New Derivatization Strategies for Installation of Fixed, Permanent Charges onto Analytes of Biological and Environmental Concern

Mass spectrometry (MS) is a highly sensitive analytical technique that can be used to identify thousands of analytes from a single biological matrix. Chemical derivatization (CD) reagents can enhance analyte detection and quantification by adding a specific functional group that enhances ionization efficiency and stability. The goal of this project is to design a new CD reagent by synthesizing a Meldrum's acid derivative containing a fixed permanent charge (MAD+) to be used as a stable ketene precursor. Synthesis of a MAD+ was explored via alkylation and Knoevenagel condensation reactions but proved unfruitful. However, C-alkylation with 6-bromohexanoic acid via carbodiimide coupling, reduction and amine alkylation produced a MAD+ in generous yields. The reaction of this MAD+ with 3,5-di-tert-butylphenol demonstrated its ability to induce its fixed permanent charge onto analytes, allowing its detection in MS. Purification of the final MAD+ remained an issue and should be investigated and optimized in future works.