Carbon-based Biradicals: Structural and Magnetic Switching.

Sterically hindered C═C double bonds often deform into a bent or twisted geometry. Thus, many overcrowded ethylenes or anthraquinodimethanes can adopt multiple conformations, such as a folded form or a twisted form, which are interconvertible under the application of external stimuli. A perpendicular form with biradical character can also be adopted when designed to incorporate a stable carbon-based radical unit, which is involved in stimuli-responsive magnetic switching accompanied by a structural change. This review focuses on recent advances in the development of such strained π-electron systems and reveals the factors that affect the mutual interconversion and switching behavior. The energy barrier for the interconversion of conformational isomers is affected by the tricyclic skeleton or bulky substituents on the C═C double bonds, whereas the relative stability of the perpendicular biradical form increases with the additional insertion of 9,10-anthrylene units into the C═C double bonds.

Thermal Equilibrium Between Quinoid/Biradical Forms Enhancing Electrochemical Amphotericity.

Upon dibenzo annulation on Thiele's hydrocarbon (tetraphenyl-p-quinodimethane), the quinoid form and the biradical form adopt quite different geometries, and thus are no longer resonance structures. When these two forms can interconvert rapidly due to the small energy barrier (ΔG≠), the equilibrated mixture contains both forms in a ratio that is determined by the energy difference (ΔGo) between the two forms. For a series of tetrakis[5-(4-methoxyphenyl)-2-thienyl]-substituted derivatives, the more stable quinoid form and the metastable biradical form coexist in solution as an equilibrated mixture due to small ΔG≠ (<15 kcal mol-1) and ΔGo (1-4 kcal mol-1), in which the proportion of the two forms can be regulated by temperature. Since the biradical form can undergo easy two-electron (2e) oxidation to the corresponding dications as well as easy 2e-reduction to the dianions, it exhibits very high electrochemical amphotericity. This character with a record-small span for not only the first oxidation and reduction potentials but also the second those, [E1 sum≈E2 sum=E2 ox-E2 red=ca. 1.4 V], is attained through thermally enhanced conversion to the biradical form from the corresponding quinoid form, the latter of which is less amphoteric due to higher Eox and lower Ered values.

Cation-Stacking Approach Enabling Interconversion between Bis(xanthylium) and its Reduced Species.

Cyclophane-type dications with two units of xanthylium were designed, with the expectation that intramolecular interaction between cation units could induce changes in absorption and redox behavior. The desired dications were synthesized via the macrocyclic diketone as a key intermediate, which was efficiently obtained by a stepwise etherification. X-ray and UV/Vis measurements revealed that the cyclophane-type dications adopt a stacking structure in both the crystal and solution. Due to the intramolecular interaction caused by π-π stacking of the xanthylium units, a considerable blue shift compared to the corresponding monocations and a two-stage one-electron reduction process were observed in the dications. Furthermore, upon electrochemical reduction of dications, the formation of biradicals via radical cation species was demonstrated by UV/Vis spectroscopy with several isosbestic points at both stages. Therefore, the cation-stacking approach is a promising way to provide novel properties due to perturbation of their molecular orbitals and to stabilize the reduced species even though they have open-shell characters.

Optical Property Control by the Interligand Charge Transfer Excited State in Brominated Homoleptic and Heteroleptic Aluminum Dinuclear Triple-Stranded Helicates.

The utilization of aluminum, an abundant and inexpensive element, for the synthesis of novel functional complexes is extremely important, but the design and control of photofunctionality are still unexplored. In this study, we focused on our previously developed dinuclear triple-stranded helicates incorporating two aluminum ions (ALPHY) to synthesize both homoleptic and heteroleptic complexes with bromine atoms at the 3-position of the pyrrole moiety in the Schiff base ligands. The brominated Schiff base ligands were reacted with AlCl3 to synthesize homoleptic complexes, while different ligands were mixed to prepare heteroleptic complexes. Single-crystal X-ray structural analysis revealed the structures of these novel complexes. We found that increasing the degree of bromination resulted in a tunable emission color, shifting progressively from 550 (yellow) to 566 nm (orange). Optical resolution of the complexes facilitated the observation of mirror-image circular dichroism and circularly polarized luminescence. Furthermore, employing ultrafast spectroscopy techniques, we have elucidated that the optical properties are governed by the interligand charge transfer (ILCT) among the three ligands. The formation of heteroleptic complexes induces the ILCT state even in nonpolar environments, thereby accelerating nonradiative decay and intersystem crossing. These findings mark significant advancements in photofunctional materials based on multinuclear complexes.

