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."

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.

Ligand-Controlled Regiodivergence in Nickel-Catalyzed Vinylcyclopropane Rearrangement.

A ligand-controlled regiodivergence in Ni-catalyzed rearrangement of vinylcyclopropanes to 1,4- or 1,5-disubstituted cyclopentenes is reported. The 1,4- or 1,5-disubstituted cyclopentene is selectively obtained depending on the choice of ligands. Detailed kinetic studies and density functional theory calculations on the catalytic cycle revealed that the product selectivity is determined at the reductive elimination step from the six-membered η1 -allyl intermediate.

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.

Synthesis, Structure, and Dynamics of Chiral Eight-Membered Cyclic Molecules with Thienylene and Cyclopropylene Units Alternately Connected.

A rhodium(II)-catalyzed asymmetric cyclooligomerization of bifunctional monomers possessing triazolyl and vinyl groups at 2,3- and 3,4-positions on the thiophene ring is studied. Structurally interesting cyclic dimers in which thienylene and cyclopropylene units are alternately connected are obtained as the major components. The eight-membered rings in the center are non-planar and adopt a tub-shaped conformation. We also observe the phenomenon of racemization caused by a tub-to-tub ring-flipping, the activation energy of which is determined as 108 kJ mol-1 by electronic circular dichroism spectra measurement.

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.

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.

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.

Chiral Macrocycles Having C3 Symmetry Resulting from Orientation of Thiophene Rings.

An chiral RhII -catalyzed cyclooligomerization reaction of thiophenes having triazolyl and vinyl substituents at the 2- and 4-positions was studied. Structurally interesting cyclic trimers, having chirality that is ascribed only to the orientation of the 2,4-disubstituted thiophene rings, are obtained. The 2,4-disubstitution of the starting thiophene monomer allows production of each of the enantiomers. The observed electronic circular-dichroism spectra are in accord with those simulated by density-functional theory calculations.

Asymmetric Synthesis and Stereochemical Assignment of 12C/13C Isotopomers.

A synthesis of chiral hydrocarbons having C1 axis and C3 symmetry, which owe their chirality due to asymmetrical distribution of 12C/13C isotopes, is reported. Their absolute configurations assigned using the vibrational circular dichroism technique conform with those deduced from the absolute configurations of the parent α-formyl cyclopropanes.

Enantioselective Denitrogenative Annulation of 1H-Tetrazoles with Styrenes Catalyzed by Rhodium.

Sulfonylation of 1H-tetrazoles with triflic anhydride in the presence of chiral rhodium(II) carboxylate dimers causes denitrogenation to generate α-azo rhodium(II) carbenoid species as new types of donor/acceptor carbenoids, which then readily react with styrenes to afford 3,5-diaryl-2-pyrazolines with a high degree of enantioselectivity.

Synthesis of Enantiopure C3 -Symmetric Triangular Molecules.

An asymmetric synthesis of C3 -symmetric triangular macrocycles is reported. 1-Methylsulfonyl-4-(4-vinylphenyl)-1,2,3-triazole undergoes a rhodium(II)-catalyzed cyclotrimerization to establish an enantiopure C3 -symmetric triangular macrocycle motif. This method can be applied to the synthesis of an enantiopure hydrocarbon, which owes its chirality to asymmetric distribution of H/D atoms on the benzene rings.

Palladium-Catalyzed Enantioselective Intermolecular Coupling of Phenols and Allylic Alcohols.

An enantioselective intermolecular coupling of oxygen nucleophiles and allylic alcohols to give ß-aryloxycarbonyl compounds is disclosed using a chiral pyridine oxazoline-ligated palladium catalyst under mild conditions. As opposed to the formation of traditional Wacker-type products, enantioselective migratory insertion is followed by ß-hydride elimination toward the adjacent alcohol. Deuterium labeling experiments suggest a syn-migratory insertion of the alkene into the Pd-O bond. A broad scope of phenols, various allylic alcohols, and an alkyl hydroperoxide are viable coupling partners in this process.

A syn-Selective Aza-Aldol Reaction of Boron Aza-Enolates Generated from N-Sulfonyl-1,2,3-Triazoles and 9-BBN-H.

A syn-selective aza-aldol reaction of boron aza-enolates, generated from N-sulfonyl-1,2,3-triazoles and 9-BBN-H, is reported. It provides a sequential one-pot procedure for the stereoselective construction of 1,3-amino alcohols, having contiguous stereocenters, starting from terminal alkynes.

Synthesis of trans-cycloalkenes via enantioselective cyclopropanation and skeletal rearrangement.

An efficient one-pot two-step procedure for asymmetric synthesis of piperidine-fused trans-cycloalkenes is reported. The method comprises the initial enantioselective installation of another cyclopropane ring onto methylenecyclopropanes and the subsequent thermal skeletal rearrangement in which the installed and inherent cyclopropane rings are both opened. A concerted mechanism is proposed for the latter thermal rearrangement reaction together with a closed transition state model.

Cinematographic study of stochastic chemical events at atomic resolution.

The advent of single-molecule atomic-resolution time-resolved electron microscopy (SMART-EM) has created a new field of 'cinematic chemistry,' allowing for the cinematographic recording of dynamic behaviors of organic and inorganic molecules and their assembly. However, the limited electron dose per frame of video images presents a major challenge in SMART-EM. Recent advances in direct electron counting cameras and techniques to enhance image quality through the implementation of a denoising algorithm have enabled the tracking of stochastic molecular motions and chemical reactions with sub-millisecond temporal resolution and sub-angstrom localization precision. This review showcases the development of dynamic molecular imaging using the SMART-EM technique, highlighting insights into nanomechanical behavior during molecular shuttle motion, pathways of multistep chemical reactions, and elucidation of crystallization processes at the atomic level.

Melting entropy of crystals determined by electron-beam-induced configurational disordering.

Upon melting, the molecules in a crystal explore numerous configurations, reflecting an increase in disorder. The molar entropy of disorder can be defined by Boltzmann's formula ΔSd = Rln(Wd), where Wd is the increase in the number of microscopic states, so far inaccessible experimentally. We found that the Arrhenius frequency factor A of the electron diffraction signal decay provides Wd through an experimental equation A = AINTWd, where AINT is an inelastic scattering cross section. The method connects Clausius and Boltzmann experimentally and supplements the Clausius approach, being applicable to a femtogram quantity of thermally unstable and biomolecular crystals. The data also showed that crystal disordering and crystallization of melt are reciprocal, both governed by the entropy change but manifesting in opposite directions.

Cinematographic Recording of a Metastable Floating Island in Two- and Three-Dimensional Crystal Growth.

Many chemical reactions go through a cascade of events in which a series of metastable intermediates appear, and crystal nucleation is no exception. Although the consensus on the energetics of nucleation suggests the formation of metastable states preceding the crystal growth, little experimental evidence has been reported for their dynamics at an atomistic level. Operando imaging of two-dimensional nucleation on a defect-free NaCl nanocrystal in carbon nanotubes using a millisecond angstrom-resolution transmission electron microscope revealed the formation of a metastable "floating island" (FI) that migrates thermally on the (100) facet of NaCl as the first intermediate of epitaxy. The speed of the migration at 298 K is estimated to be larger than 0.3 nm ms-1. When a crystal tumbles in a container, a space repeatedly forms between the crystal and the container wall that hosts the FI. Tumbling changes the surface energy repeatedly and promotes the conversion of the FI into a new epitaxial layer. We anticipate that this surface catalysis mechanism found on the nanoscale also operates in bulk heterogeneous nucleation where agitation and attrition accelerate crystallization.