Добірка наукової літератури з теми "Resonance-assisted hydrogen bonding"

Triply β-dicarbonyl-embedded 1,3,5-triazine derivatives result in formation of circular linkage of resonance-assisted hydrogen bonding interactions, which can be regarded as well-delocalized resonance hybrids.

The experimental electron densities of two chromone derivatives have been determined from X-ray synchrotron diffraction data at low temperature (100 K). Topological analysis of the electron density has been used to analyze the formation of resonance-assisted hydrogen bonds (RAHBs). Geometrical and topological parameters confirm π-electron delocalization within the hydrogen-bonded ring. In addition, weak C—H...O interactions were identified in both structures. Hydrogen-bond energies allowed medium and weak hydrogen bonds to be distinguished.

Protein structure, including its dynamics, is of pervasive significance in biology. A protein’s structure determines its bindings with other molecules [1], and from that its roles in signal transduction, enzymatic activity and mechanical structure. Few cellular processes have no protein involvement. The relationship between a protein’s sequence of amino-acid residues and its three-dimensional structure, partial or otherwise, has long been of considerable interest [2]. A theory of protein folding is proposed in Section 4.10.4 (Hypotheses/Protein folding). This theory varies and extends the backbone-based theory proposed by Rose et al. [3]. This theory may prove to be the most significant offering of the thesis. Overall, this thesis investigates the variation in peptide group resonance and its implications for Resonance-Assisted Hydrogen Bonding [4, 5], RAHB, such as exists in inter-peptide group hydrogen bonding. Natural Bond Orbital [6], NBO, analysis is used for this investigation, and Section 2.1 summarizes the virtues of NBO. Chapter 3 is concerned with methods for computational investigation of protein structures, and finds that methods and basis sets most often used for these investigations are particularly unsuitable when any beta sheets are present due to poor modelling of amide resonance and hence of RAHB that features in the hydrogen-bonded chains of backbone amides of protein secondary structures such as beta sheets [7] and alpha helices [8]. Chapter 4 reports experiments quantifying the sensitivity of amide resonance to electrostatic field with component parallel or antiparallel to the amide C-N bond. This sensitivity allows electrostatic properties including permittivity of amino-acid residue sidechains to influence backbone amide resonance and hence secondary structure RAHB chains, giving a novel mechanism relating residue sequence to structure. Also, this variation in amide resonance is energetically significant even without considering a hydrogen bonding context. Variation of peptide group resonance is expected to vary the barrier height of prolyl isomerization [9]. Subsequent to quantifying this effect in isolated amides and in a RAHB chain, hypotheses are offered concerning the stability of beta sheets, amyloid fibrils [10] and polyproline helices [11]. An analogous sensitivity in nitrogenous base pairing [12] is conjectured. A hypothesis is offered concerning protein complexation and molecular chaperone [13] action. Chapter 5 is motivated by the observed increase of stabilization when cooperative hydrogen bonding chains are cyclized in non-protein contexts [6] and by the phenomena anticipated if these cycles exist in proteins as described in the chapter. The question of the optimal geometry for amide-amide hydrogen bonding is revisited with emphasis on the inequivalence of amide oxygen lone pairs. A possible avenue for the design of HB-chain polymers with improved stability is discussed. Chapter 6 studies a dependency of amino acid residue preference against beta sheet secondary structure by backbone hydration in the presence of cation, doing so by Quantum Molecular Dynamic simulation of a beta sheet with a full quantum mechanical treatment of each solvent molecule.
Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2016

The thesis entitled “Exploring Diverse Facets of Small Molecules by NMR Spectroscopy” consists of six chapters. The main theme of the thesis is to exploit one and two dimensional NMR methodologies for understanding the diverse facets of small organic molecules, such as, weak intra- and inter- molecular interactions, chiral discrimination, quantification of enantiomeric excess and assignment of absolute configuration. Several new pulse sequences have also been designed to solve specific chemical problems, in addition to extensive utility of existing one and two dimensional NMR experiments. The results obtained on different problems, are discussed under six chapters in the thesis. The brief summary of each of these chapters is given below. Chapter 1 begins with the discussion on the importance of small molecules and their various facets, the analytical techniques available in the literature to study them. The role of NMR spectroscopy as powerful analytical technique to understand the diverse facets of organic molecules and their importance is set out in brief. A short introduction to the basic principles of NMR, the interaction parameters, the commonly employed one and two dimensional homo- and herero- nuclear NMR experiments are also given. The basic introduction to product operators essential for understanding the spin dynamics in the developed pulse sequences is given. The application of diffusion ordered spectroscopy (DOSY), the general problems encountered in the analysis of combinatorial mixtures and the matrix assisted method in circumventing such problems are discussed. Chapter 2 focuses on the chiral discrimination and the measurement of enatiomeric excess. The NMR approach to discriminate enantiomers using chiral auxiliaries such as, solvating agents, derivatizing agents, lanthanide shift reagents, the choice of such auxiliaries and the limitations are discussed in detail. The in-depth discussion on the new protocols developed using both the solvating and derivatizing agents for enantiomeric discrimination of chiral amines, hydroxy acids and diacids are discussed. The new three-component protocols that serve as chiral derivatizing agents for the discrimination of primary amines, diacids and hydroxy acids are discussed. Also the role of organic base such as DMAP in the chiral discrimination is explored for discrimination of acids using BINOL as a chiral solvating agent. Accordingly the discussion is classified into two sections. In the first section the protocol developed utilizing an enantiopure mandelic acid, a primary amine substrate and 2-formylphenylboronic acid that is ideally suited for testing the enantiopurity of chiral primary amines is discussed. The broad applicability of the protocols for testing enantiopurity has been demonstrated on number of chiral molecules using 1H and 19F NMR. The second section contains the results on the new concept developed for discrimination of hydroxy acids. The strategy involves the formation of three component protocol using chiral hydroxy acid, R-alphamethylbenzylamine and 2-formylphenylboronic acid for 1H-NMR discrimination of diacids. The section also includes the utility of ternary ion-pair complex for the discrimination of acids. The ternary ion-pair not only permitted the testing of enantiopurity of chiral acids, but is also found useful for the measurement of enantiomeric excess. Chapter 3 discusses the utilization of the developed three-component protocols for the assignment of absolute configurations of molecules of different functionality. The protocols for the assignments of absolute configuration of primary amines using 2-formylphenylboronic acid and mandelic acid yielded the substantial chemical shift differences between diastereomers. The consistent trend in the direction of change of chemical shifts of the discriminated proton(s) gave significant evidence for employing them as parameters for the assignment of spatial configuration of primary amines. Another protocol using 2-formylphenylboronic acid, hydroxy acids and enantiopure alphamethylbenzylamine permitted their configurational assignment. In the second section a novel solvating agent, obtained by the formation of an ion-pair complex among enantiopure BINOL, DMAP and chiral hydroxy acid for the assignment of the spatial configuration of hydroxy acids is discussed. Chapter 4 focuses on the development of novel NMR methodologies, and also the utility of existing two-dimensional experiments for addressing certain challenging problems. This chapter has been divided into three sections. In Section-I the utilization of well-known homonuclear 2D-J-resolved methodology for unravelling the overlapped NMR spectra of enantiomers, an application for chiral discrimination and the measurement of enantiomeric excess is discussed. The utilization of the chiral auxiliaries, such as, chiral derivatizing agents, chiral solvating agents and lanthanide shift reagents permits enantiodiscrimination and the measurement of excess of one form over the other. Nevertheless many a times one encounters severe problems due to small chemical shift difference, overlap of resonances, complex multiplicity pattern because of the