Resolving Atomic-Scale Defects in Conjugated Polymers On-Surfaces.

Atomic scale defects significantly affect the mechanical, electronic, and optical properties of π-conjugated polymers. Here, isolated atomic-scale defects are deliberately introduced into a prototypical anthracene-ethynylene π-conjugated polymer, and its local density of states is carefully examined on the atomic scale to show how individual defects modify the inherent electronic and magnetic properties of this one-dimensional systems. Scanning tunneling and atomic force microscopy experiments, supplemented with density functional theory calculations, reveal the existence of a sharp electronic resonance at the Fermi energy around certain defects, which is associated with the formation of a local magnetic moment accompanied by substantial mitigation of the mobility of charge carriers. While defects in traditionally synthesized polymers lead to arbitrary conformations, the presented results clearly reflect the preferential formation of low dimensional defects at specific polymer sites, which may introduce the possibility of engineering macroscopic defects in surface-synthesized conjugated polymers.

Unusual Scaffold Rearrangement in Polyaromatic Hydrocarbons Driven by Concerted Action of Single Gold Atoms on a Gold Surface.

Chemical transformation of polyaromatic hydrocarbon (PAH) molecules following different reaction strategies has always been the focus of organic synthesis. In this work, we report the synthesis of a PAH molecule, formation of which consists of an unusual C-C bond cleavage accompanied by a complex π-conjugated molecular scaffold rearrangement. We demonstrate that the complex chemical transformation is steered by concerted motion of individual Au0 gold atoms on a supporting Au(111) surface. This observation underpins the importance of single-atom catalysis mediated by adatoms in on-surface synthesis as well as catalytic activity of single Au0 atoms facilitating cleavage of covalent carbon bonds.

On-Surface Strain-Driven Synthesis of Nonalternant Non-Benzenoid Aromatic Compounds Containing Four- to Eight-Membered Rings.

The synthesis of polycyclic aromatic hydrocarbons containing various non-benzenoid rings remains a big challenge facing contemporary organic chemistry despite a considerable effort made over the last decades. Herein, we present a novel route, employing on-surface chemistry, to synthesize nonalternant polycyclic aromatic hydrocarbons containing up to four distinct kinds of non-benzenoid rings. We show that the surface-induced mechanical constraints imposed on strained helical reactants play a decisive role leading to the formation of products, energetically unfavorable in solution, with a peculiar ring current stabilizing the aromatic character of the π-conjugated system. Determination of the chemical and electronic structures of the most frequent product reveals its closed-shell character and low band gap. The present study renders a new route for the synthesis of novel nonalternant polycyclic aromatic hydrocarbons or other hydrocarbons driven by internal stress imposed by the surface not available by traditional approaches of organic chemistry in solution.

On-Surface Synthesis of a Dicationic Diazahexabenzocoronene Derivative on the Au(111) Surface.

The atomically precise control over the size, shape and structure of nanographenes (NGs) or the introduction of heteroatom dopants into their sp2 -carbon lattice confer them valuable electronic, optical and magnetic properties. Herein, we report on the design and synthesis of a hexabenzocoronene derivative embedded with graphitic nitrogen in its honeycomb lattice, achieved via on-surface assisted cyclodehydrogenation on the Au(111) surface. Combined scanning tunnelling microscopy/spectroscopy and non-contact atomic force microscopy investigations unveil the chemical and electronic structures of the obtained dicationic NG. Kelvin probe force microscopy measurements reveal a considerable variation of the local contact potential difference toward lower values with respect to the gold surface, indicative of its positive net charge. Altogether, we introduce the concept of cationic nitrogen doping of NGs on surfaces, opening new avenues for the design of novel carbon nanostructures.

Diradical Organic One-Dimensional Polymers Synthesized on a Metallic Surface.

