STUDIES OF INTERACTION OF SMALL MOLECULES WITH WATER CONDENSED MEDIA<br /><br /> The present work reports experimental and theoretical studies of the intermolecular interactions in condensed water media. The chemical objects comprise pristine ice and polar organic substances: acetone, acetaldehyde, methanol and chloroform and bi-component water-organic deposits. The experimental part of the studies includes the Fourier Transform Infrared Reflection Absorption spectral (FTIR RAS) examination of the processes of film growth by vapor deposition on cold metal substrate and subsequent annealing. The theoretical studies include <em>ab initio</em> (<em>MP2</em>) and semi-empirical (<em>B3LYP</em>) calculations on the small water and water-organic clusters and classical molecular dynamics simulations of the adsorption of inert guests (Xe/Rn) on the ice surface. The FTIR RA spectral studies reveal that depending on the deposition conditions condensed water media exist in two principal structural forms: noncrystalline and polycrystalline. The former is characterized by porous structure while the latter exists as a non-porous medium with smooth external interface. On annealing, characteristic spectral changes indicate on a rapid crystallization occurring at a certain temperature range. The initial adsorption of organic molecules is accompanied by the hydrogen-bonded coordination between the functional group of organic species and non-coordinated hydroxyl group of the ice surface, the topology of which depends on the electronic properties of the functional group. The computational studies of small water-organic clusters reveal, in particular, two major coordination minima for carbonyl group: a single hydrogen-bonded in-plane complex and a double hydrogen-bonded in-plane complex. The classical molecular dynamics of Xe/Rn species on the ice interface is consistent with two distinctly different surface adsorption sites: one that delocalized over the entire surface and one that confined to small opening in the top ice layer, disrupted by the thermal molecular motion. The penetration barrier is associated with van der Walls repulsion of guest species from the ordered water hexagonal arrangement. A thermo-disruption of latter leads to a rapid diffusion of guest species inside ice medium.

Ultra-violet and visible light induced processes in small organic molecules play very important roles in many fields, e.g., environmental sciences, biology, material development, chemistry, astrophysics and many others. Thus it is of great importance to better understand the mechanisms behind these processes. To achieve this, a bottom-up approach is most effective, where the photo-induced dynamics occurring in the simplest organic molecule (ethylene) are used as a starting point. Simple substituents and functional groups are added in a controlled manner to ethylene, and changes in the dynamics are investigated as a function of these modifications. In this manner, the dynamics occurring in more complex systems can be explored from a known base. In this thesis, the excited state dynamics of small organic molecules are studied by a combination of time-resolved photoelectron spectroscopy and various computational methods in order to determine the basic rules necessary to help understand and predict the dynamics of photo-induced processes. The dynamics occurring in ethylene involve a double bond torsion on the ππ* excited state, followed by the decay to the ground state coupled with pyramidalization and hydrogen migration. Several different routes of chemical modification are used as the basis to probe these dynamics as the molecular complexity is increased. (i) When ethylene is modified by the addition of an alkoxyl group (-OCnH2n+1), a new bond cleavage reaction is observed on the πσ* state. When modified by a cyano (-CN) group, a significant change in the carbon atom involved in pyramidalization is observed. (ii) When ethylene used to build up small cyclic polyenes, it is observed that the motifs of the ethylene dynamics persist, expressed as ring puckering and ring opening. (iii) In small heteroaromatic systems, i.e., an aromatic ring containing an ethylene-like sub-structure and one or two non-carbon atoms, the type of heteroatom (N: pyrrole, pyrazole O: furan) gives rise to different bond cleavage and ring puckering channels. Furthermore, adding an aldehyde group (-C=O) onto furan, as a way to lengthen the delocalised ring electron system, opens up additional reaction channels via a nπ* state. The results presented here are used to build up a more complete picture of the dynamics that occur in small molecular systems after they are excited by a visible or UV photon, and are used as a basis to motivate further investigations. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: Manuscript. Paper 6: Manuscript.</p>

