Alkane Solvent-Derived Acylation Reaction Driven by Electric Fields.

Electric field acceleration of alkyl hydroperoxide activation to acylate amines in the scanning tunneling microscope-based break-junction is reported. Alkyl hydroperoxide mixtures, generated from hydrocarbon autoxidation in air, were found to be competent reagents for the functionalization of gold surfaces. Intermolecular coupling on the surface in the presence of amines was observed, yielding normal alkylamides. This novel mode of alkyl hydroperoxide activation to generate acylium equivalents was found to be responsive to the magnitude of the bias in the break junction, indicating an electric field influence on this novel reactivity.

Doping-Induced Superconductivity in the van der Waals Superatomic Crystal Re6Se8Cl2.

Superatomic crystals are composed of discrete modular clusters that emulate the role of atoms in traditional atomic solids. Owing to their unique hierarchical structures, these materials are promising candidates to host exotic phenomena, such as doping-induced superconductivity and magnetism. Low-dimensional superatomic crystals in particular hold great potential as electronic components in nanocircuits, but the impact of doping in such compounds remains unexplored. Here we report the electrical transport properties of Re6Se8Cl2, a two-dimensional superatomic semiconductor. We find that this compound can be n-doped in situ through Cl dissociation, drastically altering the transport behavior from semiconducting to metallic and giving rise to superconductivity with a critical temperature of ∼8 K and upper critical field exceeding 30 T. This work is the first example of superconductivity in a van der Waals superatomic crystal; more broadly, it establishes a new chemical strategy to manipulate the electronic properties of van der Waals materials with labile ligands.

Intermolecular Resonance Correlates Electron Pairs Down a Supermolecular Chain: Antiferromagnetism in K-Doped p-Terphenyl.

Recent interest in potassium-doped p-terphenyl has been fueled by reports of superconductivity at Tc values surprisingly high for organic compounds. Despite these interesting properties, studies of the structure-function relationships within these materials have been scarce. Here, we isolate a phase-pure crystal of potassium-doped p-terphenyl: [K(222)]2[p-terphenyl3]. Emerging antiferromagnetism in the anisotropic structure is studied in depth by magnetometry and electron spin resonance. Combining these experimental results with density functional theory calculations, we describe the antiferromagnetic coupling in this system that occurs in all 3 crystallographic directions. The strongest coupling was found along the ends of the terphenyls, where the additional electron on neighboring p-terphenyls antiferromagnetically couple. This delocalized bonding interaction is reminiscent of the doubly degenerate resonance structure depiction of polyacetylene. These findings hint toward magnetic fluctuation-induced superconductivity in potassium-doped p-terphenyl, which has a close analogy with high Tc cuprate superconductors. The new approach described here is very versatile as shown by the preparation of two additional salts through systematic changing of the building blocks.

Conjugated Macrocycles in Organic Electronics.

This Account describes a body of research on the design, synthesis, and application of a new class of electronic materials made from conjugated macrocycles. Our macrocyclic design takes into consideration the useful attributes of fullerenes and what properties make fullerenes efficient n-type materials. We identified four electronic and structural elements: (1) a three-dimensional shape; (2) a conjugated and delocalized π-space; (3) the presence of an interior and exterior to the π-surface; and (4) low-energy unoccupied molecular orbitals allowing them to accept electrons. The macrocyclic design incorporates some of these properties, including a three-dimensional shape, an interior/exterior to the π-surface, and low-lying LUMOs maintaining the n-type semiconducting behavior, yet we also install synthetic flexibility in our approach in order to tune the properties further. Each of the macrocycles comprises perylenediimide cores wound together with linkers. The perylenediimide building block endows each macrocycle with the ability to accept electrons, while the synthetic flexibility to install different linkers allows us to create macrocycles with different electronic properties and sizes. We have created three macrocycles that all absorb well into the visible range of the solar spectrum and possess different shapes and sizes. We then use these materials in an array of applications that take advantage of their ability to function as n-type semiconductors, absorb in the visible range of the solar spectrum, and possess intramolecular cavities. This Account will discuss our progress in incorporating these new macrocycles in organic solar cells, organic photodetectors, organic field effect transistors, and sensors. The macrocycles outperform acyclic controls in organic solar cells. We find the more rigid macrocyclic structure results in less intrinsic charges and lower dark current in organic photodetectors. Our macrocyclic-based photodetector has the highest detectivity of non-fullerene acceptors. The macrocycles also function as sensors and are able to recognize nuanced differences in analytes. Perylenediimide-based fused oligomers are efficient materials in both organic solar cells and field effect transistors. We will use the oligomers to construct macrocycles for use in solar energy conversion. In addition, we will incorporate different electron-rich linkers in our cycles in an attempt to engineer the HOMO/LUMO gap further. Looking further into the future, we envision opportunities in applying these conjugated macrocycles as electronic host/guest materials, as concatenated electronic materials by threading the macrocycles with electroactive oligomers, and as a locus for catalysis that is driven by light and electric fields.

