The ability of multidimensional mass spectrometry (MS) approaches, interfacing different ionization methods with tandem mass spectrometry (MS2) fragmentation and ion mobility (IM) separation, to characterize synthetic polymers is demonstrated for poly(α-peptoid)s synthesized by N-heterocyclic carbene (NHC)-mediated zwitterionic ring-opening polymerization. Matrix-assisted laser desorption ionization (MALDI) causes elimination of the NHC initiator, if performed in the presence of cationizing salts. Electrospray ionization (ESI) is softer, allowing for the detection of the intact sample. It also shows that in proper solvents self-assembly of the poly(α-peptoid) occurs to form supramacromolecules; since these noncovalent self-assemblies overlap with the main product, separation by IM MS is essential for their conclusive identification. MS2 confirms the connectivity of the poly(α-peptoid)s, whereas MS2 combined with IM separation renders valuable insight into the binding interactions in the supramolecular assemblies and on the structures and conformations of the poly(α-peptoid) resulting after NHC elimination. Performing all analyses inside the mass spectrometer (“top-down”) enables fast, sensitive, and cost-effective analysis of polymer composition, structure, and architecture without prior derivatization, separation, or degradation.

The self-assembly of Zn(II) ions and bis(terpyridine) (tpy) ligands carrying 120° or 180° angles between their metal binding sites was utilized to prepare metallosupramolecular libraries with the connectivity. These combinatorial libraries were separated and characterized by ion mobility mass spectrometry (IM MS) and tandem mass spectrometry (MS(2)). The 180°-angle building blocks generate exclusively linear complexes, which were used as standards to determine the architectures of the assemblies resulting from the 120°-angle ligands. The latter ligand geometry promotes the formation of macrocyclic hexamers, but other n-mers with smaller (n = 5) or larger ring sizes (n = 7-9) were identified as minor products, indicating that the angles in the bis(terpyridine) ligand and within the coordinative tpy-Zn(II)-tpy bonds are not as rigid, as previously believed. Macrocyclic and linear isomers were detected in penta- and heptameric assemblies; in the larger octa- and nonameric assemblies, ring-opened conformers with compact and folded geometries were observed in addition to linear extended and cyclic architectures. IM MS(2) experiments provided strong evidence that the macrocycles present in the libraries were already formed in solution, during the self-assembly process, not by dissociation of larger complexes in the gas phase. The IM MS/MS(2) methods provide a means to analyze, based on size and shape (architecture), supramolecular libraries that are not amenable to liquid chromatography, LC-MS, NMR, and/or X-ray techniques.

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