Supramolecular Dye Aggregate Assembly Enables Ratiometric Detection and Discrimination of Lysine and Arginine in Aqueous Solution

Abstract

Constructing sensor systems for rapid and selective detection of small biomolecules such as amino acids is a major area of focus in bioanalytical chemistry. Considering the biological relevance of arginine and lysine, significant efforts have been directed to develop fluorescent sensors for their detection. However, these developed sensors suffer from certain disadvantages such as poor aqueous solubility, technically demanding and time-consuming synthetic protocols, and more importantly, most of them operate through single wavelength measurements, making their performance prone to small variations in experimental conditions. Herein, we report a ratiometric sensor that operates through lysine- and arginine-induced dissociation of a supramolecular assembly consisting of emissive H-aggregates of a molecular rotor dye, thioflavin-T (ThT), on the surface of a polyanionic supramolecular host, sulfated β-cyclodextrin. This disassembly brings out the modulation of monomer–aggregate equilibrium in the system which acts as an ideal scheme for the ratiometric detection of lysine and arginine in the aqueous solution. Besides facile framework of our sensor system, it employs a commercially available inexpensive probe molecule, ThT, which provides an added advantage over other sensor systems that employ synthetically demanding probe molecules. Importantly, the distinctive feature of the ratiometric detection of arginine and lysine provides an inherent advantage of increased accuracy in quantitative analysis. Interestingly, we have also demonstrated that arginine displays a multiwavelength distinctive recognition pattern which distinguishes it from lysine, using a single supramolecular ensemble. Furthermore, our sensor system also shows response in heterogeneous, biologically complex media of serum samples, thus extending its possible use in real-life applications.

Thioflavin T: A versatile optical probe for chemo and biosensing

“…9). This proposition was well supported by absorbance, fluorescence CD spectroscopy and emission life time studies (Pettiwala and Singh, 2017).…”

“…This red-shift in absorption spectra indicated the dissociation of ThT aggregates from SCD surface, and release of ThT monomer in bulk water. The excited-state lifetime results were in conjunction with fluorescence and absorbance studies wherein it was observed that addition of arginine in ThT-SCD results in faster excited-state lifetime, thus indicating the disruption of ThT-SCD complex and release of ThT monomer in solution (Pettiwala and Singh, 2017).…”

“…In 2017, this ThT-SCD supramolecular dye aggregate template was explored to devise sensors for important biomolecules-arginine and lysine (Pettiwala and Singh, 2017). This sensor system was based on the principle that basic amino acids such as arginine and lysine would interact electrostatically with the anionic SCD which, may result in dissociation of ThT aggregates from SCD.…”

“…ThT H-aggregates from the surface of SCD towards monomeric form of ThT resulted in decrease of emission intensity. The shift in the population of ThT-SCD aggregate form (highly emissive) to ThT monomer form (weakly emissive) on addition of arginine, allows ratiometric detection of arginine by monitoring the ratio of emission intensities at 545 nm (aggregate form) and 490 nm (monomeric form), thus yielding a quantitative estimation of arginine (Pettiwala and Singh, 2017).…”

“…One such cationic dye which has been extensively used as fluorescent probe for sensing wide variety of analyte is Thioflavin-T. Thioflavin-T (ThT) belongs to the class of ultrafast molecular rotor dye, which has the inherent ability to undergo the nonradiative ultrafast bond twisting process around single C-C bond (Scheme 1) that makes this molecule practically non-emissive in free state and in solvents of low viscosity (Haidekker et al, 2010;Singh et al, 2010a). However, in a highly viscous media or in a 518 Aafrin M Pettiwala et al have also provided a brief account of the supramolecular interactions between ThT and macrocyclic host molecules which have been further used for efficient and selective sensing of proteins (Pettiwala and Singh, 2018a) and amino acids (Pettiwala and Singh, 2017). Thus, through this short account, we aim to provide the key sensory applications of Thioflavin-T in chemo and bio-sensing field.…”