STUDIES OF INTERACTION OF SMALL MOLECULES WITH WATER CONDENSED MEDIA<br /><br /> The present work reports experimental and theoretical studies of the intermolecular interactions in condensed water media. The chemical objects comprise pristine ice and polar organic substances: acetone, acetaldehyde, methanol and chloroform and bi-component water-organic deposits. The experimental part of the studies includes the Fourier Transform Infrared Reflection Absorption spectral (FTIR RAS) examination of the processes of film growth by vapor deposition on cold metal substrate and subsequent annealing. The theoretical studies include <em>ab initio</em> (<em>MP2</em>) and semi-empirical (<em>B3LYP</em>) calculations on the small water and water-organic clusters and classical molecular dynamics simulations of the adsorption of inert guests (Xe/Rn) on the ice surface. The FTIR RA spectral studies reveal that depending on the deposition conditions condensed water media exist in two principal structural forms: noncrystalline and polycrystalline. The former is characterized by porous structure while the latter exists as a non-porous medium with smooth external interface. On annealing, characteristic spectral changes indicate on a rapid crystallization occurring at a certain temperature range. The initial adsorption of organic molecules is accompanied by the hydrogen-bonded coordination between the functional group of organic species and non-coordinated hydroxyl group of the ice surface, the topology of which depends on the electronic properties of the functional group. The computational studies of small water-organic clusters reveal, in particular, two major coordination minima for carbonyl group: a single hydrogen-bonded in-plane complex and a double hydrogen-bonded in-plane complex. The classical molecular dynamics of Xe/Rn species on the ice interface is consistent with two distinctly different surface adsorption sites: one that delocalized over the entire surface and one that confined to small opening in the top ice layer, disrupted by the thermal molecular motion. The penetration barrier is associated with van der Walls repulsion of guest species from the ordered water hexagonal arrangement. A thermo-disruption of latter leads to a rapid diffusion of guest species inside ice medium.

In der vorliegenden Arbeit wurde das hochgeordnete Wachstum von großen organischen Molekülen auf kristallinen Substraten mit Hilfe der Quaterrylenderivate QT, QTCDI und QTCMI untersucht. Um derartige Schichten herstellen und charakterisieren zu können, wurde eine Organische Molekularstrahlepitaxy (OMBE)-Anlage aufgebaut. Allerdings stellt OMBE bisher nur ein Standardverfahren für die Präparation hochgeordneter Schichten bestehend aus kleineren Molekülen dar. Im Zusammenhang mit größeren Molekülen ergibt sich die Frage, ob auf Grund der höheren Sublimationstemperatur diese unzersetzt aufgedampft werden können. Optische Spektroskopieexperimente haben gezeigt, daß dies im Fall von QT möglich ist. Andererseits beginnt die Zersetzung von QTCDI bereits unterhalb seiner Sublimationstemperatur, wobei als eines der Produkte QTCMI entsteht. Ein wesentliches Anliegen dieser Arbeit bestand darin, die Frage zu klären, inwieweit diese großen Aromate epitaktisch auf anorganischen als auch organischen Substraten aufwachsen. Organisch-anorganische Schichtsysteme wurden durch Aufdampfen der Quaterrylenderivate auf einkristalline, rekonstruierte Goldoberflächen erzeugt und anschließend mit LEED und STM charakterisiert. Trotz der eingeschränkten thermischen Stabilität von QTCDI konnten sowohl hochgeordnete QT als auch QTCDI Monolagen auf Au(111) hergestellt werden, die jeweils aus flachliegenden Molekülen bestehen. Im Falle von QTCDI konnte dieses Resultat durch eine Optimierung der Probenherstellung erreicht werden. Im Unterschied zur Anordnung der QT Moleküle in Reihen, bilden die QTCDI Moleküle eine dazu deutlich verschiedene brickwall Struktur, die durch