Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal–Organic Framework (MOF)

Encapsulating a drug molecule into a water‐reactive metal–organic framework (MOF) leads to amorphous drug confined within the nanoscale pores. Rapid release of drug occurs upon hydrolytic decomposition of MOF in dissolution media. Application to improve dissolution and solubility for the hydrophobic small drug molecules curcumin, sulindac, and triamterene is demonstrated. The drug@MOF composites exhibit significantly enhanced dissolution and achieves high supersaturation in simulated gastric and/or phosphate buffer saline media. This combination strategy where MOF inhibits crystallization of the amorphous phase and then releases drug upon MOF irreversible structural collapse represents a novel and generalizable approach for drug delivery of poorly soluble compounds while overcoming the traditional weakness of amorphous drug delivery: physical instability of the amorphous form.MOF‐Transporter: Eine Wirkstofftransportstrategie, bei der ein Metall‐organisches Gerüst die Kristallisation der amorphen Phase hemmt und dann unter hydrolytischer Zersetzung den Wirkstoff freisetzt, stellt einen neuartigen Ansatz für die Verabreichung schwerlöslicher Verbindungen dar und überwindet zugleich den traditionellen Schwachpunkt amorpher Wirkstoffe: die physikalische Instabilität der amorphen Form.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152895/1/ange201907652.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152895/2/ange201907652-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152895/3/ange201907652_am.pd

Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal–Organic Framework (MOF)

Encapsulating a drug molecule into a water‐reactive metal–organic framework (MOF) leads to amorphous drug confined within the nanoscale pores. Rapid release of drug occurs upon hydrolytic decomposition of MOF in dissolution media. Application to improve dissolution and solubility for the hydrophobic small drug molecules curcumin, sulindac, and triamterene is demonstrated. The drug@MOF composites exhibit significantly enhanced dissolution and achieves high supersaturation in simulated gastric and/or phosphate buffer saline media. This combination strategy where MOF inhibits crystallization of the amorphous phase and then releases drug upon MOF irreversible structural collapse represents a novel and generalizable approach for drug delivery of poorly soluble compounds while overcoming the traditional weakness of amorphous drug delivery: physical instability of the amorphous form.MOF carrier: A drug delivery strategy where a metal–organic framework inhibits crystallization of the amorphous drug phase and then releases the drug upon hydrolytic decomposition represents a novel approach for delivery of poorly soluble compounds while overcoming the traditional weakness of amorphous drug delivery: physical instability of the amorphous form.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152844/1/anie201907652-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152844/2/anie201907652_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152844/3/anie201907652.pd

Achieving Balanced Energetics through Cocrystallization

Achieving energetic materials with a balanced ratio of oxidant to fuel is a challenge that has been difficult to meet through molecular synthesis. The alternative approach, composite formulation, fails to achieve intimate association of the components to the detriment of performance. Herein, the energetic oxidizer ammonium dinitramide (ADN) is combined with fuel‐rich pyrazine‐1,4‐dioxide via cocrystallization. The result is a material with a balanced oxidant/fuel ratio in which the components maintain intimate association. The material exhibits desirable physical and energetic properties which are much improved over ADN and comparable to contemporary energetics.Balanceakt: Eine neu entwickelte Methode ermöglicht die Herstellung von sauerstoffbalancierten energetischen Materialien durch Kokristallisation. Sie vermeidet die Risiken der molekularen Synthese und erreicht eine innige Verbindung von oxidierenden und Brennstoffgruppen. Angewendet auf Ammoniumdinitramid macht die Methode ein energetisches Material mit verbesserten physikalischen und energetischen Eigenschaften zugänglich.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152711/1/ange201908709-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152711/2/ange201908709.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152711/3/ange201908709_am.pd

Crystal polymorphism in a carbamazepine derivative: Oxcarbazepine

Although crystal polymorphism of carbamazepine (CBZ), an anticonvulsant used to treat epilepsy, has been known for decades, the phenomenon has only recently been noted for its keto-derivative oxcarbazepine (OCB). Here it is demonstrated that OCB possesses at least three anhydrous polymorphs. Although all forms are morphologically similar, making differentiation between crystal modifications by optical microscopy difficult, powder X-ray diffraction, Raman spectroscopy, and thermomicroscopy show distinctive differences. These techniques provide an efficient method of distinguishing between the three polymorphs. The crystal structure of form II of OCB is reported for the first time and the structure of form I has been redetermined at low temperature. Remarkably, both the molecular conformation and crystal packing of form II are in excellent agreement with the blind prediction made in 2007. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:794–803, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64542/1/21873_ftp.pd

Vapor sensing with arrays of carbon black-polymer composites

Thin films of carbon black-organic polymer composites have been deposited across two metallic leads, with swelling- induced resistance changes of the films signaling the presence of vapors. To identify and classify vapors, arrays of such vapor-sensing elements have been constructed, with each element containing a different organic polymer as the insulating phase. The differing gas-solid partition coefficients for the various polymers of the sensor array produce a pattern of resistance changes that can be used to classify vapors and vapor mixtures. This type of sensor array has been shown to resolve all organic vapors that have been analyzed, and can even resolve H_2O from D_2O. Blends of poly(vinyl acetate) and poly(methyl methacrylate) have been used to produce a series of sensor that response to vapors with a change in resistance of a magnitude that is not simply a linear combination of the responses of the pure polymers. These compatible blend composite detectors provided additional analyte discrimination information relative to a reference detector array that only contained composites formed using the pure polymer phases. Vapor signatures from chemicals used in land mine explosives, including TNT, DNT, and DNB, have been detected in air in short sampling time and discriminated from each other using these sensor arrays

