11 research outputs found
Catalytic intramolecular hydroamination of aminoallenes using titanium and tantalum complexes of sterically encumbered chiral sulfonamides
Catalysis using earth abundant metals is an important goal due to the relative scarcity and expense of precious metal catalysts. It would be even more beneficial to use earth abundant catalysts for the synthesis of common pharmaceutical structural motifs such as pyrrolidine and pyridine. Thus, developing titanium catalysts for asymmetric ring closing hydroamination is a valuable goal. In this work, four sterically encumbered chiral sulfonamides derived from naturally occurring amino acids were prepared. These compounds undergo protonolysis reactions with Ti(NMe₂)₄ or Ta(NMe₂)₅ to give monomeric complexes as determined by both DOSY NMR and X-ray crystallography. The resulting complexes are active for the ring closing hydroamination hepta-4,5-dienylamine to give a mixture of tetrahydropyridine and pyrrolidine products. However, the titanium complexes convert 6-methylhepta-4,5-dienylamine exclusively to 2-(2-methylpropenyl)pyrrolidine in higher enantioselectivity than those previously reported, with enantiomeric excesses ranging from 18–24%. The corresponding tantalum complexes were more selective with enantiomeric excesses ranging from 33–39%
Catalytic intramolecular hydroamination of aminoallenes using titanium complexes of chiral, tridentate, dianionic imine-diol ligands
Alkylation of D- or L-phenylalanine or valine alkyl esters was carried out using methyl or phenyl Grignard reagents. Subsequent condensation with salicylaldehyde, 3,5-di-tert-butylsalicylaldehyde, or 5-fluorosalicylaldehyde formed tridentate, X_2L type, Schiff base ligands. Chiral shift NMR confirmed retention of stereochemistry during synthesis. X-ray crystal structures of four of the ligands show either inter- or intramolecular hydrogen bonding interactions. The ligands coordinate to the titanium reagents Ti(NMe_2)_4 or TiCl(NMe_2)_3 by protonolysis and displacement of two equivalents of HNMe_2. The crystal structure of one example of Ti(X_2L)Cl(NMe_2) was determined and the complex has a distorted square pyramidal geometry with an axial NMe_2 ligand. The bis-dimethylamide complexes are active catalysts for the ring closing hydroamination of di- and trisubstituted aminoallenes. The reaction of hepta-4,5-dienylamine at 135 °C with 5 mol% catalyst gives a mixture of 6-ethyl-2,3,4,5-tetrahydropyridine (40–72%) and both Z- and E-2-propenyl-pyrrolidine (25–52%). The ring closing reaction of 6-methyl-hepta-4,5-dienylamine at 135 °C with 5 mol% catalyst gives exclusively 2-(2-methyl-propenyl)-pyrrolidine. The pyrrolidine products are obtained with enantiomeric excesses up to 17%
Stabilization of an enzyme cytochrome c in a metal-organic framework against denaturing organic solvents
Summary: Enzymes are promising catalysts with high selectivity and activity under mild reaction conditions. However, their practical application has largely been hindered by their high cost and poor stability. Metal-organic frameworks (MOFs) as host materials show potential in protecting proteins against denaturing conditions, but a systematic study investigating the stabilizing mechanism is still lacking. In this study, we stabilized enzyme cytochrome c (cyt c) by encapsulating it in a hierarchical mesoporous zirconium-based MOF, NU-1000 against denaturing organic solvents. Cyt c@NU-1000 showed a significantly enhanced activity compared to the native enzyme, and the composite retained this enhanced activity after treatment with five denaturing organic solvents. Moreover, the composite was recyclable without activity loss for at least three cycles. Our cyt c@NU-1000 model system demonstrates that enzyme@MOF composites prepared via post-synthetic encapsulation offer a promising route to overcome the challenges of enzyme stability and recyclability that impede the widespread adoption of biocatalysis
Probing Structural Imperfections: Protein-Aided Defect Characterization in Metal–Organic Frameworks
Defect engineering proves to be a highly effective approach
for
introducing additional open metal sites and porosity into metal–organic
frameworks (MOFs), thereby enhancing their gas storage, separation,
and chemical catalysis capabilities. However, characterizing defective
MOFs, which often exhibit nonuniform pores, presents a significant
challenge. While probe molecules have been widely utilized to explore
the physical and chemical properties of MOF pores, their application
has predominantly been limited to gas- or vapor-phase molecules. In
this study, we present a novel approach by employing a size-selective
fluorescent protein probe to characterize macroporous defects induced
by tartaric acid in a zirconium-based MOF, NU-1000. The spatial visualization
of defects using a hemoglobin-based fluorescent probe allows for the
identification of distinct structural weak points and defect formation
