What happens if you introduce a chiral side chain to a conjugated polymer backbone? The conjugated polymer is forced to answer the question: to twist or not to twist? The ability of conjugated polymers to form helical nanostructures depends on the molecular structure of the conjugated backbone. Two conjugated polymers, PCPDTBT* and PCDTPT*, containing chiral side chains, were synthesized in order to study their secondary structures using circular dichroism (CD) spectroscopy. PCPDTBT* provides a strong chiral response. However, the single structural difference of the substitution of a nitrogen atom on the PCDTPT* monomer for a –CH group on the PCPDTBT* monomer decreases the CD signal, indicating a less chiral aggregation. Theoretical calculations suggest the CDT-PT monomer has a higher rotational barrier compared to the CDT-BT monomer. This higher barrier to rotation provides an explanation for the planar conformation of the PCDTPT backbone, its promising transistor performance, and the inability of PCDTPT* to form a helical nanostructure.

Where did that chiral side chain come from anyway? Biocatalysts, such as Baker’s yeast, contain enzymes particularly suited to synthesizing chiral molecules such as chiral side chains. Biocatalysis is advantageous for chemical production as reaction conditions tend to be mild and environmentally-friendly. However, the cell membrane can often act as a barrier; preventing the starting material from entering the cell and the product from leaving. Just as conjugated polymers can be forced into unnatural structures, yeast can be forced to perform biocatalysis. Conjugated oligoelectrolytes (COEs) provide a potential solution based on their ability to intercalate into membranes, resulting in cell membrane permeabilization. Yeast cells were stained with these molecules and used in a model biocatalysis reaction (the conversion of fumaric acid to L-malic acid) where membrane diffusion is known to be the limiting step. As the number of phenylenevinylene units in the conjugated backbone is increased, the permeabilization ability of the COE decreases, along with the biocatalytic yield. The highest improvement utilized DSBN+, containing the smallest number of phenylenevinylene units, to achieve 4.5 times greater yield compared to a control reaction with unpermeabilized cells. If this result proves to be generalizable, a variety of reactions, with applications from pharmaceuticals to nanoparticles, could benefit from a simple and easy-to-use method of biocatalysis acceleration.

Lipid bilayers are omnipresent in biological systems as a barrier protecting intracellular components from the external environment. The semi-permeable behavior of membranes selectively controls flux of chemicals into and out of the cells maintaining chemical balances. This behavior is also a main obstacle for delivering or harvesting chemicals into and from cells. Modifying membrane properties to enhance chemical transport therefore has implications for many cell-based applications.

Conjugated oligoelectrolytes (COEs) are a class of synthetic compounds that contain a π-conjugated backbone with aliphatic linkers bearing ionic functionalities. Given appropriate molecular dimensions and hydrophobic/hydrophilic balance that resemble lipid bilayers, a subset of COEs possess an ability to spontaneously intercalate into membranes and subsequently modify membrane properties. In this work, rational design and structure-property relationships of COEs and their ability to permeabilize and disrupt membranes will be presented.

In the first work, as an effort to improve membrane permeabilization for whole- cell biocatalysis, a COE containing a non-planar conjugated core will be presented and its impact on lipid bilayers will be discussed. Escherichia coli and Saccharomyces cerevisiae (yeast) will be used as model organisms to show an ability of COEs to accelerate whole-cell biocatalysis rates with reduced toxicity to microorganisms.

In a separate study, a homologous series of distyrylbenzene-based COEs will be presented to elucidate the relationship between their structures and their antimicrobial activities and mammalian cell cytotoxicity. The criteria required to achieve high antibacterial selectivity will be discussed. A subsequent study will investigate the impact of hydrogen bonds—another intermolecular force apart from electrostatic and hydrophobic interactions that can be important in lipid interactions—on antimicrobial activities of the COEs. Activities on periplasmic and cytoplasmic membranes of Escherichia coli will be discussed. Additionally, another series of COEs containing amidine moieties will be presented along with preliminary data of their antimicrobial activities against a broad panel of pathogenic bacteria with a focus on Pseudomonas aeruginosa—a clinically relevant pathogen associated with difficult-to-treat infections and with a high propensity for developing antibiotic resistance. Finally, additional results towards developing COEs as a novel class of antibiotics and a method to estimate the “hydrophobicity” of COEs will be discussed.

