Analysis of Solvation and Gelation Behavior of Methylcellulose Using Atomistic Molecular Dynamics Simulations

Abstract

We adopt atomistic molecular dynamics (MD) simulations to study the solvation and gelation behavior of homogeneous methylcellulose (MC) and model random oligomers that represent the commercial cellulosic polymer product METHOCEL A in water and acetone solvents. We demonstrate that the two carbohydrate-specific GROMOS force fields, GROMOS 45A4 and 56Acarbo, are capable of reproducing characteristic angle distributions and the persistence length of MC chains reported in the literature. We then use the GROMOS 56Acarbo force field in both single-chain and multiple-chain simulations to characterize their solvation behavior through radial distribution functions, hydrogen-bond counts, and contact map analyses. We find that the un-methylated O6 position on the cellulose ring forms the most hydrogen bonds, followed by O2 and O3, implying that methylation at the 6 position reduces hydrogen bonding more than does methylation at other positions. O6-O6 is the most probable intermolecular hydrogen bond between different MC molecules. Dimethylated and trimethylated MCs form aggregated structures at low temperatures and precipitate-like structures at high temperatures in water but disperse randomly in acetone. This is consistent with experimental observations of gelation at elevated temperatures in water. The heterogeneous METHOCEL A model shows increased aggregation of trimethylated monomer units at elevated temperatures, suggesting that hydrophobic interaction is the main factor that induces the gelation, rather than hydrogen bonding.

O-Methylation in Carbohydrates: An NMR and MD Simulation Study with Application to Methylcellulose

“…The observations presented herein agree with earlier simulations of methylated cellobiose in water using the same force field, 21 which also noted an increase in ϕ and ψ upon 3-O-methylation. However, in a study of methylated cellononaose in water 24 using the same force field, a slight decrease of both ϕ and ψ was observed.…”

Conformation of Methylcellulose as a Function of Poly(ethylene glycol) Graft Density

“…Methylcellulose (MC) is an abundant and sustainable cellulose derivative that enjoys an impressive range of consumer applications, from clinical excipients to construction materials. , One of the most interesting and rheologically significant properties of MC is its ability to self-assemble into highly elastic fibrous networks, upon heating in aqueous solution. − Interestingly, the detailed mechanism and internal structure of the fibrils is still an open fundamental question; − further addition of relatively few hydroxypropyl groups, to produce hydroxypropyl methylcellulose (HPMC), suppresses fibril formation. , Other straightforward chemical modifications to the MC backbone could also tune physical properties and thereby broaden the breadth of applications. For example, small molecular grafts are predicted to increase the stiffness of an otherwise flexible or semiflexible polymer. − Increasing stiffness is expected to modify MC self-assembly, thereby enabling new application opportunities, and also could ultimately contribute to a more detailed understanding of the nature of MC fibril formation.…”

Feasibility Investigation of Cellulose Polymers for Mucoadhesive Nasal Drug Delivery Applications

“…31,32 Briefly, in a solution state at lower temperatures, the polymer molecules are hydrated by a cagelike structure of water molecules with few polymer−polymer interactions. Upon heating, the hydrogen bonding of the water molecules is weakened, causing partial dehydration and phase separation.…”