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.

The interplay between fluorescence and phosphorescence with luminescent gold(i) and gold(iii) complexes bearing heterocyclic arylacetylide ligands

“…Tricyclohexylphosphine (PCy 3 ) was used as the auxiliary ligand in these complexes because (1) it is optically transparent at wavelength >250 nm so that it is not involved in the emissive excited states in the UV-visible spectral region and (2) its steric bulkiness would prevent the gold ions from coming into close contact that could lead to low-lying excited states originated from metal–metal and π–π interactions. It is worth mentioning that several recently reported Au( i ) alkynyl complexes bearing similar benzothiadiazole, 7 coumarin 8 and naphthalimide 9 derivatives also show similar luminescence properties as our Au( i ) complexes. 10,11 The effects of auxiliary ligands on the photophysical properties of Au( i ) complexes were also studied by comparing 1a with two derivatives containing 2,6-dimethylphenyl isocyanide (RNC, 5a ) and 1,3-dimethylimidazol-2-ylidene (NHC, 6a ) instead of the phosphine auxiliary ligand, respectively.…”

Polypyridyl-functionalizated alkynyl gold(i) metallaligands supported by tri- and tetradentate phosphanes

“…11,12,14 This interest in gold(I) complexes mainly arises from their rich luminescence properties 1,[15][16][17][18][19] as well as their predisposition to establish aurophilic interactions. [20][21][22][23][24] In particular, gold(I) alkynyl systems 25,26 are especially attractive due to the preference for linear two-coordinate geometry of gold(I), together with the linearity of the alkynyl unit and its π-unsaturated nature.…”

Anticancer, Azonafide‐Inspired Fluorescent Ligands and Their Rhenium(I) Complexes for Cellular Imaging

“…More recently, we have explored the use of substituted naphthalimide fluorophores as components of cell imaging agents. Ligands based upon 4‐amino‐1,8‐naphthalimide can be functionalised to allow conjugation with either Re I (via a dipicolylamine unit) or Au I (via a terminal alkyne) . In all of these cases the specific nature of functionalisation at the naphthalimide core promotes very distinct intracellular localisation patterns .…”

“…Ligands based upon 4‐amino‐1,8‐naphthalimide can be functionalised to allow conjugation with either Re I (via a dipicolylamine unit) or Au I (via a terminal alkyne) . In all of these cases the specific nature of functionalisation at the naphthalimide core promotes very distinct intracellular localisation patterns . Interest in the biological application and cell imaging capability of substituted naphthalimide fluorophores has grown significantly over the last five years.…”

“…Our initial interest in naphthalimide derivatives, emanated from the biological properties of the structurally related species amonafide (Scheme ), an anticancer drug, currently in phase III clinical trials . However, the anthracene‐1,9‐dicarboximide derivative azonafide, which is a prospective anticancer drug, has shown dramatically enhanced anticancer properties versus amonafide.…”