{"id":{"repo_id":"gmu","oai_identifier":"oai:MARS:1920/14820"},"canonical_url":"https://search.dev.ndltd.org/etd/gmu/oai:MARS:1920/14820","repository":{"repo_id":"gmu","name":"George Mason University","base_url":"https://mars.gmu.edu/server/oai/request"},"display":{"title":"Thermoresponsive Polymers in Viscous Solvents through Molecular Dynamics","abstract":"Thermoresponsive polymers in liquid solutions undergo a coil-to-globule phase transition above a lower critical solution temperature (LCST), making them suitable for a wide range of biomedical and industrial applications, including biosensing, drug delivery, water treatment, and desalination. This phase transition is governed by the hydrophilic-hydrophobic balance of polymer-solvent interactions. If heated above the LCST, these polymers abruptly change from a soluble to an insoluble state. This type of phase transition may be tuned through several solvent characteristics such as salinity, co-solvent molar concentration, and pH. As a result, the LCST of a given thermoresponsive polymer is not fixed but depends heavily on its solvent conditions. Most experimental and computational studies have focused on understanding these transitions in aqueous-rich environments. However, little attention has been given to the behavior of thermoresponsive polymers in more viscous solvents, which may alter the solvation dynamics significantly by impacting the polymer conformation and responsiveness. Along this dissertation research, multiple all-atom molecular dynamics (MD) simulations were performed to investigate oligomers of acrylamide-derived syndiotactic polymers, including polyacrylamide (PAM), poly(n-isopropylacrylamide) (PNIPAM), and poly(n,n-diethylacrylamide) (PDEA). First, the structural, energetic, and dynamical properties of a collection of n-PAM oligomers were evaluated when solvated in water, glycerol, and a 90:10 glycerol:water mixture. The solutes were modeled with the all-atom general AMBER force field (GAFF) using custom restrained electrostatic potential (RESP) partial atomic charges, while the solvent was modeled within the implicit solvent approach. All n-PAM oligomers collapsed into prolate spheroids termed globules. These globules revealed a distinct size trend by displaying a clear scaling behavior between shorter oligomer chains (n < 20) and longer chains (20 ≤ n ≤ 50). Oligomers with longer chains acquired the maximum possible compactness in three-dimensions. Second, both solute and solvent in the analyzed solutions were modeled via all-atom MD, with explicit solvent modeled via custom-modified GAFF revealing that oligomers in pure water adopted very flexible, randomly-coiled structures, while oligomers in glycerol or in the 90:10 glycerol:water mixture became trapped in inflexible coiled structures. These results highlight the importance of explicitly modeling oligomer-solvent interactions, and indicate that for acrylamide-based polymers, an implicit solvent description is not sufficient for predicting solubility behaviors. Next, the thermoresponsive behavior of 30-PNIPAM and 30-PDEA was evaluated in water, glycerol, and 50:50 and 90:10 glycerol:water mixtures. A refined MD methodology was developed, including a custom modified optimized potentials for liquid simulations, all-atom (OPLS/AA) force field, which modeled effectively the oligomer hydrophobic and hydrophilic character along microsecond-scale simulations. The structural and energetic properties of the oligomers were analyzed, including radius of gyration, solvent-accessible surface area, oligomer-solvent hydrogen bonding, intra-oligomer potential energies and solute-solvent interaction energies. The analysis revealed that both oligomers do indeed undergo a coil-to-globule phase transition in glycerol-rich solvents. However, the phase transition occurs at significantly higher LCSTs when compared to the LCST in water-dominant solutions. The oligomer globular conformation attained when the oligomers become insoluble were similar in all the studied solvents. This discovery establishes a novel range of temperatures and solvents that is advantageous for applications at temperatures in the range of the water boiling point. Finally, non-equilibrium MD simulations were performed to estimate the threshold directed solvent flow velocity required to counteract the coil-to-globule phase change behavior of 30-PNIPAM and 30-PDEA in water and glycerol-based solvents, at temperatures above their LCST. Results indicate that for solutions of thermoresponsive polymers above the LCST, if a current is established along a nanochannel and the solvent velocities along the flow direction exceed approximately 1.0 m/s in water, or 0.2 m/s in glycerol, the globular