Domino-Redox Reaction Induced by An Electrochemically Triggered Conformational Change.

The concept of a domino-type reaction has been applied in a wide range of fields such as synthetic organic chemistry, material engineering, and life science. To extend the domino concept to redox chemistry, we designed and synthesized a dimeric quinodimethane (QD) with a nonplanar dithiin spacer. The domino-redox properties can be activated by raising the temperature, based on a thermally equilibrated twisted conformation of QD, which has a higher HOMO level that is more readily oxidized. After one QD unit is oxidized (trigger), steric repulsion and electronic interaction between electrophores make the neighboring QD unit adopt a twisted conformation (domino process), which facilitates the following oxidation. Thus, a domino-redox reaction was achieved for the first time by a change in the HOMO level due to a drastic change in the molecular conformation.

Dibenzotropylium-Capped Orthogonal Geometry Enabling Isolation and Examination of a Series of Hydrocarbons with Multiple 14π-Aromatic Units.

A series of six dications composed of pure hydrocarbons with one to six non-substituted 9,10-anthrylene units end-capped with two dibenzotropyliums were designed and synthesized to elucidate the electronic properties of huge oligo(9,10-anthrylene) backbones. Their structures were successfully determined by X-ray analyses even in the case of eight planar 14π-electron units, revealing that all dications adopt almost orthogonally twisted structures between neighboring units. Spectroscopic and voltammetric analyses show that neither the significant overlap of orbitals nor the delocalization of electrons between 14π-electron units occurs due to the orthogonally twisted geometry even in solution. As a result, sequential oxidation processes were observed with the reversible formation of multivalent cations with the release of the same number of electrons as the number of anthrylene units. Upon two-electron reduction, a closed-shell butterfly-shaped form was obtained from the dication containing one anthrylene unit, whereas open-shell twisted biradicals were isolated as stable entities in the cases of derivatives containing three to six anthrylene units. Notably, from the derivative with two anthrylene units, a metastable open-shell isomer was obtained quantitatively and underwent slow thermal conversion to the most stable closed-shell isomer (Ea = 23.1 kcal mol-1). There is a drastic change in oxidation potentials between two neutral species (ΔE = 1.32 V in CH2Cl2). Since the present dications were regenerated upon oxidation of the isolated reduction products, these systems may contribute to the development of advanced response systems capable of switching color, magnetic properties, and oxidative properties by using a "cation-capped orthogonal geometry".

Smart Lipid Nanoparticle that Remodels Tumor Microenvironment for Activatable H2S Gas and Photodynamic Immunotherapy.

Hydrogen sulfide (H2S) has shown promise for gas therapy. However, it is still controversial whether H2S can remodel the tumor microenvironment (TME) and induce robust antitumor immunity. Here, a tumor-targeting and TME-responsive "smart" lipid nanoparticle (1-JK-PS-FA) is presented, which is capable of delivering and releasing H2S specifically in tumor tissues for on-demand H2S gas and photodynamic immunotherapy. 1-JK-PS-FA enables a burst release of H2S in the acidic TME, which promptly reduces the embedded organic electrochromic materials and consequently switches on near-infrared fluorescence and photodynamic activity. Furthermore, we found that high levels of H2S can reprogram the TME by reducing tumor interstitial fluid pressure, promoting angiogenesis, increasing vascular permeability, ameliorating hypoxia, and reducing immunosuppressive conditions. This leads to increased tumor uptake of 1-JK-PS-FA, thereby enhancing PDT efficacy and eliciting strong immunogenic cell death during 808 nm laser irradiation. Therefore, 1-JK-PS-FA permits synergistic H2S gas and photodynamic immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence. This work showcases the capacity of H2S to reprogram the TME to enhance H2S gas and immunotherapy.

Enhancement of NIR-Absorbing Ability of Bis(diarylmethylium)-Type Dicationic Dyes Based on an Ortho-Substitution Strategy.

