The Hydration Blueprint of Polylactic Acid: Computational Decoding of Noncovalent Interactions for Predictive...

The biodegradation of polylactic acid (PLA) is essentially controlled by its interaction with water although little is known about the molecular-level mechanisms that trigger hydrolysis. This limitation hinders the rational design of polymers with desired degradation kinetics. In this work, we unveil the hydration-induced degradation of PLA using a multilevel computational approach, combining DFT with M06-2X functional and cc-pVDZ basis set along with the estimation of solvent effect using solvation model density (SMD), natural bond orbital (NBO) analysis, noncovalent interaction (NCI) index and Quantum Theory of Atoms in Molecules (QTAIM). Our findings demonstrate that the aqueous stability of PLA is determined by a delicate interplay between opposing forces: strong, directional hydrogen bonds to water carbonyls complemented by widespread van der Waals interactions, which in turn are partly countered by intrinsic steric repulsion within the polymer. The AIM analysis finds that all hydrogen bonds are quantitatively classified as weak, closed-shell interactions and thus exhibit an electrostatic character of the hydration network. In addition, AIMD simulations provide insights into the early-stage process of hydrolytic chain scission, revealing a proton transfer facilitated by water and an ester bond cleavage. Supported by molecular docking, key microbial enzymes are identified and binding affinities (up to -5.8 kcal mol^-1) transpire through comprehensive hydrogen bonding networks. The work offers a first-ever electronic-level blueprint of PLA, providing a mechanistic basis for predictions of degradation kinetics and aiding in the design of the next generation of environmentally benign degradable polymers. By unmasking the molecular inception of water-induced PLA degradation, this study demonstrates coherent tuning of polymer stability as well as lifetime. The insights provide the design and development of next-generation biodegradable polymers with regulated breakdown behavior for industrial and environmental interests.