Browsing by Subject "Supramolecular chemistry"
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Item Aromatic electron donor-acceptor interactions in novel supramolecular assemblies(2006) Reczek, Joseph James; Iverson, Brent L.Molecular self-assembly using non-covalent interactions mediate the structure and function of many critical biological and synthetic molecules. Aromatic donor-acceptor interactions are a type of non-covalent interaction that have been utilized by the Iverson group in the development of aedamers, a class of foldamers that adopt specific secondary structures in aqueous solution. These molecules and their derivatives exploit the complexation of electron-rich 1,5-dialkoxy-naphthalene (Dan) with electron-deficient 1,4,5,8-naphthalene tetracarboxylic diimide (Ndi) within linear charged oligomers to achieve both inter and intra-molecular assemblies not found in nature. This dissertation describes the use of the Dan:Ndi interaction in new systems and environments, expanding the potential and scope for applications of this chemistry. This work specifically focuses on inter-molecular assemblies, with novel molecular designs for solution interactions as well as the group’s first exploration of designed solid state and bulk properties. Chapter 2 describes incorporation of either Dan or Ndi units into independent polymer strands. When mixed together, the Dan and Ndi polymers are shown to associate in solution and upon processing form macrostructures in films and fibers. Chapter 3 reports experiments in which a series of Dan and Ndi monomers are synthesized, melted together, and then allowed to cool to afford columnar mesophases. The results demonstrate the ability to predictably control the structure and phase transition temperatures of mesophases by mixing and matching Dan and Ndi components. Chapter 4 presents the solution phase synthesis of neutral Dan oligomers and describes their potential to increase the association constants of Dan and Ndi oligomers in aqueous solution. Chapter 5 describes work developing alternative designs in the structure and connectivity of Dan and Ndi units for intermolecular assembly. Overall the work described herein implements aromatic electron donor-acceptor interactions in novel supramolecular chemistry, with a focus on the use of Dan and Ndi complexation in the formation of materials. These studies have taken the first difficult steps towards making uniquely controllable and functional materials based on noncovalent aromatic interactions a practical reality.Item Boronic acid and guanidinium based synthetic receptors: new applications in differential sensing(2003) Wiskur, Sheryl Lynn; Anslyn, Eric V.In the field of supramolecular chemistry a common goal is to design a receptor that is highly selective for a targeted analyte. While this is a worthwhile goal, many of these synthetic receptors are less selective than their natural counterparts such as enzymes or antibodies. Many aspects of the work shown herein demonstrate that these less selective synthetic receptors are still useful chemosensors. Just as Nature utilizes differential receptors in our sense of taste and smell, synthetic sensor arrays can be developed to achieve similar results. Chapter 1 is an overview of the development of a sensor. It begins with the aspects of binding carboxylates and diols, specifically by guanidiniums and boronic acids. Next, signaling motifs of a sensor are discussed, leading to the advantages of using an indicator displacement assay. Finally, differential sensors are discussed, introducing the idea of incorporating non-selective synthetic sensors for the detection of multiple analytes with the use of pattern recognition. Chapter 2 discusses the use of non-selective synthetic receptors in a number of sensing schemes. First a receptor was used to bind a class of age related analytes found in scotch whiskies. A correlation was found between the age of the scotch and the sensing ensemble’s response to the beverage. In another sensing application, a high degree of selectivity was achieved by using two receptors and two indicators together in solution. Due to the differential response of the receptors to the indicators and the guests, the simultaneous quantification of tartrate and malate was achieved with the aid of pattern recognition. Finally, initial efforts were put forth for incorporating the receptor into a differential sensing array by immobilizing the receptor on a solid support. The selectivity of the receptor was investigated, showing that the receptor still had a higher affinity for tartrate over malate. Chapter 3 investigated the thermodynamics of guanidiniums and boronic acids binding carboxylates and