Twisted Intramolecular Charge Transfer Research Articles

FRET-based fluorescent probe with favorable water solubility for simultaneous detection of SO2 derivatives and viscosity

The intracellular viscosity is an important parameter of the microenvironment and SO2 is a vital gas signal molecule. At present, some dual-response fluorescence probes for simultaneous measurements of viscosity and SO2 derivatives (HSO3−/SO32−) possessed poor water solubility. In this work, we developed a water-soluble fluorescence probe CIJ (0.0864 g/100 mL of water at 20 °C) for simultaneous measurements of viscosity and SO2 derivatives. CIJ exhibited a sensitive fluorescence enhancement to environmental viscosity from 0.97 to 28.04 cP based on a twisted intramolecular charge transfer mechanism and was applied to effective measurement of viscosity in vitro and in vivo. CIJ could also respond to SO2 derivatives with a low detection limit (44 nM) and a fast response time (5 min) based on the nucleophilic addition reaction. Furthermore, CIJ was applied to monitor SO2 derivatives in ratiometric response manner in living cells.

Fluorescence Modulation by Amines: Mechanistic Insights into Twisted Intramolecular Charge Transfer (TICT) and Beyond

Amine groups are common constituents of organic dyes and play important roles in tuning fluorescence properties. In particular, intensive research works have demonstrated the tendency and capabilities of amines in influencing chromophore brightness. Such properties have been explained by multiple mechanisms spanning from twisted intramolecular charge transfer (TICT) to the energy gap law and beyond, which introduce additional nonradiative energy dissipation pathways. In this review, we aim to provide a focused overview of the mechanistic insights mainly for the TICT mechanism, accompanied by a few other less common or influential fluorescence quenching mechanisms in the amine-containing fluorescent molecules. Various aspects of current scientific findings including the rational design and synthesis of organic chromophores, theoretical calculations, steady-state and time-resolved electronic and vibrational spectroscopies are reviewed. These in-depth understandings of how the amine groups with diverse chemical structures at various atomic sites affect excited-state nonradiative decay pathways will facilitate the strategic and targeted development of fluorophores with desired emission properties as versatile chemosensors for broad applications.

A Deep Understanding on the Effective Generation of Twisted Intramolecular Charge Transfer by Protonation in Thiazolo[5,4-d]thiazole Derivatives.

The exploration of the intrinsic relationship between the phototautomerization and photoelectric properties is of great significance for the application of the emerging novel organic materials, such as the (bi)heterocyclic thiazolo[5,4-d]thiazole derivatives (TzTz). Here, by introducing the chemical-controlling protonation, a barrierless spontaneous rotation movement of the designed TzTz derivative (2,5-diyl-amino-thiazolo[5,4-d]thiazole, DA-TzTz) was ensured through the facilitation of the excited-state intramolecular proton transfer (ESIPT) triggered twisted intramolecular charge transfer (TICT) process by the enhancement of the intramolecular hydrogen bonds, steric hindrance effect, and conjugative effect. It is further verified that the hetero S atoms could mostly effect the proton accepting ability of -N═ through comparing with the influences to the intramolecular H-bond between the protonated/nonprotonated amino groups and the -N═ atoms brought by the replacement of them with N or O atoms. As a result, the dissociation and rearrangement of the π conjugation in DA-TzTz accompanying with the variation of the optoelectronic characteristics was benefited from the establishment of the preferential charge-transfer and separation. We expect this tentative study could establish a new concept of designing an efficient charge-transfer and separation method, paving the way for the development of the TzTz derivatives and other optoelectronic organic materials.