Electrochromic systems capable of switching near-infrared (NIR) absorption are fascinating from the viewpoint of applications in the materials and life sciences. Although 11,11,12,12-tetraaryl-9,10-anthraquinodimethanes (AQDs) with a folded form undergo one-stage two-electron oxidation to produce twisted dicationic dyes exhibiting NIR absorption, there is a need to establish a design strategy that can enhance the NIR-absorbing abilities of the corresponding dicationic dyes. In this study, we designed and synthesized a series of AQD derivatives with various substituents introduced at the ortho-position(s) of the 4-methoxyphenyl group. X-ray and spectroscopic analyses revealed that NIR-absorbing properties can be changed by introduction of the ortho-substituents. Thus, control of the steric and electronic effects of the ortho-substituents on the 4-methoxyphenyl groups was demonstrated to be an effective strategy for fine-tuning of the HOMO and LUMO levels for neutral AQDs and twisted dications, respectively, resulting in the modification of electrochemical and spectroscopic properties under an "ortho-substitution strategy".

One-Pot Synthesis of Helical Azaheptalene and Chiroptical Switching of an Isolable Radical Cation.

A nitrogen-centered heptalene, azaheptalene, was designed as a representative of a new class of redox-responsive molecules with a large steric strain that originates from the adjacent seven-membered rings. The pentabenzo derivative of azaheptalene was efficiently synthesized by a palladium-catalyzed one-pot reaction of commercially available reagents. Bromination led to mono- and dibrominated derivatives, the latter of which is interconvertible with isolable radical cation species exhibiting near-infrared absorption. Since the azaheptalene skeleton shows configurationally stable helicity with a large torsion angle, enantiomers could be successfully separated. Thus, optically pure azaheptalenes with P- or M-helicity showed strong chiroptical properties (|gabs |≥0.01), which could be changed by an electric potential.

Strain-Sensitive On-Surface Ladderization by Non-Dehydrogenative Heterocyclization.

On-surface cyclodehydrogenation recently became an important reaction to planarize π-conjugated molecules and oligomers. However, the high-activation barrier to cleave the C-H bond often requires high-temperature annealing, consequently restricting structures of precursor molecules and/or leading to random fusion at their edges. Here, we present a synthesis of pyrrolopyrrole-bridged ladder oligomers from 11,11,12,12-tetrabromo-1,4,5,8-tetraaza-9,10-anthraquinodimethane molecules on Ag(111) with bond-resolved scanning tunnelling microscopy. This non-dehydrogenative cyclization between pyrazine and ethynylene/cumulene groups has a low-activation barrier for forming intermediary dimeric oligomer containing dipyrazinopyrrolopyrrolopyrazine units, thus giving new insight into the strain-sensitive in ladder-oligomer formation.

Double Dynamic Structural Change Enabling Tricolor Chromism by the Realization of Apparent Two-Electron Transfer to Skip the Open-Shell State.

Most redox systems generally cannot avoid the involvement of open-shell species upon generating multiply charged species, which often reduces reversibility in multi-color electrochromic systems. In this study, we newly synthesized octakis(aminophenyl)-substituted pentacenebisquinodimethane (BQD) derivatives and their hybrids with alkoxyphenyl analogues. Thanks to apparent two-electron transfer accompanied by double dramatic changes in the structure of the arylated quinodimethane skeleton, the dicationic and tetracationic states were generated and isolated quantitatively because of the negligible steady-state concentration of intermediary open-shell species such as monocation or trication radicals. When two electrophores with different donating abilities are attached to the BQD skeleton, a dicationic state with a different color can be isolated in addition to the neutral and tetracationic states. For these tetracations, an interchromophore interaction induces a red-shift of the NIR absorptions, thus realizing tricolor UV/Vis/NIR electrochromic behavior involving only closed-shell states.

Near-Infrared Electrochromic Behavior of Dibenzothiepin Derivatives Attached with Two Michler's Hydrol Blue Units.

