Development Of Novel MALDI Matrices Based On Carbon Nanodots For The Analysis Of Small Molecules

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),is a powerful soft ionization method.Compared with other traditional mass spectrometry technologies,t his technique has superior advantages including simple sample preparation,small sample consumption,high throughput,good salt tolerance,high sensitivity,as well as no or little fragmentations.Therefore,MALDI-TOF MS has been widely applied in the detection of biomacromolecules,polymers,and high molecular weight compounds.In recent years,the application of MALDI MS for small molecules analysis has attracted an increasing interest.In recent years,the application of MALDI MS for small molecule analysis ha s attracted an increasing interest.However,the detection of metabolites weight less than 500 Da using MALDITOF MS are still challenging.Only few commercialized small organic matrices have been efficiently used for the analysis of low-molecular-weight(LMW)molecules by MALDI-TOF MS.More seriously,the application of these matrices usually cause interference of chemical background noise in the low m/z region as well as signal suppression and peak indistinguishable.Therefore,there is a need to develop a new MALDI matrix to solve the above problems.This paper mainly carried out the following two works:1.In this paper,reduced carbon nanodots(r-CDs)were prepared and mixed with several organic small molecule matrices,including 9-aminoacridine(9-AA),1,5-diaminonaphthalene(DAN),3-hydroxy-2-picolinic acid(3-HPA)and naphthylethylenediamine dihydrochloride(NEDC)to form different novel binary MALDI matrices.We detected a series of small molecules such as amino acids,peptide Gly-Gly,dopamine and anticancer drug erlotinib by MALDI MS.Small molecule detection can be achieved in negative ion mode.LDI MS was carried out to detect the background of r-CDs,and the different binary matrices formed by r-CDs and other small organic matrices.The amino acids mixture model was used as LMW detection model by MALDI MS.The binary matrix of DAN and rCDs had less matrix background and good analyte signals.The test of salt tolerance of the binary matrix of DAN and r-CDs showed that it had a certain degree of salt tolerance and could be used for the detection of biological samples.The above results showed that the low-background,high-sensitivity of LMW substance detection could be realized in the negative ion mode based on the novel binary MALDI matrix mixed by r-CDs and DAN.2.We synthesized 1,5-diaminonaphthalene functionalized carbon nanodots(DAN-CDs)for the first time,and it was explored as a novel matrix for direct detection of small molecules by MALDI MS in negative ion mode.We first characterized the morphology,infrared absorption,ultraviolet absorption,and X-ray photoelectron spectroscopy of DAN-CDs.Carbon dots(CDs),DAN,DANCDs and the binary matrix of CDs and DAN were used as four MALDI matrices and compared with each other.After the MALDI MS detection of a series of LMW analytes including fatty acids(FAs),amino acids,dipeptide Gly-Gly,dopamine,and antitumor drug erlotinib.Small molecule substances were detected by MALDI MS.DAN-CDs was favored because of its less matrix background and good detection sensitivity.In addition,the DAN-CDs matrix displayed good salt tolerance and was further applied for qualitative detection of endogenous FAs in a plasma sample,indicating that DAN-CDs have the ability to be applied to complex biological samples.These results demonstrated that DAN-CDs was a novel negative ion mode matrix for the analysis of small molecules with less matrix background and high detection sensitivity by MALDI MS.In summary,by combining with the organic matrix to prepare a binary matrix and functionalizing modification of the surface functional groups of CDs by DAN matrix,the CDs cooperated with the organic matrix to reduce the background interference from the matrix,enhance d the signal intensity,and enhanced the sensitivity of LMW substances by MALDI MS.Among the experiments,it was found that the DAN functionalized modification of CDs had advantages in salt tolerance and the detection of biological samples.DAN-CDs could be applied to further biological sample analysis.