Atomic-number (Z)-correlated atomic sizes for deciphering electron microscopic molecular images.

SignificanceAtomic resolution transmission electron microscopy (TEM) has opened up a new era of molecular science by providing atomic video images of dynamic motions of single organic and inorganic molecules. However, the images often look different from the images of molecular models, because these models are designed to visualize the electronic properties of the molecule instead of nuclear electrostatic potentials that are felt by the e-beam in TEM imaging. Here, we propose a molecular model that reproduces TEM images using atomic radii correlated to atomic number (Z). The model serves to provide a priori a useful idea of how a single molecule, molecular assemblies, and thin crystals of organic or inorganic materials look in TEM.

Ionization and electron excitation of C60 in a carbon nanotube: A variable temperature/voltage transmission electron microscopic study.

There is increasing attention to chemical applications of transmission electron microscopy, which is often plagued by radiation damage. The damage in organic matter predominantly occurs via radiolysis. Although radiolysis is highly important, previous studies on radiolysis have largely been descriptive and qualitative, lacking in such fundamental information as the product structure, the influence of the energy of the electrons, and the reaction kinetics. We need a chemically well-defined system to obtain such data and have chosen as a model a variable-temperature and variable-voltage (VT/VV) study of the [2 + 2] dimerization of a van der Waals dimer [60]fullerene (C60) to C120 in a carbon nanotube (CNT), as studied for several hundred individual reaction events at atomic resolution. We report here the identification of five reaction pathways that serve as mechanistic models of radiolysis damage. Two of them occur via a radical cation of the specimen generated by specimen ionization, and three involve singlet or triplet excited states of the specimen, as initiated by electron excitation of the CNT, followed by energy transfer to the specimen. The [2 + 2] product was identified by measuring the distance between the two C60 moieties, and the mechanisms were distinguished by the pre-exponential factor and the Arrhenius activation energy­the standard protocol of chemical kinetic studies. The results illustrate the importance of VT/VV kinetic analysis in the studies of radiation damage and show that chemical ionization and electron excitation are inseparable, but different, mechanisms of radiation damage, which has so far been classified loosely under the single term "ionization."

Doubly Spiro-Conjugated Chiral Carbocycles Exhibiting SOMO-HOMO Inversion in Persistent Radical Cations.

Persistent chiral organic open-shell systems have captured growing interest due to their potential applications in organic spintronic and optoelectronic devices. Nevertheless, the integration of configurationally stable chirality into an organic open-shell system continues to pose challenges in molecular design. The π-extended skeleton incorporated in spiro-conjugated carbocycles can provide robust chiroptical properties and a significant stabilization of the excited and ionic radical states. However, this approach has been relatively less explored in the design of persistent organic open-shell systems. We report here the (S,S)-, (R,R)-, and meso-isomers of doubly spiro-conjugated carbocycles featuring flat and rigid carbon-bridged para-phenylenevinylene (CPV) of different conjugation lengths connected by two spiro-carbon centers, which we denote D-spiro-CPV for its quasi-dimeric structure. Our synthetic method based on a double lithiation cyclization approach enables facile production of D-spiro-CPV. D-spiro-CPVs exhibit circularly polarized luminescence (CPL) with high fluorescence quantum yields (ΦFL) resulting in a high CPL brightness of 21 M-1 cm-1 and also exhibit high thermal and photostability. The monoradical cation of D-spiro-CPV absorbing near-infrared light is notably persistent, exhibiting a half-life of 570 h under ambient conditions due to doubly spiro-conjugative stabilization. Theoretical and electrochemical studies indicate the radical cation of D-spiro-CPVs presents a non-Aufbau electron filling, exhibiting inversion of the energy level of the singly occupied molecular orbital (SOMO) and the highest (doubly) occupied molecular orbitals with the SOMO level even below the HOMO-1 level (double SHI effect). Our discoveries provide valuable insights into non-Aufbau molecules and the development of configurationally stable, optically active persistent radicals.

Wavy Graphene-Like Network Forming during Pyrolysis of Polyacrylonitrile into Carbon Fiber.

