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This thesis deals with the synthesis of improved organic semiconductors, the detailed investigation of the molecular properties and the solid state arrangements revealed by single crystal X-ray diffraction and finally the development of structureperformance dependencies by measuring of the charge carrier mobilities of the derivatives in thin film transistors. The two main-goals of this thesis were achieved. Well soluble acene derivatives for spin-coated TFTs were obtained, showing charge carrier mobilities in the range of polymer p-type materials. Novel core-fluorinated perylene bisimide dyes were synthesized particularly and the use of electron deficient substituents lead to PBIs with outstanding air-stable mobilities in thin film transistors prepared by vacuum deposition techniques. The relationship between performance, air stability and solid state packing was elucidated in detail by single crystal X-ray diffraction analysis.
The present thesis demonstrates the potential of dipolar aggregation of merocyanine dyes as novel directional and specific supramolecular binding motif for the creation of more elaborate supramolecular architectures beyond simple dimers. Furthermore, the self-assembly studies into bis(merocyanine) nanorods gave new insights into the kinetics of morphogenesis in supramolecular aggregates.
The subject of this thesis is the synthesis and characterization of PBI-based fluorescent metallosupramolecular polymers and cyclic arrays. Terpyridine receptor functionalized PBIs of predesigned geometry have been used as building blocks to construct desired macromolecular structures through metal-ion-directed self-assembly. These metallosupramolecular architectures have been investigated by NMR, UV/Vis and fluorescence spectroscopy, mass spectrometry, and atomic force microscopy.
This work encompasses three parts. The first part provides a concise review of the most prominent metaheuristic concepts currently available and gives essential preliminaries together with definition of the combinatorial optimization problems. It substantiates the choice of the investigation direction and basis idea of the developed methods. In the second part the new nonlinear global optimization routines based on the TS strategy are described. The new approaches are the Gradient Tabu Search (GTS), the Gradient Only Tabu Search (GOTS), and the Tabu Search with Powell’s Algorithm (TSPA). In the last part of the work the GOTS is applied for such chemical optimization problems. The chapter provides a systematic approach how the variables are chosen and the adjustable parameters are set. As test cases the global minimum energy conformation of some amino acids, of two angiotensin converting enzyme (ACE) inhibitors, of 2-acetoxy-N,N,N-trimethylethanaminium, and of a HIV-1 protease inhibitor is determined.
This PhD thesis introduced several concepts for the construction of new supramolecular assem-blies in polar solvents. Although the building blocks differ in their binding mode and association strength they follow the same principle: one main driving force for the self-assembly in polar solutions in combination with one texturing force. The main self-assembly process is based on the mutual interaction of hydrogen-bond enforced ion pairs which deliver the association energy needed for stable, supramolecular structures even in polar solvents. The texturing force itself is represented by the linkers between the zwitterionic building blocks or parts of them. The different length and functionalization of the linkers have a tremendous influence on the mode of self-assembly leading to cyclic dimers, vesicles, layers or solid spheres. Hence, this principle is suitable for the construction of programmable monomers. Since the derivatisation of the main binding motive is rather simple it offers a great number of new and undoubtedly fascinating structures with potential applications in material and biomimetic science.
Artificial light-harvesting (LH) systems have been obtained by self-assembly of naphthalene diimide-functionalized zinc chlorin dyads and triad in nonpolar, aprotic solvents. UV-vis, CD, and steady-state emission spectroscopy as well as atomic force microscopy showed that rod-like structures are formed by excitonic interactions of zinc chlorin units, while the appended naphthalene diimide dyes do not aggregate at the periphery of the cylinders. In all cases, photoexcitation of the enveloping naphthalene diimides at 540 and 620 nm, respectively, was followed by highly efficient energy-transfer processes to the inner zinc chlorin backbone, as revealed by time-resolved fluorescence spectroscopy on the picosecond time-scale. As a consequence, the LH efficiencies of zinc chlorin rod aggregates were increased by up to 63%. The effective utilization of solar energy recommends these biomimetic systems for an application in electronic materials on the nanoscale.
The covalent linkage of the aryloxy-substituents through macrocyclisation was applied for the synthesis of perylene bisimide atropo-enantiomers. The synthesis of macrocyclic perylene bisimides was achieved by using a tetra(3-hydroxyphenoxy)-functionalized perylene bisimide with achiral 2,6-diisopropylphenyl as imide substituent through Williamson´s etherfication which could be realized for four different oligoethylene glycol bridging units. Two regioisomeric macrocycles, namely the diagonally bridged (1,7- and 6,12- linkage) and the laterally bridged (1,12- and 6,7-linkage) isomers, were obtained for each bridging unit. The structural assignment of the isolated regioisomeric macrocycles was unambiguously accomplished by X-ray analysis of two macrocycles and by 1H NMR spectroscopy for all isomers. The conformational influence of the aryloxy-substituents on the functional properties of this class of chromophores could be derived by comparison of the optical and electrochemical properties of all isolated macrocylces with those of an open-chained reference compound. It was shown that the aryloxy-substituents prefer a lateral conformation in solution. Furthermore, solvent dependent fluorescence studies indicated that a photoinduced electron transfer process is of importance for the fluorescence quenching of electron-rich aryloxy-substituted perylene bisimides. The resolution of the atropo-diastereomers of diagonally bridged macrocyclic perylene bisimides with chiral 2-(R)-octylamine as imide substituent and diethylene glycol bridging units could be accomplished by semi-preparative HPLC on a chiral column. The chiroptical properties of the isolated epimerically pure macrocycles were determined by CD spectroscopy. Based on the experimental CD spectra, the stereochemical assignment of the isolated epimers was accomplished by application of the excition chirality method and confirmed by quantum chemical calculation of the CD spectra. The synthetical concept was extended successfully to 1,7-diaryloxy-substituted perylene bisimides. The structure of the diagonally bridged macrocycle was unambiguously confirmed by X-ray analysis and NMR spectroscopy. The atropo-enantiomers of this macrocycle could be resolved by semi-preparative HPLC on a chiral column and the assignment of the absolute configuration was achieved by comparison of the CD spectra of the resolved enantiomers with those of epimerically pure bis(macrocycles) reported before. By comparison of the X-ray structures obtained for the racemic mixture as well as one enantiomer important information could be extracted for the formation of p-dimers of perylene bisimides. The dependence of the interconversion barrier on the bulkiness of the bay-substituents was investigated for four halogen-substituted perylene bisimides. The dynamic properties were investigated by temperature-dependent NMR spectroscopy and kinectic measurements using CD spectroscopy. By applying the concept of the “apparent overlap” a convincing linear relationship between the size of the substituents and the free enthalpy of activation could be derived. Furthermore, the resolution of the atropo-diastereomers or enantiomers of the tetrachloro and tetrabromo-substituted derivates was accomplished, whereupon especially the 1,6,7,12-tetrabromosubstituted perylene bisimide provided at room temperature stable enantiomers. Additionally, the derived structure-property relationship allows the design of conformationally stable perylene bisimide enantiomers by proper choice of the bay substituents. In order to utilize the reversibility of self-assembly for the quantitative formation of macrocyclic perylene bisimides, a tetrazinc porphyrin-functionalized perylene bisimide was synthesized. The self-assembly of the zinc porphyrin perylene bisimide bichromophoric building block and diazabicyclo-[2.2.2]-undecane into the desired 1:2 sandwich complex was investigated by UV/Vis and 1H NMR spectroscopy and the macrocyclic structure was unequivocally proven by diffusion-ordered NMR spectroscopy (DOSY NMR). Furthermore, the controlled deposition of these well-defined macrocycles on highly ordered pyrolitic graphite (HOPG) was demonstrated by atomic force microscopy (AFM) investigations. The alignment of a linear amino functionalised p-conjugated polymers upon addition of the bichromphoric tetrazinc porphyrin-perylene bisimide was investigated by UV/Vis spectroscopy and AFM measurement. The surface analysis by AFM investigations revealed that the bichromophoric system composed of perylene bisimide and zinc porphyrin is able to cross-link the linear p-conjugated polymer over a wide range of the graphite surface which provided a defined arrangement of three different functional p-systems.
