Probing the Rotary Cycle of Amine-Substituted Molecular Motors.

An understanding of the rotary cycle of molecular motors (MMs), a key component of an approach to opening cells using mechanical motion, is important in furthering the research. Nuclear magnetic resonance (NMR) spectroscopy was used for in situ analysis of illuminated light-active MMs. We found that the presence of a N,N-dimethylethylenediamine in a position conjugated to the central olefin results in changes to the rotation of a second-generation Feringa-type MM. Importantly, the addition decreases the photostability of the compound. The parent compound 1 can withstand >2 h of illumination with no signs of decomposition, while the amino 7 decomposes after 10 min. We found that the degradation can be mitigated by implementing the simple techniques of modulating the light dose, dilution, and stirring the sample while illuminating. Additionally, the presence of moisture affects the rate of the motor's rotation. The addition of the amino group to 1, without moisture present, makes the rotation of motor 7 three times slower than the unfunctionalized parent compound. We also report the use of a method that can be used to determine the molar extinction coefficient of a light-generated metastable species. This method can be used when in situ NMR illumination is not available.

A Dual Catalyst Strategy for Controlling Aluminum Nanocrystal Growth.

The synthesis of Al nanocrystals (Al NCs) is a rapidly expanding field, but there are few strategies for size and morphology control. Here we introduce a dual catalyst approach for the synthesis of Al NCs to control both NC size and shape. By using one catalyst that nucleates growth more rapidly than a second catalyst whose ligands affect NC morphology during growth, one can obtain both size and shape control of the resulting Al NCs. The combination of the two catalysts (1) titanium isopropoxide (TIP), for rapid nucleation, and (2) Tebbe's reagent, for specific facet-promoting growth, yields {100}-faceted Al NCs with tunable diameters between 35 and 65 nm. This dual-catalyst strategy could dramatically expand the possible outcomes for Al NC growth, opening the door to new controlled morphologies and a deeper understanding of earth-abundant plasmonic nanocrystal synthesis.

Predicting 1H NMR relaxation in Gd3+-aqua using molecular dynamics simulations.

Atomistic molecular dynamics simulations are used to predict 1H NMR T1 relaxation of water from paramagnetic Gd3+ ions in solution at 25 °C. Simulations of the T1 relaxivity dispersion function r1 computed from the Gd3+-1H dipole-dipole autocorrelation function agree within ≃8% of measurements in the range f0 ≃ 5 ↔ 500 MHz, without any adjustable parameters in the interpretation of the simulations, and without any relaxation models. The simulation results are discussed in the context of the Solomon-Bloembergen-Morgan inner-sphere relaxation model, and the Hwang-Freed outer-sphere relaxation model. Below f0 ≲ 5 MHz, the simulation overestimates r1 compared to measurements, which is used to estimate the zero-field electron-spin relaxation time. The simulations show potential for predicting r1 at high frequencies in chelated Gd3+ contrast-agents used for clinical MRI.

Synthesis of Structurally Diverse 3-, 4-, 5-, and 6-Membered Heterocycles from Diisopropyl Iminomalonates and Soft C-Nucleophiles.

Herein, we present a general synthetic strategy for the preparation of 3-, 4-, 5-, and 6-membered heterocyclic unnatural amino acid derivatives by exploiting facile Mannich-type reactions between readily available N-alkyl- and N-aryl-substituted diisopropyl iminomalonates and a wide range of soft anionic C-nucleophiles without using any catalyst or additive. Fully substituted aziridines were obtained in a single step when enolates of α-bromo esters were employed as nucleophiles. Enantiomerically enriched azetidines, γ-lactones, and tetrahydroquinolines were obtained via a two-step catalytic asymmetric reduction and cyclization sequence from ketone enolate-derived adducts. Finally, highly substituted γ-lactams were prepared in one pot from adducts obtained using acetonitrile-derived carbanions. Overall, this work clearly demonstrates the utility of iminomalonates as highly versatile building blocks for the practical and scalable synthesis of structurally diverse heterocycles.

Total Synthesis and Full Structural Assignment of Namenamicin.

Namenamicin is a rare natural product possessing potent cytotoxic properties that may prove useful as a lead compound for payloads of antibody-drug conjugates (ADCs). Its scarcity, coupled with the uncertainty of its full absolute configuration, elevates it to an attractive synthetic target. Herein we describe the total synthesis of the two C7'-epimers of namenamicin and assign its complete structure, opening the way for further chemical and biological studies toward the discovery of potent payloads for ADCs directed toward targeted cancer therapies.

