Quantitative Aspects of Electrochemical Detection of Amyloid‐β Aggregation

The tyrosine based electrochemical analysis of synthetic amyloid‐β (Aβ) peptide – an analog of natural peptide implicated in Alzheimer's disease pathogenesis – was applied for a quantitative estimation of peptide aggregation in vitro. The analysis was carried out by square wave voltammetry (SWV) on carbon screen printed electrodes (SPE). The electrooxidation peak current (I_p) for Aβ42 peptide in different aggregation states was directly compared with the size and structure of Aβ42 aggregates occurring in the analyzed sample. Dynamic light scattering (DLS) and thioflavin T (ThT) based fluorescence assay were employed to estimate the size and structure of Aβ42 aggregates. The I_p was found to decrease in a linear fashion when the average diameter of aggregates and the relative ThT fluorescence in Aβ42 solutions exceeded 35 nm and 3, respectively, while being nearly constant below these values. It was suggested that the electrooxidation current is mostly generated by peptide monomers and that a depletion of the monomer pool due to inclusion of Aβ42 molecules in aggregates is responsible for the decrease of electrooxidation current. The direct electrochemistry is emerging as a method complementary to methods based on aggregates’ detection and commonly employed for monitoring Aβ aggregation. The work further enlarges the basis for application of the cost‐effective and rapid electrochemical techniques, such as SWV on carbon SPE, to in vitro studies of Aβ aggregation.     

In vitro amyloid Aβ<Subscript>1-42</Subscript> peptide aggregation monitoring by asymmetrical flow field-flow fractionation with multi-angle light scattering detection

Self-assembly of the 42-amino-acid-long amyloid peptide Aβ_1-42 into insoluble fibrillar deposits in the brain is a crucial event in the pathogenesis of Alzheimer's disease. The fibril deposition occurs through an aggregation process during which transient and metastable oligomeric intermediates are intrinsically difficult to be accurately monitored and characterised. In this work, the time-dependent Aβ_1-42 aggregation pattern is studied by asymmetrical flow field-flow fractionation with on-line multi-angle light scattering detection. This technique allows separating and obtaining information on the molar mass (M _r) and size distribution of both the early-forming soluble aggregates and the late prefibrillar and fibrillar species, the latter having very high M _r. Preliminary results demonstrate that unique information on the dynamic aggregation process can be obtained, namely on the M _r and size of the forming aggregates as well as on their formation kinetics. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Enhanced self-assembly of the 7–12 sequence of amyloid-β peptide by tyrosine bromination

ABSTRACT

Alzheimer’s disease (AD) is a serious neuropathology related to the misfolded assembly state of amyloid-beta (Aβ40 and Aβ42) peptides. It has been demonstrated that protein post-translation modifications (PPTMs) of the more hydrophilic N-term moiety of the Aβ peptide affect its aggregation kinetics and interaction with the environment. Considering that chlorination and bromination are non-canonical PPTMs found in various metabolic pathways and often correlated to inflammatory responses, halogenation of the Y10 of the Aβ N-term could be a putative in vivo modification with implications in the Aβ peptide aggregation propensity. In this framework, we chose as a model system, a short peptide sequence, DSGYEV (i.e. residues 7–12 of the Aβ N-term) and studied its self-assembly behaviour in comparison to its chlorinated and brominated derivatives. Our results show that Y10 halogenation works as a molecular trigger of the peptide self-assembly in solution, promoting the formation of more structured aggregates.     

Estimation of electrokinetic and hydrodynamic global properties of relevant amyloid‐beta peptides through the modeling of their effective electrophoretic mobilities and analysis of their propensities to aggregation

Neuronal activity loss may be due to toxicity caused by amyloid‐beta peptides forming soluble oligomers. Here amyloid‐beta peptides (1–42, 1–40, 1–39, 1–38, and 1–37) are characterized through the modeling of their experimental effective electrophoretic mobilities determined by a capillary zone electrophoresis method as reported in the literature. The resulting electrokinetic and hydrodynamic global properties are used to evaluate amyloid‐beta peptide propensities to aggregation through pair particles interaction potentials and Brownian aggregation kinetic theories. Two background electrolytes are considered at 25°C, one for pH 9 and ionic strength I = 40 mM (aggregation is inhibited through NH₄OH) the other for pH 10 and I = 100 mM (without NH₄OH). Physical explanations of peptide oligomerization mechanisms are provided. The effect of hydration, electrostatic, and dispersion forces in the amyloidogenic process of amyloid‐beta peptides (1–40 and 1–42) are quantitatively presented. The interplay among effective charge number, hydration, and conformation of chains is described. It is shown that amyloid‐beta peptides (1–40 and 1–42) at pH 10, I = 100 mM and 25°C, may form soluble oligomers, mainly of order 2 and 4, after an incubation of 48 h, which at higher times evolve and end up in complex structures (protofibrils and fibrils) found in plaques associated with Alzheimer's disease.     

