(6hs) Polymer Mechanochemistry in Molecular Machines and Medical Treatments

Part 1. Current Research: Polymer mechanochemistry--New Mechanophore Systems in Molecular Machines and Medical Treatments (postdoc, 2018-current, advisor: Prof. Jeffrey Moore)

Project 1. Design and synthesis of polymer mechanochemical molecular machines

Mechanophores are functional molecular units that exhibit selective chemical responses to mechanical perturbations. Polymers embedded with mechanophores are responsive to forces (elongation, compression, ultrasonication) and the outcome involves various forms: changes in color and/or fluorescence, chemiluminescent light emitting, activation of latent catalyst, as well as the generation of reactive species such as free radicals, ylides, acids, and small organic molecules. These materials have demonstrated a variety of stress-responsive properties including stress sensing, damage reporting, remote light generation, and self-healing. Among these applications, releasing small molecules from polymer backbone is one of the most challenging tasks. Generally, to transduce the mechanical force experienced by the polymer matrix to the mechanophores, both ends of the mechanophores need to be attached to the polymer backbone. Therefore, after mechanophore activation the residual mechanophore moieties remain bonded to the polymer backbone. Therefore, releasing small molecules by mechanophore is very rare.

So far, small-molecule releasing is usually based on two approaches: (1) Activating a rearrangement reaction that release molecules; and (2) molecular fragmentation. Due to the nature of most rearrangement reactions, the former approach is usually limited to releasing simple species (e.g. HCl, SO₂). The latter fragmentation approach is an example of releasing more complex molecules; however, it generally requires specialized molecular design with limited varieties, and demands significantly higher mechanical stress for the activation process.

Herein, I’m demonstrating my research on the design and synthesize of a new mechanophore platform with molecule-releasing capability via the introduction of mechanically interlocked molecular machines. Molecular machines are molecular constructs that are controlled to perform programmed tasks from the molecular level. Most molecular machines are designed with mechanically interlocked structures, such as a rotaxane that compose of a mobile “wheel” threaded by an “axle” and trapped by bulky stopper groups. In a rotaxane molecular machine, tasks are accomplished by controlling the movement of the wheel along the axle. Therefore, we hypothesize that by guiding the directional sliding of the wheel along the axle, mechanical forces are applied to mechanophores via topological hindrance, allowing for activation of mechanophores on the axle and “extrude out” the generated small molecules.

Project 2: Mechanophore-Based Biomaterials for In-Vivo Ultrasound-Triggered Chemiluminescent Phototherapy

In contrast to the great success in materials science, the application of mechanophores in biomaterials was underdeveloped. Recently, our groups reported that the high-intensity focused ultrasound (HIFU), a non-invasive medical treatement tool, can remotely activate mechanophores in polymer networks. An interesting candidate—dioxetane mechanophore developed by Sijbesma and coworkers, attracted our attention for its ability to generate light from chemical energy via force-induced chemiluminescence. Under HIFU stimulation, blue light was clearly observed in our dioxetane containing polydimethylsiloxane (PDMS) materials at the focal spot of the ultrasound beam, providing excellent spatial and temporal control. This preliminary result opens a pathway towards biomedical applications of mechanophores such as non-invasive sono-optical treatments for optogenetics therapy. To achieve this final goal, we are aiming at two targets: (1) Improving light intensity.

In our previous experiments the light intensity did not meet the minimum threshold for optogenetics or other photo therapies. In our recent studies, we discovered that the poor solubility (max. ca. 0.5 wt%) of the energy acceptor, diphenylanthracene (DPA), was a limiting factor in the light intensity, presumably due to low energy transfer efficiency. By replacing DPA with a more soluble hexyl-functionalized DPA (HDPA), we can now incorporate up to 7.5 wt% HDPA into PDMS. As a result, the light intensity from HIFU activation was increased by 70-fold, up to 14 µW/cm². The increased intensity is higher than the reported threshold of some channelrhodopsins and thus is promising for optogenetics applications. (2): Designing an injectable and biocompatible hydrogel. With success on PDMS-based materials, I’m also working on adapting the system into injectable hydrogels. In our preliminary study, a dioxetane mechanophore was crosslinked into a DMSO-swollen PEG gel network, which successfully generates blue light upon HIFU sonication. We are modifying the molecular structure of dioxetane and DPA derivatives to achive water solubility and injectability without sacrificing the light intensity.

