Intramolecular Charge Transfer Mechanism Research Articles

The Intramolecular Charge Transfer Mechanism by Which Chiral Self-Assembled H8-BINOL Vesicles Enantioselectively Recognize Amino Alcohols

The chiral H8-BINOL derivatives R-1 and R-2 were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the enantioselective recognition of R/S-2-amino-1-phenylethanol. In addition, R-1 is much more effective than R-2. Scanning electron microscope images and X-ray analyses show that R-1 can form supramolecular vesicles through the self-assembly effect of the π-π force and strong hydrogen bonding. As determined via analysis, the fluorescence of the probe was significantly enhanced by mixing a small amount of S-2-amino-1-phenylethanol into R-1, with a redshift of 38 nm, whereas no significant fluorescence response was observed in R-2-amino-1-phenylethanol. The enantioselective identification of S-2-amino-1-phenylethanol by the probe R-1 was further investigated through nuclear magnetic titration and fluorescence kinetic experiments and DFT calculations. The results showed that this mechanism was not only a simple reactive probe but also realized object recognition through an ICT mechanism. As the intramolecular hydrogen bond activated the carbonyl group on the probe R-1, the carbonyl carbon atom became positively charged. As a strong nucleophile, the amino group of S-2-amino-1-phenylethanol first transferred the amino electrons to a carbonyl carbocation, resulting in a significantly enhanced fluorescence of the probe R-1 and a 38 nm redshift. Similarly, S-2-amino-1-phenylethanol alone caused severe damage to the self-assembled vesicle structure of the probe molecule itself due to its spatial structure, which made R-1 highly enantioselective towards it.

Swift and quantitative naked-eye detection of cyanide: A dual-mode approach using an ICT-based colorimetric and ratiometric fluorescent chemodosimeter

A chemodosimeter (1) based on dicyanovinyl with a strong intramolecular charge transfer (ICT) mechanism has been devised for the selective and sensitive detection of cyanide (CN−) in a tetrahydrofuran aqueous solution. In polar solvents, chemodosimeter 1 exhibits robust ICT-induced emission; however, in the solid state, its fluorescence weakens owing to the formation of molecular aggregates prompted by intermolecular π–π interactions. The colorimetric and ratiometric fluorescent changes observed in the chemodosimeter upon exposure to CN− result from the incorporation of CN− at the β-conjugated site of the dicyanovinyl moiety of chemodosimeter 1, effectively hindering the ICT process. This alteration is supported by 1H NMR titration experiments and density functional theory calculations, which corroborate the cyanide-induced ICT on–off switching mechanism. The detection limit of chemodosimeter 1 (5.8 × 10−7 M) for CN− falls below the maximum allowable level of cyanide in drinking water (1.9 × 10−6 M), as established by the World Health Organization. Test strips utilizing chemodosimeter 1 offer a potential solution for swift and quantitative naked-eye detection of CN− in real-time scenarios. Moreover, chemodosimeter 1 was effectively employed for detecting cyanide in actual environmental water samples.

A near-infrared fluorescent probe with thiadiazole unit as key skeleton for ICT and ESIPT mechanism and effective detection of Cu2+

Fluorescent probe L-I was synthesized to demonstrate that 1,3,4-thiadiazole is an attractive moiety and could be utilized as positive hydrogen bond acceptor for excited state intramolecular proton transfer (ESIPT) processes, guider of electrons movement for intramolecular charge transfer (ICT) process and identify group for mental ions. Furthermore, dicyanoisophorone framework was employed to improve the fluorescence characteristics and near-infrared (NIR) fluorescent emission at 695 nm accompanied by a Stoke's shift as large as 260 nm was obtained. L-I could selectively detect Cu2+ over other analytes taking advantages of high sensitivity, fast response within 30 s and low detection limit (0.026 μM). More important, L-I exhibited good performance for detection of Cu2+ in actual water samples, food products, traditional Chinese medicine and for cell imaging which demonstrates practical significance in the fields of environmental monitor, food safety and biotechnology.

