Quantification of residual organic bases in an active pharmaceutical ingredient using mixed-mode chromatography and UV detection.

The use of organic bases is ubiquitous in chemical synthesis, yet quantifying these compounds with traditional HPLC methodologies is often hampered by poor peak shape, low retention, and limited UV absorption. When employed in the manufacture of an active pharmaceutical ingredient (API), these compounds must be controlled to levels that are safe for human consumption, requiring robust analytical methods with sufficiently low quantification limits. This work describes the development of an HPLC method for the quantification of imidazole and 1,8-Diazabicyclo[5.4.0]undec­7-ene (DBU) in an API using mixed-mode chromatography. Through control of the pH and organic modifier gradients, the retention of the basic analytes and API can be tuned independently to achieve desirable retention and sensitivity for each compound. The resulting HPLC method exhibits good performance in linearity, accuracy, sensitivity, specificity, and solution stability. Notably, these conditions avoid more complex detection modalities, such as mass spectrometry, while maintaining a system pressure below 400 bar, making the method compatible with a broad range of instruments. This approach to mixed-mode chromatography method development could be extended to different organic bases in the presence of complex molecules to fit the needs of projects in an academic or industrial environment.

Proton Conductivity via Trapped Water in Phosphonate-Based Metal-Organic Frameworks Synthesized in Aqueous Media.

Metal-organic frameworks (MOFs) are promising candidates for proton-conducting applications. Herein, we report the aqueous synthesis of two new phosphonate-based MOFs comprising glyphosate linkers, [Mg(dpmp)]·2H2O (Mg-NU-225) and [Fe(dpmp)]·2H2O (Fe-NU-225), (dpmp = N,N'-diphosphonomethyl-2,5-piperazinedione), and explore their proton conductivities. Single crystal X-ray diffraction measurements revealed that both frameworks display a two-dimensional layered structure with a cyclic ring ligand which forms in situ from the condensation of two glyphosate molecules. Under humid conditions and over a wide temperature range, water molecules are trapped between adjacent layers and facilitate rapid proton conduction. Mg-NU-225 and Fe-NU-225 recorded proton conductivities of 1.5 × 10-5 and 1.7 × 10-5 S cm-1, respectively, along the plane direction and 1.6 × 10-3 and 9.1 × 10-5 S cm-1 perpendicular to the plane direction at 55 °C and 95% relative humidity, as confirmed by two-contact probe impedance methods. The mechanism of proton transport was found to be that of the Grotthuss model from the low activation energy for proton hopping.

Transient Catenation in a Zirconium-Based Metal-Organic Framework and Its Effect on Mechanical Stability and Sorption Properties.

Interpenetration of two or more sublattices is common among many metal-organic frameworks (MOFs). Herein, we study the evolution of one zirconium cluster-based, 3,8-connected MOF from its non-interpenetrated (NU-1200) to interpenetrated (STA-26) isomer. We observe this transient catenation process indirectly using ensemble methods, such as nitrogen porosimetry and X-ray diffraction, and directly, using high-resolution transmission electron microscopy. The approach detailed here will serve as a template for other researchers to monitor the interpenetration of their MOF samples at the bulk and single-particle limits. We investigate the mechanical stability of both lattices experimentally by pressurized in situ X-ray diffraction and nanoindentation as well as computationally with density functional theory calculations. Both lines of study reveal that STA-26 is considerably more mechanically stable than NU-1200. We conclude this study by demonstrating the potential of these MOFs and their mixed phases for the capture of gaseous n-hexane, used as a structural mimic for the chemical warfare agent sulfur mustard gas.

Enhancing Four-Carbon Olefin Production from Acetylene over Copper Nanoparticles in Metal-Organic Frameworks.

Four-carbon olefins, such as 1-butene and 1,3-butadiene, are important chemical feedstocks for the production of adhesives and synthetic rubber. These compounds are found in the C4 fraction of "green oil" products that can arise during the hydrogenation of acetylene. Here, we demonstrate that control of the catalyst structure increases the yield and productivity of these important olefins with a family of catalyst materials comprising Cu nanoparticles (CuNPs) bound within the pores of Zr-based metal-organic frameworks. Using carbon monoxide as a probe molecule, we characterize the surfaces of these catalytic CuNPs with diffuse reflectance infrared Fourier transform spectroscopy, revealing that the electronic structure of the CuNP surfaces is size-dependent. Furthermore, we find that as the CuNP diameter decreases, the selectivity for C4 products increases and that lowering the stoichiometric ratio of H2/acetylene improves the selectivity and productivity of the catalyst.

