Sensing Performance Investigations on Two-Photon Fluorescent Probes for Detecting β-Amyloid in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is one of the most common forms of senile disease. In recent years, the incidence of AD has been increasing significantly with the acceleration of the aging process of the global population. However, current clinical drugs can only alleviate the symptoms of AD patients without healing the disease fundamentally. Therefore, it is of great significance to develop an effective small molecule diagnostic reagent for the early diagnosis of AD. In this paper, we employ an integrated approach, including molecular docking simulation and quantum mechanics/molecular mechanics calculation, to investigate the sensing performance of a series of donor–acceptor structural probes for the marker protein of AD (β-amyloid). Results show that the probes display evident fluorescence enhancement when bound to the β-amyloid, suggesting the effect of the environment on the molecular properties. Especially, the two-photon absorption cross-section of the probes increase drastically in the β-amyloid compared to that in vacuum, which results from the larger electron delocalization and dipole moment in the fibrillary-like environment. Thus, one can propose that the studied probes are capable of application in two-photon fluorescent imaging, particularly those containing naphthalene rings as the donor or with a longer spacer group. Our calculations elucidate the experimental measurements reasonably, and further establish possible structure–property relationships that can be used to design novel biocompatible two-photon fluorescent probes for the diagnosis of Alzheimer’s.

Versatile Dicyanomethylene-Based Fluorescent Probes for the Detection of β-Amyloid in Alzheimer’s Disease: A Theoretical Perspective

“…The emission peak calculated for probes 3, 8, 11, and 13 are 629, 611, 581, and 636 nm in H 2 O, respectively, and the values shift to 548, 512, 483, and 542 nm in the fibril. This indicates the fibril environment induced changes and a donor effect on the emission properties of the probes, following the case of our previously reported results [ 27 ]. The situation also occurs for probes 16, 20, and 23, where the fluorescence maximum in H 2 O corresponds to 522, 709, and 700 nm, respectively, and blue shift to 491, 648, and 594 nm in Aβ.…”

Small Molecular Fluorescent Probes for Alzheimer's Disease Associated Active Species

“…Hu et al. performed a theoretical study of a series of fluorescent probes 45 a – 45 c (Figure 7) that also had the D‐π‐A structure for Aβ imaging [88] . The authors explored the fluorescence enhancement after binding of the probe 45 a – 45 c to Aβ via calculations.…”

“…7) that also had the D-π-A structure for Aβ imaging. [88] The authors explored the fluorescence enhancement after binding of the probe 45 a-45 c to Aβ via calculations. The detail data displayed that there were two most likely binding sites for each probe toward Aβ.…”

Computational Investigations into Two-Photon Fibril Imaging Using the DANIR-2c Probe

“…Even though the computational approaches were often shown successful in computing the optical and magnetic properties in a vacuum and solvents, the modeling in heterogeneous environments like fibrils, enzymes, membranes, DNA, RNA, and quadruplex in solvents is considerably challenging and requires use of a multiscale multiphysics approach. We can only see a limited number of studies that focus on modeling the two-photon properties of molecules in biomolecular environments such as membranes and enzymes. − …”

“…We can only see a limited number of studies that focus on modeling the two-photon properties of molecules in biomolecular environments such as membranes and enzymes. 14 − 19 …”