Dipolar Dyes Research Articles

A Nano-Aggregatable Acedan Derivative for Clathrin-Mediated Cellular Uptake and Two-Photon Imaging of Diabetes-Associated Lipid Droplets.

Lipid droplets (LDs), the essential cytosolic fat storage organelles, have emerged as pivotal regulators of cellular metabolism and are implicated in various diseases. The noninvasive monitoring of LDs necessitates fluorescent probes with precise organelle selectivity and biocompatibility. Addressing this need, we have engineered a probe by strategically modifying the structure of a conventional two-photon-absorbing dipolar dye, acedan. This innovative approach induces nanoaggregate formation in aqueous environments, leading to aggregation-induced fluorescence quenching. Upon cellular uptake via clathrin-mediated endocytosis, the probe selectively illuminates within LDs through a disassembly process, effectively distinguishing LDs from the cytosol with exceptional specificity. This breakthrough enables the high-fidelity imaging of LDs in both cellular and tissue environments. In a pioneering investigation, we probed LDs in a diabetes model induced by streptozotocin, unveiling significantly heightened LD accumulation in cardiac tissues compared to other organs, as evidenced by TP imaging. Furthermore, our exploration of a lipopolysaccharide-mediated cardiomyopathy model revealed an LD accumulation during heart injury. Thus, our developed probe holds immense potential for elucidating LD-associated diseases and advancing related research endeavors.

(Invited) Diameter-Dependent Stacking of Squaraine Dye Molecules inside Chirality-Sorted Single-Wall Carbon Nanotubes

Filling of single-wall carbon nanotubes (SWCNTs) with organic dye molecules is a promising strategy to add new functionalities, for instance by aligning dipolar dyes in a one-dimensional (1D) head-to-tail coupled chain to obtain a giant enhancement of their nonlinear optical response,[1] or by photo-sensitizing the tubes in new wavelength ranges by excitation energy transfer (EET) from the dye to the SWCNTs, useful for photo-conversion applications.[2] The 1D stacking of molecules inside SWCNTs modulates both the properties of the molecules and of the SWCNTs. We found that the EET of squaraine-dye-filled SWCNTs reveals a pronounced SWCNT-diameter-dependence of the dye absorption, indicating a diameter-dependent stacking. By performing IR fluorescence excitation spectroscopy on a range of chirality-enriched samples of dye-filled SWCNTs with different chirality distributions, each shifted dye absorption wavelength observed through the EET can be unambiguously assigned to a specific encapsulating SWCNT chirality.[3] This reveals a systematic trend with diameter that can be associated with the J-aggregate- and H-aggregate-like interactions expected in close-packed single- and double-file stackings, as corroborated by a simple geometric model, and enables tuning of the optical properties of the 1D molecular arrays through the selection of proper SWCNT diameters.[1] S. Cambré, J. Campo, C. Beirnaert, C. Verlackt, P. Cool, W. Wenseleers, Nature Nanotechnol. 10(3) 248-252 (2015). [2] S. van Bezouw, D.H. Arias, R. Ihly, S. Cambré, A.J. Ferguson, J. Campo, J.C. Johnson, J. Defillet, W. Wenseleers, J.L. Blackburn, ACS Nano 12(7) 6881-6894 (2018). [3] S. Forel, H. Li, S. van Bezouw, J. Campo, L. Wieland, W. Wenseleers, B.S. Flavel, S. Cambré, Nanoscale 14, 8385-8397 (2022).

Amplified Plasmonic Forces from DNA Origami-Scaffolded Single Dyes in Nanogaps.

Developing highly enhanced plasmonic nanocavities allows direct observation of light-matter interactions at the nanoscale. With DNA origami, the ability to precisely nanoposition single-quantum emitters in ultranarrow plasmonic gaps enables detailed study of their modified light emission. By developing protocols for creating nanoparticle-on-mirror constructs in which DNA nanostructures act as reliable and customizable spacers for nanoparticle binding, we reveal that the simple picture of Purcell-enhanced molecular dye emission is misleading. Instead, we show that the enhanced dipolar dye polarizability greatly amplifies optical forces acting on the facet Au atoms, leading to their rapid destabilization. Using different dyes, we find that emission spectra are dominated by inelastic (Raman) scattering from molecules and metals, instead of fluorescence, with molecular bleaching also not evident despite the large structural rearrangements. This implies that the competition between recombination pathways demands a rethink of routes to quantum optics using plasmonics.