die Bildung von Wasserstoffbrückenbindungen zwischen den Randgruppen der QTCDI Moleküle erklärt werden kann. In ähnlicher Weise zeigt sich der Einfluß der Substituenten auf die Anordnung der Moleküle in der Schicht an den gefunden QTCMI Strukturen. Im Unterschied zu QTCDI Monolagen auf Au(111), konnten keine reinen QTCMI Proben erzeugt werden. Die Ursache dafür ist, daß QTCMI zwar in der QTCDI Knudsenzelle angereichert werden kann, aber beide Moleküle ähnliche Verdampfungstemperaturen besitzen. Selbst die Präparation einer reinen QTCMI Probe nach vollständiger Umsetzung aller QTCDI Moleküle in der Knudsenzelle erscheint schwierig, da bei diesen Temperaturen auch die Zersetzung der QTCMI Moleküle stattfindet. Des weiteren wurden QT Monolagen auf Au(100) Substraten hergestellt. Die QT Moleküle besitzen auf dieser Oberfläche dieselbe Anordnung wie auf Au(111). Auf beiden Oberflächen wurden nur bestimmte Domänenwinkel beobachtet, die die Ausrichtung der Moleküldomänen im Bezug zum Substrat beschreiben. Da die rekonstruierten Au(100) Oberfläche typischerweise nur eine Phase je Terrasse ausbildet, entsteht eine ausgedehnte QT Domäne bereits durch eine einzige Adsorbatstruktur. Andererseits erfordert das homogene Wachstum einer ausgedehnten QT Domäne auf verschiedenen Rekonstruktionsdomänen der Au(111) Oberfläche die Existenz der drei beobachteten Adsorbatstrukturen, die sich durch unterschiedliche Domänenwinkel auszeichnen. Weiterhin wurden Anzeichen dafür gefunden, daß die rekonstruierten Au(111) und Au(100) Oberflächen durch die Adsorption von QT Molekülen verändert werden. Während dieser Effekt im Fall der Au(111) Oberfläche auch bei anderen organischen Molekülen beobachtet wurde, ist unseres Wissens nach in der Literatur eine Veränderung der Au(100) Rekonstruktion in Folge des Aufdampfens einer organischen Molekülschicht bisher nicht beschrieben worden. Darüber hinaus können alle beobachteten Adsorbatstrukturen der Quaterrylenderivate auf Au(111) und Au(100) im Rahmen des point-on-line Modells erklärt werden. Das Wachstum der zweiten Monolage QT auf Au(111) wurde als Beispiel für organisch-organische Homoepitaxy untersucht. Die Moleküle der zweiten QT Monolage bilden wiederum Reihen, die entlang der QT Reihen der ersten Monolage wachsen. Als unmittelbare Folge existiert nur eine mögliche Domänenorientierung im Bezug zur ersten Monolage QT. Im Unterschied zu den ausschließlich flachliegenden Molekülen der ersten Monolage QT wurden in der zweiten Monolage alternierend stehende und liegende Moleküle beobachtet. Die resultierende Struktur ähnelt dabei der QT Kristallstruktur. Diese Resultate zeigen, daß die Au(111) Oberfläche einen vergleichsweise starken Einfluß auf die Struktur der ersten QT Monolage hat, während sie sich deutlich weniger stark auf die Struktur der zweiten QT Monolage auswirkt. Einen weiteren Aspekt der vorliegenden Arbeit stellen organisch-organische Heterostrukturen bestehend aus QT-HBC Schichten auf Au(111) dar. Im Zusammenhang mit der Untersuchung dieser Schichten sollte geklärt werden, ob der kürzlich gefundene Epitaxytyp line-on-line das Wachstum organisch-organischer Heterostrukturen generell beschreiben kann. Im Gegensatz zu typischen STM Bildern von organisch-organischen Heterostrukturen aus der Literatur, konnten hier Bilder aufgezeichnet werden, in der beide Molekülsorten deutlich voneinander unterschieden werden können. Dabei wurde eine QT/HBC Heterostruktur gefunden, bei der flachliegende QT Moleküle Reihen bilden. Im Unterschied zu QT auf Au(111) sind diese Reihen nicht dicht aneinander gepackt. Diese Beobachtung deutet darauf hin, daß die QT Struktur durch ein energetisch günstiges Packen der QT Moleküle auf den HBC Molekülen bestimmt wird. Darüber hinaus wurden zwei weitere Adsorbatstrukturen mit deutlich verschiedenen Gitterparametern gefunden. Hochaufgelöste STM Bilder legen nahe, daß diese beiden Strukturen alternierend aus stehenden und liegenden Moleküle bestehen. Die Experimente liefern Anzeichen dafür, daß die jeweilige Anordnung der QT Moleküle in der Schicht von der Dicke der darunterliegen HBC Schicht bestimmt wird. Demnach liegen die QT Moleküle auf einer Monolage HBC infolge der stärkeren Wechselwirkung zur Au(111) Oberfläche flach, während die bei dickeren HBC Schichten schwächere Wechselwirkung mit dem Gold eine Struktur aus stehenden und liegenden Molekülen ähnlich der Kristallstruktur zur Folge hat.

