Chromium Complexes with Benzanellated N-heterocyclic Phosphenium Ligands - Synthesis, Reactivity and Application in Catalytic CO2 Reduction.

A chromium complex carrying two benzanellated N-heterocyclic phosphenium (bzNHP) ligands was prepared by a salt metathesis approach. Spectroscopic studies suggest that the anellation enhances the π-acceptor ability of the NHP-units, which is confirmed by the facile electrochemical reduction of the complex to a spectroscopically characterized radical anion. Co-photolysis with H2 allowed extensive conversion into a σ-H2-complex, which shows a diverse reactivity towards donors and isomerizes under H-H bond fission and shift of a hydride to a P-ligand. The product carrying phosphenium, phosphine and hydride ligands was also synthesized independently and reacts reversibly with CO and MeCN to yield bis-phosphine complexes under concomitant Cr-to-P-shift of a hydride. In contrast, CO2 was not only bound but reduced to give an isolable formato complex, which reacted with ammonia borane under partial recovery of the metal hydride and production of formate. Further elaboration of the reactions of the chromium complexes with CO2 and NH3BH3 allowed to demonstrate the feasibility of a Cr-catalyzed transfer hydrogenation of CO2 to methanol. The various complexes described were characterized spectroscopically and in several cases by XRD studies. Further insights in reactivity patterns were provided through (spectro)electrochemical studies and DFT calculations.

The Noble Addendum of a Phosphenium Ligand to a Base Metal: Coordination, Activation, and Hydrogenation of Alkenes and Alkynes on a Chromium Complex.

The synthesis of a new bis-NHP complex (NHP=N-heterocyclic phosphenium) of chromium via salt metathesis and studies of its reactivity are reported. Photochemical reactions with H2 and selected olefins give rise to non-isolable H2- and π-alkene complexes identified spectroscopically, while internal alkynes react via activation of the triple bond to yield isolable metalla-phospha-cyclobutenes characterized by spectroscopic and XRD data. DFT studies give a preliminary account of the bonding in H2- and alkene-complexes and explain the different reactivity towards alkenes and alkynes as the consequence of kinetic effects. Photolysis of the bis-NHP-complex in the presence of H2 and olefins or alkenes enables the catalytic hydrogenation of the organic substrates, while the π-ethene complex mediates the catalytic hydrogenation of ethene in a dark reaction. The similarities and differences between both catalytic processes are shortly discussed.

Annellated 1,3,4,2-Triazaphospholenes-Simple Modular Synthesis and a First Exploration of Ligand Properties.

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P-Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P-Br bonds in TAPs as in better known isoelectronic diazaphospholenes.

A neutral analogue of a phosphamethine cyanine.

Reaction of an imidazolio-phosphide with an N-heterocyclic bromo-borane and NaH afforded a neutral analogue of a phosphamethine cyanine cation. DFT studies were used to analyse the dative bonding across P-C/B bonds and the conformational preferences and imply that the observed conformation is imposed by sterics.

A PH-functionalized dicationic bis(imidazolio)diphosphine.

Reaction of the iodide salt of a secondary imidazolio-iodophosphine [(L)PHI]I (L+ = 1,3-diarylimidazolium-yl) with an imidazolio-phosphide (L)PH in the presence of GaI3 afforded the isolable salt of a dicationic, bis(imidazolio)-substituted dihydro-diphosphine [(L)2P2H2][GaI4]2. Non-preparative formation of the cationic diphosphines was also observed upon spontaneous "dehalo-coupling" of [(L)PHI]+, or in reactions of [(L)PHI]I and (L)PH in the absence of GaI3. Further reaction of [(L)2P2H2]2+ with (L)PH produced an iodide salt of a known (bis)imidazolio-diphosphide monocation [(L)2P2H]+. The identity of cationic diphosphines and diphosphides was established by single-crystal X-ray diffraction studies. NMR spectroscopy revealed that dications [(L)2P2H2]2+ exist as a mixture of meso- and rac-diastereomers in solution. Computational studies confirmed the stereochemical assignment of the isomers observed, and gave insight into the bonding situation of the diphosphine dications.

