Harnessing Compositional Gradients to Elucidate Phase Behaviors toward High Performance Polymer Semiconductor Blends.

Polymer semiconductor/insulator blends offer a promising avenue to achieve desired mechanical properties, environmental stability, and high device performance in organic field-effect transistors. A comprehensive understanding of process-structure-property relationships necessitates a thorough exploration of the composition space to identify transitions in performance, morphology, and phase behavior. Hence, this study employs a high-throughput gradient thin film library, enabling rapid and continuous screening of composition-morphology-device performance relationships in conjugated polymer blends.

Conjugated Polymer Process Ontology and Experimental Data Repository for Organic Field-Effect Transistors.

Polymer-based semiconductors and organic electronics encapsulate a significant research thrust for informatics-driven materials development. However, device measurements are described by a complex array of design and parameter choices, many of which are sparsely reported. For example, the mobility of a polymer-based organic field-effect transistor (OFET) may vary by several orders of magnitude for a given polymer as a plethora of parameters related to solution processing, interface design/surface treatment, thin-film deposition, postprocessing, and measurement settings have a profound effect on the value of the final measurement.

Improvement of α-amino Ester Hydrolase Stability via Computational Protein Design.

Amino ester hydrolases (AEHs) are capable of rapid synthesis of cephalexin but suffer from rapid deactivation even at low temperatures. Previous efforts to engineer AEH have generated several improved variants but have been limited in scope in part due to limitations in activity assay throughput for β-lactam synthesis reactions. Rational design of 'whole variants' was explored to rapidly improve AEH thermostability by mutating between 3-15% of residues.

Quantifying Dense Multicomponent Slurries with In-Line ATR-FTIR and Raman Spectroscopies: A Hanford Case Study.

The multiphase nature of slurries can make them difficult to process and monitor in real time. For example, the nuclear waste slurries present at the Hanford site in Washington State are multicomponent, multiphase, and inhomogeneous. Current analytical techniques for analyzing radioactive waste at Hanford rely on laboratory results from an on-site analytical laboratory, which can delay processing speed and create exposure risks for workers.

Selectivity and kinetic modeling of penicillin G acylase variants for the synthesis of cephalexin under a broad range of substrate concentrations.

The kinetics of cephalexin synthesis and hydrolysis of the activated acyl-donor precursor phenylglycine methyl ester (PGME) were characterized under a broad range of substrate concentrations. A previously developed model by Youshko-Svedas involving the formation of the acyl-enzyme complex followed by binding of the nucleophilic β-lactam donor does not fully estimate the maximum reaction yields for cephalexin synthesis at different concentrations using initial-rate data. 7-aminodesacetoxycephalosporanic acid (7-ADCA) was discovered to be a potent inhibitor of cephalexin hydrolysis, which may account for the deviation from model predictions.

Water-Based Dynamic Depsipeptide Chemistry: Building Block Recycling and Oligomer Distribution Control Using Hydration-Dehydration Cycles.

The high kinetic barrier to amide bond formation has historically placed narrow constraints on its utility in reversible chemistry applications. Slow kinetics has limited the use of amides for the generation of diverse combinatorial libraries and selection of target molecules. Current strategies for peptide-based dynamic chemistries require the use of nonpolar co-solvents or catalysts or the incorporation of functional groups that facilitate dynamic chemistry between peptides.

Reactor Design and Optimization of -Amino Ester Hydrolase- Catalyzed Synthesis of Cephalexin.

Pharmaceutical production quality has recently been a focus for improvement through incorporation of end-to-end continuous processing. Enzymatic -lactam antibiotic synthesis has been one focus for continuous manufacturing, and α-amino ester hydrolases (AEHs) are currently being explored for use in the synthesis of cephalexin due to their high reactivity and selectivity. In this study, several reactors were simulated to determine how reactor type and configuration impacts reactant conversion, fractional yield toward cephalexin, and volumetric productivity for AEH-catalyzed cephalexin synthesis.

Differential Oligomerization of Alpha versus Beta Amino Acids and Hydroxy Acids in Abiotic Proto-Peptide Synthesis Reactions.