We report on the synthesis and characterization of atomically precise one-dimensional diradical peripentacene polymers on a Au(111) surface. By means of high-resolution scanning probe microscopy complemented by theoretical simulations, we provide evidence of their magnetic properties, which arise from the presence of two unpaired spins at their termini. Additionally, we probe a transition of their magnetic properties related to the length of the polymer. Peripentacene dimers exhibit an antiferromagnetic (S=0) singlet ground state. They are characterized by singlet-triplet spin-flip inelastic excitations with an effective exchange coupling (Jeff ) of 2.5 meV, whereas trimers and longer peripentacene polymers reveal a paramagnetic nature and feature Kondo fingerprints at each terminus due to the unpaired spin. Our work provides access to the precise fabrication of polymers featuring diradical character which are potentially useful in carbon-based optoelectronics and spintronics.

On-Surface Synthesis of Ethynylene-Bridged Anthracene Polymers.

Engineering low-band-gap π-conjugated polymers is a growing area in basic and applied research. The main synthetic challenge lies in the solubility of the starting materials, which precludes advancements in the field. Here, we report an on-surface synthesis protocol to overcome such difficulties and produce poly(p-anthracene ethynylene) molecular wires on Au(111). To this aim, a quinoid anthracene precursor with =CBr2 moieties is deposited and annealed to 400 K, resulting in anthracene-based polymers. High-resolution nc-AFM measurements confirm the nature of the ethynylene-bridge bond between the anthracene moieties. Theoretical simulations illustrate the mechanism of the chemical reaction, highlighting three major steps: dehalogenation, diffusion of surface-stabilized carbenes, and homocoupling, which enables the formation of an ethynylene bridge. Our results introduce a novel chemical protocol to design π-conjugated polymers based on oligoacene precursors and pave new avenues for advancing the emerging field of on-surface synthesis.

Submolecular Resolution by Variation of the Inelastic Electron Tunneling Spectroscopy Amplitude and its Relation to the AFM/STM Signal.

Here we show scanning tunneling microscopy (STM), noncontact atomic force microscopy (AFM), and inelastic electron tunneling spectroscopy (IETS) measurements on an organic molecule with a CO-terminated tip at 5 K. The high-resolution contrast observed simultaneously in all channels unambiguously demonstrates the common imaging mechanism in STM/AFM/IETS, related to the lateral bending of the CO-functionalized tip. The IETS spectroscopy reveals that the submolecular contrast at 5 K consists of both renormalization of vibrational frequency and variation of the amplitude of the IETS signal. This finding is also corroborated by first principles simulations. We extend accordingly the probe-particle AFM/STM/IETS model to include these two main ingredients necessary to reproduce the high-resolution IETS contrast. We also employ the first principles simulations to get more insight into a different response of frustrated translation and rotational modes of the CO tip during imaging.

Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers.

In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562).

Atomically Precise Control of Topological State Hybridization in Conjugated Polymers.

Realization of topological quantum states in carbon nanostructures has recently emerged as a promising platform for hosting highly coherent and controllable quantum dot spin qubits. However, their adjustable manipulation remains elusive. Here, we report the atomically accurate control of the hybridization level of topologically protected quantum edge states emerging from topological interfaces in bottom-up-fabricated π-conjugated polymers. Our investigation employed a combination of low-temperature scanning tunneling microscopy and spectroscopy, along with high-resolution atomic force microscopy, to effectively modify the hybridization level of neighboring edge states by the selective dehydrogenation reaction of molecular units in a pentacene-based polymer and demonstrate their reversible character. Density functional theory, tight binding, and complete active space calculations for the Hubbard model were employed to support our findings, revealing that the extent of orbital overlap between the topological edge states can be finely tuned based on the geometry and electronic bandgap of the interconnecting region. These results demonstrate the utility of topological edge states as components for designing complex quantum arrangements for advanced electronic devices.

Atomically resolved imaging of the conformations and adsorption geometries of individual ß-cyclodextrins with non-contact AFM.

