A2B- and A3-Type Boron(III)Subchlorins Derived from meso-Diethoxycarbonyltripyrrane: Synthesis and Photophysical Exploration.

The first direct fabrication of A2B- and A3-type B(III)subchlorins from meso-ethoxycarbonyl-substituted tripyrrane has been realized by condensation with appropriate acid chlorides (benzoyl chloride, butyryl chloride, and ethyl chlorooxoacetate). The aliphatic acid chloride-based annulation reaction is new to subporphyrinoid chemistry. The phenyl (6a)- or n-propyl (6b)-substituted derivatives could be oxidized to the corresponding B(III)subporphyrins upon refluxing with DDQ, whereas the triethoxycarbonyl moiety (6c) was found to be resistant to oxidation and exhibits the most red-shifted absorption (587 nm) and emission (604 nm). The study indicates that absorption and emission behaviors of the B(III)subchlorin can be tuned by the introduction of electron-rich or electron-deficient substituents at the meso-position. B(III)subchlorins 6a and 6c generate singlet oxygen efficiently (44 and 40%, respectively) and, thus, may find application as potential photosensitizers in photodynamic therapy (PDT).

Structural Stability and Conformational Dynamics of Cytochrome c in Hydrated Deep Eutectic Solvents.

Many deep eutectic solvents (DESs) are currently being explored as environment-friendly media for biorelated applications. As an understanding of the effect of these solvents on the structure of biomolecules is crucial for these applications, we study how two DESs comprising trimethylglycine (TMG) and ethylene glycol (EG) or glycerol (GL) influence the structural stability and conformational dynamics of cytochrome c (Cytc) using single-molecule-based fluorescence correlation spectroscopy (FCS) technique and several other ensemble-based biophysical methods. The FCS studies on A488-labeled Cytc enable an estimation of the size (20.5 ± 1.5 Å) of the protein and capture its conformational dynamics (54 ± 2 µs) in aqueous buffered solution. It is observed that both size and conformational dynamics of the protein are influenced in the presence of the DESs, but this effect is more pronounced in the case of TMG-EG. The ensemble measurements on both labeled and wild-type Cytc reveal that the protein structure is unfolded completely by TMG-EG, whereas the structure is slightly altered by TMG-GL. The results suggest that the behavior of Cytc in hydrated DESs is determined by the strength of interactions between the DES constituents as well as that between the constituents and the water molecules present in the system.

Sensing and modulation of amyloid fibrils by photo-switchable organic dots.

Abnormal aggregation of amyloidogenic proteins (like Aß 42, amylin, α-synuclein, insulin) and the deposition of these aggregates is believed to be associated with several diseases known as amyloidosis. The pathway of aggregation involves three distinct phases: the oligomeric, elongation and plateau phases. Among them, the oligomeric phase of Aß 42 and α-synuclein involves the generation of transient oligomeric species suspected to cause several neurological disorders, including Alzheimer's and Parkinson's diseases. Over the past few years, scientists have devoted much more effort to devising new fluorescent molecular probes to estimate the mechanisms of formation, and have gained vital information about possible therapeutic routes for amyloidosis. However, such fluorescent probes face serious limitations because of self-quenching at high concentrations of the probe; therefore, they are inappropriate for quantitative analysis and bio-imaging experiments. Hence, smart biocompatible fluorescent probes are indispensable, as they not only overcome the drawbacks of conventional fluorescent probes, but also have the potential ability to fight amyloidosis through modulation of the pathways involved. In this work, for the first time we introduce a series of promising photo-switchable aggregation-induced emission (AIE) dots (DPAPMI, CPMI) and aggregation caused quenching (ACQ) dots (DMAPMI) which can detect amyloid fibrils in terms of switching and enhancing their fluorescence emission. Interestingly, the organic dots enhance the aggregation rate of insulin by speeding up the microscopic processes, specifically secondary nucleation (with rate constant k2) and the elongation process (with rate constant k+). Moreover, the comparison of kinetics studies with ThT suggests that our organic dots can sense pre-fibrillar aggregates of insulin during the aggregation process, which may be beneficial for the early detection of amyloid fibrils. In summary, our study indicates that these organic dots can be used for the imaging and early stage detection of amyloid fibril formation and the modulation of amyloid formation pathways.

Complete Solvation Dynamics of Coumarin 153 in Tetraalkylammonium Bromide-Based Deep Eutectic Solvents.

Deep eutectic solvents (DESs) are novel environment-friendly media for a variety of applications. In order to obtain insight into the structure and dynamics of some less-explored DESs comprising ethylene glycol and tetraalkylammonium bromide salts with variable alkyl chain length, we have captured complete dynamics occurring in these solvents in a timescale of few femtoseconds to several nanoseconds by monitoring the time-dependent fluorescence Stokes shift of coumarin 153 employing a combination of time-correlated single-photon counting and fluorescence upconversion techniques. The solvent response function constructed from the measured data reveals a sub-picosecond component (∼0.8 ps, 20-35%) in addition to a slow component (180-475 ps) with a distribution of relaxation time. The slow time component is found to be strongly dependent on the viscosity of the medium, indicating that it arises from the diffusive motions of the solvent constituents into and out of the solvation shell, whereas the ultrafast time component, which is nearly independent of the solvent viscosity, arises from fast local motions of the constituents in the immediate vicinity of the solute molecule.