Carbon fiber (CF) obtained by pyrolysis of polyacrylonitrile (PAN-CF) surpasses metals in properties suitable for diverse applications such as aircraft manufacture and power turbine blades. PAN-CF obtained by pyrolysis at 1200-1400 °C shows a remarkably high tensile strength of 7 GPa, much higher than pitch-based CF (pb-CF) consisting of piles of pure graphene networks. However, little information has been available on the atomistic structure of PAN-CF and on how it forms during pyrolysis. We pyrolyzed an acrylonitrile 9-mer in a carbon nanotube, monitored the course of the reaction using atomic-resolution electron microscopy and Raman spectroscopy, and found that this oligomer forms a thermally reactive wavy graphene-like network (WGN) at 1200-1400 °C during slow graphitization taking place between 900 and 1800 °C. Ptychographic microscopic analysis indicated that such material consists of 5-, 6-, and larger-membered rings; hence, it is not flat but wavy. The experimental data suggest that, during PAN-CF manufacturing, many layers of WGN hierarchically pile up to form a chemically and physically interdigitated noncrystalline phase that resists fracture and increases the tensile strength─the properties expected for high-entropy materials. pb-CF using nearly pure carbon starting material, on the other hand, forms a crystalline graphene network and is brittle.

Iron-Catalyzed C-H Activation for Heterocoupling and Copolymerization of Thiophenes with Enamines.

C-H/C-H coupling via C-H activation provides straightforward synthetic access to the construction of complex π-conjugated organic molecules. The palladium-catalyzed Fujiwara-Moritani (FM) coupling between an arene and an electron-deficient olefin presents an early example but is not applicable to enamines such as N-vinylcarbazoles and N-vinylindoles. We report herein iron-catalyzed C-H/C-H heterocoupling between enamines and thiophenes and its application to copolymerization of bisenamine and bisthiophene using diethyl oxalate as an oxidant and AlMe3 as a base, as a result of our realization that synthetic limitations in oxidative C-H/C-H couplings imposed by the high redox potential of the Pd(II)/Pd(0) catalytic cycle can be circumvented by the use of iron, which has a lower Fe(III)/Fe(I) redox potential. The trisphosphine ligand provides a coordination environment for iron to achieve the reaction's regio-, stereo-, and chemoselectivity. The reaction includes C-H activation of thiophene via σ-bond metathesis and subsequent enamine C-H cleavage triggered by nucleophilic enamine addition to the Fe(III) center, thereby differing from the FM reaction in mechanism and synthetic scope. The copolymers synthesized by the new reaction possess a new type of enamine-incorporated polymer backbone.

Time-Resolved Imaging of Stochastic Cascade Reactions over a Submillisecond to Second Time Range at the Angstrom Level.

Many chemical reactions, such as multistep catalytic cycles, are cascade reactions in which a series of transient intermediates appear and disappear stochastically over an extended period. The mechanisms of such reactions are challenging to study, even in ultrafast pump-probe experiments. The dimerization of a van der Waals dimer of [60]fullerene producing a short carbon nanotube is a typical cascade reaction and is probably the most frequently studied in carbon materials chemistry. As many as 23 intermediates were predicted by theory, but only the first stable one has been verified experimentally. With the aid of fast electron microscopy, we obtained cinematographic recordings of individual molecules at a maximum frame rate of 1600 frames per second. Using Chambolle total variation algorithm processing and automated cross-correlation image matching analysis, we report on the identification of several metastable intermediates by their shape and size. Although the reaction events occurred stochastically, varying the lifetime of each intermediate accordingly, the average lifetime for each intermediate structure could be obtained from statistical analysis of many cinematographic images for the cascade reaction. Among the shortest-living intermediates, we detected one that lasted less than 3 ms in three independent cascade reactions. We anticipate that the rapid technological development of microscopy and image processing will soon initiate an era of cinematographic studies of chemical reactions and cinematic chemistry.

Time-Resolved Atomistic Imaging and Statistical Analysis of Daptomycin Oligomers with and without Calcium Ions.

Daptomycin (DP) is effective against multiple drug-resistant Gram-positive pathogens because of its distinct mechanism of action. An accepted mechanism includes Ca2+-triggered aggregation of the DP molecule to form oligomers. DP and its oligomers have so far defied structural analysis at a molecular level. We studied the ability of DP molecule to aggregate by itself in water, the effects of Ca2+ ions to promote the aggregation, and the connectivity of the DP molecules in the oligomers by the combined use of dynamic light scattering in water and atomic-resolution cinematographic imaging of DP molecules captured on a carbon nanotube on which the DP molecule is installed as a fishhook. We found that the DP molecule aggregates weakly into dimers, trimers, and tetramers in water, and strongly in the presence of calcium ions, and that the tetramer is the largest oligomer in homogeneous aqueous solution. The dimer remains as the major species, and we propose a face-to-face stacked structure based on dynamic imaging using millisecond and angstrom resolution transmission electron microscopy. The tetramer in its cyclic form is the largest oligomer observed, while the trimer forms in its linear form. The study has shown that the DP molecule has an intrinsic property of forming tetramers in water, which is enhanced by the presence of calcium ions. Such experimental structural information will serve as a platform for future drug design. The data also illustrate the utility of cinematographic recording for the study of self-organization processes.