Glycans, consisting of covalently linked sugar units, are a major class of biopolymers essential to all known living organisms. To better understand their biological functions and further applications in fields from biomedicine to materials science, detailed knowledge of their structure is essential. However, due to the extraordinary complexity and conformational flexibility of glycans, state-of-the-art glycan analysis methods often fail to provide structural information with atomic precision. Here, we combine electrospray deposition in ultra-high vacuum with non-contact atomic force microscopy and theoretical calculations to unravel the structure of ß-cyclodextrin, a cyclic glucose oligomer, with atomic-scale detail. Our results, established on the single-molecule level, reveal the different adsorption geometries and conformations of ß-cyclodextrin. The position of individual hydroxy groups and the location of the stabilizing intramolecular H-bonds are deduced from atomically resolved images, enabling the unambiguous assignment of the molecular structure and demonstrating the potential of the method for glycan analysis.

Single-Molecule Identification of the Isomers of a Lipidic Antibody Activator.

Molecular structural elucidation can be accomplished by different techniques, such as nuclear magnetic resonance or X-ray diffraction. However, the former does not give information about the three-dimensional atomic arrangement, and the latter needs crystallizable solid samples. An alternative is direct, real-space visualization of the molecules by cryogenic scanning tunneling microscopy (STM). This technique is usually limited to thermally robust molecules because an annealing step is required for sample deposition. A landmark development has been the coupling of STM with electrospray deposition (ESD), which smooths the process and widens the scope of the visualization technique. In this work, we present the on-surface characterization of air-, light-, and temperature-sensitive rhamnopolyene with relevance in molecular biology. Supported by theoretical calculations, we characterize two isomers of this flexible molecule, confirming the potential of the technique to inspect labile, non-crystallizable compounds.

The effect of water on gold supported chiral graphene nanoribbons: rupture of conjugation by an alternating hydrogenation pattern.

In the last few years we have observed a breakpoint in the development of graphene-derived technologies, such as liquid phase filtering and their application to electronics. In most of these cases, they imply exposure of the material to solvents and ambient moisture, either in the fabrication of the material or the final device. The present study demonstrates the sensitivity of graphene nanoribbon (GNR) zigzag edges to water, even in extremely low concentrations. We have addressed the unique reactivity of (3,1)-chiral GNR with moisture on Au(111). Water shows a reductive behaviour, hydrogenating the central carbon of the zigzag segments. By combining scanning tunnelling microscopy (STM) with simulations, we demonstrate how their reactivity reaches a thermodynamic limit when half of the unit cells are reduced, resulting in an alternating pattern of hydrogenated and pristine unit cells starting from the terminal segments. Once a quasi-perfect alternation is reached, the reaction stops regardless of the water concentration. The hydrogenated segments limit the electronic conjugation of the GNR, but the reduction can be reversed both by tip manipulation and annealing. Selective tip-induced dehydrogenation allowed the stabilization of radical states at the edges of the ribbons, while the annealing of the sample completely recovered the original, pristine GNR.

Coverage-modulated halogen bond geometry transformation in supramolecular assemblies.

Halogen bonding (HB) has emerged as a promising route for designing supramolecular assemblies due to its directional nature and versatility in modifying interactions through the choice of halogens and molecular entities. Despite this, methods for tuning these interactions on surfaces, particularly in terms of directionality, are limited. In this study, we present a strategy for tuning the directionality of self-assembly processes in homomolecular organic compounds on inert metal surfaces. A variety of halogen-halogen geometries can promote highly-extended one-dimensional or two-dimensional self-assembly depending on the molecular coverage. Our results indicate that under lower molecular coverage conditions, robust one-dimensional (1D) structures promote the self-assembly of halogen-bonded molecules on Au(111). At certain coverage, a transformation from type-I to synthon halogen bonding is observed, leading to an extended hexagonal pattern of molecular assembly. The atomistic details of the structures are experimentally studied using high-resolution atomic force microscopy and supported by first-principle calculations. We employed DFT to evaluate the interplay between electrostatics and dispersion forces driving both type-I and synthon assemblies. The results reveal a halogen-bond geometry transformation induced by a subtle balance of molecule-molecule interaction. Finally, we investigate the capability of the halogen-bonded supramolecular assembly to periodically confine electronic quantum states and single atoms. Our findings demonstrate the versatility of sigma-bonding in regulating molecular assembly and provide new insights for tailoring functional molecular structures on an inert metal substrate.

On-surface synthesis of non-benzenoid conjugated polymers by selective atomic rearrangement of ethynylarenes.

