Design,Synthesis And Phototherapy Properties Of Near-Infrared Ⅱ Organic Small-Molecule Fluorescent Based On Donor-Receptor Scaffold

Phototherapy has attracted wide attention due to its non-invasive,easy operation,lack of native and acquired resistance,minimal side effect,security,adjustable laser power.Notably,phototherapy agents were the key elements of phototherapy.More recently,fluorescence imaging in the NIR-Ⅱ region holds great promise with the deep tissuepenetration,minimal autofluorescence,and photon scattering,which was in favor of phototherapy.Therefore,developing NIR-Ⅱ photosensitizers with excellent PCE(Photothermal Conversion Efficiency)or singlet oxygen quantum yield is crucial and highly demanded.Comparing with the inorganic phototherapy agents which possess longterm toxicity,small-molecule phototherapy agents remain to be the most desirable and optimal candidate for clinical transformation because of their unambiguous chemical structures,good biocompatibility,clear metabolic pathways.Design and synthesis of the NIR-Ⅱ organic small-molecule phototherapy agents thus have high significance and direct impact on the field of cancer therapy.Recently,there was literature reported on how to regulate the fluorescence performance of NIR-Ⅱ fluorophores through molecular engineering has been documented.However,how to adjust their phototherapy performance was still rare.Therefore,this thesis focus on the molecular engineer to improve the phototherapy performance,the main research contents were as follow:(1)Xanthene in rhodamine skeleton severed as the electron acceptor,the terminal group in polymethine dyes served as the electron donor.Then,the D-A skeleton formed.Herein,we choose the 4-methyl-2,6-bis(thiophene-2-yl)thiopyran as the terminal group due to the weak electronegative atoms sulfur caused wavelength redshift.Also,we choose the benzoindole as a terminal donor due to its large π conjugate plane and excellent electron donor ability.Based on this concept,we have designed and synthesized NIR-Ⅱ smallmolecule dyes LDM-SN and LDM-IN.It was found that both of their maximum emission wavelengths extend to the NIR-Ⅱ region and both of them could generate ROS under light stimulation.The ROS generation ability of LDM-SN is threefold of previous reported LDM-CH2CH3.Unfortunately,the photothermal ability of LDM-SN and LDM-IN are weak.(2)To improve the phototherapeutic performance of the above-mentioned dyes,we introduced carbazole as the electron donor to improve the ISC rate,which could further enhance the PDT performance of the molecule.Otherwise,we also introduced the rotationfree tetraphenyl-ethylene as the second electron donor to improve the PTT performance.Meanwhile,3,4-dialkyloxythiophene served π bridging unit to decrease the π-π stacking of molecule.TPE,TPE-COOH and N-TPE based on D-A-D structure were successfully synthesized as organic materials.The result indicated that both TPE,TPE-COOH and NTPE possessed excellent photothermal ability.Among them,the PCE of TPE-COOH and N-TPE was 43.6%and 59.0%respectively.Thanks to the introduction of N,Ndiethylamino on TPE scaffold,the photodynamic ability had greatly improved up to 5 fold.In consideration of the excellent phototherapy and fluorescence performance of N-TPE,it had great potential for imaging guide phototherapy.