Halogen Atom Transfer-Induced Homolysis of C-F Bonds by the Excited-State Boryl Radical.

A novel reactivity toward C-F bond functionalization has been developed, which could be designated as fluorine atom transfer (FAT). A photoexcited state of an N-heterocyclic carbene-ligated boryl radical exhibits a transcendent reactivity, capable of activating chemically inert carbon-fluorine bonds through homolysis. Combined experimental and computational studies suggest that the ligated boryl radical species directly abstracts a fluorine atom from the organofluoride substrates to provide valuable carbon-centered radicals.

Enhancing Circularly Polarized Phosphorescence via Integrated Top-Down and Bottom-Up Approach.

In the dynamic domain of chiroptical technologies, it is imperative to engineer emitters endowed with circularly polarized luminescence (CPL) properties. This research demonstrates an advancement by employing a combined top-down and bottom-up strategy for the simultaneous amplification of photoluminescence quantum yield (Φ) and the luminescence dissymmetry factor (glum ). Square-planar Pt(II) complexes form helical assemblies, driven by torsional strain induced by bis(nonyl) chains. Integration of chiral anions leads these assemblies to prefer distinct helical sense. This arrangement activates the metal-metal-to-ligand charge transfer (MMLCT) transition that is CPL-active, with Φ and |glum | observing an upswing contingent on the charge number and aryl substituents in chiral anions. Utilizing the soft-lithographic micromolding in capillaries technique, we could fabricate exquisitely-ordered, one-dimensional co-assemblies to achieve the metrics to Φ of 0.32 and |glum | of 0.13. Finally, our spectroscopic research elucidates the underlying mechanism for the dual amplification, making a significant stride in the advancement of CPL-active emitters.

Circularly Polarized Luminescence Active Supramolecular Nanotubes Based on PtII Complexes That Undergo Dynamic Morphological Transformation and Helicity Inversion.

Circularly polarized luminescence (CPL) with tunable chirality is currently a challenging issue in the development of supramolecular nanomaterials. We herein report the formation of helical nanoribbons which grow into helical tubes through dynamic helicity inversion. For this, chiral PtII complexes of terpyridine derivatives, namely S-trans-1 and R-trans-1, with respective S- and R-alanine subunits and incorporating trans-double bonds in the alkyl chain were prepared. In DMSO/H2 O (5 : 1 v/v), S-trans-1 initially forms a fibrous self-assembled product, which then undergoes dynamic transformation into helical tubes (left-handed or M-type) through helical ribbons (right-handed or P-type). Interestingly, both helical supramolecular architectures are capable of emitting CPL signals. The metastable helical ribbons show CPL signals (glum =±4.7×10-2 ) at 570 nm. Meanwhile, the nanotubes, which are the thermodynamic products, show intense CPL signals (glum =±5.6×10-2 ) at 610 nm accompanied by helicity inversion. This study provides an efficient way to develop highly dissymmetric CPL nanomaterials by regulating the morphology of metallosupramolecular architectures.

Twist to Boost: Circumventing Quantum Yield and Dissymmetry Factor Trade-Off in Circularly Polarized Luminescence.

Circularly polarized luminescence (CPL) enables promising applications in asymmetric photonics. However, the performances of CPL molecules do not yet meet the requirements of these applications. The shortcoming originates from the trade-off in CPL between the photoluminescence quantum yield (PLQY) and the photoluminescence dissymmetry factor (gPL). In this study, we developed a molecular strategy to circumvent this trade-off. Our approach takes advantage of the strong propensity of [Pt(N^C^N)Cl], where the N^C^N ligand is 1-(2-oxazoline)-3-(2-pyridyl)phenylate, to form face-to-face stacks. We introduced chiral substituents, including (S)-methyl, (R)- and (S)-isopropyl, and (S)-indanyl groups, into the ligand framework. This asymmetric control induces torsional displacements that give homohelical stacks of the Pt(II) complexes. X-ray single-crystal structure analyses for the (S)-isopropyl Pt(II) complex reveal the formation of a homohelical dimer with a Pt···Pt distance of 3.48 Å, which is less than the sum of the van der Waals radii of Pt. This helical stack elicits the metal-metal-to-ligand charge-transfer (MMLCT) transition that exhibits strong chiroptical activity due to the electric transition moment making an acute angle to the magnetic transition moment. The PLQY and gPL values of the MMLCT phosphorescence emission of the (S)-isopropyl Pt(II) complex are 0.49 and 8.4 × 10-4, which are improved by factors of ca. 6 and 4, respectively, relative to the values of the unimolecular emission (PLQY, 0.078; gPL, 2.4 × 10-4). Our photophysical measurements for the systematically controlled Pt(II) complexes reveal that the CPL amplifications depend on the chiral substituent. Our investigations also indicate that excimers are not responsible for the enhanced chiroptical activity. To demonstrate the effectiveness of our approach, organic electroluminescence devices were fabricated. The MMLCT emission devices were found to exhibit simultaneous enhancements in the external quantum efficiency (EQE, 9.7%) and the electroluminescence dissymmetry factor (gEL, 1.2 × 10-4) over the unimolecular emission devices (EQE, 5.8%; gEL, 0.3 × 10-4). These results demonstrate the usefulness of using the chiroptically active MMLCT emission for achieving an amplified CPL.