Many properties of organic semiconductors, such as charge transport or optical absorbance, are governed by the solid-state organization of the material, which is in turn determined by its chemical structure. Developing a fundamental understanding of molecular features that can be used to control the solid-state properties of organic semiconductors is key to designing materials with improved performance or unique new properties. In my research, I have employed a diverse set of techniques, such as theory, experiment and device characterization, to better understand the relationship between molecular structure and solid-state properties of molecular organic semiconductors. Herein, the relationship between the chemical structure of molecular and oligomeric organic semiconductors and their response to thermal stresses and changes in temperature are described. First, I will describe the tolerance of an organic field-effect transistor to operation at temperatures up to 200 ºC and over multiple high-temperature cycles, with only slight changes in charge carrier mobility and properties. The active layer of this device is composed of an oligomeric organic semiconductor whose structure is very similar to that of two well-known ambipolar conjugated polymers. Heating to 200 ºC or above results in appearance ambipolar charge transport in the oligomeric active layer as well. Then, the solid-state organization of a nearly isostructural series of oligomeric organic semiconductors–including the material discussed above–is characterized. As-cast, the first half of the series orients edge-on relative to the substrate while the second half is oriented face-on. This difference is likely due to kinetic trapping during the spin-coating process because melt-annealing of thin films of the four different materials results in edge-on orientation of crystallites for all four molecules. Finally, I describe a combined theoretical and experimental approach to probing aspects of molecular organization and topology based on solid-state NMR. Using this approach, a previously hypothesized change in molecular shape upon crystallization of a molecular organic semiconductor is confirmed. The novel molecular design element of a tail-to-tail couple hexyl-bithiophene core removes the trade-off between solubility and solid-state order in molecular semiconductors.

A three-dimensional conjugated oligoelectrolyte (COE), COE2-3-pCp, was synthesized to study its effects on lipid bilayers. Its structure evolved from previously reported planar COEs via the incorporation of [2.2]paracyclophane within the delocalized central unit thus introducing an additional dimension to molecular format. The biological activity of COE2-3-pCp, in particular its insertion into and effects on biological membranes, was determined using both in vitro and molecular dynamic simulation techniques relative to its planar counterpart (COE2-3C). COE2-3-pCp induced higher lipid disorder, but without marked antimicrobial activity. In addition, COE2-3-pCp permeabilized lipid vesicles and cell membranes to an extent similar to that of COE2-3C. Combined, the data suggest that the non-inhibitory nature of COE2-3-pCp may result from a lower tendency to aggregate in the bilayer revealing that toxicity can be decoupled from membrane permeabilizing activity. Hence, subsequent generations of COEs may be designed to maximize membrane permeabilization while maintaining good biocompatibility for applications in whole-cell biocatalysis.

Bioelectronics concerns the integration of electronic elements with biological systems to form functional devices including biosensors for detection and analysis, neuroelectronic junctions, and biofuel cells for energy conversion and catalysis. A fundamental part of any bioelectronic system is the electronic coupling and transport at the various biotic/abiotic interfaces between biomaterials and electronic supports. The development and study of materials that modulate charge transport across these interfaces is therefore an area of interest. Advances in increasing the synergy between electronics and biology will see impacts in not only our understanding of system, cell, and molecular biology, but also more efficient electronics for conversion of bioenergy. In this development, we have focused on the implementation of redox-active conjugated electrolytes at the biotic/abiotic interface for amplifying biocurrent collection.

In specifically-designed microbial bioelectrochemical systems, bacteria interface with electrodes to catalyze the interconversion of chemical and electrical energy. Membrane modifiers called conjugated oligoelectrolytes (COEs), defined by their conjugated core and peripheral ionic pendant groups, have been shown to increase the ability of electrogenic microbes to electronically communicate with abiotic components through a number of indirect factors including increasing electrode colonization and coulombic efficiency. However, precise control over the mechanism of current enhancement remained to be seen. Two ferrocene-containing COEs called DVFBO and F4-DVFBO were designed to test voltammetric control over biocatalytic current production. Both COEs have a π-delocalized core capped on each end by ferrocene units and show similar optical properties, affinity for the membrane, and toxicity, but fluorination of the core (F4-DVFBO) results in a higher redox potential (422 ± 5 mV compared to 365 ± 4 mV vs Ag/AgCl for DVFBO). The COEs were tested in anaerobic microbial three-electrode electrochemical cells (M3Cs) containing the model electrogenic bacterium Shewanella oneidensis MR-1. At a low electrode potential, the addition of the COEs produced negligible current enhancement compared to controls. However, at E = 365 mV, DVFBO increased steady-state biocurrent 67 ± 12% relative to controls while F4-DVFBO only increased biocurrent by 30 ± 5%. With no change in electrode colonization, cyclic voltammetry supports that DVFBO is the primary conduit of the increased catalytic current and shows F4-DVFBO has less activity at this poised potential. Overall, this work demonstrates the ability to modulate electron transfer from microbial species exclusively via the oxidation potential of the COE.

