Ruthenium ion catalysed C-C bond activation in lignin model compounds - towards lignin depolymerisation.

Lignin is the most abundant renewable feedstock to produce aromatic chemicals, however its depolymerisation involves the breaking of several C-O and C-C inter-unit linkages that connect smaller aromatic units that are present in lignin. Several strategies have been reported for the cleavage of the C-O inter-unit linkages in lignin. However, till today, only a few methodologies have been reported for the effective breaking or the conversion of the recalcitrant C-C inter unit linkages in lignin. Here we report the ruthenium ion catalysed oxidative methodology as an effective system to activate or convert the most recalcitrant inter unit linkages such as ß-5 and 5-5' present in lignin. Initially, we used biphenyl as a model compound to study the effectiveness of the RICO methodology to activate the 5-5' C-C linkage. After 4 h reaction at 22 °C, we achieved a 30% conversion with 75% selectivity towards benzoic acid and phenyl glyoxal as the minor product. To the best of our knowledge this is the first ever oxidative activation of the C-C bond that connects the two phenyl rings in biphenyl. DFT calculation revealed that the RuO4 forms a [3 + 2] adduct with one of the aromatic C-C bonds resulting in the opening of the phenyl ring. Biphenyl conversion could be increased by increasing the amount of oxidant; however, this is accompanied by a reduction in the carbon balance because of the formation of CO2 and other unknown products. We extended this RICO methodology for the oxidative depolymerisation of lignin model hexamer containing ß-5, 5-5' and ß-O-4 linkages. Qualitative and quantitative analyses of the reaction mixture were done using 1H, 13C NMR spectroscopy methods along with GC-MS and Gel Permeation Chromatographic (GPC) methods. Advanced 2D NMR spectroscopic methods such as HSQC, HMBC and 31P NMR spectroscopy after phosphitylation of the mixture were employed to quantitatively analyse the conversion of the ß-5, 5-5' and ß-O-4 linkages and to identify the products. After 30 min, >90% of the 5-5' and linkages and >80% of the ß-5' are converted with this methodology. This is the first report on the conversion of the 5-5' linkage in lignin model hexamer.

Determinants of the use of contraceptive methods by adolescents in the Democratic Republic of the Congo: results of a cross-sectional survey.

BACKGROUND: Family planning (FP) is an effective strategy to prevent unintended pregnancies of adolescents. We aimed at identifying the socio-demographic factors underlying the low use of contraceptive methods by teenage girls in the Democratic Republic of the Congo (DRC). METHODS: A secondary analysis targeting teenage girls aged 15-19 was carried out on the Performance, Monitoring and Accountability project 2020 (PMA 2020) round 7 data, collected in Kinshasa and Kongo Central provinces. The dependent variable was the "use of contraceptive methods by sexually active teenage girls", calculated as the proportion of teenagers using modern, traditional or any contraceptive methods. Independent variables were: level of education, age, province, religion, marital status, number of children, knowledge of contraceptive methods and household income. Pearson's chi-square and logistic regression tests helped to measure the relationship between variables at the alpha significance cut point of 0.05. RESULTS: A total of 943 teenagers were interviewed; of which 22.6, 18.1 and 19.9% ​​used any contraceptive method respectively in Kinshasa, Kongo Central and overall. The use of modern contraceptive methods was estimated at 9.9, 13.4 and 12.0% respectively in Kinshasa, Kongo Central and overall. However, the use of traditional methods estimated at 8.0% overall, was higher in Kinshasa (12.7%) and lower (4.7%) in Kongo Central (p < .001). Some factors such as poor knowledge of contraceptive methods (aOR = 8.868; 95% CI, 2.997-26.240; p < .001); belonging to low-income households (aOR = 1.797; 95% CI, 1.099-2.940; p = .020); and living in Kongo central (aOR = 3.170; 95% CI, 1.974-5.091; p < .001) made teenagers more likely not to use any contraceptive method. CONCLUSION: The progress in the use of contraceptive methods by adolescent girls is not yet sufficient in the DRC. Socio-demographic factors, such as living in rural areas, poor knowledge of FP, and low-income are preventing teenagers from using FP methods. These findings highlight the need to fight against such barriers; and to make contraceptive services available, accessible, and affordable for teenagers.