Streamlined Total Synthesis of Shishijimicin A and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues thereof and Practical Syntheses of PhthNSSMe and Related Sulfenylating Reagents.

Shishijimicin A is a scarce marine natural product with highly potent cytotoxicities, making it a potential payload or a lead compound for designed antibody-drug conjugates. Herein, we describe an improved total synthesis of shishijimicin A and the design, synthesis, and biological evaluation of a series of analogues. Equipped with appropriate functionalities for linker attachment, a number of these analogues exhibited extremely potent cytotoxicities for the intended purposes. The synthetic strategies and tactics developed and employed in these studies included improved preparation of previously known and new sulfenylating reagents such as PhthNSSMe and related compounds.

Structural Studies of Hydrographenes.

As a result of the unique physical and electrical properties, graphene continues to attract the interest of a large segment of the scientific community. Since graphene does not occur naturally, the ability to exfoliate and isolate individual layers of graphene from graphite is an important and challenging process. The interlayer cohesive energy of graphite that results from van der Waals attractions has been determined experimentally to be 61 meV per carbon atom (61 meV/C atom). This requires the development of a method to overcome the strong attractive forces associated with graphite. The exfoliation process that we, and others, have investigated involves electron transfer into bulk graphite from intercalated lithium to yield lithium graphenide. The resulting graphenide can be reacted with various reagents to yield functionalized graphene. As a part of our interest in the functionalization of graphene, we have explored the Birch reduction as a route to hydrographenes. The addition of hydrogen transforms graphene into an insulator, leading to the prediction that important applications will emerge. This Account focuses mainly on the characterization of the hydrographenes that are obtained from different types of graphite including synthetic graphite powder, natural flake graphite, and annealed graphite powder. Analysis by solid state 13C NMR spectroscopy proved to be important since it was shown that the hydrographenes are composed of interior, isolated aromatic (predominantly fully substituted benzene) rings surrounded by saturated rings. The expected clusters of benzene rings were not found. NMR spectroscopy also offers strong evidence for the presence of tert-butyl alcohol and ethanol (workup solvent) that could not be removed in vacuo from the samples. These compounds could be observed to move freely within the layers of the hydrographene. High-resolution transmission electron microscopy images revealed a remarkable change in morphology that results when hydrogen is added to the graphenide. The appearance of edge and circular dislocations and increased distances between graphitic layers are most visible in the case of the hydrographenes that are formed from annealed graphite. The repetitive hydrogenation of synthetic graphite powder leads to an increase in the distances between the graphitic layers in the (002) direction from 3.4 Å for the initial graphite to 4.11 Å after the first reduction and to 4.29 Å after a third reduction of the same material. Defect-free graphite is formed when the hydrographenes are heated. The distance between carbon layers decreases from 4.11 to 3.44 Å after heating the samples to 1200 °C. This trend toward the spacing of graphite confirms the reversibility of the functionalization process. The C-H bonds have been broken yielding hydrogen, and the exposed carbon orbitals are in close enough proximity to have reverted to graphite. This Account introduces only a narrow area of materials chemistry, and many applications of graphene and its derivatives can be expected as researchers exploit this burgeoning field.

Structural Characteristics and Properties of a New Graphitic-Based Material.

The hydrogenation of commercial graphite using lithium/ammonia as the reducing agent and tert-butyl alcohol as a proton source was investigated. Characterization of the products after successive reductions of the same material by high-resolution transmission electron microscopy revealed a new material that was replete with edge and circular dislocations. Analysis by solid-state (13)C NMR spectroscopy indicates that after three reductions, the remaining aromatic rings appear to be interior benzene rings. NMR spectroscopy also offers strong evidence for the presence of small amounts of tert-butyl alcohol and ethanol (workup solvent) that could not be removed in vacuo from the samples. These compounds could be observed to move freely between the layers of the hydrographene.

Reduction of hydroxylated fullerene (fullerol) in water by zinc: reaction and hemiketal product characterization.

