Electrical Network of Single‐Crystalline Metal Oxide Nanoclusters Wired by π‐Molecules

In a mixed‐valence polyoxometalate, electrons are usually delocalized within the cluster anion because of low level of inter‐cluster interaction. Herein, we report the structure and electrical properties of a single crystal in which mixed‐valence polyoxometalates were electrically wired by cationic π‐molecules of tetrathiafulvalene substituted with pyridinium. Electron‐transport characteristics are suggested to represent electron hopping through strong interactions between cluster and cationic π‐molecules.     

Chemical Probes for the Functionalization of Polyketide Intermediates

A library of functionalized chemical probes capable of reacting with ketosynthase‐bound biosynthetic intermediates was prepared and utilized to explore in vivo polyketide diversification. Fermentation of ACP mutants of S. lasaliensis in the presence of the probes generated a range of unnatural polyketide derivatives, including novel putative lasalocid A derivatives characterized by variable aryl ketone moieties and linear polyketide chains (bearing alkyne/azide handles and fluorine) flanking the polyether scaffold. By providing direct information on microorganism tolerance and enzyme processing of unnatural malonyl‐ACP analogues, as well as on the amenability of unnatural polyketides to further structural modifications, the chemical probes constitute invaluable tools for the development of novel mutasynthesis and synthetic biology.     

Cyclic‐Disulfide‐Based Prodrugs for Cytosol‐Specific Drug Delivery

The cytosolic conversion of therapeutically relevant nucleosides into bioactive triphosphates is often hampered by the inefficiency of the first kinase‐mediated step. Nucleoside monophosphate prodrugs can be used to bypass this limitation. Herein we describe a novel cyclic‐disulfide class of nucleoside monophosphate prodrugs with a cytosol‐specific, reductive release trigger. The key event, a charge‐dissipating reduction‐triggered cyclodeesterification leads to robust cytosolic production of the cyclic 3′,5′‐monophosphate for downstream enzymatic processing. The antiviral competence of the platform was demonstrated with an O‐benzyl‐1,2‐dithiane‐4,5‐diol ester of 2′‐C‐methyluridine‐3′,5′‐phosphate. Both in vitro and in vivo comparison with the clinically efficacious ProTide prodrug of 2′‐deoxy‐2′‐α‐fluoro‐β‐C‐methyluridine is provided. The cytosolic specificity of the release allows for a wide range of potential applications, from tissue‐targeted drug delivery to intracellular imaging.     

Cationic Vesicles Based on Amphiphilic Pillar[5]arene Capped with Ferrocenium: A Redox‐Responsive System for Drug/siRNA Co‐Delivery

A novel ferrocenium capped amphiphilic pillar[5]arene (FCAP) was synthesized and self‐assembled to cationic vesicles in aqueous solution. The cationic vesicles, displaying low cytotoxicity and significant redox‐responsive behavior due to the redox equilibrium between ferrocenium cations and ferrocenyl groups, allow building an ideal glutathione (GSH)‐responsive drug/siRNA co‐delivery system for rapid drug release and gene transfection in cancer cells in which higher GSH concentration exists. This is the first report of redox‐responsive vesicles assembled from pillararenes for drug/siRNA co‐delivery; besides enhancing the bioavailability of drugs for cancer cells and reducing the adverse side effects for normal cells, these systems can also overcome the drug resistance of cancer cells. This work presents a good example of rational design for an effective stimuli‐responsive drug/siRNA co‐delivery system.     

Identification and Accurate Size Characterization of Nanoparticles in Complex Media

We have developed a new method for the identification and accurate size characterization of nanoparticles (NPs) in complex media based on capillary electrokinetic (CE) separation coupled to inductively coupled plasma mass spectrometry (ICP‐MS). Through mass scanning and Gaussian fitting of electropherogram peaks, we can obtain multidimensional information on chemical compositions, size distributions, and ionic species of multiple NPs in a single run. The results are more accurate than those obtained by using conventional methods. This method provides a powerful tool for investigating polydisperse NP systems and rapid screening of NP‐containing products.     

Sequence and Chiral Selectivity of Drug–DNA Interactions Revealed by Force Spectroscopy

Differential binding force has been used to precisely characterize the mechanical effect of a drug molecule binding to a DNA duplex. The high‐resolution binding forces measured by the force‐induced remnant magnetization spectroscopy (FIRMS) enable the binding behavior of drug molecules with different chirality and DNA of various sequences to be distinguished. The sequence specificity of Hg²⁺ and daunomycin was revealed by force spectroscopy for the first time, and the results are consistent with those obtained by other techniques. Furthermore, the two isomers of d,l ‐tetrahydropalmatine showed selectivity for two different DNA sequences. One particular useful feature of this approach is that the small molecules under study do not require any labels.     

Ionizable Amphiphilic Dendrimer‐Based Nanomaterials with Alkyl‐Chain‐Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo

A library of dendrimers was synthesized and optimized for targeted small interfering RNA (siRNA) delivery to different cell subpopulations within the liver. Using a combinatorial approach, a library of these nanoparticle‐forming materials was produced wherein the free amines on multigenerational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length, and evaluated for their ability to deliver siRNA to liver cell subpopulations. Interestingly, two lead delivery materials could be formulated in a manner to alter their tissue tropism within the liver—with formulations from the same material capable of preferentially delivering siRNA to 1) endothelial cells, 2) endothelial cells and hepatocytes, or 3) endothelial cells, hepatocytes, and tumor cells in vivo. The ability to broaden or narrow the cellular destination of siRNA within the liver may provide a useful tool to address a range of liver diseases.     

Colloidal Nanocrystals of Lithiated Group 14 Elements

The synthesis of colloidal nanocrystals (NCs) of lithiated group 14 elements (Z=Si, Ge, and Sn) is reported, which are Li_4.4Si, Li_3.75Si, Li_4.4Ge, and Li_4.4Sn. Li_xZ compounds are highly reactive and cannot be synthesized by existing methods. The success relied on separating the surface protection from the crystal formation and using a unique passivating ligand. Bare Li_xZ crystals were first produced by milling elemental Li and Z in an argon‐filled jar. Then, under the assistance of additional milling, hexyllithium was added to passivate the freshly generated Li_xZ NCs. This ball‐milling‐assisted surface protection method may be generalized to similar systems, such as Na_xZ and K_xZ. Moreover, Li_4.4Si and Li_4.4Ge NCs were conformally encapsulated in carbon fibers, providing great opportunities for studying the potential of using Li_xZ to mitigate the volume‐fluctuation‐induced poor cyclability problem confronted by Z anodes in lithium‐ion batteries.     

Highly Stable Water‐Soluble Platinum Nanoparticles Stabilized by Hydrophilic N‐Heterocyclic Carbenes

Controlling the synthesis of stable metal nanoparticles in water is a current challenge in nanochemistry. The strategy presented herein uses sulfonated N‐heterocyclic carbene (NHC) ligands to stabilize platinum nanoparticles (PtNPs) in water, under air, for an indefinite time period. The particles were prepared by thermal decomposition of a preformed molecular Pt complex containing the NHC ligand and were then purified by dialysis and characterized by TEM, high‐resolution TEM, and spectroscopic techniques. Solid‐state NMR studies showed coordination of the carbene ligands to the nanoparticle surface and allowed the determination of a ¹³C–¹⁹⁵Pt coupling constant for the first time in a nanosystem (940 Hz). Additionally, in one case a novel structure was formed in which platinum(II) NHC complexes form a second coordination sphere around the nanoparticle.