The use of contraceptive methods remains low among adolescents aged 15 to 19 in the Democratic Republic of the Congo. However, family planning (FP) methods can help to prevent unintended pregnancies. This study aimed at identifying the socio-demographic factors that prevent teenage girls from using FP methods. We analyzed the data from the Performance, Monitoring and Accountability project (PMA 2020), seventh round, collected in Kinshasa and Kongo Central provinces. The use of contraceptive methods by sexually active adolescents was measured according to the level of education, age, province, religion, marital status, number of children, knowledge of contraceptive methods and household income. For the 943 adolescent girls interviewed, the use of any contraceptive method was calculated at 22.6, 18.1 and 19.9%, respectively in Kinshasa, Kongo Central and overall. The use of traditional methods was estimated at 8.0% overall, higher in Kinshasa (12.7%) and lower (4.7%) in Kongo Central. However, the use of modern contraceptive methods was estimated at 9.9, 13.4 and 12.0% respectively in Kinshasa, Kongo Central and overall. Poor knowledge of contraceptive methods; low-income and living in Kongo central province were the factors associated with the low use of any contraceptive method. In conclusion, the progress in the use of contraceptive methods by adolescent girls is not yet sufficient, due to some socio-demographic barriers. These results suggest to fight against such factors; and to make contraceptive services available, accessible, and affordable for teenagers.

Canagliflozin Markedly Decreased Proteinuria in a Patient With IgA Nephropathy.

IgA nephropathy (IgAN) remains one of the most common forms of glomerulonephritis, especially in developed countries with a low prevalence of infectious diseases. Despite supportive measures that slow the rate of progression of chronic kidney disease (CKD) in IgAN, many patients still progress to end-stage kidney disease. Proteinuria has been shown to be an adverse prognostic factor in IgAN. Data support the use of proteinuria reduction as a reasonably likely surrogate endpoint for a treatment's effect on progression to end-stage renal disease (ESRD) in IgAN. Currently employed immunosuppressive strategies lack conclusive efficacy data, while there is evidence for treatment-induced toxicity. The current standard of care for the management of IgAN is intensive goal-directed supportive care. Recently the role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in decreasing proteinuria and progression of CKD is widely being recognized. In this case report, we present a 44-year-old male with proteinuria and biopsy-proven IgAN who remained in remission after six months of steroids using the Pozzi protocol. He developed proteinuria five years after remission. At this point, canagliflozin was added to his angiotensin-receptor blocker (ARB) therapy resulting in a significant reduction in his proteinuria. Our case report may intrigue researchers to look into the role of canagliflozin in decreasing albuminuria in non-diabetic kidney disease, thus slowing the progression to ESRD.

Gas Phase Glycerol Valorization over Ceria Nanostructures with Well-Defined Morphologies.

Glycerol solutions were vaporized and reacted over ceria catalysts with different morphologies to investigate the relationship of product distribution to the surface facets exposed, particularly, the yield of bio-renewable methanol. Ceria was prepared with cubic, rodlike, and polyhedral morphologies via hydrothermal synthesis by altering the concentration of the precipitating agent or synthesis temperature. Glycerol conversion was found to be low over the ceria with a cubic morphology, and this was ascribed to both a low surface area and relatively high acidity. Density functional theory calculations also showed that the (100) surface is likely to be hydroxylated under reaction conditions which could limit the availability of basic sites. Methanol space-time-yields over the polyhedral ceria samples were more than four times that for the cubic material at 400 °C, where 201 g of methanol was produced per hour per kilogram of the catalyst. Under comparable glycerol conversions, we show that the rodlike and polyhedral catalysts produce a major intermediate to methanol, hydroxyacetone (HA), with a selectivity of ca. 45%, but that over the cubic sample, this was found to be 15%. This equates to a 13-fold increase in the space-time-yield of HA over the polyhedral samples compared to the cubes at 320 °C. The implications of this difference are discussed with respect to the reaction mechanism, suggesting that a different mechanism dominates over the cubic catalysts to that for rodlike and polyhedral catalysts. The strong association between exposed surface facets of ceria to high methanol yields is an important consideration for future catalyst design in this area.