Insights into the Folding Pathway of a c-MYC-Promoter-Based i-Motif DNA in Crowded Environments at the Single-Molecule Level.

Cytosine-rich DNA sequences fold into secondary structures called i-Motifs, which are usually stable at acidic pH. However, molecular crowding agents, such as poly(ethylene glycol) (PEG), are known to facilitate the formation of these structures even at neutral pH. As crowding mimics the intracellular environment and not much is known about the folding pathway of i-Motifs in such constrained media, we have probed, in detail, the conformational changes of a 22-mer c-MYC-promoter-based C-rich sequence (Py22) in the presence of PEG, employing Förster resonance energy transfer and fluorescence lifetime measurements at the single-molecule level. We find that the folding process is not a simple two-state transition between a random coil and a folded i-Motif structure. Rather, it involves a partially folded conformation as an intermediate in which the bases are not as efficiently stacked as in the completely folded i-Motif form. The relative population of each species is governed by the size and concentration of PEG, and 30% (w/w) PEG6000 is the optimum condition for the folding of Py22. Under this condition, ∼80% of Py22 exists in the fully folded i-Motif form and ∼20% of it is in the partially folded state.

Liquid Structure and Dynamics of Tetraalkylammonium Bromide-Based Deep Eutectic Solvents: Effect of Cation Chain Length.

Deep eutectic solvents (DESs) have emerged in recent years as environmentally sustainable media across several fields. However, knowledge of liquid structure, dynamics, and solute-solvent interactions in many DESs that is essential for exploiting their potential is still lacking. In this work, we make an attempt to obtain some insight into these aspects of a set of less-explored DESs comprising tetraalkylammonium bromide salts and ethylene glycol (EG) by monitoring the fluorescence response of some carefully chosen dipolar (C153 and 4-AP) and nonpolar (9-PA) solutes in these media. Specifically, we have studied the translational and rotational diffusion dynamics of these molecular systems using single-molecule-based fluorescence correlation spectroscopy technique and ensemble-based time-resolved fluorescence anisotropy measurements. These results point to spatial and dynamic heterogeneity of these DESs, which becomes prominent in systems comprising cations with a longer alkyl chain length. This study reveals that diffusion dynamics of the probe molecules is determined not only by the solvent bulk viscosity but also dependent on their microenvironments and solute-solvent interactions experienced in these media.

Interactions between a Bioflavonoid and c-MYC Promoter G-Quadruplex DNA: Ensemble and Single-Molecule Investigations.

Small molecules capable of stabilizing the G-quadruplex structure of the nuclease hypersensitivity element III1 (NHE III1) are useful in controlling the overexpression of the c-MYC oncogene. In this study, we have probed the interactions of a 22-mer c-MYC promoter quadruplex-forming sequence (Pu22) with a bioflavonoid 3,4',5,7-tetrahydroxyflavone, commonly known as kaempferol (KF). Ensemble fluorescence resonance energy transfer experiments on labeled Pu22 indicate that KF decreases the affinity of the former toward its complimentary strand, suggesting the stabilization of the quadruplex structure of Pu22. Considering that binding dynamics plays an important role in supramolecular interactions, there is hardly any information on this aspect for quadruplex-flavonoid systems; we have studied the kinetics of KF-Pu22 complexation and decomplexation processes on the single-molecule level by employing fluorescence correlation spectroscopy technique. The binding dynamics is characterized by a fast relaxation time of 10-50 µs. This leads to a high association rate constant ( k+) of ∼109 M-1 s-1, which is close to the pure diffusion controlled limit. However, it is the low dissociation rate constant ( k-) of ∼104 s-1 that is mainly responsible for the stability of the KF-Pu22 complex. Molecular docking study shows that KF binds near the 3'-end of Pu22 by forming several H-bonds with the bases. These findings suggest that KF is a potential binder of the c-MYC promoter quadruplex DNA and can be useful in anticancer therapies.

Two-dimensional lanthanide coordination polymer nanosheets for detection of FOX-7.

