Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Asymmetric synthesis and catalysis is one of the leading research areas in chemistry society, for its versatility and efficiency in obtaining chiral molecules that found the vast majority in natural active compounds and synthetic drugs. Developing asymmetric catalytic methodology is at the frontier in both industrial and academic research laboratories. Enantioselective organocatalysis has emerged as a powerful synthetic tool that is complementary to metal-catalyzed transformations. The development of chiral phosphoric acid and metal phosphate as catalysts has been a breakthrough in recent years. Chiral phosphoric acids have been shown to be powerful catalysts in many organic transformations. Moreover, chiral metal phosphates, which formed by simply replacing the proton in phosphoric acid with metals, have introduced new catalytic activations and broaden the scope of phosphoric acids. This thesis details new highly enantioselective chiral phosphoric acid-catalyzed Pinacol rearrangement and robust alkaline phosphates catalytic system, which utilizes novel carbonyl activation. The Pinacol rearrangement has long been known to be difficult to control in terms of regioselectivity and stereoselectivity. The initial studies found that indolyl-diol compounds can be treated with chiral phosphoric acids to afford the Pinacol rearrangement with high regio- and enantioselectivity. Over 16 chiral phosphoric acids were screened, and it was found an H8-BINOL-phosphoric acid variant with 1-naphthyl groups at 3 and 3' position was the excellent catalyst. This asymmetric transformation is tolerant toward variety of substituents both on the indole ring and migrating groups. During the study, it was found that different ways to generate the catalyst had critical effect on this catalytic transformation. Only those phosphoric acids washed with HCl after column chromatography afforded the rearrangement products with high enantioselectivity. And those without treating with HCl were found contaminated by alkaline metals. These "contamination" catalysts were also found active with carbonyl activations. A highly enantioselective catalytic hetero-Diels-Alder reaction of alpha-keto esters has been developed with chiral alkaline metal phosphates. A calcium 1-naphthyl-BINOL phosphate was found to be the optimum catalyst. A large range of alpha-keto esters as well as isatins can be applied in this alkaline phosphates catalytic system with high efficiency and selectivity. The structure of the catalyst is detailed for the first time by X-ray crystal structure analysis. A proposed Transition state model is provided based on the catalyst crystal structure and Raman spectroscopy analysis. This methodology was further developed with an asymmetric Mukaiyama-Michael addition of beta,gamma-unsaturated alpha-keto ester. The best catalyst was found to be a magnesium chiral phosphate. And the transformation was found capable of tolerating a wide variety of beta,gamma-unsaturated alpha-keto esters.

Owing to the growing demand for enantiopurity in biological and chemical processes, tremendous efforts have been devoted to the synthesis of homochiral metal-organic materials (MOMs) because of their potential applications in chiral separation and asymmetric catalysis. In this dissertation, the synthetic strategies for homochiral MOMs are discussed keeping the focus on their applications. Two distinct approaches have been taken to synthesize chiral structures with different topologies and accessible cavities. The chiral MOMs have been utilized in enantioselective separation of racemates. Chiral variants of the prototypal metal-organic framework MOF-5, δ-CMOF-5 and [lambda]-CMOF-5, have been synthesized by preparing MOF-5 in the presence of L-proline or D-proline, respectively. CMOF-5 crystallizes in chiral space group P213 instead of Fm-3m as exhibited by MOF-5. The phase purity of CMOF-5 was validated by single crystal and powder X-ray diffraction, IR spectroscopy, TGA, N2 adsorption, microanalysis and solid-state CD. CMOF-5 undergoes a reversible single crystal to single crystal phase change to MOF-5 when immersed in a variety of organic solvents although N-methyl-2-pyrolidone, NMP, does not induce loss of chirality. Indeed, MOF-5 undergoes chiral induction when immersed in NMP, affording racemic CMOF-5. A pair of homochiral network materials (CNMs), [Co2(S-man)2(bpy)3](NO3)2·guests (1S) and [Co2(R-man)2(bpy)3](NO3)2·guests (1R) based upon S-mendelic acid and R-mendelic acid were synthesized and characterized, respectively. The cationic networks contain 1D homochiral channels with the cross section of 8.0 Å × 8.0 Å. The chiral amphiphilic channel surfaces lined with hydrophilic nitrate anions and hydrophobic phenyl groups are capable for multiple interactions with guest species. Chiral resolution of 1-phenyl-1-propanol (PP) enantiomers was performed utilizing the homochiral porosity of 1S and 1R through different time period at different temperatures with/without additives. The mechanism for enantioselective separation of PP was fully investigated through single crystal structural analysis of guest exchanged 1S and 1R. Chiral resolution of PP revealed enhanced performance with additive, which can significantly improve the ee value from 32% to 60%.

