Inhibition of c-Rel expression in myeloid and lymphoid cells with distearoyl -phosphatidylserine (DSPS) liposomal nanoparticles encapsulating therapeutic siRNA.

c-Rel, a member of the nuclear factor kappa B (NF-κB) family, is preferentially expressed by immune cells and is known to regulate inflammation, autoimmune diseases and cancer. However, there is a lack of therapeutic intervention to specifically inhibit c-Rel in immune cells. Recent success with Pfizer and Moderna mRNA lipid-encapsulated vaccines as well as FDA approved medicines based on siRNA prompted us to test a lipid nanoparticle-based strategy to silence c-Rel in immune cells. Specifically, we encapsulated c-Rel-targeting siRNA into distearoyl-phosphatidylserine (DSPS)-containing nanoparticles. DSPS is a saturated phospholipid that serves as the "eat-me" signal for professional phagocytes such as macrophages and neutrophils of the immune system. We demonstrated here that incorporation of DSPS in liposome nanoparticles (LNP) improved their uptake by immune cells. LNP containing high concentrations of DSPS were highly effective to transfect not only macrophages and neutrophils, but also lymphocytes, with limited toxicity to cells. However, LNP containing low concentrations of DSPS were more effective to transfect myeloid cells than lymphoid cells. Importantly, DSPS-LNP loaded with a c-Rel siRNA were highly effective to inhibit c-Rel expression in several professional phagocytes tested, which lasted for several days. Taken together, our results suggest that DSPS-LNP armed with c-Rel siRNA could be exploited to target immune cells to limit the development of inflammatory diseases or cancer caused by c-Rel upregulation. In addition, this newly developed DSPS-LNP system may be further tested to encapsulate and deliver other small molecule drugs to immune cells, especially macrophages, neutrophils, and lymphocytes for the treatment of diseases.

General Synthetic Route to High-Quality Colloidal III-V Semiconductor Quantum Dots Based on Pnictogen Chlorides.

The synthesis of colloidal III-V quantum dots (QDs), particularly of the arsenides and antimonides, has been limited by the lack of stable and available group V precursors. In this work, we exploit accessible InCl3- and pnictogen chloride-oleylamine as precursors to synthesize III-V QDs. Through coreduction reactions of the precursors, we achieve size- and stoichiometry-tunable binary InAs and InSb as well as ternary alloy InAs1-xSbx QDs. On the basis of structural, analytical, optical, and electrical characterization of the QDs and their thin-film assemblies, we study the effects of alloying on their particle formation and optoelectronic properties. We introduce a hydrazine-free hybrid ligand-exchange process to improve carrier transport in III-V QD thin films and realize InAs QD field-effect transistors with electron mobility > 5 cm2/(V s). We demonstrate that III-V QD thin films are promising candidate materials for infrared devices and show InAs1-xSbx QD photoconductors with superior short-wavelength infrared (SWIR) photoresponse than those of the binary QD devices.

Tuning the Electrocatalytic Oxygen Reduction Reaction Activity of Pt-Co Nanocrystals by Cobalt Concentration with Atomic-Scale Understanding.

The development of a suitable catalyst for the oxygen reduction reaction (ORR), the cathode reaction of proton exchange membrane fuel cells (PEMFC), is necessary to push this technology toward widespread adoption. There have been substantial efforts to utilize bimetallic Pt-M alloys that adopt the ordered face-centered tetragonal (L10) phase in order to reduce the usage of precious metal, enhance the ORR performance, and improve catalyst stability. In this work, monodisperse Pt-Co nanocrystals (NCs) with well-defined size (4-5 nm) and cobalt composition (25-75 at%) were synthesized via colloidal synthesis. The transformation from the chemically disordered A1 (face-centered cubic, fcc) to the L10 phase was achieved via thermal annealing using both a conventional oven and a rapid thermal annealing process. The structure of the Pt-Co catalysts was characterized by a variety of techniques, including transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy in high-angle annular dark-field scanning transmission electron microscopy (STEM-EDS), small-angle X-ray scattering (SAXS), X-ray diffraction (XRD), and inductively coupled plasma-optical emission spectrometry (ICP-OES). The effects of annealing temperature on the composition-dependent degree of ordering and subsequent effect on ORR activity is described. This work provides insights regarding the optimal spatial distribution of elements at the atomic level to achieve enhanced ORR activity and stability.

