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

• Published in: Angewandte Chemie International Edition Vol. 57; no. 25; pp. 7473 - 7477
• Main Authors: Ren, Tian‐Bing, Xu, Wang, Zhang, Qian‐Ling, Zhang, Xing‐Xing, Wen, Si‐Yu, Yi, Hai‐Bo, Yuan, Lin, Zhang, Xiao‐Bing
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 18.06.2018; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Animals; anti-solvatochromism; Biological properties; Biological samples; Biomedical materials; Chemical compounds; Chemistry; Chemistry, Multidisciplinary; Chromophores; Cirrhosis; Density Functional Theory; Dyes; Fluorescence; fluorescent dyes; Fluorescent Dyes - chemistry; Fluorophores; Green fluorescent protein; Green Fluorescent Proteins - chemistry; Hydrogen Bonding; Hydrogen bonds; Hydrogen sulfide; hydrogen-bond network; Imaging; Liver; Liver cirrhosis; Liver Cirrhosis - diagnostic imaging; Molecular chains; Photons; Physical Sciences; Proteins; Rats; Science & Technology; Solvents - chemistry; two-photon probes; hydrogen-bond network; FLUOROPHORES; DYES; anti-solvatochromism; two-photon probes; TISSUE; UNIQUE; INTRAMOLECULAR CHARGE-TRANSFER; PROBES; SULFIDE; GFP; fluorescent dyes; LIVER; SYSTEMS; cirrhosis
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201800293

Two‐photon imaging is an emerging tool for biomedical research and clinical diagnostics. Electron donor–acceptor (D–A) type molecules are the most widely employed two‐photon scaffolds. However, current D–A type fluorophores suffer from solvatochromic quenching in aqueous biological samples. To address this issue, we devised a novel class of D–A type green fluorescent protein (GFP) chromophore analogues that form a hydrogen‐bond network in water to improve the two‐photon efficiency. Our 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 a sulfide probe based on TPC dyes and monitored endogenous H2S generation and scavenging in the cirrhotic rat liver for the first time. Turn bane into a boon: A unique class of two‐photon dyes with anti‐solvatochromic fluorescence, optically tunable groups, high fluorescence quantum yields, and large two‐photon action cross sections in water are developed. Their use for in vivo imaging, was demonstrated in the monitoring of endogenous H2S generation and scavenging in the cirrhotic rat liver.