Hydrogen Bond-Inhibited C=N Isomerization And Its Application In The Design Of Cys/Hcy Fluorescenct Probe

Fluorescence spectroscopy has become a powerful tool for sensing and imaging trace amounts of samples because of its simplicity, sensitivity, fast response times, as well as its application not only for in vitro assays but also for in vivo imaging studies. Many fluorescence mechanisms, such as photoinduced electron transfer (PET), excimer/exciplex formation, intramolecular charge transfer (ICT), metal-ligand charge transfer (MLCT), fluorescence resonance energy transfer (FRET), and recently developed aggregation-induced emission (AIE), excited-state intramolecular proton transfer (ESIPT), and spirolactam to ring-open equilibrium of rhodamine derivatives, have been used in the design of fluorescent probes for various species.Among the various fluorescence mechanisms, C=N isomerization has been actively developed in recent years. It was found that C=N isomerization is the predominant decay process of excited states in compounds, thus those compounds are often nonfluorescent. In2007, Wang et al. reported the pioneer work that this non-radiative process can be inhibited by the complexation of metal cations to the C=N group (Complexation approach), thereby leading to strong fluorescence emission. Following the strategy, a number of excellent C=N isomerization-based probes have been exploited for sensing various metal cations. Recently, Li et al. reported a new design strategy for the development of fluorescent turn-on probe by the removal, but not the general inhibition, of the C=N isomerization (Removal approach), thus expanding the mechanism into detection of ClO-, a biologically important reactive oxygen species (ROS). However, the attractive mechanism has scarcely been exploited to design fluorescent probes for the detection of other important species other than metal cations and ROS, presumably due to the absence of the appropriate interaction induced by these species to prevent the C=N bond isomerization-induced quenching. In fact, hydrogen bonding is an important non-covalent force often involved in the formation of supramolecular structures. In the area of photophysics research, it has been generally recognized that formation of hydrogen bonds can restrict the intramolecular rotations, and rigidity the molecular structures, and thus, help minimize the nonradiative energy losses of their excitons and maximize their probability of radiative transitions (turns on the emission). Such interaction has been successfully used in the design of AIE-and ESIPT-based fluorescent materials. Encouraged by the above results, in this thesis, we reported that the C=N isomerization could be inhibited by an intramolecular hydrogen bond (Hydrogen bond approach), and applied this strategy to construct a C=N isomerization-based fluorescence turn-on probe, i.e. naphthalimide-based glyoxal hydrazone (2-1), for Cysteine/homocysteine (Cys/Hcy). We hope the attractive hydrogen bond-inhibited C=N isomerization-reduced quenching mechanism could be used in the design of various biological important molecules. These results have been published in Organic Letters, and highlighted in Noteworthy Chemistry by Professor Benzhong Tang in February27,2012.Besides, we also developed a colorimetric probe for thiols by using an anthracene molecule (3-1) based on the Michael addition of thiol to nitroolefin. The Michael addition of a thiol group to nitroolefin of1blocked the intramolecular charge transfer (ICT) from the electron-rich anthracene group to the electron-poor nitroolefin group, leading to a blue shift in the absorption spectra with an evident color change from yellow to colorless. The probe exhibited higher selectivity toward thiols (Cys, Hey and GSH) than other amino acids.