10,11-Bis[bis(4-dimethylaminophenyl)methylene]dibenzo[bf]thiepin (1) and -oxepin (2) were prepared as stable yellow crystalline compounds, which are the cyclic analogues of electron-donating hexaarylbutadienes. Upon two-electron oxidation, they are reversibly transformed into the title dications (12+ and 22+ ) exhibiting near-infrared (NIR) absorptions, which were also isolated as stable salts. These redox pairs can serve as new entries into less well-explored organic NIR-electrochromic systems, and the separation of redox peaks (electrochemical bistability) was attained for 1/12+ and 2/22+ , thanks to drastic geometrical changes between neutral and dicationic states, as revealed by a series of X-ray analyses. Thiepin-S,S-dioxide analogue (3/32+ ) exhibits quite similar dynamic redox behavior due to nonaromatic nature of the dibenzothiepin and -oxepin unit in 12+ and 22+ , whereas the thiepin-S-oxide derivative (4/42+ ) does not exhibit bistability due to the smaller change in geometry upon electron transfer, showing that a subtle change of a bridging atom in the central seven-membered ring can modify the redox properties.

Multiple molecular interactions between alkyl groups and dissociated bromine atoms on Ag(111).

Multiple intermolecular interactions offer a high degree of controllability of on-surface molecular assemblies. Here, two kinds of molecular networks were formed by depositing 11,11,12,12-tetrabromo-1,4,5,8-tetraaza-9,10-anthraquinodimethane derivatives with two different alkyl groups in length (C4 and C8) on clean Ag(111) surfaces under ultrahigh vacuum. The detailed structures of each network before and after the cleavage of the C-Br bonds were investigated with high-resolution scanning tunneling microscopy at low temperature. We found that the diffusion of the Br atoms by high-temperature annealing plays a role in the formation of Br-mediated self-assembly. While dissociated Br atoms interacted with alkyl groups by hydrogen bonding through C-H⋯Br contacts in both systems, the different strengths of the van der Waals interactions between the alkyl groups resulted in the formation of different structures.

A Ratiometric Photoacoustic Probe with a Reversible Response to Hydrogen Sulfide and Hydroxyl Radicals for Dynamic Imaging of Liver Inflammation.

Reversible imaging probes that allow for the dynamic visualization of the redox cycle between hydroxyl radical (⋅OH) and hydrogen sulfide (H2 S) are vital to probe the redox imbalance-involved pathological process in vivo. Herein, we report a reversible ratiometric photoacoustic (PA) imaging nanoprobe (1-PAIN) for the real-time imaging of ⋅OH/H2 S redox cycle in vivo. 1-PAIN displays a low PA ratio between 690 and 825 nm (PA690 /PA825 ), which significantly increases by ≈5-fold upon oxidation by ⋅OH, and is switched back to the initially low PA690 /PA825 value upon reduction by H2 S. 1-PAIN could dynamically report on the hepatic ⋅OH production in mice during the lipopolysaccharide (LPS)-induced liver inflammation process, and visualize hepatic H2 S generation during the N-acetyl cysteine (NAC)-induced anti-inflammation process. 1-PAIN can act as a useful tool to probe the redox state in living biology, beneficial for the study of redox imbalance-related diseases.

An Activatable Afterglow/MRI Bimodal Nanoprobe with Fast Response to H2 S for In Vivo Imaging of Acute Hepatitis.

Accurate detection of hepatic hydrogen sulfide (H2 S) to monitor H2 S-related enzymes' activity is critical for acute hepatitis diagnosis, but remains a challenge due to the dynamic and transient nature of H2 S. Here, we report a H2 S-activatable near-infrared afterglow/MRI bimodal probe F1-GdNP, which shows an "always-on" MRI signal and "off-on" afterglow signal toward H2 S. F1-GdNP shows fast response, high sensitivity and specificity toward H2 S, permitting afterglow imaging of H2 S and evaluation of cystathionine γ-lyase (CSE)'s activity in living mice. We further employ the high spatial-resolution MRI signal of F1-GdNP to track its delivery and accumulation in liver. Importantly, F1-GdNP offers a high signal-to-background ratio (SBR=86.2±12.0) to sensitively report on the increased hepatic H2 S level in the acute hepatitis mice via afterglow imaging, which correlated well with the upregulated CSE activity in the liver, showcasing the good potential of F1-GdNP for monitoring of acute hepatitis process in vivo.

Hysteretic Three-State Redox Interconversion among Zigzag Bisquinodimethanes with Non-fused Benzene Rings and Twisted Tetra-/Dications with [5]/[3]Acenes Exhibiting Near-Infrared Absorptions.

