Precision Molecular Engineering of Miniaturized Near-Infrared Fluorophores

Organic fluorophores with near-infrared (NIR) emissions and reduced molecular weights are crucial for advancing bioimaging and biosensing technologies. Traditional methods, such as conjugation expansion and heteroatom engineering, often fail to reduce fluorophore size without sacrificing NIR emission properties. Addressing this challenge, our study utilized computational screening and structure-property relationship analysis to establish comprehensive design principles for compact, single-benzene-based NIR fluorophores. These newly developed fluorophores not only exhibit emissions above 700 nm but also maintain molecular weights under 200 g/mol, approximately 25% of that of Cy7. Additionally, they display unique environmental sensitivity—non-emissive in aqueous solutions but highly emissive in lipid environments. This property significantly enhances their utility in live cell imaging by enabling wash-free applications. Our findings mark a substantial breakthrough in fluorophore engineering, paving the way for more efficient and adaptable imaging methodologies.