Application of an Electrochemical Method to Evaluation of Amyloid‐β Aggregation Inhibitors: Testing the RGKLVFFGR‐NH2 Peptide Antiaggregant

The aggregation of amyloid‐β peptide (Aβ) is believed to play a crucial role in the Alzheimer's disease (AD) pathogenesis and is considered as a therapeutic target for treating AD. The Aβ electrooxidation via a Tyr‐10 residue, sensitive to a depletion of a pool of Aβ monomers and oligomers in the course of Aβ aggregation, may be employed for testing natural and synthetic organic compounds (including short peptides) potentially able to inhibit the pathological Aβ aggregation (antiaggregants). In the present work, using the known peptide antiaggregant RGKLVFFGR‐NH₂ (OR2) and its scrambled variant KGLRVGFRF‐NH₂ as a control, we demonstrate that the electrochemical method based on electrooxidation of an Aβ42 Tyr‐10 residue, when combined with methods allowing for the evaluation of the Aβ42 aggregate structure and size, can provide essential information regarding the antiaggregant impact on Aβ42 aggregation. Electrochemical measurements were performed using square wave voltammetry on carbon screen printed electrodes whereas the Aβ42 aggregate structure and size were analyzed by means of the conventional thioflavin T (ThT) based fluorescence assay and dynamic light scattering. While inhibiting Aβ42 fibrillation as manifested by the unchanged level of ThT fluorescence, the OR2 peptide antiaggregant had no effect on the decrease of Aβ42 electrooxidation current in the course of Aβ42 aggregation. These observations suggest that OR2 does not stop the aggregation but redirects it into a pathway where amorphous rather than fibrillar aggregates are formed. Hence, the direct electrochemistry appears to offer a simple and cost‐effective approach for probing potential peptide antiaggregants, which is complementary to methods based on detecting Aβ aggregates.     

What is Best Strategy for Water Soluble Fluorescence Dyes?—A Case Study Using Long Fluorescence Lifetime DAOTA Dyes**

The lipophilic nature of organic dyes complicates their effectiveness in aqueous solutions. In this work we investigate three different strategies for achieving water-solubility of the diazaoxatriangulenium (DAOTA⁺) chromophore: hydrophilic counter ions, aromatic sulfonation of the chromophore, and attachment of charged side chains. The long fluorescence lifetime (FLT, τ_f=20 ns) of DAOTA⁺ makes it a sensitive probe to analyze solvation and aggregation effects. Direct sulfonation of the chromophore was found to increase solubility drastically, but at the cost of greatly reduced quantum yields (QYs) due to enhanced non-radiative deactivation processes. The introduction of either cationic (4) or zwitterionic side chains (5), however, brings the FLT (τ_f=18 ns) and QY (ϕ_f=0.56) of the dye to the same level as the parent chromophore in acetonitrile. Time-resolved fluorescence spectroscopy also reveals a high resistance to aggregation and non-specific binding in a high loading of bovine serum albumin (BSA). The results clearly show that addition of charged flexible side chains is preferable to direct sulfonation of the chromophore core.     