A combined periodic DFT and QM/MM approach to understand the radical mechanism of the catalytic production of methanol from glycerol.

The production of methanol from glycerol over a basic oxide, such as MgO, using high reaction temperatures (320 °C) is a promising new approach to improving atom efficiency in the production of biofuels. The mechanism of this reaction involves the homolytic cleavage of the C3 feedstock, or its dehydration product hydroxyacetone, to produce a hydroxymethyl radical species which can then abstract an H atom from other species. Obtaining a detailed reaction mechanism for this type of chemistry is difficult due to the large number of products present when the system is operated at high conversions. In this contribution we show how DFT based modelling studies can provide new insights into likely reaction pathways, in particular the source of H atoms for the final step of converting hydroxymethyl radicals to methanol. We show that water is unlikely to be important in this stage of the process, C-H bonds of C2 and C3 species can give an energetically favourable pathway and that the disproportionation of hydroxymethyl radicals to methanol and formaldehyde produces a very favourable route. Experimental analysis of reaction products confirms the presence of formaldehyde. The calculations presented in this work also provide new insight into the role of the catalyst surface in the reaction showing that the base sites of the MgO(100) are able to deprotonate hydroxymethyl radicals but not methanol itself. In carrying out the calculations we also show how periodic DFT and QM/MM approaches can be used together to obtain a rounded picture of molecular adsorption to surfaces and homolytic bond cleavage which are both central to the reactions studied.

Role of the Support in Gold-Containing Nanoparticles as Heterogeneous Catalysts.

In this review, we discuss selected examples from recent literature on the role of the support on directing the nanostructures of Au-based monometallic and bimetallic nanoparticles. The role of support is then discussed in relation to the catalytic properties of Au-based monometallic and bimetallic nanoparticles using different gas phase and liquid phase reactions. The reactions discussed include CO oxidation, aerobic oxidation of monohydric and polyhydric alcohols, selective hydrogenation of alkynes, hydrogenation of nitroaromatics, CO2 hydrogenation, C-C coupling, and methane oxidation. Only studies where the role of support has been explicitly studied in detail have been selected for discussion. However, the role of support is also examined using examples of reactions involving unsupported metal nanoparticles (i.e., colloidal nanoparticles). It is clear that the support functionality can play a crucial role in tuning the catalytic activity that is observed and that advanced theory and characterization add greatly to our understanding of these fascinating catalysts.

Distribution and quality of emergency obstetric care service delivery in the Democratic Republic of the Congo: it is time to improve regulatory mechanisms.

BACKGROUND: The Demographic and Health Survey 2013-14 indicated that the Democratic Republic of the Congo (DRC) is still challenged by high maternal and neonatal mortality. The aim of this study was to assess the availability, quality and equity of emergency obstetric care (EmOC) in the DRC. METHODS: A cross-sectional survey of 1,568 health facilities selected by multistage random sampling in 11 provinces of the DRC was conducted in 2014. Data were collected through interviews, document reviews, and direct observation of service delivery. Collected data included availability, quality, and equity of EmOC depending on the location (urban vs. rural), administrative identity, type of facility, and province. Associations between variables were tested by Pearson's chi-squared test using an alpha significance level of 0.05. RESULTS: A total of 1,555 health facilities (99.2%) were surveyed. Of these, 9.1% provided basic EmOC and 2.9% provided comprehensive EmOC. The care was unequally distributed across the provinces and urban vs. rural areas; it was more available in urban areas, with the provinces of Kinshasa and Nord-Kivu being favored compared to other provinces. Caesarean section and blood transfusions were provided by health centers (6.5 and 9.0%, respectively) and health posts (2.3 and 2.3%, respectively), despite current guidelines disallowing the practice. None of the facilities provided quality EmOC, mainly due to the lack of proper standards and guidelines. CONCLUSIONS: The distribution and quality of EmOC are problematic. The lack of regulation and monitoring appears to be a key contributing factor. We recommend the Ministry of Health go beyond merely granting funds, and also ensure the establishment and monitoring of appropriate standard operating procedures for providers.