Octaaryl-substituted bisquinodimethanes (BQDs) with a zigzag structure were designed as redox-switchable molecules that undergo four-electron oxidation to produce tetracationic pentacenes with a doubly twisted structure. In contrast to one-stage four-electron oxidation of BQDs, stepwise two-electron reduction of tetracationic pentacenes occurs to give dicationic anthracenes and then the original BQDs, step-by-step. Since both tetracations and dications exhibit near-infrared (NIR) absorptions (-1400 nm) based on an intramolecular charge-transfer interaction, changes in not only their structures but also their UV-vis-NIR spectra can be controlled by redox stimuli. In this Communication, we present an unprecedented one-step π-extension to pentacene from non-fused benzene rings by oxidation, and subsequent two-stage deannulation to benzene rings via anthracene upon reduction. All structures were determined by single-crystal X-ray analyses, and their properties were characterized by spectroscopic and theoretical studies.

Heterocyclic Ring-Opening of Nanographene on Au(111).

Cyclo-dehydrogenation is of importance to induce the planarization of molecules on noble surfaces upon annealing. In contrast to a number of successful syntheses of polycyclic aromatic hydrocarbons by forming carbon-carbon bonds, it is still rare to conduct conjugation and cleavage of carbon-nitrogen bonds in molecules. Here, we present a systematic transformation of the C-N bonds in11,11,12,12-tetraphenyl-1,4,5,8-tetraazaanthraquinodimethane as well as three other derivatives on Au(111). With bond-resolved scanning tunneling microscopy, we discovered novel the "heterocyclic segregation" reaction of one pyrazine ring with two nitrogen atoms to form two quinoline rings with one nitrogen each. Density functional theory calculations showed that the intramolecular ring-forming and -opening of N-heterocycles are strongly affected by the initial hydrogen-substrate interaction.

Flexible C-C Bonds: Reversible Expansion, Contraction, Formation, and Scission of Extremely Elongated Single Bonds.

Since carbon-carbon (C-C) covalent bonds are rigid and robust, the bond length is, in general, nearly constant and depends only on the bond order and hybrid orbitals. We report herein direct visualization of the reversible expansion and contraction of a C(sp3 )-C(sp3 ) single bond by light and heat. This flexibility of a C-C bond was demonstrated by X-ray analysis and Raman spectroscopy of hexaphenylethane (HPE)-type hydrocarbons with two spiro-dibenzocycloheptatriene units, the intramolecular [2+2] photocyclization of which and thermal cleavage of the resulting cyclobutane ring both occur in a single-crystalline phase. The force constant of the contracted C-C bond is 1.6 times greater than that of the expanded bond. Since formation of the cyclobutane ring and contraction of the C-C bond lower the HOMO level by approximately 1 eV, the oxidative properties of these HPEs with a flexible C-C bond can be deactivated/activated by light/heat.

Switching of Redox Properties Triggered by a Thermal Equilibrium between Closed-Shell Folded and Open-Shell Twisted Species.

Thermally switchable redox properties have been reported to be due to a change in the spin state of newly designed overcrowded ethylenes, which can adopt closed-shell folded and open-shell twisted forms. In this study, tetrathienylanthraquinodimethane derivatives were designed to be in thermal equilibrium between a more stable folded form and less stable but more donating twisted diradical in solution, so that the oxidation potential can be controlled by heating/cooling. This is the first example of a switching of redox properties based on a thermally equilibrated twisted diradical, which can be more readily oxidized to the twisted dication.

Photo- and Thermal Interconversion of Multiconfigurational Strained Hydrocarbons Exhibiting Completely Switchable Oxidation to Stable Dicationic Dyes.

Highly strained hydrocarbons with two di/tribenzocycloheptatriene units were designed as electrochromic overcrowded ethylenes that undergo reversible interconversion with stable dicationic dyes. Due to severe steric repulsion, two configurational isomers (anti,anti-folded and syn,anti-folded forms) were isolated as stable entities. Photo- and thermal interconversion of these isomers proceeded cleanly: one-way photoisomerization occurred from anti,anti- to syn,anti-form and one-way thermal isomerization was observed from syn,anti- to anti,anti-form. Even though both isomers undergo two-electron oxidation into the same twisted dications, quite different oxidation potentials enable completely selective oxidation of syn,anti-isomers. Thus, the present multiconfigurational strained hydrocarbons are capable of switching of activation/deactivation of their electrochromic properties by light/heat.