Diethylamino Coumarin Research Articles

Orange-red emissive coumarin based quadrupolar dyes: Synthesis, photophysical and DFT studies

Designing and synthesized dyes with diethylamino coumarin as fixed and diethylamino coumarin, julolidine, and pyrene-based donors with dicynovinylene acceptor, the effects of donor and π-linker on linear and non-linear optical (NLO) properties were examined. Density functional theory (DFT) and time-dependent DFT were used for this investigation. Maximum absorption and emission were seen in the range of 500–547, 525–569, and 420–429 nm, as well as 576–653, 592–653, and 492–536 nm for diethylamino coumarin, julolidine, and pyrene-based dyes. A julolidine-based donor dye showed red-shifted absorption and emission properties compared to diethylamino and pyrene-based coumarin. All dyes in polar demonstrated significant viscosity sensitivity (PEG: methanol) solutions. Furthermore, above 250°C, the title dyes demonstrated good thermal stability. Additionally, the theoretical analysis suggested that dyes based on julolidine have superior linear and NLO properties in solvent phases and better CT (as determined by FMO, MEP, BLA, and BOA calculations).

Super-resolution imaging lysosome vesicles and establishing a gallbladder-visualizable zebrafish model via a fluorescence probe

Advanced probes for imaging viscous lipids microenvironment in vitro and in vivo are desirable for the study of membranous organelles and lipids traffic. Herein, a reaction-based dihydroquinoline probe (DCQ) was prepared via linking a diethylamino coumarin fluorophore with a N-methylquinoline moiety. DCQ is stable in low viscous aqueous mediums and exhibits green fluorescence, which undergoes fast autoxidation in high viscous mediums to form a fluorescent product with deep-red to near-infrared (NIR) emission, rendering the ability for dual-color imaging. Living cell imaging indicated that DCQ can effectively stain lysosomal membranes with deep-red fluorescence. Super-resolution imaging of lysosome vesicles has been achieved by DCQ and stimulated emission depletion (STED) microscopy. In addition, DCQ realizes multiple organs imaging in zebrafish, whose dual-color emission can perfectly discriminate zebrafish's yolk sac, digestive tract and gallbladder. Most importantly, DCQ has been successfully used to establish a gallbladder-visualizable zebrafish model for the evaluation of drug stress.

Effect of donor and π-spacer for non-linear optical property: Synthesis, photophysical studies, and Z-scan analysis

The impact of donor and π-spacer on linear and non-linear optical (NLO) properties was investigated by designing and synthesizing dyes having diethylamino coumarin and julolidine-based coumarin donors containing thiophene and phenyl-spacer with ethyl cyanoacrylate acceptor. Density functional theory (DFT), time-dependent DFT, and Z-scan methods were opted for this study. Diethylamino coumarin and julolidine-based coumarin dyes showed maximum absorption and emission in the range of 462–524 and 480–544, and 515–641 and 520–663 nm, respectively. A julolidine-based coumarin and thiophene spacer containing dye and diethylamino-based coumarin with phenyl spacer showed the most red-shifted and blue-shifted absorption and emission properties, respectively. All dyes showed considerable viscosity sensitivity in polar (PEG: ethanol) and non-polar (Paraffin: toluene) media. Also, the title dyes showed good thermal stability above 300 °C. Further, the theoretical investigation suggested dyes with julolidine-based coumarin and thiophene-spacer have better CT (through FMO, MEP, BLA, BOA, and QC calculations) λVert and hence showed superior linear and NLO properties in solvent phases. Lastly, the results obtained from the Z-scan method also showed similar results as revealed by the theoretical study.

Blue light emitting fluorophore for the effective detection of cyanide ion and electronic test kit development for real time measurement

This work deals with the blue light emitting fluorophore containing indolium/coumarin fused conjugated system probe JE5, for the effective detection of cyanide ion. The probe holding diethylamino coumarin unit as a donor unit and indolium as an acceptor unit that is connected by a π-conjugation. The cyanide ion sensing ability of the probe has been monitored by UV–visible and fluorescence measurement. The probe exhibits a vivid color change from deep blue to pale yellow before and after sensing cyanide ion. The color change confirmed by visual and UV–visible titration studies. Fluorescence enhancement was observed for the probe after cyanide addition. The obtained color change was due to the disconnection of ICT between the donor and acceptor unit resulting in color change with the added cyanide ion. The limit of detection of the probe JE5 found to be 1.99 μM and 0.97 nM by UV–Visible and fluorescence methods. Electronic device with proper coding data developed for the effective detection of cyanide ion. The stoichiometry of 1:1 binding between JE5 and cyanide ion was obtained.