Concentration-, Temperature- and Solvent-Dependent Self-Assembly: Merocyanine Dimerization as a Showcase Example for Obtaining Reliable Thermodynamic Data.

Mathematical models for the concentration-, temperature- and solvent-dependent analysis of self-assembly equilibria are derived for the most simple case of dimer formation, to highlight the assumptions these models and the thus determined thermodynamic parameters are based on. The three models were applied to UV/Vis absorption data for the dimerization of a highly dipolar merocyanine dye in 1,4-dioxane. Isothermal titration calorimetry (ITC) dilution experiments were performed as an independent reference technique. While the concentration-dependent analysis is according to our studies the most reliable method, also the less time-consuming temperature-dependent evaluation can give accurate results in the present example, despite small thermochromic effects. In contrast, the strong negative solvatochromism of the merocyanine tampers with the results from the solvent-dependent evaluation. Even though the studies presented in this work are limited to the monomer-dimer equilibrium of a dipolar dye, the basic principles can be transferred to other chromophores and different self-assembly models, including those for supramolecular polymerization.

Predicting the Second-Order Nonlinear Optical Responses of Organic Materials: The Role of Dynamics.

The last 30 years have witnessed an ever-growing application of computational chemistry for rationalizing the nonlinear optical (NLO) responses of organic chromophores. More specifically, quantum chemical calculations proved highly helpful in gaining fundamental insights into the factors governing the magnitude and character of molecular first hyperpolarizabilities (β), be they either intrinsic to the chromophore molecular structure and arising from symmetry, chemical substitution, or π-electron delocalization, or induced by external contributions such as the laser probe or solvation and polarization effects. Most theoretical reports assumed a rigid picture of the investigated systems, the NLO responses being computed solely at the most stable geometry of the chromophores. Yet, recent developments combining classical molecular dynamics (MD) simulations and DFT calculations have evidenced the significant role of structural fluctuations, which may induce broad distributions of NLO responses, and even generate them in some instances.This Account presents recent case studies in which theoretical simulations have highlighted these effects. The discussion specifically focuses on the simulation of the second-order NLO properties that can be measured experimentally either from Hyper-Rayleigh Scattering (HRS) or Electric-Field Induced Second Harmonic Generation (EFISHG). More general but technical topics concerning several aspects of the calculations of hyperpolarizabilities are instead discussed in the Supporting Information.Selected examples include organic chromophores, photochromic systems, and ionic complexes in the liquid phase, for which the effects of explicit solvation, concentration, and chromophore aggregation are emphasized, as well as large flexible systems such as peptide chains and pyrimidine-based helical polymers, in which the relative variations of the responses were shown to be several times larger than their average values. The impact of geometrical fluctuations is also illustrated for supramolecular architectures with the examples of nanoparticles formed by organic dipolar dyes in water solution, whose soft nature allows for large shape variations translating into huge fluctuations in time of their NLO response, and of self-assembled monolayers (SAMs) based on indolino-oxazolidine or azobenzene switches, in which the geometrical distortions of the photochromic molecules, as well as their orientational and positional disorder within the SAMs, highly impact their NLO response and contrast upon switching. Finally, the effects of the rigidity and fluidity of the surrounding are evidenced for NLO dyes inserted in phospholipid bilayers.