The current thesis presents fundamental studies of phthalocyanines (Pcs), a group of organic macro-cycle molecules. The use of phthalocyanine molecular films in devices with a variety of possible technological applications has been the reason of the many studies dedicated to such molecules during the last decades. Core and valence photoelectron spectroscopies (PES), X-ray absorption spectroscopy (XAS) and scanning tunneling microscopy (STM) techniques are used to study phthalocyanine molecules in gas phase and adsorbed on gold (111) and silicon Si(100)-2x1 substrates. Density functional theory (DFT) is used to obtain further insights in the electronic structure of the phthalocyanines. The aim of our studies is to get a deeper understanding into the molecule-molecule and molecule-substrate interactions, a fundamental requirement for improving the devices based on such molecular materials. Gas phase PES and XAS studies and single molecule DFT calculations are performed on the valence band (VB) of iron phthalocyanine (FePc), manganese phthalocyanine (MnPc) and metal-free phthalocyanine (H2Pc). The VB simulations have shown how the metal atom of the Pc influences the inner valence states of the molecules. The HOMO of the H2Pc and FePc is formed by mostly C2p states, whereas the HOMO of MnPc has mainly Mn3d character. PES studies of H2Pc on Au(111) have revealed the influence of the surface on the adsorption of the monolayer. XAS studies indicate formation of ordered monolayer with the Pc ligands parallel to the surface and the change of the molecular tilt angle with increasing thicknesses. For LuPc2 adsorbed on Au(111), STM study demonstrates a formation of bilayer instead of a monolayer. A comparison between the results of LuPc2 adsorbed on pristine or passivated Si(100)-2x1 confirmes the different reactivities of these surfaces: LuPc2 retains many molecular-like characters, when adsorbed on the innert passivated Si. Instead, on the more reactive pristine Si surface, the spectroscopic results have indicated a more significant interaction, possible hybridization and charge redistribution between the molecules and the surface. Moreover, STM images show a modification of the geometrical shape of the molecules, which are proposed to adsorb in two different geometries on the pristine Si surface.

La physique des surfaces et nanosciences est une discipline qui permet la conception d’une diversité de matériaux innovants pour mieux répondre aux besoins de la technologie actuelle. Dans ce contexte, nous nous sommes intéressés à caractériser les propriétés de différentes structures 2D élaborées sur des substrats d’argent en combinant différentes techniques d'analyses de surface.D'une part nous avons étudié des films 2D auto-assemblés à base de phtalocyanine de cobalt adsorbées sur Ag(100). Au régime de la monocouche, deux phases ont été essentiellement observées : la (5x5) et la (7x7). La spectroscopie de pertes d'énergie nous a permis de mettre en évidence deux mécanismes de transfert de charge métal/molécule différents en raison des sites d'adsorption différents.D'autre part, nous avons synthétisé, par évaporation d'atomes de silicium sur de l'Ag(111), du silicene en monocouche et multicouche. Ainsi nous avons entrepris des mesures dans le but de comprendre les propriétés structurales du silicene en multicouche. Pour cela nous avons engagé des mesures par spectroscopie de photoémission et diffraction de photoélectrons, et comparé nos données avec des simulations réalisées dans le cadre la diffusion multiple. Plusieurs hypothèses concernant la nature de ce matériau ont pu être testées. Par ailleurs nous avons étudié la fonctionnalisation du silicene par hydrogénation et adsorption de molécules de F4TCNQ. / Nanosciences and surface science are key elements in the conception of a diversity of innovative materials designed to better cope with the needs of current technology. Within this context, we have resolved to characterise the properties of different two-dimensional structures grown on silver substrates with the help of several complementary techniques of surface analysis.Firstly, we have studied auto-assembled 2D films of cobalt phthalocyanine on Ag(100) substrates. In situations with coverages close to the monolayer, two phases were observed: the (5x5) and the (7x7). The electron energy loss spectroscopy has allowed us to support the existence of two inequivalent charge transfer mechanisms between the substrate and the molecules due to differences in the adsoprtion sites. Secondly, we have synthesised both monolayer and multilayer silicene by evaporating silicon atoms on Ag(111) substrates. We have decided to delve into the characteristics of multilayer silicene as it’s less well-known than its monolayer counterpart. With this aim, the system has been subjected to experiments of photoemission spectroscopy and diffraction. In this manner, several hypotheses on the very nature of this material have been tested. On another matter also related to silicene, we have studied its functionalization by adsorption of F4TCNQ molecules and atomic hydrogen.