Benzothiazole Synthesis: Mechanistic Investigation of an In Situ-Generated Photosensitizing Disulfide.

The use of a visible light absorbing intermediate as a photosensitizer makes a chemical process simple and sustainable, obviating the need for the use of chemical additives. Herein, the formation of a photosensitizing disulfide in benzothiazole synthesis from 2-aminothiophenol and aldehydes was proposed and confirmed through in-depth mechanistic studies. A series of photophysical and electrochemical investigations revealed that an in situ-generated disulfide photosensitizes molecular oxygen to generate the key oxidants, singlet oxygen and superoxide anion, for the dehydrogenation step.

Deep-Red-Fluorescent Zinc Probe with a Membrane-Targeting Cholesterol Unit.

Organelle-targeting fluorescence probes are valuable because they can provide spatiotemporal information about the trafficking of analytes of interest. The spatiotemporal resolution can be improved by using low-energy emission signals because they are barely contaminated by autofluorescence noises. In this study, we designed and synthesized a deep-red-fluorescent zinc probe (JJ) with a membrane-targeting cholesterol unit. This zinc probe consists of a boron-azadipyrromethene (aza-BODIPY) fluorophore and a zinc receptor that is tethered to a tri(ethylene glycol)-cholesterol chain. In aqueous solutions buffered to pH 7.4, JJ exhibits weak fluorescence with a peak wavelength of 663 nm upon excitation at 622 nm. The addition of ZnCl2 elicits an approximately 5-fold enhancement of the fluorescence emission with a fluorescence dynamic range of 141000. Our electrochemical and picosecond transient photoluminescence investigations indicate that the fluorescence turn-on response is due to the zinc-induced abrogation of the formation of a nonemissive intramolecularly charge-separated species, which occurs with a driving force of 0.98 eV. The fluorescence zinc response was found to be fully reversible and to be unaffected by pH changes or the presence of biological metal ions. These properties are due to tight zinc binding with a dissociation constant of 4 pM. JJ was found to be nontoxic to HeLa cells up to submicromolar concentrations, which enables cellular imaging. Colocalization experiments were performed with organelle-specific stains and revealed that JJ is rapidly internalized into intracellular organelles, including lysosomes and endoplasmic reticula. Unexpectedly, probe internalization was found to permeabilize the cell membrane, which facilitates the influx of exogens such as zinc ions. Such permeabilization does not arise for a control probe without the tri(ethylene glycol)-cholesterol chain (JJC). Our results show that the membrane-targeting cholesterol unit can disrupt membrane integrity.

Photodelivery of ß-phenylethylamines.

We have developed the first photodonors for the trace amino neurotransmitters, ß-phenylethylamine (DPSY1) and ß-methylphenylethylamine (DPSY2). Our photodonors react rapidly with photosensitized singlet dioxygen (1O2) to yield the amines. The photodelivery of ß-phenylethylamine into aqueous solutions by employing liposome scaffolds is successfully demonstrated.

Generation of N-Centered Radicals via a Photocatalytic Energy Transfer: Remote Double Functionalization of Arenes Facilitated by Singlet Oxygen.

An unprecedented approach to the generation of an N-centered radical via a photocatalytic energy-transfer process from readily available heterocyclic precursors is reported, which is distinctive of the previous electron transfer approaches. In combination with singlet oxygen, the in-situ-generated nitrogen radical from the oxadiazoline substrate in the presence of fac-Ir(ppy)3 undergoes a selective ipso addition to arenes to furnish remotely double-functionalized spiro-azalactam products. The mechanistic studies provide compelling evidence that the catalytic cycle selects the energy-transfer pathway. A concurrent activation of molecular oxygen to generate singlet oxygen by energy transfer is also rationalized. Furthermore, the occurrence of the electron transfer phenomenon is excluded on the basis of the negative driving forces for one-electron transfer between oxadiazoline and the excited state of fac-Ir(ppy)3 with a consideration of their redox potentials. The necessity of singlet oxygen as well as the photoactivated oxadiazoline substrate is clearly supported by a series of controlled experiments. Density functional studies have also been carried out to support these observations. The scope of substrates is explored by synthesizing diversely functionalized cyclohexadienone moieties in view of their utility in complex organic syntheses and as potential targets in pharmacology.