This thesis describes the use of 2H-azirines, three-membered unsaturatednitrogen-containing heterocycles, as reactive intermediates ina number of Lewis acid promoted alkylations and Diels-Alderreactions providing synthetically useful aziridines. In order to carry out this investigation a new generalprocedure for the ring closure of vinyl azides, forming theresultant 3-substituted-2H-azirines, was developed applying low boiling solventsin closed reaction vessels at elevated temperatures. The addition of organolithium reagents in the presence ofcommercially available chiral ligands, to the 3-(2-naphthyl)-2H-azirine was studied, which gave the correspondingaziridines. Several Lewis acids were shown to catalyze the normalelectron-demand Diels-Alder reaction between 3-alkyl-,3-aromatic-, and 3-ester-substituted 2H-azirines and various dienes. These reactions gave theexpected cycloadducts in moderate yields. Using a chiral auxiliary high diastereoselectivity wasobtained in the addition of alkyl radicals to a8-phenylmenthyl-substituted 2H-azirine-3-carboxylate. The alkyl radicals weregenerated from the corresponding trialkyl borane and molecularoxygen. Hydroborations and transmetallations were used toprepare these trialkylboranes. Catalytic amounts of CuClincreased the diastereoselectivity in the radical additionreactions. Attempts were made to explain how the coordination of aLewis acid to the azirine nitrogen atom affects thereactivity/stability of the azirine. DFT calculations and NMRexperiments involving Lewis acid-azirine complexes wereperformed. Keywords:Enantioselective, diastereoselective, vinylazide, 2H-azirines, aziridines, Lewis acid, chiral ligand,chiral auxiliary, organolithiums, Diels-Alder reaction, alkylradicals, triethylborane.

The research presented in this dissertation involves the development of chiral and achiral analysis using capillary electrochromatography (CEC) and CEC coupled to mass spectrometry (CEC-MS). Chapter 1 briefly reviews CEC fundamentals and latest development on chiral CEC and CEC-MS. The CEC-UV enantioseparations for several acidic compounds are described in Chapter 2. The optimum resolutions for these acidic enantiomers are achieved in ion-suppression mode, i.e. with an acidic mobile phase. One of major drawback in coupling CEC with MS is the bubble formation at the column outlet end, resulting in irreproducible retention time and erratic baseline, or even current breakdown. By introducing internal tapered columns, the aforementioned limitations of CEC-MS are successfully overcome in Chapter 3. The CEC-MS enantioseparation of warfarin and coumachlor is carefully investigated and applied to quantify R- and S-warfarin in human plasma. For individual enantiomers, a concentration of 25 ng/mL is detectable. To further improve the robustness of CEC-MS column, a new procedure of fabricating internal tapered columns is reported in Chapter 4. These internal tapered columns demonstrate excellent ruggedness, low background noise, and good compatibility in reversed-phase and polar organic modes of CEC-MS. In chapter 5, the feasibility of using internal tapered columns packed with vancomycin chiral stationary phase (CSP) is explored for simultaneous enantioseparation of eight â-blockers using CEC-MS. After a careful optimization of the mobile phase composition, sheath liquid and spray chamber parameter, 15 out of 16 enantiomers could be simultaneously resolved with excellent efficiency and detection sensitivity. The synthesis and characterization of sulfated and sulfonated cellulose phenylcarbamate CSPs is described in Chapter 6. The use of these CSPs, especially the sulfonated one, significantly enhances the EOF profile and sample throughput but maintain high enantiomeric resolving power under various modes of CEC and CEC-MS. By combining CEC and atmospheric pressure photo-ionization (APPI) MS, Chapter 7 demonstrates the separation and detection of mono-methylated benzo[a]pyrene (MBAP) isomers with ~100 times enhancement on detection sensitivity than CEC-UV. In Appedix 2, monolithic columns are synthesized through photopolymerized sol-gel approach and utilized for CEC and CEC-APPI-MS of polyaromatic hydrocarbons, and alkyl phenyl ketones.

