Noncovalent intermolecular interactions, widely found in molecular clusters and bio-molecules, play a key role in many important processes, such as phase changes, folding of proteins and molecular recognition. However, accurate calculation of interaction energies is a very difficult task because the interactions are normally very weak. Rigorous expressions for the electrostatic and polarization interaction energies between two molecules A and B, in term of the electronic densities, have been programmed: (see formula in document). Z is atomic charge, ρ0 is the electron density of the isolated molecule and Δρind is the electron density change of the molecule caused by polarization. With some approximations, procedures for electrostatic and polarization energy calculations were developed that involve numerical integration. Electrostatic and polarization energies for several bimolecular systems, some of which are hydrogen bonded, were calculated and the results were compared to other theoretical and experimental data. A second method for the computing of intermolecular interaction energies has also been developed. It involves a “supermolecule” calculation for the entire system, followed by a partitioning of the overall electric density into the two interacting components and then application of eq. (1) to find the interaction energy. In this approach, according to Feynman’s explanation to intermolecular interactions, all contributions are treated in a unified manner. The advantages of this method are that it avoids treating the supersystem and subsystems separately and no basis set superposition error (BSSE) correction is needed. Interaction energies for several hydrogen-bonded systems are calculated by this method. Compared with the result from experiment and high level ab initio calculation, the results are quite reliable.

Thesis advisor: Jianmin Gao / The oligomerization of membrane proteins has been shown to play a critical role in a myriad of cellular processes, some of which include signal propagation, cell-to-cell communication, and a cell's ability to interact with its surroundings. Diseases that are associated with disruption of protein-protein interactions in the membrane include cystic fibrosis, certain cancers, and bone growth disorders. Although significant progress has been made in our mechanistic understanding of protein-protein interactions in membranes, it remains difficult to predict the oligomerization state of transmembrane domains and explain the physiological consequences of a point mutation within a membrane embedded protein. The development of novel classes of chemical tools will allow us to better understand the energetics of transmembrane domain association at the molecular level. Herein, we demonstrate that fluorinated aromatic amino acids offer intriguing potential as chemical mediators of transmembrane protein association. We have systematically examined the effects of fluorination on the physical properties of aromatic systems in the context of a soluble protein model system. Our results illustrate the ability of fluorinated aromatic amino acids to simultaneously stabilize protein structure and facilitate highly specific protein self-assembly. An improved understanding of the fundamental energetics of aromatic interactions should allow for their more efficient incorporation into designed inhibitors of transmembrane protein association. In addition to chemical tools, the development of simple methods for directly monitoring transmembrane domain association in vitro and in vivo is necessary to advance our understanding of these interactions. Towards this goal, we have established FlAsH-tetracysteine display as an effective approach to quantifying the association propensities of transmembrane α-helices (TMHs) in vitro. Our assay is compatible with two of the most commonly utilized model membrane systems, detergent micelles and vesicles. The high spatial resolution of FlAsH binding (˂ 10 Å) allows for the differentiation of parallel and antiparallel oligomerization events. Importantly, preliminary studies suggest the assay's ability to detect inhibition from exogenous TMHs. Encouraged by our understanding of aromatic interactions and the success of our assay, we are beginning to incorporate fluorinated aromatics in the model TMHs and monitoring their ability to associate. The ultimate goal is to modulate the association of endogenous TMHs such as ErbB2. Research in this direction is ongoing. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Mass spectrometry has become an important tool for analysis of protein complexes. This study utilizes electrospray ionization (ESI) coupled to a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) to analyze noncovalent complexes in the gas phase. Binding of cucurbit[7]uril (CB7) to intact bovine insulin and the B-chain of insulin was investigated. Competition experiments involving the B-chain and a mutant B-chain were performed to probe the solution-phase binding site. Electron capture dissociation (ECD) of CB7 complexed to intact insulin and to the B-chain, produced a series of peptidic fragments of insulin in complex with CB7. Analysis of these fragments allowed the determination of the apparent gas-phase binding site, which appears different than the proposed solution-phase binding-site. These studies thus suggest that CB7 migrates when the complex is transferred from solution to gas phase. The results of this study caution against using ECD-MS as a stand-alone structural probe of solutionphase binding.