Preparation of Light‐responsive Unnatural RNA Bases via a Chromogenic Morita‐Baylis‐Hillman Adduct Path

RNA‐based tools for biological and pharmacological research are raising an increasing interest. Among these, RNA aptamers whose biological activity can be controlled via illumination with specific wavelengths represent an important target. Here, we report on a proof‐of‐principle study supporting the viability of a systematic use of Morita‐Baylis‐Hillman adducts (MBHAs) for the synthesis of light‐responsive RNA building blocks. Accordingly, a specific acetylated MBHA derivative was employed in the functionalization of the four natural RNA bases as well as two unnatural bases (5‐aminomethyl uracil and 5‐methylaminomethyl uracil). The results reveal a highly selective functionalization for both unnatural bases. The conjugation products were then investigated spectroscopically, photochemically and computationally. It is shown that when a single light‐responsive unit is present (i.e. when using 5‐methylaminomethyl uracil), the generated unnatural uracil behaves like a cinnamic‐framework‐based photochemical switch that isomerizes upon illumination through a biomimetic light‐induced intramolecular charge transfer mechanism driving a barrierless and, therefore, ultrafast reaction path.

Design and Screening of Fluorescent Probes Based upon Hemicyanine Dyes for Monitoring Mitochondrial Viscosity in Living Cells.

Viscosity, at the subcellular level, plays a crucial role as a physicochemical factor affecting microenvironment homeostasis. Abnormal changes in mitochondrial viscosity often lead to various diseases in the organism. Based on the twisted intramolecular charge transfer mechanism, four hemicyanine dye fluorescent probes (HT-SA, HT-SA-S, HT-Bzh, and HT-NA) were designed and synthesized for viscosity response. The single bond between the nitrogen-containing heterocycle and the carbon-carbon double in the structure of the probe bond served as the viscosity response site. Finally, the probe HT-Bzh was screened as the optimal mitochondrial viscosity probe according to its responsiveness, targeting, and interference resistance. The fluorescence intensity of the probe HT-Bzh increased 22-fold when the viscosity was increased from 13.75 to 811.2 cP. In summary, all four viscosity probes we have developed can be used in different applications depending on the external environment, providing a valuable reference for the design of potential tools to address viscosity monitoring in biological systems.

A highly sensitive ratiometric fluorescent probe for detecting HSO3−/SO32− and viscosity change based on FRET/TICT mechanism

BackgroundSulfur dioxide (SO2) is a significant gas signaling molecule in organisms, and viscosity is a crucial parameter of the cellular microenvironment. They are both involved in regulating many physiological processes in the human body. However, abnormalities in SO2 and viscosity levels are associated with various diseases, such as cardiovascular disease, lung cancer, respiratory diseases, neurological disorders, diabetes and Alzheimer's disease. Hence, it is essential to explore novel and efficient fluorescent probes for simultaneously monitoring SO2 and viscosity in organisms. ResultsWe selected quinolinium salt with good stability, high fluorescence intensity, good solubility and low cytotoxicity as the fluorophore and developed a highly sensitive ratiometric probe QQD to identify SO2 and viscosity changes based on Förster resonance energy transfer/twisted intramolecular charge transfer (FRET/TICT) mechanism. Excitingly, compared with other probes for SO2 detection, QQD not only identified HSO3−/SO32− with a large Stokes shift (218 nm), low detection limit (1.87 μM), good selectivity, high energy transfer efficiency (92 %) and wide recognition range (1.87–200 μM), but also identified viscosity with a 26-fold fluorescence enhancement and good linearity. Crucially, QQD was applied to detect HSO3−/SO32− and viscosity in actual water and food samples. In addition, QQD had low toxicity and good photostability for imaging HSO3−/SO32− and viscosity in cells. These results confirmed the feasibility and reliability of QQD for HSO3−/SO32− and viscosity imaging and environmental detection. SignificanceWe reported a unique ratiometric probe QQD for detecting HSO3−/SO32− and viscosity based on the quinolinium skeleton. In addition to detecting HSO3−/SO32− and viscosity change in actual water and food samples, QQD could also monitor the variations of HSO3−/SO32− and viscosity in cells, which provided an experimental basis for further exploration of the role of SO2 derivatives and viscosity in biological systems.

An efficient lipid droplet-targeted fluorescent probe for detection of intracellular viscosity.

