TD-DFT-Validated Guidelines for BOPHY Molecular Rotors as Fluorescent Viscosity Sensors

Abstract

Fluorescent molecular rotors (FMRs) based on BOPHY (a boron bis(pyrrolyl-methylene)hydrazine chelate) platforms are emerging as promising viscosity sensors for biological imaging, yet the rational design of new derivatives lacks reliable computational guidelines. We present a systematic TD-DFT study of 30 derivatives of BOPHY and its five-membered-ring diphenylboron isomer, PYDBO, in two stages. First, benchmarking four exchange-correlation functionals against experiment identifies TPSSh/6-31+G** for absorption and PBE0/LR/6-31+G** for emission as optimal levels of theory; crucially, the linear-response solvation formalism outperforms the more rigorous state-specific approach for emission in these rigid, low-polarity boron platforms, a result with broad implications for TD-DFT studies of BODIPY-related fluorophores. Second, each derivative is multiparametrically screened against six rational design indicators spanning conformational, spectral, and dynamic properties (Förster–Hoffmann criterion). This screening identifies six viscosity-sensing candidates─3a, 5a, 6a, 1b, 4b (BOPHY 1), and 1f (PYDBO 3)─and reveals a counterintuitive platform–rotor compatibility: xylyl rotors are far less hindered on BOPHY 2/PYDBO 3 than on BOPHY 1. Among the candidates, 5a shows the lowest excited-state barrier, 4b the highest oscillator strength, and 1f the most red-shifted emission─priority targets for experimental synthesis and cellular viscosity imaging.