Nanocrystal Core Size and Shape Substitutional Doping and Underlying Crystalline Order in Nanocrystal Superlattices.

Substitutional doping is a potentially powerful technique to control the properties of nanocrystal (NC) superlattices (SLs). However, not every NC can be substituted into any lattice, as the NCs have to be close in size and shape, limiting the application of substitutional doping. Here we show that this limitation can be overcome by employing ligands of various size. We show that small NCs with long ligands can be substituted into SLs of big NCs with short ligands. Furthermore, we show that shape differences can also be overcome and that cubes can substitute spheres when both are coated with long ligands. Finally, we use the NC effective ligand size, softness, and effective overall size ratio to explain observed doping behaviors.

3D Nanofabrication via Chemo-Mechanical Transformation of Nanocrystal/Bulk Heterostructures.

Planar nanocrystal/bulk heterostructures are transformed into 3D architectures by taking advantage of the different chemical and mechanical properties of nanocrystal and bulk thin films. Nanocrystal/bulk heterostructures are fabricated via bottom-up assembly and top-down fabrication. The nanocrystals are capped by long ligands introduced in their synthesis, and therefore their surfaces are chemically addressable, and their assemblies are mechanically "soft," in contrast to the bulk films. Chemical modification of the nanocrystal surface, exchanging the long ligands for more compact chemistries, triggers large volume shrinkage of the nanocrystal layer and drives bending of the nanocrystal/bulk heterostructures. Exploiting the differential chemo-mechanical properties of nanocrystal and bulk materials, the scalable fabrication of designed 3D, cell-sized nanocrystal/bulk superstructures is demonstrated, which possess unique functions derived from nanocrystal building blocks.

The dendritic effect and magnetic permeability in dendron coated nickel and manganese zinc ferrite nanoparticles.

The collective magnetic properties of nanoparticle (NP) solid films are greatly affected by inter-particle dipole-dipole interactions and therefore the proximity of the neighboring particles. In this study, a series of dendritic ligands (generations 0 to 3, G0-G3) have been designed and used to cover the surface of magnetic NPs to control the spacings between the NP components in single lattices. The dendrons of different generations introduced here were based on the 2,2-bis(hydroxymethyl)propionic acid (Bis-MPA) scaffold and equipped with an appropriate surface binding group at one end and several fatty acid segments at the other extremity. The surface of the NPs was then modified by partial ligand exchange between the primary stabilizing surfactants and the new dendritic wedges. It was shown that this strategy permitted very precise tuning of inter-particle spacings in the range of 2.9-5.0 nm. As expected, the increase in the inter-particle spacings reduced the dipole-dipole interactions between magnetic NPs and therefore allowed changes in their magnetic permeability. The dendron size and inter-particle distance dependence was studied to reveal the dendritic effect and identify the optimal geometry and generation.

Preparation and Self-Assembly of Dendronized Janus Fe3O4-Pt and Fe3O4-Au Heterodimers.

Janus nanoparticles (NPs) often referred to as nanosized analogs of molecular surfactants are amphiphilic structures with potential applications in materials science, biomedicine, and catalysis, and their synthesis and self-assembly into complex architectures remain challenging. Here, we demonstrate the preparation of Janus heterodimers via asymmetric functionalization of Fe3O4-Pt and Fe3O4-Au heterodimeric NPs. The hydrophobic and hydrophilic dendritic ligands that carry phosphonic acid and disulfide surface binding groups selectively coat the iron oxide and platinum (or gold) parts of the heterodimer, respectively. Such an approach allows simple and efficient preparation of amphiphilic structures. Moreover, liquid-air interface self-assembly studies of each ligand exchange step revealed a drastic improvement in film crystallinity, suggesting the dendronization induced improvement of the whole particle polydispersity of the heterodimers.

A semi-combinatorial approach for investigating polycatenar ligand-controlled synthesis of rare-earth fluoride nanocrystals.

