A complex array of intermolecular forces controls the interactions between and within biological molecules. The desire to empirically explore these fundamental forces has led to the development of several biophysical techniques. Of these, the atomic force microscope (AFM) and the optical tweezers have been employed throughout this thesis to monitor the intermolecular forces involved in biomolecular interactions. The AFM is a well-established force sensing technique capable of measuring biomolecular interactions at a single molecule level. However, its versatility has not been extrapolated to the investigation of a drug-enzyme complex. The energy landscape for the force induced dissociation of the DHFR-methotrexate complex was studied. Revealing an energy barrier to dissociation located ~0.3nm from the bound state. Unfortunately, the AFM has a limited range of accessible loading rates and in order to profile the complete energy landscape alternative force sensing instrumentation should be considered, for example the BFP and optical tweezers. Thus, this thesis outlines the development and construction of an optical trap capable of measuring intermolecular forces between biomolecules at the single molecule level. To demonstrate the force sensing abilities of the optical set up, proof of principle measurements were performed which investigate the interactions between proteins and polymer surfaces subjected to varying degrees of argon plasma treatment. Complementary data was gained from measurements performed independently by the AFM. Changes in polymer resistance to proteins as a response to changes in polymer surface chemistry were detected utilising both AFM and optical tweezers measurements. Finally, the AFM and optical tweezers were employed as ultrasensitive biosensors. Single molecule investigations of the antibody-antigen interaction between the cardiac troponin I marker and its complementary antibody, reveals the impact therapeutic concentrations of heparin have up on the association and dissociation of the complex. In the thesis the AFM and optical tweezers independently provide complementary data towards the understanding of biomolecular interactions.

This thesis describes investigations towards the self-assembly of heterocyclic amino acids to form cyclopeptides, including the natural products dendroamide A and nostacyclamide. The Introduction highlights a variety of different natural products including the lissoclinum cyclopeptides and other oxazole and thiazole based natural products. The conformation of the lissoc1inum cyclopeptides and the affect different substituents have on their conformation is explored. The ability of a variety of natural products to chelate metal ions and the evidence for metal ion chelation within the lissoclinum cyclopeptides is also discussed. The Introduction is concluded with a statement of the aims and objectives of our research. The Results and Discussion section of the thesis details the development of a novel cyc1ooligomerisation reaction of heterocyclic amino acids. This cyc1ooligomerisation is applied to the self-assembly of thiazole and oxazole amino acids to form analogues of naturally occurring cyc1opeptides. The protocol is then extended to the self-assembly of the natural products dendroamide A and nostacyclamide. Additionally the ability of metal ions to act as templates and promote the formation of particular products is illustrated throughout these studies. Detailed discussions are also presented within this section into the methods for thiazole and oxazole formation. The third part of the thesis is the Experimental section containing full details of the preparative work completed and listing spectroscopic and analytical data on all new compounds synthesised during this study.

The research described in this thesis was conducted over a total of three years during the period October 1990 to October 1994, and is the sole work of the author, unless indicated otherwise by reference. A series of mildly dealuminated Y zeolites has been prepared by hydrothermal treatment using a low partial pressure of water vapour. These materials, together with samples previously dealuminated under more severe conditions, were characterised by the temperature programmed desorption of ammonia and the catalytic activity for suitable test reactions. Advances in technique permitted simultaneous monitoring of both the deammoniation and dehydroxylation processes. Interesting features were observed in the dehydroxylation traces which were related to changes in the acid site strength and amount of extraframework aluminium. The activity for both n-hexane cracking and toluene disproportionation reaches a maximum, corresponding to a framework concentration of 25-30 structural aluminium atoms per unit cell, consistent with the maximum number of strong acid sites. Slight deviation from this behaviour was noted, with the mildly steamed catalysts having lower activities than would be expected on the basis of their framework compositions alone. An in-depth analysis of the cracking of n-hexane has revealed that the extent of reaction is also critically dependent on the density of the available acid sites, which is explained in terms of the reaction mechanism. The disproportionation of toluene has highlighted differences in the nature of the extrastructural aluminium. The catalytic activity of the materials is either decreased or enhanced on extraction depending on whether the catalysts have been prepared by mild or severe dealumination. Variations in product distribution with time on stream have been observed and accounted for by changes in the reaction. The lifetime and activity profile of the catalyst could be altered by exposure of the catalyst to small amounts of toluene prior to the main reaction. This supports the concept of active coke enhancing this reaction. Cumene dealkylation was found to proceed on weaker acid sites than the cracking of n-hexane and the disproportionation of toluene, although a maximum in activity was still observed. This indicates that the weakest sites are not capable of catalysing this reaction, and that some heterogeneity of site strength exists between strong and weak acid sites. The dehydration of propan-2-01 was confirmed as a reaction which assesses the total number of acid sites, regardless of strength. However, changes in the selectivity of the products with the strength of the acid sites were found, implying that the formation of di-isopropylether is favoured by strong sites. Deliberate coking of the catalyst surface by exposure to propan-2-01 at elevated temperatures was found to increase the measured activity, in addition to changing the selectivity almost entirely in favour of propene. Extraframework aluminium was found to play an important role in all of the reactions studied. This emphasises the view that although structural aluminium has the larger influence on the overall activity of a catalyst for a particular reaction, the nature of the extraframework aluminium cannot be overlooked.

