Assessing the Structural Heterogeneity of Isomeric Homo and Copolymers: an Approach Combining Ion Mobility Mass Spectrometry and Molecular Dynamics Simulations

Abstract

Synthetic polymers occupy a unique place in the field of ion mobility mass spectrometry (IMS−MS). Indeed, due to their intrinsic dispersity, they have the asset to offer a broad range of homologous ions with different lengths that can be detected in several charge states. In addition, the gas-phase structure of polymer ions mostly depends on their ability to screen the adducted charges. Several works dealing with linear, cyclic, and star-shaped polymers have already shown that the gas-phase structure of polymer ions heavily relies on the polymer architecture, i.e., the primary structure. In the present work, we move a step further by evaluating whether a relationship exists between the primary and secondary structures of synthetic homo and copolymers. The IMS−MS experiments will be further complemented by MD simulations. To highlight the effectiveness of IMS separation, we selected isomeric homo and copolymers made of lactide (LA) and propiolactone (PL) units. In this way, the mass analysis becomes useless since isomeric comonomer sequences can coexist for any given chain length. An UPLC method was implemented in the workflow to successfully separate all PL−LA comonomer sequences before infusion in the IMS−MS instrument. The analysis of doubly charged copolymers showed that the comonomer sequence has an impact on the IMS response. However, this only holds for copolymer ions with precise sizes and charge states, and this is therefore not a rule of thumb.

Gas‐phase structure of polymer ions: Tying together theoretical approaches and ion mobility spectrometry

“…AMBER (Gidden et al, 2002; Gidden, Jackson, et al, 1999; Gidden, Wyttenbach, et al, 1999; Jackson et al, 2004; Morsa et al, 2014; von Helden et al, 1995a), CHARMM (Duez et al, 2018; Kim et al, 2014), DREIDING (De Winter et al, 2011; Duez, Metwally, et al, 2020; Duez, Moins, et al, 2020; Hoyas et al, 2020; Mayo et al, 1990), UFF (De Winter et al, 2011), MM2 (Kokubo & Vana, 2016, 2017), constitute a nonexhaustive list of the force fields used to study polymer ions in gas phase. Most of these force fields are developed to study compounds in solution rather than in gas phase.…”

“…In this context, some force fields are being derived from generic force fields, to adequately describe the gas‐phase conformational space of polymer ions. For instance, our group reported the parametrization of the DREIDING force field against QM calculations to describe the gas‐phase behavior of polyesters, namely poly( l ‐lactide) (PLA), and poly(propiolactone) (PPL) (Duez, Metwally, et al, 2020; Duez, Moins, et al, 2020) but also of other original polymeric compounds such as peptoids (Hoyas et al, 2018). However, the parametrization of gas‐phase force fields is still scarcely explored and it is hoped that more approaches will be developed in the future, especially with the development of instruments that enable the evaluation of spectroscopic data in gas phase, such as infrared and circular dichroism (Daly et al, 2020; Jašík et al, 2013; Martens et al, 2012).…”

“…A valid and common approach to compare experimental CCS to the MD results consists in extracting a few hundreds of geometries from the production MD and submit them individually to one of the CCS algorithms discussed above, typically the TM. Generally, the averaged CCS of the entire set of candidate geometries is compared to experimental CCS data (De Winter et al, 2011; Duez, Moins, et al, 2020; Haler et al, 2020; Hoyas et al, 2020; Morsa et al, 2014). However, it is also good practice to analyze the time‐evolution of the CCS or the CCS distribution (Duez, Moins, et al, 2020) to potentially spot any conformational rearrangements that would lead to distinct conformations along the MD.…”

“…Generally, the averaged CCS of the entire set of candidate geometries is compared to experimental CCS data (De Winter et al, 2011; Duez, Moins, et al, 2020; Haler et al, 2020; Hoyas et al, 2020; Morsa et al, 2014). However, it is also good practice to analyze the time‐evolution of the CCS or the CCS distribution (Duez, Moins, et al, 2020) to potentially spot any conformational rearrangements that would lead to distinct conformations along the MD.…”

“…IMS‐MS has also been successfully applied as an stand‐alone analytical tool to separate isomeric polymers with different topologies (Alexander et al, 2018; Foley et al, 2015; Hoskins et al, 2011; Liénard et al, 2020; Mao et al, 2019), complex polymer blends (Barrère et al, 2014; Snyder & Wesdemiotis, 2021; Trimpin et al, 2007; Trimpin & Clemmer, 2008), or copolymers (Amalian et al, 2019; Baker et al, 2004; Duez, Moins, et al, 2020; Ito et al, 2019; Jackson et al, 2004). While these topic will not be discussed in this review, we refer the readers to a recent review with a broader scope about polymer analysis with IMS‐MS (Charles et al, 2020).…”