Precision Synthesis and Atomistic Analysis of Deep-Blue Cubic Quantum Dots Made via Self-Organization.

As a crystal approaches a few nanometers in size, atoms become nonequivalent, bonds vibrate, and quantum effects emerge. To study quantum dots (QDs) with structural control common in molecular science, we need atomic precision synthesis and analysis. We describe here the synthesis of lead bromide perovskite magic-sized nanoclusters via self-organization of a lead malate chelate complex and PbBr3- under ambient conditions. Millisecond and angstrom resolution electron microscopic analysis revealed the structure and the dynamic behavior of individual QDs─structurally uniform cubes made of 64 lead atoms, where eight malate molecules are located on the eight corners of the cubes, and oleylammonium cations lipophilize and stabilize the edges and faces. Lacking translational symmetry, the cube is to be viewed as a molecule rather than a nanocrystal. The QD exhibits quantitative photoluminescence and stable electroluminescence at ≈460 nm with a narrow half-maximum linewidth below 15 nm, reflecting minimum structural defects. This controlled synthesis and precise analysis demonstrate the potential of cinematic chemistry for the characterization of nanomaterials beyond the conventional limit.

Triarylamine/Bithiophene Copolymer with Enhanced Quinoidal Character as Hole-Transporting Material for Perovskite Solar Cells.

Polytriarylamine is a popular hole-transporting materials (HTMs) despite its suboptimal conductivity and significant recombination at the interface in a solar cell setup. Having noted insufficient conjugation among the triarylamine units along the polymer backbone, we inserted a bithiophene unit between two triarylamine units through iron-catalyzed C-H/C-H coupling of a triarylamine/thiophene monomer so that two units conjugate effectively via four quinoidal rings when the molecule functions as HTM. The obtained triarylamine/bithiophene copolymer (TABT) used as HTM showed a high-performance in methylammonium lead iodide perovskite (MAPbI3 ) solar cells. Mesityl substituted TABT forms a uniform film, shows high hole-carrier mobility, and has an ionization potential (IP=5.40 eV) matching that of MAPbI3 . We fabricated a solar cell device with a power conversion efficiency of 21.3 % and an open-circuit voltage of 1.15 V, which exceeds the performance of devices using reference standard such as poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine (PTAA) and Spiro-OMeTAD.

Iron-Catalyzed Tandem Cyclization of Diarylacetylene to a Strained 1,4-Dihydropentalene Framework for Narrow-Band-Gap Materials.

Carbon bridging in a form of a strained 1,4-dihydropentalene framework is an effective strategy for flattening and stabilizing oligophenylenevinylene systems for the development of optoelectronic materials. However, efficient and flexible methods for making such a strained ring system are lacking. We report herein a mild and versatile synthetic access to the 1,4-dihydropentalene framework enabled by iron-catalyzed single-pot tandem cyclization of a diarylacetylene using FeCl2 and PPh3 as catalyst, magnesium/LiCl as a reductant, and 1,2-dichloropropane as a mild oxidant. The new annulation method features two iron-catalyzed transformations used in tandem, a reductive acetylenic carboferration and an oxidation-induced ring contraction of a ferracycle under mild oxidative conditions. The new method provides access not only to a variety of substituted indeno[2,1-a]indenes but also to their thiophene congeners, 4,9-dihydrobenzo[4,5]pentaleno[1,2-b]thiophene (CPTV) and 4,8-dihydropentaleno[1,2-b:4,5-b']dithiophenes (CTV). With its high highest occupied molecular orbital level and narrow optical gap, CTV serves as a donor unit in a narrow-band-gap non-fullerene acceptor, which shows absorption extending over 1000 nm in the film state, and has found use in a near-infrared photodetector device that exhibited an external quantum efficiency of 72.4% at 940 nm.

Capturing the Moment of Emergence of Crystal Nucleus from Disorder.