oligomers unfold into an extended coil configuration within 200 ns. This trend highlights a strong dependence on solvent viscosity, with lower directed solvent flow velocities required to drive the conformational change in more viscous environments. A detailed analysis of the velocity field at the nanometer scale was conducted to understand how local shear forcescontribute to the oligomer chain extension. Additionally, the simulations included a comprehensive evaluation of oligomer-solvent interactions under the directed flow, revealing how hydrodynamic stress competes with thermally stabilized intra-chain atomic interactions. These findings offer fundamental insights into how thermoresponsive polymers behave in viscous, non-aqueous environments. By identifying the effects of solvent composition and flow conditions on polymer conformational states, this work deepens the understanding of solubility and responsiveness at the nanoscale. These results provide fundamental information in the design of microfluidic systems, smart sensors, and other industrial technologies that rely on precise control of polymer behavior under elevated temperatures and complex fluid environments.","abstract_html":"Thermoresponsive polymers in liquid solutions undergo a coil-to-globule phase transition above a lower critical solution temperature (LCST), making them suitable for a wide range of biomedical and industrial applications, including biosensing, drug delivery, water treatment, and desalination. This phase transition is governed by the hydrophilic-hydrophobic balance of polymer-solvent interactions. If heated above the LCST, these polymers abruptly change from a soluble to an insoluble state. This type of phase transition may be tuned through several solvent characteristics such as salinity, co-solvent molar concentration, and pH. As a result, the LCST of a given thermoresponsive polymer is not fixed but depends heavily on its solvent conditions. Most experimental and computational studies have focused on understanding these transitions in aqueous-rich environments. However, little attention has been given to the behavior of thermoresponsive polymers in more viscous solvents, which may alter the solvation dynamics significantly by impacting the polymer conformation and responsiveness. Along this dissertation research, multiple all-atom molecular dynamics (MD) simulations were performed to investigate oligomers of acrylamide-derived syndiotactic polymers, including polyacrylamide (PAM), poly(n-isopropylacrylamide) (PNIPAM), and poly(n,n-diethylacrylamide) (PDEA). First, the structural, energetic, and dynamical properties of a collection of n-PAM oligomers were evaluated when solvated in water, glycerol, and a 90:10 glycerol:water mixture. The solutes were modeled with the all-atom general AMBER force field (GAFF) using custom restrained electrostatic potential (RESP) partial atomic charges, while the solvent was modeled within the implicit solvent approach. All n-PAM oligomers collapsed into prolate spheroids termed globules. These globules revealed a distinct size trend by displaying a clear scaling behavior between shorter oligomer chains (n &lt; 20) and longer chains (20 ≤ n ≤ 50). Oligomers with longer chains acquired the maximum possible compactness in three-dimensions. Second, both solute and solvent in the analyzed solutions were modeled via all-atom MD, with explicit solvent modeled via custom-modified GAFF revealing that oligomers in pure water adopted very flexible, randomly-coiled structures, while oligomers in glycerol or in the 90:10 glycerol:water mixture became trapped in inflexible coiled structures. These results highlight the importance of explicitly modeling oligomer-solvent interactions, and indicate that for acrylamide-based polymers, an implicit solvent description is not sufficient for predicting solubility behaviors. Next, the thermoresponsive behavior of 30-PNIPAM and 30-PDEA was evaluated in water, glycerol, and 50:50 and 90:10 glycerol:water mixtures. A refined MD methodology was developed, including a custom modified optimized potentials for liquid simulations, all-atom (OPLS/AA) force field, which modeled effectively the oligomer hydrophobic and hydrophilic character along microsecond-scale simulations. The structural and energetic properties of the oligomers were analyzed, including radius of gyration, solvent-accessible surface area, oligomer-solvent hydrogen bonding, intra-oligomer potential energies and solute-solvent interaction energies. The analysis revealed that both oligomers do indeed undergo a coil-to-globule phase transition in glycerol-rich solvents. However, the phase transition occurs at significantly higher LCSTs when compared