Synthesis and Characterization of Novel Thienothiadiazole-Based D-π-A-π-D Fluorophores as Potential NIR Imaging Agents

Nicholas E Sparks; Sajith M Vijayan; Juganta K Roy; Austin Dorris; Ethan Lambert; Dilan Karunathilaka; Nathan I Hammer; Jerzy Leszczynski; Davita L Watkins

doi:10.1021/acsomega.3c02602

Synthesis and Characterization of Novel Thienothiadiazole-Based D-π-A-π-D Fluorophores as Potential NIR Imaging Agents

ACS Omega. 2023 Jun 28;8(27):24513-24523. doi: 10.1021/acsomega.3c02602. eCollection 2023 Jul 11.

Authors

Affiliations

¹ Department of Chemistry and Biochemistry, University of Mississippi University, Oxford, Mississippi 38677, United States.
² Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
³ Interdisciplinary Center for Nanotoxicity, Department of Chemistry, Physics and Atmospheric Sciences, Jackson-State University, Jackson, Mississippi 39217, United States.
⁴ William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 151 W Woodruff Avenue, Columbus, Ohio 43210, United States.

Abstract

As fluorescence bioimaging has increased in popularity, there have been numerous reports on designing organic fluorophores with desirable properties amenable to perform this task, specifically fluorophores with emission in the near-infrared II (NIR-II) region. One such strategy is to utilize the donor-π-acceptor-π-donor approach (D-π-A-π-D), as this allows for control of the photophysical properties of the resulting fluorophores through modulation of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels. Herein, we illustrate the properties of thienothiadiazole (TTD) as an effective acceptor moiety in the design of NIR emissive fluorophores. TTD is a well-known electron-deficient species, but its use as an acceptor in D-π-A-π-D systems has not been extensively studied. We employed TTD as an acceptor unit in a series of two fluorophores and characterized the photophysical properties through experimental and computational studies. Both fluorophores exhibited emission maxima in the NIR-I that extends into the NIR-II. We also utilized electron paramagnetic resonance (EPR) spectroscopy to rationalize differences in the measured quantum yield values and demonstrated, to our knowledge, the first experimental evidence of radical species on a TTD-based small-molecule fluorophore. Encapsulation of the fluorophores using a surfactant formed polymeric nanoparticles, which were studied by photophysical and morphological techniques. The results of this work illustrate the potential of TTD as an acceptor in the design of NIR-II emissive fluorophores for fluorescence bioimaging applications.