Polarity-Dependent Twisted Intramolecular Charge Transfer in Diethylamino Coumarin Revealed by Ultrafast Spectroscopy

Twisting intramolecular charge transfer (TICT) is a common nonradiative relaxation pathway for a molecule with a flexible substituent, effectively reducing the fluorescence quantum yield (FQY) by swift twisting motions. In this work, we investigate coumarin 481 (C481) that contains a diethylamino group in solution by femtosecond transient absorption (fs-TA), femtosecond stimulated Raman spectroscopy (FSRS), and theoretical calculations, aided by coumarin 153 with conformational locking of the alkyl arms as a control sample. In different solvents with decreasing polarity, the transition energy barrier between the fluorescent state and TICT state increases, leading to an increase of the FQY. Correlating the fluorescence decay time constant with solvent polarity and viscosity parameters, the multivariable linear regression analysis indicates that the chromophore’s nonradiative relaxation pathway is affected by both hydrogen (H)-bond donating and accepting capabilities as well as dipolarity of the solvent. Results from the ground- and excited-state FSRS shed important light on structural dynamics of C481 undergoing prompt light-induced intramolecular charge transfer from the diethylamino group toward –C=O and –CF3 groups, while the excited-state C=O stretch marker band tracks initial solvation and vibrational cooling dynamics in aprotic and protic solvents (regardless of polarity) as well as H-bonding dynamics in the fluorescent state for C481 in high-polarity protic solvents like methanol. The uncovered mechanistic insights into the molecular origin for the fluorogenicity of C481 as an environment-polarity sensor substantiate the generality of ultrafast TICT state formation of flexible molecules in solution, and the site-dependent substituent(s) as an effective route to modulate the fluorescence properties for such compact, engineerable, and versatile chemosensors.

Light-Activating PROTACs in Cancer: Chemical Design, Challenges, and Applications

Nonselective cell damage remains a significant limitation of radiation therapies in cancer. Decades of successful integration of radiation therapies with other medicinal chemistry strategies significantly improved therapeutic benefits in cancer. Advancing in such technologies also led to the development of specific photopharmcology-based approaches that improved the cancer cell selectivity and provided researchers with spatiotemporal control over the degradation of highly expressed proteins in cancer (proteolysis targeting chimeras, PROTACs) using a monochrome wavelength light source. Two specific strategies that have achieved notable successes are photocage and photoswitchable PROTACs. Photocaged PROTACs require a photolabile protecting group (PPG) that, when radiated with a specific wavelength of light, irreversibly release PPG and induce protein degradation. Thus far, diethylamino coumarin for estrogen-related receptor α (ERRα), nitropiperonyloxymethyl (BRD4 bromodomain protein), and 4,5-dimethoxy-2-nitrobenzyl for (BRD4 bromodomain protein, as well as BTK kinase protein) were successfully incorporated in photocaged PROTACs. On the other hand, photoswitches of photoswitchable PROTACs act as an actual ON/OFF switch to target specific protein degradation in cancer. The ON/OFF function of photoswitches in PROTACs (as photoswitchable PROTACs) provide spatiotemporal control over protein degradation, and to an extent are correlated with their photoisomeric state (cis/trans-configuration), showcasing an application of the photochemistry concept in precision medicine. This study compiles the photoswitchable PROTACs targeted to bromodomain proteins: BRD 2, 3, and 4; kinases (BCR-ABL fusion protein, ABL); and the immunophilin FKBP12. Photocaging of PROTACs found successes in selective light-controlled degradation of kinase proteins, bromodomain-containing proteins, and estrogen receptors in cancer cells.