Crystallization is the process of atoms or molecules forming an organized solid via nucleation and growth. Being intrinsically stochastic, the research at an atomistic level has been a huge experimental challenge. We report herein in situ detection of a crystal nucleus forming during nucleation/growth of a NaCl nanocrystal, as video recorded in the interior of a vibrating conical carbon nanotube at 20-40 ms frame-1 with localization precision of <0.1 nm. We saw NaCl units assembled to form a cluster fluctuating between featureless and semiordered states, which suddenly formed a crystal. Subsequent crystal growth at 298 K and shrinkage at 473 K took place also in a stochastic manner. Productive contributions of the graphitic surface and its mechanical vibration have been experimentally indicated.

Rim Binding of Cyclodextrins in Size-Sensitive Guest Recognition.

Cyclodextrins (CDs) are doughnut-shaped cyclic oligosaccharides having a cavity and two rims. Inclusion binding in the cavity has long served as a classic model of molecular recognition, and rim binding has been neglected. We found that CDs recognize guests by size-sensitive binding using the two rims in addition to the cavity, using single-molecule electron microscopy and a library of graphitic cones as a solid-state substrate for complexation. For example, with its cavity and rim binding ability combined, γ-CD can recognize a guest of radius between 4 and 9 Å with a size-recognition precision of better than 1 Å, as shown by structural analysis of thousands of individual specimens and statistical analysis of the data thereof. A 2.5 ms resolution electron microscopic video provided direct evidence of the process of size recognition. The data suggest the occurrence of the rim binding mode for guests larger than the size of the CD cavity and illustrate a unique application of dynamic molecular electron microscopy for deciphering the spatiotemporal details of supramolecular events.

Nano- and Microspheres Containing Inorganic and Biological Nanoparticles: Self-Assembly and Electron Tomographic Analysis.

Organofullerene amphiphiles show diverse behaviors in water, forming vesicles, micelles, Langmuir-Blodgett films, and anisotropic nanostructures. We found that gradual in situ protonation of an organic solution of (4-heptylphenyl)5C60-K+ by water or buffer generates the corresponding protonated molecule, (4-heptylphenyl)5C60H, which self-assembles to form nano- and microspheres of organofullerene (fullerspheres) with uniform diameters ranging from 30 nm to 2.5 µm that are controlled by the preparation or pH of the buffer. By using an aqueous solution of an organic dye, inorganic nanoparticle, protein, and virus, we encapsulated these entities in the fullersphere. This approach via self-assembly is distinct from other preparations of organic core-shell particles that generally require polymerization for the construction of a robust shell. The sphere is entirely amorphous, thermally stable up to 300 °C under vacuum, and resistant to electron irradiation, and we found the unconventional utility of the sphere for electron tomographic imaging of nanoparticles and biomaterials.

Alternating Heterochiral Supramolecular Copolymerization.

In stacking-based supramolecular polymerization, chiral hydrogen bonding (H-bonding) monomers often prefer to adapt a homochiral monomer sequence. Herein, we investigated the polymerization of a chiral thiophene-fused cyclooctatetraene (COT) as a novel nonplanar-core monomer and found the first example of the formation of an alternating heterochiral supramolecular copolymer. Although single enantiomer (-) or (+)-COT alone did not polymerize, when (-) and (+)-COT were mixed together, supramolecular polymerization took place to give a stereochemically alternating copolymer. By means of the microcrystal electron crystallography of a shorter side-chained COT analogue, we found that the resulting heterochiral supramolecular copolymer adapted an alternating arrangement of H-bonded and polar π-stacked parts. A computational study using density-functional theory (DFT) suggested that such an alternating heterochiral preference occurs because it allows two thiophene amide moieties facing each other to effectively cancel their in-plane dipole moments.

Axially Chiral Spiro-Conjugated Carbon-Bridged p-Phenylenevinylene Congeners: Synthetic Design and Materials Properties.