Part 2. Selected Past Research:

Project 1: Poly[n]catenanes: Synthesis of molecular interlocked chains (Ph.D. 2011-2016, postdoc 2016-2018, advisor: Prof. Stuart Rowan)

As the macromolecular version of mechanically interlocked molecules, mechanically interlocked polymers are promising candidates for the creation of sophisticated molecular machines and smart soft materials. Poly[n]catenanes, where the molecular chains consist solely of interlocked macrocycles, contain one of the highest concentrations of topological bonds. As a molecular analog to the chains we use in daily life, poly[n]catenane chains are predicted to exhibit high flexibility and good robustness. It is also an ideal candidate for the study of entanglement in polymer materials. The synthesis of poly[n]catenanes, however, remains a challenge for decades.

We reported the first synthetic approach toward this distinctive polymer architecture in high yield (~75%) via efficient ring closing of rationally designed metallosupramolecular polymers. Light-scattering, mass spectrometric, and nuclear magnetic resonance characterization of fractionated samples support assignment of the high–molar mass product (number-average molar mass ~21.4 kilograms per mole) to a mixture of linear poly[7–26]catenanes, branched poly[13–130]catenanes, and cyclic poly[4–7]catenanes. Increased hydrodynamic radius (in solution) and glass transition temperature (in bulk materials) were observed upon metallation with Zn²⁺.

Selected Publications:

(1) Q. Wu et al., Poly[n]catenanes: Synthesis of molecular interlocked chains. Science, 358, 1434-1439

(2) R. Wojtecki, Q. Wu et al., Optimizing the formation of 2,6-bis(N-alkyl-benzimidazolyl)pyridine-containing [3]catenates through component design. Chemical Science, 4, 4440-4448

Project 2: Graphene based composite materials for electrochemical supercapacitors (M.S. 2009-2011, advisor: Prof. Gaoquan Shi)

Graphene-based materials are excellent candidates for electrochemical energy storage because of the outstanding electrical conductivity, good mechanical strength and huge specific surface area. My M.S. research was focused on the incorporation of redox-active polymers (e.g. polyaniline) and small molecules (e.g. anthraquinone) to prepare graphene-based composite materials with large capacity, good rate capability and long cycle life.

Selected Publications:

(1) Q. Wu et al., Supercapacitors based on flexible graphene/polyaniline nanofiber composite films. ACS Nano, 4, 1963-1970.

(2) Q. Wu et al. High-performance supercapacitor electrodes based on graphene hydrogels modified with 2-aminoanthraquinone moieties. Phys. Chem. Chem. Phys. 13, 11193-11198.

(3) Y. Sun, Q. Wu and G. Shi, Graphene based new energy materials. Energy Environ. Sci. 4, 1113-1132

Teaching Interests:

1. Teaching and mentoring experience

During my PhD I’ve been working as instructor for the departmental MALDI-TOF instrument for three years (2013-2016) and taught at least thirty 1-hour training sessions (up to 4 new users per session). The training session covers the basic mechanism of MALDI-TOF methodology, instrument operation, data processing and sample preparation. I’ve mentored/co-mentored three graduate students, five undergraduate students and one high-school student. Currently, I’m supervising three undergraduate students working on three different research projects, respectively.

2.Teaching capability and philosophy

Besides solid education I received on polymers—I ranked overall #1 GPA for all polymer-related courses during every stage (B.S., M.S. and Ph.D.), another advantage of mine the multidisciplinary background—B.S. from department of chemical engineering, M.S. from department of chemistry. In my future teaching, I will add more chemical engineering and chemistry components into polymer courses. Also, I have the capability to teach some fundamental chemical engineering as well as chemistry classes. My key philosophy for good teaching is understanding my audience (students) before trying to teach them. I will find out their prior knowledge and their limits at the beginning of each semester and modify my teaching accordingly. My favorite strategy is activating their curiosity as intrinsic driving force to obtain more knowledge.