While microbial membrane modification with redox-active COEs led to improvement in current extraction, a two-dimensional electrode structure limits the surface area for electroactive bacteria attachment and restricts efficient substrate and buffer diffusion. Conjugated polyelectrolytes represent a complementary interfacial materials strategy to enhance biotic/abiotic electronic coupling. First, the mixed ionic-electronic conduction properties of the self-doped conjugated polyelectrolyte CPE-K were investigated with respect to hydration. Films of CPE-K showed both increasing ionic and electronic conduction with hydration. Results indicate that the increase in electronic conduction was due to both increased number of free charge carriers and closer π-π stacking.

Following this characterization, CPE-K was used as a conductive matrix to electronically connect a three-dimensional network of Shewanella oneidensis MR-1 to a gold electrode. At critical CPE-K concentrations, these biocomposites spontaneously assemble from solution into an intricate arrangement of cells within a conductive polymer matrix, thereby increasing biocurrent ~150-fold over control biofilms in M3C tests. While increased biocurrent is due to more cells in communication with the electrode, current extracted per cell is also enhanced indicating efficient long-range electron transport. Further, biocomposites show almost an order-of-magnitude lower charge transfer resistance than CPE-K alone, supporting that the electroactive bacteria and the conjugated polyelectrolyte work synergistically towards an effective electronic biocomposite. Examination of these biocomposites in microbial fuel cell configurations reinforces the need for continued pursuit of synthetic designs to improve the biotic/abiotic interface in bioelectronics.

Conjugated oligoelectrolytes (COEs) contain a conjugated backbone and pendant groups with ionic functionalities. This unique structure combines the properties of semiconducting and water solubility. COEs have similar optical and electronic properties as compare to conjugated polyelectrolytes (CPEs), which have been widely studied for their unique combination of semiconductivity and water solubility, COE are relatively easier to be synthesized and purified. Certain COEs, such as DSBN+ and DSSN+, have been shown to spontaneously insert into liposomes and within the membranes of yeast, and to incorporate into the membranes of Escherichia coli leads to improvement of the current generation in MFCs. In order to study whether the structure variation would affect the biocompatibility of COEs and thus affect the performance of related devices, several new COEs in series with various conjugation length, molecular length, substitution groups with different electron withdrawing/donating group have been designed and synthesized.

Organic photovoltaics (OPV) have garnered a large amount of attention due to their potential for making light-weighted, flexible and low-cost devices in large scale application However, despite the power conversion efficiencies (PCEs) of OSC have steadily increased

through improvements in materials design, mechanistic insight and device architectures, less viii

attention has been put on the sustainability of future application. The vast majority of high performing devices with bulk heterojunction (BHJ) structure are deposited out of chlorinated or aromatic solvents, such as chloroform and chlorobenzene, which require harsh preparation, costly clean up procedure. These solvents are quite toxic to environment and human being. Thus, to develop OSC system be processed out of alternative green solvents is of importance to the future application, especially in mass manufacturing. 2-MeTHF is used to process organic solar cell in the work. 2-MeTHF fits within the class of solvents sought from renewable resources and the concept of capitalizing on waste to generate useful chemicals. The power conversion efficiency of the solar cell processed out of 2-MeTHF is over 5%, which is quite decent and comparable to devices that processed out of chloroform. These findings open new opportunities for considering mass production of organic solar cells, and other optoelectronic devices. It also highlights that substantial molecular design may not be fundamentally necessary for opening environmentally benign processing.

Cellular membranes exist across all domains of life, essentially acting as a barrier that separates the conditions of life from the non-living environment. In gram-negative bacteria, such as Escherichia coli, the cell envelope is comprised of an outer membrane (OM), a peptidoglycan layer (ca. 35–55 nm) and an inner membrane (IM). The core structural component to each membrane is the lipid bilayer, which is electrically insulating and impermeable to most ions and polar molecules. Membrane proteins are the other major component in microbial membranes, conferring function to the membrane and enabling the passive and active transport of ions, molecules and water. Critical biological processes, such as energy generation and molecular sensing, are inherently electronic—driven by the flow of electrons and ions across the membranes of cells. Thus, modification of the transmembrane flux of ions or electrons may enable manipulation of a wide-range of intracellular biological processes pertinent to biotechnological applications.