Equatorial ligand plane perturbations lead to a spin-state change in an iron(iii) porphyrin dimer.

A complete reversal of the spin state of iron(iii) is observed upon a small change to the diporphyrin bridge from ethane to ethene by keeping all other factors intact. Combined analysis using single crystal X-ray structure determination, Mössbauer, variable-temperature magnetic, 1H NMR and EPR studies has confirmed the spin states of iron(iii) complexes both in solid and solution phases.

Task shifting in the management of hypertension in Kinshasa, Democratic Republic of Congo: a cross-sectional study.

BACKGROUND: The Democratic Republic of the Congo (DRC) is characterized by a high prevalence of hypertension (HTN) and a high proportion of uncontrolled HTN, which is indicative of poor HTN management. Effective management of HTN in the African region is challenging due to limited resources, particularly human resources for health. To address the shortage of health workers, the World Health Organization (WHO) recommends task shifting for better disease management and treatment. Although task shifting from doctors to nurses is being implemented in the DRC, there are no studies, to the best of our knowledge, that document the association between task shifting and HTN control. The aim of this study was to investigate the association between task shifting and HTN control in Kinshasa, DRC. METHODS: We conducted a cross-sectional study in Kinshasa from December 2015 to January 2016 in five general referral hospitals (GRHs) and nine health centers (HCs). A total of 260 hypertensive patients participated in the study. Sociodemographic, clinical, health care costs and perceived health care quality assessment data were collected using a structured questionnaire. To examine the association between task shifting and HTN control, we assessed differences between GRH and HC patients using bivariate and multivariate analyses. RESULTS: Almost half the patients were female (53.1%), patients' mean age was 59.5 ± 11.4 years. Over three-fourths of patients had uncontrolled HTN. There was no significant difference in the proportion of GRH and HC patients with uncontrolled HTN (76.2% vs 77.7%, p = 0.771). Uncontrolled HTN was associated with co-morbidity (OR = 10.3; 95% CI: 3.8-28.3) and the type of antihypertensive drug used (OR = 4.6; 95% CI: 1.3-16.1). The mean healthcare costs in the GRHs were significantly higher than costs in the HCs (US$ 34.2 ± US$3.34 versus US$ 7.7 ± US$ 0.6, respectively). CONCLUSION: Uncontrolled HTN was not associated with the type of health facility. This finding suggests that the management of HTN at primary healthcare level might be just as effective as at secondary level. However, the high proportion of patients with uncontrolled HTN underscores the need for HTN management guidelines at all healthcare levels.

Prevalence and determinants of use of complementary and alternative medicine by hypertensive patients attending primary health care facilities in Kinshasa, Democratic Republic of the Congo: a cross-sectional study.

BACKGROUND: In the Democratic Republic of the Congo the control of hypertension is poor, characterized by an increasing number of reported cases of hypertension related complications. Poor control of hypertension is associated with non-adherence to antihypertensive medication. It is well established that the use of complementary and alternative medicine is one of the main factors of non-adherence to antihypertensive medication. The aim of this study is to determine the prevalence and factors associated with the use of complementary and alternative medicine. METHODS: A cross-sectional study was carried out at the Kinshasa Primary Health-care (KPHC) facilities network in November 2014. A structured interview questionnaire was administrated to a total of 280hypertensive patients. Complementary and alternative medicine were defined according to the National Institute of Health classification as a group of diverse medical and healthcare systems, practices, and products that are not presently considered to be part of conventional medicine. Data were summarized using proportion and mean (with standard deviation). The student's t test and χ2 test were used respectively for mean and proportion comparison. Logistic regression analysis identified determinants of the use of complementary and alternative medicine. RESULTS: The prevalence of use of complementary and alternative medicine was 26.1% (95% CI: 20.7% - 31.8%).Determinants of use of complementary and alternative medicine included misperception about hypertension curability (OR = 2.1; 95%CI: 1.1-3.7) and experience of medication side effects (OR = 2.9; 95%CI: 1.7-5.1). CONCLUSION: The use of CAM for hypertensive patients is a major problem; antihypertensives with fewer side effects must be emphasized. Religious leaders must become involved in the communication for behavioral change activities to improve the quality of life for hypertensive patients.

