MOF-Thermogel Composites for Differentiated and Sustained Dual Drug Delivery.

In recent years, multidrug therapy has gained increasing popularity due to the possibility of achieving synergistic drug action and sequential delivery of different medical payloads for enhanced treatment efficacy. While a number of composite material release platforms have been developed, few combine the bottom-up design versatility of metal-organic frameworks (MOFs) to tailor drug release behavior, with the convenience of temperature-responsive hydrogels (or thermogels) in their unique ease of administration and formulation. Yet, despite their potential, MOF-thermogel composites have been largely overlooked for simultaneous multidrug delivery. Herein, we report the first systematic study of common MOFs (UiO-66, MIL-53(Al), MIL-100(Fe), and MOF-808) with different pore sizes, geometries, and hydrophobicities for their ability to achieve simultaneous dual drug release when embedded within PEG-containing thermogel matrices. After establishing that MOFs exert small influences on the rheological properties of the thermogels despite the penetration of polymers into the MOF pores in solution, the release profiles of ibuprofen and caffeine as model hydrophobic and hydrophilic drugs, respectively, from MOF-thermogel composites were investigated. Through these studies, we elucidated the important role of hydrophobic matching between MOF pores and loaded drugs in order for the MOF component to distinctly influence drug release kinetics. These findings enabled us to identify a viable MOF-thermogel composite containing UiO-66 that showed vastly different release kinetics between ibuprofen and caffeine, enabling temporally differentiated yet sustained simultaneous drug release to be achieved. Finally, the MOF-thermogel composites were shown to be noncytotoxic in vitro, paving the way for these underexploited composite materials to find possible clinical applications for multidrug therapy.

UiO-66 metal organic frameworks with high contents of flexible adipic acid co-linkers.

Adipic acid, an industrially-important chemical that can be sustainably derived from biomass and post-consumer nylon, is traditionally overlooked as a linker for MOFs. Herein, we report the first direct one-pot method for synthesising UiO-66 MOFs with an unprecedented 69 mol% adipate content, as well as the feasibility of these materials for MOF defect engineering by rapid and selective adipate thermolysis.

Reactivity of Diamines in Acyclic Diamino Carbene Gold Complexes.

Acyclic diamino carbenes (ADCs) are interesting alternatives to their more widely studied N-heterocyclic carbene counterparts, particularly due to their greater synthetic accessibility and properties such as increased sigma donation and structural flexibility. ADC gold complexes are typically obtained through the reaction of equimolar amounts of primary/secondary amines on gold-coordinated isocyanide ligands. As such, the reaction of diamine nucleophiles to isocyanide gold complexes was expected to lead to bis-ADC gold compounds with potential applications in catalysis or as novel precursors for gold nanomaterials. However, the reaction of primary diamines with two equivalents of isocyanide gold chlorides resulted in only one of the amine groups reacting with the isocyanide carbon. The resulting ADC gold complexes bearing free amines dimerized via coordination of the amine to the partner gold atom, resulting in cyclic, dimeric gold complexes. In contrast, when secondary diamines were used, both amines reacted with an isocyanide carbon, leading to the expected bis-ADC gold complexes. Density functional theory calculations were performed to elucidate the differences in the reactivities between primary and secondary diamines. It was found that the primary amines were associated with higher reaction barriers than the secondary amines and hence slower reaction rates, with the formation of the second carbenes in the bis-ADC compounds being inhibitingly slow. It was also found that diamines have a unique reactivity due to the second amine serving as an internal proton shuttle.

Template-Controlled Synthesis of Polyimidazolium Salts by Multiple [2+2] Cycloaddition Reactions.

The tetrakisimidazolium salt H4 -2(Br)4 , featuring a central benzene linker and 1,2,4,5-(nBu-imidazolium-Ph-CH=CH-) substituents reacts with Ag2 O in the presence of AgBF4 to yield the tetranuclear, oktakis-NHC assembly [3](BF4 )4 . Cation [3]4+ features four pairs of olefins from the two tetrakis-NHC ligands perfectly arranged for a subsequent [2+2] cycloaddition. Irradiation of [3](BF4 )4 with a high pressure Hg lamp connects the two tetra-NHC ligands through four cyclobutane linkers to give compound [4](BF4 )4 . Removal of the template metals yields the novel oktakisimidazolium salt H8 -5(BF4 )8 . The tetrakisimidazolium salt H4 -2(BF4 )4 and the oktakisimidazolium salt H8 -5(BF4 )8 have been used as multivalent anion receptors and their anion binding properties towards six different anions have been compared.

Site-selective metallation of dicarbene precursors.

An imidazolium/2-chlorobenzimidazole bis-NHC precursor has been reacted with Ag2O followed by transmetallation with [AuCl(THT)] to give the Au-NHC complex via metallation of the imidazolium site, while the reaction of the same bis-NHC precursor with [Pd(PPh3)4] yields exclusively the azolato complex by oxidative addition of the C2-Cl bond to Pd0. Both complexes have been converted into the heterobimetallic Au/Pd-complex by reaction with [Pd(PPh)3]4 (for the NHC complex) or Ag2O/[AuCl(THT)] (for the azolato complex), respectively.

Template Synthesis of Three-Dimensional Hexakisimidazolium Cages.