Here, we report a new on-surface synthetic strategy to precisely introduce five-membered units into conjugated polymers from specifically designed precursor molecules that give rise to low-bandgap fulvalene-bridged bisanthene polymers. The selective formation of non-benzenoid units is finely controlled by the annealing parameters, which govern the initiation of atomic rearrangements that efficiently transform previously formed diethynyl bridges into fulvalene moieties. The atomically precise structures and electronic properties have been unmistakably characterized by STM, nc-AFM, and STS and the results are supported by DFT theoretical calculations. Interestingly, the fulvalene-bridged bisanthene polymers exhibit experimental narrow frontier electronic gaps of 1.2 eV on Au(111) with fully conjugated units. This on-surface synthetic strategy can potentially be extended to other conjugated polymers to tune their optoelectronic properties by integrating five-membered rings at precise sites.

Tactile multisensing on flexible aluminum nitride.

The integration of a polycrystalline material such as aluminum nitride (AlN) on a flexible substrate allows the realization of elastic tactile sensors showing both piezoelectricity and significant capacitive variation under normal stress. The application of a normal stress on AlN generates deformation of the flexible substrate on which AlN is grown, which results in strain gradient of the polycrystalline layer. The strain gradient is responsible for an additional polarization described in the literature as the flexoelectric effect, leading to an enhancement of the transduction properties of the material. The flexible AlN is synthesized by sputtering deposition on kapton HN (poly 4,4'-oxydiphenyl pyromellitimide) in a highly oriented crystal structure. High orientation is demonstrated by X-ray diffraction spectra (FWHM = 0.55° of AlN (0002)) and HRTEM. The piezoelectric coefficient d(33) and stress sensitive capacitance are 4.7 ± 0.5 pm V(-1) and 4 × 10(-3) pF kPa(-1), respectively. The parallel plate capacitors realized for tactile sensing present a typical dome shape, very elastic under applied stress and sensitive in the pressure range of interest for robotic applications (10 kPa to 1 MPa). The flexibility of the device finalized for tactile applications is assessed by measuring the sensor capacitance before and after shaping the sensing foil on curved surfaces for 1 hour. Bending does not affect sensor's operation, which exhibits an electrical Q factor as high as 210, regardless of the bending, and a maximum capacitance shift of 0.02%.

Microfluidics for 3D Cell and Tissue Cultures: Microfabricative and Ethical Aspects Updates.

The necessity to improve in vitro cell screening assays is becoming ever more important. Pharmaceutical companies, research laboratories and hospitals require technologies that help to speed up conventional screening and therapeutic procedures to produce more data in a short time in a realistic and reliable manner. The design of new solutions for test biomaterials and active molecules is one of the urgent problems of preclinical screening and the limited correlation between in vitro and in vivo data remains one of the major issues. The establishment of the most suitable in vitro model provides reduction in times, costs and, last but not least, in the number of animal experiments as recommended by the 3Rs (replace, reduce, refine) ethical guiding principles for testing involving animals. Although two-dimensional (2D) traditional cell screening assays are generally cheap and practical to manage, they have strong limitations, as cells, within the transition from the three-dimensional (3D) in vivo to the 2D in vitro growth conditions, do not properly mimic the real morphologies and physiology of their native tissues. In the study of human pathologies, especially, animal experiments provide data closer to what happens in the target organ or apparatus, but they imply slow and costly procedures and they generally do not fully accomplish the 3Rs recommendations, i.e., the amount of laboratory animals and the stress that they undergo must be minimized. Microfluidic devices seem to offer different advantages in relation to the mentioned issues. This review aims to describe the critical issues connected with the conventional cells culture and screening procedures, showing what happens in the in vivo physiological micro and nano environment also from a physical point of view. During the discussion, some microfluidic tools and their components are described to explain how these devices can circumvent the actual limitations described in the introduction.

Circumventing the stability problems of graphene nanoribbon zigzag edges.