Despite the recent surge of interest in two-dimensional (2D) inorganic nanosheets derived from photoactive coordination polymers of lanthanide ions having interesting optical properties, research in this area is still in its infancy. Luminescent lanthanide ions, Eu(iii) or/and Tb(iii), as well as a bis-terpyridine ligand (L), were used in this study as the building blocks for the synthesis of the archetypical layered structure of coordination polymers (CPs) (L·Eu/L·Tb). 2D-nanosheets were obtained through exfoliation of the layered precursor of CPs in a suitable solvent system following a sonication-assisted strategy. These nanosheets exhibit lateral sizes on the micrometer scale (0.3-1 µm) and an ultrathin thickness of 2-6.5 nm. 1,1-Diamino-2,2-dinitroethene or FOX-7 is an insensitive high explosive; in a binder mixture, it exhibits a slightly superior detonation velocity of 8870 m s-1 in comparison to RDX. The insensitive nature of FOX-7 makes it a key component for the development of low vulnerable high explosive compositions for further application in weaponry. The growing demand for FOX-7, for use as a suitable replacement of conventional explosives, is of serious concern to human security. Achieving rapid and efficient detection of this unexplored explosive is a challenging task. In the present study, the developed luminescent nanosheets were used for the first time for micromolar level detection of FOX-7 both in solution and in the solid state. A visually distinct color change of the nanosheets from red (L·Eu) and green (L·Tb) to colorless was witnessed upon UV light irradiation during the detection process. Notably, the solid-state detection technique could be exploited for developing a commercial spray kit for quick onsite screening of this important explosive.

How do the hydrocarbon chain length and hydroxyl group position influence the solute dynamics in alcohol-based deep eutectic solvents?

Deep eutectic solvents (DESs) have received considerable attention in recent years as new sustainable green media and some of their interesting properties have stimulated investigations on the microscopic solution structure, solute-solvent interactions and solute/solvation dynamics in these media. Even though the alcohol-based DESs, due to their low viscosity, serve as useful media in various applications, little is known about the structure and dynamics of these solvents. In order to obtain insight into the microscopic structure and interactions operating in these media, we have studied the rotational and translational diffusion dynamics of some carefully chosen molecular systems (both dipolar and nonpolar) using time-resolved fluorescence anisotropy and fluorescence correlation spectroscopy techniques in a series of choline chloride/alcohol based DESs differing in hydrocarbon chain length and positioning of the hydroxyl group on the hydrogen bond donor. The results reveal an increase of both spatial and dynamic heterogeneity upon an increase in chain length of one of the components of these solvents. No significant variation of heterogeneity, however, could be observed with the change in the hydroxyl group position. The analysis of the experimental results indicates that solute-solvent hydrogen-bonding interaction plays a dominant role in determining both rotational and translational diffusion dynamics of AP in these DESs.

Solute Rotation and Translation Dynamics in an Ionic Deep Eutectic Solvent Based on Choline Chloride.

Deep eutectic solvents (DESs) are an emerging class of environment-friendly media useful in a variety of applications. However, the microscopic structure of these liquids is quite unclear, and issues like whether spatial and dynamic heterogeneity is a generic feature of the ionic DESs and whether the solute molecules experience similar environment and interactions with the medium irrespective of their charge are still open. In this work, we have attempted to address some of these issues for ethaline, a less viscous and ionic DES consisting of a mixture of 1:2 mole ratio of choline chloride and ethylene glycol by monitoring the fluorescence response of a number of carefully chosen neutral and charged probe molecules in ensemble and single molecule conditions. Specifically, we have examined the liquid state structure of ethaline by studying the rotational and translational diffusion dynamics of the solutes measured by monitoring the time dependence of fluorescence anisotropy in ensemble condition and fluorescence correlation signal of extremely dilute samples diffusing through confocal volume. These studies clearly reveal dynamic heterogeneity of the medium, though no spatial heterogeneity is observable through excitation wavelength dependent fluorescence measurements. The insights obtained from this study will be helpful in understanding the nature of solute-solvent interactions in this type of complex media.

Roles of the methyl and methylene groups of mercapto acids in the photoluminescence efficiency and carrier trapping dynamics of CdTe QDs.

Surface protection using an appropriate ligand is essential for controlling the size, stability and luminescence properties of the quantum dots (QDs). Though 3-mercaptopropanoic acid (3-MPA) is regarded as the most suitable protecting ligand among the mercapto acids for water soluble CdTe QDs, one receives a different picture from recent studies, which report a much higher luminescence efficiency of 3-mercaptobutyric acid (3-MBA) capped QDs compared with those capped by 3-MPA and attribute the observation to the influence of the side methyl group of mercapto acids. Herein we report the luminescence properties and carrier trapping dynamics of four different, but structurally related mercapto acid capped CdTe QDs prepared using a different method. The results show that these QDs are much more fluorescent than those prepared directly in an aqueous environment and surprisingly, no enhanced luminescence for the QDs capped by mercapto acids containing a side methyl group is observed. Ultrafast pump-probe measurements confirm these results in addition to providing insight into the carrier trapping dynamics of these systems. It is shown that our findings, which appear to be in conflict with the recent literature, can be rationalized and the exact role of the side methyl group of the mercapto acids can be understood by careful analysis of the results taking into consideration the difference in the methods of preparation of the QDs in the two cases.