Supramolecular Assemblies for Electronic Materials.

This work presents a synergy between organic electronics and supramolecular chemistry, in which a host-guest complex is designed to function as an efficacious electronic material. Specifically, the noncovalent recognition of a fullerene, phenyl-C61 -butyric acid methyl ester (PC61 BM), by an alternating perylene diimide (P)-bithiophene (B) conjugated macrocycle (PBPB) results in a greater than five-fold enhancement in electron mobility, relative to the macrocycle alone. Characterization and quantification of the binding of fullerenes by host PBPB is provided alongside evidence for intermolecular electronic communication within the host-guest complexes.

Synthesis, Regioselective Bromination, and Functionalization of Coronene Tetracarboxydiimide.

A new method for the effective synthesis of coronene tetracarboxydiimide (CDI) was developed by utilizing inexpensive and nontoxic potassium vinyltrifluoroborate. Controllable brominations of CDI were accomplished to yield CDI mono-, di-, tri-, and tetra-bromides, which could be used as synthon and functionalized by aromatic nucleophilic substitution and the Sonogashira coupling reaction.

Rigid, Conjugated Macrocycles for High Performance Organic Photodetectors.

Organic photodetectors (OPDs) are attractive for their high optical absorption coefficient, broad wavelength tunability, and compatibility with lightweight and flexible devices. Here we describe a new molecular design that enables high performance organic photodetectors. We use a rigid, conjugated macrocycle as the electron acceptor in devices to obtain high photocurrent and low dark current. We make a direct comparison between the devices made with the macrocyclic acceptor and an acyclic control molecule; we find that the superior performance of the macrocycle originates from its rigid, conjugated, and cyclic structure. The macrocycle's rigid structure reduces the number of charged defects originating from deformed sp2 carbons and covalent defects from photo/thermoactivation. With this molecular design, we are able to suppress dark current density while retaining high responsivity in an ultrasensitive nonfullerene OPD. Importantly, we achieve a detectivity of ∼1014 Jones at near zero bias voltage. This is without the need for extra carrier blocking layers commonly employed in fullerene-based devices. Our devices are comparable to the best fullerene-based photodetectors, and the sensitivity at low working voltages (<0.1 V) is a record for nonfullerene OPDs.

Macrocyclization in the Design of Organic n-Type Electronic Materials.

Here, we compare analogous cyclic and acyclic π-conjugated molecules as n-type electronic materials and find that the cyclic molecules have numerous benefits in organic photovoltaics. This is the first report of such a direct comparison. We designed two conjugated cycles for this study. Each comprises four subunits: one combines four electron-accepting, redox-active, diphenyl-perylenediimide subunits, and the other alternates two electron-donating bithiophene units with two diphenyl-perylenediimide units. We compare the macrocycles to acyclic versions of these molecules and find that, relative to the acyclic analogs, the conjugated macrocycles have bathochromically shifted UV-vis absorbances and are more easily reduced. In blended films, macrocycle-based devices show higher electron mobility and good morphology. All of these factors contribute to the more than doubling of the power conversion efficiency observed in organic photovoltaic devices with these macrocycles as the n-type, electron transporting material. This study highlights the importance of geometric design in creating new molecular semiconductors. The ease with which we can design and tune the electronic properties of these cyclic structures charts a clear path to creating a new family of cyclic, conjugated molecules as electron transporting materials in optoelectronic and electronic devices.

