Molecular Mechanism of Viscosity Sensitivity in BODIPY Rotors and Application to Motion-Based Fluorescent Sensors

Abstract

Viscosity in the intracellular microenvironment shows a significant difference in various organelles and is closely related to cellular processes. Such microviscosity in live cells is often mapped and quantified with fluorescent molecular rotors. To enable the rational design of viscosity-sensitive molecular rotors, it is critical to understand their working mechanisms. Herein, we systematically synthesized and investigated two sets of BODIPY-based molecular rotors to study the relationship between intramolecular motions and viscosity sensitivity. Through experimental and computational studies, two conformations (i.e., the planar and butterfly conformations) are found to commonly exist in BODIPY rotors. We demonstrate that the transformation energy barrier from the planar conformation to the butterfly conformation is strongly affected by the molecular structures of BODIPY rotors and plays a critical role in viscosity sensitivity. These findings enable rational structure modifications of BODIPY molecular rotors for highly effective protein detection and recognition.

A Systematic Study on the Relationship Between Viscosity Sensitivity and Temperature Dependency of BODIPY Rotors

“…For the transition from the planar state to the butterfly state, the energy barrier BDP2 needed to overcome was 0.016 eV, slightly lower than that of BDP1 (0.022 eV). 6 Therefore, it is reasonable for BDP2 to show a better viscosity response than BDP1, which is consistent with our previous work.…”

“…5 For BODIPY rotors, the conformational change between different excited states determines the viscosity response. 6 In the nonviscous environment, the low-energy barrier for conformation conversion makes BODIPY rotors enter the nonradiative state, showing low fluorescence. In the highly viscous environment, the transformation of molecular rotors to the nonemissive state is blocked, and most of the energy can only be relaxed through emission, producing strong fluorescence.…”

“…In our previous study, we have demonstrated BDP1 as a good molecular rotor with excellent viscosity sensitivity in the ethylene glycol-glycerol system. 6 Therefore, based on the structure of BDP1, we first synthesized BDP2-4 by changing the core structure of BODIPY for the systematic exploration of their viscosity sensitivities and temperaturedependent properties (Scheme 1(a)). The fundamental photophysical properties were first investigated ( Table 1 and Supporting Information Figure S1).…”

Photophysics of Fluorescent Contact Sensors Based on the Dicyanodihydrofuran Motif

“…Near the polarity where the maximum fluorescence quantum yield is found, the nonradiative decay rate due to the twisting motions is relatively small, and the dynamic range of the application of the viscosity probe is smaller than in solvents in which the twisting rate is high. The higher barrier to rotation may, however, reduce the sensitivity to solvent viscosity, as was recently found for BODIPY molecular rotors [36] . Finally, when two measurements are compared in which viscosity and polarity both change it may be difficult to disentangle the two effects on the fluorescence quantum yield or lifetime.…”

Quantum Chemical Study Aimed at Modeling Efficient Aza-BODIPY NIR Dyes: Molecular and Electronic Structure, Absorption, and Emission Spectra

“…The introduction of certain substituents into the parent compound allows aimed modification of its physicochemical properties. In this study, we focused on several aza-BODIPY dyes with red-shifted fluorescence and the potential for the environmental response via charge transfer [10], internal rotation [11], and aggregation causing mechanisms [8,12].…”