Probing functional self-assembled molecular architectures with solution/solid scanning tunnelling microscopy.

Over the past two decades, solution/solid STM has made clear contributions to our fundamental understanding of the thermodynamic and kinetic processes that occur in molecular self-assembly at surfaces. As the field matures, we provide an overview of how solution/solid STM is emerging as a tool to elucidate and guide the use of self-assembled molecular systems in practical applications, focusing on small molecule device engineering, molecular recognition and sensing and electronic modification of 2D materials.

Photosensitized Membrane Permeabilization Requires Contact-Dependent Reactions between Photosensitizer and Lipids.

Although the general mechanisms of lipid oxidation are known, the chemical steps through which photosensitizers and light permeabilize lipid membranes are still poorly understood. Herein we characterized the products of lipid photooxidation and their effects on lipid bilayers, also giving insight into their formation pathways. Our experimental system was designed to allow two phenothiazinium-based photosensitizers (methylene blue, MB, and DO15) to deliver the same amount of singlet oxygen molecules per second to 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine liposome membranes, but with a substantial difference in terms of the extent of direct physical contact with lipid double bonds; that is, DO15 has a 27-times higher colocalization with ω-9 lipid double bonds than MB.

TMV Disk Scaffolds for Making sub-30 nm Silver Nanorings.

Nanosized bioscaffolds can be utilized to tackle the challenge of size reduction of metallic rings owing to their miniature features as well as their well-known biomineralization capacity. The tobacco mosaic virus coat protein is used as a command surface to grow and assemble silver nanoparticles into sub-30 nm rings. The versatility of TMV allows the formation of both solid silver rings and rings consisting of discrete silver nanoparticles.

DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand patterns.

As colloidal self-assembly increasingly approaches the complexity of natural systems, an ongoing challenge is to generate non-centrosymmetric structures. For example, patchy, Janus or living crystallization particles have significantly advanced the area of polymer assembly. It has remained difficult, however, to devise polymer particles that associate in a directional manner, with controlled valency and recognition motifs.

Development of a Fluorogenic Reactivity Palette for the Study of Nucleophilic Addition Reactions Based on -Formyl BODIPY Dyes.

We describe herein a fluorescence-based assay to characterize and report on nucleophilic addition to carbonyl moieties and highlight the advantages a fluorescence-based assay and multiplex analysis can offer. The assay relies on the fluorogenic properties of -formyl boron-dipyrromethene (BODIPY) dyes that become emissive following nucleophilic addition. A reactivity palette is assembled based on the increasing electrophilic character of five -formyl BODIPY compounds tested.

Mitochondria Alkylation and Cellular Trafficking Mapped with a Lipophilic BODIPY-Acrolein Fluorogenic Probe.

Protein and DNA alkylation by endogenously produced electrophiles is associated with the pathogenesis of neurodegenerative diseases, to epigenetic alterations and to cell signaling and redox regulation. With the goal of visualizing, in real-time, the spatiotemporal response of the cell milieu to electrophiles, we have designed a fluorogenic BODIPY-acrolein probe, AcroB, that undergoes a >350-fold fluorescence intensity enhancement concomitant with protein adduct formation. AcroB enables a direct quantification of single post-translational modifications occurring on cellular proteins via recording fluorescence bursts in live-cell imaging studies.

Redox-Based Photostabilizing Agents in Fluorescence Imaging: The Hidden Role of Intersystem Crossing in Geminate Radical Ion Pairs.

Here we report transient absorption studies on the ground-state recovery dynamics of the single-molecule fluorophore Cy3B in the presence of four different photostabilizing agents, namely β-mercaptoethanol (β-ME), Trolox (TX), n-propyl gallate (n-PG), and ascorbic acid (AA). These are triplet-state quenchers that operate via photoinduced electron transfer (PeT). While quantitative geminate recombination was recorded following PeT for β-ME (∼100%), for Trolox, n-propyl gallate, and ascorbic acid the extent of geminate recombination was >48%, >27%, and >13%, respectively.

Patchy Nanofibers from the Thin Film Self-Assembly of a Conjugated Diblock Copolymer.

An unexpected morphology comprising patchy nanofibers can be accessed from the self-assembly of an all-conjugated, polyselenophene-block-polythiophene copolymer. This morphology consists of very small (<10 nm), polythiophene- and polyselenophene-rich domains and is unprecedented for both conjugated polymers and diblock copolymers in general. We propose that the patchy morphology occurs from the enhanced miscibility of the blocks arising from the longer alkyl chains in comparison to similar block copolymers with shorter alkyl chains, which fully phase separate, as well as the difference in rigidity between the polythiophene and polyselenophene blocks.

