Synthesis And Activity Of Novel Diboronic Acid Fluorescent Probes With Double Recognition Sites

Endogenous small molecules such as carbohydrates and catecholamines play an important role in the development and progression of the disease.For example,D-ribose can promote the recovery of ischemia and hypoxic tissue and its abnormal content is also significantly correlated with diseases such as leukoencephalopathy and diabetes.Abnormal concentrations of dopamine in the body often lead to psychotic diseases of Parkinson's disease and endocrine diseases.Therefore,endogenous small molecule substances are often used clinically as indicators for the diagnosis,treatment and prognosis of certain diseases.The traditional methods of diagnosis and monitoring have the defects of long detection time and large radiation damage to living organisms.There are a variety of disease-related substances in the body that are structurally similar.How to accurately detect endogenous small molecular substances and achieve rapid diagnosis and treatment of diseases is an urgent problem to be solved.Compared with traditional diagnostic methods,optical imaging technology has the advantages of non-ionization,high resolution and specific combination.Endogenous small molecules are targeted for recognition by fluorescent small molecules for clinical detection.Therefore,Endogenous small molecules are targeted by fluorescent small molecules,which has great potential for clinical detection.Boronic acid can interact with cis diol to cause a change in fluorescence intensity,which can be used as a fluorescent probe for identifying saccharide compounds.However,the presence of a large fluorophore in most boric acid-based fluorescent probes results in poor water solubility and poor selectivity.In this paper,a series of diboronic acid compounds were designed and synthesized for the activity test by using water-soluble boronic acid2-?4-dihydroxyborane?phenylquinoline-4-carboxylic acid?PBAQA?as building unit.In order to find the ideal fluorescent molecules for disease detection and optical imaging.In terms of synthesis,the key intermediate PBAQA is prepared by a series of reactions such as palladium catalysis using eosin and 4-bromoacetophenone as starting materials.Another phenylboronic acid was introduced as a second recognition site.In the process of amide condensation,a new condensing agent is used to optimize the reaction route.The two boronic acid groups are connected by an intermediate chain.Compared with the previous synthesis method,This method used a low toxicity and low boiling point alcohol as a solvent and mild reaction conditions.It has the advantages of high reactivity,few by-products and simple post-treatment.7 monoboronic acid compounds and 52 diboronic acid compounds were synthesized.Among them,30 compounds are new compounds that have not been reported.All compounds were confirmed by mass spectrometry,nuclear magnetic resonance spectroscopy,and high resolution mass spectrometry.Fluorescence activity test results show that when diboronic acid compounds with a fatty amine as a linker binds with different sugars and it has different fluorescence responses.The fluorescence of the compound was reduced after binding to glucose,ribose and maltose;the fluorescence intensity increasesed after binding to D-mannose,D-fructose,D-galactose,D-glycosamine,sialic acid.The different fluorescence response of compounds to sugars may be related to the binding of sugars to triols or diols to probes.In particular,when compound 12b was combined with 0.0146 mol×L^-1 of D-ribose,the fluorescence intensity of the compound was reduced by 50%and was 4.6 times that of D-glucose.The binding constant of this compound to D-ribose is 212 L×mol^-1,which is also much larger than the binding constant of glucose(24L×mol^-1).Further,the fluorescence of the compound 12b significantly increased in combination with fructose,mannose,galactose,glucosamine,sialic acid,sorbitol,and arabinose.It has been reported that fluorescent probes that recognize D-ribose are less and poor in water solubility result in inability to detect in biological fluids.Compound 12b can recognize D-ribose by fluorescence quenching under conditions in which only 1%of the organic solvent is present.Compound 12b was also able to detect D-ribose in rabbit plasma.The test results also found that the binding constant of compound 12i to dopamine(5204±106 L×mol^-1)was twice that of levodopa(2383±273 L×mol^-1)and catechol(2588±273 L×mol^-1).The fluorescence intensity of compound 12i has a good linear relationship with dopamine concentration in the concentration range of 0.05-0.5 mol×L^-1.There was no change in fluorescence of compound 12i after binding to dopamine analogs?phenol,hydroquinone,hydroquinone,tyrosine?.This compound is selective for dopamine.Compound 12i is capable of detecting dopamine concentrations in biological fluids.In addition,a series of long-wavelength compounds were constructed using an aromatic amine as a linker.The emission wavelength of the series of compounds at around 500 nm was significantly longer than the emission wavelength of the lead compound and it had a large Stokes shift.A series of compounds can overcome the interference of fluorescent background and avoid damage of biological samples by ultraviolet light.Under the premise that the group of typical aggregation-induced effect is not introduced,a series of compounds have different degrees of aggregation-induced effect,which can overcome the aggregation caused quenching in the conventional fluorescent molecules.Fluorescence tests showed that the fluorescence intensity of this series of compounds combined with sugars decreased and the mechanism may cause sugar to induce dissociation of the aggregation state of the series of compounds.This mechanism may be caused by sugar-induced dissociation of the aggregation state of the series of compounds.This series of compounds has a strong fluorescence response to D-ribose and its application needs further research.In summary,a series of diboronic acid probes were constructed based on PBAQA and the fluorescence activity was studied.This study found fluorescent probes for the selective recognition of D-ribose and dopamine.The binding activity test results in rabbit plasma were consistent with the buffer results.This study provides a material basis for further realization of cell fluorescence imaging,related disease diagnosis and mechanism research.