Synthesis and structural characterizations of [chromophore]+‐saponite/polyurethane nanocomposites

In this study, three chromophores—p‐nitroaniline, 4‐(4‐nitrophenylazo)aniline, and 4‐[(E)‐2‐{4‐[(E)‐2‐(4‐nitrophenyl)‐1‐diazenyl]phenyl}‐1‐diazenyl]aniline—were intercalated into layered aluminosilicate saponite and then dispersed into the polyurethanes matrix. The intercalated chromophore/saponite complexes were examined by inductively coupled plasma emission and element analysis technologies. The molecular orbital package computation simulation and X‐ray diffraction (XRD) analysis showed that possible configurations of chromophore ions on the gallery surfaces of saponite suggest that the chromophore molecules lie parallel to the basal planes of silicate as an inclined paraffin structure or as pseudo‐multilayers. The XRD and transmission electron microscopy analysis indicated that the delamination of organoclay in the polyurethanes matrix exhibited nanolayers, exfoliated structure, or both. In particular, even at high doping levels up to 15 wt % of organoclay, the [chromophore]⁺‐saponite/polyurethanes film did not display a macroscopic aggregation of layered silicates and showed high transparency. The thermal stability of chromophore was significantly enhanced as intercalated into the layered aluminosilicate saponite, and the glass‐transition temperature of [chromophore]⁺‐saponite/polyurethanes nanocomposites proportionally increased with increased clay content. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1690–1703, 2002     

Photoresponsive soft materials: Synthesis and photophysical studies of a stilbene‐based diblock copolymer

An amphiphilic diblock copolymer composed of a photoresponsive dialkoxycyanostilbene polymethacrylate and poly(ethylene oxide) (PDACS‐b‐PEO) was synthesized and its photophysical and aggregation properties were investigated. The amphiphilic nature of the polymer caused it to self‐assemble in water, and dynamic light scattering studies indicated formation of spherical aggregates with an average size of 160 nm. Atomic force microscopy images of dried films cast from solutions containing the polymer aggregates revealed supramolecular aggregates with a spherical morphology. Photoisomerization of the stilbene chromophore in PDACS‐b‐PEO on UV irradiation resulted in the destruction of the self‐assembled superstructures which could be attributed both to change in shape of the chromophore from the linear trans isomer to the bent cis isomer which would hinder self‐aggregation of the molecules and the higher dipole moment of the cis isomer leading to a reduction of the hydrophobic nature of the stilbene containing block of PDACS‐b‐PEO. It was observed that hydrophobic dyes such as curcumin could be encapsulated within the hydrophobic interior of the spherical micellar aggregates from which the encapsulated dye could be released on UV irradiation. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Intermolecular π‐Electron Perturbations Generate Extrinsic Visible Contributions to Eumelanin Black Chromophore in Model Polymers with Interrupted Interring Conjugation

The key structural factors underlying the unique black chromophore of eumelanin biopolymers have so far defied elucidation. Capitalizing on the ability of 1% polyvinylalcohol (PVA) to prevent pigment precipitation during melanogenesis in vitro, we have investigated the visible chromophore properties of soluble eumelanin‐like polymers produced by biomimetic oxidation of 5,6‐dihydroxyindole (DHI) and 5,6‐dihydroxyindole‐2‐carboxylic (DHICA) in 1% PVA‐containing buffer at pH 7. Upon dilution DHI‐eumelanin solutions exhibited almost linear visible absorbance changes, whereas DHICA‐eumelanin displayed a remarkable deviation from linearity in simple buffer, but not in PVA‐containing buffer. It is suggested that in DHICA polymers, exhibiting repeated interruptions of interring conjugation due to lack of planar conformations, the black chromophore is not due to an overlap of static entities defined intrinsically by the conjugation length across the carbon frame, but results largely from aggregation‐related intermolecular perturbations of the π‐electron systems which are extrinsic in character.     

Peptide‐poly(tert‐butyl methacrylate) conjugate into composite micelles in organic solvents versus peptide‐poly(methacrylic acid) conjugate into spherical and worm‐like micelles in water: Synthesis and self‐assembly

Peptide–polymer conjugates are versatile class of biomaterials composed of a peptide block covalently linked with a synthetic polymer block. This report demonstrates the synthesis of peptide‐poly(tert‐butyl methacrylate) (Peptide‐P^tBMA) conjugates of varying molecular weights via a “grafting from” atom transfer radical polymerization (ATRP) technique using as‐synthesized peptide‐based initiator in toluene. Peptide‐P^tBMA conjugate is soluble in many organic solvents and undergoes self‐assembly into micro/nanospheres in DMF/THF as observed from both FESEM and DLS results. The conjugate micro/nanospheres are nothing but the composite micelles formed by the secondary aggregation of primary micelles generated initially in these organic solvents. The hydrolysis of tert‐butyl groups of Peptide‐P^tBMA conjugate leads to the formation of peptide‐poly(methacrylic acid) (Peptide‐PMA) conjugate. The circular dichroism (CD) analysis exhibits the presence of β‐sheet conformation of peptide moiety in synthesized conjugates. The formed Peptide‐PMA conjugate is soluble in water and owing to its amphiphilic character, the conjugate molecules self‐assemble into spherical micelles as well as worm‐like micelles upon increasing the concentration of conjugate in water. However, the sodium salt of Peptide‐PMA conjugates (Peptide‐PMAS) self‐assembles into only spherical swollen micelles in water at higher (pH ～10). The critical aggregation concentrations (CACs) of both Peptide‐PMA and Peptide‐PMAS micelles are measured by fluorescence spectroscopy. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3019–3031     

