title: Alkynyl-naphthalimide Fluorophores: Gold Coordination Chemistry and Cellular Imaging Applications.
abstract: A range of fluorescent alkynyl-naphthalimide fluorophores has been synthesized and their photophysical properties examined. The fluorescent ligands are based upon a 4-substituted 1,8-naphthalimide core and incorporate structural variations (at the 4-position) to tune the amphiphilic character: chloro (L1), 4-[2-(2-aminoethoxy)ethanol] (L2), 4-[2-(2-methoxyethoxy)ethylamino] (L3), piperidine (L4), morpholine (L5), 4-methylpiperidine (L6), and 4-piperidone ethylene ketal (L7) variants. The amino-substituted species (L2-L7) are fluorescent in the visible region at around 517-535 nm through a naphthalimide-localized intramolecular charge transfer (ICT), with appreciable Stokes' shifts of ca. 6500 cm(-1) and lifetimes up to 10.4 ns. Corresponding two-coordinate Au(I) complexes [Au(L)(PPh3)] were isolated, with X-ray structural studies revealing the expected coordination mode via the alkyne donor. The Au(I) complexes retain the visible fluorescence associated with the coordinated alkynyl-naphthalimide ligand. The ligands and complexes were investigated for their cytotoxicity across a range of cell lines (LOVO, MCF-7, A549, PC3, HEK) and their potential as cell imaging agents for HEK (human embryonic kidney) cells and Spironucleus vortens using confocal fluorescence microscopy. The images reveal that these fluorophores are highly compatible with fluorescence microscopy and show some clear intracellular localization patterns that are dependent upon the specific nature of the naphthalimide substituent.
authors.affiliation: †School of Chemistry, Main Building, Cardiff University, Cardiff CF10 3AT, United Kingdom.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Langdon-Jones
authors.affiliation: ‡School of Biosciences, Main Building, Cardiff University, Cardiff CF10 3AT, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Lloyd
authors.affiliation: ‡School of Biosciences, Main Building, Cardiff University, Cardiff CF10 3AT, United Kingdom.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hayes
authors.affiliation: ‡School of Biosciences, Main Building, Cardiff University, Cardiff CF10 3AT, United Kingdom.
authors.forename: Shane D
authors.initials: SD
authors.lastname: Wainwright
authors.affiliation: §School of Pharmacy, Redwood Building, Cardiff University, Cardiff CF10 3NB, United Kingdom.
authors.forename: Huw J
authors.initials: HJ
authors.lastname: Mottram
authors.affiliation: ∥UK National Crystallographic Service, Chemistry, Faculty of Natural and Environmental Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Coles
authors.affiliation: ∥UK National Crystallographic Service, Chemistry, Faculty of Natural and Environmental Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Horton
authors.affiliation: †School of Chemistry, Main Building, Cardiff University, Cardiff CF10 3AT, United Kingdom.
authors.forename: Simon J A
authors.initials: SJ
authors.lastname: Pope
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000494:pharmacology; D006046:Gold / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D015394:Molecular Structure; D053644:Naphthalimides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D056831:Coordination Complexes; D005456:Fluorescent Dyes; D053644:Naphthalimides; D006046:Gold