A Water‐Stable and Red‐Emissive Radical Cation for Mutp53 Cancer Therapy

Abstract

Compared with conventional closed-shell fluorophores, radical cations provide an opportunity for development of red-to-NIR fluorophores with small sizes and easy preparation. However, most radical cations reported in the literature suffer from poor stability in water solution and are almost non-emissive. To tackle this challenge, we herein develop a deep-redemissive and water-stable pyrrole radical cation P * + À DPAÀ Zn, which can be easily generated from PÀ DPAÀ Zn by air oxidation. The deep-red-emissive P * + À DPAÀ Zn can be used for imaging-guided mitochondria-targeted delivery of Zn 2 + into cancer cells to promote mutant p53 proteins degradation and abrogate mutp53-manifested gain of function, including reduced chemotherapy resistance, inhibited cancer cell migration, decreased tumor cell colony and sphere formation. The water-stable and deep-red emissive pyrrole radical cation is thus promising for cancer theranostic applications.Red-to-NIR fluorescence imaging has significant advantages in terms of high penetration ability and less interference from autofluorescence. However, most of current redto-NIR fluorophores, such as cyanine and squaraine derivatives, are featured with complicated structures and suffer from difficulties for further decoration with therapeutic

Luminescent Radicals

“…330 This electronic transition was mainly composed of NLUMO → SOMO and SOMO → NHOMO transitions (Figure 68b−d), and had the In 2022, Tang, Gao, Zhang, Liu, and co-workers reported a zinc complex coordinated with an emissive pyrrole radical cation (P •+ -DPA-Zn) (Chart 11, Table 7, entry 14). 328 This red-to-NIR emitting complex was easily prepared by oxidation in air using P-DPA-Zn as a radical precursor. In particular, it was highly stable in water compared with previously reported emissive radicals.…”

“…In 2022, Tang, Gao, Zhang, Liu, and co-workers reported a zinc complex coordinated with an emissive pyrrole radical cation (P •+ -DPA-Zn) (Chart , Table , entry 14) . This red-to-NIR emitting complex was easily prepared by oxidation in air using P-DPA-Zn as a radical precursor.…”

“…The atom C, H, O, N, and Zn are silver, white, red, blue, and cyan, respectively (isovalue = 0.015). Adapted with permission from ref . Copyright 2022 Wiley-VCH Verlag GmbH.…”

Supramolecular pyrrole radical cations for bacterial theranostics

“…Recently, we found that weak acids ( pH ∼ 2-3) can induce the generation of pyrrole radical cations (P •+ ), which are stable in a water solution containing supramolecular host CB [7]. [26][27][28] Inspired by the fact that CB [7] also features an acidic cavity and its pK a can downshift up to 4.5 units, 29 herein, we systematically investigate the substituent effect of pyrroles for the direct preparation of the corresponding radical cations in a water solution by simple mixing of pyrroles and CB [7]. Furthermore, based on the positively charged structure of pyrrole radical cations with deep-red fluorescence emission, we investigate their promising applications for bacterial theranostics, including selective imaging and killing of Gram-positive bacteria, imaging of dead Gram-negative bacteria killed by drugs, and in vivo monitoring of phagocytosis of bacteria by innate immune cells in zebrafish (Scheme 1).…”

One pot oxygen mediated syntheses of stable radicals

“…10,11 Recently, Tang and coworkers synthesized oxygen-mediated radical cations from pyrrole-substituted derivatives (Scheme 1a and b). 12 However, to the best of our knowledge, there is no report of oxygen-mediated synthesis of air and thermally stable neutral organic radicals. Immediate separation of this reactive oxygen species would be one of the potential ways to overcome the limitation of air-stable CCR synthesis.…”