Hartley, Scott
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Item Data archive for "Mechanisms of Chiral Induction in Foldamers"
Devkota, Govinda Prasad; Lama, Roshan; Hartley, C. ScottFoldamers, oligomers that adopt well-defined conformations, represent an efficient strategy toward nanoscale structural complexity. While most foldamers fold into (chiral) helices, many abiotic foldamers are built from achiral repeat units. They therefore do not have a preferred twist sense. The handedness can, however, be controlled by attaching groups with chirality centers to the foldamer backbone. This process allows the chiral information from readily available feedstocks to be amplified into larger-scale structural asymmetry and, ultimately, translated into functional behavior. This review describes mechanisms whereby the point chirality of chiral “controller” groups direct the helicity of the foldamer to which they are attached in illustrative examples of aromatic oligoamides, oligohydrazides, oligoindoles, oligo(ortho-phenylenes), and oligo(aminoisobutyric acids). We consider cases where the controller groups are attached at either the oligomers’ termini or side-chains. Our emphasis is on applying intuitive concepts from conformational analysis and, where appropriate, computational models of small substructures. In each case, we consider first short-range interactions that orient the controller group in space relative to its direct point of attachment to the foldamer. We then consider long-range interactions between the controller group and more-distant parts of the oligomer, typically one turn farther along the helix. Together, these interactions allow the twist sense to be predicted (or rationalized). Understanding these mechanisms should facilitate the design of systems with dynamic control over helicity.Item Data archive for "Controlling Carbodiimide-Driven Reaction Networks Through the Reversible Formation of Pyridine Adducts"
Salvia, William S.; Mantel, Georgia; Saha, Nirob K.; Rajawasam, Chamoni W. H.; Konkolewicz, Dominik; Hartley, C. ScottCarbodiimide-driven anhydride formation from carboxylic acids is useful in a variety of non-equilibrium systems. While multiple strategies to control deactivation rates (anhydride hydrolysis) have been reported, control over activation rates (anhydride formation) is currently limited. We show that pyridines reversibly form adducts with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide methiodide in water. These adducts are unreactive with carboxylic acids and thus reduce the anhydride formation rate while prolonging carbodiimide lifetime. The best results are obtained with 4-methoxypyridine. This strategy can be used to control the formation of transient polymer network hydrogels, in one example increasing the time to reach peak modulus by 86% and the lifetime by 43%.Item Data archive for "Transient Polymers through Carbodiimide-driven Assembly"
Saha, Nirob K.; Salvia, William S.; Konkolewicz, Dominik; Hartley, C. ScottBiochemical systems make use of out-of-equilibrium polymers generated under kinetic control. Inspired by these systems, abiotic supramolecular polymers driven by chemical fuel reactions have recently been reported. Conversely, polymers based on transient covalent bonds have received little attention, although they have the potential to complement supramolecular systems by generating transient structures based on stronger bonds and offering a straightforward approach to tuning the reaction kinetics. In this study, we show that simple aqueous dicarboxylic acids give poly(anhydrides) when treated with the carbodiimide EDC. Transient covalent polymers with molecular weights exceeding 15,000 are generated which decompose over the course of days. Disassembly kinetics can be controlled using simple substituent effects in the monomer design. The impact of solvent polarity, carbodiimide concentration, and monomer concentration on polymer properties and lifetimes has been investigated. The results reveal substantial control over polymer assembly and disassembly kinetics, highlighting the potential for fine-tuned kinetic control in nonequilibrium polymerization systems.Item Data archive for "Carbodiimide-driven toughening of interpenetrated polymer networks"
