Development of Xanthene‐Based Fluorescent Dyes: Machine Learning‐Assisted Prediction vs. TD‐DFT Prediction and Experimental Validation

Abstract

A large number of xanthene-based fluorescent dyes have been reported with unique photophysical properties. Further development of this group of useful chemicals processes challenges due to the massive amount of discrete data and unavoidable human errors in analyzing the data. Given recent advances in data analysis techniques, we integrated machine learning methods with a chemical database to assist identification of useful xanthene dyes in this study. Based on the xanthene dye database a machine learning model (named ATTRNN) was developed and applied in predicting excitation and emission wavelengths of six new dyes. The comparison of machine learning prediction with time-dependent density functional theory (TD-DFT) calculation, as well as experimental validation demonstrated the usefulness of ATTRNN. Moreover, the new dyes were used to develop fluorescent sensors for hydrogen sulfide and cysteine, which further proved the value of datadriven dye discovery.

Machine Learning Spectroscopy Using a 2-Stage, Generalized Constituent Contribution Protocol

“…The prediction of spectral properties often depends on computer modeling. For example, time dependent-density functional theory (TD-DFT) has been employed to predict the electron absorption spectrum and maximum absorption wavelength [ 18 – 20 ]. In fact, TD-DFT has been developed for decades and achieved success in spectra prediction [ 21 ].…”

Benzothiazole-Derived Sulfones and Sulfoxides as Reactive Templates for Biothiols and Sulfane Sulfurs

“…For comparison the corresponding sulfones (11a−d) were also tested. Since oxadiazole and tetrazole sulfones (13,15) react similarly as benzothiazole sulfones in thiol-blocking, 5 their sulfoxides (12,14) were also prepared and tested. These compounds were treated with a model RSH substrate 2 in a 1:1 DMF/PBS solution.…”

“…To further demonstrate the efficiency of these sulfoxides in blocking thiols under cellular environments, we carried out cell imaging with Cys-Fl4, a thiol-specific probe. 15 As shown in Figure 6, HeLa cells treated with Cys-Fl4 showed obvious red fluorescence, reflecting cellular free thiols. However, if the cells were pretreated with 10b, the addition of Cys-Fl4 resulted in significantly decreased fluorescence.…”

“…Having demonstrated that compound 1 was a selective fluorescent sensor for H 2 S n , we next prepared and tested two more sensors ( 8 and 9 , Figure ) employing O -methylfluorescein and Fl4, a near-infrared fluorophore developed by our group, as the fluorophores. Similar to 1 , their fluorescence was turned on by H 2 S n in ∼20 min while they showed little response to Cys and GSH under the same conditions.…”