diols, respectively. Four hosts were investigated with a variety of guests. The association constants were determined through UV/vis analysis, while the entropy and enthalpy were determined with isothermal titration calorimetry. The binding of boronic acids to more than just aliphatic diols was also investigated. Chapter 4 discussed the development of new sensor for catechol containing analytes. The sensor’s design is based on iron binding siderophores. The iron is both the binding site and the signaling motif for the sensor. Upon addition of catechol guests, a signal modulation did occur.Item Colorimetric bisulfite sensing and thio-amine click and declick reactions with applications in polymer chemistry and biotechnology(2017-08-07) Kolesnichenko, Igor Vladimir; Anslyn, Eric V., 1960-; Sessler, Jonathan L; Jones, Richard A; Hoffman, David W; Lynd, Nathaniel ASulfur dioxide and its derivative, bisulfite, are crucial components of food and wine because of their antioxidant and antibacterial properties. While these compounds, often referred to as “sulfites,” are important, their optimal concentration range is very narrow and exceeding it can cause adverse effects, ranging from altered taste to allergic reactions in consumers. The current internationally recognized methods used for sensing sulfites have drawbacks, such as lengthy procedures and low accuracy. Thus, the motivation of this research is to develop an efficient and more accurate technique for sensing sulfites. The initial approach was to couple the host-guest chemistry of cucurbiturils with the known reactivity of bisulfite with carbonyl compounds to cause a shift in λ [subscript max] of the complexes; however, a compound was found which could alone cause a color change upon reaction with bisulfite. Moreover, hydrogen peroxide was formed in the process and the current focus is to quantitatively measure the amount of peroxide generated to back-calculate the amount of bisulfite initially present. Separately, an important goal of organic chemistry has centered on the development of methods to assemble and disassemble molecular modules. The focus of this work is the development of a molecular tether to reversibly bind amines and thiols in aqueous conditions at neutral pH. Herein, are the details of reactions using a Meldrum’s acid-derived conjugate acceptor and its utility in peptide and polymer chemistries, which could greatly benefit from the introduction of reversible covalent bonding units. A current focus of pharmaceutical companies is the attachment of polyethylene glycol (PEG) groups to drugs and proteins to improve water solubility and increase hydrodynamic radius. However, high molecular weight PEG chains can bioaccumulate within the body. One focus of this work is the development of high molecular weight PEG chains that can be chemically triggered to break down into smaller units. In a separate field, a trend in the development of new bactericidal compounds is the use of antibacterial peptides that withstand decomposition through cyclization. Thus, another application of the aforementioned conjugate acceptor is the reversible cyclization of antibacterial peptides to both mask them from enzymes and modulate their activity.Item Design and synthesis of artificial receptors for selective and differential sensing(2007-12) Zhang, Tianzhi, 1973-; Anslyn, Eric V., 1960-This dissertation consists of four chapters. The first chapter provides an in-depth background of synthetic receptors for recognitions of phosphorylated molecules. This chapter covers synthetic receptors developed within the last two decades, and it focuses on the diverse functionalities and detection techniques involved in the receptor design. Chapter 2 discusses the synthesis and employment of a metalated receptor for the selective recognition of organic phosphates and phospho-amino acids, and describes a receptor with a pseudo tetrahedral cavity, which was found to be selective to phosphate, was synthesized utilizing a new and efficient synthetic route. UV-Vis titrations were used to determine binding constants for various organic phosphates and phospho-amino acids. The receptor:Cu(II) complex was found to differentiate the degree and size of phosphate substitutions. Chapter 3 describes the synthesis and application of a type of differential receptors for the recognition of phosphorylated tri-peptides from regular tri-peptides. The tri-peptide couples described in this chapter were part of sequences in protein Filamentous R-synuclein, which was discovered to have a close relation to Parkinson's disease. Extensive Ser129 phosphorylation was observed in diseased brains. Both solid phase and solution phase differential receptors were obtained