity (I2 = 98.8%). The pooled all-cause standardized mortality ratio (SMR) was 6.13 (95% CI = 4.15, 9.05; n = 16 cohorts). Suicide (SMR = 6.26, 95% CI = 2.84, 13.80), accidental injury (SMR = 6.36, 95% CI = 4.18, 9.68), homicide (SMR = 9.38, 95% CI 3.45-25.48) and AIDS-related mortality (SMR = 23.12, 95% CI = 11.30, 47.31) were all elevated compared with age and sex peers in the general population.Conclusions: There are elevated rates of mortality among people with regular or problematic cocaine use for traumatic deaths and deaths attributable to infectious disease