Tailor-Made Stable Zr(IV)-Based Metal–Organic Frameworks for Laser Desorption/Ionization Mass Spectrometry Analysis of Small Molecules and Simultaneous Enrichment of Phosphopeptides

Although thousands of metal-organic frameworks (MOFs) have been fabricated and widely applied in gas storage/separations, adsorption, catalysis, and so on, few kinds of MOFs have been used as adsorption materials while simultaneously serving as matrixes to analyze small molecules for laser desorption/ionization mass spectrometry (LDI-MS). Herein, a new concept is introduced to design and synthesize MOFs as both adsorption materials and matrixes according to the structure of ligands and common matrixes. The proof of concept design was demonstrated by selection of 2,5-pyridinedicarboxylic acid (PDC) and 2,5-dihydroxyterephthalic acid (DHT) as ligands for synthesis of MOFs. Two Zr(IV)-based MOFs of UiO-66-PDC and UiO-66-(OH)2 were synthesized and applied for the first time as new matrixes for analysis of small molecules by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Both of them showed low matrix interferences, high ionization efficiency, and good reproducibility when used as matrixes. A variety of small molecules, including saccharides, amino acids, nucleosides, peptides, alkaline drugs, and natural products, were analyzed. In addition, UiO-66-(OH)2 exhibited potential for application in the quantitative determination of glucose and pyridoxal 5'-phosphate. Furthermore, thanks to its intrinsically large surface area and highly ordered pores, UiO-66-(OH)2 also showed sensitive and specific enrichment of phosphopeptides prior to MS analysis. These results demonstrated that this strategy can be used to efficiently screen tailor-made MOFs as matrixes to analyze small molecules by MALDI-TOF-MS.