Unraveling surface enabled phenomena in low-dimensional molecular systems

This thesis focuses on the investigation of on-surface molecular architectures which exhibit extraordinary magnetic and quantum properties originating from the reduced dimensionality at surfaces. Many different combinations of spin-bearing square planar molecules and substrates were used and probed by local techniques as well as by spatial averaging techniques. Probing low-dimensional molecular magnetism by combination of several complementary techniques provides a more complete insight into the subtle interplay of the interactions involved at the surfaces. The comprehensive study of magnetism of Cr-phthalocyanine molecules supported on several different ferromagnetic and non-magnetic substrates demonstrated how the spin state of such molecules depends on the interaction with the substrate. Also in my work I have shown that the relative orientation of the molecule’s and the substrate’s easy magnetization axes is of great importance, even for molecules which are paramagnetic in the bulk. This is further supported by the example of interactions of Cr-based adsorbates with the Au(111) substrate where, for example, a very strong anisotropy of the Cr magnetic moment is observed. At the same time, the exchange coupling interactions with bare ferromagnetic substrates, Co and Ni are different in both the intensity and sign. These observations indicate that a refinement of the current models describing interface magnetism is needed to understand the peculiar magnetic coupling in these systems. Study of various phthalocyanine molecules on Pb(111) demonstrate the importance of employment of X-ray based techniques to complement the local probe investigations of these spin systems coupled to a superconductor. Although such experiments can drive a system out of the superconductive phase by the presence of a magnetic field, it was shown that some magnetic properties of these molecules won’t depend greatly on whether the system is or is not in the superconducting state. This fact is making X-ray based investigations even more important. The emergence of interesting magnetic phenomena through intra- and inter-molecular interactions was addressed next. Pilot experiments performed on triply-fused bisporphyrin molecules opened up the field for a new class of molecules containing two spin centers that can be exchanged providing a plethora of possibilities for tuning the molecule’s magnetic properties. Following up on our recent observation of long range 2D ferrimagnetic ordering in heteromolecular checkerboard assemblies of Fe and Mn phthalocyanine molecules supported on Au(111), we performed the experiments with similar binary 2D systems to further glimpse into the role of 3d orbitals, their symmetries and filling in maintaining long range ordering. It was shown that depending on the configuration and filling of their 3d orbitals the metallo-phthalocyanine molecules will interact by the RKKY interaction or not. In addition, I reported on a significant asymmetry in the mixing of hetero molecular layers that is occurring due to the pinning of one of the molecular types to the surface. Surprisingly this process modifies the layer structure of multilayers and therefore needs to be taken into account for on-surface metalation reactions or for the design of spintronic devices. Further on, different ways of modification of magnetic properties have been investigated. We reported on how spin states of various phthalocyanine molecules can be altered upon exposure to molecular and atomic hydrogen. In the former case, this process is completely reversible, while in the latter case it leads to irreversible changes of both the spin state of the metal center and of the molecule. Also, the ability to induce a Co surface functionalization with both N and Cl adlayers is demonstrated. Here, X-ray Photoelectron Diffraction has been employed to precisely determine interatomic distances in the created functionalized surfaces. In the last part the importance of development of new preparation/characterization techniques is demonstrated. It is shown how we successfully implemented the technique of deposition of large non-sublimable molecules into the UHV directly from solution, and how we have adapted a detector that is commonly used in time-of-flight mass spectrometry for acquiring fast, time-resolved XAS signal at SIM beamline of the SLS. In short, this thesis represents a collection of several pieces of a larger scientific puzzle grazing through several aspects of molecular magnetism

Application of Computational Methods for the Design of New Potential Therapeutic Agents

