Small is Beautiful: Electronic Origin and Synthetic Evolution of Single-Benzene Fluorophores.

ConspectusSingle-benzene fluorophores (SBFs) are small molecules that produce visible light by using only one benzene ring as the sole aromatic core. This Account centers around the chemistry of a new class of SBF that we accidentally discovered but rationally developed and refined afterward. In a failed experiment that took an unintended reaction pathway, we encountered the bright green fluorescence of ortho-diacetylphenylenediamine (o-DAPA). Despite its uninspiring look, reminiscent of textbook examples of simple benzene derivatives, this molecule had neither been synthesized nor isolated before. This discovery led to our studies on the larger DAPA family, including isomeric m-DAPA and p-DAPA. Remarkably, p-DAPA is the lightest red fluorophore, with a molecular weight of only 192. While o- and p-DAPA are emissive, m-DAPA rapidly undergoes internal conversion, facilitated by sequential proton transfer reactions in the excited state.Leveraging the synthetic utility of the amine group, we carried out straightforward single-step modifications to create a full-color SBF library from p-DAPA as the common precursor. During the course of the investigation, we made another fortuitous discovery. With increasing acidity of the N-H group, the excited-state intramolecular proton transfer reaction is promoted, opening up additional pathways for emission to occur at even longer wavelengths. Tipping the balance between the two excited-state tautomers enabled the first example of a single-benzene white-light emitter. We demonstrated the practical utility of these molecules in white light-emitting devices and live cell imaging.According to the particle-in-a-box model, it is difficult to expect a molecule with only one small aromatic ring to produce long-wavelength emission. SBFs rise to this challenge by exploiting electron donor-acceptor pairs around the benzene core, which lowers the energy of light absorption. However, this answers only half of the question. Where do the exceptionally large spectral shifts in the light emission of SBFs originate from? Chemists have long been curious about the molecular mechanisms underlying the dramatic spectral shifts observed in SBFs. Prevailing paradigms invoke the charge transfer (CT) between electron donor and acceptor groups in the excited state. However, without a large π-skeleton for effective charge separation, how could benzene support a CT-type excited state? Our experimental and theoretical studies have revealed that large excited-state antiaromaticity (ESAA) of the benzene core itself is responsible for this remarkable phenomenon. The core matters, not the periphery. With appropriate molecular design, large and extended π-conjugation is no longer a prerequisite for long-wavelength light emission.

Design of 2-Pyridone Fluorophores for Brighter Emissions at Longer Wavelengths.

The recent discovery of blue fluorophores with high quantum yields based on pyridone structures inspired the development of new low-molecular-weight fluorophores with bright emissions at tunable wavelengths, which are highly attractive for various applications. In this study, we propose a rational design strategy for 2-pyridone-based fluorophores with bright emissions at long wavelengths. With a detailed understanding of the positional substitution effects on each carbon atom of the 2-pyridone core, we developed a bright blue fluorophore (λabs =377 nm; λem =433 nm; ϵ=13,200 M-1 cm-1 ; ϕF =88 %) through C3 -aryl and C4 -ester substitutions followed by cyclization. Furthermore, by applying the intramolecular charge transfer (ICT) principle, we invented a bright green fluorophore through C3 - and C4 -diester and C6 -aryl substitutions. The ICT fluorophore based on the pyridone structure shows large molar absorptivity (ϵ=20,100 M-1 cm-1 ), longer emission wavelength (λem =539 nm), high emission quantum yield (ϕF =74 %), and large Stokes shift (Δv=5720 cm-1 ), which are comparable to those of practical fluorescent probes.

All-Graphene Quantum Dot-Derived Battery: Regulating Redox Activity Through Localized Subdomains.