Different competition mechanism between ESPT and TICT process regulated by protic and aprotic solvent in DHP

In this study, we adopt density functional theory and time-dependent density functional theory (DFT/TDDFT) methods to compare and analyze the disparate competing mechanisms of excited state proton transfer (ESPT) and twisted intramolecular charge transfer (TICT) process of 2-(4′-diethylamino-2′-hydroxyphenyl)-1H-imidazo-[4,5-b] pyridine (DHP) in protic and aprotic solvent. The results show that the DHP molecule undergoes excited state intramolecular proton transfer (ESIPT) in aprotic solvent ether. Differently, ESIPT is effectively inhibited in protic solvent methanol, whereas the coupling process of excited state double proton transfer (ESDPT) and TICT occurs. Combined with the analysis of potential energy surfaces, we clarify that DHP molecule in ether is more inclined to the channel of TICT → ESIPT → reverse TICT process to implement the ESIPT process. In DHP-MeOH complex, we confirm that the significant redshift phenomenon of fluorescence spectra observed in the experiment is attributed to the ESDPT induced TICT process. Our work offers a new avenue for switching ESPT and TICT competing mechanisms through protic and aprotic solvent, and considerably help the synthesis and development of highly efficient molecular photoswitch.

An Activatable NIR-II Fluorescent Reporter for In Vivo Imaging of Amyloid-β Plaques.

Fluorescence imaging in the second near-infrared (NIR-II) window holds great promise for in vivo visualization of amyloid-β (Aβ) pathology, which can facilitate characterization and deep understanding of Alzheimer's disease (AD); however, it has been rarely exploited. Herein, we report the development of NIR-II fluorescent reporters with a donor-π-acceptor (D-π-A) architecture for specific detection of Aβ plaques in AD-model mice. Among all the designed probes, DMP2 exhibits the highest affinity to Aβ fibrils and can specifically activate its NIR-II fluorescence after binding to Aβ fibrils via suppressed twisted intramolecular charge transfer (TICT) effect. With suitable lipophilicity for ideal blood-brain barrier (BBB) penetrability and deep-tissue penetration of NIR-II fluorescence, DMP2 possesses specific detection of Aβ plaques in in vivo AD-model mice. Thus, this study presents a potential agent for non-invasive imaging of Aβ plaques and deep deciphering of AD progression.

An Activatable NIR‐II Fluorescent Reporter for In Vivo Imaging of Amyloid‐β Plaques

AbstractFluorescence imaging in the second near‐infrared (NIR‐II) window holds great promise for in vivo visualization of amyloid‐β (Aβ) pathology, which can facilitate characterization and deep understanding of Alzheimer's disease (AD); however, it has been rarely exploited. Herein, we report the development of NIR‐II fluorescent reporters with a donor‐π‐acceptor (D‐π‐A) architecture for specific detection of Aβ plaques in AD‐model mice. Among all the designed probes, DMP2 exhibits the highest affinity to Aβ fibrils and can specifically activate its NIR‐II fluorescence after binding to Aβ fibrils via suppressed twisted intramolecular charge transfer (TICT) effect. With suitable lipophilicity for ideal blood–brain barrier (BBB) penetrability and deep‐tissue penetration of NIR‐II fluorescence, DMP2 possesses specific detection of Aβ plaques in in vivo AD‐model mice. Thus, this study presents a potential agent for non‐invasive imaging of Aβ plaques and deep deciphering of AD progression.

Solvent-Controlled Photoswitching of Azobenzene: An Excited State Shuttle.

Light controlled excited state trans-cis isomerization process is a key to the development of conversion of light energy to mechanical motion at the molecular level. Considerable efforts have been made in tuning the isomerization process with electron donor and acceptor substituents by altering the excited state reaction coordinate. Here, we report a two novel push-pull series of para-diethylamino (DEA) and diphenylamino (DPA) substituted (E)-4'-((4-(diethylamino)phenyl)diazenyl)-N,N-diphenyl-[1,1'-biphenyl]-4-amine (1) and (E)-4'-((4-(diphenylamino)phenyl)diazenyl)-N,N-diphenyl-[1,1'-biphenyl]-4-amine (2). Compound 1 and 2 undergoes both photochemical and photophysical excited state deactivation pathways which can be controlled by varying the solvent polarity. These structural motifs of 1 and 2 would undergo torsional motions upon excitation to exhibit either trans → cis photoisomerization or to form a twisted intramolecular charge transfer state and both the process originates from the same excited state and competes with each other. Thus, alternations in the surrounding environment such as solvent polarity, solution viscosity, and protonation were employed to understand the preferential excited state deactivation pathway and thereby these systems could be employed as a new class of azobenzene-based luminescent photochromic molecules. For instance, in nonpolar solvent, toluene photoisomerization is preferred over TICT, but polar solvent, ethanol preferentially stabilizes the TICT state by virtue of N-C rotation which renders the energy barrier unfavourable for photoisomerization. The photostationary state of 1 in toluene is predominantly the Z isomer, whereas in ethanol E isomer is nearly two-fold higher than the Z isomer. These feature sets up a new approach towards the construction of multinary molecular switches and subsequent development in diverse fields.