presence of number of interacting spins, and enormous line broadening due to paramagnetic nature of the metal complex. This section is focused on combating such problems utilizing 2D-J-1JNH resolved spectroscopy where a 450 tilting of the spectrum in the F2 dimension, yielded the pure shift NMR spectrum. The method circumvents several problems involved in chiral discrimination and allows the accurate measurement of enantiomeric excess. In Section-II, the development of novel NMR experimental methodology cited in the literature as C-HetSERF and its application for the study of symmetric molecules, such as, double bonded cis- and trans- isomers, and extraction of magnitudes and signs of long range homo- and hetero- nuclear scalar couplings among chemically equivalent protons in polycylic aromatic hydrocarbons is discussed. The extensive utility of the new pulse sequence has been demonstrated on number of symmetric molecules, where the conventional one dimensional experiment fails to yield spectral parameters. In section III, yet another novel pulse sequence called RES-TOCSY developed for unravelling of the overlapped NMR spectrum of enantiomers and the measurement of enantiomeric contents, has been utilized for the accurate measurement of magnitudes and signs of 1H-19F couplings in fluorine containing molecules. The method has distinct advantages as the strengths of the couplings and their relative signs could be extracted on diverse situations, such as, couplings smaller than line widths, the spectrum where the coupling fine structures are absent. Chapter 5 covers the study of nature of intra- and inter- molecular hydrogen bond in amide and its derivative. The chapter is accordingly divided into two sections. In the first section the study of acid and amide hydrogen bonding is discussed and the hydrogen bonded interactions are probed by extensive utility of 1H, 13C and 15N-NMR. The temperature perturbation experiments, measurements of the variation in the couplings, monitoring of diffusion coefficients and the association constants, detection of through space correlation have given unambiguous evidence for the hydrogen bond formation. The results were also supported by DFT calculations. Similar interaction in the solid state has also been derived by obtaining the crystal structure of complex phenylacetic acid with benzamide. In the second section of the chapter the hydrogen bond interaction of organic fluorine in trifluoromethyl derivatives of benzanilides has been explored and the involvement of CF3 group in the hydrogen bonding has been detected. The evidence for the participation of CF3 group in hydrogen bond has been confirmed by number of experiments, such as, the detection of through space couplings, viz., 1hJFH, 1hJFN, and 2hJFF , where the spin polarization between the interacting spins is transmitted through hydrogen bond, the temperature and solvent dependent studies, variation in the 1JNH and two dimensional heteronuclear correlation experiments. In an interesting example of a molecule containing two CF3 groups situated on two phenyl rings of benzanilide, the simultaneous participation of fluorines of two CF3 groups in hydrogen bond has been detected. The confirmatory evidence for such an interaction, where hydrogen bond mediated couplings are not reflected in the NMR spectrum, has been derived by 19F−19F NOESY. Significant deviations in the strengths of 1JNH, in addition to variable temperature, and the solvent induced perturbation studies yielded additional evidence. The NMR results are corroborated by both DFT calculations and MD simulations, where the quantitative information on different ways of involvement of fluorine in two and three centered hydrogen bonds, their percentage of occurrences, and geometries have been obtained. The hydrogen bond interaction energies have also been calculated. The study revealed the rare observation and the first example of the C-F…H-N hydrogen bond in solution state in the molecules containing CF3 groups. Chapter 6 focuses on the mixture analysis using the diffusion ordered spectroscopy (DOSY). High Resolution-DOSY works when the NMR spectrum is well resolved and the diffusion coefficients of the combinatorial mixtures are substantially different from each other. DOSY technique fails when the mixture contains the molecules of nearly identical weights and similar hydrodynamic radii. Thus, the positional isomers, enantiomers consequent to their nearly identical rates of diffusion, are not differentiated. Some of these problems can be overcome by Matrix-Assisted Diffusion Order Spectroscopy (MAD-spectroscopy), where an external reagent acts as a matrix and aids in their diffusion edited separation, provided the molecules embedded in it possess differential binding abilities with the matrix. Such different binding properties of the matrix are the basis for resolution of many isomeric species. In the present study three different novel auxiliaries, micelles-reverse micelles, crown ether and cyclodextrin are introduced for the resolution of positional isomers, double bonded isomers, viz., fumaric acid and maleic acid and also enantiomers. Accordingly, the results of each of these studies are discussed in three different sections.