Domino synthesis of a new class of red-shifted and antimicrobial imidazole-based azo dyes from 5-aminoimidazole-4-carboxamidrazones

Abstract

Combining antimicrobial activity with halochromic properties offers an enticing opportunity to both combat and detect microbial infection in the medical field. Previous research has identified a class of compounds that demonstrate potent antimicrobial activity, particularly against pathogenic yeasts. Notably, these compounds also exhibit vibrant pink-blue colours and a halochromic behaviour within the therapeutic pH range. Aiming at developing a more sustainable synthetic method and to generate better red-shifted and pH-responsive imidazole-based azo dyes, a new domino reaction was dis-covered yielding a novel class of green-coloured 2-aminoimidazole azo-dyes. A strategy based on circular chemistry was achieved by introducing the accessible and environmentally benign O₂/KI oxidant system, which is able not only to regenerate the oxidants but also minimize side reactions. The isolation of two key intermediates was also an important achievement in comprehending the underlying mechanisms. As expected, this new class of 2-aminoimidazole dyes also presented significant solvatochromism and pronounced halochromism with colours changing from green to purple as the pH decreases. ab initio molecular quantum mechanics calculations supported the data obtained experimentally. A great number of compounds (12 in 18 compounds) showed potent fungicidal activity against C. neoformans and moderate activity against C. krusei.