A coumarin-based fluorescent probe: Small but multi-signal

There remains a challenge for elegantly designing structurally simple but multi-signal fluorescence probes to visualize simultaneously various intracellular redox species and microenvironmental parameters. Herein we present such a design in the small probe COU-Mito featuring the graft of a strong electron-withdrawing 4-pyridiniumylacrylonitrile unit to an electron-donating diethylamino coumarin. The introduction of the cyano group destroys the coplanarity of the total push-pull π-conjugation system, thus the probe exhibits very weak background red fluorescence but a turn-on response to increased viscosity which restricts the rotation of the molecular rotor between the push and pull parts around a single bond. More importantly, the introduction of the cyano group together with the 4-pyridinium moiety improves significantly the electrophilicity of the carbon-carbon double bond in the probe that allows selective oxidative cleavage and nucleophilic addition on the double bond by peroxynitrite (ONOO-) and sulfur dioxide (SO2), respectively. Hence the probe, whilst superficially simple, is in fact a multifunctional probe capable of simultaneously discriminating viscosity, ONOO- and SO2 in a fashion of three sets of distinct signals: red for viscosity, green for ONOO-, and blue for SO2. The probe was successfully employed to visualize the change of mitochondrial viscosity and the fluctuation of mitochondrial ONOO- and SO2 levels in living cells and zebrafish, and to probe into their roles in the hepatotoxicity induced by acetaminophen, a widely used analgesic and antipyretic drug.

A highly selective fluorescent probe based on coumarin and pyrimidine hydrazide for Cu2+ ion detection

A novel diethylamino coumarin Schiff base modified with a pyrimidine-hydrazide (EDMP) was synthesized as Cu2+ fluorescent probe. Its photophysical properties and recognition ability to Cu2+ were studied by UV–Vis, fluorescence, IR and mass spectrum. Under UV light, EDMP probe showed a strong bright green fluorescence. After introducing Cu2+, the probe solution was changed from light green to orange and the maximum absorption wavelength bathochromically shifted from 445 nm to 475 nm. Meanwhile, fluorescence quenching phenomenon was observed. Fluorescence titration experiment showed that EDMP exclusively reacted with Cu2+ and the stoichiometric ratio was 1:1. The lowest detection limit was calculated to be 1.153 μM by fitting the titration curve. Additionally, DFT calculation method was utilized to analyze the action mechanism of EDMP toward Cu2+.

Design, synthesis and perception of fluorescently labeled isoprenoid cytokinins

Isoprenoid cytokinins play a number of crucial roles in the regulation of plant growth and development. To study cytokinin receptor properties in plants, we designed and prepared fluorescent derivatives of 6-[(3-methylbut-2-en-1-yl)amino]purine (N6-isopentenyladenine, iP) with several fluorescent labels attached to the C2 or N9 atom of the purine moiety via a 2- or 6-carbon linker. The fluorescent labels included dansyl (DS), fluorescein (FC), 7-nitrobenzofurazan (NBD), rhodamine B (RhoB), coumarin (Cou), 7-(diethylamino)coumarin (DEAC) and cyanine 5 dye (Cy5). All prepared compounds were screened for affinity for the Arabidopsis thaliana cytokinin receptor (CRE1/AHK4). Although the attachment of the fluorescent labels to iP via the linkers mostly disrupted binding to the receptor, several fluorescent derivatives interacted well. For this reason, three derivatives, two rhodamine B and one 4-chloro-7-nitrobenzofurazan labeled iP were tested for their interaction with CRE1/AHK4 and Zea mays cytokinin receptors in detail. We further showed that the three derivatives were able to activate transcription of cytokinin response regulator ARR5 in Arabidopsis seedlings. The activity of fluorescently labeled cytokinins was compared with corresponding 6-dimethylaminopurine fluorescently labeled negative controls. Selected rhodamine B C2-labeled compounds 17, 18 and 4-chloro-7-nitrobenzofurazan N9-labeled compound 28 and their respective negative controls (19, 20 and 29, respectively) were used for in planta staining experiments in Arabidopsis thaliana cell suspension culture using live cell confocal microscopy.

A light-triggered transmembrane porin.

Porins are ideal model systems for channel engineering. OmpG is a robust, monomeric, transmembrane β-barrel without ion selectivity. Here, we present a photocaged diethylaminocoumarin (DEACM) hybrid of OmpG. Blockage of the pore by DEACM is confirmed by reduced conductivity. An optimal effect was obtained when two bulky butyl-substituted coumarin cages were attached on the inside of the pore. Irradiation at 385 nm removed the photocages, leading to a restoration of channel conductivity.