Thesis (Ph. D.)--Syracuse University, 2004. / "Publication number AAT 3160378."

The work presented in this thesis describes the development and application of strategies to evaluate the influence of extreme confinement within narrow single-walled carbon nanotubes (SWNT) on the pathways of preparative chemical reactions. Methodologies to reduce carbon nanotube length were critically assessed in order to aid the access and egress of reactants and products to and from the SWNT internal channel during confined reactions. A reliable procedure for the encapsulation of organic molecules within carbon nanotubes was developed utilising a novel fractional distillation procedure which exploits the effect of nanoscale confinement on the phase behaviour of liquids. Confinement of the halogenation of N-phenylacetamide within SWNT demonstrated, for the first time, that narrow SWNT are effective hosts for chemical reactions on a preparative scale in the absence of metallic catalysts. The selective formation of the para-brominated regioisomer improved from 68 to 97% as a direct result of confinement. Furthermore, the confinement of a range of azide-alkyne 1,3-dipolar cycloaddition reactions within SWNT showed a consistent increase in selectivity for the 1,4-triazole (up to a 55% increase). The magnitude of this effect can be tuned by varying the SWNT diameter or the steric bulk of the reactant substituents. In addition to the dominant steric factors, the results herein suggest that the electronic properties of carbon nanotubes induce an additional, more subtle influence on selectivity. Investigating the autocatalytic Soai reaction in the presence of carbon nanotubes demonstrated, on a fundamental level, that the helicity of SWNT induces an effect on the formation of chiral molecules. Since carbon nanotubes exist as a racemic mixture of P and M enantiomers, their presence has a symmetrising effect whereby an enantioselective Soai reaction affording 90% ee becomes racemic upon the addition of (6,5)-SWNT. These results clearly demonstrate the ability of carbon nanotubes to influence the properties of preparative chemical reactions.

High-quality potential energy curves (PECs) for several series of M+RG complexes (M = B, Be-Ra, and Zn-Hg, and RG = He-Rn) have been calculated using coupled cluster theory and large basis sets. Spectroscopic constants for these species have been calculated, and using trends in these in conjunction with orbital contour plots, partial atomic charges, and total local energy density analyses, the natures of the interactions are investigated. In general, high binding energies for rare gas complexes were obtained for many of these species. In particular, interactions between the metal cations, B+ and Be+, and the heavier rare gas atoms show very high dissociation energies, with some covalent component to the nature of bonding deduced. The anionic MH- (M = Be-Ra) and RGH- (RG = He-Rn) series are investigated through use of high quality PECs calculated at the coupled cluster level of theory using large basis sets, with spectroscopic constants being subsequently appraised. Dissociation energies in the RGH- series are found to be weak, although reaching moderate values for the heavier rare gases. Conversely, the MH- series possess much higher dissociation energies, especially in the case of BeH-. These differences are discussed in the context of hybridisation on the Group 2 metal centres, and comparison is also made to the isoelectronic BeHe complex. Laser ablation has been employed to produce gas-phase copper atoms suitable for study by resonance-enhanced multiphoton ionisation spectroscopy (REMPI). Since the copper atoms result from an initial copper plasma, many excited electronic states are prepared, which can yield interesting results when studied by electronic spectroscopy. REMPI spectra are presented of transitions from the ground state to the two spin-orbit split components of the low-lying 3d104p state, and to a series of higher lying 3d10nd Rydberg states. Contributions from metastable initial electronic states are also seen, and assignments discussed. Complexes between NO and the alkanes (alkane = methane, ethane, propane, and n-butane) have been studied by REMPI via the A state, where the excitation is localised to the NO molecule. For NO-methane, only the 1:1 complex was observed, but for the longer chain alkanes additional higher-order NO-alkane(n) complexes were observed. Binding energies are deduced for the excited and ground states, and structures for these complexes elucidated, aided by use of ab initio calculations.