The thesis entitled “Benzimidazole based Novel Ligands for Specific Recognition of Duplex and G-Quadruplex DNA” deals with the design, synthesis and modeling of several benzimidazole based molecules and their interaction with duplex and G-quadruplex DNA structures. It also elucidates the inhibition effect of the ligands on the activity of Topoisomerase I and Telomerase. The work has been divided into six chapters. Chapter 1. DNA Interacting Small Organic Molecules: Target for Cancer Therapy This first chapter presents an overview on the various types of small molecules that interact with duplex and G-quadruplex structures of DNA or interfere with the activity of DNA targeted enzymes like topoisomerase and telomerase. The importance of such molecules as chemotherapeutic agents is highlighted. Chapter 2. DNA Recognition: Conformational Switching of Duplex DNA by Mg2+ ion Binding to Ligand Bis-benzimidazoles like Hoechst 33258 are well known ligands that bind to duplex DNA (ds-DNA) minor grooves. Here a series of dimeric bisbenzimidazole based ligands in which two Hoechst units are connected via oxyethylene based hydrophilic [Ho-4ox-Ho (1), Ho-3ox-Ho (2)] or via hydrophobic oligomethylene [Ho-(CH2)8-Ho (3)](Figure 1) spacers have been synthesized. The aim of this investigation is to examine the binding property of these dimers on the ds-DNA to explore whether the variation in the length of the spacer has any effect on DNA binding properties particularly in presence of selected metal ions. The changes of individual dimers in DNA binding efficiency was studied in detail by fluorescence, circular dichroism spectral titrations and thermal denaturation experiment with selected duplex DNA formed from appropriate oligonucleotides. We have also examined the changes that occur in geometry of the molecules from linear to hairpin motif in presence of Mg2+ ion. A large difference was observed in [ligand]/ [DNA] ratio and binding efficiency with ds-DNA upon change in the ligand geometry from linear to hairpin motif. The experimental results were then substantiated using docking and molecular dynamics simulations using a model ds-DNA scaffold. Both experimental and theoretical studies indicate that the DNA binding is highly dependent on the spacer type and length between the two monomeric Hoechst units. The spacer length actually helps to achieve shape complimentarity with the double-helical DNA axis. Figure1: Chemical structures of the dimeric ligands Ho-4ox-Ho, Ho-3ox-Ho, Ho-(CH2)8-Ho and Hoechst 33258 (Ho) used in this study. Chapter 3. DNA Binding and Topoisomerase I Inhibiting Properties of New Benzimidazole Substituted Polypyridyl Ruthenium (II) Mixed-Ligand Complexes In this study, we have synthesized and fully characterized three new Ru(II) based polypyridyl and benzimidazole mixed complexes: (1) [Ru(bpy)2(PMI)], 2+ (2) [Ru(bpy)2(PBI)]2+ and (3) [Ru(bpy)2(PTI)]2+ (Figure 2) . The affinities of these complexes toward duplex DNA were investigated. In addition, the photocleavage reaction of DNA and topoisomerase I inhibition properties of these metal complexes were also studied. The DNA binding efficiency of individual complexes was studied in detail by absorbance, fluorescence spectral titrations and thermal denaturation experiment using natural calf-thymus DNA. Upon irradiation at 365 nm, all three Ru(II) complexes were found to promote the cleavage of plasmid DNA from negatively supercoiled to nicked circular and subsequently to linear DNA. The inhibition of topoisomerase I mediated by these Ru(II) complexes was also examined. These experiments demonstrate that each complex serves as an efficient inhibitor toward topoisomerase I and such inhibition activity is consistent with interference with the DNA religation step catalyzed by topoisomerase. Figure 2. Chemical structures of the metal complexes used in this present study. Chapter 4. Synthesis and Evaluation of a Novel Class of G-Quadruplex-Stabilizing small molecules based on the 1,3-Phenylene-bis (piperazinyl benzimidazole) syatem Achieving stabilization of telomeric DNA in the G-quadruplex conformation by various organic compounds is an important goal for the medicinal chemists seeking to develop new anticancer agents. Several compounds are known to stabilize the G-quadruplexes. However, relatively few are known to induce their formation and/or alter the topology of the pre-formed G-quadruplex DNA. Herein, four compounds having the 1,3-phenylene-bis(piperazinyl benzimidazole) (Figure 3) unit as a basic skeleton have been synthesized, and their interactions with the 24-mer telomeric DNA sequences from Tetrahymena thermophilia d(T2G4)4 have been investigated using high-resolution techniques such as circular dichroism (CD) spectropolarimetry, CD melting, emission spectroscopy, and polyacrylamide gel electrophoresis. The data obtained, in the presence of one of three ions (Li+, Na+ or K+), indicate that all the new compounds have a high affinity for G-quadruplexDNA, and the strength of the binding with G-quadruplex depends on (i) phenyl ring substitution, (ii) the piperazinyl side chain, and (iii) the type of monovalent cation present in the buffer. Results further suggest that these compounds are able to abet the conversion of the intramolecular G-quadruplex DNA into parallel stranded intermolecular G-quadruplex DNA. Notably, these compounds are also capable of inducing and stabilizing the parallel stranded G-quadruplex DNA from randomly structured DNA in