Author ORCID Identifier

Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation




Chemical and Materials Engineering

First Advisor

Dr. Barbara L. Knutson

Second Advisor

Dr. Stephen E. Rankin


Capitalizing on byproducts of industrial and agricultural economies is among the utmost goals of sustainability. Of particular interest for commercial upgrading is lignin, a phenolic biopolymer found in the cell walls of plants which is the second most abundant biopolymer on Earth after cellulose. Due to its heterogeneous structure, deconstructing lignin to selected small molecules for use as chemicals or advanced materials has been elusive. This work capitalizes on a “bottom up” approach to the synthesis of lignin oligomers of known bond chemistry to better understand their interfacial interactions.

The potential pharmacological mechanism of lignin deconstruction components and their toxicological effect on biological systems is currently relatively unexplored. Herein, the interaction of three lignin-derived small molecules (lignin dimers with varying chemical functionality) with lipid bilayers (model cell membranes) was investigated via quartz crystal microbalance with dissipation monitoring (QCM-D) studies of binding and differential scanning calorimetry (DSC) measurements of the change in lipid bilayer phase behavior as a function of dimer concentration. Our results demonstrate that minor differences in structure of lignin molecules have a significant impact on their ability to penetrate into model cell membranes.

To show that the lignin oligomers under investigation have the potential to impart surfaces with lignin-like properties (e.g. pharmacological and toxicological properties), a hydrophobic lignin dimer which was previously shown to interacts strongly with model cell membrane was chemically modified to covalently attach to mesoporous silica nanoparticles (MSNPs). The ability of lignin dimer-functionalized particles to interact with and disrupt lipid bilayers was compared to MSNPs functionalized with eugenol, a natural aromatic pharmaceutical found in cloves. While eugenol-grafted particles showed evidence of weak interactions with the bilayer, dimer-grafted particles with the same concentration caused considerable lipid mass loss associated with disruption of up to ~93% of the membrane, suggesting higher biocidal activity.

The structure of lignin suggests that it is not only a potential therapeutic and pharmacological substance, but also a promising source of aromatic chemicals. Developing methods to selectively separate and purify lignin oligomers from the complex lignin depolymerization mixture remains an ongoing challenge. Binding of β-cyclodextrin (CD) (a truncated cone-shaped molecule with a hydrophilic exterior and a hydrophobic cavity) to three lignin dimers with different chemical structures was studied using Isothermal Titration Calorimetry (ITC). The thermodynamic parameters (K, ΔH, ΔS, and ΔG) of formation of dimer:β-CD complexes were measured and compared. The results demonstrated that differences in the thermodynamics of CD-lignin interactions can be used to develop selective separation strategies for lignin-derived small molecules. For example, binding with β-CD of a dimer containing a bb bond is entropically driven (due to hydrophobic effects) while favorable enthalpy of interactions drives binding of a dimer with a different bond (bO4). A surface modification technique was also proposed to attach β-CD directly to mesoporous silica nanoparticles, with a goal of using the silica particles for selective capture of lignin-derived small molecules.

In sum, this work established structure−function relationships for well-defined lignin derivatives at biologically relevant surfaces. A strategy to create lignin-conjugated silica surfaces was developed and it was shown that bio-inspired materials comprising lignin small molecules have the potential to serve as a platform for novel antimicrobial coatings and therapeutic carriers. Moreover, the potential of β-cyclodextrin to selectively separate lignin oligomers from lignin deconstruction mixture was studied, and a strategy to create immobilized cyclodextrin-functionalized surfaces was proposed.

Digital Object Identifier (DOI)

Funding Information

This study was supported by the National Science Foundation (NSF) EPSCoR (Established Program to Stimulate Competitive Research) Track-2 RII, grant (no.: OIA1632854) in 2016-2021. This funding was awarded to University of Kentucky (several departments), Louisiana State University Agricultural Center, and Louisiana State University representing the EPSCoR states of Kentucky and Louisiana as an integrated partnership.