The density-functional theory (DFT) of Hohenberg and Kohn [1] has become the Swiss army knife of the quantum chemist, able to tackle nearly all electronic structure problems with impressive accuracy and efficiency, and it is common to see DFT calculations reported alongside experimental observations in the wider chemical literature. Some systems remain problematic for DFT however and, as DFT was constructed to simulate the systems commonly encountered in the chemistry lab, magnetic fields and the electron currents they induce are completely absent from the theory. Instead, DFT must be generalised for use in a magnetic field by including these currents directly, becoming current-density-functional theory (CDFT) [2]. By making this generalisation it is hoped that the practical utility of standard DFT can be leveraged to investigate molecules in both weak and strong magnetic fields. Whilst the study of molecular systems in strong magnetic fields is clearly of astrochemical and academic interest [3–7], it is reasonable to ask what place such calculations have with regards to laboratory problems, and what the eventual goal of CDFT is. To answer this one should look, for example, to the laboratory field semi-conductor systems that have been shown to be good analogues of molecules in strong fields [8,9]. Empirical studies of such systems show that a proper description of the magnetic effects is likely to be essential for their accurate simulation and, with the large size of these systems, the low cost correlated description of CDFT is likely to be instrumental in understanding their electronic structure. The theoretical framework for CDFT has long been established, only very recently however has a computer code, London, been available to actually perform self-consistent molecular CDFT calculations in strong magnetic fields [10, 11]. As a result of this absence, the functionals and approximations that comprise CDFT remain relatively untested. This thesis aims to utilise the London code to address this absence, first establishing the accuracy of existing CDFT functionals before developing the ideas to investigate the effect of a strong magnetic field on various aspects of electronic structure. The thesis begins by establishing the necessary theoretical foundations of DFT in Chapter 1 and its extension to CDFT in Chapter 2. The accuracy of a number of CDFT functionals is tested in Chapter 3 for predicting both the weak field magnetic phenomena encountered on earth, and the more exotic physics found in strong fields. The course of this study reveals a modified implementation of the meta-generalised gradient approximation (mGGA) class of functionals to be particularly well suited to strong field CDFT, providing a promising route to high accuracy descriptions of strong field phenomena. Using the modified mGGA functionals, Chapter 4 makes use of the interpretive powers of CDFT and the Kohn–Sham orbitals in order to develop a qualitative understanding of strong field electronic structure, and the origins of a new bonding mechanism, termed perpendicular paramagnetic bonding. This exploration of strong field phenomena provides a rationalisation for the the successes of the mGGA functionals, highlighting the importance of self-interaction error in strong magnetic fields. The presence of a strong magnetic field has a complicated effect on the excited electronic states, with important consequences for molecular structure in a field. The maximum overlap method (MOM) of Gilbert et al. [12] is employed in Chapter 5 in the context of strong field Hartree–Fock theory to facilitate the study of excited states in magnetic fields. The MOM method is shown to give an excellent agreement with high accuracy calculations and paves the way for a MOM-CDFT program capable of giving an accurate, correlated description of excited states in a field. The rest of the thesis moves away from directly dealing with the complications of a magnetic field, and instead considers the optimised effective potential (OEP) method in DFT as a means to fully orbital dependent functionals. This investigation is made with an eye to the future extension of CDFT to incorporate the OEP method, enabling the use of orbital dependent functionals in the CDFT description of molecules in magnetic fields. Such functionals are expected to be an effective route to higher accuracy calculations, as the currents induced by the magnetic field are inherently orbital dependent quantities themselves. The core framework of magnetic field free OEP is explored in Chapter 6 and a previously unrecognised connection between the recently proposed variational principle of Gidopolous [13] and the Lieb functional [14] is established. The optimised effective potential problem is notoriously ill behaved in a finite basis representation and the problem of regularising its equations to give physical potentials remains unsolved, despite considerable effort. Previous regularisation schemes are severely limited by their requirement for a user defined regularisation strength parameter, with no a priori guide towards the correct choice. This requirement prevents the OEP method from being used as a black box method and restricts the basis set combinations that can be considered. Chapter 7 addresses the absence of a satisfactory regularisation solution by first thoroughly studying the general ill-posed problem and the classical techniques employed in its regularisation. From this base, a fully automatic regularisation scheme is constructed to automatically tune regularisation strength from measures that are internal to the OEP. In doing so, an optimal regularisation is applied throughout the calculation, removing the need for a manually set parameter. The automatic scheme is then augmented with information from the potential basis set and shown to produce a physically meaningful potential from a single OEP calculation, regardless of the basis sets chosen. Finally, Chapter 8 summarises the work and discusses future directions for the continued development of the field.