Rajawasam, Chamoni W. H.; Tran, Corvo; Sparks, Jessica L.; Krueger, William; Hartley, C. Scott; Konkolewicz, DominikRecent work has demonstrated that temporary crosslinks in polymer networks generated by chemical “fuels” afford materials with large, transient changes in their mechanical properties. This can be accomplished in carboxylic-acid-functionalized polymer hydrogels using carbodiimides, which generate anhydrides with lifetimes on the order of minutes to hours. Here, the impact of the polymer architecture on the mechanical properties of materials was explored. Single networks (SNs) were compared to interpenetrated networks (IPNs). Notably, semi-IPN precursors that give IPNs on treatment with the carbodiimide gave much higher fracture energies (i.e., resistance to fracture) and superior resistance to compressive strain compared to other network structures. A precursor semi-IPN material featuring acrylic acid in only the free polymer chains yields, on treatment with carbodiimide, an IPN with a fracture energy of 2400 J/m2, a fourfold increase compared to an analogous semi-IPN precursor that yields a SN. This resistance to fracture enables the formation of macroscopic complex cut patterns, even at high strain, underscoring the pivotal role of polymer architecture in mechanical performance.Item Data archive for "Carbodiimide-induced formation of transient polyether cages"
Hossain, Mohammad Mosharraf; Jayalath, Isuru M.; Baral, Renuka; Hartley, C. ScottThe use of “fuel” compounds to drive chemical systems out of equilibrium is currently of interest because of the potential for temporally controlled, responsive behavior. We have recently shown that transiently formed crown ethers exhibit counterintuitive templation effects when generated in the presence of alkali metal cations: “matched” cations, such as K+ with an 18-crown-6 analogue, suppress the formation of the macrocycles (negative templation). In this work, we describe two macrocyclic diacids that, on treatment with carbodiimides, give transient macrobicyclic cages analogous to polyether cages. Negative templation effects are observed for the smaller cage when generated in the presence of K+ and Na+, but there is a weak, but reproducible, positive templation effect in the presence of Li+. The larger cage behaves similarly in the presence of Li+, K+, Rb+, and Cs+, but differently with Na+, which appears to bind to both the cage and the initial macrocycle.Item Data archive for "Engineering chiral induction in centrally functionalized ortho-phenylenes"
Peddi, Sumalatha; Livieri, Juliana M.; Vemuri, Gopi Nath; Hartley, C. ScottWork on foldamers, non-biological oligomers that mimic the hierarchical structure of biomacromolecules, continues to yield new architectures of ever increasing complexity. o-Phenylenes, a class of helical aromatic foldamers, are well-suited to this area because of their structural simplicity and the straightforward characterization of their folding in solution. However, combining multiple foldamer subunits into single species requires, by definition, control over folding handedness to obtain well-defined species. Control over o-phenylene twist sense is currently lacking. While chiral induction from groups at their termini has been demonstrated, it would be useful to instead direct twisting from internal positions in order to leave their ends free. Here, we explore chiral induction in a series of o-phenylenes with chiral imides at their centers. Conformational behavior has been studied by NMR and CD spectroscopies and DFT calculations. Chiral induction in otherwise unfunctionalized o-phenylenes is generally poor. However, strategic functionalization of the helix surface with trifluoromethyl and methyl groups allows it to better interact with the imide groups, greatly increasing diastereomeric excesses. The sense of chiral induction is consistent with computational models that suggest that it primarily arises from a steric effect.Item Data archive for "Conformational control of ortho-phenylenes by terminal amides"
Devkota, Govinda Prasad; Carson, William P.; Hartley, C. ScottControl over the folding of oligomers, be it broad induction of a preferred helical handedness or subtle changes in the orientations of individual functional groups, is important for applications ranging from molecular recognition to long-range conformational communication. Here, we report a series of ortho-phenylene hexamers functionalized with achiral and chiral amides at their termini. NMR spectroscopy, taking advantage of F-19 labeling, allows multiple conformers to be detected for each compound. In combination with CD spectroscopy and DFT calculations, specific geometries corresponding to each conformer have been identified and quantified. General conclusions about the effect of sterics and the amide linker on conformational behavior have been drawn, revealing some similarities and key differences with previously reported imines. A model for twist sense control has been developed that is supported by computational models.Item Data archive for "Guest-driven control of folding in a crown-ether-functionalized ortho-phenylene"
