A multiscale study on photophysical properties of a novel fluorescent probe for imaging amyloid-β in Alzheimer's disease

Detection of amyloid-beta deposition in the brain region is of significant importance for early diagnosis of Alzheimer's disease (AD). In the last few decades, the fluorescent imaging technique has been considered an effective tool for detecting amyloid-beta plaques due to its safety, sensitivity, and operability. Thus, numerous fluorescent probes for amyloid-beta have been developed. The design of a probe with high selectivity and improved sensing performance requires knowledge about the potential binding sites for the probe in amyloid-beta and local microstructure of the probe in different sites. In this study, amyloid-beta-specific photophysical properties of a novel fluorescent probe (cis-PAD-1) are theoretically investigated by using multiscale simulations, including molecular docking and quantum mechanics/molecular mechanics calculations. Binding profile of cis-PAD-1 in amyloid-beta has been simulated, and binding affinity of the probe in various sites is calculated. An excited-state property study on cis-PAD-1 illustrates that the probe shows remarkable fluorescence enhancement in amyloid-beta due to the influence of the microenvironment, which is consistent with the experimental observation. Most importantly, two-photon absorption cross section of the probe is greatly increased in the near-infrared region when targeting with amyloid-beta owing to the enhanced transition dipole moment. Therefore, one can propose the usage of cis-PAD-1 as an excellent candidate in two-photon fluorescent imaging for amyloid-beta. The detailed investigations provide information on the development and design strategy of a new fluorescent probe for amyloid-beta imaging in AD.