the absence of any stabilizing cation. The kinetics of the structural changes induced by these compounds could be followed by recording the changes in the CD signal as a function of time. Figure 3. Chemical structures of the ligands used in this study. Chapter 5A. The Spacer Segment in the Dimeric 1,3-phenylene-bis (piperazinyl benzimidazole) has a Dramatic Influence on the Binding and Stabilization of Human Telomeric G-Quadruplex DNA Ligand-induced stabilization of G-quadruplex structures formed by human telomeric DNA is an active area of basic and clinical research. The compounds which stabilize the G-quadruplex structures lead to suppression of telomerase activity. Herein, we present the interaction of a series of monomeric and dimeric compounds having 1,3-phenylene-bis(piperazinyl benzimidazole) (Figure 4) as basic pharmacophore unit with G-quadruplex DNA formed by human telomeric repeat d[(G3T2A)3G3]. These new compounds provide an excellent stabilization property to the pre-formed G-quadruplex DNA in the presence of one of three ions (100 mM Li+, Na+ or K+ ions). Also the G-quadruplex DNA formed in the presence of low concentrations of ligands in 100 mM K+, adopts a parallel-stranded conformation which attains an unusual thermal stability. The dimeric ligands having oxyethylene based spacer provide much higher stability to the pre-formed G-quadruplex DNA and the G-quadruplexes formed in presence of the dimeric compounds than the corresponding monomeric counterparts. Consistent with the above observation, the dimeric compounds exert significantly higher telomerase inhibition activity than the monomeric compounds. The ligand induced G-quadruplex DNA complexes were further investigated by computational molecular modeling, which provide useful information on their structure-activity relationship. Figure 4. Chemical structures of the monomeric and dimeric ligands used in this study. Chapter 5B. Role of Spacer in Symmetrical Gemini bisbenzimidazole based Ligands on the Binding and Stabilization of Dimeric G-Quadruplex DNA derived from Human Telomeric Repeats The design and development of anticancer agents that act via stabilization of the telomeric G-quadruplex DNA is an active area of research because of its importance in the negative regulation of telomerase activity. Several classes of G-quadruplex DNA binding ligands have been developed so far, but they mainly act on the DNA sequences which are capable of forming a single Gquadruplex unit. In the present work, we have developed few new dimeric (Gemini) bisbenzimidazole ligands (Figure 5), in which the spacer joining the two bisbenzimidazole units have been varied using oligooxyethylene units of different length. Herein we show the interaction of each of these ligands, with the G-quadruplex DNA, derived from oligodeoxynucleotides d(T2AG3)4 and d(T2AG3)8, which fold into a monomeric and dimeric (having two folded G-tetrad units) G-quadruplex DNA, respectively. We also present evidence that the G-quadruplex DNA structure formed by these sequences in K+ solution in presence of the ligands is parallel, with unusual stability, and the spacer length between the two bisbenzimidazole units has critical role on the G-quadruplex stability, particularly on the G-quadruplex structures formed by the 48-mer sequence. The computational aspects of the ligand-G-quadruplex DNA association have also been analyzed. Interestingly, the gemini ligand having longer spacer was highly potent in the inhibition of telomerase activity than the corresponding gemini ligands having shorter spacer or the monomeric ligand. Also, the dimeric ligands are more cytotoxic toward the cancer cells than normal cells. Figure 5. Chemical structures of the monomeric and gemini ligands used in this study. Chapter 6. Stabilization and Structural Alteration of G-Quadruplex DNA made from Human Telomeric Repeat Mediated by Novel Benzimidazole Derivatives based on Tröger’s Base Ligand-induced stabilization of G-quadruplex formation by the telomeric DNA single stranded 3'-overhang is a nice strategy to inhibit telomerase from catalyzing telomeric DNA synthesis and form capping telomeric ends. Herein we present the first report of the interactions of two novel bisbenzimidazoles (TBBz1 and TBBz2)(Figure 6) based on the Tröger’s base skeleton with the G-quadruplex DNA. These molecules stabilize the G-quadruplex DNA derived from a human telomeric sequence. Significantly strong binding affinity of these molecules to G-quadruplex DNA relative to duplex DNA was observed by CD spectroscopy, thermal denaturation and UV-vis titration studies. The above results obtained are in excellent agreement with the biological activity, measured in vitro using a modified TRAP assay. Additionally exposure of cancer cells to these compounds showed a remarkable decrease in the population growth. Also, it has been observed that the ligands are selectively more cytotoxic toward the cancerous cells than the corresponding noncancerous cells. To understand further, the ligand-G-quadruplex DNA complexes were investigated by computational molecular modeling. This provided additional insights on the structure activity relationship. Computational studies suggest that the adaptive scaffold not only allows these ligands to occupy the G-quartet but also binds with the grooves of the G-quadruplex DNA. Figure 6. Chemical structures of the ligands, TBBz1 and TBBz2 used in this study, (For structural formula pl see the abstact.pdf file.)

