Surface patterning of nanoparticles with polymer patches.

Patterning of colloidal particles with chemically or topographically distinct surface domains (patches) has attracted intense research interest. Surface-patterned particles act as colloidal analogues of atoms and molecules, serve as model systems in studies of phase transitions in liquid systems, behave as 'colloidal surfactants' and function as templates for the synthesis of hybrid particles. The generation of micrometre- and submicrometre-sized patchy colloids is now efficient, but surface patterning of inorganic colloidal nanoparticles with dimensions of the order of tens of nanometres is uncommon. Such nanoparticles exhibit size- and shape-dependent optical, electronic and magnetic properties, and their assemblies show new collective properties. At present, nanoparticle patterning is limited to the generation of two-patch nanoparticles, and nanoparticles with surface ripples or a 'raspberry' surface morphology. Here we demonstrate nanoparticle surface patterning, which utilizes thermodynamically driven segregation of polymer ligands from a uniform polymer brush into surface-pinned micelles following a change in solvent quality. Patch formation is reversible but can be permanently preserved using a photocrosslinking step. The methodology offers the ability to control the dimensions of patches, their spatial distribution and the number of patches per nanoparticle, in agreement with a theoretical model. The versatility of the strategy is demonstrated by patterning nanoparticles with different dimensions, shapes and compositions, tethered with various types of polymers and subjected to different external stimuli. These patchy nanocolloids have potential applications in fundamental research, the self-assembly of nanomaterials, diagnostics, sensing and colloidal stabilization.

Metal-Catalyzed Approaches toward the Oxindole Core.

The oxindole scaffold is a privileged structural motif that is found in a variety of bioactive targets and natural products. Moreover, derivatives of the oxindole structure are widely present in a number of biologically relevant compounds and are key intermediates in the synthesis of diverse natural products and pharmaceuticals. Therefore, novel methods to obtain oxindoles remain of high priority in synthetic organic chemistry.Over the past several decades, novel transition-metal-catalyzed methodologies have been applied toward the synthesis of a variety of heterocycles. A detailed mechanistic understanding facilitates the disruption of traditional catalytic pathways to access useful synthetic intermediates. The strategies employed have generally revolved around the generation of high-energy organometallic intermediates, which undergo cyclization reactions through domino processes. Domino cyclization methodologies are therefore attractive, as they allow facile access to functionalized oxindoles containing all-carbon quaternary centers or tetrasubstituted olefins with high chemo- and stereoselectivities. Furthermore, these developed synthetic strategies can often be easily applied in the syntheses of other related scaffolds.In this Account, we discuss the three unique strategies that our group has leveraged for the synthesis of valuable oxindole scaffolds. The first section in this Account outlines the use of an initial oxidative addition to a C(sp2)-X bond, followed by a migratory insertion, yielding a neopentyl species amenable to a variety of subsequent functionalizations. From this reactive neopentyl metal species, we have reported C-X reductive eliminations, anionic capture cascade reactions, and intramolecular C-H functionalization processes. The second section of this Account summarizes our group's findings on 1,2-insertions of a metal-nucleophile species across an unsaturation, generating a reactive organometallic intermediate; subsequent reactions with tethered electrophiles form the desired heterocyclic core. We have explored a wide array of transition metal-catalyzed strategies using this approach, including rhodium-catalyzed conjugate additions, an asymmetric copper-catalyzed borylcupration, and a palladium(II)-catalyzed chloropalladation protocol. The final section of this Account details the use of dual-metal catalysis to perform a cyclization through a C-H functionalization-allylation domino reaction. Throughout this Account, we provide details of mechanistic studies that better enabled our understanding of the domino processes.Overall, our group has developed methods exploiting the unique reactivity of palladium, nickel, copper, rhodium, and ruthenium catalysts to develop methods toward a wide array of oxindole scaffolds. On the basis of the utility, diversity, and applicability of the strategies developed, we believe that they will prove to be highly useful in the syntheses of other important targets and inspire further development and mechanistic understanding of various metal-catalyzed processes.

Iron-Catalyzed Reductive Cyclization by Hydromagnesiation: A Modular Strategy Towards N-Heterocycles.

A reductive cyclization to prepare a variety of N-heterocycles, through the use of ortho-vinylanilides, is reported. The reaction is catalyzed by an inexpensive and bench-stable iron complex and generally occurs at ambient temperature. The transformation likely proceeds through hydromagnesiation of the vinyl group, and trapping of the in situ generated benzylic anion by an intramolecular electrophile to form the heterocycle. This iron-catalyzed strategy was shown to be broadly applicable and was utilized in the synthesis of substituted indoles, oxindoles and tetrahydrobenzoazepinoindolone derivatives. Mechanistic studies indicated that the reversibility of the hydride transfer step depends on the reactivity of the tethered electrophile. The synthetic utility of our approach was further demonstrated by the formal synthesis of a reported bioactive compound and a family of natural products.

Intramolecular Copper(I)-Catalyzed Interrupted Click-Acylation Domino Reaction.

Acyl substituted triazoles are valuable scaffolds, but the direct synthesis of these moieties from terminal alkynes by copper catalysis remains unexplored. We report a robust, general, and efficient method using a simple CuI/2,2'-bipyridine catalytic system. This transformation involves a copper catalyzed azide-alkyne cycloaddition (CuAAC) followed by an intramolecular acylation onto a carbamoyl chloride. The reaction proceeds under mild conditions, tolerates several functional groups, and is readily scalable. This method represents a novel strategy towards the synthesis of complex heterocycles by a CuAAC/acylation domino process.