Photolabile coumarins with improved efficiency through azetidinyl substitution.

Azetidinyl substituents have been recently used to improve the fluorescence quantum yield of several classes of fluorophores. Herein, we demonstrate that other useful photochemical processes can be modulated using this strategy. In particular, we prepared and measured the quantum yield of photorelease of a series of 7-azetidinyl-4-methyl coumarin esters and compared it to their 7-diethylamino and julolidine-fused analogues. The efficiency of the photorelease reactions of the azetidinyl-substituted compounds was 2- to 5-fold higher than the corresponding diethylamino coumarins. We investigated the origin of this effect in model fluorophores and in the photoactivatable esters, and found that H-bonding with the solvent seems to be the prominent deactivation channel inhibited upon substitution with an azetidinyl ring. We anticipate that this substitution strategy could be used to modulate other photochemical processes with applications in chemical biology, catalysis and materials science.

Synergistic effect of intramolecular charge transfer toward supramolecular pKa shift in cucurbit[7]uril encapsulated coumarin dyes.

This article presents the process and mechanism of supramolecular pKa shift in two bichromophoric coumarin laser dyes, namely, coumarin 7 (C7), (ΔpK(a) = 4.6) and coumarin 30 (C30), (ΔpK(a) = 3.0), achieved by introducing a synthetic macrocyclic receptor, cucurbit[7]uril (CB7), in aqueous media. The intramolecular charge transfer, from the diethylamino coumarin moiety toward the benzimidazolyl moiety and its protonation, even at pH ∼8, is facilitated by the interaction of the cucurbituril host in a 2:1 (CB7/dye) stoichiometric ratio. The CB7 macrocycle interacts with C7/C30 dyes in a stepwise manner with binding constants of the order of K(1) ≅10(5) M(-1), K2 ≅10(4) M(-1) for both C7 and C30 dyes. This study underlines a structure-property relationship to explain the host induced changes in the stereoelectronic distributions in the guest dyes supporting the supramolecular pK(a) shifts and is appropriately established by both experimental and theoretical considerations. On the other hand, the increased solubility (>250 times) and enhancement in fluorescence intensity (>13-fold) of the coumarin dyes in the presence of CB7 also find applications for developing aqueous dye laser systems where this supramolecular strategy will largely suppress the disadvantages of low solubility, aggregation, lower emission, or low stability of the dye in aqueous medium.

Spectral Evolution of a Photochemical Protecting Group for Orthogonal Two-Color Uncaging with Visible Light

Caged compounds are molecules rendered functionally inert by derivatization with a photochemical protecting group. We describe the design logic behind the development of a diethylaminocoumarin (DEAC) caging chromophore, DEAC450, that absorbs blue light strongly (ε450 = 43,000 M(-1) cm(-1)) and violet light 11-fold more weakly. The absorption minimum is in the wavelength range (340-360 nm) that is traditionally used for photolysis of many widely used nitroaromatic caged compounds (e.g., 4-carboxymethoxy-5,7-dinitroindolinyl(CDNI)-GABA). We used this chromophore to synthesize DEAC450-caged cAMP and found this probe was very stable toward aqueous hydrolysis in the electronic ground state but was photolyzed with a quantum efficiency of 0.78. When DEAC450-cAMP and CDNI-GABA where co-applied to striatal cholinergic interneurons, the caged compounds were photolyzed in an chromatically orthogonal manner using blue and violet light so as to modulate the neuronal firing rate in a bidirectional way.

Coumarin-Caged dG for Improved Wavelength-Selective Uncaging of DNA

Herein we report on diethylaminocoumarin (DEACM) as a new photoremovable protecting group for 2'-deoxyguanosine in oligonucleotides. An oligonucleotide with O(6)-DEACM-caged dG was synthesized and photochemically analyzed. The DEACM group shows superior photochemical properties at 405 nm with an uncaging efficiency (ε·φ) for deprotection that is 17 times higher than that for 2-(o-nitrophenyl)-propyl NPP caging groups in the same position. Wavelength-selective deprotection in the presence of NPP groups proceeds up to 80 times faster.

