The Multifaceted Opportunities Provided by the Pheomelanin-Inspired 1,4-Benzothiazine Chromophore: A Still-Undervalued Issue

Abstract

1,4-Benzothiazines are the main building blocks of the naturally occurring pheomelanin pigments, and their chromophoric properties have been strongly related to the well-known phototoxicity of these pigments, partly responsible for the high incidence of melanoma and other skin cancers in red-haired people. However, some peculiar features of the 1,4-benzothiazine chromophore could be functionally exploited in several sectors. Within this context, in this perspective, an overview of the very recently reported applications of the 1,4-benzothiazine chromophore in pH sensing, filter permeability control, smart packaging, electrochromic device fabrication, bioimaging, photocatalysis, and HPLC detection systems is provided, together with a brief presentation of recently developed synthetic approaches to the 1,4-benzothiazine scaffold, with the aim of emphasizing the still-undervalued multifunctional opportunities offered by this class of compounds.

Keywords: 1,4-benzothiazine; 2-aminothiophenol; acidichromism; bioimaging; electrochromism; pH sensing; pheomelanin; photocatalysis; smart packaging.

Figure 1

Schematic overview of eumelanin and pheomelanin biosynthesis.

Figure 2

Overview of the synthetic approaches to 1,4-benzothiazines by coupling of 2-aminothiophenols with carbonyl compounds.

Figure 3

Synthetic approaches to 1,4-benzothiazines based on the use of (A) 2-bromothiophenol and α-halohydroxamates, (B) benzothiazoles and 3-oxo-3-arylpropanenitriles, or (C) acetophenones, anilines, and elemental sulfur (C) [49,50,51].

Figure 4

Chromatographic paper dipped in a solution of 2Z,2′Z-(1,2-ethanediylidene)bis(3-phenyl-2H-1,4-benzothiazine) as a colorimetric sensor for acidic pHs compared to a universal pH indicator paper [52].

Figure 5

pH sensing via reversible chromophoric changes for the 2-((1H-indol-3-yl)methylene)-3-phenyl-2H-1,4-benzothiazine) system [53].

Figure 6

Cellulose acetate filter permeability control through coating with 2Z,2′Z-(1,2-ethanediylidene)bis(3-phenyl-2H-1,4-benzothiazine) [52].

Figure 7

Smart poly(lactic acid) films loaded with the protonated form of 2Z,2′Z-(1,2-ethanediylidene)bis(3-phenyl-2H-1,4-benzothiazine) for detection of decomposing fish fillets [52].

Figure 8

(Pyrrolo)bis(1,4-benzothiazine) TRPZ as a suitable scaffold for electrochromic device fabrication [54].

Figure 9

(Pyrrolo)bis(1,4-benzothiazine) TRPZ as a suitable scaffold for fluorescent nanoparticle preparation for applications in diagnostics [55].

Figure 10

Benzothiazine-fused coumarin derivative for hypochlorite sensing. Photos: confocal fluorescence image of cellular ClO⁻ detected by use of PBC and digital picture of fluorescence response of PBC upon addition of ClO⁻ under 365 nm irradiation [56].

Figure 11

N-phenyl quinoxaline-phenothiazine (QXPT-NPh) as a photoredox catalyst in (A) the light-mediated [3 + 2] cycloadditions of cyclopropylamines with olefins or (B) for the difunctionalization of unactivated olefins through intermolecular addition of α-bromoketones, -esters, or -nitriles [58,59].

Figure 12

Fluorescent 1,4-benzothiazine derivative through reaction of 2-aminothiophenol with glyoxylic acid in acidic medium [60].