TICT compounds by design: comparison of two naphthalimide-π-dimethylaniline conjugates of different lengths and ground state geometries.

Two new twisted intramolecular charge transfer (TICT) donor-π-acceptor compounds were designed by combining a well-known electron acceptor naphthalimide unit with a classic electron donor dimethylaniline through two types of different rigid linkers. The combined steady-state and time-resolved spectroscopy of molecules in solvents of different polarities in comparison to solid-state solvation experiments of doped polymer matrixes of different polarities allowed distinguishing between solvation and conformation determined processes. The photophysical measurements revealed that non-polar solutions possess high fluorescence quantum yields of up to 70% which is a property of pre-twisted/planar molecules in the excited charge transfer (CT) states. The increase of polarity allows tuning the Stokes shift through all the visible wavelength range up to 8601 cm-1 which is accompanied by a three orders of magnitude drop of fluorescence quantum yields. This is a result of the emerged TICT states as dimethylaniline twists to a perpendicular position against the naphthalimide core. The TICT reaction of molecules enables an additional non-radiative excitation decay channel, which is not present if the twisting is forbidden in a rigid polymer matrix. Transient absorption spectroscopy was employed to visualize the excited state dynamics and to obtain the excited state reaction constants, revealing that TICT may occur from both the Franck-Condon region and the solvated pre-twisted/planar CT states. Both molecules undergo the same photophysical processes, however, a longer linker and thus a higher excited state dipole moment determines the faster excited state reactions.

Molecular torsion controls the excited state relaxation pathways of multibranched tetraphenylpyrazines: effect of substitution of morpholine vs. phenoxazine.

Multibranched donor-acceptor derivatives exhibiting desirable photophysical properties are efficiently used in optoelectronic devices, in which the excited state relaxation dynamics of the derivatives control the efficiency of the devices. Here, the effect of intramolecular torsion on the excited state relaxation dynamics of tetraphenylpyrazine (TPP) derivatives in non-polar (toluene) and polar (THF) solvents is investigated by substituting the electron donor of morpholine (TPP-4MOP) and phenoxazine (TPP-4PHO) leading to the planar and twisted configurations, respectively, using femtosecond and nanosecond transient absorption spectroscopy. In the steady state, TPP-4MOP showed feeble emission (ΦF ∼0.03) due to the weak donor by the delocalization of electron density supported by theoretical optimization. The TPP-4PHO exhibited strong emission (ΦF ∼0.18) in toluene compared to that in THF, in which it showed a large Stokes shift (∼9691 cm-1) with low fluorescence quantum yield (ΦF ∼0.01). The observation of large Stokes shifts, inherent nature and theoretical calculations of TPP-4PHO suggest the twisting of the dihedral angle between tetraphenylpyrazine and phenoxazine in the excited state leading to the twisted intramolecular charge transfer state (TICT). The femtosecond and nanosecond transient absorption and picosecond time-resolved emission spectra of TPP-4PHO revealed the signature of the existence of both the partial TICT and TICT states in THF leading to the triplet state. Whereas in the case of TPP-4MOP, the transient absorption spectra showed the formation of the triplet state from the local excited state without the involvement of the TICT state. Aggregation studies of TPP-4PHO in a THF and water mixture reflect the elimination of the TICT state by the restriction of intramolecular torsion in the aggregates leading to an increase of 12-fold of the fluorescence intensity along with shifting of the maximum towards the blue region. These studies revealed that the excited state relaxation pathways of the derivatives are controlled by polarity-dependent torsional motion.

