Julien De Winter, a Vincent Lemaur, b Philippe Marsal, b,d Olivier Coulembier, c Jérôme Cornil, b Philippe Dubois, c Pascal Gerbaux a a Mass Spectrometry Research Group, Interdisciplinary Center of Mass Spectrometry (CISMa), b Laboratory for Chemistry of Novel Materials, c Center of Innovation and Research in Materials and Polymers (CIRMAP), Laboratory of Polymeric and Composite Materials, University of Mons, 20 Place du Parc, B-7000 Mons d CINaM-CNRS, Université Aix-Marseille 2 & 3, Campus de Luminy, Case Marseille Cedex 9, France Mechanistic study of the collision-induced dissociation of sodium-cationized polylactide oligomers : A joint experimental and theoretical investigation 1° CID spectrum of Na + cationized CH 3 -PLA-OH Results and discussion B Theoretical Calculations 2° CID spectrum of Na+ cationized linear CH 3 -PLA-acetyl A Experiments Introduction Amongst the biodegradable polyesters, polylactic acid (PLA) is nowadays a product of great interest and technological developments needed for mass production of high molecular weight PLA at low cost are thus awaited. Ring-opening polymerization of lactide, a cyclic dimer of lactic acid, is the most important method of synthesizing biodegradable and biocompatible PLA. In the case of macromolecular engineering, the study of PLA end groups is necessary. In this optic, it is suggested to analyze sodium- cationized polylactide oligomers by tandem mass spectrometry (MS/MS). Indeed, the collision induced dissociation spectrum is often considered as characteristic of the structure of the investigated ions and so should be oligomers’end group specific. In the present report, the tandem mass spectrometry characteristics of different sodium- cationized PLA oligomers were investigated. α-methyl, ω-hydroxy polylactide α-methyl, ω-acetyl polylactide Materials The polylactide oligomers were prepared following a state of the art polymerization procedure that relies on the use of a non-organometallic catalysis. The SEC and NMR characterized oligomers were then subjected to Electrospray Ionization. The obtained sodium-cationized oligomers were mass selected and their low-kinetic energy CID mass spectra were recorded. All the experiments were performed on a QToF instrument. Since the systems are too large to be fully optimized at a quantum-chemical level, the most stable conformation of each system was first determined by using molecular mechanics and molecular dynamics calculations based on the Universal Force Field. DFT calculations (B3LYP/6-31 g(d,p)) have also been performed to evaluate the total energy of the different systems without further geometry optimizations. CH 3 -PLA-OHCH 3 -PLA-acetyl The 2 end-group specific fragments McLafferty-Like fragmentation ? Does the 72u loss involve the H from the hydroxyl end-group? No! 3° Proposed mechanism for the unspecific fragment To get more information and to prove that the loss of 72 u from the middle of the chain is competitive with the end- groups specific fragmentations, some calculations were performed The formation of all the complexes is thermodynamically competitive Molecular Dynamics to prove that the elimination of a neutral is kinetically competitive Investigations of end-groups modified PLA reveal that, upon collisional activation, PLA.Na+ systematically suffers from end-group specific dissociations. In addition to those structurally -indicative dissociations, we demonstrated that collisionally-excited PLA.Na+ competitively suffers from two consecutive backbone cleavages leading to the loss of an unspecific fragment (72u). The experimental observations, performed on a hydrid Q-ToF instrument, were totally corroborated by a theoretical study involving DFT calculations, molecular mechanics and molecular dynamics simulations. Conclusion Acknowledgments The MS laboratory acknowledges the “Fonds de la Recherche Scientifique (FRS-FNRS)” for its contribution to the acquisition of the QToF2 Mass Spectrometer. J.C., P.G., O.C., and J.D.W. are FNRS research fellows. This work was partially supported by the Belgian Federal Government Office of Science Policy (SSTC-PAI 6/27). In Press DOI: /j.jasms H-NMR spectra before and after acetylation