Kinetic investigation of hydroxide ion and DNA attack on some high spin iron (II) chelates Bearing ONO Donors amino acid Schiff bases

The reactivity of few novel high spin Fe(II) complexes of Schiff base ligands derived from 2-hydroxynaphthaldehyde and some variety of amino acids with OH- ion has been examined in aqueous mixture at temperature in the range 10–40 Co. Based on the kinetic investigations, the rate law and a plausible mechanism were proposed and discussed. The general rate equation was suggested as follows: rate = kobs [Complex], where kobs.= k1 + k2 [OH-]. Base catalyzed hydrolysis kinetics measurements imply pseudo-first order doubly stage rates due the presence of merand fac-isomers. The observed rate constants kobs are correlated the effect of substituent R in the structure of the ligands. From the effect of temperature on the rate; various thermodynamic parameters have been evaluated. The evaluated rate constants and activation parameters are in a good agreement with the stability constants of the investigated complexes

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Solvent effect on reactivity trends for base hydrolysis of 2-oxo-, 2-thio- benzopyran-3-thiocarboxamide, and 2-iminobenzopyran-3-carbonitrile

1575-1579Kinetics of base-catalysed hydrolyses of 2-oxobenzopyron-3-carboxamide, 2-thiobenzopyron-3-carboxamide, and 2-iminobenzopyran-3-carbonitrile are studied in aqueous methanol mixture and the effect of solvent on change in the activation barrier (δmΔG≠) is measured. Solvent effects on reactivity trends for base hydrolysis of these compounds have been analysed into initial state and transition state components which are determined from transfer chemical potentials and kinetic data. It is observed that the substituents O, S or N in position two and thiocarboxamide or carbonitrile in position three affect the rate constant and change the activation barrier

Kinetic investigation of hydroxide ion and DNA attack on some high spin iron (II) chelates Bearing ONO Donors amino acid Schiff bases

The reactivity of few novel high spin Fe(II) complexes of Schiff base ligands derived from 2-hydroxynaphthaldehyde and some variety of amino acids with OH- ion has been examined in aqueous mixture at temperature in the range 10–40 Co. Based on the kinetic investigations, the rate law and a plausible mechanism were proposed and discussed. The general rate equation was suggested as follows: rate = kobs [Complex], where kobs.= k1 + k2 [OH-]. Base catalyzed hydrolysis kinetics measurements imply pseudo-first-order doubly stage rates due the presence of merandfac-isomers. The observed rate constants kobs are correlated the effect of substituent R in the structure of the ligands.From the effect of temperature on the rate; various thermodynamic parameters have been evaluated. The evaluated rate constants and activation parameters are in a good agreement with the stability constants of the investigated complexes.Keywords: Base catalyzed hydrolysis, Isomer, Reaction mechanism, Thermodynamic parameters

Kinetics, reactivity, initial-transition state analysis and thermodynamic parameters of base-catalyzed hydrolysis of coumalic acid in solvents with different polarities

Base-catalyzed hydrolysis of coumalic acid (COU) in binary aqueous-methanol and aqueous-acetone mixtures has been studied kinetically at a temperature range from 283 to 313 K. Moreover, the change in the activation energy barrier of COU from water to water–methanol and water–acetone mixtures is estimated from the kinetic data. Solvent effects on reactivity trends have been analyzed into initial and transition state components by using transfer chemical potentials of the reactants and kinetic data. The transfer chemical potentials δmμθ for COU− anion are derived from solubility data from its calcium, cerium and lanthanum salts. The decrease in rate constant of the base hydrolysis reaction of COU as the percentage of methanol or acetone increases is dominated by transition state (TS). The base hydrolysis reaction of COU follows a rate law with kobs = k2[OH−] and the reaction mechanism was suggested. The high negative values of entropy of activation support the proposal mechanism, i.e. the investigated reaction takes place via the formation of an intermediate complex. Thus, the ring opening of the intermediate complex would be the rate controlling step

Hydrophobicity, reactivity trends of base catalyzed hydrolysis of some novel high spin Fe(II) Schiff base amino acid chelates in some binary aqueous solvent mixtures: Initial-transition state analysis

Rate constants for the base hydrolysis of bis(naphthylidene alanate)iron (II) (nali), bis(naphthylidene phenylalanate)iron(II) (nphali), bis(naphthylidene aspartate)iron(II) (nasi), (naphthylidene histidinate)iron(II) (nhi), bis(naphthylidene arginate)iron(II) (nari) have been reported in different binary aqueous solvent mixtures at 298 K. The observed reactivity trends are discussed in terms of the hydrophilic and hydrophobic forms of the complexes investigated, as well as the transfer chemical potentials of the hydroxide ion and the complex. Both the solvent–solute and solvent–solvent interactions have been considered. The hydrophobic character of the complexes studied was manifested by a decrease in reactivity. Solvent effect on reactivity trends of the investigated complexes have been analyzed into initial and transition state components. This can be achieved by using the transfer chemical potentials of the reactants and the kinetic data of the studied compounds. The decrease in the observed rate constant values (kobs) of the base hydrolysis of the investigated complexes with increase of solvent% is dominated by the initial state (IS)

Hydrophobicity and kinetic inspection of hydroxide ion attack on some chromen-2-one laser dyes in binary aqueous–methanol and aqueous–acetone mixtures: Initial state-transition state analysis

AbstractIn the present study, reactivity base-catalyzed hydrolysis of 7-dimethylamino-4-methyl-2H-chromen-2-one (DMAC) and 7-diethylamino-4-methyl-2H-chromen-2-one (DEAC) in binary aqueous–methanol and aqueous–acetone mixtures was examined at 298K. Kinetic results, rate laws and reaction mechanisms were established. Moreover, the change in the activation energy barrier of the investigated compounds from water to water–methanol and water–acetone mixtures was estimated from the kinetic data. Base-catalyzed hydrolysis of (DMAC) and (DEAC) in aqueous–methanol and aqueous–acetone mixtures follows a rate law with kobs=k2[OH]. The decrease in the rate constants of (DMAC) and (DEAC) as the proportion of methanol and acetone is due to the destabilization of OH− ion. The solubilities of the studied compounds, DMAC and DEAC in water–methanol and water–acetone mixtures were established and their transfer chemical potentials were calculated. Solvent effect on reactivity trends of the investigated compounds has been analyzed into initial and transition state components by using the transfer chemical potentials of the reactants and the kinetic data of the studied compounds. The decrease in the observed rate constant values (kobs) of the base hydrolysis of DMAC and DEAC with increasing of methanol% or acetone% is dominated by the initial state (IS)

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

BackgroundFuture trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050.MethodsUsing forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.FindingsIn the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]).InterpretationGlobally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions.FundingBill & Melinda Gates Foundation.</p