Rare-earth nanocrystals (RE NCs) are a valuable class of nanomaterials due to their ability to bring the attractive properties of rare earth bulk crystals to biomedical applications and solution-processable engineering. Of the bottom-up synthesis approaches, solvothermal methods yield highly crystalline and monodisperse RE NCs. Herein, we report a polycatenar ligand controlled synthesis of RE NCs using a semi-combinatorial approach with a microreactor setup that enables the investigation of the influences of several reaction parameters on the growth of the RE NCs. This approach enabled the discovery of conditions that yield highly monodisperse elongated plates with neutral, positive, and negative curvatures, as well as provide evidence of the formation of chiral morphologies.

Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers.

2,2-Bis(azidomethyl)propionic acid was prepared in four steps and 85% yield from the commercially available 2,2-bis(hydroxymethyl)propionic acid and used as the starting building block for the divergent, convergent, and double-stage convergent-divergent iterative methods for the synthesis of dendrimers and dendrons containing ethylenediamine (EDA), piperazine (PPZ), and methyl 2,2-bis(aminomethyl)propionate (COOMe) cores. These cores have the same multiplicity but different conformations. A diversity of synthetic methods were used for the synthesis of dendrimers and dendrons. Regardless of the method used, a self-interruption of the synthesis was observed at generation 4 for the dendrimer with an EDA core and at generation 5 for the one with a PPZ core, whereas for the COOMe core, self-interruption was observed at generation 6 dendron, which is equivalent to generation 5 dendrimer. Molecular modeling and molecular-dynamics simulations demonstrated that the observed self-interruption is determined by the backfolding of the azide groups at the periphery of the dendrimer. The latter conformation inhibits completely the heterogeneous hydrogenation of the azide groups catalyzed by 10% Pd/carbon as well as homogeneous hydrogenation by the Staudinger method. These self-terminated polyamide dendrimers are enzymatically and hydrolytically stable and also exhibit antimicrobial activity. Thus, these nanoscale constructs open avenues for biomedical applications.

Polycatenar Ligand Control of the Synthesis and Self-Assembly of Colloidal Nanocrystals.

Hydrophobic colloidal nanocrystals are typically synthesized and manipulated with commercially available ligands, and surface functionalization is therefore typically limited to a small number of molecules. Here, we report the use of polycatenar ligands derived from polyalkylbenzoates for the direct synthesis of metallic, chalcogenide, pnictide, and oxide nanocrystals. Polycatenar molecules, branched structures bearing diverging chains in which the terminal substitution pattern, functionality, and binding group can be independently modified, offer a modular platform for the development of ligands with targeted properties. Not only are these ligands used for the direct synthesis of monodisperse nanocrystals, but nanocrystals coated with polycatenar ligands self-assemble into softer bcc superlattices that deviate from conventional harder close-packed structures (fcc or hcp) formed by the same nanocrystals coated with commercial ligands. Self-assembly experiments demonstrate that the molecular structure of polycatenar ligands encodes interparticle spacings and attractions, engineering self-assembly, which is tunable from hard sphere to soft sphere behavior.

Dendronization-induced phase-transfer, stabilization and self-assembly of large colloidal Au nanoparticles.

The phase-transfer of CTAB-coated aqueous, spherical gold nanoparticles, with metallic core diameters ranging from ca. 27 to 54 nm, into organic solvents by exchanging the primitive polar bilayer with lipophilic, disulfide dendritic ligands is reported. The presence of such a thick nonpolar organic shell around these large nanoparticles enhances their stabilization against aggregation, in addition to enabling their transfer into a variety of solvents such as chloroform, toluene or tetrahydrofuran. Upon the slow evaporation of a chloroform suspension deposited on a solid support, the dendronized hybrids were found to self-assemble into ring structures of various diameters. Moreover, their self-assembly at the liquid-air interface affords the formation of fairly long-range ordered monolayers, over large areas, that can then be entirely transferred onto solid substrates.

Quantifying "Softness" of Organic Coatings on Gold Nanoparticles Using Correlated Small-Angle X-ray and Neutron Scattering.

