10 research outputs found
An Interface-Directed Coassembly Approach To Synthesize Uniform Large-Pore Mesoporous Silica Spheres
A facile
and controllable interface-directed coassembly (IDCA)
approach is developed for the first time to synthesize uniform discrete
mesoporous silica particles with a large pore size (ca. 8 nm) by using
3-dimensional macroporous carbon (3DOMC) as the nanoreactor for the
confined coassembly of template molecules and silica source. By controlling
the amount of the precursor solution and using Pluronic templates
with different compositions, we can synthesize mesoporous silica particles
with diverse morphologies (spheres, hollow spheres, and hemispheres)
and different mesostructure (e.g., 2-D hexagonal and 3D face centered
cubic symmetry), high surface area of about 790 m<sup>2</sup>/g, and
large pore volume (0.98 cm<sup>3</sup>/g). The particle size can be
tunable from submicrometer to micrometer regimes by changing the macropore
diameter of 3DOMC. Importantly, this synthesis concept can be extended
to fabricate multifunctional mesoporous composite spheres with a magnetic
core and a mesoporous silica shell, large saturated magnetization
(23.5 emu/g), and high surface area (280 m<sup>2</sup>/g). With the
use of the magnetic mesoporous silica spheres as a magnetically recyclable
absorbent, a fast and efficient removal of microcystin from water
is achieved, and they can be recycled for 10 times without a significant
decrease of removal efficiency for microcystin
Polymerization-Induced Colloid Assembly Route to Iron Oxide-Based Mesoporous Microspheres for Gas Sensing and Fenton Catalysis
Iron oxide materials
have wide applications due to their special physicochemical properties;
however, it is a great challenge to synthesize mesoporous iron oxide-based
microspheres conveniently and controllably with high surface area,
large pore volume, and interconnected porous structures. Herein, mesoporous
α-Fe<sub>2</sub>O<sub>3</sub>-based microspheres with high porosity
are synthesized via a facile polymerization induced colloid assembly
method through polymerization of urea–formaldehyde resin (UF
resin) and its simultaneously cooperative assembly with FeÂ(OH)<sub>3</sub> colloids in an aqueous solution, followed by subsequent thermal
treatment. Remarkably, by controlling the cross-linking degree of
UF, pure mesoporous α-Fe<sub>2</sub>O<sub>3</sub> and α-Fe<sub>2</sub>O<sub>3</sub>/carbon hybrid microspheres can be synthesized
controllably, respectively. They exhibit a uniform spherical morphology
with a particle size of around 1.0 μm, well-interconnected mesopores
(24.5 and 8.9 nm, respectively), and surface area of 54.4 m<sup>2</sup>/g (pure mFe<sub>2</sub>O<sub>3</sub> microspheres) and 144.7 m<sup>2</sup>/g (hybrids), respectively. As a result, mesoporous pure α-Fe<sub>2</sub>O<sub>3</sub> microspheres exhibited excellent H<sub>2</sub>S sensing performance with a good selectivity, high response to low
concentration H<sub>2</sub>S at 100 °C, and quick response (4
s)/recovery (5 s) dynamics owing to the high surface area, open mesopores,
and crystalline structure of the n-type α-Fe<sub>2</sub>O<sub>3</sub> semiconductor. Moreover, mesoporous α-Fe<sub>2</sub>O<sub>3</sub>/carbon hybrid microspheres were used as a novel Fenton-like
catalyst for the decomposition of methylene blue in a mild condition
and exhibit quick degradation rate, high removal efficiency (∼93%
within 35 min), and stable recycling performance owing to the synergetic
effect of a high surface area and the carbon-protected α-Fe<sub>2</sub>O<sub>3</sub>
A General Chelate-Assisted Co-Assembly to Metallic Nanoparticles-Incorporated Ordered Mesoporous Carbon Catalysts for Fischer–Tropsch Synthesis
The organization of different nano objects with tunable
sizes,
morphologies, and functions into integrated nanostructures is critical
to the development of novel nanosystems that display high performances
in sensing, catalysis, and so on. Herein, using acetylacetone as a
chelating agent, phenolic resol as a carbon source, metal nitrates
as metal sources, and amphiphilic copolymers as a template, we demonstrate
a chelate-assisted multicomponent coassembly method to synthesize
ordered mesoporous carbon with uniform metal-containing nanoparticles.
The obtained nanocomposites have a 2-D hexagonally arranged pore structure,
uniform pore size (∼4.0 nm), high surface area (∼500
m<sup>2</sup>/g), moderate pore volume (∼0.30 cm<sup>3</sup>/g), uniform and highly dispersed Fe<sub>2</sub>O<sub>3</sub> nanoparticles,
and constant Fe<sub>2</sub>O<sub>3</sub> contents around 10 wt %.
By adjusting acetylacetone amount, the size of Fe<sub>2</sub>O<sub>3</sub> nanoparticles is readily tunable from 8.3 to 22.1 nm. More
importantly, it is found that the metal-containing nanoparticles are
partially embedded in the carbon framework with the remaining part
exposed in the mesopore channels. This unique semiexposure
structure not only provides an excellent confinement effect and exposed
surface for catalysis but also helps to tightly trap the nanoparticles
and prevent aggregating during catalysis. Fischer–Tropsch synthesis
results show that as the size of iron nanoparticles decreases, the
mesoporous Fe–carbon nanocomposites exhibit significantly improved
catalytic performances with C<sub>5+</sub> selectivity up to 68%,
much better than any reported promoter-free Fe-based catalysts due
to the unique semiexposure morphology of metal-containing nanoparticles
confined in the mesoporous carbon matrix
Templated Fabrication of Core–Shell Magnetic Mesoporous Carbon Microspheres in 3‑Dimensional Ordered Macroporous Silicas
A confined synthesis strategy is
demonstrated for the fabrication
of core–shell magnetic mesoporous carbon microspheres by solvent
evaporation induced self-assembly of ethanolic solutions of precursors
(containing resol as carbon source, Pluronic F127 as a structure directing
agent) in the cavity of presynthesized 3-dimensional ordered macroporous
silica materials with each macropore filled with a magnetite particle.