Spiro-conjugated systems are attracting considerable interest for their chiroptical properties and because of their compact structure the small reorganization energy upon electronic excitation or ionization. We report here a modular and convergent synthesis of axially chiral spiro-conjugated carbon-bridged p-phenylenevinylenes (spiro-CPVs) in a racemic and optically active form where two carbon-bridged p-phenylenevinylene molecules are connected by a spiro carbon atom. Our synthetic design focuses on the C2 symmetry of the spiro-CPV molecules, relying on coupling of two 3-lithio-2-arylindene molecules on a carbon monooxide molecule that serves as the spiro carbon center in the target molecule. We prepared derivatives including those possessing phenol groups that facilitate optical resolution and also serve as a platform for the synthesis of a variety of optically active derivatives, which exhibit circularly polarized photoluminescence with high fluorescence quantum yields, large dissymmetry factors, and high photostability. For example, a bis(phenylethynyl) derivative exhibited a fluorescence quantum yield of 0.99 and a dissymmetry factor in luminescence of |glum| = 2.7 × 10-4, values highest among and comparable to those of reported CPL compounds, respectively. A tetrakis-diarylamine derivative shows hole mobility (µh = 3.84 × 10-5 cm2 V-1 s-1; space charge-limited current measurement of a spin-coated film) comparable to that of a popularly used hole-transporting material, spiro-OMeTAD (µh = 2.6 × 10-5 cm2 V-1 s-1), as well as high thermal and phase stability (T5d = 382 °C, Tg = 171 °C).

Chromium(III)-Catalyzed C(sp2)-H Alkynylation, Allylation, and Naphthalenation of Secondary Amides with Trimethylaluminum as Base.

Among base metals used for C-H activation reactions, chromium(III) is rather unexplored despite its natural abundance and low toxicity. We report herein chromium(III)-catalyzed C(sp2)-H functionalization of an ortho-position of aromatic and α,ß-unsaturated secondary amides using readily available AlMe3 as a base and using bromoalkynes, allyl bromide, and 1,4-dihydro-1,4-epoxynaphthalene as electrophiles. This redox-neutral reaction taking place at 70-90 °C, requires as low as 1-2 mol % of CrCl3 or Cr(acac)3 as a catalyst without any added ligand, and tolerates functional groups such as aryl iodide, boronate, and thiophene groups. Stoichiometric and kinetics studies as well as kinetic isotope effects suggest that the catalytic cycle consists of a series of thermally stable but reactive intermediates bearing two molecules of the amide substrate on one chromium atom and also that one of these chromate(III) complexes takes part in the alkynylation, allylation, and naphthalenation reactions. The proposed mechanism accounts for the effective suppression of methyl group delivery from AlMe3 for ortho-C-H methylation.

B/N-Doped p-Arylenevinylene Chromophores: Synthesis, Properties, and Microcrystal Electron Crystallographic Study.

Linearly conjugated systems have long served as an archetype of conjugated materials, but suffer from two intrinsic structural problems: potential instability due to intermolecular interactions and the flexibility of the C-C bonds connecting C═C bonds. Efforts to solve these problems have included the insertion of aromatic units as a part of the conjugation and the introduction of carbon bridges to stop the bond rotation. We report here B/N-doped p-arylenevinylene chromophores synthesized through the incorporation of a cyclopenta[c][1,2]azaborole framework as a part of the conjugated system. The ring strain intrinsic to this new skeleton both flattens and rigidifies the conjugation, and the B--N+ dative bond is much easier to form than a C-C bond, which simplifies the synthetic design. The B-N dative bond also reduces the HOMO-LUMO gap, thereby causing a significant redshift of the absorption and emission compared with their all-carbon congeners while retaining high photostability and high fluorescence quantum yield in both solution and film states. A doubly B/N-doped compound showed emission peaks at 540 nm with a small Stokes shift of 20 nm and a fluorescence quantum yield of 98%. The molecules serve as excellent lipophilic fluorescent dyes for live-cell imaging, showing a higher photostability than that of commercially available BODIPY-based dyes.

Carbon-Bridged Oligo(phenylene vinylene)s: A de Novo Designed, Flat, Rigid, and Stable π-Conjugated System.

