Enhancing the Anti‐Solvatochromic Two‐Photon Fluorescence for Cirrhosis Imaging by Forming a Hydrogen‐Bond Network

Abstract

Tw o-photon imaging is an emerging tool for biomedical researcha nd clinical diagnostics.E lectron donoracceptor (D-A) type molecules are the most widely employed two-photon scaffolds.H owever,c urrent D-A type fluorophores suffer from solvatochromic quenching in aqueous biological samples.T oa ddress this issue,w ed evised an ovel class of D-A type green fluorescent protein (GFP) chromophore analogues that form ahydrogen-bond network in water to improve the two-photon efficiency.O ur design results in two-photon chalcone (TPC) dyes with 0.80 quantum yield and large two-photon action cross section (210 GM) in water.This strategy to form hydrogen bonds can be generalized to design two-photon materials with anti-solvatochromic fluorescence. To demonstrate the improved in vivo imaging, we designed as ulfide probe based on TPC dyes and monitored endogenous H 2 Sg eneration and scavenging in the cirrhotic rat liver for the first time.

Bioactive Aurones, Indanones, and Other Hemiindigoid Scaffolds: Medicinal Chemistry and Photopharmacology Perspectives

“…For example, 135 was able to selectively detect H 2 S, a small molecule generating during the cirrhosis process, through the reduction of the azido group to amino (136), which triggers an increase of the quantum yield, allowing two-photon fluorescence imaging of liver cells (Figure 24). 206 The aminoindanone showed remarkable antisolvatochromic properties, as the quantum yield increased with the solvent polarity (0.80 in PBS buffer, 0.53 in EtOH, 0.12 in MeCN and 0.02 in CH 2 Cl 2 ). Overall, these promising results offer a glimpse of the versatility of hemiindigoids and could endorse future research about applications of the scaffolds as biosensors.…”

“…Indeed, by reducing aromatic aggregation, restraining the donor−acceptor character and allowing the formation of a hydrogen-bond network with the solvent, waterfluorescent indanones were obtained. 206 This concept was explored for cysteine detection. This semiessential amino acid is involved in several biological processes and is associated with metabolic disorders and increased risk for health problems when present at high levels.…”

“…To enable such applications, the intrinsic solvatochromic properties of hemiindigoids could be mitigated by an appropriate design, in order to provide bright fluorescence in aqueous environments. Indeed, by reducing aromatic aggregation, restraining the donor–acceptor character and allowing the formation of a hydrogen-bond network with the solvent, water-fluorescent indanones were obtained . This concept was explored for cysteine detection.…”

Hydrogen Bond-Enhanced Nanoaggregation and Antisolvatochromic Fluorescence for Protein-Recognition by Si-Coumarins

“…In sporadic systems, fluorescence intensity (F) raised with the polarity or proticity, leading to antisolvatochromic fluorophores. 20 Here, in polar or protic solvents the F of SiC-BZA1 are much higher than SiC-BZA2 (Figure S4, Table S1).…”

Molecular Engineering of Novel Fluorophores for High‐Contrast Bioimaging

“…[ 9 ] Based on these advantages of GFP, we developed a series of anti‐solvatochromic, D–A‐type fluorophores by replacing the dihydroimidazole ring of GFP with cyclopentanone inserted on dimethylaminobenzene (Figure 1b). [ 10 ] In an aqueous environment, a hydrogen‐bond network was formed between H 2 O and carbonyl, which enhanced the electron‐withdrawing ability of the carbonyl group and consequently facilitated ICT. Furthermore, the hydrogen‐bond network increased the steric hindrance surrounding the benzene ring, which restrained its internal rotation.…”