In the quest for materials sustainability for grid-scale applications, graphene quantum dot (GQD), prepared via eco-efficient processes, is one of the promising graphitic-organic matters that have the potential to provide greener solutions for replacing metal-based battery electrodes. However, the utilization of GQDs as electroactive materials has been limited; their redox behaviors associated with the electronic bandgap property from the sp2 carbon subdomains, surrounded by functional groups, are yet to be understood. Here, the experimental realization of a subdomained GQD-based anode with stable cyclability over 1000 cycles, combined with theoretical calculations, enables a better understanding of the decisive impact of controlled redox site distributions on battery performance. The GQDs are further employed in cathode as a platform for full utilization of inherent electrochemical activity of bio-inspired redox-active organic motifs, phenoxazine. Using the GQD-derived anode and cathode, an all-GQD battery achieves a high energy density of 290 Wh kgcathode -1 (160 Wh kgcathode+anode -1 ), demonstrating an effective way to improve reaction reversibility and energy density of sustainable, metal-free batteries.

Assembling Molecular Clips To Build π-Stacks.

Nature utilizes an intimate stacking of aromatic motifs to construct functional structures, as demonstrated in protein folding and polynucleotide assembly. However, organized π-stacks of artificial molecules are difficult to build, primarily due to the weak, non-directional, and context-sensitive nature of van der Waals forces. To overcome these challenges, chemists have invented ingenious architectural designs to construct π-stacked supramolecular assemblies using clip-like molecules. This Concept article focuses on molecular clips that enable precise spatial control over assembly patterns, beyond the scope of simple host-guest chemistry. Different design strategies are analyzed and compared that leverage non-covalent interactions to create multi-layer π-stacks. Particular emphasis is placed on the choice of spine units as they play a crucial role in controlling the (i) spacing, (ii) orientation, and (iii) conformational pre-organization of linked aromatics to achieve long-range spatial ordering.

Single-Benzene Dual-Emitters Harness Excited-State Antiaromaticity for White Light Generation and Fluorescence Imaging.

Molecular emitters simultaneously generating light at different wavelengths have wide applications. With a small molecule, however, it is challenging to realize two independent radiative pathways. We invented the first examples of dual-emissive single-benzene fluorophores (SBFs). Two emissive tautomers are generated by synthetic modulation of the hydrogen bond acidity, which opens up pathways for excited-state proton transfer. White light is produced by a delicate balance between the energy and intensity of the emission from each tautomer. We show that the excited-state antiaromaticity of the benzene core itself dictates the proton movements driving the tautomer equilibrium. Using this simple benzene platform, a fluorinated SBF was synthesized with a record high solubility in perfluorocarbon solvents. White light-emitting devices and multicolor imaging of perfluorocarbon nanodroplets in live cells demonstrate the practical utility of these molecules.

Powerful Direct C-H Amidation Polymerization Affords Single-Fluorophore-Based White-Light-Emitting Polysulfonamides by Fine-Tuning Hydrogen Bonds.

The development of white-light-emitting polymers has been actively pursued because of the importance of such polymers in various applications, such as lighting sources and displays. To generate white-light, numerous research efforts have focused on synthesizing multifluorophore-based random copolymers to effectively cover the entire visible region. However, due to their intrinsic synthetic and structural features, this strategy has limitations in securing color reproducibility and stability. Herein, we report the development of single-fluorophore-based white-light-emitting homopolymers with excellent color reproducibility. A powerful direct C-H amidation polymerization (DCAP) strategy enabled the synthesis of defect-free polysulfonamides that emit white-light via excited-state intramolecular proton-transfer (ESIPT). To gain structural insights for designing such polymers, we conducted detailed model studies by varying the electronic nature of substituents that allow facile tuning of the emission colors. Further analysis revealed precise control of the thermodynamics of the ESIPT process by fine-tuning the strength of the intramolecular hydrogen bond. By applying this design principle to polymerization, we successfully produced a series of well-defined polysulfonamides with single-fluorophore emitting white-light. The resulting polymers emitted consistent fluorescence, regardless of their molecular weights or phases (i.e., solution, powder, or thin film), guaranteeing excellent color reproducibility. With these advantages in hand, we also demonstrated practical use of our DCAP system by fabricating a white-light-emitting coated LED.