A Systematic Account on Aromatic Hydroxylation by a Cytochrome P450 Model Compound I: A Low-Pressure Mass Spectrometry and Computational Study.

Cytochrome P450 enzymes are heme-containing mono-oxygenases that mainly react through oxygen-atom transfer. Specific features of substrate and oxidant that determine the reaction rate constant for oxygen atom transfer are still poorly understood and therefore, we did a systematic gas-phase study on reactions by iron(IV)-oxo porphyrin cation radical structures with arenes. We present herein the first results obtained by using Fourier transform-ion cyclotron resonance mass spectrometry and provide rate constants and product distributions for the assayed reactions. Product distributions and kinetic isotope effect studies implicate a rate-determining aromatic hydroxylation reaction that correlates with the ionization energy of the substrate and no evidence of aliphatic hydroxylation products is observed. To further understand the details of the reaction mechanism, a computational study on a model complex was performed. These studies confirm the experimental hypothesis of dominant aromatic over aliphatic hydroxylation and show that the lack of an axial ligand affects the aliphatic pathways. Moreover, a two-parabola valence bond model is used to rationalize the rate constant and identify key properties of the oxidant and substrate that drive the reaction. In particular, the work shows that aromatic hydroxylation rates correlate with the ionization energy of the substrate as well as with the electron affinity of the oxidant.

A phase II, open-label trial of bortezomib (VELCADE(®)) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non-small cell lung cancer.

BACKGROUND: Bortezomib is a selective reversible proteasome inhibitor with proapoptotic effects. Preclinical and phase I clinical data suggest activity of bortezomib in NSCLC, either as monotherapy or in combination with chemotherapeutic agents including gemcitabine and cisplatin. METHODS: Chemotherapy-naïve patients with inoperable stage IIIB or IV NSCLC were administered bortezomib 1 mg/m(2) i.v. on days 1 and 8, and starting on day 21 (cycle 2), bortezomib (days 1 and 8) in combination with gemcitabine 1000 mg/m(2), (days 1 and 8), and cisplatin 70 mg/m(2) (day 1) in cycles of 21 days. Up to 8 cycles of combination therapy could be administered; single-agent bortezomib was continued until disease progression or unacceptable toxicity. RESULTS: Fifty-three patients [median age 66 years; 79.2 % male; 96.2 % stage IV; performance status (ECOG) 0/1 73.6/26.4 %; adenocarcinoma 45.3 %, squamous cell carcinoma 41.5 %] were enrolled. All patients were evaluable for toxicity and 43 for efficacy. Grade 3-4 hematologic toxicity consisted of neutropenia (22.6 %) and thrombocytopenia (17 %). Grade 2-4 non-hematologic adverse events were fever (9.4 %), fatigue (20.8 %), infection (18.9 %), and dyspnea (15.1 %). There was no >grade 2 neurotoxicity. Febrile neutropenia occurred in two (1.9 %) patients, and there were three possibly treatment-related deaths (5.4 %). In the intention-to-treat population, the objective response rate was 17 % (95 % CI 6.9-27.1 %). No difference in response rate was observed for squamous versus other histology (18.2 vs. 16.1 %, p = 0.845). The median progression-free survival was 2.5 months, the median overall survival 10.6 months and the 1-year survival rate 38.1 %. CONCLUSION: The incorporation of bortezomib into the gemcitabine/cisplatin regimen, in the dose and schedule used in this study, could not improve the efficacy of the chemotherapy regimen and has not to be further investigated.