This thesis is about excitation, detection, properties and applications of multiple quantum coherences applied to different dipolar coupled spin systems. Major focus of the work is on spectral simplification, measurement of residual dipolar couplings and discrimination of enantiomers in chiral aligning media. The first chapter gives a brief account on the fundamentals of nuclear magnetic resonance spectroscopy and multiple quantum coherences. This includes a description of product operator and polarization operator formalisms of pulses and evolution of magnetization. Subsequently a detailed account of two dimensional multiple quantum – single quantum (MQ-SQ) correlation experiments is given. Demonstration of the homonuclear MQ-SQ pulse sequence on a weakly coupled spin system and analysis of the spectrum obtained are also discussed. Homo-nuclear multiple quantum studies carried out to obtain relative the signs of the couplings have been reported in the initial part of the second chapter. The technique has been applied on doubly labeled acetonitrile (13CH313C15N) aligned in a liquid crystalline medium. Special situations like ambiguity in the determination of relative signs of the couplings from the appearance of two dimensional MQ-SQ spectra and the explanation for the same are also discussed. Homo-nuclear MQ experiments on indistinguishable spins, like protons in a methyl group of 13CH313C15N oriented in liquid crystal, and distinguishable spins, like the two carbons in the same molecule, have been carried out. Different directions of approach in which these results need to be analyzed have been discussed. Subsequent part of the chapter is about the correlation of connected MQ-SQ coherences. These experiments are significant in reducing the cross-peaks further from the MQ-SQ spectra. This concept is extended for the discrimination of optical enantiomers dissolved in chiral aligning medium made of poly-Γ-benzyl-L-glutamate (PBLG) and CDCl3. In molecules of Chemical and biological interest one encounters several nuclei such as, 1H, 13C, 15N and 19F. It will be of general interest to determine magnitudes and relative signs of the couplings among these coupled nuclei by NMR experiments. Utilization of hetero-nuclear MQ Experiments in solving such problems is discussed in the third Chapter. Hetero-nuclear MQ experiments were carried out on dipolar coupled 13CH313C15N, with the aim of obtaining the values and signs of various hetero-nuclear couplings in the molecule. The splitting of transitions in the spectra of oriented molecules is always influenced by the sum of dipolar and scalar couplings. Hence precise determination of dipolar couplings requires the knowledge of scalar couplings. To determine the J couplings, experiments were carried out on the same molecule in isotropic medium. When many coupled nuclei are involved one has to carry out several experiments to derive all the spectral parameters. In circumventing this problem heteronuclear multiple quantum experiments involving more than two nuclei as active spins are advantageous. This reduces the number of experiments and thereby reducing the total experimental time. Second part of this chapter demonstrates how a triple resonance triple quantum experiment can provide majority of the couplings from a given coupled system. The feasibility of the experiment is demonstrated even for molecules containing natural abundant isotopes. Application of multiple quantum j-resolved technique for chiral discrimination and obtaining complete one dimensional spectrum of each enantiomer from their racemic mixture is discussed in the fourth chapter. The two dimensional experiment consists of a selective double quantum excitation period followed by selective refocusing during indirect time domain, isotropic mixing and nonselective detection of SQ transitions. Hence this pulse sequence is named as DQSERF-COSY (Double Quantum Selective Refocused Correlation Spectroscopy). The experiment exploits the existence of different intra-methyl couplings between the enantiomers dissolved in chiral liquid crystal medium to separate the one dimensional spectra of each enantiomer in different cross sections. This is possible due to the fact that all the nuclei in any one of the enantiomers are coupled among themselves and there is no inter molecular interaction between the two enantiomers. Also one can extract all the couplings between protons in each enantiomer, which can subsequently be utilized for determination of the residual dipolar couplings, structure and orientation parameters.