Visible-Light-Induced Trifluoromethylation of Unactivated Alkenes with Tri(9-anthryl)borane as an Organophotocatalyst.

Tri(9-anthryl)borane was successfully applied as an organophotocatalyst for the visible-light-induced trifluoromethylation of unactivated alkenes with CF3I. The mild reaction conditions tolerated a variety of functional groups, and the reaction could be extended to perfluoroalkylations with C3F7I and C4F9I. Mechanistic studies revealed that the photoredox catalysis involves an oxidative quenching pathway.

Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)-Nitrosyl Complex.

Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time-dependent dynamics to discriminate the endogenous and exogenous inputs. For a real-time stimulation of cell signaling, we synthesized a photo-cleavable metal-nitrosyl complex, [CoIII (MDAP)(NO)(CH3 CN)]2+ (MDAP=N,N'-dimethyl-2,11-diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosol, and used this to study the extracellular signal-regulated kinases (ERKs), revealing how cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be to understand how diverse cellular signaling networks are dynamically interconnected and also to control drug delivery systems.

Birch Reduction of Aromatic Compounds by Inorganic Electride [Ca2N]+•e- in an Alcoholic Solvent: An Analogue of Solvated Electrons.

Birch reduction of aromatic systems by solvated electrons in alkali metal-ammonia solutions is widely recognized as a key reaction that functionalizes highly stable π-conjugated organic systems. In spite of recent advances in Birch reduction with regard to reducing agent and reaction conditions, there remains an ongoing challenge to develop a simple and efficient Birch reaction under mild conditions. Here, we demonstrate that the inorganic electride [Ca2N]+•e- promotes the Birch reduction of polycyclic aromatic hydrocarbons (PAHs) and naphthalene under alcoholic solvent in the vicinity of room temperature as a solid-type analogy to solvated electrons in alkali metal ammonia solutions. The anionic electrons from electride [Ca2N]+•e- are transferred to PAHs and naphthalene via alcoholysis in a polar cosolvent medium. It is noteworthy that a high conversion yield to the hydrogenated products is ascribed to the extremely high electron transfer efficiency of 98%. This simple protocol utilizing an inorganic electride offers a direct and practical strategy for the reduction of aromatic compounds and provides an outstanding reducing agent for synthetic chemistry.

Monocycloplatinated Solvento Complex Displays Turn-on Ratiometric Phosphorescence Responses to Histamine.

The study of biological histamine (HA) requires probes capable of ratiometric photoluminescence detection of HA. We discovered that a monocycloplatinated complex having two solvento ligands ([Pt(2-(2-naphthyl)quinolinate)(NCCH3)2]ClO4) could produce ratiometric phosphorescence responses to HA in aerated aqueous solutions buffered to pH 7.4. The HA response was characterized with a hypsochromic shift of an emission peak wavelength from 635 to 567 nm. The corresponding phosphorescence intensity ratio (i.e., I567 nm/ I635 nm) increased from 0.26 to 1.90. Spectroscopic and spectrometric investigations indicated an occurrence of spontaneous displacement of the labile CH3CN ligands with HA. An independently prepared HA adduct supported this notion. The ratiometric phosphorescence responses to HA were highly tolerant to other biological stimuli, including changes in pH and the presence of biometals and biological Lewis bases such as amino acids, nucleosides, biothiols, neurotransmitters, and small molecular metabolites. Of note was the high selectivity toward HA over common biological ligands, including histidine, cysteine, and homocysteine, which was ascribed to tighter HA binding. Our phosphorescence measurements employing Boc-protected derivatives of HA suggested that the bis-chelate motif involving imidazolyl and terminal amino groups was crucial for eliciting the ratiometric phosphorescence signaling. Finally, the bioimaging utility of the HA probe was validated using RAW 264.7 macrophages that were exogenously supplemented with HA or stimulated with thapsigargin to enrich intracellular HA. Ratiometric phosphorescence imaging microscopy experiments demonstrated the ability of the probe for monitoring intracellular HA uptake. In addition, photoluminescence lifetime imaging microscopy techniques could be applied for visualization of HA within the RAW 264.7 cells, because the HA binding elongated the photoluminescence lifetime. Our study demonstrated the promising utility of inner-sphere interactions of phosphorescent Pt(II) complexes for detection of biological HA.