The origin of biopolymers is a central question in origins of life research. In extant life, proteins are coded linear polymers made of a fixed set of twenty alpha--amino acids. It is likely that the prebiotic forerunners of proteins, or protopeptides, were more heterogenous polymers with a greater diversity of building blocks and linkage stereochemistry.

Urea and Acetamide Rich Solutions Circumvent the Strand Inhibition Problem to Allow Multiple Rounds of DNA and RNA Copying.

For decades prebiotic chemists have attempted to achieve replication of RNA under prebiotic conditions with only limited success. One of the long-recognized impediments to achieving true replication of a duplex (copying of both strands) is the so-called strand inhibition problem. Specifically, while the two strands of an RNA (or DNA) duplex can be separated by heating, upon cooling the strands of a duplex will reanneal before mononucleotide or oligonucleotide substrates can bind to the individual strands.

Chemical control of peptide material phase transitions.

Progressive solute-rich polymer phase transitions provide pathways for achieving ordered supramolecular assemblies. Intrinsically disordered protein domains specifically regulate information in biological networks conformational ordering. Here we consider a molecular tagging strategy to control ordering transitions in polymeric materials and provide a proof-of-principle minimal peptide phase network captured with a dynamic chemical network.

Towards Efficient Nonenzymatic DNA Ligation: Comparing Key Parameters for Maximizing Ligation Rates and Yields with Carbodiimide Activation*.

Chemical ligation is an important tool for the generation of synthetic DNA structures, which are used for a wide range of applications. Surprisingly, reported chemical ligation yields can range from 30 to 95 % for the same chemical activating agent and comparable DNA structures. We report a systematic study of DNA ligation by using a well-defined bimolecular test system and a water-soluble carbodiimide (EDC) as a phosphate-activating agent.

The pH dependent mechanisms of non-enzymatic peptide bond cleavage reactions.

The non-enzymatic cleavage rates of amide bonds located in peptides in aqueous solution is pH-dependent and involves two distinct mechanisms: direct hydrolysis (herein termed "scission") and intramolecular aminolysis by the N-terminal amine (herein termed "backbiting"). While amide bond cleavage has been previously characterized using a variety of peptides, no systematic study has yet been reported addressing the effect of the pH on the interplay between the two amide bond cleavage pathways. In this study, the cleavage rates of the glycine dimer (GG), the glycine trimer (GGG), and the cyclic dimer (cGG), as well as the alanine trimer (AAA), were measured at pH 3, 5, 7, and 10 at 95 °C employing quantification based on 1H NMR.

Control of Nucleation Density in Conjugated Polymers via Seed Nucleation.

The development of processing methods to precisely control the solution state properties of semiconducting polymers in situ have remained elusive. Herein, a facile solution seed nucleation processing method is presented in which nucleated poly(3-hexylthiophene) (P3HT) solutions are blended with well-solvated, non-nucleated counterparts as a means to promote the formation of interconnected polymer networks. Nucleation and growth of these networks was induced by preprocessing the solution with UV irradiation and subsequent solution aging prior to deposition via blade-coating.

Understanding the Coacervate-to-Vesicle Transition of Globular Fusion Proteins to Engineer Protein Vesicle Size and Membrane Heterogeneity.

Protein-rich coacervates are liquid phases separate from the aqueous bulk phase that are used by nature for compartmentalization and more recently have been exploited by engineers for delivery and formulation applications. They also serve as an intermediate phase in an assembly path to more complex structures, such as vesicles. Recombinant fusion protein complexes made from a globular protein fused with a glutamic acid-rich leucine zipper (globule-Z) and an arginine-rich leucine zipper fused with an elastin-like polypeptide (Z-ELP) show different phases from soluble, through an intermediate coacervate phase, and finally to vesicles with increasing temperature of the aqueous solution.

Systems Analysis for Peptide Systems Chemistry.

Living systems employ both covalent chemistry and physical assembly to achieve complex behaviors. The emerging field of systems chemistry, inspired by these biological systems, attempts to construct and analyze systems that are simpler than biology, while still embodying biological design principles. Due to the multiple phenomena at play, it can be difficult to predict which phenomena will dominate and when.

