Poly(aspartic acid), PA, is a biodegradable, water-soluble poly(amino acid) used for drug delivery, corrosion inhibition, superadsorbants and more. Established synthetic routes to α-linked PA include ring-opening polymerization (ROP) of the corresponding N-carboxyanhydride (NCA) monomer, solution and solid phase peptide synthesis. Protease-catalyzed peptide synthesis has several advantages to the above methods that include reduced use of protection-deprotection steps and toxic chemical reagents. Previous work showed oligomer mixtures from protease-catalyzed polymerization of L-aspartic acid diethyl ester (LAspEt2) have a degree of polymerizations (DP) from about 9-19. This paper reports the bulk immobilized CAL-B catalyzed polymerization of LAspEt2 catalyzed at 80 oC (24 h) to give primarily (~95%) α-linked PA (DPavg=50) in 70% yield. One-dimensional proton (1H) NMR as well as 2D 1H-13C HMBC was used to assign the relative content of α- and β-links. All signals were assigned based on 2D 1H-1H COSY and 1H-13C HSQC. Both conversion and yield gradually increase from 17% and 9%, respectively, at 2 h to 98% and 70%, respectively, at 24 h. Furthermore, from 2 to 24 h the DPavg increases from 6 to 50. The semi-logarithmic plot of conversion vs. time, when fit by linear regression analysis, has an R2 of 0.9597. Hence, the polymerization does not proceed by a conventional step-growth mechanism but, instead, by chain growth. Furthermore, the DPavg linearly increases with conversion up to 90%. Thereafter, a large linear increase in DPavg from 37 to 50 occurs with a small increase in conversion (from 90% to 98%). This corresponds to a change in the dominant mechanism from chain to step-growth at high monomer conversions (&gt;90%). The results of this study provide a simple, cost-effective and environmentally friendly route to α-linked PA with DPavg = 50 (Mn ≈5,800).

CAL-B catalyzed regioselective bulk polymerization of L-aspartic acid diethyl ester to α-linked polypeptides

254th National Meeting (2017)

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