A Miniaturized Impedimetric Immunosensor for the Competitive Detection of Adrenocorticotropic Hormone.

Adrenocorticotropic hormone (ACTH) plays an essential role in regulating corticosteroid hormone production, which has important functions in a myriad of critical physiological functions. In this proof-of-concept study, a miniaturized immunosensor was developed for the highly sensitive detection of ACTH using electrochemical impedance spectroscopy (EIS) in connection with disposable screen-printed gold electrodes (SPGEs). A film of 3,3'-dithiobis[sulfosuccinimidylpropionate] (DTSSP) was prepared to immobilize anti-ACTH antibodies covalently on the nanostructured SPGE surface. The surface-immobilized anti-ACTH antibodies captured the biotinylated ACTH (biotin-ACTH) and non-labelled ACTH for the competitive immunoassay. After coupling of a streptavidin-alkaline phosphatase conjugate (Streptavidin-ALP), the bio-catalysed precipitation of an insoluble and insulating product onto the sensing interface changed the charge transfer resistance (Rct) characteristics significantly. The detection limit of 100 fg/mL was determined for ACTH in a 5 µL sample volume, which indicated that this versatile platform can be easily adapted for miniaturized electrochemical immunosensing of cancer marker biomolecules. High selectivity and sensitivity of our immunoassay to detect ACTH in real samples demonstrated its promising potential for future development and applications using clinical samples.

Rhodium-Catalyzed Enantioselective Reductive Arylation: Convenient Access to 3,3-Disubstituted Oxindoles.

A rhodium-Josiphos(L*) catalyzed enantioselective intramolecular hydroarylation reaction is described. The reductive cyclization of o-bromoaniline-derived acrylamides provides convenient access to 3,3-disubstituted oxindoles in good yields and with excellent enantioselectivity across a range of substrates. We propose that the key cyclization proceeds via a rhodium(III) intermediate. Overall, this method represents an unusual mode of reactivity for rhodium catalysis and is complementary to palladium(0)-catalyzed α-arylation methods.

Reactivity and Selectivity of Azaspirocycles in Radical C-H Functionalization.

Investigations of saturated spirocycles toward selective C-H functionalization reactions are scarce, despite their potential applications. In this work, we uncovered fundamental reactivity and selectivity differences between saturated heterocycles and their spirocyclic analogues using a model radical C-H xanthylation coupled with computational analysis. Ultimately, this study sheds light on the fundamental, understudied radical reactivity of spirocycles, thereby allowing for a pronounced chemical tunability that will prove to be advantageous in the expansion of their chemical space and applications in medicinal chemistry.

One-Pot, Three-Step Synthesis of Benzoxazinones via Use of the Bpin Group as a Masked Nucleophile.

The utilization of the Bpin group as a pronucleophile to facilitate the assembly of cyclic carbamates has been achieved. This one-pot process involves an initial copper-catalyzed borylation, a subsequent C-B bond oxidation to generate the reactive alcohol intermediate, and a cyclization. We report the use of this efficient, scalable, and simple method toward the synthesis of a wide range of benzoxazinone scaffolds, including enantioselective results. Subsequent transformations into useful scaffolds showcase the utility of this strategy.

Enantio- and diastereoselective conjugate borylation/Mannich cyclization.

Strategies to capitalize on enolate intermediates generated from stereoselective conjugate borylation to α,ß-unsaturated carbonyl systems are surprisingly rare despite the ubiquity of Michael acceptors, and the potential to generate valuable scaffolds bearing multiple stereocenters. Herein, we report a mild and stereoselective copper-catalyzed conjugate borylation/Mannich cyclization reaction. This strategy is feasible with a broad range of Michael acceptors, and can be leveraged to generate versatile borylated tetrahydroquinoline scaffolds bearing three contiguous stereocenters. The synthetic potential of these complex heterocycles has been explored through a series of derivatization studies.

Rhodium-Catalyzed Enantioselective Synthesis of Oxazinones via an Asymmetric Ring Opening-Lactonization Cascade of Oxabicyclic Alkenes.

The rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes is shown to be an efficient method for synthesizing chiral heterocycles. We demonstrate that the pairwise combination of chiral catalyst with chiral amino-acid-derived pronucleophiles results in a stereodivergent synthesis of diastereomeric hydroxyesters. A favorable conformational preference induces the subsequent lactonization of one diastereomer leading to the highly enantioselective synthesis of oxazinones.

Colloidal cholesteric liquid crystal in spherical confinement.

The organization of nanoparticles in constrained geometries is an area of fundamental and practical importance. Spherical confinement of nanocolloids leads to new modes of packing, self-assembly, phase separation and relaxation of colloidal liquids; however, it remains an unexplored area of research for colloidal liquid crystals. Here we report the organization of cholesteric liquid crystal formed by nanorods in spherical droplets. For cholesteric suspensions of cellulose nanocrystals, with progressive confinement, we observe phase separation into a micrometer-size isotropic droplet core and a cholesteric shell formed by concentric nanocrystal layers. Further confinement results in a transition to a bipolar planar cholesteric morphology. The distribution of polymer, metal, carbon or metal oxide nanoparticles in the droplets is governed by the nanoparticle size and yields cholesteric droplets exhibiting fluorescence, plasmonic properties and magnetic actuation. This work advances our understanding of how the interplay of order, confinement and topological defects affects the morphology of soft matter.