Water-soluble, hydroxylated fullerene (fullerol) materials have recently gained increasing attention as they have been identified as the primary product(s) during the exposure of fullerenes (as water stable, nanoscale aggregated C60) to UV light in water. The physical properties and chemical reactivity of resulting fullerols, however, have not been thoroughly studied. In this paper, we identified and characterized the reductive transformation of fullerol (C60(OH)x(ONa)y) by solid zinc metal (Zn(0)) through a series of batch reaction experiments and product characterization, including (13)C NMR, FTIR, XPS, UV-vis, DLS, and TEM. Results indicated the facile formation of water stable, pH sensitive hemiketal functionality as part of a relatively reduced fullerol product. Further, aqueous physical behavior of the product fullerol, as measured by octanol partitioning and surface deposition rates, was observed to significantly differ from the parent material and is consistent with a relative increase in molecular (product) hydrophobicity.

Additional insights from very-high-resolution 13C NMR spectra of long-chain n-alkanes.

New information has been obtained from very-high-resolution (13) C NMR studies of a series of long-chain n-alkanes. These compounds are fundamentally important in the petroleum industry and are essential to the life of some plants, flowers, and insects. At least partial resolution of the ten different (13) C NMR signals of n-C20 H42 is observed at 11.7 T for solutions in C6 D6 or C6 D5 CD3 . A (13) C T1 inversion-recovery experiment provides much more detailed information than in previous studies of long-chain n-alkanes, demonstrates a steady increase in the relaxation times of the ten different carbons proceeding from the middle to the end of the chain because of segmental motion, and thus confirms the assignments for the interior carbons. In contrast, there is significant overlap for the signals for C-7 and the more interior carbons in a solution of n-C16 or longer chain alkanes in CDCl3 . Not only are the chemical shifts sensitive to the solvent used, but also the relative chemical shifts change. Signals for the interior carbons of the odd-number alkanes in CDCl3 are better resolved than in the spectra of their even-number counterparts. Some mixed aromatic solvent systems give increased dispersion of the cluster of C-6 through C-10 signals of n-C20 H42 , n-C21 H44 , and n-C22 H46 . However, none of the solvents used could even partially resolve the C-10 and C-11 signals of n-C21 H44 or n-C22 H46 at 11.7 T, which may result from a different distribution of conformers for n-C21 H44 or n-C22 H46 than for n-C20 H42 and shorter n-alkanes.

Graphene quantum dots derived from carbon fibers.

Graphene quantum dots (GQDs), which are edge-bound nanometer-size graphene pieces, have fascinating optical and electronic properties. These have been synthesized either by nanolithography or from starting materials such as graphene oxide (GO) by the chemical breakdown of their extended planar structure, both of which are multistep tedious processes. Here, we report that during the acid treatment and chemical exfoliation of traditional pitch-based carbon fibers, that are both cheap and commercially available, the stacked graphitic submicrometer domains of the fibers are easily broken down, leading to the creation of GQDs with different size distribution in scalable amounts. The as-produced GQDs, in the size range of 1-4 nm, show two-dimensional morphology, most of which present zigzag edge structure, and are 1-3 atomic layers thick. The photoluminescence of the GQDs can be tailored through varying the size of the GQDs by changing process parameters. Due to the luminescence stability, nanosecond lifetime, biocompatibility, low toxicity, and high water solubility, these GQDs are demonstrated to be excellent probes for high contrast bioimaging and biosensing applications.

Three-dimensional covalent organic frameworks with pto and mhq-z topologies based on Tri- and tetratopic linkers.

Three-dimensional (3D) covalent organic frameworks (COFs) possess higher surface areas, more abundant pore channels, and lower density compared to their two-dimensional counterparts which makes the development of 3D COFs interesting from a fundamental and practical point of view. However, the construction of highly crystalline 3D COF remains challenging. At the same time, the choice of topologies in 3D COFs is limited by the crystallization problem, the lack of availability of suitable building blocks with appropriate reactivity and symmetries, and the difficulties in crystalline structure determination. Herein, we report two highly crystalline 3D COFs with pto and mhq-z topologies designed by rationally selecting rectangular-planar and trigonal-planar building blocks with appropriate conformational strains. The pto 3D COFs show a large pore size of 46 Å with an extremely low calculated density. The mhq-z net topology is solely constructed from totally face-enclosed organic polyhedra displaying a precise uniform micropore size of 1.0 nm. The 3D COFs show a high CO2 adsorption capacity at room temperature and can potentially serve as promising carbon capture adsorbents. This work expands the choice of accessible 3D COF topologies, enriching the structural versatility of COFs.

