Theoretical Design And Experimental Study On Near Infrared Al³⁺ Fluorescent Probes

Aluminum is the most abundant metal element in the earth's crust,which plays an important role in human life,industry and agriculture.However,high concentration of aluminum can not only inhibit the growth of animals and plants,but also cause some neurodegenerative diseases for humans,such as Alzheimer's disease and Parkinson's disease,etc.Therefore,it is urgent to develop an efficient and convenient method to detect Al³⁺.At present,fluorescent probes have attracted wide attention due to their advantages of high sensitivity,high selectivity and simplicity,and have been applied in many fields,such as detecting neutral small molecules,metal cations,anions and biomolecules.Among the numerous fluorescent probes,the near-infrared?NIR,650-900 nm?fluorescent probes have attacted much attention because of their advantages such as long wavelength,good tissue permeability and less interference from biological spontaneous background fluorescence.However,the emission wavelength of Al³⁺ fluorescent probes that have been reported is almost in the visible region.So far as we know,there are only a few near-infrared Al³⁺ fluorescent probes reported in literatures.Therefore,it is of great significance to develop new NIR Al³⁺ fluorescent probes.For metal ion fluorescent probes,the traditional research route is to start with an experimental synthesis,and then test its selectivity towards metal ions.This is relatively time-consuming,labor-intensive,and consumables.Here a new research route is adopted,that is to design molecules and predict molecular properties from theoretical aspect firstly,and then to choose better one to synthesize experimentally.Under this thinking,we designed several Al³⁺fluorescent probes that could emit NIR fluorescence on the basis of the experimentally synthesized Al³⁺ fluorescent probes in the visible region,combined with NIR fluorophore.Then theoretical predictions were conducted on the performance of the probes by using quantum chemical approaches.At last,conclusions were made on which one could be used to detect Al³⁺.The specific research contents are as follows:1.Theoretical design of near-infrared Al³⁺ fluorescent probe based on salicylaldehyde acylhydrazone Schiff base derivativesDensity functional theory?DFT?and time-dependent density functional theory?TD-DFT?were used to study the properties of the salicylaldehyde hydrazone Schiff base probe molecule e1,and a suitable theoretical method for studying the probe was found.The method is then applied to e2 and e3 which are structurally similar to e1 to further verify the accuracy and feasibility of the method.Considering that benzo[h]quinoline derivative HBQ/ABQ can emit near infrared fluorescence,we combined HBQ/ABQ and e3 to design two new Schiff base derivatives HBQ-Th and ABQ-Th.Using the above method to conduct theoretical research on the newly designed molecules,it was found that the newly designed molecules showed a high selectivity for Al³⁺,and their corresponding Al³⁺ complexes can emit NIR fluorescence.Finally,the water solubility of experimental molecule e1 and the designed molecules was calculated,and it was found that the designed molecules had better water solubility than e1.Therefore,the newly designed molecules HBQ-Th and ABQ-Th are expected to become potential water soluble ratiometric NIR Al³⁺ fluorescent probes.2.Theoretical design of near-infrared aza-BODIPY Al³⁺ fluorescent probe based on photo-induced electron transfer?PET?mechanismNIR aza-BODIPY fluorophore ABT has the advantages of larger molar absorption coefficient,higher fluorescence quantum yield and narrower emission band.Therefore,combined ABT with Al³⁺ receptor PSI,two new molecules ABT-PSI and ABT-ASI were designed.We first calculated the properties of PSI before and after reacting with Al³⁺ theoretically,including electrostatic potential,electron absorption and emission spectra,frontier molecular orbital and energy levels,and the thermodynamic reactions of PSI with different metal ions.Then we obtained a suitable method to study this kind of system and verified the method by studying the fluorophore ABT.Finally,the above methods were used to analyze the newly designed molecules ABT-PSI and ABT-ASI.It was found that both ABT-PSI and ABT-ASI could emit strong NIR fluorescence.However,after coordination with Al³⁺,the emission wavelength and fluorescence intensity of ABT-PSI was almost unchanged,while the fluorescence of ABT-ASI was quenched due to PET mechanism.In order to study the selectivity,the interaction between ABT-ASI and different metal ions was explored,and the bonding characters between ABT-ASI and Al³⁺ was revealed by natural bond orbital analysis.It was found that the interaction between ABT-ASI and Al³⁺ was the strongest.Therefore,ABT-ASI is a potential “ON-OFF” NIR Al³⁺ fluorescent probe.3.Theoretical design and experimental study of Al³⁺ fluorescent probe based on pyrazolone derivativePyrazolone derivative PIP is easy to synthesize,which was used to prepare catalyst.Considering that the structure of PIP is similar to PSI and it should have similar properties to PSI,we predicted that PIP could have new application in Al³⁺ fluorescent probe.Based on previous theoretical method,we took PIP as the research object.First,the sensing properties of the molecule were predicted by DFT and TD-DFT methods.It was found that the molecule showedhigh selectivity for Al³⁺,and the fluorescence was significantly enhanced after reacting with Al³⁺.So according to the theoretical prediction results,it could be used as a potential Al³⁺ fluorescent probe.Then the molecule was synthesized experimentally,and the single crystal was obtained.The selectivity was performed by fluorescence spectroscopy,which showed that PIP had a high selectivity towards Al³⁺ and the fluorescence was enhanced significantly after reacting with Al³⁺.This is in good agreement with theoretical predictions.As a result,PIP can be used as Al³⁺fluorescent probe.In order to design NIR Al³⁺ fluorescent probe,we extended the conjugate structure of PIP to make its emission wavelength reach the NIR region,and designed a new molecule PIP-CN.By investigating its spectral properties theoretically,it was found that PIP-CN had almost no fluorescence.After reacting with Al³⁺,the fluorescence was remarkably enhanced.So PIP-CN may be a potential “OFF-ON” NIR Al³⁺ fluorescent probe.