Synthesis and Ambiphilic Reactivity of Metalated Diorgano-Phosphonite Boranes.

Unprecedented metalated phosphonite boranes were prepared from PH-substituted precursors and silyl amides. Although potassium derivatives were thermally stable and could even be isolated and structurally characterised, lithiated analogues proved to be unstable towards self-condensation under cleavage of LiOR at ambient temperature. Reaction studies revealed that the metalated phosphonite boranes exhibit ambiphilic character. Their synthetic potential as nucleophilic building blocks was demonstrated in the synthesis of the first stannylated phosphonite representing a new structural motif in phosphine chemistry.

Proton transfer vs. oligophosphine formation by P-C/P-H σ-bond metathesis: decoding the competing Brønsted and Lewis type reactivities of imidazolio-phosphines.

Studies of the protonation and alkylation of imidazolio-phosphides and deprotonation of imidazolio-phosphines reveal a complex behaviour that can be traced back to an interplay of Brønsted-type proton transfers and Lewis-type P-P bond formation reactions. As a consequence, the expected (de)protonation and (de)alkylation processes compete with reactions producing cyclic or linear oligophosphines. A careful adjustment of the conditions allows us to selectively address each reaction channel and devise specific synthesis methods for primary, secondary and tertiary imidazolio-phosphines, imidazolio-alkylphosphides, and cyclic oligophosphines, respectively. Mechanistic studies reveal that oligophosphines assemble in sequential P-P bond formation steps involving the condensation of cationic imidazolio-phosphines viaσ-bond metathesis and concomitant elimination of an imidazolium ion. Imidazolio-phosphides catalyse these transformations. Computational model studies suggest that the metathesis proceeds in two stages via an initial nucleophilic substitution under expulsion of a carbene, and a subsequent proton transfer step that generates an imidazolium cation and provides the driving force for the whole transformation. As energy barriers are predicted to be low or even absent, different elementary steps are presumed to form a network of mutually coupled equilibrium processes. Cyclic oligophosphines or their dismutation products are identified as the thermodynamically favoured final products in the reaction network.

Reversible cooperative dihydrogen binding and transfer with a bis-phosphenium complex of chromium.

The reversible reaction of H2 with a bis-phosphenium complex of chromium provides a rare example of 3d transition metal/phosphenium cooperativity. Photolysis induces the activation of H2 and yields a spectroscopically detectable phosphenium-stabilized (σ-H2)-complex, readily showing exchange with gaseous H2 and D2. Further reaction of this complex affords a phosphine-functionalized metal hydride, representing a unique example of reversible H2 cleavage across a 3d M[double bond, length as m-dash]P bond. The same species is also accessible via stepwise H+/H- transfer to the bis-phosphenium complex, and releases H2 upon heating or irradiation. Dihydrogen transfer from the H2-complex to styrene is exploited to demonstrate the first example of promoting hydrogenation with a phosphenium complex.

A randomized, controlled trial of oral propranolol in infantile hemangioma.

BACKGROUND: Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. METHODS: We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. RESULTS: Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. CONCLUSIONS: This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).

Changes in mood predict disease activity and quality of life in patients with psoriasis following emotional disclosure.

OBJECTIVE: The present study examined the effects of emotional disclosure (ED) intervention on both disease severity and quality of life in patients with psoriasis. METHODS: Fifty-nine patients were recruited (mean age, 50 years; 32 men and 27 women; mean length of diagnosis, 22 years). Individuals were randomly assigned to receive ED intervention or standard control writing intervention. Disease severity, quality of life, and mood were assessed at baseline and at 2, 8, and 12 weeks postintervention. RESULTS: Disease severity and quality of life improved in both groups over the follow-up period. Preliminary analysis suggested no differences in the magnitude of improvement between the groups. However, predictors of improvement were found to differ. Disease severity on Week 12 was predicted by changes in mood in intervention patients and seasonal variation in control patients. In contrast, quality of life on Week 12 was predicted by baseline quality of life in intervention patients, while seasonal variation approached significance for control patients. CONCLUSIONS: Changes in mood following ED predicted improvements in disease severity in patients with psoriasis. However, the degree of improvement did not differ between intervention and control patients.

