Materials properties from electron density distributions: Molecular magnetism and linear optical properties

The general goal of this thesis is correlating observable properties of organic and metal-organic materials with their ground-state electron density distribution. In a long-term view, we expect to develop empirical or semi-empirical approaches to predict materials properties from the electron density of their building blocks, thus allowing to rationally engineering molecular materials from their constituent subunits, such as their functional groups. In particular, we have focused on linear optical properties of naturally occurring amino acids and their organic and metal-organic derivatives, and on magnetic properties of metal-organic frameworks. For analysing the optical properties and the magnetic behaviour of the molecular or sub-molecular building blocks in materials, we mostly used the more traditional QTAIM partitioning scheme of the molecular or crystalline electron densities, however, we have also investigated a new approach, namely, X-ray Constrained Extremely Localized Molecular Orbitals (XC-ELMO), that can be used in future to extracted the electron densities of crystal subunits. With the purpose of rationally engineering linear optical materials, we have calculated atomic and functional group polarizabilities of amino acid molecules, their hydrogen-bonded aggregates and their metal-organic frameworks. This has enabled the identification of the most efficient functional groups, able to build-up larger electric susceptibilities in crystals, as well as the quantification of the role played by intermolecular interactions and coordinative bonds on modifying the polarizability of the isolated building blocks. Furthermore, we analysed the dependence of the polarizabilities on the one-electron basis set and the many-electron Hamiltonian. This is useful for selecting the most efficient level of theory to estimate susceptibilities of molecular-based materials. With the purpose of rationally design molecular magnetic materials, we have investigated the electron density distributions and the magnetism of two copper(II) pyrazine nitrate metal-organic polymers. High-resolution X-ray diffraction and DFT calculations were used to characterize the magnetic exchange pathways and to establish relationships between the electron densities and the exchange-coupling constants. Moreover, molecular orbital and spin-density analyses were employed to understand the role of different magnetic exchange mechanisms in determining the bulk magnetic behaviour of these materials. As anticipated, we have finally investigated a modified version of the X-ray constrained wavefunction technique, XC-ELMOs, that is not only a useful tool for determination and analysis of experimental electron densities, but also enables one to derive transferable molecular orbitals strictly localized on atoms, bonds or functional groups. In future, we expect to use XC-ELMOs to predict materials properties of large systems, currently challenging to calculate from first-principles, such as macromolecules or polymers. Here, we point out advantages, needs and pitfalls of the technique. This work fulfils, at least partially, the prerequisites to understand materials properties of organic and metal-organic materials from the perspective of the electron density distribution of their building blocks. Empirical or semi-empirical evaluation of optical or magnetic properties from a preconceived assembling of building blocks could be extremely important for rationally design new materials, a field where accurate but expensive first-principles calculations are generally not used. This research could impact the community in the fields of crystal engineering, supramolecular chemistry and, of course, electron density analysis.

Experimental and Theoretical Electron Density Analysis of Copper Pyrazine Nitrate Quasi-Low-Dimensional Quantum Magnets

The accurate electron density distribution and magnetic properties of two metal-organic polymeric magnets, the quasi-one-dimensional (1D) Cu(pyz)(NO3)2 and the quasi-two-dimensional (2D) [Cu(pyz)2(NO3)]NO3·H2O, have been investigated by high-resolution single-crystal X-ray diffraction and density functional theory calculations on the whole periodic systems and on selected fragments. Topological analyses, based on quantum theory of atoms in molecules, enabled the characterization of possible magnetic exchange pathways and the establishment of relationships between the electron (charge and spin) densities and the exchange-coupling constants. In both compounds, the experimentally observed antiferromagnetic coupling can be quantitatively explained by the Cu-Cu superexchange pathway mediated by the pyrazine bridging ligands, via a σ-type interaction. From topological analyses of experimental charge-density data, we show for the first time that the pyrazine tilt angle does not play a role in determining the strength of the magnetic interaction. Taken in combination with molecular orbital analysis and spin density calculations, we find a synergistic relationship between spin delocalization and spin polarization mechanisms and that both determine the bulk magnetic behavior of these Cu(II)-pyz coordination polymers.