Although known about and investigated since the late 1970’s, the picture of the basic principles governing inhibitor strengths and the structure-activity relationships of the cysteine protease inhibition mechanism is still very incomplete. Computational approaches can be a very useful tool for investigating such questions, as they allow the inspection of single, specific effects in isolation from all others, in a manner very difficult to achieve experimentally. The ab initio treatments of such large systems like proteins are still not feasible. However, there is a vast number of computational approaches capable of dealing with protein structures with reasonable accuracy. This work presents a summary of theoretical investigations into cysteine protease cathepsin B using a range of methods. We have concentrated on the investigation of cysteine protease inhibition by epoxide- and aziridine-based inhibitors in order to obtain better insight into these important topics. Various model systems are simulated by means of pure quantum mechanical methods and by hybrid (QM/MM) methods. Both approaches provide a static picture. Dynamical effects are then accounted for by additional molecular dynamics (MD) simulations, using both classical and QM/MM MD approaches. The quantum mechanical approach was used to study very small model systems consisting only of the electrophilic warhead of the inhibitor (both substitituted and not) and molecular moieties simulating a very simplified protein active site (methylthiolate instead of Cys29 and methylimidazolium instead of His199 residue) and solvent surroundings (two waters or two ammonium ions, in combination with a continuum solvent model). Although simple, such a system provides a good description of the most important interactions involved in the inhibition reaction. It also allows investigation of the influence of the properties of the electrophilic warhead on the reaction rate. Beside the properties of the electrophilic warhead, the protein and solvent environment is also an important factor in the irreversible deactivation of the enzyme active site by the inhibitor. The non-covalent interactions of the inhibitor with the oxyanion hole and other subsites of the enzyme, as well as its interaction with the solvent molecules, need to be explicitly taken into account in the calculations, because of their possible impact on the reaction profile. As molecular modeling methods allow the treatment of such large systems, but lack the possibility of describing covalent interactions, our method of choice was the combined quantum mechanics/molecular modeling approach. By splitting the system into a smaller part that undergoes the bond cleavage/formation process and must be treated quantum mechanically, and a larger part, comprised of the rest of the protein, which could be treated using force fields, we managed to simulate the system at the desired precision. Our investigations concentrated on the role of His199 in the inhibition mechanism as well as on the structure-reactivity relationships between cysteine protease and various inhibitors, yielding new insight into the kinetics, regio- and stereospecificity of the inhibition. In particular, our calculations provide the following insights: i.) an explanation for the regioselectivity of the reaction, and original insight into which interactions affect the stereoselectivity; ii.) a clear model which explains the known structure-activity relationships and connects these effects with the pH-dependency of the inhibition; iii.) our computations question the generally accepted two-step model by showing that substituent effects accelerate the irreversible step to such an extent that the achievement of an equilibrium in the first step is doubtful; iv.) by way of theoretical characterizations of aziridine models, the reasons for similarities and differences in the mode of action of epoxide- and aziridine-based inhibitors are elucidated; and finally, v.) combining our results with experimental knowledge will allow rational design of new inhibitors. To account for dynamical effects as well, molecular dynamics (MD) computations were also performed. In these calculations the potential energy was computed at the force field level. The results not only supported and clarified the QM/MM results, but comparison with previous X-ray structures helped correct existing errors in the available geometrical models and resolved inconsistencies in the weighting of various factors governing the inhibition. In the work the first QM/MM MD calculations on the active site of the cysteine proteases are presented. In contrast to the MD simulations, these calculations used potential energies computed at the QM/MM-level. With the help of these computations we sought to address strongly disputed questions about the reasons for the existence of the active site ion pair and its role in the high activity of the enzyme.
In the first part of this work a new approach to measure transient absorption spectra of fluorescent compounds by means of laser flash photolysis technique was presented. Generally, the recorded transient absorption signal consists of transient absorption, fluorescence and ground state bleaching. Thus, for fluorescent chromophores a fluorescence correction is indispensable in order to obtain undisturbed absorption decay curves as well as accurate transient absorption spectra. Due to time response characteristics of the PMT detector the fluorescence contribution cannot be corrected by recording the fluorescence separately. Measuring two transient absorption signals with probe light differing in intensity, compounds with quantum yields up to ~ 35 % can be investigated. This is a major improvement because transient absorption spectroscopy is a powerful method to gain insight into the kinetics and the energy of excited states and information in the time domain of fluorescence are no longer lost. In the second part the synthesis and the photophysical characterisation of redox cascades were reported. These cascades consist of an acridine acceptor and up to three triarylamine donor subunits. The redox potentials of the triarylamines were tuned by adequate substituents in the para-position of the phenyl ring to ensure a directed redox gradient. Upon photoexcitation a locally excited state or a CT state is populated which then injects a hole onto the adjacent donor and consequently results in a CS state. Fluorescence and transient absorption measurements revealed that HT depends strongly on donor strength and solvent polarity. Formation of a CS state was only observed in case of strong terminal donors or polar solvents. A low lying localised triplet state acts as an energy trap and quenches all CS states even in case of the cascade with the strongest terminal donor in very polar solvents. Furthermore, population of a CS state catalyses the formation of this triplet states which results in a shorter lifetime of the CS state compared to the lifetime of the CT state of the corresponding reference compound. Compared to redox cascades already reported in literature, the electronic coupling between the redox centres was decreased by sterical as well as electronic effects. To prolong the lifetime of the CS state saturated spacers on the one hand and a perpendicular orientation of the acceptor and the adjacent donor on the other hand were selected. The twisting of the subunits forming the CT state results in a higher degree of charge separation but its contribution to increase the lifetimes of the CS states is of minor importance. The longer lifetime of the CS states can be ascribed to the saturated spacers. Experimental data in combination with calculated values indicate that charge recombination takes place in the Marcus normal region by a superexchange mechanisms. Although charge recombination of the known cascades is located in the Marcus inverted region, these CS states decay faster than the CS states of the compounds investigated in this work.
The present work deals with the synthesis and the investigation of the photophysical properties of covalently constructed calix[4]arene–perylene bisimide dye arrays containing various PBI units. The obtained conjugates are characterized with respect towards their application in a new, zigzag-type architecture of artificial light-harvesting systems. For this purpose, orange (core-unsubstituted), red (6,7,11,12-tert-butylphenoxy-functionalized) and green (1,7-pyrrolidino-substituted) perylene bisimide building blocks have been attached to the calix[4]arene scaffold. First, the monochromophoric reference systems have been studied, and second, the photophysical properties of a comprehensive series of newly synthesized, multichromophoric calix[4]arene–perylene bisimide conjugates showing efficient energy transfer processes between the individual dye subunits have been investigated. Furthermore, a series of bichromophoric compounds containing identical chromophoric units has been obtained. Towards this goal, a variety of spectroscopic techniques such as UV/vis absorption, steady state and time-resolved fluorescence emission, and femtosecond transient absorption spectroscopy as well as a spectrotemporal analysis of the obtained data has been applied. This work presents a new concept for an artificial light-harvesting system positioning the dye units by means of calix[4]arene spacers along a zigzag chain. The investigations start with the syntheses and optical properties of the monochromophoric building blocks and result in an elaborate study on the energy and electron transfer processes occurring after photoexcitation in a comprehensive series of multichromophoric calix[4]arene–perylene bisimide conjugates. Finally, the photophysical properties of a series of compounds containing each two identical PBI units are discussed.
