Titre de la dissertation: « Probing the Structure of Complex Functional Polymers Using Ion Mobility Mass Spectrometry and Molecular Dynamics Simulations. »

Promoteurs: Pascal Gerbaux et Christopher Barner-Kowollik

Résumé de la dissertation: Nature achieves extraordinary functionality through macromolecules such as proteins and enzymes, which fold into precise three-dimensional structures enabling selective and efficient catalysis. Inspired by these systems, synthetic chemists have developed single-chain polymeric nanoparticles (SCNPs), in which individual polymer chains undergo intramolecular cross-linking and collapse into compact nanostructures. SCNPs are versatile biomimetic materials with applications in catalysis, drug delivery, sensing, and imaging. Among them, metallo-folded SCNPs—formed through coordination between metal ions and ligand sites along the polymer backbone—function as catalytic nanoreactors, closely mimicking enzymatic activity while offering advantages in reusability and solubility tuning.A central challenge in advancing SCNPs lies in their intrinsic heterogeneity. Synthetic polymers are typically polydisperse, with variations in chain length, sequence, and functional group positioning. Consequently, individual chains can exhibit distinct folding behaviors and catalytic properties. Conventional characterization techniques such as dynamic light scattering, size exclusion chromatography, and diffusion-ordered NMR provide valuable ensemble-averaged information but fail to resolve this single-chain diversity. Gaining molecular-level insights into SCNP folding and function therefore requires new analytical strategies capable of probing individual polymer chains.The current thesis addresses this need by developing and applying ion mobility spectrometry coupled with mass spectrometry (IMS-MS) to characterize SCNP precursor polymers and their collapse processes. MS allows isolation and analysis of complex species, including metallo-folded SCNPs. IMS yields experimental collisional cross sections (CCSexp), i.e., two-dimensional projections of ion structures. These can be directly compared with theoretical values (CCSth) obtained from atomistic molecular dynamics simulations, enabling structural interpretation of individual polymer ions. Complementary density functional theory (DFT) calculations were employed to explore the energetic landscape underlying folding and identifying the interactions that stabilize compact conformations.Through this integrated experimental–computational approach, the thesis establishes IMS-MS as a powerful methodology for probing the size, shape, and folding behavior of synthetic polymer chains. The insights gained advance understanding of SCNP structure–activity relationships and lay the foundation for the rational design of functional nanostructures that emulate Nature precision.