Conformational Changes Spanning Angstroms to Nanometers via a Combined Protein-Induced Fluorescence Enhancement-Förster Resonance Energy Transfer Method.

Förster resonance energy transfer (FRET)-based single-molecule techniques have revolutionized our understanding of conformational dynamics in biomolecular systems. Recently, a new single-molecule technique based on protein-induced fluorescence enhancement (PIFE) has aided studies in which minimal (<3 nm) displacements occur. Concerns have been raised regarding whether donor fluorophore intensity (and correspondingly fluorescence quantum yield Φ) fluctuations, intrinsic to PIFE methods, may adversely affect FRET studies when retrieving the donor-acceptor dye distance.

Monitoring Chemical and Biological Electron Transfer Reactions with a Fluorogenic Vitamin K Analogue Probe.

We report herein the design, synthesis, and characterization of a two-segment fluorogenic analogue of vitamin K, B-VK, prepared by coupling vitamin K, also known as menadione (a quinone redox center), to a boron-dipyrromethene (BODIPY) fluorophore (a lipophilic reporter segment). Oxidation-reduction reactions, spectroelectrochemical studies, and enzymatic assays conducted in the presence of DT-diaphorase illustrate that the new probe shows reversible redox behavior on par with that of vitamin K, provides a high-sensitivity fluorescence signal, and is compatible with biological conditions, opening the door to monitor remotely (i.e.

meso-Acetoxymethyl BODIPY dyes for photodynamic therapy: improved photostability of singlet oxygen photosensitizers.

We report two BODIPY based photosensitizers (Br2BOAc and I2BOAc) featuring an acetoxymethyl substituent at the meso-position. These photosensitizers show improved photostability against singlet oxygen, when compared to a BODIPY photosensitizer lacking the acetoxymethyl group. Both compounds were evaluated for photodynamic therapy against HeLa cells and photodynamic inactivation against E.

Nanoring formation via in situ photoreduction of silver on a virus scaffold.

The fabrication of plasmonic nanorings remains of substantial interest by virtue of their enhanced electric and magnetic response to light fields which can be subsequently exploited in diverse applications. Scaling down the size of nanorings holds promise in creating artificial magnetism at wavelengths matching the solar spectrum. Nanosized bioscaffolds can be utilized to tackle the challenge of size reduction of metallic rings owing to their miniature features as well as their well-known biomineralization capacity.

Improving the Photostability of Red- and Green-Emissive Single-Molecule Fluorophores via Ni Mediated Excited Triplet-State Quenching.

Methods to improve the photostability/photon output of fluorophores without compromising their signal stability are of paramount importance in single-molecule fluorescence (SMF) imaging applications. We show herein that Ni provides a suitable photostabilizing agent for three green-emissive (Cy3, ATTO532, Alexa532) and three red-emissive (Cy5, Alexa647, ATTO647N) fluorophores, four of which are regularly utilized in SMF studies. Ni works via photophysical quenching of the triplet excited state eliminating the potential for reactive intermediates being formed.

Synthesis of Macrocyclic Poly(3-hexylthiophene) and Poly(3-heptylselenophene) by Alkyne Homocoupling.

Here we report the synthesis of cyclic samples of poly(3-hexylthiophene) (P3HT, degrees of polymerization = 25, 40, and 75) and poly(3-heptylselenophene) (P37S, DP = 30). Cyclization was accomplished using a mild alkyne-alkyne homocoupling procedure. Alkyne-terminated poly(ethylene glycol) was then coupled to residual uncyclized polymers, which were subsequently removed by column chromatography, enabling isolation and characterization of pure cyclic polymers.

Optimized DNA "Nanosuitcases" for Encapsulation and Conditional Release of siRNA.

We set out to design, synthesize, and optimize a DNA-minimal cage capable of encapsulating oligonucleotide drugs to facilitate their delivery. Through rational design and optimization using in vitro assays, we have assembled the first DNA "nanosuitcase" that can encapsulate a siRNA construct and release it upon recognition of an oligonucleotide trigger. The latter may be a mRNA or a microRNA (miRNA) which offers potential for dual or synergistic therapy.

DNA micelles as nanoreactors: efficient DNA functionalization with hydrophobic organic molecules.

We report a micelle-templated method to enhance the reactivity of DNA with highly hydrophobic molecules. Lipids, chromophores and polymers can be conjugated to DNA in high yield and under mild conditions. This method expands the range of DNA-templated reactions for DNA-encoded libraries, oligonucleotide and drug delivery, nanopore mimetics and DNA nanotechnology.

Fluorogenic Ubiquinone Analogue for Monitoring Chemical and Biological Redox Processes.