in the investigations of peptide differentiation. A series of screening methods were applied to narrow down the system combinations. Linear discrimant analysis (LDA) statistical analysis generated a large spatial separation among six tripeptides. Chapter 4 describes the synthesis of a boronic acid based receptor for carboxy and phospho sugars recognition. Due to the large affinity to gluconic acid, which is the only product of enzyme catalyzed glucose oxidation, this receptor was successfully applied in determination of glucose concentration in human serum.Item Design of self-assembling nucleo-peptide hydrogels for molecular self-assembly study and functional biomaterials development(2019-04-26) Baek, Kiheon; Suggs, Laura J.; Ren, Pengyu; Zoldan, Janeta; Rosales, AdrianneSelf-assembling peptide-based biomaterials are promising for use in biomedical applications due to their inherent extracellular matrix-like structure, comparable nanofiber dimensions and responsiveness to cells and proteins. Among them, short peptides and their derivatives have been studied because of their ease of synthesis and bottom-up design for controlling fibrillar supra-structure. In this dissertation, nucleo-tripeptides which can self-assemble into a hydrogel form were designed based on considerations of their gelation conditions and applications to functional cell scaffolds and controlled drug release. From the result of Fmoc modified short depsipeptides study, showing functional potential but cytotoxicity upon degradation, nucleobases were evaluated as a replacement for the Fmoc group. A small library, composed of 16 nucleo-tripeptides, was constructed in order to control the self-assembly conditions and to identify a molecule which can form a hydrogel under physiologic conditions. The resulting supra-structures were analyzed experimentally and computationally. We found that nucleo-tripeptides can self-assemble into nano-fibers which then lead to hydrogel formation under physiologic pH. Self-assembled nano-fibers have DNA-like structures, exhibiting nucleobase stacking and Watson-Crick-like interactions. By using these DNA-like structures as well as the self-healing capability of the nucleo-tripeptide hydrogel, applications as functional cell scaffolds and controlled drug release were studied. The self-assembled nucleo-tripeptide hydrogel can be functionalized via mixing with a second molecule having a complementary nucleobase via Watson-Crick interactions. A molecule possessing arginine-glycine-aspartic acid (RGD), interacting with integrin located on the surface of cells, and a nucleobase was incorporated into the self-assembled nucleo-tripeptide hydrogel. This incorporation resulted in improved viability and cell attachment during 3D culture of fibroblasts. Nucleobase stacking structures were applied to the sequestration and controlled release of the doxorubicin, a cancer drug which exerts its action by intercalated DNA. The self-assembled nucleo-tripeptide hydrogel was able to load doxorubicin effectively through its DNA-like interactions, and in vitro and in vivo studies showed that controlled release of doxorubicin can inhibit tumor growth over a long-term period.Item Electron transfer within tetrathiafulvalene calix[4]pyrrole supramolecular ensembles(2014-12) Davis, Christina Marie; Sessler, Jonathan L.; Krische, Michael J; Siegel, Dionicio R; Hoffman, David W; Brodbelt, Jennifer S; Anslyn, Eric VOver the last decade, the ecological need for clean and renewable energy sources has resulted in considerable resources being directed toward the development of systems capable of converting light energy into chemical energy. This has led to a focus on artificial photosynthetic systems and solar cell devices. These types of devices are desirable since they do not contribute to greenhouse gas emissions, as compared with fossil fuels. Organic solar cells (OSCs) are able to convert solar energy into chemical energy via photon absorption that creates a potential difference in the medium and results in electron transfer. The evolution and lifetime of the charge-separated state produced upon this electron transfer has proved difficult to mimic with synthetic materials. One well recognized problem is that to achieve efficient electron transfer, the rate of back electron transfer must be slower than that of forward electron transfer. Creating a molecular dyad that undergoes rapid electron transfer and results in a long lifetime is a key step in the creation of an organic solar cell that permits efficient solar energy conversion. One such way to achieve these systems is to employ supramolecular interactions to pre-organize the donors and acceptors in solution. The goal of the studies