A procedure for the synthesis of three-dimensional hexakisimidazolium cage compounds has been developed. The reaction of the trigonal trisimidazolium salts H3 L(PF6 )3 , decorated with three N-olefinic pendants, and silver oxide yielded trinuclear trisilver(I) hexacarbene molecular cylinders of the type [Ag3 L2 ]3+ with the olefinic pendants from the two different tricarbene ligands arranged in three pairs. Subsequent UV irradiation gave three cyclobutane links between the two tris-NHC ligands in three [2+2] cycloaddition reactions, thereby generating a three-dimensional hexakis-NHC ligand. Removal of the metal ions resulted in the formation of three-dimensional hexakisimidazolium cages with a large internal cavity.

High-Fidelity, Narcissistic Self-Sorting in the Synthesis of Organometallic Assemblies from Poly-NHC Ligands.

Highly selective, narcissistic self-sorting has been observed in the one-pot synthesis of three organometallic molecular cylinders of type [M3 {L-(NHC)3 }2 ](PF6 )3 (M=Ag+ , Au+ ; L=1,3,5-benzene, triphenylamine, or 1,3,5-triphenylbenzene) from L-(NHC)3 and silver(I) or gold(I) ions. The molecular cylinders contain only one type of tris-NHC ligand with no crossover products detectable. Transmetalation of the tris-NHC ligands from Ag+ to Au+ in a one-pot reaction with retention of the supramolecular structures is also demonstrated. High-fidelity self-sorting was also observed in the one-pot reaction of benzene-bridged tris-NHC and tetrakis-NHC ligands with Ag2 O. This study for the first time extends narcissistic self-sorting in metal-ligand interactions from Werner-type complexes to organometallic derivatives.

Turn-On Fluorescence in Tetra-NHC Ligands by Rigidification through Metal Complexation: An Alternative to Aggregation-Induced Emission.

Two tetraphenylethylene (TPE) bridged tetraimidazolium salts, [H4 L-Et](PF6 )4 and [H4 L-Bu](PF6 )4 , were used as precursors for the synthesis of the dinuclear AgI and AuI tetracarbene complexes [Ag2 (L-Et)](PF6 )2 , [Ag2 (L-Bu)](PF6 )2 , [Au2 (L-Et)](PF6 )2 , and [Au2 (L-Bu)](PF6 )2 . The tetraimidazolium salts show almost no fluorescence (ΦF <1 %) in dilute solution while their NHC complexes display fluorescence "turn-on" (ΦF up to 47 %). This can be ascribed to rigidification mediated by the restriction of intramolecular rotation within the TPE moiety upon complexation. DFT calculations confirm that the metals are not involved in the lowest excited singlet and triplet states, thus explaining the lack of phosphorescence and fast intersystem crossing as a result of heavy atom effects. The rigidification upon complexation for fluorescence turn-on constitutes an alternative to the known aggregation-induced emission (AIE).

Tris(imidazolin-2-ylidenamino)phosphine: A Crystalline Phosphorus(III) Superbase That Splits Carbon Dioxide.

We report the synthesis and remarkable properties of the phosphine P(NIiPr)3 (NIiPr=1,3-diisopropyl-4,5-dimethylimidazolin-2-ylidenamino), a crystalline solid accessible through a short and scalable route. Evaluation of the electron-donor properties reveals a Tolman electronic parameter (TEP) value of 2029.7 cm-1 for the new phosphine that is significantly lower than those of all known phosphines or even N-heterocyclic carbenes. Moreover, P(NIiPr)3 is more basic [pKBH+ (MeCN)=38.8] than Verkade's proazaphosphatranes, thus being the strongest reported nonionic phosphorus(III) superbase. The coordination chemistry of the new phosphine towards different metal centers has been explored, and due to its unique electron-releasing character, the phosphine is capable of capturing and cleaving the CO2 molecule.

Motorized Janus metal organic framework crystals.

We describe Janus metal organic framework crystals that are propelled by bubble ejection. The Janus crystals are prepared by selective epitaxial growth of ZIF-67 on ZIF-8. The Janus crystals catalyse the decomposition of H2O2 into H2O and O2 on the ZIF-67 surface but not on the zinc containing ZIF-8 surface, resulting in propulsion of the Janus crystals.

Two-dimensional metal-organic framework with wide channels and responsive turn-on fluorescence for the chemical sensing of volatile organic compounds.

We report a 2D layered metal-organic framework (MOF) with wide channels named NUS-1 and its activated analogue NUS-1a composed of Zn4O-like secondary building units and tetraphenylethene (TPE)-based ligand 4,4'-(2,2-diphenylethene-1,1-diyl)dibenzoic acid. Due to its special structure, NUS-1a exhibits unprecedented gas sorption behavior, glass-transition-like phase transition under cryogenic conditions, and responsive turn-on fluorescence to various volatile organic compounds. Our approach using angular ligand containing partially fixed TPE units paves a way toward highly porous MOFs with fluorescence turn-on response that will find wide applications in chemical sensing.

Tuning omniphobicity via morphological control of metal-organic framework functionalized surfaces.

Fabrication of microstructures for imparting omniphobicity to a surface generally requires the use of lithographic techniques and specialized equipment. We report instead a simple strategy for the synthesis of microstructured surfaces via metal­organic framework (MOF) self-assembly. Our method allows us to localize epitaxial growth of MOF at the tips of needle crystals to create mushroom-shaped structures, thus conferring re-entrant textures to the MOF-functionalized surfaces. These structures synthesized via wet chemistry were found to have omniphobic properties due to the resulting re-entrant texture.