Lipid droplet, an intracellular lipid reservoir, is vital for energy metabolism and signal transmission in cells. The viscosity directly affects the metabolism of lipid droplets, and the abnormal viscosity is associated with the occurrence and development of various diseases. Therefore, it is indispensable to develop techniques that can detect viscosity changes in intracellular lipid droplets. Based on twisted intramolecular charge transfer (TICT) mechanism, a novel small-molecule lipid droplet-targeted viscosity fluorescence probe PPF-1 was designed. The probe was easy to synthesize, it had a large Stokes shift, stable optical properties, and low bio-toxicity. Compared to being in methanol solution, the fluorescence intensity of PPF-1 in glycerol solution was increased 26.7-fold, and PPF-1 showed excellent ability to target lipid droplets. Thus, the probe PPF-1 could provide an effective means of detecting viscosity changes of lipid droplets and was of great value for physiological diagnosis of related diseases, pathological analysis, and medical research.

A Near-Infrared Fluorescent Probe for the Rapid Detection of Nitroxyl in Living Cells.

Nitroxyl (HNO) plays an important role in various physiological activities. It has the potential to be used as a treatment for certain diseases such as alcohol poisoning, acute hypertension, and atherosclerosis. However, traditional methods for detecting HNO are challenging due to its rapid polymerization and elimination into N2O. Therefore, it is crucial to establish direct and effective HNO detection methods to comprehend these physiological processes better. In this study, a new near-infrared fluorescent probe called HXM-P based on the intramolecular charge transfer (ICT) mechanism was designed and synthesized. This probe employs 2-((6-hydroxy-2,3dihydro-1H-xanthen-4-yl)methylene)malononitrile as a fluorophore and 2-(diphenylphosphine) benzoate as a recognition group. The results showed that probe HXM-P can detect HNO with high sensitivity (1.07 × 10- 8 M). A good linear correlation was observed between the fluorescence intensities at 640nm and the concentrations of HNO in the range of 0-80 µM (R2 = 0.997). Moreover, probe HXM-P exhibited a rapid response rate (within 15s) toward HNO, and the fluorescent intensity reached a plateau within 5min, making it easier to track the highly reactive and short-lived HNO in living systems. Additionally, HXM-P was successfully employed for imaging HNO in HepG2 cells.

A detailed theoretical investigation on intramolecular charge transfer mechanism of primary, secondary, and tertiary p-amino substituted benzaldehyde

This article reports a detailed theoretical investigation on dual fluorescence properties of p-amino substituted benzaldehyde molecules by taking specifically p-N,N-dimethylaminobenzaldehyde (3° PABA), p-N-methylaminobenzaldehyde (2° PABA), and p-aminobenzaldehyde (1° PABA) molecules. The calculations are performed in gas phase as well as in butanol (BuOH) and dichloromethane (DCM) solvents. Twisted intramolecular charge transfer emission property is particularly looked at by scanning the potential energy curves as a function of -NR2 (R = H/CH3) rotation (twisting) angle. The results suggest that there are dual emission possibilities for 3° and 2° PABA molecules. Experimental validation is available for the former but not for the latter. 1° PABA, on the other hand, does not show any possibility of dual fluorescence except in BuOH. The theoretical absorption and emission spectra are also calculated and compared with experiment where it is available, and they are in close correlation. Excited state molecular dynamics simulations show that for 3° PABA, the molecule reaches to the 90° twisting angle and stays there with a probability higher than the same probability for 2° PABA. 1° PABA, on the other hand, had showed variations in the twisting angle from 0° to above 100°, but no evidence of this molecule to have considerable lifetime at 90° twisting angle.

Development of an innovative turn-on fluorescent probe for targeted in-vivo detection of nitric oxide in rat brain extracts as a biomarker for migraine disease

Nitric oxide (NO) is one of the reactive nitrogen species (RNS) that has been proposed to be a key signaling molecule in migraine. Migraine is a neurological disorder that is linked to irregular NO levels, which necessitates precise NO quantification for effective diagnosis and treatment. This work introduces a novel fluorescent probe, 2,3-diaminonaphthelene-1,4-dione (DAND), which was designed and synthesized to selectively detect NO in-vitro and in-vivo as a migraine biomarker. DAND boasts high aqueous solubility, biocompatibility, and facile synthesis, which enable highly selective and sensitive detection of NO under physiological conditions. NO reacts with diamine moieties (recognition sites) of DAND, results in the formation of a highly fluorescent product (DAND-NO) known as 1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione at λem 450 nm. The fluorescence turn-on sensing mechanism operates through an intramolecular charge transfer (ICT) mechanism. To maximize fluorescence signal intensity, parameters including DAND concentration, reaction temperature, reaction time and pH were systematically optimized for sensitive and precise NO determination. The enhanced detection capability (LOD = 0.08 μmol L−1) and high selectivity of the probe make it a promising tool for NO detection in brain tissue homogenates. This demonstrates the potential diagnostic value of the probe for individuals suffering from migraine. Furthermore, this study sheds light on the potential role of zolmitriptan (ZOLM), an antimigraine medication, in modulating NO levels in the brain of rats with nitroglycerin-induced migraine, emphasizing its significant impact on reducing NO levels. The obtained results could have significant implications for understanding how ZOLM affects NO levels and may aid in the development of more targeted and effective migraine treatment strategies.

