Amphiphilic Molecules Exhibiting Zwitterionic Excited-State Intramolecular Proton Transfer and Near-Infrared Emission for the Detection of Amyloid ß Aggregates in Alzheimer's Disease.

Chromophores with zwitterionic excited-state intramolecular proton transfer (ESIPT) have been shown to have larger Stock shifts and red-shifted emission wavelengths compared to the conventional π-delocalized ESIPT molecules. However, there is still a dearth of design strategies to expand the current library of zwitterionic ESIPT compounds. Herein, a novel zwitterionic excited-state intramolecular proton transfer system is reported, enabled by addition of 1,4,7-triazacyclononane (TACN) fragments on a dicyanomethylene-4H-pyran (DCM) scaffold. The solvent-dependent steady-state photophysical studies, pKa measurements, and computational analysis strongly support that the ESIPT process is more efficient with two TACN groups attached to the DCM scaffold and not affected by polar protic solvents. Impressively, compound DCM-OH-2-DT exhibits a near-infrared (NIR) emission at 740 nm along with an uncommonly large Stokes shift. Moreover, DCM-OH-2-DT shows high affinity towards soluble amyloid ß (Aß) oligomers in vitro and in 5xFAD mouse brain sections, and we have successfully applied DCM-OH-2-DT for the in vivo imaging of Aß aggregates and demonstrated its potential use as an early diagnostic agent for AD. Overall, this study can provide a general molecular design strategy for developing new zwitterionic ESIPT compounds with NIR emission in vivo imaging applications.

Evaluation of the excited state dynamics, photophysical properties, and the influence of donor substitution in a donor-[Formula: see text]-acceptor system.

There have been numerous attempts for the theoretical design of a better donor-[Formula: see text]-acceptor structural framework with improved absorption and emission properties. However, for effective dye designing, it is necessary to understand the electronic and photophysical properties of the dye systems. In this work, we report a detailed density functional theory (DFT) and time-dependent density functional theory (TD-DFT) investigations of the excited state characteristics and the influence of various groups (-HCO, =CH2, (-CH3)2, (HCO)2, and (-OCH3)2) attached to the donor group (-NH2) in a p-nitroaniline D-[Formula: see text]-A system which are symbolized respectively as p-nitroaniline (A), N,N-dimethylnitroaniline (A2), N,N-dicarbonylnitroaniline (A3), N-methylenenitroaniline (A4), and N,N-dimethoxynitroaniline (A5). The first principles DFT and TD-DFT calculations from the ground state (S0) to the first five excited states: (S0→S1), (S0→S2), (S0→S3), (S0→S4), and (S0→S5) were utilized to explore the reactivity of D-[Formula: see text]-A system using the conceptual DFT approach, characterization of electron excitation using the hole-electron analysis, visual study of the various real space functions in the hole-electron framework, density of states (DOS), measurement of charge transfer (CT) length of electron excitation ([Formula: see text]), measurement of the overlapping degrees of hole and electron of electron excitation ([Formula: see text]), interfragment charge transfer (IFCT) during electron excitation, and the second-order perturbation energy analysis from the natural bond orbitals (NBO) computation. Results of the excitation studies show that all the studied compounds exhibited an n→[Formula: see text]* localized type for first excitations (S0→S1) on -NO2 group in A, A2, A4, and A5 and -NCl2 in A3. [Formula: see text]→[Formula: see text]* charge transfer excitations were confirmed for S0→S2/S4/S5 in A and A2, S0→S3/S4/S5 in A3 and A5, and S0→S4/S5 in A4. The NBO second-order perturbation energy analysis suggest that the most significant hyperconjugative interactions were [Formula: see text] (54.43kcal/mol), [Formula: see text] (40.82kcal/mol), [Formula: see text] (11.67kcal/mol), [Formula: see text] (29.52kcal/mol), [Formula: see text] (11.55kcal/mol), [Formula: see text] (23.40kcal/mol), and [Formula: see text] (24.88kcal/mol) [Formula: see text](24.64kcal/mol), which respectively corresponds to the A, A2, A3, A4, and A5 D-[Formula: see text]-A systems under investigation, and these strong interactions stabilize the systems.