Prevalence and Socio-Demographic Determinant of Overweight and Obesity among Malaysian Adult

​Overweight and obesity is a major public health problem in Malaysia. This study aims to determine the prevalence of overweight and obesity among the Malaysian adult population and their association with socio-demographic characteristics (gender, ethnic, and age groups). A total of 17,257 adults aged 18 years and older (8,252 men, 9,005 women) were assessed for BMI status, with a response rate of 97.8%, through a household survey from the National Health and Morbidity Survey (NHMS), conducted in all states of Malaysia in 2011. All socio-demographic factors were consistently associated with higher chance of being overweight (except gender and location) and obesity (except location and household income). The identified risk of overweight were Indian (aOR: 1.8, 95% CI: 1.2-2.8), aged 50-59 years (aOR: 2.8, 95% CI: 2.0-3.9), widower (aOR: 1.6, 95% CI: 1.3-2.0), subject with secondary education (aOR: 1.2, 95% CI: 1.0-1.4), Homemaker/unpaid worker (aOR: 1.3, 95% CI: 1.1-1.4), and with high household income group (aOR: 1.3, 95% CI: 1.2-1.6). The identified risk of obesity were women (aOR: 1.4, 95% CI: 1.2-1.6), Indian (aOR: 1.7, 95% CI: 0.9-3.2), aged 30-39 years (aOR: 3.6, 95% CI: 2.4-5.5), widower (aOR: 1.2, 95% CI: 0.9-1.6), subjects with primary education (aOR: 1.2, 95% CI: 0.9-1.6), Homemaker/unpaid worker (aOR: 1.3, 95% CI: 1.1-1.6), and with middle household income group (aOR: 1.3, 95% CI: 1.2-1.6). Our data indicate a high prevalence of overweight and obesity in the population. Several sociodemographic characteristics are associated with both overweight and obesity. This study highlights the serious problem of overweight and obesity among Malaysia adults. Documentation of these problems may lead to research and policy agendas that will contribute both to our understanding and to the reduction of these problems.

Assessment of hypertension management in primary health care settings in Kinshasa, Democratic Republic of Congo.

BACKGROUND: Hypertension-related complications have become more diagnosed at secondary and tertiary care levels, in the Democratic Republic of the Congo (DRC), probably indicative of poor management of hypertensive patients at primary health care level. This study aimed to assess the management of hypertension in primary health care settings by using guidelines of the International Forum for Prevention and Control of HTN in Africa (IFHA). METHODS: A multi-center cross-sectional study was carried out in primary health care settings. A total of 102 nurses were surveyed using a structured interview. Mean and proportion comparisons were performed using the t Student test and the Chi-square test respectively. The Kinshasa Primary Health Care network facilities were compared with non-Kinshasa Primary Health Care network facilities. RESULTS: From the 102 nurses surveyed; 52.9% were female with a mean age of 41.1, (SD = 10) years, merely 9.5% benefited from in-job training on cardiovascular diseases or their risk factors, and 51.7% had guidelines on the management of hypertension. Less than a quarter of the nurses knew the cut-off values of hypertension, diabetes and obesity. Merely 14.7% knew the therapeutic goals for uncomplicated hypertension. Several of the indicators for immediate referral recommended by IFHA were unmentioned. The content of patient education was lacking, avoiding stress being the best advice provided to hypertensive patients. The antihypertensive most used were unlikely to be recommended by the IFHA. CONCLUSIONS: This study showed a considerable gap of knowledge and practices in the management of hypertensive patients at primary health care facilities in Kinshasa pertaining to the IFHA guidelines. We think that task-shifting for management of hypertension is feasible if appropriate guidelines are provided and nurses trained.

Predictors of non-adherence to antihypertensive medication in Kinshasa, Democratic Republic of Congo: a cross-sectional study.