depicted in this dissertation was to explore whether tetrathiafulvalene substituted calix[4]pyrroles (TTF–C4Ps) paired with suitable electron acceptors would lead to systems that undergo electron transfer, either thermal or photoinduced, followed by the formation of stable charge-separated states. We chose to employ fullerenes (Chapter 2) and a porphyrin substituted with a carboxylate functional group (Chapter 3) as the acceptors in the putative electron transfer complexes since both are well known as photoabsorbers that have been extensively studied in photosynthetic model systems. The electron transfer from a TTF moiety of the calix[4]pyrrole to either fullerene or porphyrin was studied via UV-Vis-NIR, fluorescence, and electron spin resonance spectroscopies as well as with laser flash photolysis measurements and theoretical calculations. Chapter 4 details work in which TTF oxidation states were used to create a stable TTF mixed-valence dimer as well as a redox switched “on—off—on” fluorescent system.Item Enantiomeric excess determination using circular dichroism spectroscopy and studies of reversible covalent reactions(2017-06-14) Seifert, Helen Maria; Anslyn, Eric V., 1960-; Dalby, Kevin N; Keatinge-Clay, Adrian T; Liu, Hung-Wen; Iverson, Brent LThe unifying topic of this thesis is that of supramolecular and reversible covalent chemistry. Both supramolecular and reversible covalent reactions operate under thermodynamic control, leading to a proofreading effect and equilibration to the most stable structures. Similarly, these systems are able to respond to applied stimuli, making them useful for the development of sensors, as well as the templated formation of receptors and drug-like molecules. Part 1 of this thesis focuses on the development and improvement of supramolecular and reversible covalent systems for the determination of enantiomeric excess using circular dichroism spectroscopy. We were able to improve the error of enantiomeric excess determination by exploiting the Majority Rules effect exhibited by certain helical polymers. Determination of the enantiomeric excess of a sample using optical methods generally requires the generation of a calibration curve, requiring the availability of enantio-enriched samples with known enantiomeric excess. Our group showed that Charton parameters can be used to predict circular dichroism values of our assemblies upon incorporation of new analytes, circumventing the need for a calibration curve. However, the number of Charton parameters tabulated in the literature is limited, and measurement of these parameters is non-trivial. Therefore, we decided to explore the use of computationally derived Sterimol parameters for the prediction of calibration curves. Part 2 of this thesis focuses on the topic of dynamic covalent reactions for the use in dynamic combinatorial chemistry. We were able to find a set of four reversible covalent reactions that react reversibly under identical reaction conditions and do not exhibit any cross-reactivity, which was unprecedented. Based on these four reactions, we set out to develop photo-cleavable protecting groups for the functionalities used in those reactions. We also developed photo-cleavable reaction partners that would be able to react in a dynamic combinatorial fashion with other reactive groups, but would release their reacting partner unchanged upon photolysis. Finally, we set out to study the reaction kinetics and mechanism of aniline-based catalysis of hydrazone exchange using linear free energy relationships, allowing for fine-tuning of the exchange rateItem Experimental contributions to the theory and application of molecular recognition(2008-05) Hughes, Andrew Dike, 1980-; Anslyn, Eric V., 1960-Molecular recognition is a major branch of modern organic chemistry, and it resides at the forefront of supramolecular chemistry. Supramolecular chemistry refers to the study of the noncovalent intermolecular interaction that are crucial for biological processes, catalytic systems, the organization of crystalline or solution phase superstructures, and molecular recognition to name a few examples. The following dissertation reports research efforts from the Anslyn group into three topics of fundamental interest to the molecular recognition community: cooperativity, array sensing, and the development of highly selective sensors for minimally functionalized analytes. Chapter 1 is a review of the most fundamental points of molecular recognition as it applies to the experimental work that follows. Intermolecular association phenomena are driven by multiple discrete, noncovalent interactions, and cooperativity is a measure of the efficiency with which these interactions are