Mass Spectrometry and Ion Mobility Characterization of Bioactive Peptide–Synthetic Polymer Conjugates

A detailed characterization of polymeric matrices and appropriate degradation monitoring techniques are required to sustain the development of new materials as well as to enlarge the applications of the old ones. In fact, polymer analysis is essential for the clarification of the intrinsic relationship between structure and properties that ascertains the industrial applications in diverse fields. In bioresorbable and biodegradable polymers, the role of analytical methods is dual since it is pointed both at the polymeric matrices and at degradation tracking. The structural architectures, the mechanical and morphological properties, and the degradation rate, are of outstanding importance for a specific application. In some cases, the complexity of the polymer structure, the processes of decomposition or the low concentration of the degradation products need the concurrent use of different complementary analytical techniques to give detailed information of the reactions taking place. Several analytical methods are used in bioresorbable polymer development and degradation tracking. Among them, mass spectrometry (MS) plays an essential role and it is used to refine polymer syntheses, for its high sensitivity, to highlight degradation mechanism by detecting compounds present in trace amounts, or to track the degradation product profile and to study drug release. In fact, elucidation of reaction mechanisms and polymer structure, attesting to the purity and detecting defects as well as residual catalysts, in biodegradable and bioresorbable polymers, requires sensitive analytical characterization methods that are essential in providing an assurance of safety, efficacy and quality. This review aims to provide an overview of the MS strategies used to support research and development of resorbable polymers as well as to investigate their degradation mechanisms. It is focused on the most significant studies concerning synthetic bioresorbable matrices (polylactide, polyglycolide and their copolymers, polyhydroxybutyrate, etc.), published in the last ten years.

Section: Characterization Of Bioresorbable Polymers By Msmentioning

confidence: 97%

Section: Characterization Of Bioresorbable Polymers By Msmentioning

confidence: 99%

Mass spectrometry in bioresorbable polymer development, degradation and drug‐release tracking

Rizzarelli

Rapisarda

Valenti

2020

“…In addition to metal adduction, protonation was also envisaged in particular cases where synthetic polymers were conjugated with moieties of high proton affinity, in particular peptides . For example, Wesdemiotis and co‐workers reported that the helical structure of alanine‐rich peptides is further stabilized upon conjugation with PEG via their C‐terminus .…”

Section: Investigation Of Gas‐phase Ion Structuresmentioning

confidence: 99%

Ion mobility spectrometry – Mass spectrometry coupling for synthetic polymers

Charles

Chendo

Poyer

2020

This review covers applications of ion mobility spectrometry (IMS) hyphenated to mass spectrometry (MS) in the field of synthetic polymers. MS has become an essential technique in polymer science, but increasingly complex samples produced to provide desirable macroscopic properties of high‐performance materials often require separation of species prior to their mass analysis. Similar to liquid chromatography, the IMS dimension introduces shape selectivity but enables separation at a much faster rate (milliseconds vs minutes). As a post‐ionization technique, IMS can be hyphenated to MS to perform a double separation dimension of gas‐phase ions, first as a function on their mobility (determined by their charge state and collision cross section, CCS), then as a function of their m/z ratio. Implemented with a variety of ionization techniques, such coupling permits the spectral complexity to be reduced, to enhance the dynamic range of detection, or to achieve separation of isobaric ions prior to their activation in MS/MS experiments. Coupling IMS to MS also provides valuable information regarding the 3D structure of polymer ions in the gas phase and regarding how to address the question of how charges are distributed within the structure. Moreover, the ability of IMS to separate multiply charged species generated by electrospray ionization yields typical IMS‐MS 2D maps that permit the conformational dynamics of synthetic polymer chains to be described as a function of their length.

“…1,2 When coupled with molecular simulations and modeling, IM-MS can provide conclusive evidence about the spatial arrangement and conformation of proteins, [3][4][5] glycans, 6 and lipids, 7 as well as the topology and architecture of synthetic polymers [8][9][10][11][12][13] and bioconjugates. [13][14][15] Over the past years, significant progress has been made in the development of simple, one-step, quantitative methods for the conversion of polyfunctional monomers with well-defined geometries into supramolecular constructs with useful physicochemical properties. [16][17][18][19][20] Terpyridine (tpy)-based coordinative chemistry with various metal 2+ ions, in particular, has enabled the synthesis of a vast array of macrocyclic and multicyclic compounds carrying the <tpy-Metal 2+ -tpy> connectivity and having precise metal/ligand stoichiometries and specific, predesigned 3D geometries, depending on the molecular structure of the tpy ligand.…”

Section: Introductionmentioning

confidence: 99%

Collision cross‐section analysis of self‐assembled metallomacrocycle isomers and isobars via ion mobility mass spectrometry

Endres

Barthelmes

Winter

et al. 2020

Self Cite

Rationale Coordinatively driven self‐assembly of transition metal ions and bidentate ligands gives rise to organometallic complexes that usually contain superimposed isobars, isomers, and conformers. In this study, the double dispersion ability of ion mobility mass spectrometry (IM‐MS) was used to provide a comprehensive structural characterization of the self‐assembled supramolecular complexes by their mass and charge, revealed by the MS event, and their shape and collision cross‐section (Ω), revealed by the IM event. Methods Self‐assembled complexes were synthesized by reacting a bis(terpyridine) ligand exhibiting a 60o dihedral angle between the two ligating terpyridine sites (T) with divalent Zn, Ni, Cd, or Fe. The products were isolated as (Metal2+[T])n (PF6)2n salts and analyzed using IM‐MS after electrospray ionization (ESI) which produced several charge states from each n‐mer, depending on the number of PF6ˉ anions lost upon ESI. Experimental Ω data, derived using IM‐MS, and computational Ω predictions were used to elucidate the size and architecture of the complexes. Results Only macrocyclic dimers, trimers, and tetramers were observed with Cd2+, whereas Zn2+ formed the same plus hexameric complexes. These two metals led to the simplest product distributions and no linear isomers. In sharp contrast, Ni2+ and Fe2+ formed all possible ring sizes from dimer to hexamer as well as various linear isomers. The experimental and theoretical Ω data indicated rather planar macrocyclic geometries for the dimers and trimers, twisted 3D architectures for the larger rings, and substantially larger sizes with spiral conformation for the linear congeners. Adding PF6ˉ to the same complex was found to mainly cause size contraction due to new stabilizing anion–cation interactions. Conclusions Complete structural identification could be accomplished using ESI‐IM‐MS. Our results affirm that self‐assembly with Cd2+ and Zn2+ proceeds through reversible equilibria that generate the thermodynamically most stable structures, encompassing exclusively macrocyclic architectures that readily accommodate the 60o ligand used. In contrast, complexation with Ni2+ and Fe2+, which form stronger coordinative bonds, proceeds through kinetic control, leading to more complex mixtures and kinetically trapped less stable architectures, such as macrocyclic pentamers and linear isomers.