Oligopeptide Helical Conformations Control Gold Nanoparticle Cross-Linking

Peptide sequences functionalized with primary amines at the N- and C-terminus are able to induce the aggregation of gold nanoparticles in ethanol as a consequence of their folding into a helical conformation. Random coil peptides are unable to induce such an aggregation process. Aggregation can be monitored spectrophotometrically by following the shift of the surface plasmon resonance (SPR) band of the nanoparticles and is confirmed by transmission electron microscopy and dynamic light scattering analyses. Partial denaturation of the peptides results in diminished cross-linking ability. The helicity parameter θ₂₂₂/θ₂₀₈ correlates fairly well with the shift of the SPR band to longer wavelengths, supporting the relationship between the amount of helical content of a peptide sequence and its ability to induce aggregation.     

Physicochemical characterization of a novel surfactant peptide containing an arginine cation and laurate anion

 A novel surfactant peptide consisting of an arginine cation with laurate anion has been synthesized, purified and characterized. The critical micellar concentration (cmc) of peptide in aqueous solutions has been determined using spectroscopic techniques and is found to increase from 0.06 to 0.11 mM with increasing temperature (15–45 °C). Cmc is also determined in the presence of salts like NaCl, KCl and sodium acetate and it is found that these electrolytes hinder aggregation with a significant increase in the case of sodium acetate. The aggregation number of the surfactant peptide has been determined using fluorescence quenching measurements and is observed to decrease from 14 to 6 with increasing temperature (15–45 °C). The standard free energy change (ΔG ⁰ _m) and standard enthalpy change (ΔH ⁰ _m) of the peptide aggregate are found to be negative with a small positive value for standard entropy change (ΔS ⁰ _m). The peptide aggregate seems to undergo phase transition above 50 °C as observed from UV–vis and fluorescence spectroscopy. From pyrene binding studies, it is shown that the interior dielectric constant increases from 5.08 at 34 °C to 8.77 at 50 °C and further decreases with increase in temperature indicating a phase change at 50 °C. Also, the ratio of excimer intensity to monomer intensity, which is a measure of microviscosity of the aggregate, decreases with increase in temperature with a change at 50 °C indicating a phase change. Received: 14 February 1997 Accepted: 13 August 1997     

Modification of amyloid-beta peptide aggregation via photoactivation of strained Ru(ii) polypyridyl complexes

Alzheimer''s disease (AD) is a chronic neurodegenerative disorder characterized by progressive and irreversible damage to the brain. One of the hallmarks of the disease is the presence of both soluble and insoluble aggregates of the amyloid beta (Aβ) peptide in the brain, and these aggregates are considered central to disease progression. Thus, the development of small molecules capable of modulating Aβ peptide aggregation may provide critical insight into the pathophysiology of AD. In this work we investigate how photoactivation of three distorted Ru(ii) polypyridyl complexes (Ru1–3) alters the aggregation profile of the Aβ peptide. Photoactivation of Ru1–3 results in the loss of a 6,6′-dimethyl-2,2′-bipyridyl (6,6′-dmb) ligand, affording cis-exchangeable coordination sites for binding to the Aβ peptide. Both Ru1 and Ru2 contain an extended planar imidazo[4,5-f][1,10]phenanthroline ligand, as compared to a 2,2′-bipyridine ligand for Ru3, and we show that the presence of the phenanthroline ligand promotes covalent binding to Aβ peptide His residues, and in addition, leads to a pronounced effect on peptide aggregation immediately after photoactivation. Interestingly, all three complexes resulted in a similar aggregate size distribution at 24 h, forming insoluble amorphous aggregates as compared to significant fibril formation for peptide alone. Photoactivation of Ru1–3 in the presence of pre-formed Aβ_1–42 fibrils results in a change to amorphous aggregate morphology, with Ru1 and Ru2 forming large amorphous aggregates immediately after activation. Our results show that photoactivation of Ru1–3 in the presence of either monomeric or fibrillar Aβ_1–42 results in the formation of large amorphous aggregates as a common endpoint, with Ru complexes incorporating the extended phenanthroline ligand accelerating this process and thereby limiting the formation of oligomeric species in the initial stages of the aggregation process that are reported to show considerable toxicity.