Conjugated oligoelectrolytes (COEs) are a class of small molecules designed for membrane modification. The structure of COEs are described by a pi- conjugated, phenylenevinylene backbone of a few repeat units tethered at the two terminal ends by ionic functionalities. COEs have been demonstrated to spontaneously intercalate and align in lipid bilayers, thereby allowing modification of membrane properties and function of cells in bioelectrochemical systems. One COE, namely DSSN+, has been applied in a variety of microbial electronic devices utilizing Yeast, E. coli, Shewanella oneidensis, and even naturally occurring microorganisms in wastewater to improve current generation. It is generally acknowledged that ability of COEs to intercalate into microbial membranes is paramount for increasing charge transfer in bioelectrochemical systems, however the specific mechanism of action is not well understood. Previous investigations on the mechanism for improved current in S. oneidensis suggest that DSSN+ amplifies the native biological electron transfer pathway. However, this suggested mechanism does not universally apply across microbial species. For example, COEs have been demonstrated to increase in current and power generation in E. coli microbial fuel cells and this organism lacks a native extracellular electron transfer pathway.

A unifying mechanism by which COEs improve charge transfer processes and modify microbial membranes is the underlying motivation for this work. First, COEs varying in length and structural features are compared with respect to their association with E. coli. Quantification of COEs associated with the cell reveals a morphologically impossible amount, approaching or surpassing a 1:1 lipid:COE ratio, indicating association is not exclusive to membrane intercala- tion. Using zeta potential measurements on COE modified cells, it is determined that COEs are able to tune cell surface charge. Second, considering permeabilization as one possible mode for improved bioelectrochemical performance, the effect of DSSN+ on the permeability of the inner and outer membrane of E. coli is examined, revealing a plausible explanation. Lastly, performance of E. coli in bioelectrochemical systems is examined while taking these effects on membrane properties into consideration. An ultimate hypothesis is proposed, that the combined effects of COEs on membrane properties are the underlying cause for the increased current in E. coli. A better understanding of the effects of COEs on microbial membrane properties can thus inform the molecular design of future COEs and uncover potential new areas of application.

Microorganisms like bacteria have evolved over billions of years to survive in diverse environments and have developed unique functions and metabolic pathways as a result. Manipulating and harnessing their abilities has been a hallmark of the biotechnology revolution and has the potential to solve problems in areas as diverse as health, environmental remediation and energy production. With genetic engineering we now have the ability to install in microbes beneficial functionalities and chemical production processes, but have really just scratched the surface of what is possible. Truly disruptive innovations will come from controllably interfacing these microscopic workhorses with non- living systems in an effort that will likely require both genetic engineering and materials science approaches.

It is with this premise that I present my research on a class of synthetic small molecules known as conjugated oligoelectrolytes (COEs). These water-soluble oligomers spontaneously intercalate into biological membranes and in turn modify the ionic and electronic transport properties of this ubiquitous interface in a variety of microorganisms.

COEs have previously been shown to improve the performance of microbial electronic devices for power production and contaminant removal in wastewater. The research presented here demonstrates the use of COEs for the inverse process of powering a microbe, Shewanella, in order to drive metabolic activity, specifically the reduction of fumarate to succinate. A mechanistic investigation of this process utilizing various voltammetry techniques, microscopy, liquid chromatography, and visible spectroscopy reveals possible membrane permeabilization and enzyme excretion, contradicting a previous hypothesis of COEs acting like transmembrane “molecular wires.” In addition, structure-function relationships for COEs are developed through examination of the effects of different molecular features on various biological systems. Using microscopy and electrochemistry, some effects of ionic group type and arrangement on the biological interactions of COEs are revealed. It is determined that cationic charges are necessary for interaction with E. coli and that a terminal end-only arrangement of charges is beneficial for lipid membrane intercalation. Finally through visible spectroscopy and zeta potential measurements it is determined that longer COEs associate in less quantity with E. coli but affect the cell surface charge to a greater degree than do shorter COEs. It is these relationships that will ultimately lead to new biological applications and inform future molecular design of this exciting class of molecules.