to the LCST in water-dominant solutions. The oligomer globular conformation attained when the oligomers become insoluble were similar in all the studied solvents. This discovery establishes a novel range of temperatures and solvents that is advantageous for applications at temperatures in the range of the water boiling point. Finally, non-equilibrium MD simulations were performed to estimate the threshold directed solvent flow velocity required to counteract the coil-to-globule phase change behavior of 30-PNIPAM and 30-PDEA in water and glycerol-based solvents, at temperatures above their LCST. Results indicate that for solutions of thermoresponsive polymers above the LCST, if a current is established along a nanochannel and the solvent velocities along the flow direction exceed approximately 1.0 m/s in water, or 0.2 m/s in glycerol, the globular oligomers unfold into an extended coil configuration within 200 ns. This trend highlights a strong dependence on solvent viscosity, with lower directed solvent flow velocities required to drive the conformational change in more viscous environments. A detailed analysis of the velocity field at the nanometer scale was conducted to understand how local shear forcescontribute to the oligomer chain extension. Additionally, the simulations included a comprehensive evaluation of oligomer-solvent interactions under the directed flow, revealing how hydrodynamic stress competes with thermally stabilized intra-chain atomic interactions. These findings offer fundamental insights into how thermoresponsive polymers behave in viscous, non-aqueous environments. By identifying the effects of solvent composition and flow conditions on polymer conformational states, this work deepens the understanding of solubility and responsiveness at the nanoscale. These results provide fundamental information in the design of microfluidic systems, smart sensors, and other industrial technologies that rely on precise control of polymer behavior under elevated temperatures and complex fluid environments.","abstract_has_math":false,"creators":["Hopkins, Scott David"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-27T19:51:56Z","subjects":["directed flow","glycerol","LCST","PNIPAM","thermoresponsive","viscous"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/14820"],"render_values":[{"text":"hdl:1920/14820","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["directed flow","glycerol","LCST","PNIPAM","thermoresponsive","viscous"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/14820"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["Thermoresponsive polymers in liquid solutions undergo a coil-to-globule phase transition above a lower critical solution temperature (LCST), making them suitable for a wide range of biomedical and industrial applications, including biosensing, drug delivery, water treatment, and desalination. This phase transition is governed by the hydrophilic-hydrophobic balance of polymer-solvent interactions. If heated above the LCST, these polymers abruptly change from a soluble to an insoluble state. This type of phase transition may be tuned through several solvent characteristics such as salinity, co-solvent molar concentration, and pH. As a result, the LCST of a given thermoresponsive polymer is not fixed but depends heavily on its solvent conditions. Most experimental and computational studies have focused on understanding these transitions in aqueous-rich environments. However, little attention has been given to the behavior of thermoresponsive polymers in more viscous solvents, which may alter the solvation dynamics significantly by impacting the polymer conformation and responsiveness. Along this dissertation research, multiple all-atom molecular dynamics (MD) simulations were performed to investigate oligomers of acrylamide-derived syndiotactic polymers, including polyacrylamide (PAM), poly(n-isopropylacrylamide) (PNIPAM), and poly(n,n-diethylacrylamide) (PDEA). First, the structural, energetic, and dynamical properties of a collection of n-PAM oligomers were evaluated when solvated in water, glycerol, and a 90:10 glycerol:water mixture. The solutes were modeled with the all-atom general AMBER force field (GAFF) using custom restrained electrostatic potential (RESP) partial atomic charges, while the solvent was modeled within the implicit solvent approach. All n-PAM oligomers collapsed into prolate spheroids termed globules. These globules revealed a distinct size trend by displaying a clear scaling behavior between shorter oligomer chains (n < 20) and longer chains (20 ≤ n ≤ 50). Oligomers with longer chains acquired the maximum possible compactness in three-dimensions. Second, both solute and solvent in