Understanding the electronic structure and dynamics of cyclic organic molecules is becoming increasingly the subject of investigations from different perspectives due to their unique chemical and physical properties. Since they are largely involved in the biochemistry of living organisms, studies on this class of compounds are also valuable to understand biologically relevant complex systems. Compared to other techniques, high-order harmonic generation (HHG) has been increasingly considered as a powerful spectroscopic tool with Angstrom spatial and attosecond temporal resolutions. This thesis demonstrates that high-order harmonic spectroscopy is capable of providing structural and dynamical information on the electronic systems of representative cyclic organic molecules comprising randomly oriented five-membered or six-membered rings. The first part of this thesis shows that the HHG from these molecules is sensitive to their aromatic character, which results from the de-localized pi electrons, and can potentially be a useful qualitative measure of aromaticity. We show that the advantage of utilizing HHG in this direction stems from the result that only pi molecular orbitals, associated with aromatcity, are responsible for the HHG emission in aromatic systems. The capability of HHG to distinguish cyclic isomers is demonstrated in the case of xylene molecules. Supported by numerical calculations, differences in the isomers are attributed to both tunnel ionization and photorecombination, the first and last steps of HHG. These results enable further HHG-based time-resolved studies of the dynamics associated with isomeric effects that these molecules exhibit. The present work also challenges the well-established prediction that strong field ionization from a molecular orbital is suppressed along nodal planes, where the electron density is zero. In fact, our study shows that considerable tunnel ionization in some cyclic molecules can occur near or along nodal planes. This unusual ionization is reported to have its signature on the quantitative and qualitative dependence of harmonic yield on laser ellipticity. The high symmetry displayed by the cyclic molecule, 1,4 cyclohexadiene, is shown to leave its imprints on the HHG in the form of structural interferences even if the target is randomly oriented. Two-color HHG from this molecule also indicates that hole dynamics could be involved in the generation process. A general study on high harmonic spectroscopy of the Cooper minimum in molecules is also reported. The presence of this minimum could affect the interpretation of harmonics spectra in any molecule containing S or Cl atoms. The molecular environment is shown to influence the position of this spectral modulation.

Dans cette thèse, la formation de monocouches auto-assemblées de différentes molécules de chalcogénure et de molécules p-conjuguées planaire et leurs caractéristiques structurelles et électroniques ont été systématiquement étudiées principalement par spectroscopie photoélectronique à rayons X effectuée utilisant la lumière synchrotron, microscopie à effet tunnel à balayage et diffraction d'électrons à faible énergie. Une étude de la formation de structures hybrides organiques-inorganiques auto-assemblées a été réalisée par assemblage couche par couche d'un dithiol sur ZnO (0001) avec dépôt de métal intermédiaire. De plus en complément de l'étude des molécules comportant un atome de chalcogènure, les caractéristiques d'adsorption du sélénium et du soufre ont été étudiées. La spectroscopie XPS à haute résolution et la spectroscopie de structure fine d’absorption au seuil d’excitation (NEXAFS) ont permis d'étudier les caractéristiques des monocouches auto-assemblées du sélénure de benzène et du sélénophène sur Cu (100) et dihexyldiselénure sur Ni (111) et Pd (111) et ont montré en particulier l’existence de processus de rupture de liaison Se-C ainsi que l’existence de différents sites d'adsorption de molécules. Ces conclusions ont été soutenues par l'étude de l'adsorption atomique du sélénium, qui montre également l'existence de différents sites d'adsorption pour le Se atomique avec différents environnements chimiques. Ces conclusions sont principalement basées sur une étude XPS haute résolution des spectres caractéristiques Se3d, Se3p, du spectre de bande de valence et de l'imagerie LEED. La formation de monocouche de 5,5-bis (mercaptéthyl) -2,20-bipyridine (BPD) avec terminaison SH libre sur ZnO(0001) a été démontrée, permettant le greffage ultérieur d'Ag et Ni et de l’ assemblage d’une autre couche de BPD sur cette couche de métal-dithiol. Les changements dans les propriétés électroniques ont été déterminés à partir des spectres de la bande de valence. La molécule π-conjuguée, NTCDA, a été déposée sur différentes surfaces métalliques et sa morphologie structurelle et ses propriétés chimiques par rapport à la surface métallique ont été étudiées. Les molécules NTCDA affichent une structure « couchée » avec deux domaines différents sur Ag (110) et Cu (100) mais trois domaines sur la surface