Integrated and Passive 1,2,3-Triazolyl Groups in Fluorescent Indicators for Zinc(II) Ions: Thermodynamic and Kinetic Evaluations

Abstract

In addition to being a covalent linker in molecular conjugation chemistry, the function of a 1,2,3-triazolyl moiety resulting from the copper(I)-catalyzed azide-alkyne cycloaddition reaction as a ligand for metal ions is receiving considerable attention. In this work, we characterize the thermodynamic and kinetic effects of incorporating a 1,2,3-triazolyl group in a multidentate ligand scaffold on metal coordination in the context of fluorescent zinc(II) indicator development. Ligands L14, BrL14, and FL14 (1,4-isomers) contain the 1,4- disubstituted-1,2,3-triazolyl group that is capable of binding with zinc(II) in conjunction with a di(2-picolylamino) (DPA) moiety within a multidentate ligand scaffold. The 1,2,3-triazolyl in the 1,4-isomers is therefore “integrated” in chelation. The 1,5-isomers L15, BrL15, and FL15 contain 1,2,3-triazolyls that are excluded from participating in zinc(II) coordination. These 1,2,3- triazolyls are “passive linkers”. Zinc(II) complexes of 2:1 (ligand/metal) stoichiometry are identified in solution using 1H NMR spectroscopy and isothermal titration calorimetry (ITC), and in one case, characterized in the solid state. The 1:1 ligand/zinc(II) affinity ratio of L14 over L15, which is attributed to the affinity enhancement of a 1,2,3-triazolyl group to zinc(II) over that of the solvent acetonitrile, is quantified at 18 (−1.7 kcal/mol at 298 K) using an ITC experiment. Fluorescent ligands FL14 and FL15 are evaluated for their potential in zinc(II) sensing applications under pH neutral aqueous conditions. The 1,4-isomer FL14 binds zinc(II) both stronger and faster than the 1,5-isomer FL15. Visualization of free zinc(II) ion distribution in live HeLa cells is achieved using both FL14 and FL15. The superiority of FL14 in staining endogenous zinc(II) ions in live rat hippocampal slices is evident. In summation, this work is a fundamental study of 1,2,3-triazole coordination chemistry, with a demonstration of its utility in developing fluorescent indicators.

Synthesis of a Phenazine‐Based 1,2,3‐Triazole from Naturally Occurring Naphthoquinone Designed as a Probe for Cd2+ Ions

“…Studies to determine the binding model by using the method of continuous variations (Job's plot, see Figure S9) suggest a 2:1 stoichiometry for the Cd 2+ complex with the ligand. We suggest a possible way in which the Cd 2+ ions interact with the binding sites in 6 on the basis of previous reports [2][3][4][5][6] (Figure 5). Figure 6 shows that in the presence of Cd 2+ ions the absorption band of probe 6 does not undergo displacement, but a hypochromic effect (fluorescence quenching as a result of photoinduced electron transfer) is observed that is possibly related to interactions between the probe and the…”

“…[1] Zhu and co-workers described coumarins linked with this ligand obtained by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and the versatility of the obtained compound as a zinc-selective fluorescent sensor. [2] A similar approach was used by Rosenthal and Lippard to prepare a boron-dipyrromethene (BODIPY)-based ligand designed as a nitric oxide sensor. [3] Torroba and co-workers developed a colorimetric and fluorescent probe to detect Cu II ions selectively.…”

Bis[N-alkyl-NN-di(2-pyridylmethyl)amine]zinc(II) perchlorates display cis-facial stereochemistry in solid state and solution

“…The solution structure of [Zn(1) 2 ](ClO 4 ) 2 replicates that in the solid state (13). The two 2-pyridylmethyl groups on one DPA ligand are no longer in the same chemical environment.…”

“…The downfield shifts are expected because the positively charged zinc(II) ion deshields the protons via the inductive effect. The methylene protons H(x) next to the 2-pyridyl are now non-equivalent, as they are part of the kinetically stable five-membered coordination rings (13). Therefore, two doublets for two H(x) 0 s are observed.…”

Water soluble and efficient amino acid Schiff base receptor for reversible fluorescence turn-on detection of Zn2+ ions: Quantum chemical calculations and detection of bacteria

“…The investigation on fluorescent sensing of metal ions is promising because heavy metals play crucial roles in ecological, biological, and clinical applications [1][2][3][4][5]. In biological systems, zinc(II) is the second most abundant transition metal only next to iron [6,7].…”