Investigating New Applications of a Photoswitchable Fluorescent Norbornadiene as a Multifunctional Probe for Delineation of Amyloid Plaque Polymorphism.

Amyloid beta (Aß) plaques are a major pathological hallmark of Alzheimer's disease (AD) and constitute of structurally heterogenic entities (polymorphs) that have been implicated in the phenotypic heterogeneity of AD pathology and pathogenesis. Understanding amyloid aggregation has been a critical limiting factor to gain understanding of AD pathogenesis, ultimately reflected in that the underlying mechanism remains elusive. We identified a fluorescent probe in the form of a turn-off photoswitchable norbornadiene derivative (NBD1) with several microenvironment-sensitive properties that make it relevant for applications within advanced fluorescence imaging, for example, multifunctional imaging. We explored the application of NBD1 for in situ delineation of structurally heterogenic Aß plaques in transgenic AD mouse models. NBD1 plaque imaging shows characteristic broader emission bands in the periphery and more narrow emission bands in the dense cores of mature cored plaques. Further, we demonstrate in situ photoisomerization of NBD1 to quadricyclane and thermal recovery in single plaques, which is relevant for applications within both functional and super-resolution imaging. This is the first time a norbornadiene photoswitch has been used as a probe for fluorescence imaging of Aß plaque pathology in situ and that its spectroscopic and switching properties have been studied within the specific environment of senile Aß plaques. These findings open the way toward new applications of NBD-based photoswitchable fluorescent probes for super-resolution or dual-color imaging and multifunctional microscopy of amyloid plaque heterogeneity. This could allow to visualize Aß plaques with resolution beyond the diffraction limit, label different plaque types, and gain insights into their physicochemical composition.

A Memristive Element Based on an Electrically Controlled Single-Molecule Reaction.

The exponential proliferation of data during the information age has required the continuous exploration of novel storage paradigms, materials, and devices with increasing data density. As a step toward the ultimate limits in data density, the development of an electrically controllable single-molecule memristive element is reported. In this device, digital information is encoded through switching between two isomer states by applying a voltage signal to the molecular junction, and the information is read out by monitoring the electrical conductance of each isomer. The two states are cycled using an electrically controllable local-heating mechanism for the forward reaction and catalyzed by a single charge-transfer process for the reverse switching. This single-molecule device can be modulated in situ, is fully reversible, and does not display stochastic switching. The I-V curves of this single-molecule system also exhibit memristive character. These features suggest a new approach for the development of molecular switching systems and storage-class memories.

Improved Interfacial Bonding Strength and Reliability of Functionalized Graphene Oxide for Cement Reinforcement Applications.

Poor bonding strength between nanomaterials and cement composites inevitably lead to the failure of reinforcement. Herein, a novel functionalization method for the fabrication of functionalized graphene oxide (FGO), which is capable of forming highly reliable covalent bonds with cement hydration products, and therefore, suitable for use as an efficient reinforcing agent for cement composites, is discussed. The bonding strength between cement and aggregates was improved more than 21 times with the reinforcement of FGO. The fabricated FGO also demonstrated many important features, including high reliability in cement pastes, good dispersibility, and efficient structural refinement of cement hydration products. With the incorporation of FGO, cement mortar samples demonstrated up to 40 % increased early and ultimate strength. Such results make the fast demolding and manufacture of light constructions become highly possible, and show strong advantages on improving productivity, saving cost, and reducing CO2 emissions in practical applications.

Three-Input Molecular Keypad Lock Based on a Norbornadiene-Quadricyclane Photoswitch.

The photo- and acidochromic properties of a new generation norbornadiene derivative have been harnessed for the realization of a three-input keypad lock, where a specific sequence of inputs induces a unique output. Reversible quadricyclane/norbornadiene photoisomerization is reported, and this rare feature allows the first example of a norbornadiene-based molecular logic system. The function of this system is clearly rationalized in terms of the interconversion scheme and the absorption spectra of the involved species.

Parallel Fabrication of Self-Assembled Nanogaps for Molecular Electronic Devices.

Single molecule electronics might be a way to add additional function to nanoscale devices and continue miniaturization beyond current state of the art. Here, a combined top-down and bottom-up strategy is employed to assemble single molecules onto prefabricated electrodes. Protodevices, which are self-assembled nanogaps composed by two gold nanoparticles linked by a single or a few molecules, are guided onto top-down prefabricated nanosized nickel electrodes with sandwiched palladium layers. It is shown that an optimized geometry of multilayered metallic (top-down) electrodes facilitates the assembly of (bottom-up) nanostructures by surface charge interactions. Moreover, such assembly process results in an electrode-nanoparticle interface free from linking molecules that enable electrical measurements to probe electron transport properties of the nanoparticle-molecule-nanoparticle protodevices.

