Design And Synthesis Of Tetraphenylethene Derivatives:Application In Bio-detection And Bio-imaging

AIE materials with water solubility and red emission are required for their applications in bio-systems.With good water solubility,they can have high sensitivity in bio-detection while with long wavelength emission they can avoid the fluorescence from the cells and achieve high signal to noise ratio in bio-imaging.What’s more,materials with two-photon fluorescence can penetrate much deeper into tissues than normal one-photo fluorescence and disclose more biological information.Up to now,however,only limited number of relevant reports have been documented due to the difficulty in synthesis and purification of red-emitting water soluble AIE-gens.In this thesis,we prepare AIE materials with red emission and water solubility via several different methods and try to find their applications in bio-detection and bio-imaging.Firstly,as an improvement of the pre-work in our lab,two compounds with TPE moiety modified on the N-term of perylene bisimide(PBI)were synthesized.They displayed quite different optical property and aggregate behavior with the derivatives with TPE unit on their 1,6-and 1,7-positions.As the rigid structure and the steric effect of the TPE moiety,both of the two compounds formed X-aggregate in the solvent/non-solvent mixtures.Owing to the photo-induced charge transfer between TPE and PBI subunits,the dyes showed quite weak fluorescence in solution,aggregate and solid state.As a result,these N-term modified compounds are one kind of TPE-PBI Dyads.Secondly,we prepared two AIE molecules with red-emission,TPE-TCF and TPE,DTCF,by simply modified strong electronic acceptor to the TPE units.Both of them showed TICT and AIE properties in the THF/water mixtures and their quantum yield in solid state were as high as 24.8%and 13.8%,respectively,which was perfect when comparing with other reported red emissive AIE materials.Owing to their D-A structure,they had obvious solvatochromic effect,with the increasing of the solvent polarity,they showed 120 nm and 80 nm red-shift on the emission wavelength,respectively.What’s more,TPE-TCF also had mechanochromic property based on the transition between its crystal and amorphous states.While because of its A-π-D-π-A structure,TPE-DTCF exhibited two-photon fluorescence with two photon absorption cross-section value as 150 GM and 280 GM in solution and aggregate,respectively.Then,we prepared their AIE nanoparticals with good water solubility encapsulated by DSPE-PEG2000-MI modified with Tat protein,which could help them go through the cell membrane smoothly.The obtained nanoparticals had uniform size with diameters as about 100 nm.Meanwhile,they could emit strong red fluorescence with large Stokes wavelength,which was suitable for cell imaging.After incubated with HeLa cells for 2 h,strong red emission could be observed by the confocal laser scanning microscopy(CLSM),demonstrated that they could go into the cytoplasm and displayed perfect results.For the TPE-DTCF nanoparticals with two-photon fluorescence,strong fluorescence could also be observed in the cytoplasm by a two-photon fluorescence microscopy,indicated it as a new probe for two-photon cell imaging.Afterwards,we prepared two other water soluble TPE derivatives,which were decorated by quaternary ammonium group(TPE-4MN)and sulfonate group(TPE-2SO3Na),respectively.Both of them are AIE-active.TPE-4MN could detect heparin with high sensitivity and selectivity and the fluorescent intensity of the solution enhanced linearly with the increasing of heparin concentration.It had been figured out that the interaction between TPE-4MN and heparin was electrostatic interaction,which is not specific but can be influenced by the charge density and the steric effect.TPE-2SO3Na was used in the study on its interaction with heparin/protamine complexes.As a result,it could bind to protamine by aid of the interaction between positive and negative charges,as well as the hydrophobic binding process.What’s more,the fluorescence of the mixture was influenced by the order of the addition of compounds.At last,we separated the cis-and trans-isomers of boric acid modified TPE and distinguish their structures by 1D-and 2D-NMR spectra as well as the theoretical simulation.Both of the isomers were AIE-active but showed different fluorescence enhancement in the DMSO/water mixture.What’s more,they can dissolve in carbonate buffer with pH = 10.5 well and exhibited different response to β-cyclodextrin,which was owing to their different binding modes.This is a classic case about the specific detection of biomolecules based on the synergistic effect of multiple weak interactions.It provided us a new strategy on the study of weak interactions as well as a new method for the isomers purification in organic synthesis.