Strain-induced stereoselective formation of blue-emitting cyclostilbenes.

We describe the synthesis of two conjugated macrocycles that are formed from the end-to-end linking of stilbenes. We have named these macrocycles cyclostilbenes. The two cyclostilbene isomers created in this study differ in the configuration of the double bond in their subunits. These macrocycles are formed selectively through a stepwise reductive elimination from a tetraplatinum precursor and subsequent photoisomerization. Single-crystal X-ray diffraction reveals the formation of channel architectures in the solid state that can be filled with guest molecules. The cyclostilbene macrocycles emit blue light with fluorescence quantum yields that are high (>50%) and have photoluminescence lifetimes of ∼0.8-1.5 ns. The breadth and large Stokes shift in fluorescence emission, along with broad excited-state absorption, result from strong electronic-vibronic coupling in the strained structures of the cyclostilbenes.

Chiral Conjugated Corrals.

We present here a new design motif for strained, conjugated macrocycles that incorporates two different aromatics into the cycle with an -A-B-A-B- pattern. In this study, we demonstrate the concept by alternating electron donors and acceptors in a conjugated cycle. The donor is a bithiophene, and the acceptor is a perylene diimide derivative. The macrocycle formed has a persistent elliptiform cavity that is lined with the sulfur atoms of the thiophenes and the π-faces of the perylene diimide. Due to the linkage of the perylene diimide subunits, the macrocycles exist in both chiral and achiral forms. We separate the three stereoisomers using chiral high-performance liquid chromatography and study their interconversion. The mechanism for interconversion involves an "intramolecular somersault" in which one of the PDIs rotates around its transverse axis, thereby moving one of its diimide heads through the plane of the cavity. These unusual macrocycles are black in color with an absorption spectrum that spans the visible range. Density functional theory calculations reveal a photoinduced electron transfer from the bithiophene to the perylene diimide.

Catalytic site-selective thiocarbonylations and deoxygenations of vancomycin reveal hydroxyl-dependent conformational effects.

We have examined peptide-based catalysts for the site-selective thiocarbonylation of a protected form of vancomycin. Several catalysts were identified that either enhanced or altered the inherent selectivity profile exhibited by the substrate. Two catalysts, one identified through screening and another through rational design, were demonstrated to be effective on 0.50-g scale. Deoxygenations led ultimately to two new deoxy-vancomycin derivatives, and surprising conformational consequences of deoxygenation were revealed for one of the new compounds. These effects were mirrored in the biological activities of the new analogues and support a structural role for certain hydroxyls in the native structure.

Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection.

K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by the bacteria in the host cells shapes an immune response that tolerates infection. We combined in situ metabolic imaging and transcriptional analyses to demonstrate that Kp ST258 activates host glutaminolysis and fatty acid oxidation. This response creates an oxidant-rich microenvironment conducive to the accumulation of anti-inflammatory myeloid cells. In this setting, metabolically active Kp ST258 elicits a disease-tolerant immune response. The bacteria, in turn, adapt to airway oxidants by upregulating the type VI secretion system, which is highly conserved across ST258 strains worldwide. Thus, much of the global success of Kp ST258 in hospital settings can be explained by the metabolic activity provoked in the host that promotes disease tolerance.

Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19.

The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation and replication cycle. Based on the conservation of 3CL protease substrate binding pockets across coronaviruses and using screening, we identified four structurally distinct lead compounds that inhibit SARS-CoV-2 3CL protease. After evaluation of their binding specificity, cellular antiviral potency, metabolic stability, and water solubility, we prioritized the GC376 scaffold as being optimal for optimization. We identified multiple drug-like compounds with <10 nM potency for inhibiting SARS-CoV-2 3CL and the ability to block SARS-CoV-2 replication in human cells, obtained co-crystal structures of the 3CL protease in complex with these compounds, and determined that they have pan-coronavirus activity. We selected one compound, termed coronastat, as an optimized lead and characterized it in pharmacokinetic and safety studies in vivo. Coronastat represents a new candidate for a small molecule protease inhibitor for the treatment of SARS-CoV-2 infection for eliminating pandemics involving coronaviruses.

