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

Yujin Zhang,Kan Li,Ni Luan,Wei Hu,Jiancai Leng

doi:10.3390/s20061760

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.

Highlights

Alzheimer’s disease (AD) is a progressive disease, in which dementia symptoms gradually worsen over a number of years
Two-photon absorption (TPA) properties for the probes were calculated by employing the response theory method with the density functional theory (DFT)/B3LYP functional and 6-31G+(d,p) basis set using
Molecular docking simulations on the probes show that there are two most likely binding sites for each probe toward β-amyloid, as demonstrated in Figure 2 and Figure S2. Both binding sites for P1, P2, and P3 are inside the fibril, which might be dominated by the volume of the locus [36]

Summary

Introduction

Alzheimer’s disease (AD) is a progressive disease, in which dementia symptoms gradually worsen over a number of years. We aim to set out possible structure–property relationships for the future design of improved diagnostic probes by analyzing the effect of donor moieties and the length of spacers on the sensing performance of the probes To this end, another three derivatives of the same series named P4, P5, and P6 (see Figure S1) are investigated, and only the first three with a higher affinity are reported in this text. The future design of improved diagnostic probes by analyzing the effect of donor moieties and the length of spacers on the sensing performance of the probes

Molecular Docking

Property Calculations

Binding Sites for the Probes with β-Amyloid

OPAmoment wavelength

Conclusions