Abstract
Fluorescence analysis is a highly sensitive, specific, and non-destructive technology that enables real-time detection and analysis in diverse fields such as biology, medicine, materials science, and environmental studies. Despite its extensive use and importance, the development of fluorescence technology is limited by the insufficient understanding of its mechanisms and the availability of suitable fluorophores. In addition, traditional methods for screening high-performance fluorophores rely on trial-and-error approaches that are time-consuming, labor-intensive, and generate significant amounts of chemical waste during synthesis. However, with the advent of computational analysis, it is now possible to generate large amounts of virtual data and conduct virtual screens of fluorophore candidates to optimize molecular designs, thereby addressing the existing challenges associated with the development of fluorescence technology. Furthermore, this approach offers a low-cost and high-speed alternative to traditional screening methods, making it a powerful tool for advancing fluorescence technology. In this paper, we first presented a new mechanism: the energy transfer followed by the electron transfer (ETET) process in the molecular dyad TPE-NBD. Energy transfer enhances the fluorescence of TPE-NBD in non-polar solvents; in contrast, the activation of electron transfer in polar solvents markedly quenched TPE-NBD emissions. Collectively, ETET endows TPE-NBD with significant environmental sensitivities, enabling many functional materials with remarkable properties. Furthermore, we developed two models to design fluorophores with specific properties. One is the multi-donor strategy that leads to desirable bathochromic shifts, and large Stokes shifts with minimal structural changes for creating long-wavelength fluorescent proteins (LWFPs). Our analysis provides rational guidelines for selecting (1) the substituent position, (2) the electron-donating strength, and (3) the number of electron-donating groups for developing LWFPs. Another model revealed the molecular origin of low quantum yields in the closed-form rhodamines and proposed a design method to enhance their emissions. This is achieved by judiciously choosing three molecular fragments in rhodamine analogs with matched frontier molecular orbitals to stabilize the locally excited state. Such dual-emission rhodamine analogs have potential applications in advanced bioimaging and biosensing. Our research vision is to transform fluorophore chemistry through computational techniques and data-driven insights. Rather than employing a trial-and-error approach, we seek to enable the molecular engineering of tailored fluorescent properties. By achieving this vision, we aim to provide researchers with an unparalleled ability to engineer fluorophores with targeted attributes.