Unambiguous Determination of the ¹³C and ¹H NMR Stereosequence Assignments of Polylactide Using High-Resolution Solution NMR Spectroscopy

Abstract

Polylactide (PLA) is a biodegradable polyester formed by the ring-opening polymerization of lactide, the cyclic dimer of lactic acid. Many of the physical properties of PLA are influenced by the amount and distribution of the R and S stereocenters in the polymer chain. NMR spectroscopy is the most common technique used to determine the stereosequence distribution of the polymer. The correct determination of the stereosequence distribution is contingent upon the assignment of the peaks in the NMR spectrum to specific stereosequences. Recently, alternative assignments to the commonly accepted stereosequence assignments have been proposed. If any of these alternative assignments are found to be correct, it would invalidate the conclusions of much of the previous work in understanding the kinetics of lactide polymerization and determining the stereoselectivity of new catalysts. The most significant problem is reconciling the commonly accepted peak assignments, which were based upon statistical probabilities, with contradictory connectivity data observed in a HETCOR NMR experiment. To describe the directionality in PLA, we have modified the nomenclature used to describe directionality in peptides and proteins. For PLA, the end containing the carboxylic group is referred to as the C terminus, and the end with the hydroxyl group is the O terminus. We had previously proposed that the central pairwise relationship (isotactic or syndiotactic, denoted i or s) in the 1 H NMR spectrum is determined by the stereocenter in the lactic acid unit attached to the O terminus and that in the 13 C NMR spectrum it is determined by the central pairwise relationship of the stereocenter in the lactic acid unit attached to the C terminus. One-and two-dimensional NMR techniques, in combination with selective isotopic labeling, were used to show that this relationship is correct and that the commonly accepted assignments are correct. In addition, all of the nondegenerate resonances in the 1 H and 13 C NMR spectrum of polylactide at the tetrad stereosequence level have been assigned.

Chemical Properties of Poly(lactic Acid)

“…The 1 H and 13 C resonance relationship is shown in Figure 4.9. A similar situation can be found in the overlapping of the sis resonance Kricheldorf et al (1996) and (b) Zell et al (2002) tetrad stereosequence assignments of the methine carbon and proton in PLA synthesized using meso-lactide. The lines between peaks in the 1 H and 13 C NMR spectra indicate connectivity observed in the heteronuclear correlation NMR spectra (i designates isotactic, s designates syndiotactic).…”

“…Figure 4.8 shows the 1 H and 13 C solution NMR spectra of PLA synthesized using 5% L-lactide and 95% D-lactide. As observed by Zell et al (2002) in the 1 H spectrum, the direct integration of the isi resonance is impossible due to the overlapping of the isi resonance with the iii resonance. The 1 H and 13 C resonance relationship is shown in Figure 4.9.…”

“…Kricheldorf and Kreiser-Saunders (1990) has pioneered the use of methine resonance in 1 H and 13 C NMR spectra on various synthesis methods of PLA as well as the initiators/catalysts involved. Meanwhile, Zell et al (2002) has revised the tetrad stereosequence assignment for the methane carbon and proton of Kricheldorf et al (1996) (see Figure 4.7). The revised tetrad stereosequence is an extension to the methine stereosequence assignments in PLA for upgrading to hexad level and includes a method for quantifying the amount of L-, D-and meso-lactide in PLA.…”

NMR analysis and chemical shift calculations of poly(lactic acid) dimer model compounds with different tacticities

“…The four energetically stable states generated from the combination of two preferred conformations in the Ramachandran conformational energy map of the monomer model compound 30 were the initial four preferred conformations of the dimer model compounds (1). The D-isomer of syndiotactic dimer model was derived by flipping the sign of the Z-coordinate of the X-Y-Z coordinates.…”

“…[23][24][25][26][27][28][29][30][31][32][33] Most recently, we reported the calculation of 1 H and 13 C chemical shifts in PLA model compounds. 30 The 1 H and 13 C chemical shifts calculated with the quantum chemical method were compared with the observed chemical shifts, and good agreement was obtained for the relative chemical shifts of the 1 H and 13 C peaks of the CH group between isotactic and syndiotactic dimer model compounds.…”