Multidimensional mass spectrometry characterization of isomeric biodegradable polyesters

Abstract

The biodegradable polyester copolymer poly(propylene fumarate) (PPF) is increasingly utilized in bone tissue engineering studies due to its suitability as inert cross-linkable scaffold material. The well-defined poly(propylene fumarate) oligomers needed for this purpose are synthesized by post-polymerization isomerization of poly(propylene maleate), which is prepared by ring opening polymerization of maleic anhydride and propylene oxide. In this study, multidimensional mass spectrometry methodologies, interfacing matrix-assisted laser desorption ionization and electrospray ionization with mass analysis, tandem mass spectrometry fragmentation and/or ion mobility mass spectrometry, have been employed to characterize the composition, end groups, chain connectivity and isomeric purity of the isomeric copolyesters poly(propylene maleate)and poly(propylene fumarate). It is demonstrated that the polymerization catalyst is incorporated into the polymer chain (as the initiating chain end) and that the poly(propylene maleate) to poly(propylene fumarate) isomerization using an amine base proceeds with quantitative yield. Hydrolytic degradation is shown not to alter the double bond geometry of the poly(propylene fumarate) or poly(propylene maleate) chains.

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

“…In addition, IM‐MS was used to differentiate the isomeric PPM and PPF samples and evaluate the extent and efficiency of PPM to PPF (i.e. all‐cis to all‐trans polymer chains) isomerization (Figure ) …”

“…All ions are sodiated species with the composition [R n + EG s + Na] + , where R and EG s designate the PPM/PPF repeat unit (C 7 H 8 O 4 , 156 Da) and the corresponding end groups (in red color), respectively. Reprinted with permission from Sallam et al, copyright (2017) Sage Publications…”

“…An asterisk above the fragment notation (*) indicates ions cationized by H + (Na + is eliminated with the neutral fragment). Reprinted with permission from Sallam et al, copyright (2017) Sage Publications…”

“…PPM leads to very similar ESI‐IM‐MS characteristics, except for the absence of (C 2 H 5 ) 2 NH 2 + adducts. Reprinted with permission from Sallam et al, copyright (2017) Sage Publications…”

“…Information on the nature of monomers and end groups can also be obtained from the accurate mass measurement of the individual oligomers. As a consequence, MALDI MS has become a routinely used tool for polymer characterization and it has also been applied in the structural characterization of biodegradable and bioresorbable polymers . In MALDI analysis, the selection of the matrix and the sample preparation procedures play an essential role.…”