Conformationally Controlled Electron Delocalization in n-Type Rods: Synthesis, Structure, and Optical, Electrochemical, and Spectroelectrochemical Properties of Dicyanocyclophanes

A series of dicyanobiphenyl-cyclophanes 1-6 with various pi-backbone conformations and characteristic n-type semiconductor properties is presented. Their synthesis, optical, structural, electrochemical, spectroelectrochemical, and packing properties are investigated. The X-ray crystal structures of all n-type rods allow the systematic correlation of structural features with physical properties. In addition, the results are supported by quantum mechanical calculations based on density functional theory. A two-step reduction process is observed for all n-type rods, in which the first step is reversible. The potential gap between the reduction processes depends linearly on the cos(2) value of the torsion angle phi between the pi-systems. Similarly, optical absorption spectroscopy shows that the vertical excitation energy of the conjugation band correlates with the cos(2) value of the torsion angle phi. These correlations demonstrate that the fixed intramolecular torsion angle phi is the dominant factor determining the extent of electron delocalization in these model compounds, and that the angle phi measured in the solid-state structure is a good proxy for the molecular conformation in solution. Spectroelectrochemical investigations demonstrate that conformational rigidity is maintained even in the radical anion form. In particular, the absorption bands corresponding to the SOMO-LUMO+i transitions are shifted bathochromically, whereas the absorption bands corresponding to the HOMO-SOMO transition are shifted hypsochromically with increasing torsion angle phi.

Modern charge density studies: the entanglement of experiment and theory

This tutorial review article is intended to provide a general guidance to a reader interested to learn about the methodologies to obtain accurate electron density mapping in molecules and crystalline solids, from theory or from experiment, and to carry out a sensible interpretation of the results, for chemical, biochemical or materials science applications. The review mainly focuses on X-ray diffraction techniques and refinement of experimental models, in particular multipolar models. Neutron diffraction, which was widely used in the past to fix accurate positions of atoms, is now used for more specific purposes. The review illustrates three principal analyses of the experimental or theoretical electron density, based on quantum chemical, semi-empirical or empirical interpretation schemes, such as the quantum theory of atoms in molecules, the semi-classical evaluation of interaction energies and the Hirshfeld analysis. In particular, it is shown that a simple topological analysis based on a partition of the electron density cannot alone reveal the whole nature of chemical bonding. More information based on the pair density is necessary. A connection between quantum mechanics and observable quantities is given in order to provide the physical grounds to explain the observations and to justify the interpretations.

Probing Charge Transfer in Benzodifuran-C-60 Dumbbell-Type Electron Donor-Acceptor Conjugates: Ground- and Excited-State Assays

Rigid electron donor-acceptor conjugates (1-3) that combine -extended benzodifurans as electron donors and C-60 molecules as electron acceptors with different linkers have been synthesized and investigated with respect to intramolecular charge-transfer events. Electrochemistry, fluorescence, and transient absorption measurements revealed tunable and structure-dependent charge-transfer processes in the ground and excited states. Our experimental findings are underpinned by density-functional theory calculations.

Scanning electron microscope study of the developing microvasculature in the postnatal rat lung.

During postnatal growth the parenchymal septa of rat lung undergo an impressive restructuring. While immature septa are thick and contain two capillary layers, mature septa are slender and contain a single microvascular network. Using the Mercox casting technique and scanning electron microscopy, we investigated the mode and the timing of the transformation of the pulmonary capillary bed. During the third postnatal week the parenchymal septa rapidly mature to match adult morphology. Even in adult lungs, however, remnants of the immature status are present: A capillary bilayer is regularly found at the base and the tip of the septa. Our observations support the concept that reduction of intervening tissue, partial fusion of the two capillary networks, and preferential growth lead to the mature vascular arrangement. The fact that true mature interalveolar septa show a denser capillary network than alveolar walls abutting onto pleura, bronchi, or larger vessels is consonant with the fusion theory. Towards the nonparenchyma, the capillary network surrounding every airspace had no counterpart to fuse with. From quantitative data it can be calculated that owing to lung growth, mesh size should increase more than four times between birth and adult age. The adult lung network, however, is denser than the one in young animals. This means that new meshes must be added during growth. We propose that small holes observed in sheet-like regions of the microvasculature enlarge to form new capillary meshes. With this mechanism of in-itself or intussusceptional growth, sprouting of individual capillary segments to increase network size is no longer needed.

Anti-PSMA antibody-coupled gold nanorods detection by optical and electron microscopies

While cancer is one of the greatest challenges to public health care, prostate cancer was chosen as cancer model to develop a more accurate imaging assessment than those currently available. Indeed, an efficient imaging technique which considerably improves the sensitivity and specificity of the diagnostic and predicting the cancer behavior would be extremely valuable. The concept of optoacoustic imaging using home-made functionalized gold nanoparticles coupled to an antibody targeting PSMA (prostate specific membrane antigen) was evaluated on different cancer cell lines to demonstrate the specificity of the designed platform. Two commonly used microscopy techniques (indirect fluorescence and scanning electron microscopy) showed their straightforwardness and versatility for the nanoparticle binding investigations regardless the composition of the investigated nanoobjects. Moreover most of the research laboratories and centers are equipped with fluorescence microscopes, so indirect fluorescence using Quantum dots can be used for any active targeting nanocarriers (polymers, ceramics, metals, etc.). The second technique based on backscattered electron is not only limited to gold nanoparticles but also suits for any study of metallic nanoparticles as the electronic density difference between the nanoparticles and binding surface stays high enough. Optoacoustic imaging was finally performed on a 3D cellular model to assess and prove the concept of the developed platform.