Peddi, Sumalatha; Bookout, Molly C.; Vemuri, Gopi Nath; Hartley, C. ScottA crown-ether-functionalized o-phenylene tetramer has been synthesized and coassembled with monotopic and ditopic, achiral and chiral secondary ammonium ion guests. NMR spectroscopy shows that the o-phenylene forms both 1:1 and 1:2 complexes with monotopic guests while remaining well-folded. Binding of an elongated ditopic guest, however, forces the o-phenylene to misfold by pulling the terminal rings apart. A chiral ditopic guest biases the o-phenylene twist sense.Item Data archive for "Fluorine Labeling of ortho-Phenylenes to Facilitate Conformational Analysis"
Kirinda, Viraj C.; Vemuri, Gopi Nath; Kress, Nicholas G.; Flynn, Kaitlyn M.; Kumarage, Nuwanthika Dilrukshi; Schrage, Briana R.; Tierney, David L.; Ziegler, Christopher J.; Hartley, C. Scott1H NMR spectroscopy is a powerful tool for the conformational analysis of ortho-phenylene foldamers in solution. However, as o-phenylenes are integrated into ever more complex systems, we are reaching the limits of what can be analyzed by 1H- and 13C-based NMR techniques. Here, we explore fluorine labeling of o-phenylene oligomers for analysis by 19F NMR spectroscopy. Two series of fluorinated oligomers have been synthesized. Optimization of monomers for Suzuki coupling enables an efficient stepwise oligomer synthesis. The oligomers all adopt well-folded geometries in solution, as determined by 1H NMR spectroscopy and X-ray crystallography. 19F NMR experiments complement these methods well. The resolved singlets of one-dimensional 19F1H spectra are very useful for determining relative conformer populations. The additional information from two-dimensional 19F NMR spectra is also clearly valuable when making 1H assignments. The comparison of 19F isotropic shielding predictions to experimental chemical shifts is not, however, currently sufficient by itself to establish o-phenylene geometries.Item Data archive for "Substituent effects on transient, carbodiimide-induced geometry changes in diphenic acids"
Jayalath, Isuru M.; Gerken, Madelyn M.; Mantel, Georgia; Hartley, C. ScottNucleotide-induced conformational changes in motor proteins are key to many important cell functions. Inspired by this biological behavior, we report a simple chemically fueled system that exhibits carbodiimide-induced geometry changes. Bridging via transient anhydride formation leads to a significant reduction of the twist about the biaryl bond of substituted diphenic acids, giving a simple molecular clamp. The kinetics are well-described by a simple mechanism, allowing structure–property effects to be determined. The kinetic parameters can be used to derive important characteristics of the system such as the efficiencies (anhydride yields), maximum anhydride concentrations, and overall lifetimes. Transient diphenic anhydrides tolerate steric hindrance ortho to the biaryl bond but are significantly affected by electronic effects, with electron-deficient substituents giving lower yields, peak conversions, and lifetimes. The results provide useful guidelines for the design of functional systems incorporating diphenic acid units.Item Data archive for "Folding-controlled assembly of ortho-phenylene-based macrocycles"
Kirinda, Viraj C.; Hartley, C. ScottThe self-assembly of foldamers into macrocycles is a simple approach to non-biological higher-order structure. Previous work on the co-assembly of ortho-phenylene foldamers with rod-shaped linkers has shown that folding and self-assembly affect each other; that is, the combination leads to new emergent behavior, such as access to otherwise unfavorable folding states. To this point this relationship has been passive. Here, we demonstrate control of self-assembly by manipulating the foldamers' conformational energy surfaces. A series of o-phenylene decamers and octamers have been assembled into macrocycles using imine condensation. Product distributions were analyzed by gel-permeation chromatography and molecular geometries extracted from a combination of NMR spectroscopy and computational chemistry. The assembly of o-phenylene decamers functionalized with alkoxy groups or hydrogens gives both [2 + 2] and [3 + 3] macrocycles. The mixture results from