Balancing volumetric and gravimetric uptake in highly porous materials for clean energy.

A huge challenge facing scientists is the development of adsorbent materials that exhibit ultrahigh porosity but maintain balance between gravimetric and volumetric surface areas for the onboard storage of hydrogen and methane gas-alternatives to conventional fossil fuels. Here we report the simulation-motivated synthesis of ultraporous metal-organic frameworks (MOFs) based on metal trinuclear clusters, namely, NU-1501-M (M = Al or Fe). Relative to other ultraporous MOFs, NU-1501-Al exhibits concurrently a high gravimetric Brunauer-Emmett-Teller (BET) area of 7310 m2 g-1 and a volumetric BET area of 2060 m2 cm-3 while satisfying the four BET consistency criteria. The high porosity and surface area of this MOF yielded impressive gravimetric and volumetric storage performances for hydrogen and methane: NU-1501-Al surpasses the gravimetric methane storage U.S. Department of Energy target (0.5 g g-1) with an uptake of 0.66 g g-1 [262 cm3 (standard temperature and pressure, STP) cm-3] at 100 bar/270 K and a 5- to 100-bar working capacity of 0.60 g g-1 [238 cm3 (STP) cm-3] at 270 K; it also shows one of the best deliverable hydrogen capacities (14.0 weight %, 46.2 g liter-1) under a combined temperature and pressure swing (77 K/100 bar → 160 K/5 bar).

A Flexible Interpenetrated Zirconium-Based Metal-Organic Framework with High Affinity toward Ammonia.

Flexible metal-organic frameworks (MOFs) are highly attractive porous crystalline materials presenting structural changes when exposed to external stimuli, the mechanism of which is often difficult to glean, owing to their complex and dynamic nature. Herein, a flexible interpenetrated Zr-MOF, NU-1401, composed of rare 4-connected Zr6 nodes and tetratopic naphthalenediimide (NDI)-based carboxylate linkers, was designed. The intra-framework pore opening deformation and inter-framework motions, when subjected to different solvent molecules, were investigated by single-crystal XRD. The distance and overlap angle between the stacked NDI pairs in the entangled structure could be finely tuned, and the interactions between NDI and solvent molecules led to solvochromism. Furthermore, the presence of electron-deficient NDI units in the linker and acid sites on the node of the interpenetrated porous structure offered high density of adsorption sites for ammonia molecules, resulting in high uptake at low pressures.

Metal-Organic-Framework-Supported and -Isolated Ceria Clusters with Mixed Oxidation States.

The formation of oxygen vacancies via reversible transitions between Ce(IV) and Ce(III) plays a crucial role in the propensity of cerium oxide to act as a supporting promoter in oxidative heterogeneous catalysis. An open challenge is, however, preparation of high-porosity, supported arrays of isolated ceria(IV, III) clusters with high porosity. Herein, we report two examples of oxy-Ce(IV, III) clusters supported and spatially isolated on an oxy-zirconium MOF, NU-1000. The clusters are introduced using either of two Ce complexes (precursors): CeIV(tmhd)4 (tmhd = 2,2,6,6-tetramethyl-3,5-heptanedionate) or CeIII(iPrCp)3 (iPrCp = tris(isopropyl-cyclopenta-dienyl), via SIM (solvothermal installation in MOFs). The prepared materials are named Ce-l-SIM-NU-1000 and Ce-n-SIM-NU-1000, respectively. X-ray photoelectron spectroscopy characterization shows that the ratio of Ce(III) to Ce(IV) oxidation states can be modulated. Difference envelope density analyses of X-ray scattering show that CexOyHz clusters in Ce-n-SIM-NU-1000 are located between pairs of Zr6 nodes, whereas in Ce-l-SIM-NU-1000, they are sited on MOF linkers throughout the micropores of NU-1000. Cluster size differences were further evaluated by pair function distribution (PDF) analyses of total X-ray scattering reveal that the node sited clusters contain of only a few cerium ions, whereas the linker-sited clusters each contain ∼90 cerium ions. The observed size appears to be defined by the size of NU-1000s triangular pores, that is, cluster formation appears to be pore templated. The Ce-SIM functionalized materials are catalytically active for hydrolysis of DMNP (dimethyl 4-nitrophenyl phosphate), a nerve-agent simulant. Conversion of a small fraction of the Ce(IV) ions in which the presence of small fractions of the cerium(IV) ions in Ce-l-SIM-NU-1000 to cerium(III) significantly enhances catalytic activity-perhaps by labilizing aqua ligands and facilitating simulant binding to the clusters Lewis-basic metal ions. While not explored here, the larger clusters, when partially reduced, are, we believe, candidate catalysts for O2 activation and subsequent selective oxidation of organic substrates.