mechanisms in NU-1000 crystallites prepared by various methods. In
addition to confirming findings from conventional MOF characterization
methods, such as gas sorption isotherms and powdered X-ray diffraction
analysis, the hemoglobin-based protein probe unveils structural nuances
overlooked by many traditional characterization techniques
Catalytic intramolecular hydroamination of aminoallenes using titanium and tantalum complexes of sterically encumbered chiral sulfonamides
Catalysis using earth abundant metals is an important goal due to the relative scarcity and expense of precious metal catalysts. It would be even more beneficial to use earth abundant catalysts for the synthesis of common pharmaceutical structural motifs such as pyrrolidine and pyridine. Thus, developing titanium catalysts for asymmetric ring closing hydroamination is a valuable goal. In this work, four sterically encumbered chiral sulfonamides derived from naturally occurring amino acids were prepared. These compounds undergo protonolysis reactions with Ti(NMe₂)₄ or Ta(NMe₂)₅ to give monomeric complexes as determined by both DOSY NMR and X-ray crystallography. The resulting complexes are active for the ring closing hydroamination hepta-4,5-dienylamine to give a mixture of tetrahydropyridine and pyrrolidine products. However, the titanium complexes convert 6-methylhepta-4,5-dienylamine exclusively to 2-(2-methylpropenyl)pyrrolidine in higher enantioselectivity than those previously reported, with enantiomeric excesses ranging from 18–24%. The corresponding tantalum complexes were more selective with enantiomeric excesses ranging from 33–39%
Effective Strategy toward Obtaining Reliable Breakthrough Curves of Solid Adsorbents
Metal–organic frameworks (MOFs) have demonstrated
their
versatility in a wide range of applications, including chemical separation,
gas capture, and storage. In industrial adsorption processes, MOFs
are integral to the creation of selective gas adsorption fixed beds.
In this context, the assessment of their separation performance under
relevant conditions often relies on breakthrough experiments. One
aspect frequently overlooked in these experiments is the shaping of
MOF powders, which can significantly impact the accuracy of breakthrough
results. In this study, we present an approach for immobilizing MOF
particles on the surface of glass beads (GBs) utilizing trimethylolpropane
triglycidyl ether (TMPTGE) as a binder, leading to the creation of
MOF@GB materials. We successfully synthesized five targeted MOF composites,
namely, SIFSIX-3-Ni@GB, CALF-20@GB, UiO-66@GB, HKUST-1@GB, and MOF-808@GB,
each possessing distinct pore sizes and structural topologies. Characterization
studies employing powder X-ray diffraction and adsorption isotherm
analyses demonstrated that MOFs@GB retained their crystallinity and
73–90% of the Brunauer–Emmett–Teller area of
their parent MOFs. Dynamic breakthrough experiments revealed that,
in comparison to their parent MOFs, MOF@GB configurations enhanced
the accuracy of breakthrough measurements by mitigating pressure buildup
and minimizing reductions in the gas flow rate. This work underscores
the significance of meticulous experimental design, specifically in
shaping MOF powders, to optimize the efficacy of breakthrough experiments.
Our proposed strategy aims to provide a versatile platform for MOF
powder processing, thereby facilitating more reliable breakthrough
experiments
Constraining Flexibility in the MIL-88 Topology through Integration of 3-Dimensional Linkers
ABSTRACT: Metal−organic frameworks (MOFs) make up a class of crystalline,
nanoporous materials that are recognized for their tunability. While some MOFs
demonstrate flexibility, this characteristic can pose challenges in achieving precise
pore control or establishing permanent porosity. Specifically, MIL-88B is notable
for its high flexibility, as it is constructed from metal trimer clusters and two-
dimensional linkers (2DLs) featuring planar, aromatic cores, allowing significant
structural changes. In this study, we synthesized two new MOFs, NU-2010 and
NU-2011, which are structurally analogous to MIL-88B but incorporate ditopic
three-dimensional linkers (3DLs) with sterically bulky cores and higher symmetry.
Our aim was to investigate whether the introduction of 3DLs could mitigate the
flexibility observed in MIL-88B. We employed a combination of single-crystal and powder X-ray diffraction techniques to assess the flexibility of MIL-88B, NU-2010, and NU-2011 under various conditions, including thermal activation, solvent exchange, and temperature changes. Our findings indicate that incorporating 3DLs significantly reduces the framework flexibility in NU-2010 and NU-2011 relative to MIL-88B
Rationally Tailored Mesoporous Hosts for Optimal Protein Encapsulation
Proteins play important roles in the therapeutic, medical
diagnostic,
and chemical catalysis industries. However, their potential is often
limited by their fragile and dynamic nature outside cellular environments.