Crystallization‐Driven Controlled Two‐Dimensional (2D) Assemblies from Chromophore‐Appended Poly(L‐lactide)s: Highly Efficient Energy Transfer on a 2D Surface

AbstractA rational approach towards precision two‐dimensional (2D) assemblies by crystallization‐driven self‐assembly (CDSA) of poly(L‐lactides) (PLLAs), end‐capped with dipolar dyes like merocyanine (MC) or naphthalene monoimide (NMI) and hydrophobic pyrene (PY) or benzene (Bn) is described. PLLA chains crystallize into diamond‐shaped platelets in isopropanol, which forces the terminal dyes to assemble into a 2D array on the platelet surface by either dipolar interactions or π‐stacking and exhibit tunable emission. Dipolar dyes play a critical role in imparting colloidal stability and structural uniformity to the 2D crystals, which is partly compromised for hydrophobic ones. Co‐crystallization between NMI‐ and PY‐labeled PLLAs yields similar diamond‐shaped co‐platelets with highly efficient (≈80 %) Förster Resonance Energy Transfer on the 2D surface. Further, the “living” CDSA method confers enlarged, segmented block co‐platelets using one of the homopolymers as “seed” and the other as “unimer”.

Crystallization-Driven Controlled Two-Dimensional (2D) Assemblies from Chromophore-Appended Poly(L-lactide)s: Highly Efficient Energy Transfer on a 2D Surface.

A rational approach towards precision two-dimensional (2D) assemblies by crystallization-driven self-assembly (CDSA) of poly(L-lactides) (PLLAs), end-capped with dipolar dyes like merocyanine (MC) or naphthalene monoimide (NMI) and hydrophobic pyrene (PY) or benzene (Bn) is described. PLLA chains crystallize into diamond-shaped platelets in isopropanol, which forces the terminal dyes to assemble into a 2D array on the platelet surface by either dipolar interactions or π-stacking and exhibit tunable emission. Dipolar dyes play a critical role in imparting colloidal stability and structural uniformity to the 2D crystals, which is partly compromised for hydrophobic ones. Co-crystallization between NMI- and PY-labeled PLLAs yields similar diamond-shaped co-platelets with highly efficient (≈80 %) Förster Resonance Energy Transfer on the 2D surface. Further, the "living" CDSA method confers enlarged, segmented block co-platelets using one of the homopolymers as "seed" and the other as "unimer".

Rotational Diffusion Dynamics of Fluorescein Derivatives in Binary Mixtures of Solvents: An Experimental and Computational Study

With a view to understand the nature of solute solvent interactions, rotational reorientation times (τr) of three medium sized dipolar laser dyes viz., dichlorofluorescein (DCF), sodium fluorescein (SF) and kiton red (KR) in two binary mixtures namely, aqueous-DMSO and aqueous-1-propanol have been determined employing steady state fluorescence depolarization technique. The experimental results are analyzed in the light of SED hydrodynamic and of Gierer and Wirtz (GW) and Dote, Kivelson and Schwartz (DKS) quasihydrodynamic models. Rotational reorientation times (τr) are plotted as function of viscosity (η) on the binary solvent mixtures. An interesting hook shaped profile is observed in both the binary mixtures of solvents that is likely to shed light on solute-solvent interactions. Further, theoretical study has been carried out using Gaussian 09 software. The optimized geometry, HOMO-LUMO, energy gap and molecular electron potential map (MEPM) were extracted from DFT/B3LYP 6-311g(d) basis set. The hyper conjugation or intra-molecular delocalization was estimated from NBO analysis. Strong interactions were observed between nO33→σ*C31, πN38→σ*C12 and πO32→π*(C31- O33) with E(2) energies of 203.58, 121.89 and 39.92 kJ/mol for SF, KR and DCF.

Kinetics, process design and implementation of zwitterionic adsorbent coating for dipolar dyes removal in wastewater treatment industry