Turn-off mode fluorescent norbornadiene-based photoswitches.

Single-molecule fluorescence emission of certain positive photochromic systems such as diarylethenes have been exploited for biological imaging and optical memory storage applications. However, there is a lack of understanding if negative photochromic systems can be used for such type of applications. Hence, to explore the potential of negative photochromic molecules for possible optical memory storage applications, we have here synthesized and studied a series of four norbornadiene-quadricyclane (NBD-QC) photoswitching molecules. These molecules feature either linearly conjugated or cross-conjugated pi-electron systems. Upon photoisomerization, the UV-vis absorption spectra of the molecules revealed a strong blue shift in the QC-form, with a photoisomerization quantum yield close to 80% for the cross-conjugated systems. In contrast, a strong intrinsic emission (up to Φf = 49%) for the linearly conjugated compounds in the NBD form was observed. Upon light-induced isomerization, the emission was completely turned off in the QC-form in all the compounds studied. Further, the robustness of the system was evaluated by performing several switching cycles. Under nitrogen, the emission can be turned off and recovered with almost no loss of emission. We also show that the QC-form can be photochemically triggered to convert back to the NBD-form using a low energy UV light (340 nm), allowing an all optical conversion to both species. The demonstrated properties can make the NBD-QC system attractive for potential applications such as optical memory storage devices.

Heteroaryl-linked norbornadiene dimers with redshifted absorptions.

Development of Molecular Solar Thermal (MOST) systems for harvesting and storing solar energy is based on molecular photoswitches that undergo photoisomerizations to metastable isomers. One challenge is to achieve low-molecular weight molecules that absorb at sufficiently long wavelengths to match the solar spectrum. Here we show that this can be achieved by linking two norbornadiene (NBD) photoswitches to a central heterocycle, thiophene or carbazole, via alkyne appendages. In this approach, the same heteroaryl is used to tune the properties of two photoswitches at the same time, thereby keeping the molecular weight as low as possible. A series of NBD dimers was prepared by Sonogashira coupling reactions, and these compounds showed remarkable redshifted absorptions, with onsets of absorption as high as 468 nm, and thermal half-lives ranging from 44 seconds to 16 hours.

Release of Terminal Alkynes via Tandem Photodeprotection and Decarboxylation of o-Nitrobenzyl Arylpropiolates in a Flow Microchannel Reactor.

Photocleavable protecting groups (PPGs) offer a complementary protection paradigm compared to traditional protection groups. Herein, an o-nitrobenzyl (NB) PPG was employed to protect a variety of arylpropiolic acids. Upon a cascade of light-triggered photodeprotection in a microchannel reactor (residence times of 100-500 s), followed by Cu-catalyzed decarboxylation at 60 °C, the NB-protected arylpropiolic acid afforded a terminal alkyne. This terminal alkyne was further reacted in situ with an azide via click chemistry to yield a 1,2,3-triazole in a one-pot reaction. Furthermore, the effect of different substituents (methyl, vinyl, allyl, and phenyl) at the benzylic position on the rate of photodeprotection was studied. The quantum yields of photolysis for the benzylic-substituted esters were determined to be as high as 0.45 compared to the unsubstituted ester with a 0.08 quantum yield of photolysis.

Effect of Ring Strain on the Charge Transport of a Robust Norbornadiene-Quadricyclane-Based Molecular Photoswitch.

Integrating functional molecules into single-molecule devices is a key step toward the realization of future computing machines based on the smallest possible components. In this context, photoswitching molecules that can make a transition between high and low conductivity in response to light are attractive candidates. Here we present the synthesis and conductance properties of a new type of robust molecular photothermal switch based on the norbornadiene (NB)-quadricyclane (QC) system. The transport through the molecule in the ON state is dominated by a pathway through the π-conjugated system, which is no longer available when the system is switched to the OFF state. Interestingly, in the OFF state we find that the same pathway contributes only 12% to the transport properties. We attribute this observation to the strained tetrahedral geometry of the QC. These results challenge the prevailing assumption that current will simply flow through the shortest through-bond path in a molecule.