Cyclotris(paraquat-p-phenylenes).

Reported here is the synthesis, solid-state characterization, and redox properties of new triangular, threefold symmetric, viologen-containing macrocycles. Cyclotris(paraquat-p-phenylene) (CTPQT6+ ) and cyclotris(paraquat-p-1,4-dimethoxyphenylene) (MCTPQT6+ ) were prepared and their X-ray single-crystal (super)structures reveal intricate three-dimensional packing. MCTPQT6+ results in nanometer-sized channels, in contrast with its parent counterpart CTPQT6+ which crystallizes as a couple of polymorphs in the form of intercalated assemblies. In the solid state, MCTPQT3(.+) exhibits stacks between the 1,4-dimethoxyphenylene and bipyridinium radical cations, providing new opportunities for the manipulation and control of the recognition motif associated with viologen radical cations. These redox-active cyclophanes demonstrate that geometry-matching and weak intermolecular interactions are of paramount importance in dictating the formation of their intricate solid-state superstructures.

Porosity Dependence of Compression and Lattice Rigidity in Metal-Organic Framework Series.

Porous materials, including metal-organic frameworks (MOFs), are known to undergo structural changes when subjected to applied hydrostatic pressures that are both fundamentally interesting and practically relevant. With the rich structural diversity of MOFs, the development of design rules to better understand and enhance the mechanical stability of MOFs is of paramount importance. In this work, the compressibilities of seven MOFs belonging to two topological families (representing the most comprehensive study of this type to date) were evaluated using in situ synchrotron X-ray powder diffraction of samples within a diamond anvil cell. The judicious selection of these materials, representing widely studied classes of MOFs, provides broadly applicable insight into the rigidity and compression of hybrid materials. An analysis of these data reveals that the bulk modulus depends on several structural parameters (e.g., void fraction and linker length). Furthermore, we find that lattice distortions play a major role in the compression of MOFs. This study is an important step toward developing a predictive model of the structural variables that dictate the compressibility of porous materials.

Mechanical properties of metal-organic frameworks.

As the field of metal-organic frameworks (MOFs) continues to grow, the physical stability and mechanical properties of these porous materials has become a topic of great interest. While strategies for synthesizing MOFs with desirable chemical functionalities or pore sizes have been established over the past twenty years, design principles to modulate the response of MOFs to mechanical stress are still underdeveloped. The inherent porosity of these frameworks results in many interesting and sometimes unexpected phenomena upon exposure to elevated pressures and other physical stimuli. Beyond its fundamental importance, an understanding of mechanical properties (e.g. bulk modulus, shear modulus, Young's modulus, linear compressibility, and Poisson's ratio) plays an essential role in the post-synthetic processing of MOFs, which has implications in the successful transition of these materials from academic interest to industrial relevance. This perspective provides a concise overview of the efforts to understand the mechanical properties of MOFs through experimental and computational methods. Additionally, current limitations and possible future directions for the field are also discussed briefly.

A Flexible Metal-Organic Framework with 4-Connected Zr6 Nodes.

Zr-based metal-organic frameworks (MOFs) have been known for their excellent stability; however, due to the high connectivity of the Zr6 nodes, it is challenging to introduce flexibility into Zr-MOFs. Here we present a flexible Zr-MOF named NU-1400 comprising 4-connected Zr6 nodes and tetratopic linkers. It exhibits guest-dependent structural flexibility with up to 48% contraction in the unit cell volume as evidenced by single-crystal X-ray diffraction studies. The expanded or contracted conformations of NU-1400 showed drastically different reactivity toward the hydrolysis of a nerve agent simulant owing to the size-selective effect toward the reactant.

Calcium(ii)-catalyzed enantioselective conjugate additions of amines.

The direct enantioselective chiral calcium(ii)·phosphate complex (Ca[CPA]2)-catalyzed conjugate addition of unprotected alkyl amines to maleimides was developed. This mild catalytic system represents a significant advance towards the general convergent asymmetric amination of α,ß-unsaturated electrophiles, providing medicinally relevant chiral aminosuccinimide products in high yields and enantioselectivities. Furthermore, the catalyst can be reused directly from a previously chromatographed reaction and still maintain both high yield and selectivity.