the analyzed solutions were modeled via all-atom MD, with explicit solvent modeled via custom-modified GAFF revealing that oligomers in pure water adopted very flexible, randomly-coiled structures, while oligomers in glycerol or in the 90:10 glycerol:water mixture became trapped in inflexible coiled structures. These results highlight the importance of explicitly modeling oligomer-solvent interactions, and indicate that for acrylamide-based polymers, an implicit solvent description is not sufficient for predicting solubility behaviors. Next, the thermoresponsive behavior of 30-PNIPAM and 30-PDEA was evaluated in water, glycerol, and 50:50 and 90:10 glycerol:water mixtures. A refined MD methodology was developed, including a custom modified optimized potentials for liquid simulations, all-atom (OPLS/AA) force field, which modeled effectively the oligomer hydrophobic and hydrophilic character along microsecond-scale simulations. The structural and energetic properties of the oligomers were analyzed, including radius of gyration, solvent-accessible surface area, oligomer-solvent hydrogen bonding, intra-oligomer potential energies and solute-solvent interaction energies. The analysis revealed that both oligomers do indeed undergo a coil-to-globule phase transition in glycerol-rich solvents. However, the phase transition occurs at significantly higher LCSTs when compared to the LCST in water-dominant solutions. The oligomer globular conformation attained when the oligomers become insoluble were similar in all the studied solvents. This discovery establishes a novel range of temperatures and solvents that is advantageous for applications at temperatures in the range of the water boiling point. Finally, non-equilibrium MD simulations were performed to estimate the threshold directed solvent flow velocity required to counteract the coil-to-globule phase change behavior of 30-PNIPAM and 30-PDEA in water and glycerol-based solvents, at temperatures above their LCST. Results indicate that for solutions of thermoresponsive polymers above the LCST, if a current is established along a nanochannel and the solvent velocities along the flow direction exceed approximately 1.0 m/s in water, or 0.2 m/s in glycerol, the globular oligomers unfold into an extended coil configuration within 200 ns. This trend highlights a strong dependence on solvent viscosity, with lower directed solvent flow velocities required to drive the conformational change in more viscous environments. A detailed analysis of the velocity field at the nanometer scale was conducted to understand how local shear forcescontribute to the oligomer chain extension. Additionally, the simulations included a comprehensive evaluation of oligomer-solvent interactions under the directed flow, revealing how hydrodynamic stress competes with thermally stabilized intra-chain atomic interactions. These findings offer fundamental insights into how thermoresponsive polymers behave in viscous, non-aqueous environments. By identifying the effects of solvent composition and flow conditions on polymer conformational states, this work deepens the understanding of solubility and responsiveness at the nanoscale. These results provide fundamental information in the design of microfluidic systems, smart sensors, and other industrial technologies that rely on precise control of polymer behavior under elevated temperatures and complex fluid environments."]},{"key":"dc:title","label":"Title","values":["Thermoresponsive Polymers in Viscous Solvents through Molecular Dynamics"]}]}],"canonical_facts":{"dc:date.issued":["2025"],"dc:description.other":["Thermoresponsive polymers in liquid solutions undergo a coil-to-globule phase transition above a lower critical solution temperature (LCST), making them suitable for a wide range of biomedical and industrial applications, including biosensing, drug delivery, water treatment, and desalination. This phase transition is governed by the hydrophilic-hydrophobic balance of polymer-solvent interactions. If heated above the LCST, these polymers abruptly change from a soluble to an insoluble state. This type of phase transition may be tuned through several solvent characteristics such as salinity, co-solvent molar concentration, and pH. As a result, the LCST of a given thermoresponsive polymer is not fixed but depends heavily on its solvent conditions. Most experimental and computational studies have focused on understanding these transitions in aqueous-rich environments. However, little attention has been given to the behavior of thermoresponsive polymers in more viscous solvents, which may alter the solvation dynamics significantly by impacting the polymer conformation and responsiveness. Along this