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commercially available chemosensors and published probes for in vitro Zn2+ detection in two-photon microscopy are compromised by their flawed spectroscopic properties, causing issues in selectivity or challenging multistep syntheses. Herein, we present the development of an effective small molecular GFP chromophore-based fluorescent chemosensor with a 2,2\u2032-bipyridine chelator moiety (GFZnP BIPY) for Zn2+ detection that has straightforward synthesis and uncompromised properties. Detailed experimental characterizations of the free and the zinc-bound compounds within the physiologically relevant pH range are presented. Excellent photophysical characteristics are reported, including a 53-fold fluorescence enhancement with excitation and emission maxima at 422 nm and 492 nm, respectively. A high two-photon cross section of 3.0 GM at 840 nm as well as excellent metal ion selectivity are reported. In vitro experiments on HEK 293 cell culture were carried out using two-photon microscopy to demonstrate the applicability of the novel sensor for zinc bioimaging.<\/jats:p>","DOI":"10.3390\/ijms25063504","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T09:14:33Z","timestamp":1710926073000},"page":"3504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Molecular Hybrid of the GFP Chromophore and 2,2\u2032-Bipyridine: An Accessible Sensor for Zn2+ Detection with Fluorescence Microscopy"],"prefix":"10.3390","volume":"25","author":[{"given":"Attila","family":"Csomos","sequence":"first","affiliation":[{"name":"Department of Chemistry, Femtonics Ltd., T\u0171zolt\u00f3 utca 59, H-1094 Budapest, Hungary"},{"name":"Hevesy Gy\u00f6rgy PhD School of Chemistry, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter s\u00e9t\u00e1ny 1\/A, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Madar\u00e1sz","sequence":"additional","affiliation":[{"name":"BrainVisionCenter, Liliom utca 43, H-1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Turczel","sequence":"additional","affiliation":[{"name":"NMR Research Laboratory, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok k\u00f6r\u00fatja 2, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Cseri","sequence":"additional","affiliation":[{"name":"BrainVisionCenter, Liliom utca 43, H-1094 Budapest, Hungary"},{"name":"Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, 3. 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