Photoactivation of a series of Ru(ii) polypyridyl complexes leads to ligand exchange and modulation of amyloid-beta peptide aggregation of relevance to Alzheimer''s disease.     

Sequestration within biomolecular condensates inhibits Aβ-42 amyloid formation

Biomolecular condensates are emerging as an efficient strategy developed by cells to control biochemical reactions in space and time by locally modifying composition and environment. Yet, local increase in protein concentration within these compartments could promote aberrant aggregation events, including the nucleation and growth of amyloid fibrils. Understanding protein stability within the crowded and heterogeneous environment of biological condensates is therefore crucial, not only when the aggregation-prone protein is the scaffold element of the condensates but also when proteins are recruited as client molecules within the compartments. Here, we investigate the partitioning and aggregation kinetics of the amyloidogenic peptide Abeta42 (Aβ-42), the peptide strongly associated with Alzheimer''s disease, recruited into condensates based on low complexity domains (LCDs) derived from the DEAD-box proteins Laf1, Dbp1 and Ddx4, which are associated with biological membraneless organelles. We show that interactions between Aβ-42 and the scaffold proteins promote sequestration and local increase of the peptide concentration within the condensates. Yet, heterotypic interactions within the condensates inhibit the formation of amyloid fibrils. These results demonstrate that biomolecular condensates could sequester aggregation-prone proteins and prevent aberrant aggregation events, despite the local increase in their concentration. Biomolecular condensates could therefore work not only as hot-spots of protein aggregation but also as protective reservoirs, since the heterogenous composition of the condensates could prevent the formation of ordered fibrillar aggregates.

Biomolecular condensates sequester an aggregation-prone peptide and prevent its aggregation, showing that heterotypic interactions within the condensates can prevent the formation of amyloid fibrils, despite the local increase in concentration.     

1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside: A new powerful antioxidant and inhibitor of Aβ42 aggregation isolated from the leaves of Lawsonia inermis

Mounting evidence indicates free radicals as toxic species causing damage to human cells leading to the pathogenesis of many diseases such as neurodegenerative disease. Plant derived antioxidants are considered as promising strategy to prevent free radical toxicity. In this study, the crude extract (CE), 50%MeOH, Petroleum Ether (PE) and Ethyl acetate (EA) fractions of Lawsonia inermis leaves were investigated for their antioxidant activity and their ability to counteract amyloid-β₄₂ (Aβ₄₂) aggregation. Elution of the most bioactive fraction (EA) on silica gel column chromatography led to six sub-fractions. The most active sub-fraction (1) was further resolved on silica gel column chromatography. A new compound with powerful antioxidant and anti-Aβ₄₂ aggregation properties was purified and characterised by spectroscopic methods as 1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside (THNG). This finding suggests that the antioxidant and anti-Aβ₄₂ aggregation activities of L. inermis leaves are strongly correlated to this compound.     

Licochalcone B,a chalcone derivative from Glycyrrhiza inflata,as a multifunctional agent for the treatment of Alzheimer’s disease

Abstract

Licochalcone B (LCB), an extract from the root of Glycyrrhiza inflate, has the same caffeic acid scaffold as curcumin (Cur), which is known as an anti-Alzheimer’s disease (AD) agent. However, there is no relevant research about anti-AD activity of LCB. In this study, the anti-AD activity of LCB was investigated. LCB could inhibit amyloid beta (Aβ₄₂) self-aggregation (IC₅₀?=?2.16?±?0.24?μM) and disaggregate pre-formed Aβ₄₂ fibrils, reduce metal-induced Aβ₄₂ aggregation through chelating metal ions. Molecular docking further revealed that LCB inhibited Aβ₄₂ self-aggregation through forming two hydrogen bonds with Lys28 to block the salt bridge interaction at the C-terminus of Aβ₄₂. Anti-oxidant property of LCB was also observed by DCFH-DA assay. In addition, LCB did show neuroprotective activity against H₂O₂-induced cell death in SH-SY5Y cells. In general, our results demonstrate that LCB, as a multifunctional agent, is likely to be promising therapeutics for AD.     