a subtle balance of entropic and enthalpic effects in these systems: the smaller [2 + 2] macrocycles are entropically favored but require the oligomer to misfold, whereas a perfectly folded decamer fits well within the larger [3 + 3] macrocycle that is entropically disfavored. Changing the substituents to fluoro groups, however, shifts assembly quantitatively to the [3 + 3] macrocycle products, even though the structural changes are well-removed from the functional groups directly participating in bond formation. The electron-withdrawing groups favor folding in these systems by strengthening arene–arene stacking interactions, increasing the enthalpic penalty to misfolding. The architectural changes are substantial even though the chemical perturbation is small: analogous o-phenylene octamers do not fit within macrocycles when perfectly folded, and quantitatively misfold to give small macrocycles regardless of substitution. Taken together, these results represent both a high level of structural control in structurally complex foldamer systems and the demonstration of large-amplitude structural changes as a consequence of a small structural effects.Item Data archive for "Chemically fueled transient geometry changes in diphenic acids"
Jayalath, Isuru M.; Wang, Hehe; Mantel, Georgia; Kariyawasam, Lasith S.; Hartley, C. ScottTransient changes in molecular geometry are key to the function of many important biochemical systems. Here, we show that diphenic acids undergo out-of-equilibrium changes in dihedral angle when reacted with a carbodiimide chemical fuel. Treatment of appropriately functionalized diphenic acids with EDC (N-(3-(dimethylamino)propyl)-N′-ethylcarbodiimide hydrochloride) yields the corresponding diphenic anhydrides, reducing the torsional angle about the biaryl bond by ∼45°, regardless of substitution. In the absence of steric resistance, the reaction is well-described by a simple mechanism; the resulting kinetic parameters can be used to derive important properties of the system, such as yields and lifetimes. The reaction tolerates steric hindrance ortho to the biaryl bond, although the competing formation of (transient) byproducts complicates quantitative analysis.Item Data archive for "ortho‐Phenylene‐based macrocyclic hydrocarbons assembled using olefin metathesis"
Kirinda, Viraj C.; Schrage, Briana R.; Ziegler, Christopher J.; Hartley, C. ScottWhile many foldamer systems reliably fold into well‐defined secondary structures, higher order structure remains a challenge. A simple strategy for the organization of folded subunits in space is to link them together within a macrocycle. Previous work has shown that o‐phenylenes can be co‐assembled with rod‐shaped linkers into twisted macrocycles, showing an interesting synergy between folding and thermodynamically controlled macrocyclization. In these systems the foldamer units were largely decoupled from each other both conformationally and electronically. Here, we show that hydrocarbon macrocycles, with very short ethenylene linkers, can be assembled from o‐phenylenes using olefin metathesis. Characterization by NMR spectroscopy, X‐ray crystallography, and ab initio calculations shows that the products are approximately triangular trimer macrocycles with helical o‐phenylene corners in a heterochiral configuration. Their photophysics are dominated by the 4,4′‐diphenylstilbene moieties, the longest conjugated segments, with further conjugation broken by the twisting of the o‐phenylenes.Item Data archive for "Dissipative assembly of macrocycles comprising multiple transient bonds"
Hossain, Mohammad Mosharraf; Atkinson, Joshua L.; Hartley, C. ScottDissipative (nonequilibrium) assembly powered by chemical fuels has great potential for the creation of new adaptive chemical systems. However, while molecular assembly at equilibrium is routinely used to prepare complex architectures from polyfunctional monomers, species formed out of equilibrium have, to this point, been structurally very simple. In most examples the fuel simply effects the formation of a single short‐lived covalent bond. Here, we show that chemical fuels can assemble bifunctional components into macrocycles containing multiple transient bonds. Specifically, dicarboxylic acids give aqueous dianhydride macrocycles on treatment with a carbodiimide. The macrocycles are assembled efficiently as a consequence of both fuel‐dependent and ‐independent mechanisms: they undergo slower decomposition, building up as the fuel recycles the components, and are a favored product of the dynamic exchange of the anhydride bonds. These results create new possibilities for generating structurally sophisticated out‐of‐equilibrium species.Item Data archive for "Structure–property effects in the generation of transient aqueous benzoic acid anhydrides by carbodiimide fuels"