Kinetic, thermodynamics and process design of the adsorption of dipolar dye molecules, namely Brilliant green (BG) and Naphthalene Blue 12B (NB12B), from aqueous solution using a zwitterionic adsorbent coating (ZwitAd) were investigated. This zwitterionic adsorbent coating was synthesized by a facile technique, which implied only 3 main chemicals: acrylic polymer emulsion (binder), bentonite (fillers) and EPIDMA (cationic polyelectrolyte). The scale-up of this formulation was proved showing that this coating adsorbent is viable to be adopted in a large-scale production. This novel adsorbent was synthesized in a coating form to obtain a feasible and practical application for the adsorption of both cationic and anionic dyes from wastewaters. Besides, this new adsorbent could be easily separated from the system without applying extra processing methods such as filtration or centrifugation. Adsorption studies showed that Freundlich model described satisfactorily the BG adsorption, whereas the NB12B adsorption was fitted with Langmuir isotherm. A single stage process was designed and the corresponding mathematical formulations was developed using the best adsorption models. Process design was performed to optimize the adsorbent amount for achieving a specific target of given initial effluent concentration and volume of treated wastewater. This optimization contributed to minimize the capital investment cost in order to satisfy a standard defined for the dye removal. Different alternatives for the application of this novel adsorbent in an industrial facility have been described and discussed. This study contributes with new findings to improve the implementation of novel adsorbents for water treatment and purification at industrial scale.

Self-assembling, structure and nonlinear optical properties of fluorescent organic nanoparticles in water.

Owing to their intense emission, low toxicity and solubility in aqueous medium, fluorescent organic nanoparticles (FONs) have emerged as promising alternatives to inorganic ones for the realization of exogenous probes for bioimaging applications. However, the intimate structure of FONs in solution, as well as the role played by intermolecular interactions on their optical properties, remains challenging to study. Following a recent Second-Harmonic Scattering (SHS) investigation led by two of us [Daniel et al., ACS Photonics, 2015, 2, 1209], we report herein a computational study of the structural organization and second-order nonlinear optical (NLO) properties of FONs based on dipolar chromophores incorporating a hydrophobic triphenylamine electron-donating unit and a slightly hydrophilic aldehyde electron-withdrawing unit at their extremities. Molecular dynamics simulations of the FON formation in water are associated with quantum chemical calculations, to provide insight into the molecular aggregation process, the molecular orientation of the dipolar dyes within the nanoparticles, and the dynamical behavior of their NLO properties. Moreover, the impact of intermolecular interactions on the NLO responses of the FONs is investigated by employing the tight-binding version of the recently developed simplified time-dependent density functional theory (sTD-DFT) approach, allowing the all-atom quantum mechanics treatment of nanoparticles.

Liposomal‐Encapsulated Near‐Infrared Fluorophore Based on π‐Extended Dipolar Naphthalene Platform and Its Imaging Applications in Human Cancer Cells

A new near-infrared emitting liposomal nano-formulation was developed, which has a dipolar dye in the core and demonstrated for human cancer cells' fluorescence imaging. Appendix S1. Supporting information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Ultrabright Silica-Coated Organic Nanocrystals for Two-Photon In Vivo Imaging

Herein, we demonstrate the potential of ultrabright fluorescent silica-coated organic nanocrystals for two-photon in vivo imaging. These unique nanoparticles (NPs) containing a crystalline core of small push-pull dipolar dye are specifically designed to exhibit two-photon absorption for 2 fluorescence imaging. The NPs can be easily functionalized using click chemistry in pure water, with preservation of the organic core. A novel small-volume DLS technique was used to evaluate the effect of PEGylation on the colloidal stability of the NPs in complex media containing salts and proteins, mimicking the composition of blood serum. The potential of these bright red-emitting NPs for two-photon fluorescence imaging is demonstrated both in vitro and in vivo.

A benzo[b]xanthene-derived fluorescent probe capable of two-photon ratiometric imaging of lysosomal cysteine with high specificity

Cysteine, an important biothiol, is associated with diverse biological processes, demanding efficient in vivo detection probes. Accordingly, various types of fluorescent probes have been reported so far, but still those with practical applicability are in demand. One of the challenges is how to minimize interference from other biomolecules. We disclose the benzoxanthene-based fluorescent probe that shows excellent substrate selectivity, and, furthermore, good ratiometric and two-photon imaging properties. The probe, which is also photostable and biocompatible, senses cysteine through very fast 1,6-conjugate addition to the benzoxanthene core, a new dipolar dye system that emits in the deep-red wavelength region. The probe enables reliable two-photon ratiometric imaging of the endogenous lysosomal cysteine. The cysteine adduct can be reverted to the probe by hydrogen peroxide most effectively among several reactive oxygen species both in solution as well as in cell. An application of the probe to quantify the cysteine level in human blood plasma is also demonstrated.