A novel fluorescent probe for more effective monitoring of nanosized drug delivery systems within the cells

To improve visualization of nanoparticles within the cells’ compartments, we synthesized a coumarin based fluorescent derivative, tetradecyl diethylamino coumarin amid, 14-DACA. In this compound the coumarin chromophore is linked with a tetradecyl alkyl chain that contributes to lipophilicity and slightly amphiphilic character of this probe. 14-DACA exhibits good biocompatibility, its solubility and emission spectrum are not sensitive to changes in pH value. Solid lipid nanoparticles (SLN) labeled with 14-DACA (SLN-D) and frequently used 6-coumarin (SLN-C) were utilized to evaluate probes’ properties in the trafficking and intracellular localization of nanoparticles. SLN-D were seen as distinct blue dots in the cellular environment in contrast to SLN-C which were hardly to recognize due to the self-quenching of 6-coumarin, its leakage and distribution in intracellular compartments. Spectra of 14-DACA indicated the possibility of spectral resolution from both green and red fluorophores allowing clear multicolor imaging of organelles in both fixed and living cells. The results showed valuableness of new probe for trafficking of the drug nanocarriers intracellularly in a kinetic and sensitive manner. Such studies are of great importance in investigations aimed to clarify subcellular targeted drug delivery, controlled release and even to identify toxicological changes.

7 Diethylaminocoumarin (DEAC) 레이져 염료의 광물리적 파라미터, 광분해, 형광 소광 및 Convolutive Voltammetry

7 diethylaminocoumarin (DEAC) 레이저 염료의 광물리적 특성들을 다양한 용매에서 측정하였다. DEAC의 방출 스펙트럼은 양이온성(CTAC) 미셀과 음이온성(SDS) 미셀에서 측정하였고, 레이저 파라미터는 아세톤, 다이옥산, 에탄올 및 dimethylforamide (DMF)과 같은 여러 가지 용매에 대하여 계산하였다. DEAC의 광반응성은 366 nm 빛을 사용하여 <TEX>$CCl_4$</TEX> 용매에서 연구하였고, 광화학 수득률 (<TEX>${\Phi}_c$</TEX>)과 속도 상수(k)도 결정하였다. picric acid (PA), tetracyanoethylene (TCNE), 7,7,8,8-tetracynoquinonedimethane (TCNQ)등의 유기 수용체와 DEAC의 상호 작용에 대한 연구는 acetonitrile (<TEX>$CH_3CN$</TEX>) 용액에서 형광을 측정하므로 써 수행하였다. DEAC의 전기화학적 연구는 백금 전극을 사용하여 0.1 mol/L tetrabutyl ammonium perchlorate (TBAP)/<TEX>$CH_3CN$</TEX> 용액에서 순환 전류-전압법, convolutive voltammetry 및 디지털 시뮬레이션을 조합하여 수행하였고, 전기화학 파라미터도 결정하였다. The photophysical properties of 7-diethylaminocoumarin (DEAC) laser dye have been measured in different solvents. The emission spectrum of DEAC has also been measured in cationic (CTAC) and anionic (SDS) micelles. The laser parameters have been calculated in different solvents namely acetone, dioxane, ethanol and dimethylforamide(DMF). The photoreactivity of DEAC has been studied in <TEX>$CCl_4$</TEX> solvent using 366 nm light. The values of photochemical yield (<TEX>${\Phi}_c$</TEX>) and rate constant (k) are determined. The interaction of organic acceptors such as picric acid (PA), tetracyanoethylene (TCNE) and 7,7,8,8-tetracynoquinonedimethane (TCNQ) with DEAC are also studied using fluorescence measurements in acetonitrile (<TEX>$CH_3CN$</TEX>). The electrochemical investigation of (DEAC) has been carried out using cyclic voltammetry and convolutive voltammetry combined with digital simulation technique at a platinum electrode in 0.1 mol <TEX>$L^{-1}$</TEX> tetrabutyl ammonium perchlorate (TBAP) in <TEX>$CH_3CN$</TEX> solvent. The electrochemical parameters of the investigated compound were determined using cyclic and convolutive voltammetry. The extracted electrochemical parameters were verified and confirmed via digital simulation method.