Chemical tools for the generation and detection of singlet oxygen.

Growing evidence indicates intermediacy of singlet dioxygen (1O2) in a variety of pathophysiological processes. 1O2 has also found great utility of destructive actions for clinical and environmental applications. However, many details of the molecular mechanisms mediated by 1O2 remain insufficiently understood. Efforts to elucidate the 1O2 chemistry have been hampered by the lack of chemical tools capable of generation and detection of 1O2. In this review, I summarize the recent advances in the development of the chemical tools of 1O2. This article focuses on two topics. The first part introduces chemical methods for ground-state generation of 1O2. Designs of the molecular carriers of 1O2 are also explained. The second part discloses molecular probes of 1O2. The probes are categorized into three groups, depending on signaling modalities: absorption-based probes, photoluminescent probes, and chemiluminescent probes. Focus is on the molecular design to maximize the signaling actions. Disadvantages of using the probes are also discussed to motivate the future research. I hope that this review will serve as helpful guidance to the exploitation and development of the chemical tools of 1O2.

Controlled Fluoroalkylation Reactions by Visible-Light Photoredox Catalysis.

Owing to their unique biological, physical, and chemical properties, fluoroalkylated organic substances have attracted significant attention from researchers in a variety of disciplines. Fluoroalkylated compounds are considered particularly important in pharmaceutical chemistry because of their superior lipophilicity, binding selectivity, metabolic stability, and bioavailability to those of their nonfluoroalkylated analogues. We have developed various methods for the synthesis of fluoroalkylated substances that rely on the use of visible-light photoredox catalysis, a powerful preparative tool owing to its environmental benignity and mechanistic versatility in promoting a large number of synthetically important reactions with high levels of selectivity. In this Account, we describe the results of our efforts, which have led to the development of visible-light photocatalytic methods for the introduction of a variety of fluoroalkyl groups (such as, -CF3, -CF2R, -CH2CF3, -C3F7, and -C4F9) and arylthiofluoroalkyl groups (such as, -CF2SPh, -C2F4SAr, and -C4F8SAr) to organic substances. In these studies, electron-deficient carbon-centered fluoroalkyl radicals were successfully generated by the appropriate choice of fluoroalkyl source, photocatalyst, additives, and solvent. The redox potentials of the photocatalysts and the fluoroalkyl sources and the choice of sacrificial electron donor or acceptor as the additive affected the photocatalytic pathway, determining whether an oxidative or reductive quenching pathway was operative for the generation of key fluoroalkyl radicals. Notably, we have observed that additives significantly affect the efficiencies and selectivities of these reactions and can even change the outcome of the reaction by playing additional roles during its course. For instance, a tertiary amine as an additive in the reaction medium can act not only as a sacrificial electron donor in photoredox catalysis but also as a hydrogen atom source, an elimination base for dehydrohalogenation of the intermediate, and also a Brønsted base for deprotonation. In the same context, the selection of solvent is also critical since it affects the rate and selectivity of reactions depending upon its polarity and reagent solubilizing ability and plays additional roles in the process, for example, as a hydrogen atom source. By clearly understanding the roles of additives and solvent, we designed several controlled fluoroalkylation reactions where different products were formed selectively from the same starting substrates. In addition, we could exploit one of the most important advantages of radical reactions, that is, the use of unactivated π-systems such as alkenes, alkynes, arenes, and heteroarenes as radical acceptors without prefunctionalization. Furthermore, fluoroalkylation processes under mild room-temperature reaction conditions tolerate various functional groups and are therefore easily applicable to late-stage modifications of highly functionalized advanced intermediates.

Bistable Solid-State Fluorescence Switching in Photoluminescent, Infinite Coordination Polymers.

Photo-functional infinite coordinated polymers (ICPs) were synthesized that consist of the photochromic dithienylethene (DTE) and a luminescent bridging unit to give enhanced fluorescence in the solid state. We could fabricate well-ordered micropatterns of these ICPs by a soft-lithographic method, which repeatedly showed high contrast on-off fluorescence switching.

Low-Affinity Zinc Sensor Showing Fluorescence Responses with Minimal Artifacts.