Pristine graphite oxide.

Graphite oxide (GO) is a lamellar substance with an ambiguous structure due to material complexity. Recently published GO-related studies employ only one out of several existing models to interpret the experimental data. Because the models are different, this leads to confusion in understanding the nature of the observed phenomena. Lessening the structural ambiguity would lead to further developments in functionalization and use of GO. Here, we show that the structure and properties of GO depend significantly on the quenching and purification procedures, rather than, as is commonly thought, on the type of graphite used or oxidation protocol. We introduce a new purification protocol that produces a product that we refer to as pristine GO (pGO) in contrast to the commonly known material that we will refer to as conventional GO (cGO). We explain the differences between pGO and cGO by transformations caused by reaction with water. We produce ultraviolet-visible spectroscopic, Fourier transform infrared spectroscopic, solid-state nuclear magnetic resonance spectroscopic, thermogravimetric, and scanning electron microscopic analytical evidence for the structure of pGO. This work provides a new explanation for the acidity of GO solutions and allows us to add critical details to existing GO models.

Birch reduction of graphite. Edge and interior functionalization by hydrogen.

The Birch reduction (lithium in liquid ammonia) of graphite gives a highly reduced, exfoliated product that is free of lithium. Edge and interior hydrogenation were demonstrated by solid-state (13)C NMR spectroscopy. Elemental analysis of a carefully purified sample allows the chemical composition to be expressed as (C(1.3)H)(n). Atomic force microscopy images showed that the reduced graphene was highly exfoliated. Hydrogen mapping by electron energy loss spectroscopy showed that the entire surface of the reduced sample was covered by hydrogen, consistent with the NMR studies also indicating that hydrogen was added in interior positions of the graphene lattice as well as along the edge. A large band gap (4 eV) further establishes the high level of hydrogenation.

High-Strength, Microporous, Two-Dimensional Polymer Thin Films with Rigid Benzoxazole Linkage.

Two-dimensional (2D) rigid polymers provide an opportunity to translate the high-strength, high-modulus mechanical performance of classic rigid-rod 1D polymers across a plane by extending covalent bonding into two dimensions while simultaneously reducing density due to microporosity by structural design. Thus far, this potential has remained elusive because of the challenge of producing high-quality 2D polymer thin films, particularly those with irreversible, rigid benzazole linkages. Here, we present a facile two-step process that allows the deposition of a uniform intermediate film network via reversible, non-covalent interactions, followed by a subsequent solid-state annealing step that facilitates the irreversible conversion to a 2D covalently bonded polymer product with benzoxazole linkages. We demonstrate the versatility of this synthesis method by producing films with four different aromatic core units. The resulting films show microporosity and anisotropy with a 2D layered structure that can be exfoliated into few-layer nanosheets using a freeze-thaw method. These films have promising mechanical properties with an in-plane ultimate tensile strength of nearly 40 MPa and axial tensile and transverse compressive elastic moduli on the scale of several GPa, rivaling the performance of solution-cast films of 1D polybenzoxazole, as well as several other 1D high-strength polymer films.

Hemithioindigo-Based Visible Light-Activated Molecular Machines Kill Bacteria by Oxidative Damage.

Antibiotic resistance is a growing health threat. There is an urgent and critical need to develop new antimicrobial modalities and therapies. Here, a set of hemithioindigo (HTI)-based molecular machines capable of specifically killing Gram-positive bacteria within minutes of activation with visible light (455 nm at 65 mW cm-2 ) that are safe for mammalian cells is described. Importantly, repeated exposure of bacteria to HTI does not result in detectable development of resistance. Visible light-activated HTI kill both exponentially growing bacterial cells and antibiotic-tolerant persister cells of various Gram-positive strains, including methicillin-resistant S. aureus (MRSA). Visible light-activated HTI also eliminate biofilms of S. aureus and B. subtilis in as little as 1 h after light activation. Quantification of reactive oxygen species (ROS) formation and protein carbonyls, as well as assays with various ROS scavengers, identifies oxidative damage as the underlying mechanism for the antibacterial activity of HTI. In addition to their direct antibacterial properties, HTI synergize with conventional antibiotics in vitro and in vivo, reducing the bacterial load and mortality associated with MRSA infection in an invertebrate burn wound model. To the best of the authors' knowledge, this is the first report on the antimicrobial activity of HTI-based molecular machines.

Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane.

The increasing occurrence of antibiotic-resistant bacteria and the dwindling antibiotic research and development pipeline have created a pressing global health crisis. Here, we report the discovery of a distinctive antibacterial therapy that uses visible (405 nanometers) light-activated synthetic molecular machines (MMs) to kill Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, in minutes, vastly outpacing conventional antibiotics. MMs also rapidly eliminate persister cells and established bacterial biofilms. The antibacterial mode of action of MMs involves physical disruption of the membrane. In addition, by permeabilizing the membrane, MMs at sublethal doses potentiate the action of conventional antibiotics. Repeated exposure to antibacterial MMs is not accompanied by resistance development. Finally, therapeutic doses of MMs mitigate mortality associated with bacterial infection in an in vivo model of burn wound infection. Visible light-activated MMs represent an unconventional antibacterial mode of action by mechanical disruption at the molecular scale, not existent in nature and to which resistance development is unlikely.

Investigations of valanimycin biosynthesis: elucidation of the role of seryl-tRNA.

The antibiotic valanimycin is a naturally occurring azoxy compound produced by Streptomyces viridifaciens MG456-hF10. Precursor incorporation experiments showed that valanimycin is derived from l-valine and l-serine via the intermediacy of isobutylamine and isobutylhydroxylamine. Enzymatic and genetic investigations led to the cloning and sequencing of the valanimycin biosynthetic gene cluster, which was found to contain 14 genes. A novel feature of the valanimycin biosynthetic gene cluster is the presence of a gene (vlmL) that encodes a class II seryl-tRNA synthetase. Previous studies suggested that the role of this enzyme is to provide seryl-tRNA for the valanimycin biosynthetic pathway. Here, we report the results of investigations to elucidate the role of seryl-tRNA in valanimycin biosynthesis. A combination of enzymatic and chemical studies has revealed that the VlmA protein encoded by the valanimycin biosynthetic gene cluster catalyzes the transfer of the seryl residue from seryl-tRNA to the hydroxyl group of isobutylhydroxylamine to produce the ester O-seryl-isobutylhydroxylamine. These findings provide an example of the involvement of an aminoacyl-tRNA in an antibiotic biosynthetic pathway.

Bulk Production of Any Ratio 12C:13C Turbostratic Flash Graphene and Its Unusual Spectroscopic Characteristics.

As graphene enjoys worldwide research and deployment, the biological impact, geologic degradation, environmental retention, and even some physical phenomena remain less well studied. Bulk production of 13C-graphene yields a powerful route to study all of these questions. Gram-scale synthesis of high-quality and high-purity turbostratic flash graphene with varying amounts of 13C-enrichment, from 5% to 99%, is reported here. The material is characterized by solid state NMR spectroscopy, Raman spectroscopy, IR spectroscopy, X-ray photoelectron spectroscopy, and inductively coupled plasma mass spectrometry. Notably, an unusual enhancement in the Raman spectroscopic D' peak is observed, resulting from the modification in vibrational frequency through isotopic enrichment favoring intravalley phonon scattering modes. While the IR absorbance spectrum of graphene is for the most part silent, we prepare here 13C-enhanced graphene samples that show a large aromatic 12C═13C stretch that reveals this IR-active mode.

Gas-Phase Fluorination of Hexagonal Boron Nitride.

Hexagonal boron nitride (hBN) has received much attention in recent years as a 2D dielectric material with potential applications ranging from catalysts to electronics. hBN is a stable covalent compound with a planar hexagonal lattice and is relatively unreactive to most chemical environments, making the chemical functionalization of hBN challenging. Here, a simple, scalable strategy to fluorinate hBN using a direct gas-phase fluorination technique is reported. The nature of fluorine bonding to the hBN lattice and their chemical coordination are described based on various characterization studies and theoretical models. The fluorine functionalized hBN shows a bandgap reduction and displays a semiconducting behavior due to the fluorination process. Additionally, the fluorinated hBN shows significant improvement in its thermal and friction properties, which could be substantial in applications such as lubricants and thermal fluids. Theory and simulations reveal that the enhanced friction properties of fluorinated hBN result from reduced inter-planar interaction energy by electrostatic repulsion of intercalated fluorine atoms between hBN layers without significant disruption of the in-plane lattice. This technique paves the way for the fluorination of several other 2D structures for various applications such as magnetism and functional nanoscale electronic devices.