Monitoring the formation of insulin oligomers using a NIR emitting glucose-conjugated BODIPY dye.

Protein oligomers, which are formed due to the aggregation of protein molecules under physiological stress, are neurotoxic and responsible for several neurological diseases. Early detection of protein oligomers is essential for the timely intervention in the associated diseases. Although several probes have been developed for the detection of insoluble matured protein fibrils, fluorescent probes with emission in the near infrared (NIR) region for probing protein oligomers are very rare. In the present study we have designed and synthesized a glucose-conjugated BODIPY dye with emission in the NIR spectral range. Our detailed studies show that the new probe is not only capable of detecting matured fibrils but can also probe the formation of oligomers from the native protein. The new probe shows a large increase in its emission intensity upon association with oligomers and matured fibrils. Hence, the present probe has a great potential for the in vivo imaging of protein oligomers and matured fibrils. Detailed spectroscopic properties of the new probes in molecular solvents have been performed to understand its oligomers- and fibril- sensing mechanism.

Benzothiazole-Based Neutral Ratiometric Fluorescence Sensor for Amyloid Fibrils.

Early detection of amyloid fibrils is very important for the timely diagnosis of several neurological diseases. Thioflavin-T (ThT) is a gold standard fluorescent probe for amyloid fibrils and has been used for the last few decades. However, due to its positive charge, ThT is incapable of crossing the blood-brain barrier and cannot be used for in vivo imaging of fibrils. In the present work, we synthesized a neutral ThT derivative, 2-[2'-Me,4'-(dimethylamino)phenyl]benzothiazole (2Me-DABT), which showed a strong affinity towards the amyloid fibrils. On association with the amyloid fibrils, 2Me-DABT not only showed a large increase in its emission intensity, but also, unlike ThT, a large blueshift in its emission spectrum was observed. Thus, unlike ThT, 2Me-DABT is a potential candidate for the ratiometric sensor of the amyloid fibrils. Detailed photophysical properties of 2Me-DABT in amyloid fibrils and different solvent media were studied to understand its sensory activity. Fluorescence resonance energy transfer (FRET) studies suggested that the sites of localization for ThT and 2Me-DABT in amyloid fibrils are not same and their average distance of separation in amyloid fibrils was determined. The experimental data was nicely supported by molecular docking studies, which confirmed the binding of 2Me-DABT in the inner core of the amyloid fibrils.

An ultrafast molecular rotor based ternary complex in a nanocavity: a potential "turn on" fluorescence sensor for the hydrocarbon chain.

Formation of a ternary complex by an ultrafast molecular rotor (UMR) with a macrocyclic cavitand has been investigated for the sensitive detection of the alkyl chain of a surfactant. A benzothiazole based UMR, Thioflavin-T (ThT), has been used as a fluorescent probe. It is shown that ThT forms a very weak inclusion complex with γ-cyclodextrin (γ-CD) with an association constant of 8.8 M(-1). However, the addition of a small amount of surfactant results in a significant increase in the emission intensity of ThT in γ-CD solution. From detailed steady-state and time-resolved fluorescence measurements and NMR studies, it has been inferred that the addition of the surfactant results in the formation of a ternary complex through the inclusion of its alkyl chain inside the γ-CD nanocavity. In such a ternary complex, the non-radiative torsional motion in ThT is largely prevented due to a large increase in the frictional force inside the nanocavity and results in a significant fluorescence enhancement. The formation of the binary and the ternary complexes in the present system has been further supported by the molecular docking and subsequent molecular dynamics simulation studies. The present result indicates that the inclusion complex with an UMR as a guest could be a potential candidate for the efficient detection of insoluble organic molecules, especially hydrocarbons.

Rational design of boradiazaindacene (BODIPY)-based functional molecules.

Three boradiazaindacene (BODIPY) dyes with different-coloured (greenish-yellow, orange and red) fluorescence and good Stokes shifts were synthesised starting from the greenish-yellow BODIPY dye PM546. The high Stokes shifts of the dyes are due to the release of the steric strain in their excited states relative to that in the highly twisted ground states. One of these compounds might be a useful water-soluble fluorophore, whereas the other two are promising H(+) sensors.

Ultrafast molecular rotor: an efficient sensor for premelting of natural DNA.

Structural changes in nucleic acids in the premelting region (T < melting temperature, T(m)) play an important role in the biological activity of DNA at physiological temperature. In the present communication we report the use of an ultrafast molecular rotor as an extrinsic fluorescence sensor to monitor the structural changes in natural DNA at T < T(m), which could not be detected even by circular dichroism spectroscopy. Further, the fluorescence sensor used in the present study is superior than most commonly used DNA stains.

Origin of ultrafast excited state dynamics of 1-nitropyrene.

Time-resolved emission measurements in subpicosecond time domain have been carried out for 1-nitropyrene in different solvents to understand the mechanism for the observed ultrafast decay of its first excited singlet state. Excited-state dynamics of 1-nitropyrene is found to be independent of the solvent viscosity. This result contradicts the proposition in the literature (J. Phys. Chem. A 2007, 111, 552) that the ultrafast decay in 1-nitropyrene is due to the large amplitude torsional motion of the nitro group around the pyrene moiety. Excited-state dynamics of 1-nitropyrene in solvents with different dielectric constants shows that excited-state lifetime suddenly increases after a certain value of the dielectric constant. Detailed quantum chemical calculations have been carried out to understand the process that is responsible for the observed effect of the dielectric constant on the excited-state dynamics of 1-nitropyrene. It is seen that the excited-state lifetime and the singlet-triplet energy gap follow similar variation with the dielectric constant of the medium. Such a correlation between the excited-state lifetime and the singlet-triplet energy gap supports the fact that the observed ultrafast decay for 1-nitropyrene is due to an efficient intersystem crossing rather than to the torsional motion of the nitro group as proposed in the literature.