Natural flavylium-inspired far-red to NIR-II dyes and their applications as fluorescent probes for biomedical sensing

Fluorescent probes that emit in the far-red (600-700 nm), first near-infrared (NIR-I, 700-900 nm), and second NIR (NIR-II, 900-1700 nm) regions possess unique advantages, including low photodamage and deep penetration into biological samples. Notably, NIR-II optical imaging can achieve tissue penetration as deep as 5-20 mm, which is critical for biomedical sensing and clinical applications. Much research has focused on developing far-red to NIR-II dyes to meet the needs of modern biomedicine. Flavylium compounds are natural colorants found in many flowers and fruits. Flavylium-inspired dyes are ideal platforms for constructing fluorescent probes because of their far-red to NIR emissions, high quantum yields, high molar extinction coefficients, and good water solubilities. The synthetic and structural diversities of flavylium dyes also enable NIR-II probe development, which markedly advance the field of NIR-II in vivo imaging. In the last decade, there have been huge developments in flavylium-inspired dyes and their applications as far-red to NIR fluorescent probes for biomedical applications. In this review, we highlight the optical properties of representative flavylium dyes, design strategies, sensing mechanisms, and applications as fluorescent probes for detecting and visualizing important biomedical species and events. This review will prompt further research not only on flavylium dyes, but also into all far-red to NIR fluorophores and fluorescent probes. Moreover, this interest will hopefully spillover into applications related to complex biological systems and clinical treatments, ranging in focus from the sub-organelle to whole-animal levels.