<p>This thesis describes the use of 2<i>H</i>-azirines, three-membered unsaturatednitrogen-containing heterocycles, as reactive intermediates ina number of Lewis acid promoted alkylations and Diels-Alderreactions providing synthetically useful aziridines.</p><p>In order to carry out this investigation a new generalprocedure for the ring closure of vinyl azides, forming theresultant 3-substituted-2<i>H</i>-azirines, was developed applying low boiling solventsin closed reaction vessels at elevated temperatures.</p><p>The addition of organolithium reagents in the presence ofcommercially available chiral ligands, to the 3-(2-naphthyl)-2<i>H</i>-azirine was studied, which gave the correspondingaziridines.</p><p>Several Lewis acids were shown to catalyze the normalelectron-demand Diels-Alder reaction between 3-alkyl-,3-aromatic-, and 3-ester-substituted 2<i>H</i>-azirines and various dienes. These reactions gave theexpected cycloadducts in moderate yields.</p><p>Using a chiral auxiliary high diastereoselectivity wasobtained in the addition of alkyl radicals to a8-phenylmenthyl-substituted 2<i>H</i>-azirine-3-carboxylate. The alkyl radicals weregenerated from the corresponding trialkyl borane and molecularoxygen. Hydroborations and transmetallations were used toprepare these trialkylboranes. Catalytic amounts of CuClincreased the diastereoselectivity in the radical additionreactions.</p><p>Attempts were made to explain how the coordination of aLewis acid to the azirine nitrogen atom affects thereactivity/stability of the azirine. DFT calculations and NMRexperiments involving Lewis acid-azirine complexes wereperformed.</p><p><b>Keywords:</b>Enantioselective, diastereoselective, vinylazide, 2<i>H</i>-azirines, aziridines, Lewis acid, chiral ligand,chiral auxiliary, organolithiums, Diels-Alder reaction, alkylradicals, triethylborane.</p>

The habilitation thesis covers theoretical investigations on light-induced processes in molecules. The study is focussed on changes of the molecular electronic structure and geometry, caused either by photoexcitation in the event of a spectroscopic analysis, or by a selective control with shaped laser pulses. The applied and developed methods are predominantly based on quantum chemistry as well as on electron and nuclear quantum dynamics, and in parts on molecular dynamics. The studied scientific problems deal with stereoisomerism and the question of how to either switch or distinguish chiral molecules using laser pulses, and with the essentials for the simulation of the spectroscopic response of biochromophores, in order to unravel their photophysics. The accomplished findings not only explain experimental results and extend existing approaches, but also contribute significantly to the basic understanding of the investigated light-driven molecular processes. The main achievements can be divided in three parts: First, a quantum theory for an enantio- and diastereoselective or, in general, stereoselective laser pulse control was developed and successfully applied to influence the chirality of molecular switches. The proposed axially chiral molecules possess different numbers of "switchable" stable chiral conformations, with one particular switch featuring even a true achiral "off"-state which allows to enantioselectively "turn on" its chirality. Furthermore, surface mounted chiral molecular switches with several well-defined orientations were treated, where a newly devised highly flexible stochastic pulse optimization technique provides high stereoselectivity and efficiency at the same time, even for coupled chirality-changing degrees of freedom. Despite the model character of these studies, the proposed types of chiral molecular switches and, all the more, the developed basic concepts are generally applicable to design laser pulse controlled catalysts for asymmetric synthesis, or to achieve selective changes in the chirality of liquid crystals or in chiroptical nanodevices, implementable in information processing or as data storage. Second, laser-driven electron wavepacket dynamics based on ab initio calculations, namely time-dependent configuration interaction, was extended by the explicit inclusion of magnetic field-magnetic dipole interactions for the simulation of the qualitative and quantitative distinction of enantiomers in mass spectrometry by means of circularly polarized ultrashort laser pulses. The developed approach not only allows to explain the origin of the experimentally observed influence of the pulse duration on the detected circular dichroism in the ion yield, but also to predict laser pulse parameters for an optimal distinction of enantiomers by ultrashort shaped laser pulses. Moreover, these investigations in combination with the previous ones provide a fundamental understanding of the relevance of electric and magnetic interactions between linearly or non-linearly polarized