Multi‐Use NBD‐Based Tetra‐amino Macrocycle: Fluorescent Probe for Metals and Anions and Live Cell Marker

Abstract

Ligand L (4-(7-nitrobenzo[1,2,5]oxadiazole-4-yl)-1,7-dimethyl-1,4,7,10-tetra-azacyclododecane) is a versatile fluorescent sensor useful for Cu(II), Zn(II) and Cd(II) metal detection, as a building block of fluorescent metallo-receptor for halide detection, and as an organelle marker inside live cells. Ligand L undergoes a chelation-enhanced fluorescence (CHEF) effect upon metal coordination in acetonitrile solution. In all three complexes investigated the metal cation is coordinatively unsaturated; thus, it can bind secondary ligands as anionic species. The crystal structure of [ZnLCl](ClO(4)) is discussed. Cu(II) and Zn(II) complexes are quenched upon halide interaction, whereas the [CdL](2+) species behaves as an OFF-ON sensor for halide anions in acetonitrile solution. The mechanism of the fluorescence response in the presence of the anion depends on the nature of the metal ion employed and has been studied by spectroscopic methods, such as NMR spectroscopy, UV/Vis and fluorescence techniques and by computational methods. Subcellular localization experiments performed on HeLa cells show that L mainly localizes in spot-like structures in a polarized portion of the cytosol that is occupied by the Golgi apparatus to give a green fluorescence signal.

What biologists want from their chloride reporters – a conversation between chemists and biologists

“…When complexed with cadmium(II) (Cd 2+ ), the fluorescence of nitrobenzooxadiazole (NBD) increases with increased Cl − . This fluorescence enhancement is due to increased photoinduced charge transfer of the NBD-N aromatic amine into NBD, because the halide-metal interaction weakens the interaction metal ion and the NBD-N aromatic amine (Amatori et al, 2012). Based on the hypothesis that a ligand that forces the metal ion to be closer to the aliphatic amines would improve the switch-on sensor, a bis-NBD complex was realized (Fig.…”

“…Because of this, small-molecule sensors, small molecules conjugated to macromolecules, and genetically encoded reporters have all been designed and fine-tuned to fit specific needs (Biwersi and Verkman, 1991;Kuner and Augustine, 2000;Saha et al, 2015). Furthermore, new classes of chloride-sensitive molecules continue to emerge as biologists uncover novel physiological relevance for chloride transport (Amatori et al, 2012;Collins et al, 2013;Kim et al, 2017).…”

Playing with Structural Parameters: Synthesis and Characterization of Two New Maltol-Based Ligands with Binding and Antineoplastic Properties

“…The immortalized promonocytic leukemia (U937) cell line was obtained from American Type Culture Collection (ATCC). Cells were grown in RPMI 1640 (Lonza) supplemented with 10% fetal bovine serum (FBS), 1% penicillin-streptomycin and 1% glutamine in a humidified atmosphere at 37 • C, as previously described [35]. L1 and L2 were dissolved at 10 mM in distilled water as stock solutions, stored at −80 • C and subsequently diluted 1:10 as working solutions immediately before use.…”

“…Linear and macrocyclic polyamines, generally with symmetrical topology, are also known antitumor agents [30][31][32]. Furthermore, they show well-known coordination properties towards metal ions and/or anions [33][34][35]. Due to their protonable sites, polyamines allow one to obtain water-soluble compounds; that is a crucial point for both biological activity and guest coordination in aqueous solutions.…”

A Fluorescent Sensor Array Based on Heteroatomic Macrocyclic Fluorophores for the Detection of Polluting Species in Natural Water Samples

“…Among the optical detection techniques, fluorimetry is very attractive since it provides highly selective luminescence evaluation in a tunable emission range. Moreover, the optical chemical sensors based on fluorophores can be combined in sensor arrays and coupled with chemometric approach (Lvova et al, 2014 ), thus permitting the identification and quantitation of various analytes, such as natural water pollutants (Amatori et al, 2012 ; Bazzicalupi et al, 2013 ; Arca et al, 2014 ; Kang et al, 2014 ; Guanais Goncalves et al, 2016 ), toxins (Lvova et al, 2018 ), pesticides (Lei et al, 2016 ), explosives (Bolse et al, 2017 ; Zhu et al, 2017 ), agents hazardous for human skin (Moczko et al, 2016 ), forbidden additives and pathogens in beverages (Tan et al, 2014 ; Nishi et al, 2015 ; Han et al, 2016 ) and in foodstuffs (Lvova et al, 2015 ; Mungkarndee et al, 2015 , 2016 ).…”