Variations in Complementary Hydrogen Bonds Direct Assembly Patterns of Isosteric Polyheteroaromatics at Surfaces.

Intermolecular interactions guide self-assembly on the surface. Precise control over these interactions by rational design of the molecule should allow fine control over the self-assembly patterns. Functional groups installed for electronic modulation often induce significant changes in the molecular dimensions, thereby disrupting the original assembly pattern. To overcome this challenge, we have employed a family of isosteric phenazine derivatives, DHP, DAP, and DBQD, to investigate the impacts of hydrogen bonding on two-dimensional molecular self-assembly. While these molecules are similar in size and chemical composition, the strength and directionality of hydrogen bonding differ significantly depending on the chemical structure of donor-acceptor pairs and prototropic tautomerization from positional isomerism. Scanning tunneling microscopy (STM) characterization of the assembled structures on Ag(111), Au(111), and Cu(100) surfaces revealed that minimal changes in molecular structure have a profound impact on the self-assembly patterns. While DHP exhibits highly ordered and robust assemblies, DAP and DBQD show either spatially confined or ill-defined assemblies. In conjunction with hydrogen bonding, prototropic tautomerism is a potent strategy to modulate molecular 2D lattices on surfaces.

Proton Switch in the Secondary Coordination Sphere to Control Catalytic Events at the Metal Center: Biomimetic Oxo Transfer Chemistry of Nickel Amidate Complex.

High-valent metal-oxo species are key intermediates for the oxygen atom transfer step in the catalytic cycles of many metalloenzymes. While the redox-active metal centers of such enzymes are typically supported by anionic amino acid side chains or porphyrin rings, peptide backbones might function as strong electron-donating ligands to stabilize high oxidation states. To test the feasibility of this idea in synthetic settings, we have prepared a nickel(II) complex of new amido multidentate ligand. The mononuclear nickel complex of this N5 ligand catalyzes epoxidation reactions of a wide range of olefins by using mCPBA as a terminal oxidant. Notably, a remarkably high catalytic efficiency and selectivity were observed for terminal olefin substrates. We found that protonation of the secondary coordination sphere serves as the entry point to the catalytic cycle, in which high-valent nickel species is subsequently formed to carry out oxo-transfer reactions. A conceptually parallel process might allow metalloenzymes to control the catalytic cycle in the primary coordination sphere by using proton switch in the secondary coordination sphere.

Making Waxy Salts in Water: Synthetic Control of Hydrophobicity for Anion-Induced and Aggregation-Enhanced Light Emission.

We show that multipodal polycationic receptors function as anion-responsive light-emitters in water. Prevailing paradigms utilize rigid holes and cavities for ion recognition. We instead built open amphiphilic scaffolds that trigger polar-to-nonpolar environment transitions around cationic fluorophores upon anion complexation. This ion-pairing and aggregation event produces a dramatic enhancement in the emission intensity, as demonstrated by perchlorate as a non-spherical hydrophobic anion model. A synergetic interplay of C-H⋅⋅⋅anion hydrogen bonding and tight anion-π+ contacts underpins this supramolecular phenomenon. By changing the aliphatic chain length, we demonstrate that the response profile and threshold of this signaling event can be controlled at the molecular level. With appropriate molecular design, inherently weak, ill-defined, and non-directional van der Waals interaction enables selective, sensitive, and tunable recognition in water.

Ligand Taxonomy for Bioinorganic Modeling of Dioxygen-Activating Non-Heme Iron Enzymes.