The modern history of conducting organic systems started with a fortuitous error in 1967 on acetylene polymerization, followed by a rational discovery in 1976 on the effects of doping that generates a polaron and, hence, dramatically increases conductivity. Not unexpectedly, however, the prototypical polyacetylene suffers many problems, including C-C single bond rotation, short effective conjugation length, radiationless deactivation, and instability of the polarons. Several strategies have been put in place to solve these problems. An early approach relied on partial rigidification of the polyene structure by conversion into polymers with thiophene, pyrrole, and benzene linkages. An oligo(phenylene vinylene) (OPV) is an all-carbon analogue of polyacetylene, where every other diene unit in the polyene chain is converted to a benzene unit, still leaving many C-C single bonds freely rotating in the molecule. We considered adding additional carbon bridges to rigidify the OPV skeleton entirely to create a carbon-bridged OPV (COPV). Making such a compound was an obvious challenge. This Account describes the authors' efforts to design and synthesize a series of COPV molecules, where the benzene rings in OPV are bridged by sp3 carbon atoms to form a bicyclo[3.3.0]octatriene framework bearing a tetrasubstituted olefin at the ring fusion. This olefinic bond is so strained that it resists further deformation or conversion to sp3 centers, and hence, it is chemically stable despite the strain. The sp3 carbon bridges can bear organic side chains that hinder intermolecular interactions, rendering the excited states stable and long-lived even in the solid state. They also increase solubility, a common problem among rigid molecular systems. With these structural features, the COPV molecules were found to be well behaved both at a single-molecule level and as a bulk material. We reported in 2009 a method for the synthesis of COPVs and have, since then, reported their structures and physicochemical properties, including basic photophysical properties of neutral and charged derivatives, thermal and photostability, and fast electron transfer. These properties have rendered the COPV molecules useful for electronic and photonic research, for example, lasers, solar cells, and molecular wire applications. Noteworthy discoveries in the area connecting chemistry and physics include inelastic tunneling and long-range resonance tunneling at ambient temperature, which were previously observed only for organic molecular wires placed under cryogenic conditions. Given the ready availability of the COPV skeleton bearing a wide variety of substituents, this class of molecules will serve as versatile building blocks for fundamental and applied research on physicochemical and materials chemistry.

Interfacial Chemistry of Conical Fullerene Amphiphiles in Water.

Amphiphiles are used for a variety of applications in our daily life and in industrial processes. They typically possess hydrophobic and hydrophilic moieties within the molecule, thereby performing a myriad of functions through the formation of two- and three-dimensional assemblies in water, such as Gibbs monolayers and micelles. However, these functions are often inseparable because they emerge from the same structural feature of the molecule, and are difficult to control because the structural diversity is limited to either long-chain hydrocarbons bearing a polar end group(s) or polymers bearing polar groups exposed to the exterior surface. In this Account, we describe the chemistry of a new class of amphiphiles, conical fullerene amphiphiles (CFAs), utilizing a superhydrophobic [60]fullerene group as a nonpolar apex with added structural features to make it soluble in water. By selective functionalization of only one side of the fullerene molecule, the CFA molecules spontaneously assemble in water through strong hydrophobic interactions among the fullerene apexes and exhibit unusual supramolecular and interfacial behavior. They form unilamellar micelles and vesicles at a critical aggregation concentration as low as micromolar, not showing any air-water and oil-water interfacial activity. The strong preference for self-assembly in water over monolayer formation at an air-water interface makes CFAs unique among conventional nonpolymeric surfactants. The CFA assemblies are often so mechanically robust that they can be transferred to the surface of a solid substrate and analyzed by high-resolution microscopy. Because of this rigid conical structure of a few nanometers in size, CFA molecules aggregate readily in water to form a hierarchical assembly with biomolecules and nanomaterials while maintaining the structural integrity of the CFA aggregate to form multicomponent agglomerates of controllable structural features. For instance, tissue-selective in vivo transport of DNA and siRNA has been achieved. Hybridization of a CFA vesicle with a transition metal catalyst enables the construction of a structurally defined nanospace and an interface for precise control of the nanoscale morphology of polymers. Solubilization of hydrophobic nanocarbons and nanoparticles is also achieved through hemimicelle formation on solid surfaces. The examples reported here illustrate the potential of the conical fullerene motif for the design of amphiphiles as well as supramolecular structures at molecular and tens of nanometers scale.

Ultra-Fast Electron Microscopic Imaging of Single Molecules With a Direct Electron Detection Camera and Noise Reduction.

Time-resolved imaging of molecules and materials made of light elements is an emerging field of transmission electron microscopy (TEM), and the recent development of direct electron detection cameras, capable of taking as many as 1,600 fps, has potentially broadened the scope of the time-resolved TEM imaging in chemistry and nanotechnology. However, such a high frame rate reduces electron dose per frame, lowers the signal-to-noise ratio (SNR), and renders the molecular images practically invisible. Here, we examined image noise reduction to take the best advantage of fast cameras and concluded that the Chambolle total variation denoising algorithm is the method of choice, as illustrated for imaging of a molecule in the 1D hollow space of a carbon nanotube with ~1 ms time resolution. Through the systematic comparison of the performance of multiple denoising algorithms, we found that the Chambolle algorithm improves the SNR by more than an order of magnitude when applied to TEM images taken at a low electron dose as required for imaging at around 1,000 fps. Open-source code and a standalone application to apply Chambolle denoising to TEM images and video frames are available for download.