星状多席夫碱的设计及多途径合成及表征——介绍一个化学科学训练综合实验

科学训练综合实验是理科拔尖创新人才培养过程中的一个关键环节,本文介绍了有机化学科学训练课程中一个星状多席夫碱制备及表征的综合实验。通过该实验,学生可以了解席夫碱化学的研究前沿与进展,利用所学的理论知识设计目标产物合成路线,在实验中加深学习重氮化反应、席夫碱反应、铃木偶联反应的基本原理和实验方法,掌握薄层色谱监测反应以及柱色谱分离产物的方法,学会利用核磁共振、红外光谱等现代仪器分析方法来表征和鉴定化合物的结构。通过本实验,不仅可以培养学生严谨的科学态度和科研创新意识,训练学生的科研动手技能。而且通过多样化的实验方式,培养学生的团队协作能力,激发学生的积极性、主动性和创造性,提高拔尖学生分析问题、解决问题的能力。

A"donor–acceptor"structured semiconductor polymer for near infrared fluorescence imaging guided photodynamic therapy

Near infrared(NIR)fluorescence imaging guided photodynamic therapy(PDT)is a technique which has been developed in many clinical trials due to its advantage of real-time optical monitoring,specific spatiotemporal selectivity,and minimal invasiveness.For this,photosensitizers with NIR fluorescence emission and high^(1)O_(2)generation quantum yield are highly desirable.Herein,we designed and synthesized a"donor-acceptor"(D-A)structured semiconductor polymer(SP),which was then wrapped with an amphiphilic compound(Pluronic■F127)to prepare water-soluble nanoparticles(F-SP NPs).The obtained F-SP NPs exhibit good water solubility,excellent particle size stability,strong absorbance at deep red region,and strong NIR fluorescent emission characteristics.The maximal mass extinction coe±cient and fluorescence quantum yield of these F-SPs were calculated to be 21.7 L/(g·cm)and 6.5%,respectively.Moreover,the^(1)O_(2)quantum yield of 89%for F-SP NPs has been achieved under 635 nm laser irradiation,which is higher than Methylene Blue,Ce6,and PpIX.The outstanding properties of these F-SP NPs originate from their unique D-A molecular characteristic.This work should help guide the design of novel semiconductor polymer for NIR fluorescent imaging guided PDT applications.

FRET-based two-photon benzo[a]phenothiazinium photosensitizer for fluorescence imaging-guided photodynamic therapy

To overcome the conflict between the long-wavelength excitation and high singlet oxygen quantum yield of photosensitizers,we conjugated a two-photon fluorophore,tetrahydroquinoxaline coumarin(TQ),and an efficient photodynamic therapeutic agent,benzo[a]phenothiazinium(NBS-NH_(2)),through a hexamethylene linker to build a two-photon photosensitizer,TQ-NBS.In TQ-NBS,TQ served as an energy donor and NBS-NH_(2) acted as an energy acceptor;and TQ-NBS was a F?rster resonance energy transfer(FRET)cassette with a 92.8%efficiency.The large two-photon absorption cross-section of TQ allowed photosensitizer TQ-NBS to work in a 900 nm two-photon excitation(TPE)mode,which greatly benefited the deep tissue penetration in PDT treatment.Meanwhile,the excellent phototoxicity and near-infrared fluorescence of NBS-NH2was kept in TQ-NBS under a TPE mode via a FRET process.Photosensitizer TQ-NBS exhibited a high phototoxic efficacy in living cells and tumor-bearing mice.

Cisplatin-appended BODIPY for near infraredⅡfluorescent and photoacoustic imaging-guided synergistic phototherapy and chemotherapy of cancer

Combining phototherapy and chemotherapy has been considered a promising modality for cancer therapy due to their synergistic effect.Herein,we developed three D-π-A-structured boron dipyrromethenes(BODIPYs)(named as B-B,B-C,and B-C-Pt).Due to their enlargedπ-conjugated structure and high intramolecular charge transfer effect,the synthesized BODIPYs had photothermal conversion capability,and their absorption and fluorescence spectra were red-shifted.The cisplatin-appended BODIPY(B-C-Pt)exhibited good singlet oxygen(^1O_(2))generation ability and near infrared(NIR)absorption and fluorescence(λ_(Abs)=748 nm,λ_(Em)=947 nm).After being encapsulated by distearoyl phosphoethanolamine polyethyleneglycol 2000(DSPE-PEG-2000),which could inhibit the H-aggregation of B-C-Pt,the absorption and fluorescence of the obtained B-C-Pt nanoparticles(NPs)were red-shifted to 762 and 985 nm,respectively.The^1O_(2)quantum yield and photothermal conversion efficiency of the B-C-Pt NPs were 4.0%and 40.6%,respectively.Moreover,B-C-Pt NPs had chemotherapeutic efficacy due to the presence of cisplatin.In vitro and in vivo studies further demonstrated that B-C-Pt NPs had synergistic therapeutic efficacy.Together,B-C-Pt NPs could be employed in NIRⅡfluorescent and photoacoustic imaging-guided synergistic phototherapy and chemotherapy for cancer treatment.

A lipid droplets-targetable fluorescent probe for polarity detection in cells of iron death,inflammation and fatty liver tissue

Abnormal accumulation and metabolism of lipid droplets can lead to a variety of diseases.Polarity,a key parameter of the microenvironment,is closely associated with many diseases and dysfunctions in the body.It is important to elucidate the relationship between the physiological activity of lipid droplets(LDs)and the polarity of the microenvironment.In this work,based on push-pull mechanism,a fluorescent probe(E)-3-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one(PPTH)with aggregation-induced emission(AIE)properties for the detection of polarity changes in cells was synthesized.PPTH not only visualize intracellular polarity fluctuation of iron death and inflammation but also distinguish between normal and fatty liver tissue.