The effective binding of anions like carboxylates and phosphates in aqueous solutions is of particular interest for various reasons. The natural archetypes of effective anion receptors are enzymes that contain often arginine as relevant amino acid in the binding pocket. For this reason, one class of artificial anion receptors that emerged more than two decades ago mimics the anion binding with the guanidinium group present in the amino acid side chain. In 1999, Schmuck and coworkers developed a new class of guanidinium-based oxo anion receptor that binds carboxylates even in aqueous media. The binding modes of the 2-(guanidiniocarbonyl)-1H-pyrroles are based on individually weak non-covalent interaction between artificial host and substrate like ion pairing and multiple hydrogen bonds. The zwitterionic derivative with substitution of a carboxylate group in position 5 of the pyrrole ring system shows a strong self-assembly to discrete dimers (dimer 1) with an estimated association constant of 170 M-1 even in water. In order to further improve the structure motif for an effective oxo anion binding it is therefore of great interest to quantify the different intermolecular interactions between two monomeric units of 1. Against this background several theoretical ab initio studies were conducted in order to elucidate the influences of intrinsic properties as well as solvent effects on the stability of self-assembled dimers. In chapter 4.1 the molecular interactions in dimer 1 were investigated by comparison to various “knock-out” analogues. In these analogues single hydrogen bonds were switched off by substitution of hydrogen donor atoms with either methylene groups or ether bridges. The calculations were done for vacuum and solvation, as represented by a conductor-like polarizable continuum. It could be shown that the application of a simple continuum solvent model fails to predict the absolute energies of the knock-out analogues in strongly polar solvents. However, the calculated trends can explain the relative stabilities. In chapter 4.2 the structural similarity of arginine with structure 1 was used in order to examine the dependence of self-assembly from the flexibility of the molecular structure. In chapter 4.2.1 new global minimum structures of the canonical and zwitterionic arginine in gas phase were found by means of exhaustive force field based conformational searches in conjunction with ab initio structure optimizations of the lowest energy conformers. Most of the newly identified minimum conformers of both the zwitterionic and canonical tautomer revealed geometrical arrangements with hitherto unreported stacked orientations of the terminal groups. Finally a novel global minimum structure was detected that is more than 8 kJ mol-1 lower in energy than the previously published conformers. The same strategy for finding minimum energy conformers of the arginine monomer has also been employed for the arginine dimer structures. While previous theoretical studies favoured directed hydrogen bonds the new global minimum structure MMFF1 is about 60 kJ mol-1 more stable and exhibits a stacked orientation of the guanidinium and carboxylate groups. The importance of rigidity on the dimer stability was proven by calculations of an artificially stiffened arginine dimer system. The high binding affinity dimer 1 results by about 50% from the rigidity of the monomers which prevents any intramolecular stabilization. In chapter 4.3 novel structure motifs with varying ring systems have been examined on a DFT level of theory in order to make proposals for an improved carboxylate binding motif. The direct dependency of the dimerization energy on an increasing dipole moment was demonstrated by various anellated ring structures. The influence of the delocalization in the monomer on the dimerization energy was examined by variation of the electronic structure of electronically decoupled biphenylenes. With the aid of various substituted 7-guanidinioindole-2-carboxylate derivatives we could show that the carbonyl function is mainly responsible for the advantageous preorganisation, whereas the effect on the acidity seems to be only of minor importance. In the last chapter cooperativity effects in supramolecular assemblies have been investigated. This was achieved by NMR shift calculations of adenosine-carboxylic acid complexes as model systems and comparison to experimental low-temperature NMR studies. We could demonstrate that only by applying vibrational averaged NMR shifts the experimental proton shifts obtained at very low temperatures in the hydrogen bond exchange regime could be reproduced.
Oxygen-centered radicals are important intermediates in photobiological, mechanistic and synthetic studies. The majority of precursors of reactive oxyl radicals are labile and thus delicate to handle. Therefore N-(alkoxy)-pyridinethiones and N-(Alkoxy)-thiazolethiones have attracted attention as "mild'' photochemical source of alkoxyl radicals, in the last few years. A disadvantage of the pyridine compounds, is their sensibility to daylight. Despite of their similarities, both molecules behave surprisingly different, if photolyzed in the absence of trapping reagents. The pyridinethione compounds undergo highly efficient radical chain reactions under such conditions while the corresponding thiazolethiones react surprisingly sluggish and give rise to several unwanted side products. The properties of both compounds should be understood and optimized in the frame of this work. Additionally new compounds should be suggested that can also be applied in the photochemical alkoxyl radical generation. Some background information about the generation and application of alkoxyl radicals is provided in chapter 2. Electronic excitations and UV/vis spectroscopy together with a description of quantum chemical approaches that are able to calculate such phenomena are outlined in chapter 3. Chapter 4 deals with the description of the vertical excitation spectra. During the validation CASSCF, CASPT2, TD-DFT and RI-CC2 were tested with respect to their ability to describe the vertical excitations in both compounds. The CASPT2 approach gives accurate descriptions of the electronic excitation spectra of all compounds. The time-dependent DFT results are very sensitive on the choice of the functional and a validation of the results should be always done. On the basis of these computations the spectroscopic visible absorption bands of both compounds were assigned to a pi-->pi* transition in the thiohydroxamic acid functionality. In chapter 5 the mechanism of the thermally and the photochemically induced N,O homolysis in both compounds is unveiled. The near UV-induced N,O homolysis will start from the S2 state. The expected relaxation from the S2- to the S1-state and the dissociation process is expected to be very fast in the case of the thiazolethione compound. The potential surfaces of the pyridine compound in contrast point to a slower N,O bond dissociation. Due to the resulting faster dissociation process the excess energy which results from the photochemical activation is quenched only to small amounts. The maximal possible excess energy of the fragments is lower and a quenching is much more likely in the case of the pyridinethione compounds. This explaines the different reactivities of both compounds. For the also already successfully applied precursor system N-(alkoxy)-pyridineones the computed dissociation paths show courses that clearly predict a slow bond dissociation process. Chapter 6 deals with the tuning of the initial excitation wave length of the known pyridinethiones und thiazolethiones. In the first part the effects of substituents on the thiazolethione heterocycle was examined. The UV/vis spectra of 4 and 5 substituted thiazolethiones can be interpreted like the spectrum of the parent compound. The second part of chapter 6 deals with the identification of a substitution pattern on the pyridine heterocycle which induces a blue shift of the photo active band. The computations showed that electron rich and electron poor substituents result the same effects on the electronic excitation spectra. These substituent effects are additive, but the steric orientation of the substituents has to be taken into account. Chapter 7 describes a computer aided design of new alkoxyl radical precursors. Combining the advantages of both compounds the radical formation should be initiated by an irradiation with light at about 350 nm, and the amount of side products during the radical formation process should be small. To achieve this 18 test candidates were obtained by a systematic variation of the parent compound of the thiazolethione precursor. To identify the promising new precursor systems a screening of the lower electronic excitations of all resulting 18 systems was performed with TD-DFT. For promising systems the N,O or P,O dissociation paths, respectively, were analyzed according to the developed model. N-(methoxy)-azaphospholethione and N-(methoxy)-pyrrolethione seem to be the most promising candidates. The computations predict a strong absorption at about 350 nm respectively 320 nm. Due to the amounts of maximal excess energy and the shapes of the potential surfaces of the N,O bond dissociation paths their reactivity should resemble more the behavior of the pyridinethiones.
This thesis deals with the isolation and structural elucidation of bioactive naphthylisoquinoline alkaloids and related analogs. The mode of action of the antiplasmodial activity exhibited by the naphthylisoquinoline alkaloids was explored and compared to that of the antimalarial drug chloroquine. Furthermore, the phase 1 and 2 metabolism of dioncophyllines A and C and dioncopeltine A were investigated. In detail the following results have been obtained: • From the leaves of the recently discovered East African liana A. tanzaniensis six naphthylisoquinoline alkaloids were isolated. • The leaves of a botanical yet undescribed Ancistrocladus species, collected by Prof. Dr. V. Mudogo in the Democratic Republic of Congo in the habitat Yeteto near the town Ikela, were analyzed for naphthylisoquinoline alkaloids for the first time. The isolation work led to the first identification of an N,C-coupled naphthyldihydroisoquinoline alkaloid; ancistrocladinium B. Phytochemical investigation of the roots of the Congolese Ancistrocladus species (habitat Yeteto), , afforded five new derivatives of known naphthylisoquinoline alkaloids, namely 5'-O-demethylhamatine, 5'-O-demethylhamatinine, 6-O-demethylancistroealaine A, 6,5'-O,O-didemethylancistroealaine A, and 5-epi-6-O-methylancistrobertsonine A, along with six known naphthylisoquinoline alkaloids. • The antiplasmodial activity guided purification of 60Co irradiated samples containing commercially available naphthylisoquinoline related substances, afforded the isolation of the irradiation products 3,4-dihydro-1-isoquinolinone, 3,4-dihydro-1-isoquinolineamine, and 1,2,3,4-tetrahydro-1,2-diazirino-isoquinoline. The compounds were found to be more active than the starting material, although only exhibiting weak antiplasmodial activity against P. falciparum. • The effect on the absorption spectrum of FPIX due to complex formation with the naphthylisoquinoline alkaloids dioncophyllines A and C, dioncopeltine A korupensamine A, and ancistrocladine was examined by a titration study. Job's plot analyses by UV-spectroscopy determined the stoichiometry for the complex formation of FPIX and naphthylisoquinoline alkaloids to be 2:1. Furthermore, the dissociation constants for the complexation with FPIX were determined for each of the naphthylisoquinoline alkaloids investigated. Dioncophylline C and dioncopeltine A were found to possess dissociation constants, which are comparable to the one reported for the antimalarial drug chloroquine. The ability of ESI to transfer noncovalent solution-phase assemblies intact into the gas phase, was conducted on solution mixtures of naphthylisoquinoline alkaloid and FPIX, as well as on mixtures of chloroquine and FPIX. The mass spectrometry analyses revealed several peaks, which corresponded to the complex formation of FPIX to the respective ligands investigated. The most interesting results obtained were the detection of peaks corresponding to the complex formation between a chelated dimer of FPIX and dioncophylline Cand of peaks corresponding to a double protonated tetramer of FPIX – consisting of two chelated -oxo dimers of FPIX – in complex formation with two molecules of chloroquine. • Two phase 1 metabolism products of dioncophylline A were identified. Coelution in combination with HPLC-MS/MS, NMR, and CD investigations assigned the major metabolic product as 5'-O-demethyldioncophylline A. The minor metabolic product was only present in small amounts, which disabled an unambiguous structural characterization of the compound. However, as deduced from the mass spectrometry analyses and exclusion of a possible metabolic oxidation product by coelution with authentic reference material, the metabolite should possess a 4-hydroxylated isoquinoline portion and is assumed to be represented by structure. Dioncophylline C and dioncopeltine A were found to be stable to phase 1 metabolism reactions caused by rat liver microsomes.