Cutis verticis gyrata: three cases with different aetiologies that demonstrate the classification system.

Cutis verticis gyrata describes a scalp condition where there are convoluted folds and deep furrows that resemble the surface of the cerebral cortex. We report three cases of cutis verticis gyrata that demonstrate the current classification structure. The first case is the most commonly described primary non-essential acquired form, appearing in the scalp of an 11-year-old girl with mental retardation. The second case is the primary non-essential congenital form, presenting at birth in a baby with Noonan's syndrome. An association between cutis verticis gyrata and Noonan's syndrome has been rarely described. The third case illustrates secondary cutis verticis gyrata, occurring in a 27-year-old man with discoid eczema.

Leg ulceration and perceived health: a population based case-control study.

OBJECTIVES: To quantify the effect of leg ulceration on health-related quality of life and to estimate a health state value for leg ulceration. DESIGN: Population based case-control study. SETTING: Two New Zealand health districts (population 540,468 people). SUBJECTS: 241 people with a leg ulcer of any aetiology, and 224 controls randomly selected from the electoral roll using stratified sampling. MAIN OUTCOME MEASURES: health-related quality of life as measured by the eight domains of the Short Form 36 question Health Survey, adjusted for age, sex and confounding co-morbidities; the physical component summary and mental component summary scores of the Short Form 36 question Health Survey standardised for age and sex; preference-based health state value derived from the Short Form 36 question Health Survey. RESULTS: Completed Short Form 36 question Health Survey questionnaires were available for 230 cases (95%) and 218 controls (97%). Cases reported significantly lower mean scores than controls across all eight domains of the Short Form 36 question Health Survey (P < 0.0005). Mean domain scores for cases were also significantly lower than population norms. The mean physical component summary score for cases and controls was 45.2 versus 50.1 (P < 0.0001) and the mean mental component summary score was 48.1 for cases versus 51 for controls (P < 0.0001). The mean health state values (adjusted for age and sex) were 0.80 for cases and 0.89 for controls. CONCLUSION: Leg ulcers reduce quality of life to a similar extent as other common chronic conditions, such as arthritis and diabetes.

Leg ulceration as a long-term complication of deep vein thrombosis.

OBJECTIVE: To evaluate the role of deep vein thrombosis as a cause of leg ulcers. PATIENTS AND METHODS: A population-based, case-control study was conducted in Central and North Auckland, New Zealand. Cases comprised 241 people aged 40 to 99 years and on the electoral roll, with current leg ulcers (all types). Cases were identified by means of notification from health professionals and by self-referral. Controls were 224 people in the same age group, without leg ulcers, who were selected from the electoral roll by using a stratified random sampling process. MAIN OUTCOME MEASURES: The occurrence of leg ulceration as a consequence of exposure to deep vein thrombosis or being at high risk of deep vein thrombosis (that is, people with a family history of deep vein thrombosis, and/or a history of leg fracture and/or hip, leg, or foot surgery). RESULTS: After adjustment for age, sex, and other potential confounding factors, people who had a diagnosed thromboembolism were at almost three times higher risk of having a leg ulcer (odds ratio, 2.92; 95% confidence interval (CI), 1.47 to 6.08). In addition, people who had been at high risk of a venous thrombosis but were not diagnosed with this condition (eg, people with a history of major leg surgery) were also at increased risk of ulceration (odds ratio, 2.25; 95% CI, 1.49-3.42). Overall, 56% (95% CI, 33% - 71%) of leg ulcers were attributed to being at high risk of deep vein thrombosis. CONCLUSIONS: Deep vein thrombosis and factors that place people at high risk of deep vein thrombosis are an important cause of leg ulcers in older people. This finding strengthens the rationale for the routine and long-term use of thromboprophylaxis, particularly in high-risk patients.

