The Design Of Novel Thiophene-piperazine Fluorescent Molecules And Their Photothermal/imaging Performance

Visible/near-infrared fluorescent dyes,as one of the drugs for the integration of cancer diagnosis and treatment,have become one of the key research directions in scientific research and medical circles because of their high quantum efficiency,low background interference and deep penetration.At present,some fluorescent dyes have been approved by the US FDA for tumor treatment.For example,BODIPY is a fluorescent dye in the visible region?400-700 nm?.Indocyanine green is the dye in the first region of near-infrared?NIR-I,700-900 nm?,however,the visible/near-infrared fluorescent dye is not perfect in the diagnosis and treatment of deep tissue tumors.Therefore,in recent years,the near-infrared second region?NIR-?,1000-1700 nm?Dyes are becoming a hot research topic for many researchers.In this paper,we aimed at NIR-?dyes,We synthesized a new class of D-A-D type fluorescent dyes by N,N-diacetylglycine anhydride,5-Bromothiophene-2-carbaldehyde,2-bromofluorene,alkyl chain,Its physical and chemical properties,the results are as follows:1.In this chapter,we synthesized?3Z,6Z?-3,6-bis??5-?9,9-di?nonadecan-9-yl?-9H-fluoren-2-yl?thiophen-2-yl?methylene?piperazine-2,5-dione?p-QM2AF?,it is a conjugated small molecule compound,it emits fluorescence in the near-infrared region and has light-to-heat conversion properties.The temperature of the nanoparticle solution is as high as 50.5?under laser irradiation with a wavelength of 660 nm and its concentration is 100?g/mL.Cytotoxicity experiments have shown that the cytotoxicity of p-QM2AF NPs is relatively low and its stability and biocompatibility are good.Therefore,it has the prerequisites to become photothermal material.2.Based on p-QM2AF,we synthesized?2Z,5Z?-2,5-bis??5-?9,9-di?nonadecan-9-yl?-9H-fluoren-2-yl?thiophen-2-yl?methylene?-3,6-bis??2-octyldodecyl?oxy?piperazine?p₁-AQM2AF?,electron donor's electron-donating ability is enhanced,and fluorescence quantum efficiency is also increased.The NIR-II fluorescence quantum yield is 0.38%.The temperature of the 100?g/mL nanoparticle solution is as high as52.0?when irradiated by a laser with a wavelength of 660 nm.Cytotoxicity experiments proved that p₁-AQM2AF nanoparticles have lower cytotoxicity and better stability and biocompatibility,and it can realize fluorescence/photoacoustic dual-mode imaging.3.Since the fluorescence quantum efficiency of p₁-AQM2AF is almost similar to that of existing similar products,we replaced all the long alkyl chains on the molecule with short alkyl chains?3-??³-methyl?nonane?.So we synthesized?2Z,5Z?-2,5-bis??5-?9,9-di?nonan-3-yl?-9H-fluoren-2-yl?thiophen-2-yl?methylene?-3,6-bis??2-ethyloctyl?oxy?piperazine?p₂-AQM2AF?.Because the reduction of space distortion is conducive to electron transfer,the UV-visible maximum absorption wavelength correspondingly red-shifts to 653 nm.Compared to p₁-AQM2AF red-shift 15 nm,the p₂-AQM2AF molecule has an emission peak at NIR-?with laser excitation at 808 nm,Which fully proves that it is a NIR-?fluorescent dye,which is worthy of further research and development.All in all,We synthesized a D-A-D type fluorescent dye,which is an extension based on the existing infrared two-region fluorescent dye,and different emission wavelengths can be obtained when the molecular modification method is different,and their emission wavelengths It is very wide and can extend from the first region of near-infrared to the second region of near-infrared.Therefore,NIR-?and NIR-?combination therapy can be realized.