The investigation of the ultrafast excited state deactivation mechanisms for coumarin 307 in different solvents.

The intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) processes of coumarin 307 (C307) in different solvents were investigated by performing steady-state/time-resolved transient absorption spectroscopic and steady-state photoluminescence spectroscopic characterizations in combination with time-dependent density functional theoretical calculation (TDDFT). The study unveiled the remarkable influence of solvent polarity and the strength of intermolecular hydrogen bonds formed between the solutes and solvents on the relaxation dynamics of the electronic excited state. Significantly, the emergence of the TICT state was observed in polar solvents, specifically dimethylformamide (DMF) and dimethyl sulfoxidemethanol (DMSO), owing to their inherent polarity as well as the enhanced intermolecular hydrogen bonding interactions. Interestingly, even in a weak polar solvent such as methanol (MeOH), the TICT state was also observed due to the intensified hydrogen bonding effects. Conversely, nonpolar solvents, exemplified by 1,4-dioxane (Diox), resulted in the stabilization of the ICT state due to the augmented N-H⋯O hydrogen bonding interactions. The experimental findings were corroborated by the computational calculations, thus ensuring the reliability of the conclusions drawn. Furthermore, schematic diagrams were presented to illustrate the mechanisms underlying the excited-state deactivation. Overall, this investigation contributes valuable mechanistic insights and provides a comprehensive understanding of the photochemical and photophysical properties exhibited by coumarin dyes.

A dual-mode probe based on AIE and TICT effects for the detection of the hypochlorite anion and its bioimaging in living cells.

Based on aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT) mechanisms, a fluorescent probe SWJT-12 for the detection of ClO- was designed by using the CN bond as a reactive group. This synthesized probe can react with ClO- in a high aqueous phase, and it shows a large Stokes shift (144 nm) and low biological toxicity. Its limit of detection was calculated to be 0.28 μM. Furthermore, SWJT-12 was successfully used for ratiometric imaging of the exogenous hypochlorite anion in living cells.

Solvatochromic behaviour of cyclic dithioether-functionalized triphenylamine ligands and their mechano-responsive Cu(I) coordination polymers.

Cu(I)-based coordination polymers (CPs) are known as efficient emissive materials providing an eco-friendly and cost-effective platform for the development of various functional materials and sensors. In addition to the nature of the metal center, organic ligands also play a crucial role in controlling the emissive properties of coordination polymers. Herein, we report on the synthesis of dithiane- and dithiolane-substituted triphenylamine ligands L1 and L2. These ligands were found to be emissive both in the solid state and in solution. In addition, these ligands exhibit solvatochromic behaviour due to the twisted intramolecular charge transfer (TICT) phenomenon. Next, coordination behaviour of these ligands was explored with Cu(I)X salts (X = Br and Cl) and four new 1D coordination polymers [{Cu(μ2-X)2Cu}(μ2-L)]n, CP1 (X = Br, L = L1), CP2 (X = Cl, L = L1), CP3 (X = Br, L = L2), and CP4 (X = Cl, L = L2) were synthesized and crystallographically characterized. The emission behaviour of all the CPs suggests ligand-centered transitions. On mechanical grinding, emission maxima (λem) for CP1 and CP2 were blue-shifted, whereas for CP3 and CP4 red-shifts were observed. All CPs were found to emit at 448 nm with increased intensity after grinding. It is supposed that grinding is responsible for a change in the spatial arrangement (dihedral angles) of the phenyl groups of triphenylamine, causing the observed emission shifts. Furthermore, the higher emission intensity after grinding suggests the occurrence of a similar phenomenon as an aggregation-induced quenching in these CPs.

An ESIPT-based AIE fluorescent probe to visualize mitochondrial hydrogen peroxide and its application in living cells and rheumatoid arthritis.

