Mechanistic study of the collision-induced dissociation of sodium-cationized polylactide oligomers: A joint experimental and theoretical investigation

Abstract

The low-kinetic energy collision-induced dissociation (CID) behavior of different sodiumcationized polylactide (PLA) oligomers was thoroughly investigated to shed some light on the analytical potentialities of CID experiments in the context of polymer characterization. Indeed, investigation of several end-groups modified PLA reveals that, in addition to the expected end-group specific dissociations, collisionally-excited PLA.Na ϩ suffer from a backbone cleavage. The so-obtained sodium-bound dimer cations consecutively undergo the loss of a monomeric residue that corresponds to neutral acrylic acid. The experimental observations, performed on a hybrid Q-ToF instrument, were totally corroborated by a theoretical study involving DFT calculations, molecular mechanics, and molecular dynamics calculations. . Such biodegradable polymers are often designed to degrade hydrolytically so that most of the widely studied biodegradable polymers belong to the polyester family and include polylactide (PLA), polyglycolide (PG), and associated copolymers [3]. PLA is certainly one of the most important synthetic biodegradable and biocompatible polymers attracting a huge interest for new and versatile synthetic procedures [4]. Polylactide and poly-(lactic acid) are, respectively, obtained by ring-opening polymerization (ROP) of lactide, the cyclic dimer of lactic acid, or by polycondensation of lactic acid.In the course of our research on the polymerization of lactide using non-organometallic catalysts such as N-heterocyclic carbenes, superbases, fluorinated tertiary alcohols, thiourea derivatives, and phosphazenes [5][6][7], we decided to explore the potential of mass spectrometry to provide an in-depth characterization of synthetic polymers in addition to well-established methodologies, such as gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR). Electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) represent the most significant recent developments in ionization techniques for mass spectrometry analysis of synthetic polymers [8]. State-of-the-art mass spectrometry tools hold the promise of providing not only absolute molecular mass distributions [9] but also qualitative end-group and repeat-unit composition [10], as well as structural information such as branching and intramolecular ring formation [11]. By definition, MS experiments provide the masses of the individual oligomers prepared during the polymer synthesis. On the basis of the m/z ratio of the detected cationized oligomers, compositional pieces of information such as the number and type of monomer units but also the nature of the incorporated end-groups can be derived. Nowadays, tandem mass spectrometry (MSMS) is emerging as an essential analytical methodology when accurate structural characterization of polymers cannot be unambiguously derived from single-stage MS experiments [12]. Recent MSMS investigations were successfully used to characterize individual functional groups of new polymers, to make

Electron transfer dissociation versus collisionally activated dissociation of cationized biodegradable polyesters

“…In addition to series l n AH and l n RV , the [M+2Na] 2+ precursor loses the elements of one repeat unit (72 Da) to form fragments with 1+ as well as 2+ charges ( m/z 1179.4 and 601.2, respectively); a less abundant second 72‐Da loss is also observed from the 2+ charge state ( m/z 565.2). Such fragments had been observed in the CAD spectra of singly sodiated PLA . A mechanism analogous to the one operating upon the loss of the N‐terminal amino acid residue from cationized peptides is proposed to yield these fragments, cf.…”

Size Dependence of the Folding of Multiply Charged Sodium Cationized Polylactides Revealed by Ion Mobility Mass Spectrometry and Molecular Modelling

“…The atomic charges used are those implemented in the COMPASS force field,44 the cut‐off value for the nonbonded interactions was increased to 500 Å so that none of them was neglected, and the conjugated gradient algorithm was selected to achieve the geometry optimizations. The combination of the UFF and COMPASS force fields has already proved to be very successful for the description of PLA oligomers bearing one Na + ion 14. Each optimized structure was used as the starting point of a conformational search.…”

“…Mass‐spectrometric measurements on polylactide polymers are thus of considerable interest to validate synthetic procedures. Recently, we reported a joint experimental and theoretical study on the collision‐induced dissociation of sodium‐cationized polylactides 14. In the continuity of our mass‐spectrometric studies on polylactides, we have analyzed by using ion‐mobility spectrometry the gas‐phase conformation of sodium cationized polylactide polymers.…”

“…[12] The understanding of polymer-fragmentation mechanisms is of prime importance for the analysis of MS/MS data, as illustrated in several experimental and theoretical studies. [13,14] Another major problem that is often encountered when performing MS and MS/MS analyses of polymer samples is the presence of isomeric or isobaric oligomers. Differentiation of isobaric ions can be achieved by using high-resolution analyzers.…”

Tandem Mass Spectrometric Analysis of a Mixture of Isobars Using the Survival Yield Technique

“…A 5:1 ratio was found more suitable for illustrative purposes; a detailed analysis of this aspect is presented in the following section discussing quantitative information. For convenience, and without loss of information, these spectra are presented on the same mass range going from m/z 1350 up to m/z 1700; spectrum for [PLA 23 and is shifted from the aforementioned series by −18 Th (for detailed discussions of fragmentation mechanisms and MS/MS spectra interpretations, one may refer to recent publications [13,14]). However, in the case of a mixture of PTMEG samples with PLA, which we may refer to as contamination throughout the discussion, visual inspection is not sufficient to distinguish between fragment ions (spectrum b in Figure 1).…”