Kariyawasam, Lasith S.; Kron, Julie C.; Jiang, Run; Sommer, André J.; Hartley, C. ScottThe design of dissipative systems, which operate out-of-equilibrium by consuming chemical fuels, is challenging. As yet, there are a few examples of privileged fuel chemistries that can be broadly applied in abiotic systems in the same way that ATP hydrolysis is exploited throughout biochemistry. The key issue is that designing nonequilibrium systems is inherently about balancing the relative rates of coupled reactions. The use of carbodiimides as fuels to generate transient aqueous carboxylic anhydrides has recently been used in examples of new nonequilibrium materials and supramolecular assemblies. Here, we explore the kinetics of formation and decomposition of a series of benzoic anhydrides generated from the corresponding acids and EDC under typical conditions (EDC = N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride). The reactions can be described by a simple mechanism that merges known behavior for the two processes independently. Structure–property effects in these systems are dominated by differences in the anhydride decomposition rate. The kinetic parameters allow trends in concentration-dependent properties to be simulated, such as reaction lifetimes, peak anhydride concentrations, and yields. For key properties, there are diminishing returns with the addition of increasing amounts of fuel. These results should provide useful guidelines for the design of functional systems making use of this chemistry.Item Data archive for "Macrocycles of higher ortho-phenylenes: assembly and folding"
Kinney, Zacharias J.; Kirinda, Viraj C.; Hartley, C. ScottHigher-order structure in abiotic foldamer systems represents an important but largely unrealized goal. As one approach to this challenge, covalent assembly can be used to assemble macrocycles with foldamer subunits in well-defined spatial relationships. Such systems have previously been shown to exhibit self-sorting, new folding motifs, and dynamic stereoisomerism, yet there remain important questions about the interplay between folding and macrocyclization and the effect of structural confinement on folding behavior. Here, we explore the dynamic covalent assembly of extended ortho-phenylenes (hexamer and decamer) with rod-shaped linkers. Characteristic 1H chemical shift differences between cyclic and acyclic systems can be compared with computational conformer libraries to determine the folding states of the macrocycles. We show that the bite angle provides a measure of the fit of an o-phenylene conformer within a shape-persistent macrocycle, affecting both assembly and ultimate folding behavior. For the o-phenylene hexamer, the bite angle and conformer stability work synergistically to direct assembly toward triangular [3+3] macrocycles of well-folded oligomers. For the decamer, the energetic accessibility of conformers with small bite angles allows [2+2] macrocycles to be formed as the predominant species. In these systems, the o-phenylenes are forced into unusual folding states, preferentially adopting a backbone geometry with distinct helical blocks of opposite handedness. The results show that simple geometric restrictions can be used to direct foldamers toward increasingly complex geometries.Item Data archive for "Chemically fueled covalent crosslinking of polymer materials"
Zhang, Borui; Jayalath, Isuru M.; Ke, Jun; Sparks, Jessica L.; Hartley, C. Scott; Konkolewicz, DominikTransiently crosslinked dynamic polymer networks are developed, using carbodiimide hydration to link carboxylic acids as anhydrides. From aqueous polymer solutions, non-equilibrium hydrogels are transiently formed, which dissolve upon anhydride hydrolysis. The materials can be refueled using a subsequent injection of carbodiimide. The gels exhibit higher storage moduli compared to transient supramolecular gels as a result of their covalent crosslinks.Item Data archive for "Twist sense control in terminally functionalized ortho-phenylenes"
Hartley, C. Scott; Vemuri, Gopi Nath; Pandian, Rathiesh R.; Spinello, Brian J.; Stopler, Erika B.; Kinney, Zacharias J.Item Data archive for "Linker-Directed Assembly of Twisted ortho-Phenylene-Based Macrocycles"
Kinney, Zacharias J.; Hartley, C. Scott