As a chronic inflammatory disease, rheumatoid arthritis (RA) can cause progressive damage to joints and various organs. Hydrogen peroxide plays a significant role in the pathogenesis and progression of RA and thus serves as a biomarker for diagnosing this disease. Although fluorescent probes have emerged as promising tools for detecting H2O2, most available ones suffer from the aggregation-caused quenching (ACQ) effect, short-wavelength emission, low sensitivity, and poor water solubility. Herein, a new type of "turn-on" AIE probe based on excited state intramolecular proton transfer (ESIPT) was developed, with phenylboronic acid pinacol ester-appended quinolinium as the H2O2 recognition site, which is in the quenched state due to the twisted intramolecular charge transfer (TICT) effect. The probe HTQ-R exhibits good water solubility, high sensitivity, a low detection limit (210 nM), rapid response ability, and good biocompatibility towards hydrogen peroxide, and has shown the ability to accurately target mitochondria. Furthermore, HTQ-R was successfully used to detect exogenous and endogenous hydrogen peroxide in living cells, which enabled real-time monitoring of H2O2 in RA mice, demonstrating its potential significance in the diagnosis and treatment of RA.

Caffeic acid, a natural extract, as an activatable molecular probe for viscosity detection in a liquid system.

Liquids, functioning as nutrients and energy systems, regulate various functions during storage programs. Microenvironmental viscosity is one of the most important physical parameters associated with the extent of deterioration, and it is crucial to monitor the mutation of viscosity at a molecular level. Herein, we utilized caffeic acid (CaC), a natural product extracted from thistles, as a molecular probe for viscosity sensing. CaC contains phenol hydroxyl (electron-donor) and carboxyl (electron-acceptor) groups, with both moieties connected by conjugated single and double bonds, forming a typical twisted intramolecular charge transfer system. The fluorescent probe CaC, obtained from a natural product without any chemical processing, exhibits high sensitivity (x = 0.43) toward viscosity, with an obvious visualized turn-on signal. Moreover, it displays good photostability, selectivity, and wide universality in commercial liquids. Utilizing CaC, we have successfully visualized viscosity enhancement during the spoilage process, with a positive correlation between the degree of liquid spoilage and microenvironmental viscosity. Thus, this study will provide a convenient and efficient molecular probe for food safety inspection across the boundaries of traditional biological applications.

Achieving two-photon fluorescence bioimaging and photodynamic therapy for D–A conjugated polymers through manipulating twisted intramolecular charge transfer

Two-photon fluorescence bioimaging holds immense promise for deep tissue imaging.

A fluorescent probe for imaging nitroreductase with signal amplification in high-viscosity environments.

Herein, we developed a fluorescent probe ENBT for in vitro detection of nitroreductase (NTR) as well as imaging intracellular NTR. ENBT itself is non-fluorescent and it could be catalyzed by NTR to generate a viscosity-sensitive fluorophore EBT. The fluorescence intensity of EBT could be further enhanced in cancer cells with relatively high viscosity due to the inhibition of the twisted intramolecular charge transfer effect. The probe ENBT has a good response to NTR with a detection limit of 36.8 ng mL-1, and EBT has a good response to viscosity. Furthermore, different concentrations of NTR (0-1.4 μg mL-1) were used to react with the probe and the reaction systems were subjected to different viscosity solutions, and the fluorescence signals of the products in the viscosity range of 45.86-163.60 cP were increased up to 1.69-fold. ENBT was successfully used to image NTR in cells under different hypoxic conditions as well as in Staphylococcus aureus. Finally, lipopolysaccharide was added to stimulate an increase in cellular viscosity after ENBT was catalyzed by intracellular NTR into EBT, and the fluorescence signals were observed to increase by 1.72-fold. The signal amplification capability gives ENBT higher sensitivity and immunity to interference. Moreover, it has the advantages of mitochondrial targeting, large Stokes shift (190 nm), high selectivity, and can be easily synthesized.