Mass spectrometry has become an important tool for analysis of protein complexes. This study utilizes electrospray ionization (ESI) coupled to a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) to analyze noncovalent complexes in the gas phase. Binding of cucurbit[7]uril (CB7) to intact bovine insulin and the B-chain of insulin was investigated. Competition experiments involving the B-chain and a mutant B-chain were performed to probe the solution-phase binding site. Electron capture dissociation (ECD) of CB7 complexed to intact insulin and to the B-chain, produced a series of peptidic fragments of insulin in complex with CB7. Analysis of these fragments allowed the determination of the apparent gas-phase binding site, which appears different than the proposed solution-phase binding-site. These studies thus suggest that CB7 migrates when the complex is transferred from solution to gas phase. The results of this study caution against using ECD-MS as a stand-alone structural probe of solutionphase binding.

Abstract This study was part of a project targeted at developing chemical sensors for organic cations and metal ions by exploiting the interactions between cations and anionic borate derivatives. As well, the chemical synthesis of thiophene monomers with charged or neutral ion-recognition sites was investigated. The primary task in the first part of the work was to prepare anionic receptor molecules based on synthesized borate derivatives and study their complexation with N-heteroaromatic and tropylium cations. The complexation was studied in solution by 1H NMR and ESIMS techniques and in solid state by X-ray crystallography. Crystal structures showed evidence of weak noncovalent interactions–hydrogen bonding, cation···π interactions, and π-stacking. In addition, the crystal structure of the alkali metal complex of tris[3-(2-pyridyl)pyrazolyl]hydroborate was determined. Stability constants of borate complexes were measured by 1H NMR titration in methanol/acetonitrile (1:1) solution at 30 °C. Various derivatives of aromatic borate anions synthesized within this project, some commercially available derivatives, and two neutral carriers containing aromatic anthryl groups were also studied as recognition sites for aromatic cations where N-methylpyridinium was used as primary ion in PVC membrane-based all-solid-state ion sensors. The results showed that borate derivatives offer new possibilities for molecular recognition by ion-selective electrodes (ISEs). The aim of the second part of the study was to develop chemical ion sensor materials where the ion-recognition unit and the charge-compensating ion are covalently coupled to the backbone of a conductive polymer. Sulfonated thiophenes were used as doping ions for the fabrication of Ag+-ISEs. More than 15 differently substituted monomers were synthesized. The materials differed with respect to the receptor unit, extent of oxidation, counteranion, and length of the chain.

Abstract Study was made of host-guest complexation of neutral crown ethers with five- and six-membered N-heteroaromatic cations and purinium cation. Complexation of tetraphenylborate with selected N-heteroaromatic cations and tropylium cation also was studied. Crown ether complexes were characterized by mass spectrometric and 1H NMR spectrometric methods and by X-ray crystallography. Fast atom bombardment mass spectrometry (FABMS) was used as a prelimary tool to characterize the complexes and electrospray ionization mass spectrometry (ESIMS) was used to confirm the complexation stoichiometry. Crystal structures were determined by X-ray crystallography to study the complexation in solid state, and stability constants were measured in acetonitrile by 1H NMR titration at 30 °C to study the complexation in solution. Mass spectrometric studies indicated preferential 1:1 complexation stoichiometry between crown ethers and N-heteroaromatic cations. Crystal structures of crown ether complexes showed that hydrogen bonding and to a lesser degree cation-π and π-π interactions stabilize the structures in solid state. The values of stability constants for crown ether complexes with N-heteroaromatic cations and purinium cation varied between 10 and 350 M-1. Stability constants were higher for complexes with six-membered N-heteroaromatic cations and purinium cation than for complexes with five-membered cations. The values indicated that hydrogen bonding was the main interaction in solution. Tetraphenylborate formed complexes with four N-heteroaromatic cations and tropylium cation, and reacted with six N-heteroaromatic cations through the displacement of one phenyl group by N-heterocycle to form triphenylboranes. The complexes and displacement products were characterized by 1H NMR spectrometry. Four crystal structures of complexes and three crystal structures of displacement products were resolved. Stability constants of complexes were measured in methanol/acetonitrile (1:1) solution at 30 °C by 1H NMR titration method. The values of stability constants for tetraphenylborate complexes with N-heteroaromatic cations ranged from 10 to 50 M-1. C-H···π and N-H···π interactions were found to stabilize the structures both in solid state and in solution.

