Conformational sensitivity of conjugated poly(ethylene oxide)-poly(amidoamine) molecules to cations adducted upon electrospray ionization – A mass spectrometry, ion mobility and molecular modeling study

•ESI-MS/MS, IMS and molecular modeling were combined to study PEO-PAMAM conformation.•Protonated and lithiated molecules were studied, with charge states from 2 to 4.•Protonation mostly occurred on PAMAM, with PEO units enclosing the protonated group.•Lithium adduction on PEO units lead to more expanded conformations.•Charge location strongly influenced PEO-PAMAM dissociation behavior.

Tandem mass spectrometry and ion mobility spectrometry experiments were performed on multiply charged molecules formed upon conjugation of a poly(amidoamine) (PAMAM) dendrimer with a poly(ethylene oxide) (PEO) linear polymer to evidence any conformational modification as a function of their charge state (2+ to 4+) and of the adducted cation (H+vs Li+). Experimental findings were rationalized by molecular dynamics simulations. The G0 PAMAM head-group could accommodate up to three protons, with protonated terminal amine group enclosed in a pseudo 18-crown-6 ring formed by the PEO segment. This particular conformation enabled a hydrogen bond network which allowed long-range proton transfer to occur during collisionally activated dissociation. In contrast, lithium adduction was found to mainly occur onto oxygen atoms of the polyether, each Li+ cation being coordinated by a 12-crown-4 pseudo structure. As a result, for the studied polymeric segment (Mn = 1500 g mol−1), PEO-PAMAM hybrid molecules exhibited a more expanded shape when adducted to lithium as compared to proton.

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