Caged Ceramide 1-Phosphate Analogues: Synthesis and Properties

Sphingolipid phosphate analogues bearing 7-(diethylamino)coumarin (DECM) and 4-bromo-5-hydroxy-2-nitrobenzhydryl (BHNB) groups in a photolabile ester bond were synthesized. The ability of the "caged" ceramide 1-phosphate analogues to release the bioactive parent molecule upon irradiation at 400-500 nm was demonstrated by stimulation of macrophage cell proliferation.

Coumarin-Caged Glycine that Can Be Photolyzed within 3 μs by Visible Light

The synthesis and characterization of a new photolabile precursor of glycine (coumarin-caged glycine) are reported. The new compound is suitable for rapid chemical kinetic investigations of the membrane-bound neurotransmitter receptor activated by glycine. Unlike previously used caging groups for glycine, this precursor can be photolyzed rapidly and efficiently in the visible wavelength region. This allows the use of a relatively inexpensive light source. The alpha-carboxyl group of glycine was covalently coupled to the 7-(diethylamino)coumarin (DECM) caging group. The caged compound has a major absorption band with a maximum at 390 nm (epsilon390 = 13,900 M-1 cm-1). Photolysis was performed at wavelengths of >or=400 nm (epsilon400 = 12,400 M-1 cm-1). Under physiological conditions, DECM-caged glycine is water soluble and stable. In the visible wavelength region, it photolyzes rapidly to release glycine with a half-life of approximately 2.5 micrometers and a quantum yield of 0.12 +/- 0.01. The experimental results demonstrated that neither DECM-caged glycine nor its byproduct inhibits or activates human alpha1 glycine receptors expressed on the surface of HEK 293 cells.

New strategy for multi-colour fluorescence in situ hybridisation: COBRA: COmbined Binary RAtio labelling.

Multicolour in situ hybridisation (MFISH) is increasingly applied to karyotyping and detection of chromosomal abnormalities. So far 27 colour analyses have been described using fluorescently labelled chromosome painting probes in a so-called combinatorial approach. In this paper a new strategy is presented to use efficiently the currently available number of spectrally separated fluorophores in order to increase the multiplicity of MFISH. We introduce the principle of COBRA (COmbined Binary RAtio labelling), which is based on the simultaneous use of combinatorial labelling and ratio labelling. Human chromosome painting in 24 colours is accomplished using four fluorophores only. Three fluorophores are used pair wise for ratio labelling of a set of 12 chromosome painting probes. The second set of 12 probes is labelled identically but is also given a binary label (fourth fluorophore). The COBRA method is demonstrated on normal human chromosomes and on a lymphoma (JVM) cell line, using probes enzymatically labelled with fluorescein, lissamine and cy5 as primary fluorophores, and diethylaminocoumarin (DEAC), a blue dye, as combinatorial fourth label to demonstrate incorporated digoxigenin. In addition, the principle was tested using chemical labelling. The first set of 12 painting probes was therefore labelled by ULS (Universal Linkage System), using DEAC, cy3 and cy5 as primary labels, and the second set was labelled similarly, but also contained a digoxigenin-ULS label, which was indirectly stained with fluorescein. Subsequently, a mathematical analysis is presented and methods are indicated for achieving an MFISH multiplicity of 48, 96 or even higher using existing technology.

Excited state properties of pre-twisted 7-diethylamino coumarinyl benzopyrano pyridine: an experimental and AMI study

A detailed investigation of the photophysical properties of a new coumarin heterodimer: 2-(7-diethylamino-3-coumarinyl)-5-oxo-4-methyl [1] benzopyrano(3,4- c)pyridine (CBP) has been performed in a range of nonpolar and polar solvents at room temperature. In addition, the influence of temperature on the excited state properties of CBP in dichloromethane, methanol and dimethylsulfoxide has also been investigated. These studies indicate that the fluorescence of the dye is from the pre-twisted intramolecular charge transfer (ICT) state. AM1 semiempirical calculations performed for CBP in the ground, excited singlet and triplet states are in conformity with the experimental results. The presence of second coumarin is found to introduce a larger charge transfer character to the parent coumarin molecule when compared to other diethylamino coumarins. From this study it is also evident that such coumarin hetero dimers behave more like any other single absorbing and emitting chromophoric-systems.