19 research outputs found
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Modeling, kinetic, and equilibrium characterization of paraquat adsorption onto polyurethane foam using the ion-pairing technique
We studied the adsorption of paraquat onto polyurethane foam (PUF) when it was in a medium containing sodium dodecylsulfate (SDS). The adsorption efficiency was dependent on the concentration of SDS in solution, because the formation of an ion-associate between the cationic paraquat and the dodecylsulfate anion was found to be a fundamental step in the process. A computational study was carried out to identify the possible structure of the ion-associate in aqueous medium. The obtained data demonstrated that the structure is probably formed from four units of dodecylsulfate bonded to one paraquat moiety. The results showed that 94% of the paraquat present in 45 mL of a solution containing 3.90 × 10^−5 mol L^−1 could be retained by 300 mg of PUF, resulting in the removal of 2.20 mg of paraquat. The experimental data were reasonably adjusted to the Freundlich isotherm and to the pseudo-second-order kinetic model. Also, the application of Morris–Weber and Reichenberg models indicated that both film-diffusion and intraparticle-diffusion processes were active during the control of the adsorption kinetics
Natural polyprenylated benzophenone: keto-enol tautomerism from density functional calculations and the AIM theory
The quantum theory of atoms in molecules (QTAIM) and density functional theory (DFT) calculations were employed to investigate the structure and tautomeric equilibrium of epiclusianone, a polyisoprenylated benzophenone with interesting biological activities. Two different exchange-correlation functionals were employed, namely ωB97x-D and M06-2x, including implicit solvent models (benzene and DMSO). Our results for the thermodynamic properties show that the isomer in which the H atom is bonded to the oxygen away from the benzene ring is the most stable tautomer form of the epiclusianone, thus confirming previous charge density analysis from X-ray diffraction data (Martins et al. J Braz Chem Soc 18(8):1515–1523, 2007)
Adsorption of the herbicides diquat and difenzoquat on polyurethane foam: kinetic, equilibrium and computational studies
This work reports a study about the adsorption of the herbicides diquat and difenzoquat from aqueous medium employing polyurethane foam (PUF) as the adsorbent and sodium dodecylsulfate (SDS) as the counter ion. The adsorption efficiency was shown to be dependent on the concentration of SDS in solution, since the formation of an ion-associate between cationic herbicides (diquat and difenzoquat) and anionic dodecylsulfate is a fundamental step of the process. A computational study was carried out to identify the possible structure of the ion-associates that are formed in solution. They are probably formed by three units of dodecylsulfate bound to one unit of diquat, and two units of dodecylsulfate bound to one unit of difenzoquat. The results obtained also showed that 95% of both herbicides present in 45 mL of a solution containing 5.5 mg L^−1 could be retained by 300 mg of PUF. The experimental data were well adjusted to the Freundlich isotherm (r^2 ≥ 0.95) and to the pseudo-second-order kinetic equation. Also, the application of Morris-Weber and Reichenberg equations indicated that an intraparticle diffusion process is active in the control of adsorption kinetics
Adsorption of Bitumen Model Compounds on Kaolinite in Liquid and Supercritical Carbon Dioxide Solvents: A Study by Periodic Density Functional Theory and Molecular Theory of Solvation
The
geometry of phenanthridine, benzothiophene, tetralin, and naphthalene
representative of the heterocyclic, naphthenic, and aromatic components
of bitumen adsorbed on kaolinite is optimized using density functional
theory and periodic boundary conditions in gas phase. These bitumen
model compounds preferentially adsorb on the aluminum hydroxide surface
of kaolinite with energy decreasing in the order phenanthridine >
naphthalene > tetralin ∼ benzothiophene. The adsorption
of
phenanthridine is strengthened by hydrogen bonding between the pyridinic
N atom and an axial hydroxyl group of kaolinite, while the rest of
the molecules adsorb through van der Waals interactions. The mechanism
of solvation in CO<sub>2</sub> and the effect of liquid and supercritical
CO<sub>2</sub> on the adsorption thermodynamics are studied using
the three-dimensional reference interaction site model theory with
the closure approximation of Kovalenko and Hirata (3D-RISM-KH) molecular
theory of solvation at 293–333 K and 10–30 MPa. The
CO<sub>2</sub> solvent interacts with the aluminum hydroxide surface
of kaolinite by hydrogen bonding, with the pyridinic N atom of phenanthridine
by electrostatic interactions, and with the rest of the bitumen model
compounds by hydrophobic interactions, as inferred from the 3D site
density distribution functions of CO<sub>2</sub>. The molecule–kaolinite
potentials of mean force in CO<sub>2</sub> show that the adsorption
of naphthalene and tetralin on kaolinite is substantially weakened
as the pressure is increased and the temperature is decreased. Benzothiophene
adsorption is the least sensitive to CO<sub>2</sub> temperature and
pressure changes. In liquid CO<sub>2</sub> at 30 MPa and 293 K, the
hydrocarbon molecules are weakly adsorbed and can be desorbed by CO<sub>2</sub>, while the heterocycles would remain adsorbed, suggesting
an approach for extraction of deasphalted bitumen from oil sands.