de Cu (111). Par rapport à celui sur la surface inerte de Au, une forte interaction entre les molécules et les substrats de Cu, Ag existe et joue un rôle important dans la détermination de l'orientation et de l'état de liaison des films organiques. / In this thesis, the formation of self-assembled monolayers of different chalcogenide molecules and planer π-conjugated molecules and their electronic and structural characteristics were systematically studied mainly by synchrotron based X-ray photoelectron spectroscopy, scanning tunneling microscopy and low energy electron diffraction. A study of formation of hybrid organic-inorganic self assembled structure was performed by layer by layer assembly of a dithiol on ZnO(0001) with intermediate metal deposition. Additionally as a complement to the study of chalcogen head group molecules the adsorption characteristics of selenium and sulfur were investigated. The high resolution XPS and near edge absorption fine structure spectroscopy allowed to investigate the characteristics of self-assembled monolayers of benzene selenide and selenophene on Cu (100), and dihexyldiselenide on Ni(111) and Pd(111) and showed in particular the existence of Se-C bond breaking processes and existence of different adsorption sites of molecules. These conclusions were supported by the study of atomic selenium adsorption, which also shows existence different adsorption sites for the atomic Se with different chemical environments. These conclusions are mainly based on high resolution XPS study of characteristic Se3d, Se3p spectra, valance band spectrum and LEED imaging. The formation of a 5,5- bis (mercaptomethyl)-2,20- bipyridine (BPD) with SH termination on ZnO(0001) was demonstrated allowing subsequent grafting of Ag and Ni and further assembly of BPD on this metal-dithiol layer. The changes in electronic properties were determined from valence band spectra. The large π-conjugated molecule, NTCDA, was deposited on different metal surfaces and its structure morphology and chemical properties with respect to the metal surface was investigated. The NTCDA molecules displays a lying down structure with two different domains on Ag (110) and Cu(100) but three domain on Cu(111) surface. Compared with the one on the inert Au surface, a strong interface interaction between the molecules and Cu, Ag substrates plays an important role in determining the orientation and bonding state of the organic films.

This dissertation reports on the investigation of two-photon absorption (2PA) in a series of fluorenyl molecules. Several current and emerging technologies exploit this optical nonlinearity including two-photon fluorescence imaging, three-dimensional microfabrication, site-specific photodynamic cancer therapy and biological caging studies. The two key features of this nonlinearity which make it an ideal candidate for the above applications are its quadratic dependence on the incident irradiance and the improved penetration into absorbing media that it affords. As a consequence of the burgeoning field which exploits 2PA, it is a goal to find materials that exhibit strong two-photon absorbing capabilities. Organic materials are promising candidates for 2PA applications because their material properties can be tailored through molecular engineering thereby facilitating optimization of their nonlinear optical properties. Fluorene derivatives are particularly interesting since they possess high photochemical stability for organic molecules and are generally strongly fluorescent. By systematically altering the structural properties in a series of fluorenyl molecules, we have determined how these changes affect their two-photon absorbing capabilities. This was accomplished through characterization of both the strength and location of their 2PA spectra. In order to ensure the validity of these results, three separate nonlinear characterization techniques were employed: two-photon fluorescence spectroscopy, white-light continuum pump-probe spectroscopy, and the Z-scan technique. In addition, full linear spectroscopic characterization was performed on these molecules along with supplementary quantum chemical calculations to obtain certain molecular properties that might impact the nonlinearity. Different designs in chemical architecture allowed investigation of the effects of symmetry, solvism, donor-acceptor strengths, conjugation length, and multi-branched geometries on the two-photon absorbing properties of these molecules. In addition, the means to enhance 2PA via intermediate state resonances was investigated. To provide plausible explanations for the experimentally observed trends, a conceptually simple three level model was employed. The subsequent correlations found between chemical structure and the linear and nonlinear optical properties of these molecules provided definitive conclusions on how to properly optimize their two-photon absorbing capabilities. The resulting large nonlinearities found in these molecules have already shown promise in a variety of the aforementioned applications.