Emissive H-Aggregates of an Ultrafast Molecular Rotor: A Promising Platform for Sensing Heparin

Abstract

Constructing "turn on" fluorescent probes for heparin, a most widely used anticoagulant in clinics, from commercially available materials is of great importance, but remains challenging. Here, we report the formation of a rarely observed emissive H-aggregate of an ultrafast molecular rotor dye, Thioflavin-T, in the presence of heparin, which provides an excellent platform for simple, economic and rapid fluorescence turn-on sensing of heparin. Generally, H-aggregates are considered as serious problem in the field of biomolecular sensing, owing to their poorly emissive nature resulting from excitonic interaction. To the best of our knowledge, this is the first report, where contrastingly, the turn-on emission from the H-aggregates has been utilized in the biomolecule sensing scheme, and enables a very efficient and selective detection of a vital biomolecule and a drug with its extensive medical applications, i.e., heparin. Our sensor system offers several advantages including, emission in the biologically advantageous red-region, dual sensing, i.e., both by fluorimetry and colorimetry, and most importantly constructed from in-expensive commercially available dye molecule, which is expected to impart a large impact on the sensing field of heparin. Our system displays good performance in complex biological media of serum samples. The novel Thioflavin-T aggregate emission could be also used to probe the interaction of heparin with its only clinically approved antidote, Protamine.

An Ultrafast Molecular‐Rotor‐Based Fluorescent Turn‐On Sensor for the Perrhenate Anion in Aqueous Solution

“…The average excited‐state lifetime was calculated to be 0.68 ns. Similar extended decay kinetics have been recently noted for ThT aggregates induced by a negatively charged therapeutic biomolecule . The long excited‐state lifetime suggests the presence of aggregated species in which the non‐radiative torsional relaxation of ThT fragments is significantly suppressed in comparison with the monomer form of ThT.…”

“…It should be noted that the ThT monomer, although displaying large fluorescence enhancement under confinement, does not show any significant shift in its emission maximum (490 nm) . In contrast, ThT aggregates are reported to display an appreciable redshift in the emission maximum, as well as a large increase in emission intensity . Thus, the appreciable redshift of around 35 nm in the emission maximum of ThT in the presence of the perrhenate anion indicates the presence of ThT aggregates in the present system.…”

“…Very recently, ThT has also been reported to display emission enhancement in its aggregated form, which has been further used to construct a sensor for the widely used blood anti‐coagulant Heparin . It should be noted that the ThT monomer, although displaying large fluorescence enhancement under confinement, does not show any significant shift in its emission maximum (490 nm) .…”

“…For this purpose, we chose an ultrafast molecular rotor probe, Thioflavin‐T, which shows large segmental flexibility in the monomeric form and is also very weakly emissive in the monomeric form . However, recently, the aggregates of ThT have been reported to show a large fluorescence turn‐on response . Indeed, as we expected, ThT leads to the formation of aggregates in the presence of the perrhenate anion in aqueous solution and subsequently leads to an enhanced fluorescence response, thereby providing a unique opportunity for sensing perrhenate anion in aqueous solution.…”

Molecular Viscosity Sensors with Two Rotators for Optimizing the Fluorescence Intensity–Contrast Trade‐Off

“…Synthetic molecular rotors have highp otential in various photonic, [1][2][3] electronic, [4][5][6] and biological applications. [7][8][9][10][11] In molecular rotors, rotational groups ("rotators"), linked by either covalent bonds [12][13][14] or noncovalent coordination bonds [15][16][17] to ap art of the molecular rotors, are rotated along an axle. In pconjugated molecular rotors, the rotationofr otators is affected by the p-electron delocalization characteristics, resulting in a change of photophysical properties related to electronic states, such as fluorescencea nd charge transfer.…”