The theory of cysteine two-photon fluorescence probes of coumarinocoumarin derivatives and kinetics of ICT and PET mechanisms of probe molecules

Cysteine is an essential amino acid in the synthesis of human protein. Therefore, the effective detection of cysteine in living organisms is of great significance. In this paper, first-principles are used to systematically study the fluorescence recognition mechanism and two-photon absorption properties of a series of novel two-photon (TP) fluorescent probes for cysteine. These probes are constructed based on coumarinocoumarin derivatives possessing the excellent fluorescence properties of coumarin molecules and the experimental fact that sporadic coumarinocoumarin can be used as a fluorescent probe, the recognition of which depends on enabled photo-induced electron transfer (PET) and intramolecular charge transfer (ICT) mechanisms toward cysteine. The results show that the transition dipole moments of coumarinocoumarin and monomer coumarin are significantly different, which allows the coumarinocoumarin to break the limit of the linear increase in the dipole moment vector of the monomer coumarin in the direction and magnitude. The magnitude of the two-photon cross-section value ( δ max T ) depends on the state dipole moment ( μ j j ( μ i i )) of the transition channel and the transition dipole moment ( μ i j ) of the coherent channel. Through the above research, we propose that (1) the length of the π conjugated chain can be increased along the 7-site of the coumarinocoumarin skeleton; (2) extend the π conjugated chain along different paths to change the state dipole moment of the transition channel of the target molecule and the direction of the transition dipole moment vector of the coherent channel to improve the TPA cross-section values of the probe molecule. Moreover, maximum TPA can be achieved in the range of 700–1000 nm for designed probe molecules, effectively avoiding factors such as the self-fluorescence of biological tissues and background interference. CCy-1-OH ∼ CCy-3-OH and CCy-7-OH molecules are designed to be excellent candidates for TP fluorescent probes. We hope the study can provide useful theoretical basis for cysteine imaging research.