Organic dyes incorporating 9,10-dihydrophenanthrene moiety for dye-sensitized solar cells

A series of new dipolar organic dyes containing 9,10-dihydrophenanthrene has been synthesized as sensitizers for the application in dye-sensitized solar cells. These new materials containing less rigid π–linker as sensitizers exhibit good performance with conversion efficiencies ranging from 1.58% to 6.21% reaching 11 ∼ 83% of the ruthenium dye N719-based cell under the same condition.

Articulated Structures of D-A Type Dipolar Dye with AIEgen: Synthesis, Photophysical Properties, and Applications.

Articulated structures of naphthalene-based donor (D)-acceptor (A) type dipolar dye and aggregation-induced emission luminogen (AIEgen) based on tetraphenylethylene (TPE) were synthesized, and their photophysical properties were analyzed for the first time. There are many fluorophore backbones, which have dipolar structure and AIEgen. However, there has been neither property analysis nor research that closely articulates DA and AIE through non-conjugation linker. We have therefore prepared two representative fluorophores; DA-AIE series (DA-AIE-M and DA-AIE-D), and characterized their UV/vis absorption and emission properties with quantum chemical calculations. In addition, we utilized the unique photophysical properties of DA-AIE-D for monitoring a trace of dimethyl sulfoxide (DMSO) in aqueous media, including real water samples.

Visualizing mitochondria and mouse intestine with a fluorescent complex of a naphthalene-based dipolar dye and serum albumin.

We have explored a new research field of fluorophores through the manipulation of fluorophore-binding proteins. The development of a new imaging agent for tracing a specific organelle or a particular site within a living organism has been of great interest in the field of basic science as well as translational medicine. In this work and for the first time, we will disclose a new naphthalene-based dipolar dye and its complex, with serum albumin (SA), and show their applicability for the selective imaging of mitochondria in cells and the intestine in a mouse. The SA-binding dipolar dye, IPNHC, was synthesized straightforwardly, and we identified its photophysical properties and binding mode with SA. IPNHC-SA complex showed a bright emission in the blue wavelength range with a high quantum yield and stability. In the fluorescence imaging study, bright fluorescence images of mouse intestines were observed under a UV light, as well as two-photon (TP) deep tissue imaging after intravenous injection of IPNHC and IPNHC-SA complex. The present findings hold great promise for the application of the fluorescent complex for use in the tracing and tracking of intestine-related diseases at clinical sites.

Temperature-Dependent Ultrafast Solvation Response and Solute Diffusion in Acetamide-Urea Deep Eutectic Solvent.

In the present paper, we have studied the temperature dependence of translational diffusion and solvation dynamics of a dissolved dipolar dye in the nonionic acetamide-urea deep eutectic solvent (DES), to characterize the viscosity coupling of the measured relaxation times and verify the dynamical heterogeneity aspect of this medium. Three different time-resolved experimental techniques have been employed for this purpose: fluorescence correlation spectroscopy, transient absorption (TA) spectroscopy, and optical Kerr effect (OKE) spectroscopy. The first method provides the proof that the translational diffusion time of a solute in acetamide-urea DES [fCH3CONH2 + (1 - f)CO(NH2)2, f = 0.6] exhibits a fractional viscosity dependence, with exponent 0.758, which, when compared with the viscosity-diffusion relationship for the same solute in common molecular solvents, suggests moderate deviation from the Stokes-Einstein relation. Stokes shift dynamics of a solvatochromic dye, 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran in this DES, followed via femtosecond TA measurements, have been found to be triexponential in nature and dominated by a ∼100 fs component. The other two components, which contribute to a total dynamic Stokes shift magnitude of ∼2500 cm-1, are characterized by time constants in the ∼5 and ∼50 ps regimes. Subsequent comparison with the femtosecond OKE measurements suggests that the relatively slower picosecond solvation components originate from the rapid reorientation of the solvent molecules, while the subpicosecond solvation response arises from the participation of the collective low-frequency solvent modes (such as intermolecular vibrations and librations). We find that the rotational diffusion lifetimes also exhibit fractional power dependence on medium viscosity and thus deviate from the Stokes-Einstein-Debye pprediction. All of these results therefore suggest that the nonionic acetamide-urea DES is a moderately heterogeneous medium.