The encapsulation of proteins in solid materials has been widely pursued
as a route to enhance their stability and ease of handling. Nevertheless,
the experimental investigation of protein interactions with rationally
designed synthetic hosts still represents an area in need of improvement.
In this work, we leveraged the tunability and crystallinity of metal–organic
frameworks (MOFs) and developed a series of crystallographically defined
protein hosts with varying chemical properties. Through systematic
studies, we identified the dominating mechanisms for protein encapsulation
and developed a host material with well-tailored properties to effectively
encapsulate the protein ubiquitin. Specifically, in our mesoporous
hosts, we found that ubiquitin encapsulation is thermodynamically
favored. A more hydrophilic encapsulation environment with favorable
electrostatic interactions induces enthalpically favored ubiquitin–MOF
interactions, and a higher pH condition reduces the intraparticle
diffusion barrier, both leading to a higher protein loading. Our findings
provide a fundamental understanding of host–guest interactions
between proteins and solid matrices and offer new insights to guide
the design of future protein host materials to achieve optimal protein
loading. The MOF modification technique used in this work also demonstrates
a facile method to develop materials easily customizable for encapsulating
proteins with different surface properties
Biomimetic Mineralization of Large Enzymes Utilizing a Stable Zirconium-Based Metal-Organic Frameworks
Enzymes
are natural catalysts for a wide range of metabolic chemical
transformations, including selective hydrolysis, oxidation, and phosphorylation.
Herein, we demonstrate a strategy for the encapsulation of enzymes
within a highly stable zirconium-based metal-organic framework. UiO-66-F4 was synthesized under mild conditions using an enzyme-compatible
amino acid modulator, serine, at a modest temperature in an aqueous
solution. Enzyme@UiO-66-F4 biocomposites were then formed
by an in situ encapsulation route in which UiO-66-F4 grows around the enzymes and, consequently, provides protection
for the enzymes. A range of enzymes, namely, lysozyme, horseradish
peroxidase, and amano lipase, were successfully encapsulated within
UiO-66-F4. We further demonstrate that the resulting biocomposites
are stable under conditions that could denature many enzymes. Horseradish
peroxidase encapsulated within UiO-66-F4 maintained its
biological activity even after being treated with the proteolytic
enzyme pepsin and heated at 60 °C. This strategy expands the
toolbox of potential metal-organic frameworks with different topologies
or functionalities that can be used as enzyme encapsulation hosts.
We also demonstrate that this versatile process of in situ encapsulation of enzymes under mild conditions (i.e., submerged
in water and at a modest temperature) can be generalized to encapsulate
enzymes of various sizes within UiO-66-F4 while protecting
them from harsh conditions (i.e., high temperatures, contact with
denaturants or organic solvents)
Programmed Polarizability Engineering in a Cyclen-Based Cubic Zr(IV) Metal–Organic Framework to Boost Xe/Kr Separation
Efficient
separation of xenon (Xe) and krypton (Kr) mixtures through
vacuum swing adsorption (VSA) is considered the most attractive route
to reduce energy consumption, but discriminating between these two
gases is difficult due to their similar properties. In this work,
we report a cubic zirconium-based MOF (Zr-MOF) platform, denoted as
NU-1107, capable of achieving selective separation of Xe/Kr by post-synthetically
engineering framework polarizability in a programmable manner. Specifically,
the tetratopic linkers in NU-1107 feature tetradentate cyclen cores
that are capable of chelating a variety of transition-metal ions,
affording a sequence of metal-docked cationic isostructural Zr-MOFs.
NU-1107-Ag(I), which features the strongest framework polarizability
among this series, achieves the best performance for a 20:80 v/v Xe/Kr
mixture at 298 K and 1.0 bar with an ideal adsorbed solution theory
(IAST) predicted selectivity of 13.4, placing it among the highest
performing MOF materials reported to date. Notably, the Xe/Kr separation
performance for NU-1107-Ag(I) is significantly better than that of
the isoreticular, porphyrin-based MOF-525-Ag(II), highlighting how
the cyclen core can generate relatively stronger framework polarizability
through the formation of low-valent Ag(I) species and polarizable
counteranions. Density functional theory (DFT) calculations corroborate
these experimental results and suggest strong interactions between
Xe and exposed Ag(I) sites in NU-1107-Ag(I). Finally, we validated
this framework polarizability regulation approach by demonstrating
the effectiveness of NU-1107-Ag(I) toward C3H6/C3H8 separation, indicating that this generalizable
strategy can facilitate the bespoke synthesis of polarized porous
materials for targeted separations