Solvent viscosity facilitates replication and ribozyme catalysis from an RNA duplex in a model prebiotic process.

The RNA World hypothesis posits that RNA was once responsible for genetic information storage and catalysis. However, a prebiotic mechanism has yet to be reported for the replication of duplex RNA that could have operated before the emergence of polymerase ribozymes. Previously, we showed that a viscous solvent enables information transfer from one strand of long RNA duplex templates, overcoming 'the strand inhibition problem'.

A Polymer Blend Approach for Creation of Effective Conjugated Polymer Charge Transport Pathways.

Understanding the role of the distribution of polymer chain lengths on process-structure-property relationships in semiconducting organic electronics has remained elusive due to challenges in synthesizing targeted molecular weights ( M) and polydispersity indices. Here, a facile blending approach of various poly(3-hexylthiophene) (P3HT) molecular weights is used to investigate the impact of the distribution of polymer chain lengths on self-assembly into aggregates and associated charge transport properties. Low and high M samples were blended to form a highly polydisperse sample which was compared to a similar, medium M control.

A Prototype of a Neural, Powered, Transtibial Prosthesis for the Cat: Benchtop Characterization.

We developed a prototype of a neural, powered, transtibial prosthesis for the use in a feline model of prosthetic gait. The prosthesis was designed for attachment to a percutaneous porous titanium implant integrated with bone, skin, and residual nerves and muscles. In the benchtop testing, the prosthesis was fixed in a testing rig and subjected to rhythmic vertical displacements and interactions with the ground at a cadence corresponding to cat walking.

Optimization of Stimulation Parameters for Targeted Activation of Multiple Neurons Using Closed-Loop Search Methods.

Differential activation of neuronal populations can improve the efficacy of clinical devices such as sensory or cortical prostheses. Improving stimulus specificity will facilitate targeted neuronal activation to convey biologically realistic percepts. In order to deliver more complex stimuli to a neuronal population, stimulus optimization techniques must be developed that will enable a single electrode to activate subpopulations of neurons.

Expanding the informational chemistries of life: peptide/RNA networks.

The RNA world hypothesis simplifies the complex biopolymer networks underlining the informational and metabolic needs of living systems to a single biopolymer scaffold. This simplification requires abiotic reaction cascades for the construction of RNA, and this chemistry remains the subject of active research. Here, we explore a complementary approach involving the design of dynamic peptide networks capable of amplifying encoded chemical information and setting the stage for mutualistic associations with RNA.

Multistep Conformation Selection in Amyloid Assembly.

Defining pathways for amyloid assembly could impact therapeutic strategies for as many as 50 disease states. Here we show that amyloid assembly is subject to different forces regulating nucleation and propagation steps and provide evidence that the more global β-sheet/β-sheet facial complementarity is a critical determinant for amyloid nucleation and structural selection.

Surveying the sequence diversity of model prebiotic peptides by mass spectrometry.

The rise of peptides with secondary structures and functions would have been a key step in the chemical evolution which led to life. As with modern biology, amino acid sequence would have been a primary determinant of peptide structure and activity in an origins-of-life scenario. It is a commonly held hypothesis that unique functional sequences would have emerged from a diverse soup of proto-peptides, yet there is a lack of experimental data in support of this.

Design of multi-phase dynamic chemical networks.

Template-directed polymerization reactions enable the accurate storage and processing of nature's biopolymer information. This mutualistic relationship of nucleic acids and proteins, a network known as life's central dogma, is now marvellously complex, and the progressive steps necessary for creating the initial sequence and chain-length-specific polymer templates are lost to time. Here we design and construct dynamic polymerization networks that exploit metastable prion cross-β phases.

Catalytic diversity in self-propagating peptide assemblies.

The protein-only infectious agents known as prions exist within cellular matrices as populations of assembled polypeptide phases ranging from particles to amyloid fibres. These phases appear to undergo Darwinian-like selection and propagation, yet remarkably little is known about their accessible chemical and biological functions. Here we construct simple peptides that assemble into well-defined amyloid phases and define paracrystalline surfaces able to catalyse specific enantioselective chemical reactions.