The study of the zinc biology requires molecular probes with proper zinc affinity. We developed a low-affinity zinc probe (HBO-ACR) based on an azacrown ether (ACR) and an 2-(2-hydroxyphenyl)benzoxazole (HBO) fluorophore. This probe design imposed positive charge in the vicinity of a zinc coordination center, which enabled fluorescence turn-on responses to high levels of zinc without being affected by the pH and the presence of other transition-metal ions. Steady-state and transient photophysical investigations suggested that such a high tolerance benefits from orchestrated actions of proton-induced nonradiative and zinc-induced radiative control. The zinc bioimaging utility of HBO-ACR has been fully demonstrated with the use of human pancreas epidermoid carcinoma, PANC-1 cells, and rodent hippocampal neurons from cultures and acute brain slices. The results obtained through our studies established the validity of incorporating positively charged ionophores for the creation of low-affinity probes for the visualization of biometals.

Mechanism and Applications of the Photoredox Catalytic Coupling of Benzyl Bromides.

The photoredox catalytic coupling of halomethyl arenes to bibenzyl derivatives has been demonstrated. The catalytic protocol employed the Hantzsch ester, potassium phosphate, and a photoactive cyclometalated IrIII complex catalyst. A photochemical quantum yield as high as 20 % was obtained. The catalytic mechanism was investigated in detail by performing photophysical and electrochemical measurements, as well as by quantum chemical calculations. The results suggest that two-electron mediation might be responsible for the improved photon economy. The reaction protocol was compatible with halomethyl arenes that contain a variety of functional groups. Finally, the synthetic utility of our protocol was demonstrated by the preparation of a natural dihydrostilbenoid, brittonin A.

Coreactant Strategy for the Photoredox Catalytic Generation of Trifluoromethyl Radicals under Low-Energy Photoirradiation.

Photoredox catalysis has emerged as a valuable alternative to dark-state catalysis. For the full potential of photoredox catalysis to be utilized, it is imperative to make use of low-energy photons in photoinduced radical processes. We have demonstrated that the use of oxalate as a coreactant provides a useful principle for the photocatalytic production of trifluoromethyl radicals (•CF3) from CF3I upon green or red LED photoirradiation of narrow-bandgap photocatalysts. The photocatalytic cycle involves a radical anion of carbon dioxide (CO2(•-)) as a reductant for CF3I, which is generated through photoinduced oxidative decarboxylation of oxalate. Electrochemical characterizations and steady-state and transient photophysical investigations were performed to reveal that there are two photoinduced electron-transfer pathways for oxalate-mediated •CF3 generation.

Molecular dyad approaches to the detection and photosensitization of singlet oxygen for biological applications.

The principles and prospects of a molecular dyad strategy for photocontrolling biological singlet oxygen are highlighted.

Phosphorescent Zinc Probe for Reversible Turn-On Detection with Bathochromically Shifted Emission.

Phosphorescent molecules are attractive complements to fluorescent compounds for bioimaging. Time-gated acquisition of the long-lived phosphorescence signals provides an effective means to eliminate unwanted background noises due to short-lived autofluorescence. We have previously investigated the molecular principles governing modulation of photoinduced electron transfer in phosphorescence zinc probes that were based on biscyclometalated Ir(III) complexes (Woo, H. et al. J. Am. Chem. Soc. 2013, 135, 4771-4787). The studies established that phosphorescence turn-on responses would be attainable for Ir(III) complexes with high triplet-state energies. This sets an upper limit to an emission wavelength, restricting the development of red- or near-IR-phosphorescence turn-on probes. To address this challenge, we designed and synthesized a new phosphorescent probe having an electron-deficient 2-(2-pyridyl)pyrazine diimine ligand tethering a di(2-picolyl)amine (DPA) zinc receptor. This ligand control led to red phosphorescence emission (λ(ems) = 596 nm), with an excited-state reduction potential (E*(red)) retained as high as 1.44 V versus standard calomel electrode (SCE). The E*(red) value was more positive than the ground-state oxidation potential of DPA (1.05 V vs SCE), permitting an occurrence of photoinduced electron transfer at a rate of 2 × 10(7) s(-1). Zinc binding at DPA abolished the electron transfer to produce phosphorescence turn-on signaling. The probe was capable of detecting zinc ions selectively over other competing biological metal ions in aqueous buffer solutions (pH 7.4, 20 mM piperazine-N,N'-bis(2-ethanesulfonic aid)) with the zinc dissociation constant of 109 pM. Finally, bioimaging utility of the probe has been successfully demonstrated by visualizing exogenously supplied zinc ions in live HeLa cells. The research described in this paper demonstrates that judicious ligand control enables retention of turn-on responses in the low-energy phosphorescence region.