Synthesis, optical properties, DNA, β-cyclodextrin interaction, hydrogen isotope sensor and computational study of new enantiopure isoxazolidine derivative (ISoXD)

A novel isoxazolidine derivative (ISoXD) dye was successfully synthesized and comprehensively characterized. In this study, we conducted a thorough examination of its various properties, including optical characteristics, interactions with DNA and β-cyclodextrin (β-CD), molecular docking, molecular dynamic simulation, and density functional theory (DFT) calculations. Our investigation encompassed a systematic analysis of the absorption and emission spectra of ISoXD in diverse solvents. The observed variations in the spectroscopic data were attributed to the specific solvent's capacity to engage in hydrogen bonding interactions. Remarkably, the most pronounced intensities were observed in glycol, which can establish many hydrogen bonds with ISoXD.Furthermore, our study revealed a significant distinction in the fluorescence behavior of ISoXD when subjected to different solvents, particularly between CHCl3 and CDCl3. Moreover, we explored the fluorescence intensity of the ISoXD complex in the presence of various metals, both in ethanol and water. The ISoXD complex exhibited a substantial increase of fluorescence upon interaction with different metal ions. The utilization of DFT calculations allowed us to propose an intramolecular charge transfer (ICT) mechanism as a plausible explanation for this quenching phenomenon. The interaction of ISoXD with DNA and β-CD was studied using absorption spectra. The binding constant (K) and the standard Gibbs free energy change (ΔGo) for the interaction between DNA and β-CD with ISoXD were determined. In docking study, ISoXD exhibited significant docking scores (−6.511) and MM-GBSA binding free energies (−66.27 kcal/mol) within the PARP-1 binding cavity. Its binding pattern closely resembles to the co-crystal ligand veliparib, and during a 100ns MD simulation, ISoXD displayed strong stability and formed robust hydrogen bonds with key amino acids. These findings suggest ISoXD's potential as a PARP-1 inhibitor for further investigation in therapeutic development.

Ethyl 3-aminobenzo[b]thiophene-2-carboxylate Derived Ratiometric Schiff Base Fluorescent Sensor for the Recognition of In3+ and Pb2.

An ethyl 3-aminobenzo[b]thiophene-2-carboxylate derived ratiometric Schiff base fluorescent sensor R was devised and synthesized. R exhibited a highly sensitive and selective ratiometric response to In3+ in DMF/H2O tris buffer solution. R exhibited a colorimetric/fluorescent dual-channel response to In3+. More importantly, R can distinguish In3+ from Ga3+ and Al3+ in less than 5min. R exhibited a good linear correlation with the concentration of In3+ in the 5-25μM range and the limit of detection for In3+ was found to be 8.36 × 10-9M. According to the job`s plot and MS spectra, R formed a complex with In3+ at 1:2 with a complexation constant of 8.24 × 109 M2. Based on Gaussian theory calculations, the response mechanism of R to In3+ can be explained by photo-induced electron transfer (PET) and intramolecular charge transfer (ICT) mechanisms. In addition, R can be used for the detection of indium in tap water with satisfactory recoveries. Meanwhile, R displayed a linear relationship to micromolar concentrations (0-50μM) of Pb2+ and recognized Pb2+ in a ratiometric response with a detection limit of 8.3 × 10-9M.