Computer-aided drug discovery (CADD) represents a very useful tool to search for potential drug candidates and plays a strategic role in the discovery of new potential therapeutic agents for both pharmaceutical companies and academic research groups. Nevertheless, the modelling of biological systems still represents a challenge for computational chemists, and, at present, a single computational method able to face such challenge is not available. Computational tools are therefore evolving in the direction of combining molecular-mechanic (MM), molecular dynamics (MD), and quantum-mechanical (QM) approaches in order to achieve an overall better simulation of the actual molecular behaviour. In addition, many sampling methods have been developed and applied for the characterisation and comparison of the collective motions of protein structures related to the dynamics of proteins, protein folding and ligand-protein docking simulations. This prompted us, as computational medicinal chemists, to develop various CADD approaches, depending on the specific case under study, integrating theoretical and experimental data. In particular, the research activity carried out during the three years of my PhD led to: i) the development of three-dimensional (3-D) pharmacophore models for the analysis of 3-D structure-activity relationships (SARs) of bioactive compounds, ii) the identification of new molecular targets, iii) the simulation of large-scale protein conformational changes, iv) the simulation of protein/protein and ligand/protein interactions, and v) the design of new bioactive compounds. Computational studies were always performed in the frame of multi-disciplinary projects guided by a unique research strategy, which involved several international and national research groups, and were carried out by integrating and validating our computational studies with the experimental data coming from the other researchers involved in the various projects. The results obtained enabled to: i) identify a new class of anticancer agents against paclitaxel resistant cancer cells, ii) provide important information on the mechanism of action of cationic porphyrins, a novel class of proteasome conformational regulators with great potentiality as “lead” pharmacophores, and iii) optimise the cellular pharmacokinetic and pharmacodynamic properties of a new series of antimalarial agents. In addition, I spent a training period abroad of eight-months at the Institute of Research in Biomedicine (IRB) in Barcelona, under the supervision of prof. Modesto Orozco, during which I have had the opportunity to extend my computational background by learning and, then, performing metadynamic and MD simulations, investigating the open/close conformational transition of 20S human proteasome by molecular dynamics simulations

Application of Computational Methods for the Design of New Potential Therapeutic Agents

Computer-aided drug discovery (CADD) represents a very useful tool to search for potential drug candidates and plays a strategic role in the discovery of new potential therapeutic agents for both pharmaceutical companies and academic research groups. Nevertheless, the modelling of biological systems still represents a challenge for computational chemists, and, at present, a single computational method able to face such challenge is not available. Computational tools are therefore evolving in the direction of combining molecular-mechanic (MM), molecular dynamics (MD), and quantum-mechanical (QM) approaches in order to achieve an overall better simulation of the actual molecular behaviour. In addition, many sampling methods have been developed and applied for the characterisation and comparison of the collective motions of protein structures related to the dynamics of proteins, protein folding and ligand-protein docking simulations. This prompted us, as computational medicinal chemists, to develop various CADD approaches, depending on the specific case under study, integrating theoretical and experimental data. In particular, the research activity carried out during the three years of my PhD led to: i) the development of three-dimensional (3-D) pharmacophore models for the analysis of 3-D structure-activity relationships (SARs) of bioactive compounds, ii) the identification of new molecular targets, iii) the simulation of large-scale protein conformational changes, iv) the simulation of protein/protein and ligand/protein interactions, and v) the design of new bioactive compounds. Computational studies were always performed in the frame of multi-disciplinary projects guided by a unique research strategy, which involved several international and national research groups, and were carried out by integrating and validating our computational studies with the experimental data coming from the other researchers involved in the various projects. The results obtained enabled to: i) identify a new class of anticancer agents against paclitaxel resistant cancer cells, ii) provide important information on the mechanism of action of cationic porphyrins, a novel class of proteasome conformational regulators with great potentiality as “lead” pharmacophores, and iii) optimise the cellular pharmacokinetic and pharmacodynamic properties of a new series of antimalarial agents. In addition, I spent a training period abroad of eight-months at the Institute of Research in Biomedicine (IRB) in Barcelona, under the supervision of prof. Modesto Orozco, during which I have had the opportunity to extend my computational background by learning and, then, performing metadynamic and MD simulations, investigating the open/close conformational transition of 20S human proteasome by molecular dynamics simulations

Investigations of Metal/Organic Interfaces and Metalation Reactions of Organic Semiconductors

