Exploring the Conformational Landscape of Poly(L-lysine) Dendrimers using Ion Mobility Mass Spectrometry

Ion mobility mass spectrometry (IM-MS) measures the mass, size and shape of ions in the same experiment, and structural information are provided via collision cross section (CCS) values. The majority of commercially available IM-MS instrumentation relies on the use of CCS calibrants, and here we present data from a family of poly(L-lysine) dendrimers and explore their suitability for this purpose. In order to test these compounds we employed three different IM-MS platforms (Agilent 6560 IM-QToF, Waters Synapt G2 and a home-built variable temperature drift-tube IM-MS) and used them to investigate six different generations of dendrimers in two buffer gases (helium and nitrogen). Each molecule gives a highly discrete CCS distribution suggestive of single conformers for each m/z value. The DTCCSN2 values of this series of molecules (molecular weight: 330 - 16214 Da) range from 180 to 2940 Å2, which spans the CCS range that would be found by many synthetic molecules including supramolecular compounds as well as many biopolymers. The CCS values for each charge state were highly reproducible in day to day analysis on each instrument although we find some small systematic variations between instruments. The rigidity of each dendrimer was probed using collisionally activated as well as high-temperature IM-MS experiments, where no evidence for significant CCS change ensued. Taken together, this data indicates that these polymers are candidates for CCS calibration and could also help to reconcile differences found in CCS measurements on different instrument geometries.