Does capture-recapture analysis provide more reliable estimates of the incidence and prevalence of leg ulcers in the community?

OBJECTIVE: To determine whether capture-recapture analysis provides more reliable estimates of the cumulative incidence and prevalence of leg ulcers in Auckland, New Zealand. METHODS: A population-based, cross-sectional study was conducted in the Central and North Auckland health districts of New Zealand in 1998. Cases were identified through health professional referral and by self-notification. All ages and ulcer types were investigated. Both traditional and capture-recapture methods of analysis were used to estimate the cumulative incidence and prevalence of leg ulcers in the study population. RESULTS: Four hundred and twenty-six people with current leg ulcers were identified during the 12-month study period. Using traditional methods of analysis, the annual cumulative incidence rate of leg ulcers in Auckland was 32 per 100,000, with a point prevalence of 39 per 100,000 and a period prevalence of 79 per 100,000 per year. Results from capture-recapture analysis, however, suggest an annual cumulative incidence rate of 252 per 100,000, with a point prevalence of 248 per 100,000 and a period prevalence of 530 per 100,000 per year. CONCLUSIONS: The traditional method of calculating cumulative incidence and prevalence clearly under-estimates the frequency of leg ulcers in the Auckland region. Capture-recapture analysis provides a more reliable estimate of disease frequency, since cases that remain unidentified in the population are considered.

Leg ulcers in New Zealand: age at onset, recurrence and provision of care in an urban population.

AIM: To describe the age at onset, recurrence rate, and provision of care for people with leg ulcers in New Zealand. METHODS: Between 1997 and 1998, people with current leg ulcers were identified from the North Auckland and Central Auckland health districts via notification from relevant health professionals and by self-referral. All ulcer types were investigated. Identified cases, aged between 40 and 99 years and on the general electoral roll, were interviewed as part of a case-control study. Descriptive information relating to interviewed cases is presented. RESULTS: 241 people with leg ulcers were interviewed. The average age was 75 years and almost 60% were women. The average age at ulcer onset was 65 years, 59% of people had recurrent ulcers, and 24% had been hospitalised in the last five years because of their leg ulcers. Those people with recurrent leg ulcers had lived with their condition for an average of fifteen years, with an average time to healing for their last ulcer of thirteen months. Treatment of this condition was largely community-based, with 136 different treatment options employed. CONCLUSIONS: Leg ulceration remains a chronic and recurring condition, with substantial practice variation in terms of treatment. Urgent attention needs to be given to the management of leg ulcer patients in this country, particularly given that New Zealand has a rapidly ageing population.

The occurrence of leg ulcers in Auckland: results of a population-based study.

AIM: To estimate the cumulative incidence rate and prevalence of leg ulcers in Auckland. METHODS: A cross-sectional study was conducted to identify all individuals who had or developed a leg ulcer in the North Auckland and Central Auckland health districts between 1997 and 1998. Cases were identified through multiple sources, including community-based and hospital-based health professionals and by self-notification. All ulcer types were investigated. RESULTS: 611 individuals with healed or current leg ulcers were identified during the study period, of whom 426 had current leg ulcers. The annual cumulative incidence rate was 32 per 100,000. The point prevalence of current leg ulcers was 39 per 100,000, with a period prevalence of 79 per 100,000 per year. Men had lower age-adjusted incidence rates than women, but a higher age-adjusted point prevalence of leg ulceration, indicating that ulcers take longer to heal in men. Annual cumulative incidence rates increased steeply with age (< 60 years = 4, 60-69 years = 62, 70-79 years = 191, 80+ years = 466 per 100,000 per year), as did point prevalence (< 60 years = 5, 60-69 years = 76, 70-79 years = 238, 80+ years = 564 per 100,000). CONCLUSIONS: These data indicate that the risk of developing leg ulcers increases dramatically with age, with individuals aged 60 years and over particularly at risk. Given New Zealand's rapidly ageing population, the number of older people with leg ulcers each year is expected to double in the next 25 years.