4,5,5-Trimethyl-2,5-dihydrofuran-Based Electron-Withdrawing Groups for NIR-Emitting Push-Pull Dipolar Fluorophores.

In the context of molecular engineering of push-pull dipolar dyes, we introduce a structural modification of the well-known electron-accepting group 2-dicyanomethylidene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF). Introduction of a (benzo[d]thiazol-2-yl) moiety failed, and unexpected structures were obtained. On the other hand, phenylthio and phenylsulfonyl entities were successfully introduced at position 3 of the 2-(dicyanomethylidene)-2,5-dihydrofuran ring, giving access to new electron-acceptor groups and dipolar fluorophores displaying near-infrared emission in solution or in the solid state, brighter than their TCF analogues.

(Invited) Spectroscopy of Nanocarbon Structures Synthesized in the One-Dimensional Core of Carbon Nanotubes

The hollow core and well-defined diameters of carbon nanotubes (CNTs) make them the ideal template for ordering one-dimensional (1D) arrays of molecules and for the controlled synthesis of 1D carbon nanostructures from suitable precursor molecules. For instance, we previously demonstrated that in this way dipolar dye molecules can be naturally aligned in an ideal head-to-tail arrangement to create assemblies with a giant total nonlinear optical response,[1] and that the optical properties of dye molecules encapsulated in SWCNTs can be strongly modulated by the SWCNT diameter, indicating very specific diameter-dependent stacking and interactions of the molecules.[2] By thermal conversion also well-defined carbon structures such as long 1D carbon chains (carbyne) or graphene nanoribbons can be synthesized inside the hollow core of CNTs. Here we show that the structure and properties of such 1D carbon chains are strongly modulated by the interaction with the host tube, which greatly modifies the chains’ bond-length alternation.[3] We also show how the band-gap and electronic spectrum of the encapsulated carbon structures can be measured in detail, even in heterogeneous mixtures, through extensive wavelength dependent resonance Raman (excitation) spectroscopy, disentangling the vibrational and electronic spectra of the different structures. [1] S. Cambré, J. Campo et al., Nature Nanotechnol. 10, 248 (2015). [2] S. van Bezouw, D. H. Arias et al., ACS Nano 12, 6881 (2018). [3] L. Shi et al., Phys. Rev. Mater. 1, 075601 (2017).

Defined Merocyanine Dye Stacks from a Dimer up to an Octamer by Spacer-Encoded Self-Assembly Approach.

A series of well-defined chromophore stacks is obtained upon self-assembly of merocyanine and bis(merocyanine) dyes in nonpolar solvents. Careful design of the spacer moieties linking the dipolar chromophores within the bis(merocyanine) dyes allows one to direct the dipole-dipole interaction driven aggregation into stacks of desired size from dimer up to octamer. The spacer-encoded self-assembly process was investigated by UV/vis absorption spectroscopy showing an increase of the hypsochromic shift with increasing stack size. The structure of the largest aggregate comprising eight chromophores was analyzed by 1D and 2D nuclear magnetic resonance spectroscopic studies revealing a perfectly interdigitated centrosymmetric organization of the dipolar dyes and concomitant annihilation of the ground state dipole moment is observed in the UV/vis absorption spectra. This unprecedented series of dye stacks from dimer to octamer enabled a systematic study of the optical absorption properties in dependence of the stack size disclosing that the absorption features can be rationalized by molecular exciton theory. Our results show that the noncovalent synthesis approach based on dipolar aggregation is suitable for the design of well-defined dye aggregates of specific size, allowing in-depth studies to manifest structure-property relationships.