laser pulses and (pro-)chiral molecules for either control by enantioselective excitation or distinction by enantiospecific excitation. Third, for selected light-sensitive biological systems of central importance, like e.g. antenna complexes of photosynthesis, simulations of processes which take place during and after photoexcitation of their chromophores were performed, in order to explain experimental (spectroscopic) findings as well as to understand the underlying photophysical and photochemical principles. In particular, aspects of normal mode mixing due to geometrical changes upon photoexcitation and their impact on (time-dependent) vibronic and resonance Raman spectra, as well as on intramolecular energy redistribution were addressed. In order to explain unresolved experimental findings, a simulation program for the calculation of vibronic and resonance Raman spectra, accounting for changes in both vibrational frequencies and normal modes, was created based on a time-dependent formalism. In addition, the influence of the biochemical environment on the electronic structure of the chromophores was studied by electrostatic interactions and mechanical embedding using hybrid quantum-classical methods. Environmental effects were found to be of importance, in particular, for the excitonic coupling of chromophores in light-harvesting complex II. Although the simulations for such highly complex systems are still restricted by various approximations, the improved approaches and obtained results have proven to be important contributions for a better understanding of light-induced processes in biosystems which also adds to efforts of their artificial reproduction. / Die Habilitationsschrift behandelt theoretische Untersuchungen von durch Licht ausgelösten Prozessen in Molekülen. Der Schwerpunkt liegt dabei auf Veränderungen in der Elektronenstruktur und der Geometrie der Moleküle, die durch Bestrahlung mit Licht entweder bei einer spektroskopischen Untersuchung oder bei gezielter Kontrolle durch geformte Laserpulse herbeigeführt werden. Um die dabei auftretende Elektronen- und Kerndynamik zu simulieren, wurden vornehmlich quantentheoretische Methoden eingesetzt und weiterentwickelt. Die wissenschaftlichen Fragestellungen beschäftigen sich mit dem gezielten Verändern und dem Erkennen der räumlichen Struktur von Molekülen ohne Drehspiegelachse, der sog. molekularen Chiralität, sowie mit durch Licht eingeleiteten Prozessen in biologisch relevanten Pigmenten auf sehr kurzen Zeitskalen. Die entwickelten Ansätze und gewonnenen Erkenntnisse lassen sich drei Haupterfolge unterteilen: Erstens gelang die Entwicklung einer generellen Kontrolltheorie für das Ein- und Umschalten von molekularer Chiralität mit geformten Laserpulsen. Dabei wird die räumliche Struktur der vorgeschlagenen molekularen Schalter zwischen ihren stabilen sog. stereoisomeren Formen selektiv geändert, was sich auf ihre optischen und chemischen Eigenschaften auswirkt. Für komplexere Bedingungen, wie z.B. auf einer Oberfläche verankerten molekularen Schaltern verschiedener Orientierung, wurde eine neue Pulsoptimierungsmethode basierend auf Wahrscheinlichkeiten und Statistik entwickelt. Solche laserpulskontrollierten chiralen molekularen Schalter hofft man u.a. in der Nanotechnologie zum Einsatz zu bringen, wo sie z.B. als Informationsspeicher dienen könnten. Zweitens konnte geklärt werden, welche die wesentlichen Einflüsse sind, die das Erkennen von sog. Enantiomeren, das sind spiegelbildliche Moleküle von entgegengesetzter Chiralität, nach Ionisierung durch ultrakurze zirkular polarisierte Laserpulse ermöglichen. Diese Form des sog. Zirkulardichroismus in der Ionenausbeute erlaubt die quantitative und qualitative Unterscheidung von Enantiomeren in der Massenspektrometrie. Durch Simulation der Elektronendynamik während der Laseranregung konnte u.a. erstmals gezeigt werden, dass neben der Zirkularpolarisation der Laserpulse vor allem die schwachen magnetischen Wechselwirkungen für die Unterscheidung entscheidend sind. Drittens wurden die Spektren von in der Natur vorkommenden Pigmenten simuliert, welche u.a. an wichtigen biologischen Funktionen, wie dem Sammeln von Sonnenenergie für die Photosynthese, beteiligt sind. Die Lichtanregung führt dabei zu einer Veränderung der Elektronenstruktur und Geometrie der Pigmente, wobei letzteres wichtige Konsequenzen für die Verteilung der Energie auf die spektroskopisch beobachteten Molekülschwingungen mit sich bringen. Auch der wichtige Einfluss der biochemischen Umgebung auf die Elektronenstruktur der Pigmente bzw. den Energietransfer zwischen solchen wurde untersucht. Neben der Klärung experimenteller Ergebnisse ermöglichen die Untersuchungen neue Einblicke in die fundamentalen Prozesse kurz nach der Lichtanregung -- Erkenntnisse, die auch für die technische Nachahmung der biologischen Funktionen von Bedeutung sein können.

