Abstract
As key components of antifouling material surfaces, the design and screening of polymer molecules grafted on the substrate are critical. However, current experimental and computational models still retain an empirical flavor due to the complex structure of polymers. Here, we report a simple and general strategy that enables multi-scale design and screening of easily synthesized functional polymer molecules to address this challenge. Specifically, the required functions of the antifouling material are decomposed and assigned to different modules of the polymer molecules. By designing different modules, a novel bio-inspired polymer with three zwitterionic poly (sulfobetaine methacrylate) (PSBMA) chains, three catechol (DOPA) anchors (tri-DOPA-PSBMA), and a tris(2-aminoethyl) amine (TREN) scaffold were screened out. Moreover, it was successfully synthesized via an atom transfer radical polymerization (ATRP). The excellent performance of tri-DOPA-PSBMA with a versatile and convenient grafting strategy makes it a promising material for marine devices, biomedical devices, and industrial applications.
Keywords: rational design, zwitterionic polymer, antifouling material surfaces, rapid adhesive, long-term stability
Introduction
Antifouling surfaces resisting nonspecific protein adsorption and biofilm adhesion improve function, efficiency, and safety in products such as water purification membranes, marine vehicle coatings, medical implants, and other industrial applications1, 2. The strong hydrophilicity of zwitterionic polymer gives them good biocompatibility and anti-protein adhesion properties. Zwitterionic polymer grafted surfaces have been investigated to offer high resistance toward nonspecific protein adsorption and cell adhesion under physiological conditions. Due to their highly hydrophilic nature and flexibility, zwitterionic polymer grafted surface have met with varying success in vitro and in vivo antifouling tests3. Commonly, zwitterionic polymers were immobilized to the surfaces by two strategies, i.e., adsorption of polymer from solution (so-called “graft-to” approach) and surface-initiated polymerization (SIP) of monomers from surface-bound initiators (“graft-from” approach)4, 5. In contrast to the “graft-from” approach, the “graft-to” method is simpler and more convenient, especially suitable for practical applications on a large scale. However, for the “graft-to” approach, especially for binding in the presence of water, specific surface functional groups with high binding energies and versatile feasibility to various substrate surfaces are required. Inspired by the adhesion mechanism of mussels, 3,4-dihydroxyphenylalanine (DOPA) is believed to be a versatile residue for wet adhesion. Various zwitterionic polymers with catechol adhesive groups have been designed to achieve surface adhesion in aqueous solutions6-8. Although these zwitterionic polymers, such as one zwitterionic chain with one catechol anchor, two zwitterionic chains with two catechol anchors, and zwitterionic copolymers with multiple anchors, have been proven to be effective for one-step anchoring and enhanced antifouling properties. Little attention has been paid to the adsorption kinetics and thermodynamics of rapid adhesion and long-term stability of polymer grafts, especially from the sophisticated design of different polymer structures with the construction scaffolds. Recently, Waite et al. reported that a siderophore with a robust tris(2-aminoethyl) amine (TREN) scaffold and three amino acid 3,4-dihydroxy-L-phenylalanine (DOPA) residues exhibited strong adsorption and adhesion behavior and retained adhesive integrity over a wide range of pH9, 10. However, the effects of multiple conjugations, different hydrophilic groups, and different scaffolds on the properties of the materials were still unrevealing. Therefore, there is an ongoing need for rapid and precise polymer design strategies capable of robustly anchoring zwitterionic polymers onto various material surfaces and having excellent antifouling functions.
Due to the uncertainty of polymer properties and complicated experimental procedures, it is relatively difficult and time-consuming to screen polymers with excellent antifouling properties by synthesizing a number of polymers with different structures and determining their surface properties. Related reports on machine learning have enabled rapid polymer molecular design and high-throughput screening of optimal materials by drawing on concepts and ideas from combinatorial chemistry and materials informatics11, 12, namely by combining ”building blocks” of different structures or components in parallel, systematically, and repeatedly13, 14. High-throughput screening gives us the idea of screening out advantageous ”building blocks” according to the required functions. Moreover, due to the competition between the polymer chains dissolved in water and adsorbed on the solid surface, the hydrophilic-hydrophobic balance of the polymer and extensively optimized polymer grafting conformations should be considered and adjusted comprehensively to achieve effective underwater adhesion and good antifouling property. Especially, the complex system with multiple components and multiple interactions will result in differences in the underwater adhesion mechanism, solvation free energy (G solv), and electrostatic potential of polymer molecules which need to be considered from the molecular microstructure and the adsorption configuration information15, 16. Molecular simulation and density functional theory (DFT) calculation can be used to explain the adsorption kinetics and thermodynamics of polymer molecules from the molecular information of ”block” properties17. Hence, it is necessary to propose a strategy that combines multi-scale molecular design and molecular simulation based on the actual function of the polymer rather than the blind screening of large throughput, to design and screen the specific polymer molecules which are easy to synthesize.
Herein, we propose a design and screen strategy for a novel bio-inspired zwitterionic polymer for rapid underwater adhesion and long-term antifouling stability. The target molecule is divided into three parts according to the desired function: tail chain, head group, and scaffold. In molecular design, different colors represent different functions performed in polymer molecules( Figure 1a ). Head groups conjugate to tail chains to fabricate the adhesive antifouling polymers which will be grafted to various substrates using catechol-mediated adhesion to resist protein adsorption. Twelve polymer molecules were designed by a preliminary screening of different head groups, tail chains, and scaffolds. The surface properties, G solv, and adsorption energy (E ads) with hydroxylated silicon surface of design molecules were calculated by DFT and molecular mechanics (MM) calculation, and the most stable adsorption configuration of molecules on the silica surface was analyzed by molecular dynamics (MD) annealing simulation. (Figure 1b ). By comparing these results, we selected a zwitterionic polymer with a TREN scaffold and three DOPA residues for surface anchoring, and three PSBMA polymer chains for antifouling to synthesize and investigate its adhesion behavior and antifouling property. From the calculation and the experimental results, we demonstrated that this material has a fast surface adhesion and antifouling surfaces with long-term stability in an aqueous solution. On this basis, it is interesting to note that tri-DOPA-PSBMA tethered on hydroxylated silicon wafers in 10 minutes and remained stable for more than 30 days without compromising performance, which is of great significance to industrial application. (Figure 1c )