Origins of near-infrared-II emission tail and fluorescence enhancement of albumin-chaperoned cyanine dyes from a multiscale computational study

Abstract

Repurposing the commercially available NIR-I cyanine dyes for NIR-II imaging has attracted increasing research interest. The bright tail emission of the present NIR-I dyes can afford high-performance NIR-II imaging with improved quantum yields (QYs) and absorption coefficients, thus accelerating the (pre-) clinical translation of NIR-II imaging. However, the quantum nature of the typically ignored but important NIR-II emission tail of cyanine dyes has never been revealed systematically, and an in-depth understanding of the fluorescence enhancement mechanism for cyanine–protein assemblies remains unclear. In this work, the quantum chemical calculations, molecular dynamics simulations, and fluorescence intensity measurements were used together to study the electronic and optical properties based on two representative cyanine dyes of ICG and IR783 with similar molecular skeletons. Distinct origins of NIR-II tail emission were identified, illustrating their significantly different quantum nature of the excited state: nuclear vibration versus twisted intramolecular charge transfer (TICT). Furthermore, the key roles of bovine serum albumin (BSA) protein through a supramolecular assembly strategy in building high-performance NIR-I cyanine dyes with NIR-II imaging were revealed. A rigid conformation of cyanine with optimal torsion can be maintained in the typically inaccessible hydrophobic domains of the BSA protein to avoid completely falling into the so-called fluorescence quenching trap. Notably, the first water shell plays a dominant role in fluorescence quenching, and the dipole–dipole coupling involved in the energy transfer process between the fluorophore and water is related not only to their distance but also to the relative orientation of each water molecule with respect to the fluorophore. The present study can provide a comprehensive understanding of the nature of NIR-II tail emission for conventional NIR-I dyes and further provide a general rule to explore conventional NIR-I dyes with bright NIR-II tail emission for NIR-II imaging.