Novel functions emerge from novel structures. To develop efficient catalytic systems for challenging chemical transformations, chemists often seek inspirations from enzymatic catalysis. A large number of iron complexes supported by nitrogen-rich multidentate ligands have thus been developed to mimic oxo-transfer reactivity of dioxygen-activating metalloenzymes. Such efforts have significantly advanced our understanding of the reaction mechanisms by trapping key intermediates and elucidating their geometric and electronic properties. Critical to the success of this biomimetic approach is the design and synthesis of elaborate ligand systems to balance the thermodynamic stability, structural adaptability, and chemical reactivity. In this Concept article, representative design strategies for biomimetic atom-transfer chemistry are discussed from the perspectives of "ligand builders". Emphasis is placed on how the primary coordination sphere is constructed, and how it can be elaborated further by rational design for desired functions.

Weak Links To Differentiate Weak Bonds: Size-Selective Response of π-Conjugated Macrocycle Gels to Ammonium Ions.

Molecular-level host-guest interactions can drive gel-to-sol phase transitions of the bulk material. Using supramolecular gels constructed from π-conjugated aza-crown macrocycles, we have investigated the effects of guest chemical structures on the kinetics of gel disassembly. While ammonium ions bind only weakly to the individual macrocycles in solution, gel-to-sol transitions of self-assembled macrocycles occur readily under ambient conditions. This net signal amplification process was monitored conveniently by time-dependent spectroscopic studies to reveal a straightforward correlation between the response rate and shape/size of the guest species. Well-designed weak links thus respond to subtle differences in weak bonds and translate them into visually discernible macroscopic signaling events.

Living Polymerization Caught in the Act: Direct Observation of an Arrested Intermediate in Metathesis Polymerization.

Understanding the stability and reactivity of the propagating species is critical in living polymerization. Therefore, most living olefin metathesis polymerizations require the stabilization of the catalyst by coordination of external ligands containing Lewis basic heteroatoms, e.g., phosphines and pyridines. However, in some cases, chemists postulated that the propagating metal carbene could also be stabilized by olefin chelation. Here, we disclose that stable 16-electron olefin-chelated Ru carbenes play a key role in previously reported living/controlled ring-opening metathesis polymerization of endo-tricyclo[4.2.2.02,5]deca-3,9-diene and cyclopolymerization of 1,8-nonadiynes using Grubbs catalysts. We successfully isolated these propagating species during polymerization and confirmed their olefin-chelated structures using X-ray crystallography and NMR analysis. DFT calculations and van 't Hoff plots from the equilibrium between olefin-chelated Ru carbenes and 3-chloropyridine (Py)-coordinated carbenes revealed that entropically favored olefin chelation overwhelmed enthalpically more stable Py-coordinated Ru carbenes at room temperature. Therefore, olefin chelation stabilized the propagating species and slowed down the propagation relative to initiation, thereby lowering polydispersity. This finding provides a deeper understanding of the olefin metathesis polymerization mechanism using Grubbs catalysts and offers clues for designing new controlled/living polymerizations.

Surface Self-Assembly, Film Morphology, and Charge Transport Properties of Semiconducting Triazoloarenes.

Surface-assisted molecular self-assembly is a powerful strategy for forming molecular-scale architectures on surfaces. These molecular self-assemblies have potential applications in organic electronics, catalysis, photovoltaics, and many other technologies. Understanding the intermolecular interactions on a surface can help predict packing, stacking, and charge transport properties of films and allow for new molecular designs to be tailored for a required function. We have previously studied a molecular platform, tris( N-phenyltriazole) (TPT), that exhibits planar stacking through >20 molecular layers through donor-acceptor-type intermolecular π-π contacts between the electron-deficient tris(triazole) core and electron-rich peripheral phenyl units. Here, we investigate an expanded family of TPT-based molecules with variations made on the peripheral aryl groups to modulate the molecular electron distribution and examine the impact on molecular packing and charge transport properties. Molecular-resolution scanning tunneling microscopy was used to compare the molecular packing in the monolayer and to investigate the effects that the structural and electronic modifications have on the stacking in subsequent layers. Conductivity measurements were made using the four-point probe van der Pauw technique to demonstrate charge transport properties comparable to pentacene. Although molecular packing is clearly impacted by the chemical structure, we find that the charge transport efficiency is quite tolerant to small structural variations.

