Mechanochemical preparation of kaempferol intermolecular complexes for enhancing the solubility and bioavailability

Abstract

In this study, complexes of kaempferol (KF) with polysaccharide arabinogalactan (AG) and disodium glycyrrhizinate (Na₂GA) were prepared through mechanochemical technique to improve the solubility and bioavailability of KF. The physicochemical properties and the interactions of KF with AG/Na₂GA were investigated through dissolution, SEM, XRD, and DSC studies. The reduction of particle sizes and destruction of crystal forms revealed the formation of solid dispersion which may have assisted the dissolution of the drug. The accelerated stability study showed higher stability for KF–Na₂GA complex. In vivo pharmacokinetic study was performed to observe the plasma drug concentrations for KF complexes. Mechanochemical complexation of KF with AG/Na₂GA improved the pharmacological activity as evident by the inhibitory potential of the complexes towards carbohydrate metabolic enzymes. In vivo studies were performed in STZ-induced diabetic mice, where the group treated with KF–AG complex showed better liver and kidney function and lower blood glucose levels than pure KF. Therefore, mechanochemical complexes of KF with polysaccharide or glycyrrhizate may serve as a promising formulation for the treatment of diabetes.     

Surfactant‐Free Sub‐2 nm Ultrathin Triangular Gold Nanoframes

Ultrathin triangular gold nanoframes are synthesized in high yield through selective gold deposition on the edges of triangular silver nanoprisms and subsequent silver etching with mild wet etchants. These ultrathin gold nanoframes are surfactant‐free with tailorable ridge thickness from 1.8 to 6 nm and exhibit adjustable and distinct surface plasmon resonance bands in the visible and near‐IR region. In comparison, etching of the nanoprism template by galvanic replacement can only create frame structures with much thicker ridges, which have much lower catalytic activity for 4‐nitrophenol reduction than the ultrathin gold nanoframes.     

Well‐Defined Functional Linear Aliphatic Diblock Copolyethers: A Versatile Linear Aliphatic Polyether Platform for Selective Functionalizations and Various Nanostructures

Low‐temperature anionic ring‐opening homopolymerizations and copolymerizations of two glycidol derivatives (allyl glycidyl ether (AGE) and ethoxyethyl glycidyl ether (EEGE)) are studied using a metal‐free catalyst system, 3‐phenyl‐1‐propanol (PPA) (an initiator) and 1‐tert‐butyl‐4,4,4‐tris(dimethylamino)‐2,2‐bis[tris‐(dimethylamino)phosphoranylidenamino]‐2Λ⁵,4Λ⁵‐catenadi(phosphazene) (t‐Bu‐P₄) (a promoter) in order to obtain well‐defined functional linear polyethers and diblock copolymers. With the aid of the catalyst system, AGE is found to successfully undergo anionic ring‐opening polymerization (ROP) even at room temperature (low reaction temperature) without any side reactions, producing well‐defined linear AGE‐homopolymer in a unimodal narrow molecular weight distribution. Under the same conditions, EEGE also undergoes polymerization, producing a linear EEGE‐homopolymer in a unimodal narrow molecular‐weight distribution. In this case, however, a side reaction (i.e., chain‐transfer reaction) is found to occur at low levels during the early stages of polymerization. The chemical properties of the monomers in the context of the homopolymerization reactions are considered in the design of a protocol used to synthesize well‐defined linear diblock copolyethers with a variety of compositions. The approach, anionic polymerization via the sequential step feed of AGE and EEGE as the first and second monomers, is found to be free from side reactions at room temperature. Each block of the obtained linear diblock copolymers undergoes selective deprotection to permit further chemical modification for selective functionalization. In addition, thermal properties and structures of the polymers and their post‐modification products are examined. Overall, this study demonstrates that a low‐temperature metal‐free anionic ROP using the PPA/t‐Bu‐P₄ catalyst system is suitable for the production of well‐defined linear AGE‐homopolymers and their diblock copolymers with the EEGE monomer, which are versatile and selectively functionalizable linear aliphatic polyether platforms for a variety of post‐modifications, nanostructures, and their applications.     

