Biomedically-relevant metal organic framework-hydrogel composites.

Metal organic frameworks (MOFs) are incredibly versatile three-dimensional porous materials with a wide range of applications that arise from their well-defined coordination structures, high surface areas and porosities, as well as ease of structural tunability due to diverse compositions achievable. In recent years, following advances in synthetic strategies, development of water-stable MOFs and surface functionalisation techniques, these porous materials have found increasing biomedical applications. In particular, the combination of MOFs with polymeric hydrogels creates a class of new composite materials that marries the high water content, tissue mimicry and biocompatibility of hydrogels with the inherent structural tunability of MOFs in various biomedical contexts. Additionally, the MOF-hydrogel composites can transcend each individual component such as by providing added stimuli-responsiveness, enhancing mechanical properties and improving the release profile of loaded drugs. In this review, we discuss the recent key advances in the design and applications of MOF-hydrogel composite materials. Following a summary of their synthetic methodologies and characterisation, we discuss the state-of-the-art in MOF-hydrogels for biomedical use - cases including drug delivery, sensing, wound treatment and biocatalysis. Through these examples, we aim to demonstrate the immense potential of MOF-hydrogel composites for biomedical applications, whilst inspiring further innovations in this exciting field.

Solution-Printable PEDOT Solid-Contact for Nitrate-Selective Electrodes: Enhanced Selectivity from Anion Dopant Exchange.

Poly(3,4-ethylenedioxythiophene)-polyethylene glycol (PEDOT:PEG) is a conductive material adopted in bioelectronics due to its biocompatibility and stability. While PEDOT has established its utility in cationic solid-contact ion-selective electrodes (sc-ISEs), its anionic counterpart remains less explored. Herein, we report the first example of PEDOT:PEG as a solution-printable solid-contact for all-solid-state nitrate-selective electrodes and a simple ion exchange treatment which can significantly enhance nitrate selectivity. Electrochemical impedance spectroscopy revealed that the sc-ISEs with perchlorate (ClO4-)-doped PEDOT:PEG suffered a large overall resistance. Removal of the ClO4- dopant via ion exchange reduced the resistance, resulting in significant improvement in sc-ISE performance. The optimal sc-ISE exhibited near-Nernstian response (-55.8 mV/decade) across a wide dynamic range (0.1 M to 1.12 µM) and excellent Hofmeister selectivity, which was maintained after prolonged continuous usage. This simple drop-cast and ion-exchange protocol is amenable to the scalable preparation of flexible anion sc-ISEs.

Concepts and Emerging Trends for Structural Battery Electrolytes.

The structural battery is a multifunctional energy storage device that aims to address the weight and volume efficiency issues that conventional batteries face, especially in electric transportation. By combining the functions of mechanical load bearing and energy storage, structural batteries can reduce the reliance on, or even eventually replace the main power source in an electric vehicle or a drone. However, one of the key challenges to be addressed before achieving multifunctionality in structural batteries would be the design of a suitable multifunctional structural battery electrolyte. The structural battery electrolyte is the constituent that provides mechanical integrity under flexural loads or impact and hence determines the electrochemical and much of the mechanical performance of a structural battery device. This concept paper aims to cover the key considerations and challenges facing the design of structural battery electrolytes. In addition, the main approaches to surmount these challenges are highlighted, keeping design aspects like sustainability and recyclability in view.

Halogen Bonding Ionophore for Potentiometric Iodide Sensing.

Iodide (I-) is an essential micronutrient for thyroid function. Hence, rapid and portable sensing is important for I- quantification in food and biological samples. Herein, we report the first example of a halogen bonding (XB) tripodal ionophore (XB1) which is selective for the I- anion. NMR binding studies of XB1 and its H-triazole analog HB2 with I- demonstrated the dominant influence of XB interactions between the ionophore and the I- analyte. The phase boundary model was applied to formulate iodide-selective electrodes with the ionophore XB1. The optimal electrode exhibited a near-Nernstian response of -51.9 mV per decade within a large dynamic range (10-1 to 10-6 M) and notably anti-Hofmeister selectivity for I- over thiocyanate (SCN-), enabling the in situ determination of I- in complex samples. This work establishes XB as a viable supramolecular interaction in the potentiometric sensing of anions.

Absolute Configuration Determination from Low ee Compounds by the Crystalline Sponge Method. Unusual Conglomerate Formation in a Pre-Determined Crystalline Lattice.