We report herein the synthesis and characterization of a fluorogenic analogue of ubiquinone designed to reversibly report on redox reactions in biological systems. The analogue, H2B-Q, consists of the redox-active quinone segment found in ubiquinone, 2,3-dimethoxy-1,4-benzoquinone, coupled to a boron-dipyrromethene (BODIPY) fluorophore segment that both imparts lipophilicity in lieu of the isoprenyl tail of ubiquinone, and reports on redox changes at the quinone/quinol segment. Redox sensing is mediated by a photoinduced electron transfer intramolecular switch.

Correction: Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown.

Correction for 'Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown' by Johans J. Fakhoury, et al., Nanoscale, 2015, 7, 20625-20634.

Effect of Confinement on the Properties of Sequestered Mixed Polar Solvents: Enzymatic Catalysis in Nonaqueous 1,4-Bis-2-ethylhexylsulfosuccinate Reverse Micelles.

The influence of different glycerol, N,N-dimethylformamide (DMF) and water mixtures encapsulated in 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/n-heptane reverse micelles (RMs) on the enzymatic hydrolysis of 2-naphthyl acetate by α-chymotrypsin is demonstrated. In the case of the mixtures with DMF and protic solvents it has been previously shown, using absorption, emission and dynamic light-scattering techniques, that solvents are segregated inside the polar core of the RMs. Protic solvents anchor to the AOT, whereas DMF locates to the polar core of the aggregate.

Dual emission in asymmetric "giant" PbS/CdS/CdS core/shell/shell quantum dots.

Semiconducting nanocrystals optically active in the infrared region of the electromagnetic spectrum enable exciting avenues in fundamental research and novel applications compatible with the infrared transparency windows of biosystems such as chemical and biological optical sensing, including nanoscale thermometry. In this context, quantum dots (QDs) with double color emission may represent ultra-accurate and self-calibrating nanosystems. We present the synthesis of giant core/shell/shell asymmetric QDs having a PbS/CdS zinc blende (Zb)/CdS wurtzite (Wz) structure with double color emission close to the near-infrared (NIR) region.

Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy.

Here we show the design, preparation, and characterization of a dormant singlet oxygen ((1)O2) photosensitizer that is activated upon its reaction with reactive oxygen species (ROS), including (1)O2 itself, in what constitutes an autocatalytic process. The compound is based on a two segment photosensitizer-trap molecule where the photosensitizer segment consists of a Br-substituted boron-dipyrromethene (BODIPY) dye. The trap segment consists of the chromanol ring of α-tocopherol, the most potent naturally occurring lipid soluble antioxidant.

Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown.

Therapeutic nucleic acids are powerful molecules for shutting down protein expression. However, their cellular uptake is poor and requires transport vectors, such as cationic polymers. Of these, poly(ethylenimine) (PEI) has been shown to be an efficient vehicle for nucleic acid transport into cells.

Solution and air stable host/guest architectures from a single layer covalent organic framework.

We show that the surface-supported two-dimensional covalent organic framework (COF) known as COF-1 can act as a host architecture for C60 fullerene molecules, predictably trapping the molecules under a range of conditions. The fullerenes occupy the COF-1 lattice at the solution/solid interface, and in dried films of the COF-1/fullerene network that can be synthesized through either drop-deposition of fullerene solution or by a dipstick-type synthesis in which the surface-supported COF-1 is briefly dipped into the fullerene solution.

Charge-Transfer Dynamics of Fluorescent Dye-Sensitized Electrodes under Applied Biases.

The development of dye-sensitized solar cells requires an in-depth understanding of the interfacial charge-transfer dynamics that take place between dye sensitizers and semiconductors. Here, we describe a prototype system to probe these dynamics by monitoring in real time the fluorescence of two organic sensitizers, a perylene and a squaraine, bound to a SnO2 semiconductor thin film as a function of potentiostatic control of the Fermi level. The two different sensitizer fluorophores characterized by vastly different redox potentials undergo similar fluorescence modulation with applied bias, an indication that the density of states of the semiconductor largely influences the charge-transfer dynamics while energetics play a minimal role.

Stepwise growth of surface-grafted DNA nanotubes visualized at the single-molecule level.

DNA nanotubes offer a high aspect ratio and rigidity, attractive attributes for the controlled assembly of hierarchically complex linear arrays. It is highly desirable to control the positioning of rungs along the backbone of the nanotubes, minimize the polydispersity in their manufacture and reduce the building costs. We report here a solid-phase synthesis methodology in which, through a cyclic scheme starting from a 'foundation rung' specifically bound to the surface, distinct rungs can be incorporated in a predetermined manner.