BACKGROUND: Hypertension remains a public health challenge worldwide. In the Democratic Republic of Congo, its prevalence has increased in the past three decades. Higher prevalence of poor blood pressure control and an increasing number of reported cases of complications due to hypertension have also been observed. It is well established that non-adherence to antihypertensive medication contributes to poor control of blood pressure. The aim of this study is to measure non-adherence to antihypertensive medication and to identify its predictors. METHODS: A cross-sectional study was conducted at Kinshasa Primary Health-care network facilities from October to November 2013. A total of 395 hypertensive patients were included in the study. A structured interview was used to collect data. Adherence to medication was assessed using the Morisky Medication Scale. Covariates were defined according to the framework of the World Health Organization. Logistic regression was used to identify predictors of non-adherence. RESULTS: A total of 395 patients participated in this study. The prevalence of non-adherence to antihypertensive medication and blood pressure control was 54.2 % (95 % CI 47.3-61.8) and 15.6 % (95 % CI 12.1-20.0), respectively. Poor knowledge of complications of hypertension (OR = 2.4; 95 % CI 1.4-4.4), unavailability of antihypertensive drugs in the healthcare facilities (OR = 2.8; 95 % CI 1.4-5.5), lack of hypertensive patients education in the healthcare facilities (OR = 1.7; 95 % CI 1.1-2.7), prior experience of medication side effects (OR = 2.2; 95 % CI 1.4-3.3), uncontrolled blood pressure (OR = 2.0; 95 % CI 1.1-3.9), and taking non-prescribed medications (OR = 2.2; 95 % CI 1.2-3.8) were associated with non-adherence to antihypertensive medication. CONCLUSION: This study identified predictors of non-adherence to antihypertensive medication. All predictors identified were modifiable. Interventional studies targeting these predictors for improving adherence are needed.

Alkyl Chain Growth on a Transition Metal Center: How Does Iron Compare to Ruthenium and Osmium?

Industrial Fischer-Tropsch processes involve the synthesis of hydrocarbons usually on metal surface catalysts. On the other hand, very few homogeneous catalysts are known to perform a Fischer-Tropsch style of reaction. In recent work, we established the catalytic properties of a diruthenium-platinum carbene complex, [(CpRu)2(µ²-H) (µ²-NHCH3)(µ³-C)PtCH3(P(CH3)3)2](CO)n⁺ with n=0, 2 and Cp=η5-C5(CH3)5, and showed it to react efficiently by initial hydrogen atom transfer followed by methyl transfer to form an alkyl chain on the Ru-center. In particular, the catalytic efficiency was shown to increase after the addition of two CO molecules. As such, this system could be viewed as a potential homogeneous Fischer-Tropsch catalyst. Herein, we have engineered the catalytic center of the catalyst and investigated the reactivity of trimetal carbene complexes of the same type using iron, ruthenium and osmium at the central metal scaffold. The work shows that the reactivity should increase from diosmium to diruthenium to diiron; however, a non-linear trend is observed due to multiple factors contributing to the individual barrier heights. We identified all individual components of these reaction steps in detail and established the difference in reactivity of the various complexes.

Drug metabolism by cytochrome p450 enzymes: what distinguishes the pathways leading to substrate hydroxylation over desaturation?

Cytochrome P450 enzymes are highly versatile biological catalysts in our body that react with a broad range of substrates. Key functions in the liver include the metabolism of drugs and xenobiotics. One particular metabolic pathway that is poorly understood relates to the P450 activation of aliphatic groups leading to either hydroxylation or desaturation pathways. A DFT and QM/MM study has been carried out on the factors that determine the regioselectivity of aliphatic hydroxylation over desaturation of compounds by P450 isozymes. The calculations establish multistate reactivity patterns, whereby the product distributions differ on each of the spin-state surfaces; hence spin-selective product formation was found. The electronic and thermochemical factors that determine the bifurcation pathways were analysed and a model that predicts the regioselectivity of aliphatic hydroxylation over desaturation pathways was established from valence bond and molecular orbital theories. Thus, the difference in energy of the OH versus the OC bond formed and the π-conjugation energy determines the degree of desaturation products. In addition, environmental effects of the substrate binding pocket that affect the regioselectivities were identified. These studies imply that bioengineering P450 isozymes for desaturation reactions will have to include modifications in the substrate binding pocket to restrict the hydroxylation rebound reaction.

Spin-state ordering in hydroxo-bridged diiron(III)bisporphyrin complexes.