While the most favorable thermodynamic conditions for desorption are
in liquid CO<sub>2</sub>, the kinetic barrier for desorption is the
most sensitive to small changes in the temperature and pressure in
supercritical CO<sub>2</sub>, indicating that supercritical conditions
are important for desorption rate control. These results suggest that
the investigated bitumen components can be selectively desorbed from
kaolinite by controlling the temperature and pressure of the CO<sub>2</sub> solvent and agree with experimental reports on heavy oil
recovery. These insights are valuable for the development of improved
techniques for extraction of bitumen from oil sands and deasphalting
of bitumen using liquid and supercritical CO<sub>2</sub>
Synthesis of Rubrolide Analogues as New Inhibitors of the Photosynthetic Electron Transport Chain
Many natural products have been used as a model for the
development
of new drugs and agrochemicals. Following this strategy 11 rubrolide
analogues, bearing electron-withdrawing and -donating groups at both
benzene rings, were prepared starting from commercially available
mucobromic acid. The ability of all compounds to inhibit the photosynthetic
electron transport chain in the chloroplast was investigated. The
rubrolide analogues were effective in interfering with the light-driven
ferricyanide reduction by isolated chloroplasts. The IC<sub>50</sub> values of the most active derivatives are in fact only 1 order of
magnitude higher than those of commercial herbicides sharing the same
mode of action, such as Diuron (0.27 μM). QSAR studies indicate
that the most efficient compounds are those having higher ability
to accept electrons, either by a reduction process or by an electrophilic
reaction mechanism. The results obtained suggest that the rubrolide
analogues represent promising candidates for the development of new
active principles targeting photosynthesis to be used as herbicides
Computational and Experimental Investigations of the Role of Water and Alcohols in the Desorption of Heterocyclic Aromatic Compounds from Kaolinite in Toluene
Nonaqueous
extraction is an attractive alternative to the currently
employed warm water process for extraction of bitumen from oil sands,
as it could use less energy and water. Hydroxylated cosolvents, such
as alcohols, that compete for the adsorptive clay surfaces and help
release bitumen components could help improve bitumen recovery. The
water naturally present in oil sand also affects oil–mineral
interactions. Electronic structure methods and the statistical-mechanical
3D-RISM-KH molecular theory of solvation as well as experimental desorption
measurements are employed to study the effects of water and aliphatic
alcohol cosolvents in toluene solvent on the desorption of fused pyridinic
heterocycles (ArN) from kaolinite. The geometries of phenanthridine
and acridine (representative of pyridinic heterocycles of petroleum
asphaltenes) adsorbed on the kaolinite clay surface are optimized
in periodic boundary conditions using density functional theory. The
3D-RISM-KH method is employed to calculate the solvation free energy
and potential of mean force for adsorption of the heterocycles on
kaolinite in pure and alcohol-containing toluene. The potentials of
mean force show that the adsorption of the fused pyridines on kaolinite
is stronger in pure toluene than in toluene mixed with aliphatic alcohol.
Analysis of the mechanism of desorption of phenanthridine and acridine
from kaolinite in toluene containing alcohol reveals that the alcohol
stabilizes both the pyridinic moiety and kaolinite platelet by hydrogen
bonding, thus disrupting the ArN···HO–Al(kaolinite)
hydrogen bond. A mechanism for retention of toluene on kaolinite is
also highlighted. Experimental studies of the desorption of fused
pyridines from an ArN–kaolinite aggregate show that in water-saturated
toluene the rate of desorption of the phenanthridine from kaolinite
is twice as high as that in dry toluene. The experimental and computational
results show that water and aliphatic alcohols in toluene help desorb
pyridinic heterocycles from kaolinite, a clay mineral abundant in
the oil sands. The presented insights are valuable for understanding
the molecule-clay interactions in solution and relevant to improving
the nonaqueous extraction of bitumen from oil sand