21 research outputs found
Structure of poly(propyl ether imine) (PETIM) dendrimer from fully atomistic molecular Dynamics Simulation and by Small Angle X-ray scattering
We study the structure of carboxylic acid terminated neutral poly (propyl
ether imine) (PETIM) dendrimer from generation 1 through 6 (G1-G6) in a good
solvent (water) by fully atomistic molecular dynamics (MD) simulations. We
determine as a function of generation such structural properties as: radius of
gyration, shape tensor, asphericity, fractal dimension, monomer density
distribution, and end-group distribution functions. The sizes obtained from the
MD simulations have been validated by Small Angle X-Ray Scattering (SAXS)
experiment on dendrimer of generation 2 to 4 (G2-G4). A good agreement between
the experimental and theoretical value of radius of gyration has been observed.
We find a linear increase in radius of gyration with the generation. In
contrast, Rg scales as ~ N^x with the number of monomers. We find two distinct
exponents depending on the generations: x = 0.47 for G1-G3 and x = 0.28 for
G3-G6 which reveals their non-space filling nature. In comparison with the
amine terminated PAMAM dendrimer, we find Rg of G-th generation PETIM dendrimer
is nearly equal to that of (G+1)-th generation of PAMAM dendrimer as observed
by Maiti et. al. [Macromolecules,38, 979 2005]. We find substantial back
folding of the outer sub generations into the interior of the dendrimer. Due to
their highly flexible nature of the repeating branch units, the shape of the
PETIM dendrimer deviates significantly from the spherical shape and the
molecules become more and more spherical as the generation increases. The
interior of the dendrimer is quite open with internal cavities available for
accommodating guest molecules suggesting using PETIM dendrimer for guest-host
applications. We also give a quantitative measure of the number of water
molecules present inside the dendrimer.Comment: 33 page
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
Aminofluorene-Mediated Biomimetic Domino Amination–Oxygenation of Aldehydes to Amides
A conceptually novel biomimetic strategy
based on a domino amination–oxygenation
reaction was developed for direct amidation of aldehydes under metal-free
conditions employing molecular oxygen as the oxidant. 9-Aminofluorene
derivatives acted as pyridoxamine-5′-phosphate equivalents
for efficient, chemoselective, and operationally simple amine-transfer
oxygenation reaction. Unprecedented RNH transfer involving secondary
amine to produce secondary amides was achieved. In the presence of <sup>18</sup>O<sub>2</sub>, <sup>18</sup>O-amide was formed with excellent
(95%) isotopic purity
Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct α‑CH<sub>2</sub>‑Oxygenation of Free Amines
Direct oxidation of α-CH<sub>2</sub> group of free amines
is hard to achieve due to the higher reactivity of amine moiety. Therefore,
oxidation of amines involves the use of sophisticated metallic reagents/catalyst
in the presence or absence of hazardous oxidants under sensitive reaction
conditions. A novel method for direct C–H oxygenation of aliphatic
amines through a metal-free activation of molecular oxygen has been
developed. Both activated and unactivated free amines were oxygenated
efficiently to provide a wide variety of amides (primary, secondary)
and lactams under operationally simple conditions without the aid
of metallic reagents and toxic oxidants. The method has been applied
to the synthesis of highly functionalized amide-containing medicinal
drugs, such as O-Me-alibendol and -buclosamide
Direct β‑C(sp<sup>3</sup>)–H Functionalization of Aliphatic Amines to α,β-Unsaturated Imines, Aldehydes, and Chromenes
A metal-free
method for direct β-CÂ(sp<sup>3</sup>)–H
functionalization of aliphatic amine was developed. The method is
based on a reaction that yields enamine directly from the corresponding
aliphatic amine, which otherwise requires the aid of metallic reagent
and/or external oxidant. The reaction is operationally simple, general,
and highly efficient in functionalizing both cyclic and acyclic amines.
Structurally diverse unsaturated imines were obtained from <i>N</i>-heterocycles, while acyclic amines provided 2-alkyl cinnamaldehyde
and benzopyran derivatives with excellent <i>E</i>/<i>Z</i>-selectivity
Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N‑Heterocycles to Fused Heteropolycycles
A novel C–H functionalization
enabled multicomponent reaction
involving N-heterocycles, dinucleophile, and dipolarophile has been
developed. Direct α- and more challenging β-CÂ(sp3)–H
functionalization of aliphatic N-heterocycles was achieved without
the use of metallic reagents and oxidants under either conventional
or microwave aided heating conditions. In a single operation, up to
five carbon–carbon and carbon–heteroatom bonds are formed
in a highly diastereoselective manner, providing the expeditious access
to the complex heteropolycycles
Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N‑Heterocycles to Fused Heteropolycycles
A novel C–H functionalization
enabled multicomponent reaction
involving N-heterocycles, dinucleophile, and dipolarophile has been
developed. Direct α- and more challenging β-CÂ(sp3)–H
functionalization of aliphatic N-heterocycles was achieved without
the use of metallic reagents and oxidants under either conventional
or microwave aided heating conditions. In a single operation, up to
five carbon–carbon and carbon–heteroatom bonds are formed
in a highly diastereoselective manner, providing the expeditious access
to the complex heteropolycycles
Direct β‑C(sp<sup>3</sup>)–H Functionalization of Aliphatic Amines to α,β-Unsaturated Imines, Aldehydes, and Chromenes
A metal-free
method for direct β-CÂ(sp<sup>3</sup>)–H
functionalization of aliphatic amine was developed. The method is
based on a reaction that yields enamine directly from the corresponding
aliphatic amine, which otherwise requires the aid of metallic reagent
and/or external oxidant. The reaction is operationally simple, general,
and highly efficient in functionalizing both cyclic and acyclic amines.
Structurally diverse unsaturated imines were obtained from <i>N</i>-heterocycles, while acyclic amines provided 2-alkyl cinnamaldehyde
and benzopyran derivatives with excellent <i>E</i>/<i>Z</i>-selectivity