Boroxine Nanotubes: Moisture‐Sensitive Morphological Transformation and Guest Release

Boroxines, (R‐BO)₃, which can be easily synthesized via a dehydration reaction of boronic acids, R–B(OH)₂, selectively self‐assemble in toluene into nanofibers, nanorods, nanotapes, and nanotubes, depending on the aromatic substituent (R). Spectroscopic measurements show that the nanotube consists of a J‐aggregate of the boroxine. Humidification converts the morphology from the nanotube to a sheet as a result of the hydrolysis of the boroxine components and subsequent molecular‐packing rearrangement from the J‐aggregate to an H‐aggregate. Such a transformation leads to the compulsive release of guest molecules encapsulated in the hollow cylinder of the nanotube. The hydrolysis and the molecular‐packing rearrangement described above are suppressed by coordination of pyridine to the boron atom, with the resulting moiety acting as a Lewis acid of the boroxine component. The pyridine‐coordinated nanotube is transformed into a helical coil by humidification. Guest release during the nanotube‐to‐helical‐coil transformation is much slower than during the nanotube‐to‐sheet transformation, but faster than from a nanotube that did not undergo morphological transformation. The storage and release of guest molecules from the boroxine nanotubes can be precisely controlled by adjusting the moisture level and the concentration of Lewis bases, such as amines.     

Catalytic activity and selectivity for the ORR of rapidly synthesized M@Pt (M = Pd,Fe3O4, Ru) core–shell nanostructures

We report the performance of M@Pt (M = Pd, Fe₃O₄, Ru) core–shell nanostructures for the ORR in H₂SO₄. The nanomaterials were rapidly synthesized in a total of 120 s applying magnetic (MS), mechanical (UT) and sonochemical (USS) stirring. Pt-alone nanoparticles were also synthesized by UT and served as a reference to evaluate the performance of the core–shell cathodes. Crystalline features were obtained from the Pd and the Fe₃O₄ cores, while Ru cores apparently having quasi-amorphous characteristics or too small particle sizes were formed. Nevertheless, the three core–shell materials showed crystalline Pt features. From Scherrer analysis, it was determined that core–shell nanostructures with particle sizes from 7.3 to 9.2 nm were formed. The electrochemical characterization confirmed that active core–shell cathodes were obtained, with two of the Pd@Pt materials showing catalytic activities as high as that of the Pt-alone nanoparticles, or even higher in terms of mass activity. XPS analysis indicated that mainly Pt(0) species were formed at the cathodes, along with Pt(II) and Pt(IV). It was found that catalysts with high Pt(IV):Pt(II) showed enhanced catalytic activity for the reduction of oxygen. In the presence of ethanol, the evaluated Pd@Pt cathode showed the higher selectivity towards the ORR compared to the other cathodes.     

Electrostatic Control of Structure in Self‐Assembled Membranes

Self‐assembling peptide amphiphiles (PAs) can form hierarchically ordered membranes when brought in contact with aqueous polyelectrolytes of the opposite charge by rapidly creating a diffusion barrier composed of filamentous nanostructures parallel to the plane of the incipient membrane. Following this event, osmotic forces and charge complexation template nanofiber growth perpendicular to the plane of the membrane in a dynamic self‐assembly process. In this work, we show that this hierarchical structure requires massive interfacial aggregation of PA molecules, suggesting the importance of rapid diffusion barrier formation. Strong PA aggregation is induced here through the use of heparin‐binding PAs with heparin and also with polyelectrolytes of varying charge density. Small angle X‐ray scattering shows that in the case of weak PA‐polyelectrolyte interaction, membranes formed display a cubic phase ordering on the nanoscale that likely results from clusters of PA nanostructures surrounded by polyelectrolyte chains.     

Towards Supramolecular Catalysis with Small Self-assembled Peptides

Self-assembly of small peptides offers unique opportunities for the bottom-up construction of supramolecular catalysts that aim to emulate the efficiency and selectivity of natural enzymes. Small, information-rich, simple molecules based on amino acids can self-organise autonomously into complex systems with emergent catalytic properties. The power of noncovalent interactions can be used to construct supramolecular peptidic tertiary structures. Moreover, specific functional groups present in amino acid side-chains may present either a catalytic activity by themselves or be able to bind cofactors such as metal ions. In this scenario, although relevant progress has been achieved in recent years, promising applications in biomaterials science are foreseen. In this review, we discuss the state-of-the-art of this approach at the interface between supramolecular chemistry and peptide science.