title: A Three-Photon Active Organic Fluorophore for Deep Tissue Ratiometric Imaging of Intracellular Divalent Zinc.
abstract: Deep tissue bioimaging with three-photon (3P) excitation using near-infrared (NIR) light in the second IR window (1.0-1.4 μm) could provide high resolution images with an improved signal-to-noise ratio. Herein, we report a photostable and nontoxic 3P excitable donor-π-acceptor system (GMP) having 3P cross-section (σ3 ) of 1.78×10(-80)  cm(6)  s(2)  photon(-2) and action cross-section (σ3 η3 ) of 2.31×10(-81)  cm(6)  s(2)  photon(-2) , which provides ratiometric fluorescence response with divalent zinc ions in aqueous conditions. The probe signals the Zn(2+) binding at 530 and 600 nm, respectively, upon 1150 nm excitation with enhanced σ3 of 1.85×10(-80)  cm(6)  s(2)  photon(-2) and σ3 η3 of 3.33×10(-81)  cm(6)  s(2)  photon(-2) . The application of this probe is demonstrated for ratiometric 3P imaging of Zn(2+) in vitro using HuH-7 cell lines. Furthermore, the Zn(2+) concentration in rat hippocampal slices was imaged at 1150 nm excitation after incubation with GMP, illustrating its potential as a 3P ratiometric probe for deep tissue Zn(2+) ion imaging.
authors.affiliation: Photosciences and Photonics Group, Chemical Sciences and Technology Division and Academy of Scientific and Innovative Research (AcSIR), CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, 695019, India.
authors.forename: Divya Susan
authors.initials: DS
authors.lastname: Philips
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore. ssreejith@ntu.edu.sg.
authors.forename: Sivaramapanicker
authors.initials: S
authors.lastname: Sreejith
authors.affiliation: College of Physics and Technology, Shenzhen University, Shenzhen, 518060, China.|Division of Physics and Applied Physics, Centre for Disruptive Photonic Technologies (CDPT), School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore.
authors.forename: Tingchao
authors.initials: T
authors.lastname: He
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459, Singapore, Singapore.
authors.forename: Nishanth Venugopal
authors.initials: NV
authors.lastname: Menon
authors.affiliation: Photosciences and Photonics Group, Chemical Sciences and Technology Division and Academy of Scientific and Innovative Research (AcSIR), CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, 695019, India.
authors.forename: Palapuravan
authors.initials: P
authors.lastname: Anees
authors.affiliation: Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 2, Tsukuba, 3058568, Japan.
authors.forename: Jomon
authors.initials: J
authors.lastname: Mathew
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore, Singapore.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459, Singapore, Singapore.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore.
authors.forename: Mihaiela Corina
authors.initials: MC
authors.lastname: Stuparu
authors.affiliation: Division of Physics and Applied Physics, Centre for Disruptive Photonic Technologies (CDPT), School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore. hdsun@ntu.edu.sg.
authors.forename: Handong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore. zhaoyanli@ntu.edu.sg.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Photosciences and Photonics Group, Chemical Sciences and Technology Division and Academy of Scientific and Innovative Research (AcSIR), CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, 695019, India. ajayaghosh@niist.res.in.
authors.forename: Ayyappanpillai
authors.initials: A
authors.lastname: Ajayaghosh
mesh_terms: D015082:2,2'-Dipyridyl / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D007259:Infrared Rays; D008297:Male; D008856:Microscopy, Fluorescence; D017208:Rats, Wistar; D015032:Zinc / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D015082:2,2'-Dipyridyl; D015032:Zinc
keywords: fluorescent probes; hippocampus; imaging agents; three-photon probes; zinc