Redox-Driven Folding, Unfolding, and Refolding of Bis(tetrathiafulvalene) Molecular Switch.

We report redox-driven folding, unfolding, and refolding motions of a synthetic molecular system, in which two tetrathiafulvalene (TTF) units are tethered onto a conformationally rigid yet torsionally flexible π-conjugated backbone. Upon one-electron oxidation, this molecular switch undergoes swiveling motions from a fully relaxed and freely rotating Z-shaped conformation to a compact folded conformation stabilizing π-stacked radical species. Subsequent one-electron oxidation produces dicationic intermediates, which either engage in intimate π-π interactions or transition to an open structure. Further oxidation, however, brings the molecule back to the initial conformation to minimize the repulsion between doubly-charged TTF units. Intriguingly, the reaction coordinates of this redox-driven structural change have strong dependence on the environment, such as the solvent (THF vs CH2Cl2) and supporting electrolyte (PF6- vs B(C6F5)4-). With a proper design, factors that are typically considered as "secondary effects" could dictate the solution dynamics and reaction pathways of structural folding and unfolding, all driven by controlled delivery of electrons.

Biological Nicotinamide Cofactor as a Redox-Active Motif for Reversible Electrochemical Energy Storage.

Nicotinamide adenine dinucleotide (NAD+ ) is one of the most well-known redox cofactors carrying electrons. Now, it is reported that the intrinsically charged NAD+ motif can serve as an active electrode in electrochemical lithium cells. By anchoring the NAD+ motif by the anion incorporation, redox activity of the NAD+ is successfully implemented in conventional batteries, exhibiting the average voltage of 2.3 V. The operating voltage and capacity are tunable by altering the anchoring anion species without modifying the redox center itself. This work not only demonstrates the redox capability of NAD+ , but also suggests that anchoring the charged molecules with anion incorporation is a viable new approach to exploit various charged biological cofactors in rechargeable battery systems.

From Foldable Open Chains to Shape-Persistent Macrocycles: Synthesis, Impact on 2D Ordering, and Stimulated Self-Assembly.

Small molecule self-assembly at surfaces offers an efficient route to highly ordered organic films that can be programmed for a variety of chemical and electronic applications. The success of these materials depends on the ability to program intermolecular interactions to guide precise structural ordering. Toward this objective, we have designed and synthesized a series of bis(triazolo)benzene-based π-conjugated molecules. Our synthesis exploits a last-stage C-C cross-coupling reaction to close up zigzag-shaped linear precursors to cyclized products, so that direct side-by-side comparisons can be made for their structure-dependent self-assembly behavior at surfaces and response to external stimuli. Indeed, scanning tunneling microscopy (STM) analysis revealed distinct differences as the conformational flexibility of the molecular backbone and the chemical structure of the peripheral groups are varied. Specifically, alkyl chains adsorb and form interdigitated structures, whereas oligo ethylene glycol (OEG) chains remain desorbed and thus shift self-assembly to more densely packed π-conjugated cores. While the macrocycles self-assemble immediately and spontaneously, their linear precursors exhibit slower self-assembly kinetics, which could be attributed to the difference in the degree of conformational freedom. We also found that perturbation by the STM tip and the addition of cosolutes profoundly impacted the kinetics of self-assembly and surface patterning. This highly unusual behavior highlights the importance of noncovalent interactions that are inherently weak in solution but can be made strong for symmetric and conformationally restricted molecules confined within 2D surfaces.

Non-Heme Iron Catalysts for Olefin Epoxidation: Conformationally Rigid Aryl-Aryl Junction To Support Amine/Imine Multidentate Ligands.