Second Generation MOF's for Hydrogen Storage

This final technical report summarizes work exploring strategies to generate second generation metal organic frameworks (MOFs). These strategies were (a) the formation of interpenetrated frameworks and (b) the generation of coordinatively unsaturated metal centers (open metal sites). In the first phase of the project the effectiveness of these strategies was evaluated experimentally by measuring the saturation hydrogen uptake at high pressure and low temperature of 14 MOFs. The results of these studies demonstrated that surface area is the most useful parameter that correlates with ultimate hydrogen capacity. The strategy of interpenetration has so far failed to produce MOFs with high surface areas and therefore high saturation capacities for hydrogen have not been achieved. The incorporation of coordinatively unsaturated metal centers, however, is a promising strategy that allows higher heats of H2 adsorption to be realized without compromising surface area. Based on these initial findings, research efforts in phase two have concentrated on the discovery of new ultrahigh surface area materials with metal centers capable of supporting coordinative unsaturation without structural collapse. One approach has been the synthesis of new organic linkers that have more exposed edges, which is a factor that contributes to increasing surface area, at least when considering subunits of graphene sheets. Another strategy has been to synthesize MOFs with reduced symmetry linkers in order to generate structure types that are less likely to interpenetrate. Successful implementation of these strategies has resulted in the synthesis of 7 new compounds one of which is the highest surface area Cu based MOF reported to date

Porous Solids Arising from Synergistic and Competing Modes of Assembly: Combining Coordination Chemistry and Covalent Bond Formation

Design and synthesis of porous solids employing both reversible coordination chemistry and reversible covalent bond formation is described. The combination of two different linkage modes in a single material presents a link between two distinct classes of porous materials as exemplified by metal–organic frameworks (MOFs) and covalent organic frameworks (COFs). This strategy, in addition to being a compelling material‐discovery method, also offers a platform for developing a fundamental understanding of the factors influencing the competing modes of assembly. We also demonstrate that even temporary formation of reversible connections between components may be leveraged to make new phases thus offering design routes to polymorphic frameworks. Moreover, this approach has the striking potential of providing a rich landscape of structurally complex materials from commercially available or readily accessible feedstocks.Auf gute Zusammenarbeit: Koordinationschemie und die Bildung kovalenter Bindungen können im selben Material zur gleichen Zeit auftreten. Ein Gleichgewicht zwischen Inkubationszeit der organischen Verbindungen und Solvenszerfall/Basenbildung steuert die Konkurrenz zwischen den beiden Prozessen und bestimmt die gebildete Phase. Selbst die temporäre Bildung reversibler Verknüpfungen zwischen Komponenten lässt sich zur Herstellung neuer Phasen nutzen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110844/1/ange_201411735_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110844/2/4055_ftp.pd

Rapid Guest Exchange and Ultraâ Low Surface Tension Solvents Optimize Metalâ Organic Framework Activation

Exploratory research into the critical steps in metalâ organic framework (MOF) activation involving solvent exchange and solvent evacuation are reported. It is discovered that solvent exchange kinetics are extremely fast, and minutes rather days are appropriate for solvent exchange in many MOFs. It is also demonstrated that choice of a very low surface tension solvent is critical in successfully activating challenging MOFs. MOFs that have failed to be activated previously can achieve predicted surface areas provided that lower surface tension solvents, such as nâ hexane and perfluoropentane, are applied. The insights herein aid in the efficient activation of MOFs in both laboratory and industrial settings and provide best practices for avoiding structural collapse.Ein Wechsel des Lösungsmittels mit anschlieà ender Evakuierung aktiviert Metallâ organische Gerüste (MOFs), maximiert ihre Oberflächen und verbessert ihre Eigenschaften bei der Gasspeicherung. Wenn der Austausch schnell erfolgt und Lösungsmittel mit sehr niedriger Oberflächenspannung verwendet werden, bleibt die Porosität erhalten, und die MOFâ Struktur fällt nicht in sich zusammen.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139930/1/ange201709187.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139930/2/ange201709187_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139930/3/ange201709187-sup-0001-misc_information.pd

Rapid Guest Exchange and Ultraâ Low Surface Tension Solvents Optimize Metalâ Organic Framework Activation

Exploratory research into the critical steps in metalâ organic framework (MOF) activation involving solvent exchange and solvent evacuation are reported. It is discovered that solvent exchange kinetics are extremely fast, and minutes rather days are appropriate for solvent exchange in many MOFs. It is also demonstrated that choice of a very low surface tension solvent is critical in successfully activating challenging MOFs. MOFs that have failed to be activated previously can achieve predicted surface areas provided that lower surface tension solvents, such as nâ hexane and perfluoropentane, are applied. The insights herein aid in the efficient activation of MOFs in both laboratory and industrial settings and provide best practices for avoiding structural collapse.An exchange for the better: Activation involving solvent exchange and evacuation is crucial to achieve maximum surface area and gasâ storage properties in metalâ organic frameworks (MOFs). Porosity is preserved when fast solvent exchange kinetics and ultraâ low surface tension solvents are exploited yielding MOFs without structural collapse.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140054/1/anie201709187_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140054/2/anie201709187-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140054/3/anie201709187.pd