Zielstellung der durchgeführten Arbeiten war die Entwicklung neuer hochporöser metall-organischer Gerüststrukturen (engl.: metal-organic frameworks, MOFs) durch die Verwendung aufgeweiteter Linkermoleküle. Hierfür wurden verschiedene Synthesestrategien verfolgt. Zum einen wurde die Ausbildung von Layer-Pillar-Strukturen auf der Basis von Anthracen-Linkern genutzt, um poröse und sehr stabile metall-organische Gerüstverbindungen darzustellen. Außerdem wurden aufgeweitete trigonale Linkermoleküle bzw. eine Kombination von bi- und tridentaten Liganden verwendet, um hochporöse Koordinationspolymere zu synthetisieren. Zudem wurde die Synthese chiraler poröser Koordinationspolymere durch die Nutzung des modifizierten TADDOL-Katalysators als chirale organische Komponente verfolgt, um somit einen heterogenen Katalysator für die enantioselektive Katalyse zu gewinnen. Im Rahmen der vorliegenden Arbeit konnten die verschiedenen Synthesestrategien erfolgreich angewendet werden. Durch die Umsetzung des bidentaten Linkers 4,4´-Anthracen-9,10-diyldibenzoesäure und dem Säulenliganden 1,4-Diazabicyclo[2.2.2]octan (Dabco) mit verschiedenen Metallsalzen konnte eine neue Reihe isotyper, poröser Layer-Pillar-Verbindungen (DUT-30, DUT = Dresden University of Technology) mit einer sehr guten Stabilität gegenüber Luft und Feuchtigkeit dargestellt werden. Die Strukturen zeigen eine äußerst hohe Flexibilität, sodass sieben verschiedene Phasen der Verbindungen gefunden werden konnten. Dadurch sind diese Materialien prädestiniert zur Entfernung von Schadstoffen, wie z.B. organischen Lösungsmitteldämpfen, aus der Luft. Auch die Verwendung von trigonalen Linkern kann zur Synthese hochporöse Koordinationspolymere genutzt werden. Dies wurde anhand des Linkers 1,3,5-Tri-(4´-carboxy(1,1´-biphenyl)-4-yl)benzen erprobt. Die Umsetzung des Linkers mit Zinknitrat bzw. Cobaltnitrat führte zu den hexagonalen Schichtstrukturen DUT-40 und DUT-44. DUT-43 besteht ebenfalls aus einer derartigen hexagonalen Schichtstruktur, wobei hier jedoch die Verwendung von 4,4´-Biphenyldicarbonsäure als Co-Linker eine teilweise Verknüpfung der Schichten ermöglicht. Außerdem konnte durch die Umsetzung des tridentaten Linkers mit Kupfernitrat die Struktur von DUT-54 gebildet werden. In dieser liegen eindimensionale Stränge vor, wobei es zu einer gegenseitigen Durchdringung kommt und damit eine dreidimensionale Kanalstruktur entsteht. Eine weitere Synthesestrategie zur Erzeugung hochporöser Materialien nutzt die Verwendung von Co-Linkern für die Erzeugung der Koordinationspolymere. Hier war in der Vergangenheit vor allem die Kombination von bi- und tridentaten Linkern erfolgreich. Nutzt man als bidentaten Vertreter 9,10-Anthracendicarbonsäure, so eignet sich 4,4´,4´´-Benzen-1,3,5-triyltribenzoesäure als tridentater Co-Linker. Die solvothermale Umsetzung der beiden Linker in verschiedenen Lösungsmittelgemischen führte zu zwei neuen porösen Kooordinationspolymeren, welche beide Linkerarten enthalten. Um jedoch gezielt ein hochporöses und stabiles Material erzeugen zu können wurde eine Struktur simuliert, welche isoretikulär zu der bekannten Struktur DUT-6 ist, welche ebenfalls nach dem Prinzip der Kombination von bi- und tridentaten Liganden dargestellt wurde. Die zu erzeugende Struktur beruht auf dem tridentaten Linker 1,3,5-Tri-(4´-carboxy-(1,1´-biphenyl)-4-yl)-benzen und dem bidentaten Linker 1,4-Bi-p-carboxyphenylbuta-1,3-dien, welcher exakt die richtige Länge aufweist, um in diese Struktur eingebaut zu werden. Die Umsetzung von basischem Zinkacetat mit einem Gemisch der beiden Linker führte zu der zuvor simulierten Struktur. Für diese Verbindung, DUT-60, konnte eine spezifische Oberfläche von 6500 m2g-1 und ein Porenvolumen von 3.5 cm3g-1 berechnet werden, welche zu den höchsten jemals für poröse Koordinationspolymere ermittelten Werte gezählt