employed in a given system. Cooperativity is poorly understood despite its ubiquity in biological and molecular recognition contexts. The first synthetic hostguest system exhibiting positive cooperativity in water is reported in Chapter 2. The utility of sensitive but unselective sensors when applied in an array format has recently come to light. Chapter 3 details an array of polyaromatic fluorophores dissolved in an aqueous surfactant solution that was used to sense nitrated explosives. This exceptionally unselective quenching process was able to detect and discriminate nitrated explosives such as RDX and TNT at concentrations as low as 19 [mu]M. Finally, Chapters 4 and 5 report different approaches to the sensing of enantiomeric excess in [alpha]-chiral alcohols using an indicator displacement paradigm. Chapter 4 explores unprecedented efforts to convert the Sharpless catalytic epoxidation system to the first Ti[superscript IV]-based molecular recognition system. Chapter 5 focuses upon a two-stage approach of derivatization of the [alpha]-chiral alcohol to a metal chelating ligand followed by employment of the derivative in an indicator displacement assay.Item Exploring chemistry of tetrathiafulvalene-calix[4]pyrroles : supramolecular ion mediated electron transfer(2010-12) Park, Jung Su; Sessler, Jonathan L.; Anslyn, Eric V.; Crooks, Richard M.; Siegel, Dionicio R.; Dodabalapur, AnanthMolecular recognition exploiting non-covalent interactions mediates the structure and function of many critical biological and synthetic molecules. There has thus been continuing and intense efforts in the design and synthesis of supramolecular systems with the capability of recognizing specific chemical species. Among various guest species, Prof. Sessler's group has been focused on the study of artificial anion receptors. Calix[4]pyrrole is a tetrapyrrolic macrocycle that is capable of binding anions via concerted and directional hydrogen bonding. Recently, a tetrathiafulvalene (TTF) functionalized calix[4]pyrrole (TTF-C4P) was synthesized and studied as a receptor for various guest species such as anions, electron deficient guest species, and C₆₀. This dissertation focuses on the recent discovery in supramolecular chemistry of TTF-calix[4]pyrrole derivatives. Chapter 1 provides a brief overview of the historical perspective, redox properties, and uses of TTF derivatives as functional building blocks for supramolecular assemblies, as well as previous findings involving the supramolecular chemistry of TTF-C4P. Chapter 2, as the major focus of this dissertation, describes ion mediated supramolecular and reversible electron transfer processes between TTF-C4P and bisimidazolium salts (BIQ²⁺2X⁻). We discovered that the electron transfer processes between these redox couples could be controlled reversibly by ion binding. Specifically, we found that anion binding to the TTF-C4P receptor promotes the forward ET processes. In contrast, cation complexation to the cavity of TTF-C4P causes the reverse ET processes. Such ion mediated ET processes play an essential role in biological ET systems including photosynthesis and respirations. These reversible ET processes were mapped out by spectroscopic (¹H-NMR, UV-Vis NIR titrations, and EPR analysis) and X-ray single crystallographic analyses of both the intermediate and products. Chapter 3 describes the synthesis of aromatic (thiophene and benzene) annulated TTF-calix[4]pyrroles as new and significantly improved receptors for poly-nitroexplosives. The resulting electronic modulations of the parent TTF-pyrrole structure result in significantly enhanced binding affinities for the corresponding TTF-C4Ps toward polynitro-explosives. This is reflected in a high level of positive homotropic allosterism. The degree of the cooperative effect was found to vary depending on the nature of both the receptors and guest species. The origin of the cooperative binding can be explained by conformational locking and an inductive effect of binding the first nitroaromatic guest.Item Functionalized oligopyrroles : from supramolecular fluorescent sensors to molecular self-assembly(2020-12-06) Guo, Chenxing; Sessler, Jonathan L.; Anslyn, Eric V.; Que, Emily L.; Page, Zachariah A.; Yu, GuihuaPerhaps the simplest yet most elegant oligopyrrolic macrocycles are nature’s so-called pigments of life, namely chlorophyll and Vitamin B₁₂. From the perspective of chemists, the versatility of pyrrole moieties encourages us to assemble these along with other targets and produce numerous oligopyrrole derivatives with diverse functions so as to address unmet challenges. Of particular interest are the anion binding capabilities associated with certain oligopyrroles in both cyclic