We report the synthesis, structure, and spectroscopic characterization of 1,2-bis[µ-hydroxo iron(III) 5-(2,3,7,8,12,13,17,18-octaethylporphyrinyl)]ethane with PF6(­) and SbF6(­) counteranions. The two iron centers are nonequivalent with admixed intermediate spin state (S = 3/2 with a minor contribution of S = 5/2) on each metal both in the solid and in solution. The molecules are compared with previously known µ-hydroxo complexes with other counterions, such as I3(­), BF4(­), and ClO4(­), which demonstrates that the nature of the counterion can affect the spin-state ordering dramatically. To understand how the spin-state ordering is affected by external perturbations, we also have done a comprehensive computational study. The calculations show that subtle environmental perturbations affect the spin-state ordering and relative energies and are likely to be the root cause of the variation in spin-state ordering observed experimentally.

A comprehensive test set of epoxidation rate constants for iron(iv)-oxo porphyrin cation radical complexes.

Cytochrome P450 enzymes are heme based monoxygenases that catalyse a range of oxygen atom transfer reactions with various substrates, including aliphatic and aromatic hydroxylation as well as epoxidation reactions. The active species is short-lived and difficult to trap and characterize experimentally, moreover, it reacts in a regioselective manner with substrates leading to aliphatic hydroxylation and epoxidation products, but the origin of this regioselectivity is poorly understood. We have synthesized a model complex and studied it with low-pressure Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry (MS). A novel approach was devised using the reaction of [FeIII(TPFPP)]+ (TPFPP = meso-tetrakis(pentafluorophenyl)porphinato dianion) with iodosylbenzene as a terminal oxidant which leads to the production of ions corresponding to [FeIV(O)(TPFPP+˙)]+. This species was isolated in the gas-phase and studied in its reactivity with a variety of olefins. Product patterns and rate constants under Ideal Gas conditions were determined by FT-ICR MS. All substrates react with [FeIV(O)(TPFPP+˙)]+ by a more or less efficient oxygen atom transfer process. In addition, substrates with low ionization energies react by a charge-transfer channel, which enabled us to determine the electron affinity of [FeIV(O)(TPFPP+˙)]+ for the first time. Interestingly, no hydrogen atom abstraction pathways are observed for the reaction of [FeIV(O)(TPFPP+˙)]+ with prototypical olefins such as propene, cyclohexene and cyclohexadiene and also no kinetic isotope effect in the reaction rate is found, which suggests that the competition between epoxidation and hydroxylation - in the gas-phase - is in favour of substrate epoxidation. This notion further implies that P450 enzymes will need to adapt their substrate binding pocket, in order to enable favourable aliphatic hydroxylation over double bond epoxidation pathways. The MS studies yield a large test-set of experimental reaction rates of iron(iv)-oxo porphyrin cation radical complexes, so far unprecedented in the gas-phase, providing a benchmark for calibration studies using computational techniques. Preliminary computational results presented here confirm the observed trends excellently and rationalize the reactivities within the framework of thermochemical considerations and valence bond schemes.

Prevalence, comorbidities, and cofactors associated with alcohol consumption among school-going adolescents in Malaysia.

Alcohol is deleterious to physical and mental health as well as social well-being. This study aims to examine the prevalence of alcohol consumption and factors associated with its use among school-going Malaysian adolescents. The Global School-Based Student Health Survey (GSHS) 2012 employed 2-stage clustering design to Malaysian secondary school respondents aged 12 to 17 years. The prevalence of current alcohol usage was 8.9% (95% confidence interval [CI]: 7.8-10.07) overall, 11.2% (95% CI: 9.80-12.80) among males, and 23.4 (95% CI: 21.40-25.50) among Chinese students. Multivariate logistic regression showed that adolescents who had used alcohol were more likely to have used substance (adjusted odds ratio [aOR] = 3.39; 95% CI: 2.33-4.99), experienced injury (aOR = 1.53; 95% CI: 1.20-1.95), and engaged in sexual behaviors (aOR = 1.42, 95% CI: 1.12-1.79), and fights (aOR = 1.23; 95% CI: 1.08-1.41). The current national policies on alcohol should be strengthened to curb alcohol consumption among adolescents.