The functionalities of DNA and RNA are mainly determined by the various interactions between the pairing nucleobases. To understand the complex interplay of the various interactions model systems are needed in which the interstrand pairing is less restricted by the backbone. Such systems are peptide nucleo acids (PNA) in which the sugar phosphate backbone of DNA or RNA is replaced by a peptide backbone. Diederichsen et al. were able to synthesize a large number of systems with an alpha-alanyl backbone to which canonical and non-canonical nucleobases were attached (alpha-alanyl-PNA). These systems formed aggregates with various binding motifs which do not appear in DNA or RNA. Especially the unusual binding motifs would allow a deep insight into the complex interplay of the interactions between nucleobases but the small solubility of alpha-alanyl PNA oligomers hampers the experimental determination of the geometrical arrangement by X-Ray or NMR. Only the overall stability of the various aggregates could be determined by measurements of melting temperatures via UV spectroscopy. Since a detailed knowledge about the geometrical structure and bonding motifs are necessary to obtain insight into the interplay of the various interactions it is the goal of the present work to achieve such information with the help of theoretical approaches. Additionally we are interested in the effects which govern the trends in the stabilities of the systems. This task should be simpler than an investigation of the absolute stabilities since many contributions (e.g. entropic and dynamic effects) can be expected to be similar for similar systems. Consequently, such effects are less important for our goal. For the investigation of all experimentally tested alpha-alanyl-PNA oligomers it was essential to parameterize the noncanonical nucleobases since they were not implemented in the standard version of the Amber4.1 force field. This was achieved by adding the missing parameters to the Amber Force Field. The charges of each nucleobase were determined by the R.E.D program package. The investigation started with the construction of all possible pairing modes for alpha-alanyl-PNA dimer. It could be observed that certain pairing modes were not realizable due to the geometrical arrangement of the dimer and the restriction of the backbone. For other pairing modes a construction was possible, but due to the geometrical restrictions of the backbone the strain in the system is so high that they fall apart during a first geometry optimization. Stable systems were then simulated by various molecular dynamics (MD)-runs. Information about their geometrical arrangements for T=0 K were obtained from geometry optimizations which were started from various points of the MD-run. The resulting geometries were found to be virtually identical. Information about the interactions within a dimer at T=0 K were obtained from a two step procedure in which the effects connected with the nucleobases and the influence of the backbone are determined separately. It was performed for the optimized geometries. In a first step the backbone was removed and the resulting dangling bonds were saturated by methyl groups. The total interaction energy between the nucleobases can now be estimated by the difference between the energy of the complete system and the sum of the energies of the single nucleobases computed at the geometries they take in the whole system. According to the carried out investigation and the resulting correlation of the melting temperature with the calculated stabilization energies the presented method seems to represent a reliable tool for the description of the PNA systems. Despite this success additional experimental verifications of our method are necessary to ensure its applicability. Such verifications could be based on geometrical information obtained via X-Ray or NMR investigations. More detailed data about entropic an enthalpic contribution to the stability of the various complexes would also be very helpful to verify and improve our approach. Such information could be either obtained from a careful analysis of shape of the melting temperature curve or from microcalorimetric investigations. If such tests confirm our predictions the approach could be extended and applied to neighboring fields as for examples beta-alanyl-PNA, DNA or RNA systems with unusual nucleobases. Such information is also necessary to extend our approach in a way that dynamic and/or entropic effects are also taken into account.
As a traditional industrial pigment, perylene bisimide (PBI) dyes have found wide-spread applications. In addition, PBI dyes have been considered as versatile and promising functional materials for organic-based electronic and optic devices, such as transistors and solar cells. For these novel demands, the control of self-organization of this type of dye and the investigation of the relationship between the supramolecular structure and the relevant optical and electronic properties is of great importance. The objective of this thesis focuses on gaining a better understanding of structural and functional properties of pi-stacks based on self-assembling PBIs. Studies include the synthesis and characterization of new functional PBI dyes, their aggregation in solution, in liquid crystalline state and on surfaces, and their fluorescence and charge transport properties. An overview of the formation, thermodynamics and structures of pi-stacks of functional pi- conjugated molecules in solution and in liquid crystalline phases is given in Chapter 2. Chapters 3 and 4 deal with the pi-pi aggregates of new, highly fluorescent PBIs without core-substituents. In Chapter 3, the self-assembly of a PBI with tridodecylphenyl substituents at imide N atoms both in solution and condensed phase has been studied in great detail. In condensed state, the dye exhibits a hexagonal columnar liquid crystalline (LC) phase as confirmed by DSC, OPM and X-ray diffraction analysis. The columnar stacking of this dye has been further confirmed by atomic force microscopy (AFM) where single columns could be well resolved The charge transport properties this dye have been investigated by pulse radiolysis-time resolved microwave conductivity (PR-TRMC) measurements. To shed more light on the nature of the pi-pi interaction of the unsubstituted PBIs, solvent depend aggregation properties have been investigated in Chapter 4. The studies are further extended from core-unsubstituted PBIs to core-substituted ones (Chapter 5 and 6). In Chapter 5, a series of highly soluble and fluorescent core-twisted PBIs that bear the same trialkylphenyl groups at the imide positions but different bay-substituents and were synthesized. These compounds are characterized by distortions of the perylene planes with dihedral angles in the range of 15-37° according to crystallographic data and molecular modeling studies. In contrast to the extended oligomeric aggregates formed for planar unsubstituted PBIs, this family of dyes formed discrete pi-pi-stacked dimers in apolar methylcyclohexane as concentration-dependent UV/Vis measurements and VPO analysis revealed. The Gibbs free energy of dimerization can be correlated with the twist angles of the dyes linearly. In condensed state, several of these PBIs form luminescent rectangular or hexagonal columnar liquid crystalline phases with low isotropization temperatures. The core-twisting effect on semiconducting properties has been examined in Chapter 6. In this chapter, a comparative study of the electrochemical and the charge transport properties of a series of non-substituted and chlorine-functionalized PBIs was performed. While Chapters 3-6 focus on one-component dye systems, Chapter 7 explored the possibility of a supramolecular engineering of co-aggregates formed by hydrogen-bonded 2:1 and 1:1 complex of oligo(p-phenylene vinylene)s (OPVs) and PBIs. Covalently linked donor-acceptor dye arrays have been prepared for comparison. Concentration and temperature-dependent UV/Vis spectroscopy revealed all hydrogen-bonded and covalent systems form well-ordered J-type aggregates in methylcyclohexane. With these hydrogen-bonded OPV-PBI complexes, fibers containing p-type and n-type molecules can be prepared on the nano-scale (1-20 nm). For the 2:1 OPV-PBI hydrogenbonded arrays hierarchically assembled chiral superstructures consisting of left-handed helical pi-pi co-aggregates (CD spectroscopy) of the two dyes that further assemble into right-handed nanometer-scale supercoils in the solid state (AFM study) have been observed. All of these well-defined OPV-PBI assemblies presented here exhibit photoinduced electron transfer on sub-ps timescale, while the electron recombination differs for different systems.Thus, it was suggested that such assemblies of p- and n-type semiconductors might serve as valuable nanoscopic functional units for organic electronics.
