Tuning the Optical Properties Through Hydrogen Bond-assisted H-aggregate Formation: The ODIN Case.

The current work focuses on the investigation of two functionalized naphthyridine derivatives, namely ODIN-EtPh and ODIN-But, to gain insights into the hydrogen bond-assisted H-aggregate formation and its impact on the optical properties of ODIN molecules. By employing a combination of X-ray and electron crystallography, absorption and emission spectroscopy, time resolved fluorescence and ultrafast pump-probe spectroscopy (visible and infrared) we unravel the correlation between the structure and light-matter response, with a particular emphasis on the influence of the polarity of the surrounding environment. Our experimental results and simulations confirm that in polar and good hydrogen-bond acceptor solvents (DMSO), the formation of dimers for ODIN derivatives is strongly inhibited. The presence of a phenyl group linked to the ureidic unit favors the folding of ODIN derivatives (forming an intramolecular hydrogen bond) leading to the stabilization of a charge-transfer excited state which almost completely quenches its fluorescence emission. In solvents with a poor aptitude for forming hydrogen bonds, the formation of dimers is favored and gives rise to H aggregates, with a consequent considerable reduction in the fluorescence emission. The urea-bound phenyl group furtherly stabilizes the dimers in chloroform.

A novel benzotriazole derivate with Twisted intramolecular charge transfer and Aggregation Induced emission features for proton determination.

Molecules with Aggregation-Induced Emission (AIE) effects could show strong emission in solid or aggregate form, thus they are suitable for applications in the field of solid luminescent materials. According to former reporting, AIE molecules are always J-aggregates. In this study, a new benzotriazole derivate with electron donor-acceptor structure was synthesized. (E)-4-(2-(1H-benzo[d] [1,2,3] triazol-1-yl) vinyl)-N, N-dimethylaniline (BTADA) has both TICT and AIE effect, even though it is H-aggregate. Furthermore, BTADA could respond to proton in solution and solid form. Due to its multiple binging sites, proton would bind to benzotriazole and dimethylaniline moiety successively when BTADA was exposed to acid, and the fluorescent color changed from green to yellow then blue as the concentration of proton increased. Such phenomena indicate BTADA has potential usage in proton detection.

Activatable Carbocyanine Dimers for Photoacoustic and Fluorescent Detection of Protease Activity.

Activatable contrast agents are of ongoing research interest because they offer low background and high specificity to the imaging target. Engineered sensitivity to protease activity is particularly desirable because proteases are critical biomarkers in cancer, infectious disease, inflammatory disorders, and so forth. Herein, we developed and characterized a set of peptide-linked cyanine conjugates for dual-modal detection of protease activity via photoacoustic (PA) and fluorescence imaging. The peptide-dye conjugates were designed to undergo contact quenching via intramolecular dimerization and contained n dyes (n = 2, 3, or 4) with n - 1 cleavable peptide substrates. The absorption peaks of the conjugates were blue-shifted 50 nm relative to the free dye and had quenched fluorescence. This effect was sensitive to solvent polarity and could be reversed by solvent switching from water to dimethyl sulfoxide. Employing trypsin as a model protease, we observed a 2.5-fold recovery of the peak absorbance, 330-4600-fold fluorescent enhancement, and picomolar detection limits following proteolysis. The dimer probe was further characterized for PA activation. Proteolysis released single dye-peptide fragments that produced a 5-fold PA enhancement through the increased absorption at 680 nm with nanomolar sensitivity to trypsin. The peptide substrate could also be tuned for protease selectivity; as a proof-of-concept, we detected the main protease (Mpro) associated with the viral replication in SARS-CoV-2 infection. Last, the activated probe was imaged subcutaneously in mice and signal was linearly correlated to the cleaved probe. Overall, these results demonstrate a tunable scaffold for the PA molecular imaging of protease activity with potential value in areas such as disease monitoring, tumor imaging, intraoperative imaging, in vitro diagnostics, and point-of-care sensing.

Intriguing H-Aggregates of Heptamethine Cyanine for Imaging-Guided Photothermal Cancer Therapy.

Organic small-molecule-based photothermal agents such as cyanine dyes have received increasing attention in developing novel cancer therapies with potential clinical utility but suffer from poor stability, low photothermal efficiency, and limited accumulation at tumor sites in molecular forms. Self-assembly of small-molecule dyes into supramolecular assemblies may address these concerns by controlling the molecular organization of dye monomers to form structures of a higher order. Among them, H-aggregates of dyes favor face-to-face contacts with strongly overlapping areas, which always have a negative connotation to exhibit low or no fluorescence in most cases but may emanate energy in nonradiative forms such as heat for photothermal cancer therapy applications. Here, the synergistic self-assembly of cyanine dyes into H-aggregates is developed as a new supramolecular strategy to fabricate small-molecule-based photothermal nanomaterials. Compared to the free cyanine dyes, the H-aggregates assembled from pyrene or tetraphenylethene (TPE) conjugating cyanine exhibit the expected absorption spectral blue shift and fluorescence self-quenching but unique photothermal properties. Remarkably, the obtained H-aggregates are saucer-shaped nanoparticles that exhibit passive tumor-targeting properties to induce imaging-guided photothermal tumor ablation under irradiation. This supramolecular strategy presented herein may open up new opportunities for constructing next-generation small-molecule-based self-assembly nanomaterials for PTT cancer therapy in clinics.