Separation and characterization of aggregated species of amyloid-beta peptides

We have investigated the use of isoelectric focusing and immunodetection for the separation of low molecular weight species of amyloid-beta (Aβ) peptides from their aggregates. From solutions of Aβ_1–40 or Aβ_1–42 monomeric peptides, low molecular weight material appeared at a pI value of ca. 5, while the presence of aggregates was detected as bands, observed at a pI of 6–6.5. The formation of Aβ aggregates (protofibrils) was verified by a sandwich ELISA, employing the protofibril conformation-selective antibody mAb158. In order to study the aggregation behavior when using a mixture of the monomers, we utilized the IEF separation combined with Western blot using two polyclonal antisera, selective for Aβ_1–40 and Aβ_1–42, respectively. We conclude that both monomers were incorporated in the aggregates. In a further study of the mixed aggregates, we used the protofibril conformation-selective antibody mAb158 for immunoprecipitation, followed by nanoelectrospray mass spectrometry (IP-MS). This showed that the Aβ_1–42 peptide is incorporated in the aggregate in a significantly larger proportion than its relative presence in the original monomer composition. IP-MS with mAb158 was also performed, and compared to IP-MS with the Aβ-selective antibody mAb1C3, where a monomeric Aβ_1–16 peptide was added to the protofibril preparation. Aβ_1–16 is known for its poor aggregation propensity, and acted therefore as a selectivity marker. The results obtained confirmed the protofibril conformation selectivity of mAb158.     

Peptide‐poly(2‐(dimethylamino)ethyl methacrylate) conjugates: Synthesis and aqueous/nonaqueous self‐aggregation into nanostructures of dendritic and spherical morphologies

Peptide–polymer conjugate consisting of a sequence‐defined tripeptide and poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) is synthesized by a simple “grafting from” atom transfer radical polymerization (ATRP) approach. The ATRP of PDMAEMA using peptide‐macroinitiator and CuBr/1,1,4,7,10,10‐hexamethyltriethylenetetramine system in anisole follows pseudo first order kinetics up to a conversion of about 25% within a time span of 125 min. The attachment of peptide moiety at the end of PDMAEMA chain is confirmed from MALDI‐TOF‐MS and circular dichroism analyses. The self‐assembly of as‐synthesized peptide‐PDMAEMA conjugate in organic solvents leads to the formation of spherical nanoparticles as observed through FESEM. Peptide‐PDMAEMA conjugate become soluble in water due to the protonation of the pendent —N(CH₃)₂ moiety of DMAEMA group of the conjugate. Owing to the amphiphilic nature of the protonated conjugate (peptide‐PDMAEMAH), it also undergoes self‐aggregation in water into nanostructures of various morphologies such as dendrite, small sphere and large sphere at pHs of 2, 8, and 10, respectively. Peptide‐PDMAEMA‐IBu conjugate obtained by the post‐modification of —N(CH₃)₂ moiety of DMAEMA group of the conjugate with n‐butylbromide also undergoes self‐aggregation into dendritic nanostructures in water. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3286–3297     

Single-Benzene-Based Solvatochromic Chromophores: Color-Tunable and Bright Fluorescence in the Solid and Solution States

The search for structurally simple chromophores with superior fluorescence brightness and a wide range of solvent compatibility is highly desirable. Herein, a new type of single-benzene-based solvatochromic chromophore with a symmetric bifunctional structure, in which azetidine and ethoxycarbonyl moieties serve as the electron-donating and -withdrawing groups, respectively, is reported. This chromophore exhibits an extraordinary wide range of solvent compatibility and preserves excellent fluorescence quantum yields from nonpolar n-hexane to polar methanol and even in water. Unusually, the symmetric structure of the chromophore shows a distinct color change from bright green to red with increasing solvent polarity and possesses large Stokes shifts (λ=132–207 nm) in the tested solvents. Moreover, this single-benzene-based chromophore displays good photochemical stability in both solution and solid states, and even exhibits reversible mechanochromic luminescence.