The obtained magnetic mesoporous carbon (Fe<sub>3</sub>O<sub>4</sub>@FDU-15) microspheres possess uniform diameter of ∼460 nm,
ultralarge mesopores of 13.8 nm, high surface area of ∼403
m<sup>2</sup>/g, and strong magnetization (20.7 emu/g). Sub-4 nm gold
nanoparticles are loaded in the porous shell of the magnetic microspheres,
resulting in a novel Fe<sub>3</sub>O<sub>4</sub>@FDU-15/Au nanocatalyst
with an excellent performance in catalyzing the epoxidation of styrene
with high conversion (72%) and selectivity (85%) toward styrene oxide
in 12 h and a good magnetic field-assisted recyclability
Tricomponent Coassembly Approach To Synthesize Ordered Mesoporous Carbon/Silica Nanocomposites and Their Derivative Mesoporous Silicas with Dual Porosities
Highly
ordered mesoporous carbon/silica nanocomposites and dual-mesoporous
silicas with a 3D cubic structure were successfully synthesized through
a facile tricomponent coassembly approach by using the lab-made diblock
copolymer polyÂ(ethylene oxide)-<i>b</i>-polystyrene as a
template. The mesoporous silicas exhibit a high surface area and uniform
bimodal mesopores. The bimodal mesopores can be tuned by simply changing
the ratio of carbon/silica precursors and the pyrolysis temperature
in N<sub>2</sub>. Gold nanoparticles were successfully loaded in the
primary large mesopores for use as a heterogeneous nanacatalyst, which
exhibits excellent performance in the epoxidation of styrene, demonstrating
their potential for catalyst support
Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5‑<i>a</i>]pyrazines as ATR Inhibitors
A saturation
strategy focused on improving the selectivity and
physicochemical properties of ATR inhibitor HTS hit <b>1</b> led to a novel series of highly potent and selective tetrahydropyrazoloÂ[1,5-<i>a</i>]Âpyrazines. Use of PI3Kα mutants as ATR crystal structure
surrogates was instrumental in providing cocrystal structures to guide
the medicinal chemistry designs. Detailed DMPK studies involving cyanide
and GSH as trapping agents during microsomal incubations, in addition
to deuterium-labeled compounds as mechanistic probes uncovered the
molecular basis for the observed CYP3A4 TDI in the series
Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles (ABI) as ATR Inhibitors
Compound <b>13</b> was discovered
through morphing of the
ATR biochemical HTS hit <b>1</b>. The ABI series was potent
and selective for ATR. Incorporation of a 6-azaindole afforded a marked
increase in cellular potency but was associated with poor PK and hERG
ion channel inhibition. DMPK experiments established that CYP P450
and AO metabolism in conjunction with Pgp and BCRP efflux were major
causative mechanisms for the observed PK. The series also harbored
the CYP3A4 TDI liability driven by the presence of both a morpholine
and an indole moiety. Incorporation of an adjacent fluorine or nitrogen
into the 6-azaindole addressed many of the various medicinal chemistry
issues encountered
Discovery of Novel Allosteric Mitogen-Activated Protein Kinase Kinase (MEK) 1,2 Inhibitors Possessing Bidentate Ser212 Interactions
Using structure-based design, two novel series of highly
potent
biaryl amine mitogen-activated protein kinase kinase (MEK) inhibitors
have been discovered. These series contain an H-bond acceptor, in
a shifted position compared with previously disclosed compounds, and
an adjacent H-bond donor, resulting in a bidentate interaction with
the Ser212 residue of MEK1. The most potent compound identified, <b>1</b> (G-894), is orally active in in vivo pharmacodynamic and
tumor xenograft models
Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice
A series
of trisubstituted hydroxylactams was identified as potent
enzymatic and cellular inhibitors of human lactate dehydrogenase A.
Utilizing structure-based design and physical property optimization,
multiple inhibitors were discovered with <10 μM lactate IC<sub>50</sub> in a MiaPaca2 cell line. Optimization of the series led
to <b>29</b>, a potent cell active molecule (MiaPaca2 IC<sub>50</sub> = 0.67 μM) that also possessed good exposure when
dosed orally to mice
Discovery of Novel PI3-Kinase δ Specific Inhibitors for the Treatment of Rheumatoid Arthritis: Taming CYP3A4 Time-Dependent Inhibition
PI3Kδ is a lipid kinase and a member of a larger
family of enzymes, PI3K class IAÂ(α, β, δ) and IB
(γ), which catalyze the phosphorylation of PIP2 to PIP3. PI3Kδ
is mainly expressed in leukocytes, where it plays a critical, nonredundant
role in B cell receptor mediated signaling and provides an attractive
opportunity to treat diseases where B cell activity is essential,
e.g., rheumatoid arthritis. We report the discovery of novel, potent,
and selective PI3Kδ inhibitors and describe a structural hypothesis
for isoform (α, β, γ) selectivity gained from interactions
in the affinity pocket. The critical component of our initial pharmacophore
for isoform selectivity was strongly associated with CYP3A4 time-dependent
inhibition (TDI). We describe a variety of strategies and methods
for monitoring and attenuating TDI. Ultimately, a structure-based
design approach was employed to identify a suitable structural replacement
for further optimization