Electroactive Conjugated Polymers as Charge-Transport Materials for Optoelectronic Thin-Film Devices
(2005)
In this work the electrochemical and spectroelectrochemical properties of a series of pi-conjugated organic polymers were studied. The polymers were deposited on platinum electrodes or ITO-coated glass substrates by potentiodynamic electro-polymerisation of the corresponding monomeric precursor molecules. The electro-chemical and photophysical properties of the triarylborane monomers were studied in detail in order to estimate possible influences on the behaviour of the corresponding polymer. The first part of this work aimed at the synthesis and investigation of conjugated donor–acceptor polymers which combine the prerequisites of an OLED within one material: the transport of positive and negative charges and the formation of emissive excited states. With the carbazole-substituted oxadiazoles 1–3 it was shown that on the one hand the carbazole functionality is suitable for enabling the electrochemical polymerisation of the monomers and on the other hand it facilitates reversible p-doping of the resultant polymers. Although n-doping of poly-1–poly-3 is possible due to the electron-deficient oxadiazole rings, it causes the continuous degradation of these electron-acceptor units. Interestingly, this process does not influence the capability of p-doping of the polymers. With respect to its electrochemical and spectroelectrochemical properties the behaviour of the borane polymer poly-4 is absolutely identical with that of the oxadiazole polymers. Moreover, the optical excitation of poly-4 in the solid state leads to the emission of blue-green light which suggests that this polymer might also possess electroluminescent properties. AFM-measurements of poly-4 films on ITO-coated glass substrates revealed, that the film thickness can be controlled to a certain extent by the number of polymerisation redox cycles. It was shown from the electrochemical and photophysical properties of the triarylboranes 4–6 that the pi–pi-interaction between boron and nitrogen atoms is comparably weak in these molecules. This leads to an unexpected ground-state polarisation with a partially positive boron atom and a partially negative nitrogen atom. Moreover, it was found that TAB 4 possesses a lower symmetry than D3 in solution and that excitation energy can be transferred amongst the three subchromophores of 4. By titration experiments it was also demonstrated that TAB 4 can reversibly bind fluoride ions and that the binding event significantly influences the optical absorption characteristics of the chromophore. It can be assumed, that the above mentioned properties, which have a profound influence on the photophysical behaviour of these triarylborane chromophores, also determine the behaviour of the corresponding polymer in a solid state environment. The aim of the second part of this work was the investigation of purely n-conducting materials based on electron-deficient borane and viologen polymers. The corresponding precursor molecules should be polymerised on platinum electrodes by reductive electropolymerisation. However, a reductive polymerisation was not possible for the borane monomer 19 which is thought to be due to a strong localisation of the unpaired electron on the central boron atom of the radical anion. An electropolymerisation of the cyano-substituted bispyridinio-compound 17 failed because of the poor quality of CN– as a leaving group. Thus, a synthesis of the analogous isomer 18 was developed, in which the cyano-substituents were exchanged by the better leaving group Cl–. The viologen polymer poly-18, which can be regarded as an electron-deficient iso-electronic analogue of poly(para-phenylene), was successfully deposited on a platinum electrode by reductive electropolymerisation of 18. Poly-18 can be reversibly n-doped at comparably low potentials; however, at higher potentials the polymer is overcharged and destroyed irreversibly. As the synthetic strategy for 18 allows the variation of both spacer unit and leaving group in the last two steps of the reaction sequence, a series of analogous compounds can be easily synthesised using this route.
The one electron oxidation potential of ten TAAs with all permutations of Cl , OMe- and Me-substituents in the three p-positions were determined by CV. The half wave potential of the first oxidation wave correlates linearly with the number of Cl- and OMe-substituents. AM1-CISD derived values of the absorption energies are in good agreement with the experiments but differ strongly for the oscillator strengths as well as for neutral compounds and their corresponding mono radical cations. The small solvent dependence of the experimental UV/Vis spectra in CH2Cl2 and MeCN reflects a minor charge transfer character of the electronic transitions. The UV/Vis/NIR spectra of the series of TAAs and their corresponding radical cations and the AM1 computations reveal that even small substituents may lead to strong symmetry breaking and to a modified electronic structure. The spectroscopic properties of a series of four bis-TAA donor-bridge-donor X-B-X dimers, composed of two asymmetric TAA chromophores (monomers) were investigated. UV/vis-, fluorescence and transient absorption spectra were recorded and compared with those of the corresponding X-B monomers. The excited states of the dimers are described as MV states which show, depending on the chemical nature of the bridge, a varying amount of interactions. It was found that superradiant emission only proceeds in the case of weak and medium coupling. Whether the first excited state potential energy surface of the dimers is a single minimum or a double minimum potential depends on the solvent polarity and the electronic coupling. In the latter case, the dimer relaxes in a symmetry broken CT state. The [2.2]paracyclophane bridged dimer is an example for a weakly coupled system, because the spectroscopic behavior is very similar to the corresponding p xylene monomer. In contrast, anthracene as well as p-xylene bridges mediate a stronger coupling and reveal a significant cooperative influence on the optical properties. A series of [2.2]paracylophane bridged bis-TAA MV radical cations X-B-X+ were analyzed by a GMH three-level model which takes two transitions into account: the IV-CT band and the bridge band. From the GMH analysis, one can conclude that the [2.2]paracyclophane moiety is not the limiting factor which governs the intramolecular charge transfer. The electronic interactions are of course smaller than direct conjugation but from the order of magnitude of the couplings of the [2.2]paracyclophane MV species it can be assumed that this bridge is able to mediate significant through-space and through-bond interactions. From the exponential dependence of the electronic coupling V between the two TAA localized states on the distance r between the two redox centers, it was inferred that the HT proceeds via superexchange mechanism. The analysis reveals that even significantly longer conjugated bridges should still mediate significant electronic interactions, because the decay constant of a series of conjugated MV species is small. The absorption properties of a series of bis-TAA-[2.2]paracyclophane dications X+-B-X+ were presented. The localized and the CT transitions of these dications are explained and analyzed by an exciton coupling model which also considers the photophysical properties of the monomeric TAA radical cations. Together with AM1-CISD calculated transition moments, experimental transition moments and transition energies of the bis-TAA dications were used to calculate electronic couplings by a GMH approach. These couplings are a measure for interactions of the excited MV CT states. The modification of the diabatic states reveals similarities of the GMH three-level model and the exciton coupling model. Comparison of the two models shows that the transition moment between the excited mixed-valence states of the dimer equals the dipole moment difference of the ground and the excited bridge state of the corresponding monomer. Thianthrenophane (1) has a cavity which offers enough room to potentially enable endohedral coordination to small ions or molecules. For the complexation of silver(I) perchlorate, the complex stability constants of thianthrenophane logK1=5.45 and of thianthrene logK2=9.16 were determined by UV/Vis titration. Single competition transport experiments with ten metal salts demonstrate a very high selectivity of thianthrenophane as a carrier for silver(I) and a distinctly higher transport rate compared to carriers such as thianthrene and 14-ane-S4. Although the X-ray crystal structure analysis of the polymeric [Ag(1)]ClO4 shows an exohedral coordination to silver(I), the formation of an endohedral [Ag(1)]+ complex is suggested to be the explanation for the unusual carrier selectivity of silver(I) by 1 in bulk liquid membrane.