A high-affinity fluorescent probe for human uridine-disphosphate glucuronosyltransferase 1A9 function monitoring under environmental pollutant exposure

Uridine-disphosphate glucuronosyltransferase 1A9 (UGT1A9), an important detoxification and inactivation enzyme for toxicants, regulates the exposure level of environmental pollutants in the human body and induces various toxicological consequences. However, an effective tool for high-throughput monitoring of UGT1A9 function under exposure to environmental pollutants is still lacking. In this study, 1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one (DDAO) was found to exhibit excellent specificity and high affinity towards human UGT1A9. Remarkable changes in absorption and fluorescence signals after reacting with UGT1A9 were observed, due to the intramolecular charge transfer (ICT) mechanism. Importantly, DDAO was successfully applied to monitor the biological functions of UGT1A9 in response to environmental pollutant exposure not only in microsome samples, but also in living cells by using a high-throughput screening method. Meanwhile, the identified pollutants that disturb UGT1A9 functions were found to significantly influence the exposure level and retention time of bisphenol S/bisphenol A in living cells. Furthermore, the molecular mechanism underlying the inhibition of UGT1A9 by these pollutant-derived disruptors was elucidated by molecular docking and molecular dynamics simulations. Collectively, a fluorescent probe to characterize the responses of UGT1A9 towards environmental pollutants was developed, which was beneficial for elucidating the health hazards of environmental pollutants from a new perspective.

3-Halochromones Through Oxidative α-Halogenation of Enaminones and its Photophysical Investigation: Another Case of Photo-induced Partially Aromatised Intramolecular Charge Transfer?

A versatile synthesis strategy for fluorescent 3-halo-4H-chromen-4-one derivatives is reported. The method involves the oxidative α-halogenation of enaminones performed by an efficient and sustainable oxidation system. The use of Oxone® in combination with KCl, KBr, or KI enables the preparation of 3-chloro-, 3-bromo-, or 3-iodo-4H-chromen-4-one in good to excellent yields, with great functional group tolerance where the protocol is amenable to gram-scale synthesis. The analysis of the photophysical properties of the presented 4H-chromen-4-one showed absorption in the UV region and fluorescence emission in the violet-to-cyan region with a relatively large Stokes shift. In solution, all compounds present a dual fluorescence emission, regardless of the solvent, assigned to a partially aromatised intramolecular charge transfer mechanism, considering the presence of a pseudo-aromatic ring in the chromone scaffold and the absence of the influence of substituent electronic features in optical behaviour.

A near-infrared emitting “off-on” fluorescent probe for bioimaging of Pd(Ⅱ) ions in living cells and mice

BackgroundThe surging consumption of palladium in modern industry has given rise to its accumulation in the ecosystem, posing conspicuous toxicity to aquatic organisms and human health. The investigation of palladium in biological systems is highly demanded for the in-depth understanding of its dynamics and behaviors. Fluorescence imaging serves as a powerful approach to assess palladium species in biological systems, and currently most of the sensing probes are applicable to living cells. Effective tracking of palladium species in living organisms is challenging, which requires sufficient hydrophilicity and imaging depth of the probes. ResultsBased on an intramolecular charge transfer (ICT) mechanism, a distyryl boron dipyrromethene (BODIPY) derivative (DISBDP-Pd) has been prepared for the near-infrared (NIR) fluorescence imaging of Pd2+ ions. Two additional methoxy triethylene glycol (TEG) chains could serve as flexible and hydrophilic moieties to enhance the aqueous solubility and cell permeability of the extended conjugate. Solution studies revealed that DISBDP-Pd exhibited a NIR fluorescence enhancement signal exclusively to Pd2+ ions (detection limit as low as 0.85 ppb) with negligible interference from Pd0 species and other closely related metal ions. Computational calculations have been performed to rationalize the binding mode and the mechanism of action. Fluorescence imaging assays have been conducted on A549 human non-small cell lung carcinoma cells and mouse models. Exhibiting negligible cytotoxicity, DISBDP-Pd demonstrated concentration-related fluorescence enhancement signals in response to Pd2+ ions in living cells and mice. SignificanceDISBDP-Pd exhibits advantages over many small molecule palladium probes in terms of satisfactory aqueous solubility, high sensitivity and selectivity, and biocompatible NIR emission property, which are particularly favorable for the sensing application in biological environments. The design strategy of this probe can potentially be adopted for the functionalization of other BODIPY probes implemented for NIR fluorescence bioimaging.

A benzoxazole-triphenylamine conjugated fluorogenic probe for specific detection of sarin gas mimic diethylchlorophosphate.