Modern electronic devices are increasingly based on organic semiconductors. The performance of such devices crucially depends on the properties of the interface between the organic semiconductors and the metal contacts. Understanding the influence of the topology of the organic semiconductor’s conjugated pi-electron system on the interface interaction could greatly improve the device’s performance. Furthermore, the knowledge about reactions of heteroatomic organic semiconductors with metal atoms during electrode fabrication may lead to enhanced lifetimes of such devices. This cumulative dissertation comprises several publications and a number of so far unpublished results, addressing metal/organic interface interactions and metalation reactions of heteroatomic organic semiconductors. The properties of the interfaces are tailored by investigating the alternant aromatic molecules naphthalene and pyrene as well as the nonalternant aromatic molecules azulene and azupyrene on different metallic singlecrystal surfaces. Investigations by means of temperature-programmed desorption reveal stronger desorption energies for the non-alternant molecules on both Ag(111) and Cu(111). The biggest difference is observed on Cu(111), on which azulene and azupyrene are chemisorbed, whereas naphthalene and pyrene are physisorbed. The enhanced interface interaction of the non-alternant molecules is associated with the formation of surface dipoles that lead to stronger intermolecular repulsion between the adsorbed molecules. These results are supported by additional surface science methods, such as X-ray photoelectron spectroscopy or near-edge X-ray absorption fine structure spectroscopy, as well as density functional theory calculations conducted by group members and external collaboration partners. Detailed quantitative analysis of temperature-programmed desorption data of benzene on Cu(111) and Ag(111) yields experimental desorption energies that can be used as a benchmark for theoretical adsorption energies derived by density functional theory calculations. The interactions of metal/organic interfaces are compared with organic/inorganic interfaces in the case of pentacene and its fluorinated derivative perfluoropentacene on Au(111) as well as on bulk and two-dimensional MoS2 in a collaboration project. Organic semiconductors often interact weakly with inorganic surfaces, e.g., the thermal desorption of the first molecular layer is indistinguishable from multilayer desorption. No monolayer desorption peaks are observed as is mostly the case on metal surfaces. However, monolayer desorption of pentacene and perfluoropentacene on MoS2 occurs at significantly higher temperatures than the multilayer desorption. Detailed analysis reveals that the monolayers of both molecules are entropically stabilized. Codeposition of both molecules results in strong attractive intermolecular interactions on MoS2, while these interactions are weaker on Au(111). Metalation reactions of organic semiconductors with metal atoms, e.g., Co on tetraphenylporphyrin and Ca on alpha-sexithiophene, during interface preparation were investigated by means of hard X-ray photoelectron spectroscopy and temperature-programmed desorption mass spectrometry. The thickness of the reaction zone is changed by variation of experimental properties during interface formation. It is found that only the sample temperature during metal atom deposition and the metal atom flux in the case of Ca have an impact on the reaction depth, which is usually limited to few nanometers. In contrast to Co and Ca, Li atoms readily diffuse into the organic bulk and react with tetraphenylporphyrin over several tens of nanometers, forming dilithium tetraphenylporphyrin or monolithium monohydrogen tetraphenylporphyrin depending on the deposited Li amount. Furthermore, the transmetalation reaction of lead(II) tetraphenylporphyrin with Cu atoms on the Cu(111) surface was proven by temperature-programmed desorption. In addition, the Ullmann coupling reaction of bromo- and iodobenzene on Cu(111) was examined. While bromobenzene molecules desorb intact from the Cu(111) surface, iodobenzene molecules dissociate into iodine atoms and phenyl radicals. The latter form biphenyl that desorbs in three distinct desorption peaks at different temperatures. In a collaborative project, the oxidation state and electronic structure of Pb atoms in the newly synthesized Pb3F8 were studied by hard X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure spectroscopy giving evidence for the presence of Pb(II) and Pb(IV) species. The experimental results are complemented by constructional work to improve the temperatureprogrammed desorption setup. Moreover, two Igor Pro 8 scripts were written to quickly import data from different experimental setups and speed up the data treatment

Syntheses and DNA Interactions of Acridine and Phenothiazine Based Photosensitizers