Vibrational spectroscopy has been used to study fluids within nanopores to provide an insight into the unique phase characteristics of pore confined fluids. In particular the depression in the critical temperature of carbon dioxide, difluoromethane and ethane has been studied and the relationship between pore size and the extent of this depression has also been established. Finally, the change in composition has been assessed for two pore confined binary mixtures. These mixtures were carbon dioxide/acetonitrile and difluoromethane/tetrabutylammonium tetrafluoroborate. This has been studied in a range of pore sizes and at a range of mixture compositions. It was found that as the pore size decreased, the composition of the mixture shifted further away from that of the bulk.

A commercially available NMR spectrometer has been used to investigate fluid transport within porous solids. Two water-wet porous solids were investigated. The first was a sample of Fontainebleau sandstone, and the second was an idealised porous solid made from a random packing of glass beads. The samples were saturated with two immiscible phases, i.e. an oil and water phase. Pulsed field gradient (PFG) NMR measurements of one- and two-dimensional displacement probability distributions are reported, for steady-state flow and diffusion, within two phase saturated porous solids. Measurements were made with the porous solids prepare in different steady-state saturations. NMR relaxation measurements are also reported. Using the NMR data it was possible to evaluate the physical importance of parameters such as wettability and phase saturation on transport phenomena in two phase saturated porous solids. Various computer simulations were developed to model the experimental data.

I) Synthesis of Spiroindenes by Enolate-Directed Ruthenium-Catalyzed Oxidative Annulation of Alkynes with 2-Aryl-1,3-dicarbonyl Compounds The synthesis of carbocycles by the ruthenium-catalyzed oxidative annulation of alkynes with 2-aryl cyclic 1,3-dicarbonyl substrates is described. Proceeding by the functionalization of C(sp3)–H and C(sp2)–H bonds, and the formation of all-carbon quaternary centers, the reactions provide a diverse range of spiroindenes in good yields and high levels of regioselectivity. II) Synthesis of Benzopyrans by Pd(II)- or Ru(II)-Catalyzed C–H Alkenylation of 2-Aryl-3-hydroxy-2-cyclohexenones We have explored the 2-aryl-3-hydroxy-2-cyclohexenones as competent substrates for palladium- and ruthenium-catalyzed C–H alkenylation reactions with terminal alkenes. This process affords benzopyrans, in most cases, with good functional group tolerance. III) Synthesis of Spiroindanes by Palladium-Catalyzed Oxidative Annulations of 1,3-Dienes Involving C–H Functionalization 1,3-Dienes have been an underexplored class of substrates in catalytic oxidative annulation reactions involving C‒H functionalization. The synthesis of spiroindanes by the palladium-catalyzed oxidative annulation of 1,3-dienes with 2-aryl cyclic 1,3-dicarbonyl compounds is described. Several examples of the dearomatizing oxidative annulation of 1,3-dienes with 1-aryl-2-naphthols are also presented. IV) Enantioselective Spiroindene Formation via C‒H Functionalization Using Chiral Cyclopentadienyl Rhodium Catalysts A chiral cyclopentadienyl rhodium ligand with an atropchiral biaryl backbone enables an asymmetric synthesis of spiroindenes from 2-aryl-1,3-dicarbonyl compounds and alkynes. The process affords a range of products with all-carbon quaternary center in high yields and excellent enantiselectivities. The good functional group tolerance and broad substrate generality are the advantages of this reaction.