Aggregation-Dependent Photoreactive Hemicyanine Assembly as a Photobactericide.

Organic materials that show substantial reactivity under visible light have received considerable attention due to their wide applications in chemical and biological systems. Hemicyanine pigments possess a strong intramolecular donor-acceptor structure and thereby display intense absorption in the visible spectral region. However, most excitons are consumed via the twisted intramolecular charge-transfer (TICT) process, making hemicyanines generally inert to light. Herein, we describe the development of an amphiphilic hemicyanine dye whose aggregation could be easily regulated using salt or counterions. More importantly, its intrinsic photoreactivity was successfully induced by steric restriction and cofacial arrangement within the H-aggregate, thus creating an effective photobactericide. This strategy could be extended to the development of photocatalysts for photosynthesis and a photosensitizer for photodynamic therapy.

Controlling Molecule Aggregation and Electronic Spatial Coherence in the H-Aggregate and J-Aggregate Regime at Room Temperature.

Controlling molecule aggregation in polymer films is one of the key factors in understanding the links between properties and structures in organic semiconductors. Here, we used poly(3-hexylthiophene-2,5-diyl) (P3HT) as the model system. By doping the insulating polar additive poly (ethylene oxide) (PEO) into P3HT film and controlling the processing methods, we achieved the side-to-side H-aggregate and head-to-tail J-aggregate of P3HT molecules with different extents at room temperature. We have demonstrated that the solvent solidification rate plays an important role in the controlling of molecule aggregation, which finally influenced the solid-state phase separation in the film. Furthermore, based on a series of spectroscopy investigations, we quantified the electronic spatial coherence in different aggregations combined with the modified Franck-Condon model. Subsequently, we established the relationship between the processing method, the molecule aggregation, and the electronic spatial coherence.

The Astaxanthin Aggregation Pattern Greatly Influences Its Antioxidant Activity: A Comparative Study in Caco-2 Cells.

Astaxanthin is an excellent antioxidant that can form unstable aggregates in biological or artificial systems. The changes of astaxanthin properties caused by molecular aggregation have gained much attention recently. Here, water-dispersible astaxanthin H- and J-aggregates were fabricated and stabilized by a natural DNA/chitosan nanocomplex (respectively noted as H-ADC and J-ADC), as evidenced by ultraviolet and visible spectrophotometry, Fourier transform infrared spectroscopy, and Raman spectroscopy. Compared with J-ADC, H-ADC with equivalent astaxanthin loading capacity and encapsulation efficiency showed smaller particle size and similar zeta potential. To explore the antioxidant differences between astaxanthin H- and J-aggregates, H-ADC and J-ADC were subjected to H2O2-pretreated Caco-2 cells. Compared with astaxanthin monomers and J-aggregates, H-aggregates showed a better cytoprotective effect by promoting scavenging of intracellular reactive oxygen species. Furthermore, in vitro 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radical scavenging studies confirmed a higher efficiency of H-aggregates than J-aggregates or astaxanthin monomers. These findings give inspiration to the precise design of carotenoid aggregates for efficient utilization.

Photophysical properties of fluorescent imaging biological probes of nucleic acids: SAC-CI and TD-DFT Study.

Recently, exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) probe, which shows strong emission in the near-infrared region via hybridization to the target DNA and/or RNA strand, has been developed. In this work, photophysical properties of the chromophores of these probes and the fluorescent mechanism have been investigated by the SAC-CI and TD-DFT calculations. Three fluorescent cyanine chromophores whose excitation is challenging for TD-DFT methods, have been examined regarding the photo-absorption and emission spectra. The SAC-CI method well reproduces the experimental values with respect to transition energies, while the quantitative prediction by TD-DFT calculations is difficult for these chromophores. Some stable structures of H-aggregate system were computationally located and two of the configurations were examined for the photo-absorption. The present results support for the assumption based on experimental measurement in which strong fluorescence is due to the monomer unit in nearly planar structure and its suppression of probes is to the H-aggregates of two exciton units. Stokes shifts of these three chromophores were qualitatively reproduced by the theoretical calculations, while the energy splitting due to H-aggregate in the hybridized probe was slightly overestimated. © 2018 Wiley Periodicals, Inc.

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death.