Small-angle X-ray and neutron scattering provide powerful tools to selectively characterize the inorganic and organic components of hybrid nanomaterials. Using hydrophobic gold nanoparticles coated with several commercial and dendritic thiols, the size of the organic layer on the gold particles is shown to increase from 1.2 to 4.1 nm. A comparison between solid-state diffraction from self-assembled lattices of nanoparticles and the solution data from neutron scattering suggests that engineering softness/deformability in nanoparticle coatings is less straightforward than simply increasing the organic size. The "dendritic effect" in which higher generations yield increasingly compact molecules explains changes in the deformability of organic ligand shells.

Dendron-Mediated Engineering of Interparticle Separation and Self-Assembly in Dendronized Gold Nanoparticles Superlattices.

Self-assembly of nanoparticles into designed structures with controlled interparticle separations is of crucial importance for the engineering of new materials with tunable functions and for the subsequent bottom-up fabrication of functional devices. In this study, a series of lipophilic, highly flexible, disulfide dendritic wedges (generations 0-4), based on 2,2-bis(hydroxymethyl)propionic acid, was designed to bind Au nanoparticles with a thiolate bond. By controlling the solvent evaporation rate, the corresponding dendron-capped Au hybrids were found to self-organize into hexagonal close-packed (hcp) superlattices. The interparticular spacing was progressively varied from 2.2 to 6.3 nm with increasing dendritic generation, covering a range that is intermediate between commercial ligands and DNA-based ligand shells. Dual mixtures made from some of these dendronized hybrids (i.e., same inner core size but different dendritic covering) yielded binary superlattice structures of unprecedented single inorganic components, which are isostructural with NaZn13 and CaCu5 crystals.

Synthesis and direct C2 functionalization of imidazolium and 1,2,4-triazolium N-imides.

Pd-catalyzed direct C2 arylation and Cu-catalyzed direct one-pot alkynylation/intramolecular cyclization of azolium N-imides are reported. Various acetylenes, aryl iodides, and 1-alkyl substituents were examined. The mild protocol allows direct C2 arylation of azolium N-imides without the use of specialized reagents together with novel one-pot regioselective preparations of imidazole-pyrazolo and pyrazolo-1,2,4-triazole ring systems. The electronic properties of selected examples were examined by fluorescence spectroscopy.

Push-pull triazenes derived from 1-(benzylideneamino)- and 1-(sulfonimido)-azolylidenes.

In-situ-generated neutral 1-(benzylideneamino)- and novel anionic 1-(sulfonimido)-azolylidenes react with organic azides to afford diverse classes of push-pull triazenes and triazene salts. The scope of the heterocyclic core and substituents at the N1 and N3 positions of NHC precursors together with the thermal properties of resulting compounds were examined.

Cu(I)-catalyzed regioselective synthesis of pyrazolo[5,1-c]-1,2,4-triazoles.

Cycloadditions of terminal alkynes to 1,2,4-triazolium N-imides in the presence of base and Cu(I) afford pyrazolo[5,1-c]-1,2,4-triazoles regioselectively. The scope of alkynes, the influence of the electronic nature of the leaving group, and variations in the 1-alkyl substituent were examined. Quantum chemical calculations were employed to explain the distinct reactivity of the propiolates.

Carbene-mediated transformations of 1-(benzylideneamino)benzimidazoles.

Carbene-mediated transformations of N-(3-butylbenzimidazol-3-ium-1-yl)-1-arylmethanimine iodides with carbon disulfide and benzoyl isothiocyanate gave the corresponding NHC·CS(2) betaines in 68-85% and benzoyl-[1-butyl-3-[(E)-(aryl)methyleneamino]benzimidazol-1-ium-2-carbothioyl]azanides, respectively, in 74-85% yields. However, reaction with excess isopropyl isothiocyanate in NaH/THF at room temperature yielded the 1-butyl-1',3'-diisopropyl-3-[(E)-(aryl)methyleneamino]spiro[benzimidazole-2,5'-imidazolidine]-2',4'-dithiones (74-77%).

Convenient synthesis of Ibuprofen and naproxen aminoacyl, dipeptidoyl and ester derivatives.

DL-Ibuprofen and L-naproxen were coupled with amino acids and other bioactive compounds to provide ibuprofen and naproxen bioconjugates in 61-95% yield as prodrugs or potential drug candidates.