Photosensitizing molecules and/or metal complexes that interact with DNA via intercalation and groove binding have potential applications as molecular structural probes, as footprinting reagents and in photodynamic therapeutics. To this regard, small molecules that bind to DNA and the energetics involved in these interactions, acridine-based therapeutics, photosensitization, photodynamic therapy, phenothiazine-mediated photosensitization, DNA photocleavage reaction mechanisms and photosensitizing metal complexes are introduced in Chapter I. Next, in Chapter II, the synthesis of a photonuclease consisting of a 3,6-acridinediamine chromophore attached to four metal-coordinating imidazole rings is described. The DNA photocleavage yields, emission quantum yields, and thermal denaturation studies by this acridine-imadazole conjugate in the presence of 16 metal salts are also reported. In Chapter III is the synthesis of a bisacridine covalently tethered to a copper(II)-binding pyridine linker. Additionally, DNA photocleavage studies as well as DNA binding affinity and binding mode(s) of this bisacridine incorporating the copper(II)-binding pyridine linker are examined. The syntheses, characterization, DNA photocleavage studies, DNA thermal denaturation, and viscometric measurements of three new phenothiazinium photosensitizers are described in Chapters IV and V. Collectively, markedly enhanced DNA photocleavage yields are observed in the presence of metals (Chapters II-III) or in comparison to a parent molecule, Chapters II and IV. DNA melting isotherms show higher levels of duplex stabilization with the acridines, specifically in the presence of several metals (Chapter II-III) as well as with the phenothiazine-based ligands (Chapters IV-V). Moreover, different DNA binding modes were observed depending on metal complexation (Chapter III) and nucleic acid structure (Chapter IV). Finally, Chapter VI describes a small project implemented as a National Science Foundation pedagogical laboratory exercise in which a non-invasive procedure for DNA isolation from human cheek cells was utilized with the polymerase chain reaction to amplify alleles encoding a single nucleotide polymorphism involved in normal human color vision

Ruthenium-catalyzed azide alkyne cycloaddition reaction: scope, mechanism and applications

The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry, and the construction of electronic devices. This Review discusses the mechanism, scope, and applications of the RuAAC reaction, covering the literature from the last 10 years

Synthesis of Self-Assembling Molecules for Functional Materials

The research carried out during these three years was developed as part of the MolArNet Project, supported by the European Commission, which aims at giving a first demonstration of molecular Quantum-dot Cellular Automata (QCA) elementary devices as a feasible approach to unconventional computation. Here we describe the design and synthesis of novel alkyl substituted guanosine-ferrocene derivatives, and their self-assembly at the solid/liquid interface on highly oriented pyrolitic graphite (HOPG). Supramolecular self-assembly of these derivatives has been accomplished in solutions by NMR and CD spectroscopy and on surface by STM and AFM techniques. We have shown that supramolecular structures formed by ferrocene-exposing guanosines in solutions and at surfaces can be tuned by introducing sterically demanding substituents, ranging from G-ribbons to G4 cation-free architectures. This self-assembly is governed by the formation of H-bonds between guanosines that dictates the spatial localization of ferrocenes, ultimately forming 1D conjugated arrays that may be employed as prototypes of supramolecular nanowires. In this thesis we also explored the possibility of using porphyrin derivatives carrying ferrocene residues directly connected to the porphin core, as alternative approach to QCA implementation. Preliminary electrochemical studies using cyclic voltammetry show that porphyrins can be used as a two/four dots cells. During the period at the University of Maryland, in the Prof. Jeffery Davis’ research group, I worked on the synthesis and characterization of specific dyes, containing azobenzene groups, in order to insert them in the guanosine hydrogels. These dyes are capable, in principle, to change their conformation in a reversible way, through an external light stimulus. Thus, it could be possible to obtain photoresponsive hydrophilic gels, able to break and reform themselves in a controlled manner

Computational study of Aromaticity in Porphyrinoid Systems and Photosensitizers from Chemical Bonding Descriptors

291 p.La presente tesis está dividida en dos bloques. El primer bloque se centra en una de las propiedadesafectadas por el error de deslocalización, la aromaticidad, presente en algunas aproximaciones delfuncional de la densidad. Se estudia el carácter aromático de sistemas una familia de porfirínas simples,una serie de anulenos y un anillo de seis porfirínas. También se discute el método computacionalapropiado para caracterizar la estructura electrónica de moléculas aromáticas medianas y grandes.Siguiendo la misma línea, en el segundo bloque de la tesis se han examinado diferentes familias defotosensibilizadores y catalizadores para diseñar un protocolo riguroso para el estudio de la estructuraelectrónica, la simulación de espectros UV-Vis y para el cálculo de potenciales redox. Losfotosensibilizadores son moléculas captadoras de luz que presentan excitaciones de transferencia decarga. La simulación de estas excitaciones está afectada también por las deficiencias de lasaproximaciones al funcional de la densidad