When chiral compounds with low enantiomeric excess (ee, R:S=m:n) were absorbed into the void of the crystalline sponge (CS), enantiomerically pure [(R)m (S)n ] chiral composites were formed, changing the centrosymmetric space group into non-centrosymmetric one. The absolute configuration of the analyte compounds was elucidated with a reasonable Flack (Parsons) parameter value. This phenomenon is characteristic to the "post-crystallization" in the pre-determined CS crystalline lattice, seldom found in common crystallization where the crystalline lattice is defined by an analyte itself. The results highlight the potential of the CS method for absolute configuration determination of low ee samples, an often encountered situation in asymmetric synthesis studies.

Unprecedented Acid-Promoted Polymerization and Gelation of Acrylamide: A Serendipitous Discovery.

Dilute acid polymerizes degassed, aqueous acrylamide with concomitant gelation, without the need for added free radical initiator or cross-linking agent. This reaction is accelerated by sonication or UV irradiation, but inhibited by adventitious oxygen or the addition of a free radical inhibitor, suggesting an acid-accelerated free radical process. The resulting hydrogels are thixotropic in nature and partially disrupted by the addition of chaotropic agents, indicating the importance of hydrogen bonding to the 3D network. This discovery was made while trying to prepare pectin-polyacrylamide hydrogels. We observed that pectin initiated the gelation of acrylamide, but only if the aqueous pectin samples had a pH lower than ca. 5.

Desymmetrization of meso-Dibromocycloalkenes through Copper(I)-Catalyzed Asymmetric Allylic Substitution with Organolithium Reagents.

The highly regio- and enantioselective (up to >99:1 dr, up to 99:1 er) desymmetrization of meso-1,4-dibromocycloalk-2-enes using asymmetric allylic substitution with organolithium reagents to afford enantioenriched bromocycloalkenes (ring size of 5 to 7) has been achieved. The cycloheptene products undergo an unusual ring contraction. The synthetic versatility of this Cu(I)-catalyzed reaction is demonstrated by the concise stereocontrolled preparation of cyclic amino alcohols, which are privileged chiral structures in natural products and pharmaceuticals and widely used in synthesis and catalysis.

Stereospecific Ring Contraction of Bromocycloheptenes through Dyotropic Rearrangements via Nonclassical Carbocation-Anion Pairs.

Experimental and theoretical evidence is reported for a rare type I dyotropic rearrangement involving a [1,2]-alkene shift, leading to the regio- and stereospecific ring contraction of bromocycloheptenes. This reaction occurs under mild conditions, with or without a Lewis acid catalyst. DFT calculations show that the reaction proceeds through a nonclassical carbocation-anion pair, which is crucial for the low activation barrier and enantiospecificity. The chiral cyclopropylcarbinyl cation may be a transition state or an intermediate, depending on the reaction conditions.

Total Synthesis of the Schisandraceae Nortriterpenoid Rubriflordilactone†A.

Full details of the total synthesis of the Schisandraceae nortriterpenoid natural product rubriflordilactone A are reported. Palladium- and cobalt-catalyzed polycyclizations were employed as key strategies to construct the central pentasubstituted arene from bromoendiyne and triyne precursors. This required the independent assembly of two AB ring aldehydes for combination with a common diyne component. A number of model systems were explored to investigate these two methodologies, and also to establish routes for the installation of the challenging benzopyran and butenolide rings.

An efficient synthesis of an exo-enone analogue of LL-Z1640-2 and evaluation of its protein kinase inhibitory activities.

An efficient synthesis of an exo-enone analogue (5) of resorcylic acid lactone (RAL), natural product LL-Z1640-2 (1), has been achieved using a Ni-catalysed regioselective reductive coupling macrocyclisation of an alkyne-aldehyde as a key step. The synthetic route is significantly shorter than those for the natural product and avoids the isomerisation problem of the cis-double bond in the molecule. The preliminary biological evaluation showed that the exo-enone analogue is a potent inhibitor of several important kinases relevant to cancer drug development.

Total Synthesis of (+)-Rubriflordilactone†A.

Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone A are described, which use palladium- or cobalt-catalyzed cyclizations to form the CDE rings, and converge on a late-stage synthetic intermediate. These key processes are set up through the convergent coupling of a common diyne component with appropriate AB-ring aldehydes, a strategy that sets the stage for the synthetic exploration of other members of this family of natural products.

Enantioselective synthesis of the predominant AB ring system of the Schisandra nortriterpenoid natural products.

An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a ß-lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization.

Metal-catalyzed syntheses of abridged CDE rings of rubriflordilactones A and B.

The development of complementary palladium- and cobalt-catalyzed approaches to tricyclic arylsilanes suitable for elaboration into the CDE ring systems of rubriflordilactones A and B is reported. Microwave conditions are required to effect a cobalt-catalyzed triyne cyclotrimerization, which critically depends on the substitution pattern of the triyne termini. Mild conditions to elaborate these arylsilanes to the CDE cores of the natural products are described.