Iodine-Containing Mass-Defect-Tuned Dendrimers for Use as Internal Mass Spectrometry Calibrants

Abstract

Calibrants based on synthetic dendrimers have been recently proposed as a versatile alternative to peptides and proteins for both MALDI and ESI mass spectrometry calibration. Because of their modular synthetic platform, dendrimer calibrants are particularly amenable to tailoring for specific applications. Utilizing this versatility, a set of dendrimers has been designed as an internal calibrant with a tailored mass defect to differentiate them from the majority of natural peptide analytes. This was achieved by incorporating a tris-iodinated aromatic core as an initiator for the dendrimer synthesis, thereby affording multiple calibration points (m/z range 600-2300) with an optimized mass-defect offset relative to all peptides composed of the 20 most common proteinogenic amino acids. Graphical abstract ᅟ.

SpheriCal®‐ESI: A dendrimer‐based nine‐point calibration solution ranging from m/z 273 to 1716 for electrospray ionization mass spectrometry peptide analysis

“…Dendrimers are already used for calibration of matrix‐assisted laser desorption ionization mass spectrometry (MS) instruments, 9,10 and have been suggested as internal calibrants in electrospray ionization (ESI) 11 . The ester‐based dendrimers used here tend to ionize as metal–ion adducts rather than protonated species, as opposed to nitrogen‐containing molecules, such as peptides, that tend to be protonated.…”

Syntheses and crystal structures of 2,2,5-trimethyl-1,3-dioxane-5-carboxylic acid and 2,2,5-trimethyl-1,3-dioxane-5-carboxylic anhydride

“…This solution was stirred overnight, affording a white solid that was removed via filtration and the filtrate was evaporated to yield the anhydride as a transparent viscous oil (1.956 g, 5.92 mmol, 88.4%). This was previously reported (Giesen et al, 2018) and crystals of the anhydride were grown from hexanes. Additional purification can be achieved with removal of additional DCU by dissolving the crude viscous product in warm hexanes and cooling the solution at 276 K…”

“…2,2,5-Trimethoxy-1,3-dioxane-5-carboxylic anhydride was prepared according to the literature but with an optimized purification (Malkoch et al, 2002;Giesen et al, 2018). Isopropylidene-protected acid (I, 2.334 g, 13.40 mmol) was added to a 100 ml round-bottom flask equipped with a stir bar and the solid was dissolved in dichloromethane (25 ml).…”

Solution size variation of linear and dendritic bis-MPA analogs using DOSY-1H NMR

“…[1][2][3][4][5][6][7][8][9] One attractive family of branched polymers that has seen increased interest are those based upon 2,2-bis(hydroxymethyl)propionic acid (bis-MPA). First reported by Hult et al, 10,11 the synthesis of bis-MPA dendritic materials has not only improved, but examples of their utility 12,13 have also flourished over the last three decades. 1,[8][9][10][11][14][15][16][17] This improved synthesis allows for an unprecedented level of purity, rivaling convergently-grown dendrimers.…”

“…31 With the advent of PBBM, it should now be possible to investigate the contribution the branched architecture a dendrimer provides to the overall "rigidness" of a bis-MPA dendrimer. With bis-MPA dendrimers already showing their worth as mass calibrants for MALDI-ToF MS 2,8,9,12,19 and now having a true linear analog, 31 an apparent size investigation on this dendrimer family would be of great importance.…”