In this work the influence of “active” bridge units on the electron transfer (ET) mechanism within organic donor-bridge-electrode arrays in self-assembled monolayers (SAMs) was studied by spectroscopic and electrochemical methods. In the first part of this work ferrocenealkanethiols 1 – 3 and the ferrocenearylthiols 4, 5 were investigated to get experience in the monolayer preparation for measuring ET rates. Cyclic voltammetry of the monolayers indicates that homogeneously mixed monolayers containing redox active molecules and dummy molecules were formed. For the known ferrocenealkanethiols 1 – 3 the ET rates could be confirmed compared to the ones measured by Creager et al. [206]. As expected the ET rate decreases by increasing chain length of the alkane spacer from 2 to 3. Changing the bonding between the redox centre and the alkane spacer with the same bridge lenght, e. g. by using a carboxy-group in case of 1, does not influence the ET behaviour very strong. The aromatic ferrocenethiols 4 and 5 show very high ET rates due to the strong conjugated system although the distance between the redox centre and the electrode is comparable to the C8-alkyl compound 2. The electronic coupling factors all indicate a nonadiabatic ET between the redox centre and the electrode. As expected the electronic coupling factors increase with decreasing spacer length or with an enlarged conjugated system. To sum up, experience in monolayer preparation could be obtained, the measured ET rates for well known ferrocenealkane-compounds 1 - 3 could be verified and the information could be transferred to the conjugated systems 4 and 5. In the second part the triarylamine- 29, 32 and the phenothiazinealkanethiol 35 have been examined relative to their ET behaviour in mixed monolayers. The cyclic voltammograms of the diluted monolayers indicate that homogeneously formed monolayers are present. The ET rates of triarylamine- 29, 32 and phenothiazinealkanethiols 35 are 10 to 100 times higher than compared to ferrocenealkanethiols with equal chain length[183, 206], whereas in a [Ru(bpy)2(pp)]+-containing monolayer the same value was observed [177]. Almost two parameters influence the ET rate constant: the electronic coupling matrix element and the reorganisation energy  [209]. The ET rate in donor substituted alkanethiols is mainly influenced by the reorganisation energy  [177] and even small changes have a dramatic effect on the observed processes, therefore an increasing ET rate from the ferrocene (high reorganisation energy) over the phenothiazine 35 and the [Ru(bpy)2(pp)]+ to the triarylamine chromophores 29 and 32 (low reorganisation energy) is observed. Furthermore the bonding between the redox centres and the alkane spacer plays an important role on the ET rate in case of the triarylamines 29 and 32 opposite to the assumption made by Creager et al. that the connection does not play any role. For the electron rich ether connected compound 29 the ET is not only dominated by the reorganisation energy but also by mesomeric effects where the positive charge of the electron rich derivative 29 is more located at the ether function so that the chain is formally shortend by one atom resulting in higher ET rates than compared to 32. In the third part of the thesis a series of “molecular wires” consisting of methoxy- or chloro-substituted triarylamines and phenothiazines with different bridge units and bridge length between the redox centre and the anchor thiol function have been prepared in order to investigate their ET-behaviour. Cyclic voltammetry and UV/vis-spectroscopy show that the oxidation potential and the energetic states could be controlled very well by introducing different redox centres and bridge units resulting in a decreasing oxidation potential of the redox centres and a bathochromic shift of the absorption bands in the UV/vis-spectra. Also the densitiy of the chromophores in mixed monolayers could be controlled very well for only three compounds (49, 52 and 87) with nitrile-substituted bridges reliable ET rates could be obtained. In these chromophores the ET rate decreases by increasing the density of the redox active molecules in the mixed monolayers indicating that the adsorption geometry changes with coverage with the chromophores tilting to a more upright orientation as the surface becomes more crowded. For all other compounds the measurements were limited by the fast ET rates. Conformational, as well as a very weak distance dependence of the ET resulting in very high ET rates [172] or unfavourable HOMO-LUMO energies of the donor, bridge and the electrode are reasons for this behaviour. The fact that compound 49 shows almost the same rate constant independent of the length (n = 2 or n = 3) may indicate that a hopping process is operating for which a much weaker length dependence is expected than in the case of a superexchange.
Complexation properties of 2,2':6',2''-terpyridine (tpy) have been studied with a series of first row transition metal ions by UV-vis, 1H NMR and isothermal titration calorimetry and ƒ´H values for the tpy complexation processes have been determined. These studies reveal that Zn2+ is the best suited metal ion for the reversible coordination of the terpyridine ligand. Thus, supramolecular coordination polymerization of perylene bisimide fluorophores containing terpyridine functionalities have been investigated by using Zn2+ as metal ion. The formation of the dimeric complexes in the case of monotopic model comounds and coordination polymerization of ditopic functional building blocks have been confirmed by 1H NMR studies. The optical properties of dimeric and polymeric complexes have been investigated by UV-vis and fluorescence spectroscopy. The Zn2+ coordination to the terpyridine unit does not effect the advantageous fluorescence properties of perylene bisimide moieties. The reversibility of the formation of coordination polymers has been established by 1H NMR and additionally by DOSY NMR and fluorescence anisotropy measurements. Coordination polymer strands can be visualized by atomic force microscopy (AFM), which also reveals the formation of an ordered monolayer film at higher concentration. The average polymer length has been determined by AFM to 15 repeat units, which correlates well with the value estimated by 1H NMR to >10 repeat units.
The present thesis encompasses two parts. The first supramolecular part focuses on the development of new flexible self-assembling zwitterions as building blocks for supramolecular polymers. In the second part, the aim was to develop bioorganic receptors for amino acids and dipeptides in aqueous media. Both research projects are based on the guanidiniocarbonyl pyrrole 1 as a new efficient binding motif for the complexation of carboxylates in polar solution.A necessary requirement for the realization of these research projects was to develop an efficient and mild synthetic approach for the cationic guanidiniocarbonyl pyrroles in general. The harsh reaction conditions of the previously used method and the problematic purification of the cationic guanidinocarbonyl pyrroles so far prevented a more extensive exploration in bioorganic and supramolecular research. In the course of this work I successfully developed a new synthesis starting with mono tBoc-protected guanidine that was coupled with a benzyl protected pyrrole carboxylic acid. After deprotection of the benzyl group, a key intermediate in the newly developed synthesis, the tBoc-protected guanidinocarbonyl pyrrole acid, was obtained. This new, mild and extremely efficient synthetic approach for the introduction of acyl guanidines is now the standard procedure in our group for the preparation of both solution and solid-phase guanidiniocarbonyl pyrroles. With this facile method at hand, a new class of flexible zwitterions, in which a carboxylate is linked via an alkyl chain to a guanidiniocarbonyl pyrrole cation was synthesized. The self-aggregation and the influence of the length and therefore flexibility of the alkyl spacer on the structure and stability of the formed aggregates were studied in solution and gas phase. In solution the aggregation was studied by NMR-dilution experiments in DMSO which suggest that flexible zwitterions with n = 1, 3 and 5 form oligomers. For n = 1, highly stable helical aggregates with nanometer size are formed. In the gas phase studies the stability and the fragmentation kinetics of a series of sodiated dimeric zwitterions with n = 2, 3 and 5 were investigated. This was done by infrared multiphoton dissociation Fourier transform ion cyclotron resonance mass spectrometry (IRMPD-FT-ICR-MS). These kinds of studies can be used in the future for a more directed design of supramolecular building blocks The bioorganic research part comprises three different projects. In a first project I synthesized four new arginine analogues which can be implemented in peptides as a substitute for arginine. Therefore, I developed the new multi-step synthesis shown below for these arginine analogues. As a test for their application in normal solid phase synthesis, I successfully prepared a tripeptide sequence Ala-AA1-Val (AA: arginine analogue. In a second project I studied the influence of additional ionic interactions within our binding motif. I synthesized a di-cationic and a tris-cationic receptor and evaluated the binding properties via NMR titration experiments against a variety of amino acids. Especially, the tris-cationic receptor was capable to strongly complex amino acids. The association constants were about a factor of 100 higher than those for the guanidiniocarbonyl pyrroles known so far. Even in 90 %water/10 % DMSO the association constants determined by NMR titration were extremely high with values around Kass = 2000 M-1. In the third project I developed a de-novo designed receptor for C-terminal dipeptides in a beta-sheet conformation based on molecular calculations. This receptor was studied in NMR and also UV titration experiments. In 40 % water/ 60 % DMSO the association constants were too strong to be measured by NMR titration experiments. Therefore, the complexation properties of 12 were studied by UV titration in water (with 10 % DMSO added for solubility reasons) with various dipeptides and amino acids as substrates. The data show that 12 binds dipeptides very efficiently even in water with association constants Kass > 10000 M-1, making 12 one of the most effective dipeptide receptors known so far. In contrast to that, simple amino acids are bound up to ten times less efficiently (Kass > 1000 M-1) than dipeptides. In the series of dipeptides studied the complex stability increases depending on the side chains present in the order Gly < Ala < Val which is a result of the decreasing flexibility of the peptide and the increasing hydrophobicity of the side chains. The binding properties of this receptor are superior to any other dipeptide receptor reported so far. Within my thesis I have not only developed an essential, mild and efficient synthetic approach for guanidiniocarbonyl pyrroles in general, but also a new binding motif for the complexation of amino acids 15, 11 and in addition a dipeptide receptor 12 that is superior to all dipeptides receptors known so far.
