Construct And Study Of Hyperpolarized Xe-129 Biosensors Based On Functionalized Cryptophane

129 Xe is a nontoxic and inert gas,whose chemical shift is sensitive to the molecular environment.Hyperpolarized ¹²⁹Xe NMR has high sensitivity,which makes it particularly suited to biomedical applications.Howerver,hyperpolarized ¹²⁹Xe cannot recognize target directly and selectively.Cryptophane-A cage provides most suitable xenon affinity and exchange kinetics,making it an excellent host for xenon atoms.In order to develop hyperpolarized ¹²⁹Xe cryptophane biosensor for detection of specific molecules,the cryptophane-A cage must be functionalized.In this work,we have designed and synthesized a series of functionalized cryptophane derivatives,and studied their properties by ¹²⁹Xe NMR and optical spectrum.Some compounds have good properties can be used to detect certain biomolecules.The main points and results of this work are as follows:1.A biothiols responsive cryptophane compound has been constructed.This compound was composed of a cryptophane-A cage as ¹²⁹Xe host molecule,a disulfide bond as thiols response group,and an aphthalimide as fluorescence reporter.As important roles of biothiols in metabolism,detection of intracellular biothiols is critically important.The cryptophane compound shows good selectivity for biothiols,and high stability in a broad pH range.Further,this compound can make good response for biothiols in cells,which can be monitored via fluorescence and hyperpolarized ¹²⁹Xe NMR.This is the first example for biothiols detection with ¹²⁹Xe NMR in cells,which provides a new high sensitive method for biothols detection.2.A biothiols responsive drug detection system（DDS）based on functionalized cryptophane has been constructed.This DDS was composed of a cryptophane-A cage as ¹²⁹Xe host molecule,a disulfide bond as thiols response group,an aphthalimide moiety as fluorescence reporter,and a chlorambucil as anticancer drug.This compound shows good selectivity for biothiols.When exposed to biothiols,chlorambucil will be released from the prodrug,which can be monitored by fluorescence and ¹²⁹Xe NMR.The DDS can be triggered in cancer cells effectively,and shows much higher cytotoxicity towards lung cancer cells.This study provides a new method for DDS construction and is the first example to monitor the drug releasing process by ¹²⁹Xe NMR.3.A multifunctional small molecule cryptophane compound has been constructed.This compound was composed of a cryptophann-A cage as ¹²⁹Xe host molecule,and a porphyrin moiety as a multifunctional group.This compound shows good response to pH across a wide-range of pH value.Further,this compound can make a good response to pH in cells.The compound has the ability to generate singlet oxygen around pH 6 irradiated by high-pressure mercury lamp,suggesting the potential for photodynamic therapy.The cellular fluorescence imaging demonstrated that the compound can be uptaken by cells,and shows high specificity for tumour cells.More importantly,as strong fluorescence intensity and long fluorescence emission wavelength,the compound can be used in fluorescence imaging of A549 tumor mouse model.