and acyclic forms. In this regard, the marriage of oligopyrroles with fluorophores allows us to create supramolecular fluorescent anion sensors capable of translating the host–guest binding events into optical (e.g., fluorescent) readouts. The dissertation details the author’s efforts to develop new supramolecular fluorescent anion sensors based on the above two forms of functionalized oligopyrroles, i.e., formylated dipyrromethanes and calix[4]pyrroles. Particular efforts were made to tune their substrate specificities and fluorescence sensing features. In addition, this dissertation details the author’s rudimentary investigations involving the molecular self-assembly features of calix[4]pyrrole-based host–guest complexes. Chapter 1 provides an introduction to the fundamentals and historical overview of anion receptors and fluorescent anion sensors as well as a brief review of recent advances in supramolecular fluorescent sensors for anions. Chapter 2 describes the rational design of a pyrene-linked formylated bis(dipyrromethane) that acts as a fluorescent probe for dihydrogen phosphate. Chapter 3 is focused on a molecular caliper that serves as a fluorescent sensor for dicarboxylate dianions and which is based on the marriage of the calix[4]pyrrole-based anion recognition and vibration-induced emission (VIE). Chapter 4 describes the use of a pair of meso-dipyrenyl calix[4]pyrroles to create an ion pair binding-based fluorescence-tunable supramolecular system that allows for the white light emission. Chapter 5 details the molecular recognition of pyrazine N,N’-dioxide using aryl extended calix[4]pyrroles, as well as the associated guest-directed self-assembly in the solid state. Chapter 6 consists of supplementary data and includes synthetic experimental details and characterization data for all new compounds.Item Progress towards a highly efficient and accurate platform for enantiomeric excess determination(2016-05) Lin, Chung-Yon; Anslyn, Eric V., 1960-; Sessler, Jonathan L; Keatinge-Clay, Adrian; Jones, Richard AEnantiomeric excess (ee) determination remains as the bottleneck for high throughput screening of asymmetric catalysts. The work described herein sought to expand on two previously developed ee sensing assays from our lab– an iron based amine assembly and a zinc based multicomponent assembly. To start, the substituent effect of the zinc multicomponent dynamic assembly for secondary chiral alcohol ee determination was investigated. A new assembly with a higher dynamic range and smaller error was observed. Additionally, potential cooperative binding to the multicomponent assembly was investigated. Furthermore, this work included some preliminary results for a concurrent sensing platform for molecules with chiral amine and alcohol moieties.Item Sensing approaches for the discrimination of small molecules and multivalent analytes(2014-12) Gade, Alexandra Moore; Anslyn, Eric V., 1960-; Sessler, Jonathan; Ellington, Andrew; Hoffman, David; Aldrich, RichardDifferential arrays, composed of receptors that are capable of generating unique patterns of responses, have been shown to be useful for discrimination of molecular analytes. Herein, differential arrays have been developed and utilized for the discrimination of small molecule and multivalent biological analytes using cross-reactive receptors. A variety of carboxylate-binding guanidinium-based receptors were tested for their ability to discriminate carboxylate enantiomers. Lanthanide complexes showed the most promising enantiodifferentiation. A dynamic receptor for multivalent biological analytes was developed using self-assembling components designed to target cancer cell lines in a cross-reactive manner. Using this differential array, cancer cell lines of different tissue origin were classified using principal component analysis. The receptors in the array responded to targets as hypothesized but also behaved in a cross-reactive manner that allowed for analyte differentiation. The classification response of the array was reproducible. Boronic acid receptors and receptor arrays were also developed for discrimination of cell surface glycans. In this work, the success of cross-reactive receptors with designed components in differential sensing for small molecules as well as complex multivalent analytes is demonstrated.Item Studies of anion binding in pyrrole-containing supramolecular motifs(2002) Zimmerman, Rebecca Suzanne; Sessler, Jonathan L.Anions are important in a wide range of biological as well as chemical processes. In addition to their importance in the areas of medicine and catalysis, many environmental pollutants are anionic, such as phosphates, nitrates, and pertechnetate. Anions are