Summary The nature of the chemical bond is a topic under constant debate. What is known about individual molecular properties and functional groups is often taught and rationalized by explaining Lewis structures, which, in turn, make extensive use of the valence concept. The valence concept distinguishes between electrons, which do not participate in chemical interactions (core electrons) and those, which do (single, double, triple bonds, lone-pair electrons, etc.). Additionally, individual electrons are assigned to atomic centers. The valence concept is of paramount success: It allows the successful planning of chemical syntheses and analyses, it explains the behavior of individual functional groups, and, moreover, it provides the “language” to think of and talk about molecular structure and chemical interactions. The resounding success of the valence concept may be misleading to forget its approximative character. On the other hand, quantum mechanics provide in principle a quantitative description of all chemical phenomena, but there is no discrimination between electrons in quantum mechanics. From the quantum mechanical point of view there are only indistinguishable electrons in the field of the nuclei, i.e., it is impossible to assign a given electron to a particular center or to ascribe a particular purpose to individual electrons. The concept of indistinguishability of micro particles is founded on the Heisenberg uncertainty relation, which states, that wavepackets diverge in the 6N dimensional phase space, such that individual trajectories can not be identified. Hence it is a deep-rooted and approved physical concept. As an introduction to the present work density partitioning schemes were discussed, which divide the total molecular density into chemically meaningful areas. These partitioning schemes are intimately related to either the concepts of bound atoms in a molecule (as in the Atoms In Molecules theory (AIM) according to Bader or as in the Hirshfeld partitioning scheme) or to the concept of chemical structure in the sense of Lewis structures, which divide the total molecular density into core and valence density, where the valence density is split up again into bonding and non-bonding electron densities. Examples are early and recent loge theories, the topological analysis by means of the Electron Localization Function (ELF), and the Natural Bond Orbital (NBO) approach. Of these partitioning schemes, the theories according to Bader (AIM), to Becke and Edgecomb (ELF) and according to Weinhold (NBO and Natural Resonance Theory, NRT), respectively, were reviewed in detail critically. Points of criticism were explicated for each of the mentioned theories. Since theoretically derived electron densities are to be compared to experimentally derived densities, a brief introduction into the theory of X-ray di®raction experiments was given and the multipole formalism was introduced. The procedure of density refinement was briefly discussed. Various suggestions for improvements were developed: One strategy would be the employment of model parameters, which are to a maximum degree mutually orthogonal, with the object of minimizing correlations among the model parameters, e.g., to introduce nodal planes into the radial functions of the multipole model. A further suggestion involves the guidance of the iterative refinement procedure by an extremum principle, which states, that when di®erent solutions to the least squares minimization problem are available with about the same statistical measures of quality and with about the same residual density, then the solution is to prefer, which yields a minimum density at the bond critical point (BCP) and a maximum polarity in terms of the ratio of distances between the BCP and the nuclei. This suggestion is based on the well known fact, that the bond polarity (in terms of the ratio of distances between the BCP and the respective nuclei) is underestimated in the experiment. Another suggestion for including physical constraints is the explicit consideration of the virial theorem, e.g., by evaluating the integration of the Laplacian over the entire atomic basins and comparing this value to zero and to the value obtained from the integration of the electron gradient field over the atomic surface. The next suggestion was to explicitly use the electrostatic theorem of Feynman (often also denoted as Hellmann-Feynman theorem), which states, that the forces onto the nuclei can be calculated from the purely classical electrostatic forces of the electron distribution and the nuclei distribution. For a stationary system, these forces must add to zero. This also provides an internal quality criterion of the density model. This can be performed in an iterative way during the refinement procedure or as a test of the final result. The use of the electrostatic theorem is expected to reduce significantly correlations among static density parameters and parameters describing vibrations, since it is a valuable tool to discriminate between physically reasonable and artificial static electron densities. All of these mentioned suggestions can be applied as internal quality criteria. The last suggestion is based on the idea to initiate the experimental refinement with a set of model parameters, which is, as much as possible close to the final solution. This can be achieved by performing periodic boundary conditions calculations, from which theoretically created files are obtained, which contain the Miller indices (h, k, l) and the respective intensity I. This file is used for a model parameter estimation (refinement), which excludes vibrations. The resulting parameters can be used for the experimental refinement, where, in a first step, the density parameters are fixed to determine the parameters describing vibrations. For a fine tuning, again the electrostatic theorem and the other above mentioned suggestions could be applied. Theoretical predictions should not be biased by the method of computation. Therefore the dependence of the density analyzing tools on the level of calculation (method of calculation/basis set) and on the substituents in complex chemical bonding situations were evaluated in the second part of the present work. A number of compounds containing formal single and double sulfur nitrogen bonds was investigated. For these compounds, experimental data were also available. The calculated data were compared internally and with the experimental results. The internal comparison was drawn with regard to questions of convergency as well as with regard to questions of consistency: The resulting molecular properties from NBO/NRT analyses were found to be very stable, when the geometries were optimized at the respective level of theory. This stability is valid for variations in the methods of calculation as well as for variations in the basis set. Only the individual resonance weights of the contributing Natural Lewis Structures differed considerably depending on the level of calculation and depending on the substituents. However, the deviations were in both cases to a large extent within a limit which preserves the descending order of the leading resonance structure weights. The resulting bond orders, i.e., the total, covalent and ionic bond order from NRT calculations, were not affected by the shift in the resonance weights. The analysis of the bond topological parameters resulted in a discrimination between insensitive parameters and sensitive parameters. The stable parameters do neither depend strongly on the method of calculation nor on the basis set. Only minor variation occurs in the numerical values of these parameters, when the level of calculation is changed or even when other functional groups (H, Me, or tBu) are employed, as long as the methods of calculation do not drop considerably below a standard level. The bond descriptors of the sulfur nitrogen bonds were found to be also stable with respect to the functional groups R = H, R = Me, and R = tBu. Stable parameters are the bond distance, the density at the bond critical point (BCP) and the ratio of distances between the BCP and the nuclei A and B, which varies clearly when considering the formal bond type. For very small basis sets like the 3-21G basis set, this characteristic stability collapses. The sensitive parameters are based on the second derivatives of the density with respect to the coordinates. This is in accordance with the well known fact, that the total second derivative of the density with respect to the coordinates is a strongly oscillating function with positive as well as negative values. A profound deviation has to be anticipated as a consequence of strong oscillations. lambda3, which describes the local charge depletion in the direction of the interaction line, is the most varying parameter. A detailed analysis revealed that the position of the BCP in the rampant edge of the Laplacian distribution is responsible for the sensitivity of the numerical value of lambda3 in formal double bonds. Since the slope of the Laplacian assumes very high values in its rampant edge, a tiny displacement of the BCP leads already to a considerable change in lambda3. This instability is not a failure of the underlying theory, but it yields de facto to a considerable dependence of sensitive bond topological properties on the method of calculation and on the applied basis sets. Since the total second derivative is important to judge on the nature of the bond in the AIM theory (closed shell interactions versus shared interactions), the changes in lambda3 can lead to differing chemical interpretations. The comparison of theoretically derived bond topological properties of various sulfur nitrogen bonds provides the possibility to measure the self consistency of this data set. All data sets clearly exhibit a linear correlation between the bond distances and the density at the BCP on one hand and between the bond distances and the Laplacian values at the BCP on the other hand. These correlations were almost independent of the basis set size. In this context, the linear regression has to be regarded exclusively as a descriptive statistics tool. There is no correlation anticipated a priori. The formal bond type was found to be readily deducible from the theoretically obtained bond topological descriptors of the model systems. In this sense, the bond topological properties are self consistent despite of the numerical sensitivity of the derivatives, as exemplified above. Often, calculations are performed with the experimentally derived equilibrium geometries and not with optimized ones. Applying this approach, the computationally costly geometry optimizations are saved. Following this approach the bond topological properties were calculated using very flexible basis sets and employing the fixed experimental geometry (which, of course, includes the application of tBu groups). Regression coe±cients similar to those from optimized geometries were obtained for correlations between bond distances and the densities at the BCP as well as for the correlation between bond distances and the Laplacian at the BCP, i.e. the approach is valid. However, the data points scattered less and the coe±cient of correlation was clearly increased when geometry optimizations were performed beforehand. The comparison between data obtained from theory and experiment revealed fundamental discrepancies: In the data set of bond topological parameters from the experiment, the behavior of only 2 out of 3 insensitive parameters was comparable to the behavior of the theoretically obtained values, i.e. theoretical and experimental bond distances as well as theoretical and experimental densities at the BCP correlate. From the theoretically obtained data it was easy to deduce the formal bond type from the position of the BCP, since it changed in a systematic manner. The respective experimentally obtained values were almost constant and did not change systematically. For the SN bonds containing compounds, the total second derivative assumes exclusively negative values in the experiment. Due to the different internal behavior, experimentally and theoretically sensitive bond topological values could not be compared directly. The qualitative agreement in the Laplacian distribution, however, was excellent. In the third and last part of this work, the application to chemical systems follows. Formal hypervalent molecules, i.e. molecules where some atoms are considered to hold more than 8 electrons in their valence shell, were investigated. These were compounds containing sulfur nitrogen bonds (H(NtBu)2SMe, H2C{S(NtBu)2(NHtBu)}2, S(NtBu)2 and S(NtBu)3) and a highly coordinated silicon compound. The set of sulfur nitrogen compounds also contained a textbook example for valence expansion, the sulfur triimide. For these molecules, experimental reference values were available from high resolution X-ray experiments. The experimental results were in the case of the sulfur triimide not unique. Furthermore, from the experimental bond topological data no definite conclusion about the formal bonding type could be drawn. The situation of sulfur nitrogen bonds in the above mentioned set of molecules was analyzed in terms of a geometry discussion and by means of a topological analysis. The methyl-substituted isolated molecules served as model compounds. For the interpretation of the bonding situation additional NBO/NRT calculations were preformed for the sulfur nitrogen compounds and an ELF calculation and analysis was performed for the silicon compound. The ELF analysis included not only the presentation and discussion of the ELF-isosurfaces (eta = 0.85), but also the investigation of populations of disynaptic valence basins and the percentage contributions to these populations of the individual atoms when the disynaptic valence basins are split into atomic contributions according to Bader’s partitioning scheme. The question of chemical interest was whether hypervalency is present in the set of molecules or not. In the first case the octet rule would be violated, in the second case Pauling’s verdict would be violated. While the concept of hypervalency is well established in chemistry, the violation of Pauling’s verdict is not. The quantitative numbers of the sensitive bond topological values from theory and experiment were not comparable, since no systematic relationship between the experimentally and theoretically determined sensitive bond descriptors was found. However, the insensitive parameters are in good agreement and the qualitative Laplacian distribution is, with few exceptions, in excellent agreement. The formal bonding type was deduced from experimental and theoretical topological data by considering the number and shape of valence shell charge concentrations in proximity to the sulfur and nitrogen centers. The results from NBO/NRT calculations confirmed the findings. All employed density analyzing tools AIM, ELF and NBO/NRT coincided in describing the bonding situation in the formally hypervalent molecules as highly polar. A comparison and analysis of experimentally and theoretically derived electron densities led consistently to the result, that regarding this set of molecules, hypervalency has to be excluded unequivocally.