Atom-transfer chemistry represents an important class of reactions catalyzed by metalloenzymes. As a functional mimic of non-heme iron enzymes that deliver oxygen atoms to olefins, we have designed monoiron complexes supported by new N-donor chelates. These ligands take advantage of heme-like conformational rigidity of the π-conjugated molecular backbone, and synthetic flexibility of tethering non-heme donor groups for additional steric and electronic control. Iron complexes generated in situ can be used to carry out catalytic epoxidation of a wide range of olefin substrates by using mCPBA as a terminal oxidant. The fate of initial iron-peracid adduct and the involvement of iron-oxo species in this process were investigated further by mechanistic probes and isotope exchange studies. Our findings suggest that anilidopyridyl-derived [N,N]-bidentate motif could serve as a versatile structural platform to build non-heme ligands for catalytic oxidation chemistry.

Multichromophoric π-Conjugation: Modular Design for Gated and Cascade Energy Transfer.

Multichromophore arrays allow for cascade energy transfer. As an isoelectronic analogue of indacenyl, bis(triazolo)benzene features a fused tricyclic skeleton that rigidly places two π-extended triazoles in close proximity. Such triazole-based fluorophores behave as electronically independent modules in the ground states, but become tightly coupled upon photoexcitation for highly efficient excitation energy transfer (EET) that can be gated by external stimuli. Taking this donor-acceptor fluorophore system a step further, we have designed and implemented a cascade EET. Here, the initial excitation takes part in a circular relay to arrive at the longest-wavelength emitting site as the final destination. Modularly constructed triazoloarenes should serve as versatile platforms for chemically controlled optical signaling.

BOIMPY: Fluorescent Boron Complexes with Tunable and Environment-Responsive Light-Emitting Properties.

A series of air-stable boron complexes 1-5 were prepared by using N-aryl iminopyrrolide ligands. Designed as minimalist structural mimics of the privileged BODIPY motif, these new BOIMPY (BOron complexes of IMinoPYrrolide ligands) fluorophores feature low molecular symmetry that promotes emission from CT-type excited states with large Stokes shifts and little self-quenching. Through comparative studies on the homologous set of compounds 1-4, we have confirmed that a delicate interplay between conformational twisting and donor-acceptor interaction dictates the mechanism of de-excitation, which responds sensitively to solvent polarity as well as protonation states. Over a wide visible spectral range, the structure-dependent light-emitting properties of BOIMPY molecules are well manifested, even in the solid-state. In order to exploit the environment-sensitive nature of CT-type emission, the BOIMPY motif was elaborated further into a bioprobe molecule 5. Live-cell fluorescence imaging studies have established that 5 is localized exclusively at lipid droplets to produce well-resolved staining patterns without affecting cell viability. These findings promise future elaboration of BOIMPY-based functional molecules for applications in biological imaging, chemical sensing, and molecular switching.

High-fidelity self-assembly of crystalline and parallel-oriented organic thin films by π-π stacking from a metal surface.

Organic semiconductor applications will significantly benefit from atomically precise, cofacial stacking of extended π-conjugated molecular systems for efficient charge transport. Surface-assisted self-assembly of poly(hetero)cyclic molecules via donor-acceptor type π-π stacking is a promising strategy to organize functional, many-layered architectures. We have employed tris(N-phenyltriazole) as a model system to achieve molecular-level structural ordering through more than 20 molecular layers from its own metal-templated monolayer. Effective charge transport through such layers enabled molecular-resolution imaging by scanning tunneling microscopy. The structure and chemical composition of the films, grown on Ag(111) or Au(100), were further analyzed by noncontact atomic force microscopy and X-ray photoelectron spectroscopy, revealing a cofacial stacking geometry of the molecular layers. Scanning tunneling spectroscopy measurements show a decrease of the band gap with increasing film thickness, consistent with π-π stacking and electron delocalization. The present study provides new strategies for the fabrication of normally inaccessible structural motifs, atomic precision in organic films, and the effective conduction of electrons through multiple organic molecular stacks.