Peptide-catalyzed kinetic resolution of formamides and thioformamides as an entry to nonracemic amines.

We report a fundamentally unique approach to the catalytic kinetic resolution of amine derivatives based on formamide and thioformamide substrates. Readily accessible histidine-containing peptides mediate the kinetic resolutions with as little as 5 mol % catalyst. Selectivity factors (k(rel)) as high as 43.7 were observed under simple reaction conditions utilizing Boc(2)O as the reagent at room temperature. Mechanistic experiments were conducted that established a higher level of reactivity for thioformamide substrates than for their formamide analogues. The products of these asymmetric reactions were shown to be readily converted to desirable building blocks such as N-Boc-amines and the parent chiral formamide compounds.

Directing isomerization reactions of cumulenes with electric fields.

Electric fields have been proposed as having a distinct ability to catalyze chemical reactions through the stabilization of polar or ionic intermediate transition states. Although field-assisted catalysis is being researched, the ability to catalyze reactions in solution using electric fields remains elusive and the understanding of mechanisms of such catalysis is sparse. Here we show that an electric field can catalyze the cis-to-trans isomerization of [3]cumulene derivatives in solution, in a scanning tunneling microscope. We further show that the external electric field can alter the thermodynamics inhibiting the trans-to-cis reverse reaction, endowing the selectivity toward trans isomer. Using density functional theory-based calculations, we find that the applied electric field promotes a zwitterionic resonance form, which ensures a lower energy transition state for the isomerization reaction. The field also stabilizes the trans form, relative to the cis, dictating the cis/trans thermodynamics, driving the equilibrium product exclusively toward the trans.

Molecular helices as electron acceptors in high-performance bulk heterojunction solar cells.

Despite numerous organic semiconducting materials synthesized for organic photovoltaics in the past decade, fullerenes are widely used as electron acceptors in highly efficient bulk-heterojunction solar cells. None of the non-fullerene bulk heterojunction solar cells have achieved efficiencies as high as fullerene-based solar cells. Design principles for fullerene-free acceptors remain unclear in the field. Here we report examples of helical molecular semiconductors as electron acceptors that are on par with fullerene derivatives in efficient solar cells. We achieved an 8.3% power conversion efficiency in a solar cell, which is a record high for non-fullerene bulk heterojunctions. Femtosecond transient absorption spectroscopy revealed both electron and hole transfer processes at the donor-acceptor interfaces. Atomic force microscopy reveals a mesh-like network of acceptors with pores that are tens of nanometres in diameter for efficient exciton separation and charge transport. This study describes a new motif for designing highly efficient acceptors for organic solar cells.

A novel small-molecule inhibitor reveals a possible role of kinesin-5 in anastral spindle-pole assembly.

The tetrameric plus-end-directed motor, kinesin-5, is essential for bipolar spindle assembly. Small-molecule inhibitors of kinesin-5 have been important tools for investigating its function, and some are currently under evaluation as anti-cancer drugs. Most inhibitors reported to date are ;non-competitive' and bind to a specific site on the motor head, trapping the motor in an ADP-bound state in which it has a weak but non-zero affinity for microtubules. Here, we used a novel ATP-competitive inhibitor, FCPT, developed at Merck (USA). We found that it induced tight binding of kinesin-5 onto microtubules in vitro. Using Xenopus egg-extract spindles, we found that FCPT not only blocked poleward microtubule sliding but also selectively induced loss of microtubules at the poles of bipolar spindles (and not asters or monoasters). We also found that the spindle-pole proteins TPX2 and gamma-tubulin became redistributed to the spindle equator, suggesting that proper kinesin-5 function is required for pole assembly.