The present work consists of two parts. The first one deals with theoretical questions and tests the performance of orbitals obtained from a self-interaction free KS method, the LHFapproach, in multireference ab initio methods. The purpose of this part is to enable a more efficient computation of excitation energies, which is important for the spectroscopic characterization of many organic and bioorganic molecules. The second part focuses on bioorganic questions and studies the base pairing properties of the purine base xanthine in order to explain, e.g., the unusually high stability of selfpairing xanthine alanyl-PNA double strands and the mutagenicity of xanthine formed in DNA. Part1: In contrast to HF- and standard DFT-methods, the LHF-approach leads to a fully bound virtual orbital spectrum, because Coulomb self interactions are exactly canceled in the LHFansatz. Furthermore, the energies of the occupied orbitals are not upshifted, like it is the case for standard DFT-methods, so that Koopmans' theorem remains valid. In line with this, also the occupied LHF-orbitals are somewhat more compact than standard DFT-orbitals. The present work shows that both properties are of great benefit for MR methods. The virtual LHF-orbitals are well optimized and allow an efficient description of excited states and static correlation in both MRCI- and MRPT2-approaches. Furthermore, the higher compactness of the occupied LHF- compared to standard DFT-orbitals leads to a better description of the center ion of Rydberg states. However, for each of the two advantages mentioned at least one example molecule has been found, for which LHF-orbitals actually perform worse than HF-and/or standard DFT-orbitals. This shows, that even though LHF virtual orbitals allow an excellent MRCI- and MRPT2-description for the electronically excited states of a large number of molecules, this cannot be generalized and their performance needs to be tested for each individual case. In the second part of the present work, the base pairing properties of xanthine and xanthine derivatives were studied. The purpose of this part was to find an explanation for the unexpectedly high stability of the xanthine alanyl PNA double strand. Furthermore, it was analyzed, why xanthine, that is formed from guanine in DNA under chemical stress, is able to form mismatched base pairs with the pyrimidine base thymine. Stability of xanthine alanyl PNA: In the first step, the regioisomer present in the considered alanyl PNA was identified to be the N7-regioisomer of xanthine by a theoretical analysis of the 13C-NMR spectrum. To analyze the stability of the xanthine self-pairing, a simplified model was set up, in which the stability of the PNA double strand was explained solely by the energy contributions from H-bonding and base stacking. For that purpose, the dimerization and stacking energies for the xanthine-xanthine, guaninecytosine, adenine-thymine and xanthine-2,6-diaminopurine base pairs were computed using DFT and MP2 methods. Solvent effects were taken into account by the conductor like screening model. The influence of the peptide backbone on the stacking geometry was considered by force field optimizations. While the individual contributions from hydrogen bonding and stacking do not correlate with the melting temperature Tm, the sum of both correlates linearly with Tm. This correlation is somewhat surprising, because this means that the effects of the entropy and the molecular water environment either cancel or are similar for all systems compared. In this model, the stability of the xanthine selfpairing mainly stems from an enlarged stacking interaction, while the H-bonds give only minor contributions to the stability of the xanthine selfpaired double strand of alanyl-PNA. Base pairing properties of N9-Xanthine: The computation of the base pairing properties of N9-xanthine revealed a strong variation in the individual H-bond strengths for the selfpairing of xanthine, that range from -4 to -11 kcal/mol in the gas phase and -2.5 to -5 kcal/mol in polar solvent. By comparison with model systems it was shown that the strong variance of the H-bond strength is mainly due to attractive or repulsive secondary electrostatic interactions. For the homodimer of hypoxanthine it was shown that the increase of aromaticity in the pyrimidine ring upon dimer formation leads to a strengthening of the hydrogen bonds. Mutagenicity of hypoxanthine and xanthine: Several neutral and anionic Watson-Crick base pairs of xanthine were computed with MP2- and DFT-methods in order to explain the mutagenicity of hypoxanthine and xanthine. Also basepairs involving tautomeric forms of xanthine and hypoxanthine were considered. To evaluate the dimerization energies found, the dimers were classified into pairings that have the exact geometry of the canonical base pairs and those that realize a distorted Watson-Crick pairing mode. The computations show that a stable pairing which realizes the exact geometry of a canonical Watson Crick base pairing is only possible for the pairing of xanthine to cytosine, however, the base pairs are only weakly bound. The dimerization energies of both the neutral and the anionic pairing is around 0 kcal/mol, so that the xanthine-cytosine base pairs are incorporated into DNA solely because the base pairs fulfill the geometric demands of DNA polymerase, but it does not profit from any additional stabilization due to hydrogen bonding. The bonding that in the Watson-Crick pairing mode xanthine has almost no affinity to cytosine is in correspondence with the experimental result that the cytosine-xanthine base pair is incorporated into DNA at a much lower rate than the cytosine-guanine base pair, which has a very strong hydrogen bonding. While the affinity of xanthine to cytosine is very low, the computations predict that xanthine is able to form a stable Watson-Crick pairing with thymine. However, the pairing has a somewhat distorted Watson-Crick geometry, so that its high stability is outbalanced by the worsened fit to the binding pocket of DNA-polymerase. As a consequence, the xanthinethymine pairing is incorporated into DNA not at a faster, but only at a rate comparable to that of the xanthine-cytosine pairing.
The first part of this work focuses on the characterization of systems which complex electronic structures require the application of multi-reference methods. The anti-tumor efficacy of the natural product Neocarzinostatin is based on the formation of diradicals and causes DNA cleavage and finally cytolysis. Computations on model systems performed in the present work show the influence of structural features on the mode of action and the efficacy of this antitumor-antibiotic. The cyclization of systems related to the enyne-cumulene framework like the enyne-allenes was investigated earlier and relations to the more unusual class of enyne-ketenes are analyzed. The class of enyne-ketenes (and also the enyne-allenes) show a broad spectrum of possible intermediates (diradicals, zwitterions, allenes). The electronic structures of these intermediates are also possible for the (heteroatom substituted) 1,2,4-cyclohexatriene and a model for their energetic sequence based on high-level multi-reference computations is proposed. In all three projects the application of multi-reference approaches is necessary to obtain a comprehensive picture of the reactivity and electronic structure but also shows up the limits inherently existing in the currently available programs with respect to the size of the molecules. In the second part, algorithms for a multi-reference Moller-Plesset perturbation theory (MR-MP2) program, designed to perform large-scale computations, were developed and implemented. The MR-MP2 approach represents the most cost-effective multireference ansatz and requires an efficient evaluation of the Hamilton matrix for which an algorithm is designed to instantly recognize only non-vanishing matrix elements and to employ the recurring interaction patterns of the Hamilton matrix. The direct construction of the Hamilton matrix is additionally parallelized to work on cluster environments.