No description available.

<p>Recent trends in materials science have exploited noncovalent monolayer chemistries to modulate the physical properties of 2D materials, while minimally disrupting their intrinsic properties (such as conductivity and tensile strength). Highly ordered monolayers with pattern resolutions <10 nm over large scales are frequently necessary for device applications such as energy conversion or nanoscale electronics. Scanning probe microscopy is commonly employed to assess molecular ordering and orientation over nanoscopic areas of flat substrates such as highly oriented pyrolytic graphite, but routine preparation of high-quality substrates for device and other applications would require analyzing much larger areas of topographically rougher substrates such as graphene. In this work, we combine scanning electron microscopy with polarization modulated IR reflection adsorption spectroscopy to quantify the order of lying down monolayers of diynoic acids on few layer graphene and graphite substrates across areas of ~1 cm². We then utilize these highly ordered molecular films for templating assembly of di-peptide semiconductor precursors at the nanoscale, for applications in organic optoelectronic device fabrication.<br></p><p></p>

Chirality is a key principle in organic chemistry. All chiral compounds are non-superimposable mirror images of each other and therefore lack an improper axis of rotation (Sn). These mirror images often have identical properties in an achiral environment, however when two chiral molecules interact, they produce different shapes and properties. Nature, to this extent takes advantage of this aspect through unique formation of shape defined biological macromolecules that are tailored to carry out various life processes. This level of shape control is only made possible because of natural chiral monomers such as amino acids or glycosides that make up such macromolecules. Under new methods such as Chirality Assisted Synthesis (CAS), shape and size-controlled polymers and macromolecules can be realized through the use of chiral monomers to make well defined macromolecules. Because chirality dictates shape, and shape defines function in reference to macromolecules, controlling the chirality of monomers, while concurrently dictating shape and size can lead to the potential of biomimetic methodologies and cage like structures. Accessing shape defined monomers can be difficult especially when in reference to chiral compounds. The unique structure of enantiopure tribenzotriquinacenes show promise in the formation of well-defined cage like structures through utilization of CAS methodology. Synthesis of functionalized tribenzotriquinacenes along with development of an enantioselective electrophilic aromatic nitration method was attempted. Further exploration into the effectiveness of through-space enantioselective nitrations found a dependence on solvent temperature, and the auxiliary that is used. Synthetic difficulties, results, modifications and processes toward a generalized method are presented herein. In addition, controlling the size of polymers has always been a difficult synthetic challenge. Overall selectivity toward one product over another is determined via a variety of chemical properties. However, the formation of sequence and size defined polymers are a prominent aspect of natural polymers. The size selective synthesis, of unique ABAB sequenced polymers was attempted using an iterative exponential growth method. The ability to scale up these processes and create monodisperse oligoethers is also presented and described herein.

This dissertation is mainly focused on charge assisted noncovalent interactions specially hydrogen and halogen bonds. Generally, noncovalent interactions are only weak forces of interaction but an introduction of suitable charge on binding units increases the strength of the noncovalent bonds by a several orders of magnitude. These charge assisted noncovalent interactions have wide ranges of applications from crystal engineering to drug design. Not only that, nature accomplishes a number of important tasks using these interactions. Although, a good number of theoretical and experimental studies have already been done in this field, some fundamental properties of charge assisted hydrogen and halogen bonds still lack molecular level understanding and their electronic properties are yet to be explored. Better understanding of the electronic properties of these bonds will have applications on the rational design of drugs, noble functional materials, catalysts and so on. In most of this dissertation, comparative studies have been made between charge and neutral noncovalent interactions by quantum mechanical calculations. The comparisons are primarily focused on energetics and the electronic properties. In most of the cases, comparative studies are also made between hydrogen and halogen bonds which contradict the long time notion that the H-bond is the strongest noncovalent interactions.Besides that, this dissertation also explores the long range behavior and directional properties of various neutral and charge assisted noncovalent bonds.