werden können. Ein weiterer Bereich der vorliegenden Arbeit galt der Entwicklung eines neuen chiralen und porösen Koordinationspolymers, welches in der heterogenen enantioselektiven Katalyse eingesetzt werden kann. Dafür wurde der aus der homogenen Katalyse bekannte TADDOL-Linker modifiziert. Durch die solvothermale Umsetzung dieses Linkers mit Zinknitrat konnte die Verbindung DUT-39 erhalten werden. Diese zeigt hervorragende Werte bezüglich ihres Adsorptionsverhaltens für verschiedene Gase und zählt somit zu den chiralen, metall-organischen Gerüstverbindungen mit den höchsten Porositäten. Außerdem zeigt die Verbindung eine hohe thermische Stabilität sowie eine gute Stabilität gegenüber Luftfeuchte, was sie zu einem attraktiven Kandidaten für die heterogene enantioselektive Katalyse macht.

The work described in this thesis involves the study of weak interactions by NMR spectroscopy and using them to develop novel applications. The two different applications chosen are i) using molecular interactions for chiral discrimination and ii) understanding the nature of the interaction between peptide and nanoparticles to develop potent antibacterial agents. The thesis, which is divided into five chapters starts with a general introduction of NMR spectroscopy for the study of molecular interactions in conjunction with other techniques. The remaining four chapters focus on four different areas/projects that I have worked on. Chapter 1: Introduction This chapter reviews different kinds of molecular interactions along with the introduction to NMR spectroscopy and other techniques used for all the studies. Starting with the application of chiral discrimination the chapter proceeds to the general introduction of antimicrobial peptides, silver nanoparticles and the strategy for peptide resonance assignment. Chapter 2: Chiral discrimination for versatile functionalities There are many chiral agents available for discriminating enantiomers which mainly target specific functional groups. In this study, we have explored a strategy involving ternary complexation to investigate chiral discrimination of different kind of functional groups by NMR spectroscopy. The proposed protocol was employed for the enantiodiscrimination of molecules containing functional groups, such as amino alcohols, secondary alcohols, cyanohydrins, oxazolidones, diols, thiones and epoxides, using a phosphorous based three component mixture. The simple mixing and shaking of enantiopure 1,1’-binaphthyl-2,2’-diyl hydrogenphosphate (BNPA), 4-(dimethylamino)pyridine (DMAP) and a chiral analyte in the solvent CDCl3 served as a chiral solvating agent and resulted in well-dispersed peaks for each enantiomer in the 1H NMR spectrum. Discrimination was achieved not only for the proton at the chiral center but also for multiple proton sites. The J-resolved technique was used for alleviating the spectral complexity pattern to accurately measure the chemical shift difference. The devised approach also permitted the precise measurement of the enantiomeric excess (ee). Chapter 3: Simultaneous discrimination of secondary alcohols and carboxylic acids In this chapter, I describe two novel ternary ion-pair complexes, which serve as chiral solvating agents (CSA), for enantio discrimination of secondary alcohols and carboxylic acids. The superiority of CSA over other auxiliaries arises due to the formation of diastereomeric complexes through non-covalent interactions with the analyte. By exploiting the acid-base interaction strategy and employing DMAP, which further enhanced the hydrogen bonding efficiency the discrimination for both carboxylic acids and secondary alcohols were achieved. The protocol for discrimination of secondary alcohols is designed by using one equivalent mixture each of enantiopure mandelic acid, 4-dimethylaminopyridine (DMAP) and a