High-density metallic nano-emitter arrays and their field emission characteristics

We report the fabrication and field emission properties of high-density nano-emitter arrays with on-chip electron extraction gate electrodes and up to 106 metallic nanotips that have an apex curvature radius of a few nanometers and a the tip density exceeding 108 cm−2. The gate electrode was fabricated on top of the nano-emitter arrays using a self-aligned polymer mask method. By applying a hot-press step for the polymer planarization, gate–nanotip alignment precision below 10 nm was achieved. Fabricated devices exhibited stable field electron emission with a current density of 0.1 A cm−2, indicating that these are promising for applications that require a miniature high-brightness electron source.

Synergism of peptide receptor-targeted Auger electron radiation therapy with anti-angiogenic compounds in a mouse model of neuroendocrine tumors.

BACKGROUND Neuroendocrine tumors are well vascularized and express specific cell surface markers, such as somatostatin receptors and the glucagon-like peptide-1 receptor (GLP-1R). Using the Rip1Tag2 transgenic mouse model of pancreatic neuroendocrine tumors (pNET), we have investigated the potential benefit of a combination of anti-angiogenic treatment with targeted internal radiotherapy. METHODS [Lys40(Ahx-DTPA-111In)NH2]-exendin-4, a radiopeptide that selectively binds to GLP-1R expressed on insulinoma and other neuroendocrine tumor cells, was co-administered with oral vatalanib (an inhibitor of vascular endothelial growth factor receptors (VEGFR)) or imatinib (a c-kit/PDGFR inhibitor). The control groups included single-agent kinase inhibitor treatments and [Lys40(Ahx-DTPA-natIn)NH2]-exendin-4 monotherapy. For biodistribution, Rip1Tag2 mice were pre-treated with oral vatalanib or imatinib for 0, 3, 5, or 7 days at a dose of 100 mg/kg. Subsequently, [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 was administered i.v., and the biodistribution was assessed after 4 h. For therapy, the mice were injected with 1.1 MBq [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 and treated with vatalanib or imatinib 100 mg/kg orally for another 7 days. Tumor volume, tumor cell apoptosis and proliferation, and microvessel density were quantified. RESULTS Combination of [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 and vatalanib was significantly more effective than single treatments (p < 0.05) and reduced the tumor volume by 97% in the absence of organ damage. The pre-treatment of mice with vatalanib led to a reduction in the tumor uptake of [Lys40(Ahx-DTPA-111In)NH2]-exendin-4, indicating that concomitant administration of vatalanib and the radiopeptide was the best approach. Imatinib did not show a synergistic effect with [Lys40(Ahx-DTPA-111In)NH2]-exendin-4. CONCLUSION The combination of 1.1 MBq of [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 with 100 mg/kg vatalanib had the same effect on a neuroendocrine tumor as the injection of 28 MBq of the radiopeptide alone but without any apparent side effects, such as radiation damage of the kidneys.

Charge density analysis for crystal engineering

This review reports on the application of charge density analysis in the field of crystal engineering, which is one of the most growing and productive areas of the entire field of crystallography. While methods to calculate or measure electron density are not discussed in detail, the derived quantities and tools, useful for crystal engineering analyses, are presented and their applications in the recent literature are illustrated. Potential developments and future perspectives are also highlighted and critically discussed.

The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes.

Cryo-electron microscopy of vitreous section makes it possible to observe cells and tissues at high resolution in a close-to-native state. The specimen remains hydrated; chemical fixation and staining are fully avoided. There is minimal molecular aggregation and the density observed in the image corresponds to the density in the object. Accordingly, organotypic hippocampal rat slices were vitrified under high pressure and controlled cryoprotection conditions, cryosectioned at a final thickness of approximately 70 nm and observed below -170 degrees C in a transmission electron microscope. The general aspect of the tissue compares with previous electron microscopy observations. The detailed analysis of the synapse reveals that the density of material in the synaptic cleft is high, even higher than in the cytoplasm, and that it is organized in 8.2-nm periodic transcleft complexes. Previously undescribed structures of presynaptic and postsynaptic elements are also described.