more difficult to sense via electrostatic interactions than cations because of their lower charge to radius ratio; the majority of neutral anion receptors thus utilize hydrogen bonding as the predominant binding mode. Anions also have a wide range of geometries and require a high degree of complementarity in receptor design in order to achieve selectivity. Additionally, an anion receptor must successfully compete with the solvent environment. Anions are very strongly solvated, and the free energy gained upon binding must exceed the free energy lost as the result of dehydrating the anion. This can make binding in protic or hydroxylic solvents particularly challenging. Because of the inherent difficulties associated with anion recognition, the development of anion binding agents has lagged behind corresponding work on cation receptors. Currently, there are two general classes of synthetic anion receptors, those that are positively charged and those that are neutral. The major advantage of neutral hosts is that the absence of a positive charge generally provides for more selective binding, for the simple reason that positive charges are nondirectional and lead to electrostatic attractions that cannot by definition be selective for a particular anion. Another advantage to neutral hosts is that there is no inherent competition with a receptor associated with a counterion, which can often result in a weaker affinity for the intended guest. This dissertation focuses on the anion binding behavior of neutral, pyrrole containing supramolecular systems. The first chapter will discuss the ability of ferrocene-pyrrole conjugates to sense anions electrochemically. Chapter 2 investigates the anion binding ability of an expanded calixphyrin and a strapped calixpyrrole. Chapter 3 focuses on crown ether appended dipyrrolylquinoxalines and their effectiveness as ditopic receptors. Chapter 4 provides experimental methods and characterization data.Item Synthesis and characterization studies of novel macrocyclic compounds with CH and NH donor groups(2011-12) Cai, Jiajia; Sessler, Jonathan L.; Willson, C. G.; Krische, Michael J.; Cowley, Alan H.; Fast, Walter L.The dissertation focuses on the recent discovery in supramolecular chemistry of novel macrocyclic compounds with NH and CH donor groups. Chapter 1 provides a brief overview of the anions under study, supramolecular chemistry, the relevant other anion receptors, as well as previous findings involving the use of CH donor groups as functional building blocks. Chapter 2, as the major focus of this dissertation, describes a pyrrolyl-based triazolophane, incorporating CH and NH donor groups, which acts as a receptor for the pyrophosphate anion in chloroform solution. It shows selectivity for this trianion, followed by HSO₄− > H₂PO₄− > Cl− > Br− (all as the corresponding tetrabutylammonium salts), with NH−anion interactions being more important than CH−anion interactions. In the solid state, the receptor binds the pyrophosphate anion in a clip-like slot via NH and CH hydrogen bonds. Chapter 3 describes a pyrrole–based triazolium–phane which has been prepared through “click” chemistry in moderate yield. It displays a high selectivity for tetrahedral oxyanions relative to various test monoanions and trigonal planar anions in mixed polar organic–aqueous solvent media. It was also found that the binding affinity and selectivity of the macrocycle to the anions are solvent dependent. Several crystal structures were solved. They confirm that the cationic macrocycle ring binds pyrophosphate and phosphate anions in the solid state. Finally, chapter 4 describes a novel 1,3,4-substituted 1,2,3-triazolium salt found to function as an effective precursor for the synthesis of structurally characterized cationic silver(I) and ruthenium(II) carbene complexes of overall 1:2 ligand-to-metal stoichiometry. The Ag(I) complex crystallized in the form of an eight silver atom containing cluster, whereas the Ru(II) complex proved to be a discrete species and was found to be capable of initiating the ring-opening metathesis polymerization of norbornene upon activation with (trimethylsilyl)diazomethane.Item Synthetic selective and differential receptors for the recognition of bioanalytes(2006) Wright, Aaron Todd; Anslyn, Eric V.This dissertation consists of five chapters. The first chapter provides an in-depth background of supramolecular chemistry and differential recognition. The first chapter also elaborates upon the necessary requirements for successful application of chemosensor assays and arrays. Additionally, sensing mechanisms and chemometric pattern recognition is described for clarification of the research conducted in chapters 2- 5. Chapter 