Modular Assembly of Tunable Fluorescent Chemosensors Selective for Pb²⁺ and Cu²⁺ Metal Ions via the Multicomponent Castagnoli‐Cushman Reaction

Abstract

The multicomponent Castagnoli‐Cushman reaction followed by post‐condensational modifications allowed for a flexible, modular construction of fluorescent chemosensor compounds. When tested against a panel of fourteen metal ions, one of the eight compounds investigated in this work was found to selectively respond to Cu2+ ions by fluorescence quenching (thus being a “turn‐off” chemosensor for this metal). Another compound was found to produce fluorescence increase in response to Pb2+ ions. Interestingly, the sensitivity of this “turn‐on” chemosensor to lead(II) ions was unaffected by the presence of a large excess of other metals. Analysis of the structure‐sensing property relationships of these sensors allowed developing a general understanding of the factors influencing the chemosensor properties. All of the critical structural factors employed in the chemosensor design were found to be important for the metal sensing and selectivity. These findings will allow designing next‐generation chemosensors based on the same modular construction approach in the future.

Two Annulated Azaheterocyclic Cores Readily Available from a Single Tetrahydroisoquinolonic Castagnoli–Cushman Precursor

“…Surprisingly, the classical reduction of 5 with sodium sulfide (Scheme 1, path a) gave a product with no aliphatic protons in the 1 H NMR spectrum and only one carbonyl group signal present in the 13 C NMR spectrum, which did not correspond to the expected structure 4. The structure of the isolated reaction product, compound 7, which was found to be a known [27] derivative of indolo[3,2-c]isoquinoline, was determined by X-ray diffraction analysis.…”

“…1 H NMR (400 MHz, DMSO-d 6 ) δ 13.26 (br.s, 1H), 8.21 (dd, J = 8.1, 1.5 Hz, 1H), 8.01 (dd, J = 7.5, 1.7 Hz, 1H), 7.64 (td, J = 7.6, 1.5 Hz, 1H), 7.60-7.44 (m, 3H), 7.38 (dd, J = 7.3, 1.6 Hz, 1H), 7.00 (dd, J = 7.8, 1.5 Hz, 1H), 6.33 (d, J = 1.3 Hz, 1H), 4.42 (d, J = 1.4 Hz, 1H), 3.80 (s, 3H). 13…”

“…1 H NMR (400 MHz, DMSO-d 6 ) δ 11.85 (br.s, 1H), 8.45 (s, 1H), 8.35 (dd, J = 8.1, 1.3 Hz, 1H), 8.17 (d, J = 7.9 Hz, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.95-7.75 (m, 1H), 7.61-7.47 (m, 2H), 7.29 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.18-6.99 (m, 1H). 13 A round-bottom flask was charged with compound 5 (1.4 g, 4 mmol), 10% wt. Pd/C (424 mg, 0.4 mmol), ammonium formate (2.6 g, 41 mmol) and MeOH (150 mL).…”

“…1 H NMR (400 MHz, DMSO-d 6 ) δ 8.06-7.83 (m, 1H), 7.42-7.33 (m, 1H), 7.34-7.24 (m, 1H), 7.10 (d, J = 7.5 Hz, 1H), 7.00-6.78 (m, 1H), 6.69 (d, J = 7.9 Hz, 1H), 6.51 (d, J = 7.6 Hz, 1H), 6.37 (t, J = 7.4 Hz, 1H), 5.78 (s, 1H), 5.13 (br.s, 2H), 3.72 (s, 3H), 3.18 (s, 1H). 13 To a stirred suspension of compound 4 (100 mg, 0.32 mmol) in dry chloroform (10 mL) a 50% wt. solution of propanephosphonic acid anhydride, T 3 P (410 mg, 0.64 mmol) in toluene was added at room temperature.…”

“…Metal binding properties often determine the biological activity of hydroxamic acids, which can act as siderophores [9] (bacterial iron transporters) as well as inhibitors of metalloenzymes (such as matrix metalloproteases [10], hyston deacetylases [11], and HIV integrase [12]). In one of our previous works, we demonstrated that conjugates of N-hydroxy THIQ acids (1, R 1 = OH) with various fluorophores can serve as selective fluorescent chemosensors for specific metal ions [13]. In this study, we aimed at developing a modified type of such sensors in which attachment of an external fluorescent probe would be unnecessary if the extended π-system of the probe itself would enable it to act as the source of fluorescence.…”