BACKGROUND: The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail. METHODS: We use optical techniques, including fluorescence confocal microscopy and lifetime imaging microscopy (FLIM) both in model membranes built up as giant unilamellar vesicles (GUVs) and cultured cells. These experiments are complemented with computational studies to unravel the molecular mechanism that makes NAO cytotoxic. RESULTS: We have obtained direct evidence that NAO promotes strong membrane adhesion of negatively charged vesicles. The attractive forces are derived from van der Waals interactions between anti-parallel H-dimers of NAO molecules from opposing bilayers. Semi-empirical calculations have confirmed the supramolecular scenario by which anti-parallel NAO molecules form a zipper of bonds at the contact region. The membrane remodeling effect of NAO, as well as the formation of H-dimers, was also confirmed in cultured fibroblasts, as shown by the ultrastructure alteration of the mitochondrial cristae. CONCLUSIONS: We conclude that membrane adhesion induced by NAO stacking accounts for the supramolecular basis of its cytotoxicity. GENERAL SIGNIFICANCE: Mitochondria are a potential target for cancer and gene therapies. The alteration of the mitochondrial structure by membrane remodeling agents able to form supramolecular assemblies via adhesion properties could be envisaged as a new therapeutic strategy.

A molecular rotor based ratiometric sensor for basic amino acids.

The inevitable importance of basic amino acids, arginine and lysine, in human health and metabolism demands construction of efficient sensor systems for them. However, there are only limited reports on the 'ratiometric' detection of basic amino acids which is further restricted by the use of chemically complex sensor molecules, which impedes their prospect for practical applications. Herein, we report a ratiometric sensor system build on simple mechanism of disassociation of novel emissive Thioflavin-T H-aggregates from heparin surface, when subjected to interaction with basic amino acids. The strong and selective electrostatic and hydrogen bonding interaction of basic amino acids with heparin leads to large alteration in photophysical attributes of heparin bound Thioflavin-T, which forms a highly sensitive sensor platform for detection of basic amino acids in aqueous solution. These selective interactions between basic amino acids and heparin allow our sensor system to discriminate arginine and lysine from other amino acids. This unique mechanism of dissociation of Thioflavin-T aggregates from heparin surface provides ratiometric response on both fluorimetric and colorimetric outputs for detection of arginine and lysine, and thus it holds a significant advantage over other developed sensor systems which are restricted to single wavelength detection. Apart from the sensitivity and selectivity, our system also provides the advantage of simplicity, dual mode of sensing, and more importantly, it employs an inexpensive commercially available probe molecule, which is a significant advantage over other developed sensor systems that uses tedious synthesis protocol for the employed probe in the detection scheme, an impediment for practical applications. Additionally, our sensor system also shows response in complex biological media of serum samples.

Fluorescent H-Aggregates Hosted by a Charged Cyclodextrin Cavity.

Most macrocyclic host molecules, including cyclodextrins, usually prevent self-aggregation of the guest organic molecules, by exploiting inclusion complexation of the guest with the host. In this work, it was found that a negatively charged ß-cylcodextrin derivative induces aggregation of a well-known amyloid sensing dye, Thioflavin-T, and leads to an unprecedented formation of the rarely observed emissive H-type aggregates of the dye.

Investigation on the interaction of Safranin T with anionic polyelectrolytes by spectrophotometric method.

Understanding the role played by chemical additives such as NaCl salt, acid and Cetylpyridinium Chloride (CPC) surfactant on the interaction between dye and polyelectrolyte contributes to optimization of processes using polyelectrolytes in the removal of dye from aqueous solution. Herein we focus in the interaction between Safranin T, a cationic dye, with two anionic polyelectrolytes, poly(ammonium acrylate) and poly(acrylic acid) using spectrophotometric method and conductivity measurement. In aqueous solution, each of anionic polyelectrolytes forms a complex with the dye and induces a metachromasy indicated by the blue shift of the absorbance of the dye. The stoichiometry of complexes evaluated by the molar ratio method are 1:1 for Safranin T poly(ammonium acrylate) and 2:1 in the case of Safranin T poly(acrylic acid). The effect of additives on the stability of complexes has been studied by varying concentrations of the salt and the surfactant and pH of the solution. The thermodynamic parameters of interaction ΔG, ΔH and ΔS at different temperatures were evaluated to determine the stability constant of the complexes.

One-Dimensional Singlet Exciton Diffusion in Poly(3-hexylthiophene) Crystalline Domains.

Singlet exciton dynamics in crystalline domains of regioregular poly(3-hexylthiophene) (P3HT) films was studied by transient absorption spectroscopy. Upon the selective excitation of crystalline P3HT at the absorption edge, no red shift of the singlet exciton band was observed with an elapse of time, suggesting singlet exciton dynamics in relatively homogeneous P3HT crystalline domains without downhill relaxation in the energetic disorder. Even under such selective excitation conditions, the annihilation rate coefficient γ(t) was still dependent on time, γ(t) ∝ t(-1/2), which is attributed to anisotropic exciton diffusion in P3HT crystalline domains. From the annihilation rate coefficient, the singlet exciton diffusion coefficient D and exciton diffusion length LD in the crystalline domains were evaluated to be 7.9 × 10(-3) cm(2) s(-1) and 20 nm, respectively. The origin of the time-dependent exciton dynamics is discussed in terms of dimensionality.