Carbon nanostructures with zigzag edges exhibit unique properties-such as localized electronic states and spins-with exciting potential applications. Such nanostructures however are generally synthesized under vacuum because their zigzag edges are unstable under ambient conditions: a barrier that must be surmounted to achieve their scalable integration into devices for practical purposes. Here we show two chemical protection/deprotection strategies, demonstrated on labile, air-sensitive chiral graphene nanoribbons. Upon hydrogenation, the chiral graphene nanoribbons survive exposure to air, after which they are easily converted back to their original structure by annealing. We also approach the problem from another angle by synthesizing a form of the chiral graphene nanoribbons that is functionalized with ketone side groups. This oxidized form is chemically stable and can be converted to the pristine hydrocarbon form by hydrogenation and annealing. In both cases, the deprotected chiral graphene nanoribbons regain electronic properties similar to those of the pristine nanoribbons. We believe both approaches may be extended to other graphene nanoribbons and carbon-based nanostructures.

Direct Visualization and Identification of Membrane Voltage-Gated Sodium Channels from Human iPSC-Derived Neurons by Multiple Imaging and Light Enhanced Spectroscopy.

In this study, transmission electron microscopy atomic force microscopy, and surface enhanced Raman spectroscopy are combined through a direct imaging approach, to gather structural and chemical information of complex molecular systems such as ion channels in their original plasma membrane. Customized microfabricated sample holder allows to characterize Nav channels embedded in the original plasma membrane extracted from neuronal cells that are derived from healthy human induced pluripotent stem cells. The identification of the channels is accomplished by using two different approaches, one of them widely used in cryo-EM (the particle analysis method) and the other based on a novel Zernike Polynomial expansion of the images bitmap. This approach allows to carry out a whole series of investigations, one complementary to the other, on the same sample, preserving its state as close as possible to the original membrane configuration.

On-Surface Synthesis of One-Dimensional Coordination Polymers with Tailored Magnetic Anisotropy.

One-dimensional (1D) metalloporphyrin polymers can exhibit magnetism, depending on the central metal ion and the surrounding ligand field. The possibility of tailoring the magnetic signal in such nanostructures is highly desirable for potential spintronic devices. We present low-temperature (4.2 K) scanning tunneling microscopy and spectroscopy (LT-STM/STS) in combination with high-resolution atomic force microscopy (AFM) and a density functional theory (DFT) study of a two-step synthetic protocol to grow a robust Fe-porphyrin-based 1D polymer on-surface and to tune its magnetic properties. A thermally assisted Ullmann-like coupling reaction of Fe(III)diphenyl-bromine-porphyrin (2BrFeDPP-Cl) on Au(111) in ultra-high vacuum results in long (up to 50 nm) 1D metal-organic wires with regularly distributed magnetic and (electronically) independent porphyrins units, as confirmed by STM images. Thermally controlled C-H bond activation leads to conformational changes in the porphyrin units, which results in molecular planarization steered by 2D surface confinement, as confirmed by high-resolution AFM images. Spin-flip STS images in combination with DFT self-consistent spin-orbit coupling calculations of porphyrin units with different structural conformations reveal that the magnetic anisotropy of the triplet ground state of the central Fe ion units drops down substantially upon intramolecular rearrangements. These results point out to new opportunities for realizing and studying well-defined 1D organic magnets on surfaces and demonstrate the feasibility of tailoring their magnetic properties.

Lipid-Based Nanovesicular Drug Delivery Systems.

In designing a new drug, considering the preferred route of administration, various requirements must be fulfilled. Active molecules pharmacokinetics should be reliable with a valuable drug profile as well as well-tolerated. Over the past 20 years, nanotechnologies have provided alternative and complementary solutions to those of an exclusively pharmaceutical chemical nature since scientists and clinicians invested in the optimization of materials and methods capable of regulating effective drug delivery at the nanometer scale. Among the many drug delivery carriers, lipid nano vesicular ones successfully support clinical candidates approaching such problems as insolubility, biodegradation, and difficulty in overcoming the skin and biological barriers such as the blood-brain one. In this review, the authors discussed the structure, the biochemical composition, and the drug delivery applications of lipid nanovesicular carriers, namely, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes, phytosomes, catanionic vesicles, and extracellular vesicles.