In this study, an excellent chromo-fluorogenic PMPA probe, (E)-4-(((4-(benzoxazole-2-yl)phenyl)imino)methyl)-N,N-diphenylamine, is introduced for the detection of sarin gas mimic diethyl chlorophosphate (DCP) in solution and gaseous phases. On adding DCP into PMPA solution in a pure DMSO and water-DMSO (4 : 1) medium, it exhibits a hypsochromic shift from yellow to colorless and from no fluorescence to highly intense blue-violet photoluminescence via the formation of a phosphorylated PMPA-DCP product due to the inhibition of intramolecular charge transfer (ICT) and photoinduced electron transfer (PET) mechanism. The sensor could detect DCP in the presence of several other notorious guest analytes with a detection limit in the μM range. Moreover, to accomplish the on-spot detection of DCP and explore the practical applicability of the probe, a paper strip-based test kit, "dip-stick" method, and, more interestingly, a real sample analysis was demonstrated in spiked soil samples.

Highly tunable bimane-based fluorescent probes: design, synthesis, and application as a selective amyloid binding dye.

Small molecule fluorescent probes are indispensable tools for a broad range of biological applications. Despite many probes being available, there is still a need for probes where photophysical properties and biological selectivity can be tuned as desired. Here, we report the rational design and synthesis of a palette of fluorescent probes based on the underexplored bimane scaffold. The newly developed probes with varied electronic properties show tunable absorption and emission in the visible region with large Stokes shifts. Probes featuring electron-donating groups exhibit rotor effects that are sensitive to polarity and viscosity by "intramolecular charge transfer" (ICT) and twisted intramolecular charge transfer (TICT) mechanisms, respectively. These properties enable their application as "turn-on" fluorescent probes to detect fibrillar aggregates of the α-synuclein (αS) protein that are a hallmark of Parkinson's disease (PD). One probe shows selective binding to αS fibrils relative to soluble proteins in cell lysates and amyloid fibrils of tau and amyloid-β. Finally, we demonstrate the diagnostic potential of the probe in selectively detecting αS fibrils amplified from PD with dementia (PDD) patient samples.

A novel ratiometric fluorescence probe based on the FRET-ICT mechanism for detecting fluoride ions and viscosity

Fluoride ion is not only important for dental health, but also a contributing factor in a variety of diseases. At the same time, fluoride ions and cell viscosity are both important to the physiological environment of mitochondria. We developed a dual-response ratiometric fluorescent probe BDF based on Förster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) mechanism for the detection of F− and viscosity. BDF has an outstanding intramolecular energy transfer efficiency of 97.7% and shows excellent performance for fluorine ion detection. In addition, when the system viscosity increases, the fluorescence emission intensity of BDF is greatly heightened, indicating the possibility of viscosity detection. Finally, based on the fluorescence properties of BDF, we used the probe to detect F− in the toothpaste sample and image exogenous fluoride ions in HeLa cells.

Engineering a highly selective leucine aminopeptidase near-infrared fluorescence probe for early diagnosis of diabetic nephropathy

Diabetic nephropathy (DN) is one of the most serious and general complications of diabetes, while schedules for prevention and treatment are unsatisfactory. Leucine aminopeptidase (LAP) as one of the biomarkers of DN is associated with glomerular and/or tubular injury. Imaging of LAP activity in DN disease model in vivo is thus beneficial for early diagnosis and prevention of DN, but such a strategy is still lacking. Herein, an enzyme-activated probe HD-LAP with a NIR fluorescence emission for specific detection of LAP activity in the DN model is designed and synthesized. HD-LAP has a significant fluorescence enhancement after reacted with LAP and shows a NIR fluorescence emission at 704 nm based on intramolecular charge transfer mechanism. Moreover, HD-LAP can be employed to image LAP activity in HK-2 and HepG2 cells. More importantly, HD-LAP is the first example to real-time image LAP in DN mice and clinical serum samples. These results demonstrated that HD-LAP is promising as a powerful tool for the research on LAP associated diabetic diseases in future.

Aryl-Modified Pentamethyl Cyanine Dyes at the C2' Position: A Tunable Platform for Activatable Photosensitizers.

Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited-state properties. Herein, a synthetic approach for attaching aryl substituents at the C2' position of the thio-pentamethine cyanine (TCy5) dye structure is reported for the first time. C2'-aryl substitution enables the regulation of both the twisted intramolecular charge transfer (TICT) and photoinduced electron transfer (PET) mechanisms to be regulated in the excited state. Modulation of these mechanisms allows the design of a nitroreductase-activatable TCy5 fluorophore for hypoxic tumor photodynamic therapy and fluorescence imaging. These C2'-aryl TCy5 dyes provide a tunable platform for engineering cyanine dyes tailored to sophisticated biological applications, such as photodynamic therapy.