Simultaneous Identification of Neutral and Anionic Species in Complex Mixtures without Separation

Abstract

A chemosensory system is reported that operates without the need for separation techniques and is capable of identifying anions and structurally similar bioactive molecules. In this strategy, the coordination of analytes to a metal complex with an open binding cleft generates "static structures" on the NMR timescale. Unique signals are created by strategically placing fluorine atoms in close proximity to bound analytes so that small structural differences induce distinct (19)F NMR shifts that can be used to identify each analyte. The utility of this method is illustrated by quantifying caffeine levels in coffee, by identifying ingredients in tea and energy drinks, and by discriminating between multiple biogenic amines with remote structural differences six carbon atoms away from the binding site. We further demonstrate the simultaneous identification of multiple neutral and anionic species in a complex mixture.

Keywords: N ligands; NMR spectroscopy; chemosensors; fluorine; palladium; pincer complexes.

Figure 1

¹⁹F NMR spectra (64 scans each) of a) complex 1 alone (1.0 mM in CDCl₃) showing the formation of oligomeric products, b–n) a mixture of complex 1 (1.0 mM in CDCl₃), CH₃CN (15 mM) and different analytes (0.5–2.0 mM), b) no analyte, c) mixture of seven analytes, d) superimposition of the spectra of complex 1 with each of the seven analytes collected independently, e–n) complex 1 bound to various analytes. o) ¹⁹F NMR spectrum (64 scans) of a mixture of complex 6 (2 mM in CDCl₃), CH₃CN (30 mM) and different analytes (0.5–2.0 mM).

Figure 2

¹H-decoupled ¹⁹F NMR spectra (128 scans) of mixtures of a) complex 6 and b) complex 5 (ca. 2.0 mM each), with (from left to right) 2-phenethy lamine, tyramine, tryptamine, and serotonin (ca. 0.25 mM each) in THF/D₂O. The spectra are aligned with respect to the receptor peak so that the magnitudes of the chemical shift dispersions of 5 and 6 may be directly compared.

Figure 3

¹⁹F NMR spectra (128 scans) of a mixture of complex 1 (ca. 3.0 mM in MeOH/D₂O/H₂O), internal standards (molar ratio of 4-nitrobenzotrif luoride:quinoline = 50:35.1) and coffee. a) 40 μL of regularly brewed coffee was added. b) 80 μL of decaffeinated coffee was added.

Figure 4

¹H-decoupled ¹⁹F NMR spectra (64-128 scans each): a) superimposed spectra of mixtures of complex 6 (ca. 2.8 mM) with aspartame (ca. 4.1 mM), taurine (ca. 4.1 mM), caffeine (ca. 2.0 mM), niacinamide (ca. 2.0 mM), and acesulf ame potassium (ca. 2.0 mM) in MeOH/D₂O/H₂O, each collected independently. Spectra of b) tea brewed f rom loose genmaicha green tea, c) tea brewed from Allegro brand Asian Gen Mai Cha tea bag, d) Essential Everyday brand No Calorie Sweetener, and e) 4C brand Energy Rush Tea2Go energy drink, respectively, with complex 6 (ca. 2.8 mM) in MeOH/D₂O/H₂O, with identif iable ingredients labelled.

Figure 5

¹⁹F NMR spectrum (128 scans) of a mixture of complex 6 (ca. 2.6 mM), 2-phenethy lamine (ca. 0.1 mM), tyramine (ca. 0.1 mM), tryptamine (ca. 0.1 mM), serotonin (ca. 0.1 mM), tetrabuty lammonium azide (ca. 0.2 mM), tetrabuty lammonium acetate (ca. 1.1 mM), tetrabuty lammonium iodide (ca. 0.2 mM), tetrabuty lammonium bromide (ca. 0.2 mM), and tetrabuty lammonium chloride (ca. 0.2 mM) in THF/D₂O. The distance between the most upfield and most downfield signals is 4.35 ppm.

Scheme 1

a) Cartoon representation of the chemosensory method reported herein. Structurally similar analytes bind to a metal complex, inducing distinct ¹⁹F NMR shifts in fluorine atoms placed in close proximity to the bound analyte. b) Palladium pincer complexes with fluorine probes at different locations. c) X-ray single crystal structure of 2:CH₃CN