dissertation research, multiple all-atom molecular dynamics (MD) simulations were performed to investigate oligomers of acrylamide-derived syndiotactic polymers, including polyacrylamide (PAM), poly(n-isopropylacrylamide) (PNIPAM), and poly(n,n-diethylacrylamide) (PDEA). First, the structural, energetic, and dynamical properties of a collection of n-PAM oligomers were evaluated when solvated in water, glycerol, and a 90:10 glycerol:water mixture. The solutes were modeled with the all-atom general AMBER force field (GAFF) using custom restrained electrostatic potential (RESP) partial atomic charges, while the solvent was modeled within the implicit solvent approach. All n-PAM oligomers collapsed into prolate spheroids termed globules. These globules revealed a distinct size trend by displaying a clear scaling behavior between shorter oligomer chains (n < 20) and longer chains (20 ≤ n ≤ 50). Oligomers with longer chains acquired the maximum possible compactness in three-dimensions. Second, both solute and solvent in the analyzed solutions were modeled via all-atom MD, with explicit solvent modeled via custom-modified GAFF revealing that oligomers in pure water adopted very flexible, randomly-coiled structures, while oligomers in glycerol or in the 90:10 glycerol:water mixture became trapped in inflexible coiled structures. These results highlight the importance of explicitly modeling oligomer-solvent interactions, and indicate that for acrylamide-based polymers, an implicit solvent description is not sufficient for predicting solubility behaviors. Next, the thermoresponsive behavior of 30-PNIPAM and 30-PDEA was evaluated in water, glycerol, and 50:50 and 90:10 glycerol:water mixtures. A refined MD methodology was developed, including a custom modified optimized potentials for liquid simulations, all-atom (OPLS/AA) force field, which modeled effectively the oligomer hydrophobic and hydrophilic character along microsecond-scale simulations. The structural and energetic properties of the oligomers were analyzed, including radius of gyration, solvent-accessible surface area, oligomer-solvent hydrogen bonding, intra-oligomer potential energies and solute-solvent interaction energies. The analysis revealed that both oligomers do indeed undergo a coil-to-globule phase transition in glycerol-rich solvents. However, the phase transition occurs at significantly higher LCSTs when compared to the LCST in water-dominant solutions. The oligomer globular conformation attained when the oligomers become insoluble were similar in all the studied solvents. This discovery establishes a novel range of temperatures and solvents that is advantageous for applications at temperatures in the range of the water boiling point. Finally, non-equilibrium MD simulations were performed to estimate the threshold directed solvent flow velocity required to counteract the coil-to-globule phase change behavior of 30-PNIPAM and 30-PDEA in water and glycerol-based solvents, at temperatures above their LCST. Results indicate that for solutions of thermoresponsive polymers above the LCST, if a current is established along a nanochannel and the solvent velocities along the flow direction exceed approximately 1.0 m/s in water, or 0.2 m/s in glycerol, the globular oligomers unfold into an extended coil configuration within 200 ns. This trend highlights a strong dependence on solvent viscosity, with lower directed solvent flow velocities required to drive the conformational change in more viscous environments. A detailed analysis of the velocity field at the nanometer scale was conducted to understand how local shear forcescontribute to the oligomer chain extension. Additionally, the simulations included a comprehensive evaluation of oligomer-solvent interactions under the directed flow, revealing how hydrodynamic stress competes with thermally stabilized intra-chain atomic interactions. These findings offer fundamental insights into how thermoresponsive polymers behave in viscous, non-aqueous environments. By identifying the effects of solvent composition and flow conditions on polymer conformational states, this work deepens the understanding of solubility and responsiveness at the nanoscale. These results provide fundamental information in the design of microfluidic systems, smart sensors, and other industrial technologies that rely on precise control of polymer behavior under elevated temperatures and complex fluid environments."],"dc:identifier":["hdl:1920/14820"],"dc:subject":["directed flow","glycerol","LCST","PNIPAM","thermoresponsive","viscous"],"dc:title":["Thermoresponsive Polymers in Viscous Solvents through Molecular Dynamics"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T19:51:56Z"}