chiral alcohol. For discrimination of carboxylic acids, the ternary complex is obtained by one equivalent mixture each of enantiopure chiral alcohol, DMAP, and a carboxylic acid. Furthermore, the formation of the complex was supported by calculating the energy-minimized structure of the proposed complex by density functional theory (DFT). The designed protocols also permit accurate measurement of the enantiomeric composition. Chapter 4: Enhanced potency of nanoparticle-antimicrobial peptide conjugates Antibiotic resistance is emerging as the new global health problem. Due to the blatant misuse and overuse of these drugs has resulted in the bacteria becoming resistant to a wide range of antibiotics. Researchers have found an alternative of current antibiotics which are a group of peptides known as antimicrobial peptides (AMP). But using these molecules as drug is rather costly due to high synthesis cost. Further the antibacterial activity of silver nanoparticle is well established. However, due to its toxic nature after, it cannot be used in high concentration. The conjugation of nanoparticles with antimicrobial peptides is emerging as a promising route to achieve superior anti-microbial activity. However, the nature of peptide-nanoparticle interactions in these systems remains unclear. This study describes the interactions of antimicrobial peptide with silver nanoparticles by NMR spectroscopy in conjunction with other biophysical techniques to completely understand the underlying mechanism of interaction between nanoparticles and peptide. It reveals that the conjugation process involves dynamic interaction between the nanoparticle and the peptide. This study also confirms the enhanced antibacterial efficiency of the nano-conjugate towards bacterial killing compared to the nanoparticle or the peptide alone. Chapter 5: Mechanistic insights into the action of nano-conjugates It is well established that antimicrobial peptides act as pore-formers to rupture the bacterial cells. This chapter is focused on studying the mechanism of action of the nano-conjugate with bacterial membrane mimic models. This study for the first time reveals the details of nanoconjugate membrane interaction at an atomic level. The pore formation mechanism and the enhanced efficiency of the nanoconjugate were explored using fluorescence spectroscopy, CD spectroscopy, and NMR spectroscopy. Structural changes of the peptide and the nanoparticle bound peptide have been captured which infers the propensity of the peptide to form a helical structure upon interacting with the membrane. The calculated structure of the peptide and nanoparticle bound peptide remains almost identical in presence of the membrane mimic environment. In the case of the nanoconjugate, the increase in local positive charge concentration makes the system to penetrate the bacterial membrane faster which further allows the nanoparticle to access the intercellular organelles easily. This dual mode of mechanism thus makes this nano-conjugate a promising antibacterial agent towards multi drug resistant bacteria. In summary, the thesis has focused on the studies of weak intermolecular interactions in different chemical and biological systems using NMR spectroscopy. It is demonstrated that in certain chemical systems, such interactions can be exploited to discriminate enantiomers and determine the enantiopurity of compounds by NMR. In the case of biomolecules, such weak interactions exist when protein or peptides interact with nanoparticles. Using silver nanoparticles, it is shown that such interactions result in a stable conjugate system. NMR spectroscopy provides valuable insights into the structure and dynamics of the system. Further, by using anti-microbial peptides conjugated with silver nanoparticles, new superior antibacterial agents can be developed.