All-in-one phototheranostics based on BTP-4F-DMO nanoparticles for NIR-II fluorescence/photoacoustic dual-mode imaging and combinational therapy

Various phototheranostics have recently been developed for phototherapy.Through proper molecular design,the photochemical and photophysical properties of these phototheranostics can be promoted.Herein,an acceptor-donor-acceptor(A-D-A)-structured dye,BTP-4F-DMO,was synthesized and prepared into water-soluble nanoparticles(NPs).The obtained BTP-4F-DMO NPs had strong absorption from650 nm to 850 nm and a fluorescence emission peak at~900 nm that tailed to~1100 nm.The NPs showed a superhigh photothermal conversion efficiency of 90.5%±5%and could simultaneously generate·OH and^(1)O_(2)with a^(1)O_(2)generation quantum yield of 4.6%under 808 nm laser irradiation.Due to these advanced properties,BTP-4F-DMO NPs can switch the role of autophagy from pro-survival to prodeath,thereby further promoting cancer cell death.These features make BTP-4F-DMO NPs a promising multifunctional phototheranostic agent for NIR-II fluorescence/photoacoustic dual-mode imaging-guided synergetic photodynamic/photothermal therapy.In general,this work provides a strategy for expanding the biomedical applications of organic A-D-A-structured phototheranostics.

受体-供体-受体结构光疗试剂用于近红外二区荧光成像和光声成像引导的光动力和光热联合治疗

多模态成像引导的光动力和光热治疗在癌症治疗上具有明显的优势.同时具有近红外光(NIR)吸收、高活性氧(ROS)产率和高光热转换效率的物质是非常理想的光疗试剂.本文设计合成了一种具有“受体-供体-受体”(A-D-A)结构的分子IDCIC.随后通过在IDCIC表面包裹DSPE-PEG2000-NH2得到了水溶性纳米颗粒IDCIC NPs.IDCIC NPs具有近红外吸收,峰值位于760 nm;同时还具有近红外二区荧光发射,峰值在1000 nm左右,荧光量子产率为1.2%,使得IDCIC NPs具有良好的光声成像和NIR-Ⅱ荧光成像能力.此外,IDCIC NPs在808 nm激光器照射下可以同时产生单线态氧(量子产率为9.1%)、羟基自由基(·OH)和热量(光热转换效率为78.9%).基于以上这些特性,IDCIC NPs可以用于多模态成像引导的光动力/光热联合癌症治疗.

A controllable self-localized imaging strategy capable of synchronous in situ tracking of local changes in intracellular bioactive small-molecules

In situ tracking and localization of ubiquitous bioactive small molecules(BSMs)within their native habitats is particularly challenging because of their low-molecular weight and widespread distribution properties.We report the proof of concept of a synchronous in situ imaging strategy,whereby the representative BSM amino-biothiols(ABs)mediate activation of the selflocalizable probe HYPQS,thereby releasing insoluble emissive precipitates to afford holistic distribution information of ABs.Notably,three organelle-targetable ABs inhibitors were innovatively fabricated for directed clearance of ABs in particular organelles,providing a powerful aid for HYPQS to achieve programmed in situ tracking of ABs in different organelles“on demand”.Biological transmission electron microscopy images confirmed that this probe released insoluble emissive precipitates at the reaction sites,which is of primary importance for achieving synchronous in situ tracking of BSMs.Furthermore,the probe HYPQS was successfully applied to monitor the dynamic changes in the endogenous ABs pool during diverse cell events.This strategy opens a promising avenue for investigating the undiscovered functional mechanism of local BSMs in relevant biological processes.

Coumarin-based two-photon AIE fluorophores: Photophysical properties and biological application

Based on the coumarin skeleton, we deliberately designed two groups of fluorophores, termed as CoumR and Naph-Coum-R, using the diphenylamino group as the electron donor, which displayed longwavelength emissions(red spectral region), large Stokes shift(up to 204 nm), superior AIE performance,and large two-photon absorbance cross-sections(as high as 365 GM). The electron-withdrawing substituents at the 3-position of these dyes could induce a significant red-shift in their emission spectra.Preliminary imaging experiments demonstrated the capability of these dyes as two-photon fluorophores for specifically staining lipid droplets in living cells.

Carbon dot-based fluorescent and colorimetric sensor for sensitive and selective visual detection of benzoyl peroxide

Benzoyl peroxide(BPO) has been added in wheat flour because of its bleaching effect. However, the abnormal used BPO has caused increasing concern due to its strong oxidization capability which may have adverse effects on living organisms. Herein, we present a carbon dot(CD)-based fluorescent and colorimetric probe for visually, sensitively and selectively sensing BPO. The addition of BPO could quench the red fluorescence of CDs peaked at 622 and 677 nm, and decrease the absorbance at 613 nm, while increase the absorbance at 450 nm, resulting in a fluorescence turn-off and colorimetric spectral response.Moreover, the CDs had short response time of 10 min and high sensitivity towards BPO with a low limit of detection of 28 nmol/L. The applicability of the CDs in detecting BPO in wheat, noodle and starch samples was further demonstrated, and good recovery results were obtained.

A ratiometric merocyanine-based fluorescent probe for detecting hydrazine in living cells and zebra fish

We developed a merocyanine-based fluorescent probe,NEPB,for tracing hydrazine(N2 H4)in a ratiometric manner with large Stokes shifts and long emission wavelength.The fluorescence color of probe NEPB changed from green to yellow upon addition of hydrazine.Probe NEPB displayed high selectivity and sensitivity to hydrazine in solution,and could ratiometrically monitor N2 H4 in living cells and zebrafish with low cytotoxicity.