Experimental and Computational Analysis of the Roles of Polymer Templates and pH in Glycine Crystallization

Abstract

Understanding and controlling polymorph selection during amino acid crystallization is essential for applications in pharmaceuticals and bioelectronic materials. Here, we investigate the combined effects of polymer templating and pH modulation on glycine crystallization by integrating experimental results and all-atom molecular dynamics (MD) simulations. Poly(vinyl alcohol) (PVA) and a weak polyelectrolyte, poly(acrylic acid) (PAA), were employed to assess the formation of α- and γ-glycine polymorphs across a range of solution pHs. X-ray diffraction (XRD) characterization of the polymer-glycine films confirmed that γ-glycine crystallized exclusively at low pH ranges, while high pH conditions yielded mixed phases. ATR-IR studies confirm H-bonding interactions between the PVA–OH and the carboxylate anion in glycine at pH ∼4 and 6, as well as additional strong electrostatic interactions between PAA-COO– and –NH3+ in glycine at pH ∼6 and 9. Biased simulations of evaporation-assembled PVA templates revealed the formation of interfacial glycine clusters with orientational preferences consistent with γ-glycine packing. Simulations of self-assembled monolayers (SAMs) with chemically analogous terminal hydroxyl groups reproduced similar interfacial orientational biases as the PVA templates. Simulations further showed that high surface charge densities promote close glycine functional group contacts and unfavorable orientations, disrupting nucleation of the γ-polymorph. Even for identical surface chemistries, at high pH, enhanced interfacial enrichment driven by glycinate species, which form H-bonds and ion-pairing interactions, strengthens glycine adsorption but hinders molecular alignment. These results highlight the importance of balanced surface interactions in directing molecular alignment and provide a mechanistic framework for template-driven polymorph control.