A mitochondria-targeted ratiometric NIR fluorescent probe for simultaneously monitoring viscosity and ONOO− based on two different channels in living HepG2 cells

Mitochondrial viscosity and ONOO− are involved in various pathological and physiological processes. Abnormal viscosity or irregular ONOO− concentration would disrupt the normal function of cells. Hence, we skillfully designed and synthesized a dual-responsive probe Mito-HC-TZ for the simultaneous detection of ONOO− and viscosity by different channels. 3-ethylbenzothiazolium was acted as fluorescent rotor to regulate the twisted intramolecular charge transfer (TICT) process; the C = C of 3-ethylbenzothiazolium linked to the xanthene core could be easily broken by ONOO−. Thus, the probe responded to viscosity and ONOO− by red and orange fluorescence channels, respectively. Mito-HC-TZ had high selectivity, low cytotoxicity and wide range of pH values. The results of cell imaging experiments showed the probe could be used to respectively monitor the viscosity and ONOO− level in HepG2 cells.

Construction of a TICT-AIE-Integrated Unimolecular Platform for Imaging Lipid Droplet-Mitochondrion Interactions in Live Cells and In Vivo.

Inter-organelle interactions play a vital role in diverse biological processes. Thus, chemical tools are highly desirable for understanding the spatiotemporal dynamic interplay among organelles in live cells and in vivo. However, designing such tools is still a great challenge due to the lack of universal design strategies. To break this bottleneck, herein, a novel unimolecular platform integrating the twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) dual mechanisms was proposed. As a proof of concept, two organelles, lipid droplets (LDs) and mitochondria, were selected as models. Also, the first TICT-AIE integration molecule, BETA-1, was designed for simultaneous and dual-color imaging of LDs and mitochondria. BETA-1 can simultaneously target LDs and mitochondria due to its lipophilicity and cationic structure and emit cyan fluorescence in LDs and red fluorescence in mitochondria. Using BETA-1, for the first time, we obtained long-term tracking of dynamic LD-mitochondrion interactions and identified several impressive types of dynamic interactions between these two organelles. More importantly, the increase in LD-mitochondrion interactions during ferroptosis was revealed with BETA-1, suggesting that intervening in the LD-mitochondrion interactions may modulate this cell death. BETA-1 was also successfully applied for in vivo imaging of LD-mitochondrion interactions in C. elegans. This study not only provides an effective tool for uncovering LD-mitochondrion interactions and deciphering related biological processes but also sheds light on the design of new probes with an integrated TICT-AIE mechanism for imaging of inter-organelle interactions.

A novel 1,8-naphthalimide-based fluorescent chemosensor for the detection of HSA in living cells.

Human serum albumin (HSA) is an essential protein for maintaining human health. Accurate detection and quantification of HSA are of great significance for disease diagnosis and biochemical research. Here, a new HSA fluorescent probe BNPE based on the 1,8-naphthalimide fluorophore was designed and synthesized. The probe could recognize HSA through a twisted intramolecular charge transfer mechanism, effectively avoid the interference of most substances, and realize HSA fluorescence imaging in living cells.

Phototheranostics for NIR fluorescence image guided PDT/PTT with extended conjugation and enhanced TICT

Introducing donor and acceptor into conjugated system can facilitate the intersystem crossing (ISC) rate to increase the generation of ROS. Twisted intramolecular charge transfer (TICT) state could favor enhance the nonradiative transition and photothermal conversion efficiency (PCE). Herein, diketopyrrolopyrrole (DPP) core functionalized benzene (PDDP), thiophene (TDPP), triphenylamine-conjugated benzene (TPA-PDDP) and thiophene (TPA-TDPP) derivatives were designed and synthesized. Electrochemistry experiments revealed the heavy atom effect and the introduction of triphenylamine reduced the energy level of TPA-TDPP and improved the ability to generate 1O2 (1O2 QY = 50%). In addition, in the aggregated state, introduction of thiophene, triphenylamine, and long alkyl chains promoted the twisting effect, preventing the intermolecular π-π interaction and enhancing the PCE of TPA-TDPP (38.7%). In vivo fluorescence imaging showed that TPA-TDPP NPs can target the tumor site with the enhanced permeability and retention (EPR) effect and presented excellent synergistic photodynamic/photothermal therapy.