2 discusses the synthesis and employment of a metalated receptor for the selective recognition of the tripeptide His-Lys-Lys. A receptor was synthesized with two peptide arms emanating outward from a metal ligand core using both solution and solid phase chemistry. UV/Vis titrations were used to determine binding constants for various amino acids and tripeptides to the synthetic receptor:Cu(II) complex. The receptor:Cu(II) complex was found to be selective for His-Lys-Lys over other tripeptides, amino acids, and protected amino acids. viii Chapter 3 describes the synthesis and application of a fluorescent chemosensor for the recognition of unfractionated and low-molecular weight heparin. Heparin is a commonly used clinical anticoagulant for surgical situations and post-operative outpatient care. Due to the high selectivity of the receptor for heparin, studies in crude serum were attempted. It was found that the receptor was selective for heparin in serum. Therefore, fluorescent calibration charts were prepared for quantifying heparin at clinical concentrations using the synthetic receptor. This research is one of very few to be published regarding the creation of synthetic receptors with sufficient selectivity for activity in biological media. Chapter 4 describes the combinatorial synthesis of two resin-bound receptor libraries for use in differential recognition studies. The two libraries, in conjunction with an indicator-uptake assay, were used for the detection and discrimination of three proteins and two glycoproteins as well as four tripeptides and three tripeptide mixtures using pattern recognition protocols. Chapter 5 discusses the preparation and screening of a metalated receptor library. A colorimetric mimic of a tachykinin hormone, α-neurokinin, was created and used to screen the receptor library. Seven selective receptors were identified and subsequently sequenced to determine their molecular architecture. The receptors were resynthesized and employed in solution phase binding studies with α-neurokinin.Item The uses of supramolecular chemistry in synthetic methodology development(2009-05) Shabbir, Shagufta Hasnain; Anslyn, Eric V., 1960-Enantioselective indicator displacement assays (eIDAs), was transitioned to a high-throughput screening protocols, for the rapid determination of concentration and enantioselectivity (ee) of chiral diols and α-hydroxycarboxylic acid. To improve the design of our previously established receptor based on o-(N,N-dialkylaminomethyl)arylboronate scaffolds for eIDAs. The rigidity of the receptor, which pertinent from the formation of an intramolecular N-B dative bond was investigated. o-(Pyrrolidinylmethyl)phenylboronic acid its complexes with bifunctional substrates such as catechol, [alpha]-hydroxyisobutyric acid, and hydrobenzoin was studied in detail by x-ray crystallography and ¹¹B NMR. Our structural study predicts that the formation of an N-B dative bond, and/or solvolysis to afford a tetrahedral boronate anion, depends on the solvent and the complexing substrate present. To simplify the operation of eIDAs, we introduced an analytical method, which utilize a dual-chamber quartz cuvette, which reduces the number of spectroscopic measurements from two to one and introduced artificial neural networks (ANNs) which simplifies data analysis. In a second example a high-throughtput screening protocol for hydrobenzoin was developed. The method involves the sequential utilization of what we define herein as screening, training, and analysis plates. Several enantioselective boronic-acid based receptors were screened using 96-well plates, both for their ability to discriminate the enantiomers of hydrobenzoin and to find their optimal pairing with indicators resulting in the largest optical responses. The best receptor/indicator combination was then used to train an ANN to determine concentration and ee. To prove the practicality of the developed protocol, analysis plates were created containing true unknown samples of hydrobenzoin generated by established Sharpless asymmetric dihydroxylation reactions, and the best ligand was correctly identified. The system was extended to pattern recognition for the rapid determination of identity, concentration, and ee of chiral vicinal diols. A diverse enantioselective sensor array was generated with three chiral boronic acid receptors and pH indicators. The optical response produced by the sensor array, was analyzed by two pattern recognition algorithms: principal component analysis (PCA) and ANNs. The PCA plot demonstrated good chemoselective and enantioselective separation of the analytes, and ANNs was used to accurately determine the concentration and ee of five unknown samples.