Dmytro Dudenko

Packing Interactions in Hydrated and Anhydrous Forms of the Antibiotic Ciprofloxacin: a Solid-State NMR, X-ray Diffraction, and Computer Simulation Study

We present an experimental NMR, X-ray diffraction (XRD), and computational study of the supramolecular assemblies of two crystalline forms of Ciprofloxacin: one anhydrate and one hydrate forming water wormholes. The resonance assignment of up to 51 and 54 distinct (13)C and (1)H resonances for the hydrate is reported. The effect of crystal packing, identified by XRD, on the (1)H and (13)C chemical shifts including weak interionic H-bonds, is quantified; (1)H chemical shift changes up to ∼-3.5 ppm for CH···π contacts and ∼+2 ppm (CH···O((-))); ∼+4.7 ppm (((+))NH···O((-))) for H-bonds. Water intake induces chemical shift changes up to 2 and 5 ppm for (1)H and (13)C nuclei, respectively. Such chemical shifts are found to be sensitive detectors of hydration/dehydration in highly insoluble hydrates.

Use of X-Ray Diffraction, Molecular Simulations, and Spectroscopy to Determine the Molecular Packing in a Polymer-Fullerene Bimolecular Crystal

The molecular packing in a polymer: fullerene bimolecular crystal is determined using X-ray diffraction (XRD), molecular mechanics (MM) and molecular dynamics (MD) simulations, 2D solid-state NMR spectroscopy, and IR absorption spectroscopy. The conformation of the electron-donating polymer is significantly disrupted by the incorporation of the electron-accepting fullerene molecules, which introduce twists and bends along the polymer backbone and 1D electron-conducting fullerene channels.

Empty helical nanochannels with adjustable order from low-symmetry macrocycles.

Natural channel-forming structures are mandatory for connecting different compartments within a living organism. For instance, transmembrane proteins function as ion channels, transporters, or antibiotics. Biomacromolecules that are formed during evolution self-assemble into tubular structures with precisely defined positions of functional groups. The stimuli-responsive activity of these molecules has inspired the search for artificial channel-forming structures that can mimic the functionality of the natural systems. Artificial channel systems may even include new functionalities in advanced chemical applications. Several attempts, including templating methods, have been reported for the de novo design of pore-forming structures that are stable both in solution and in the bulk state. In particular, macrocycles have an attractive topology for the formation of supramolecular channels if they organize in a columnar mesophase with close packing of successive rings. If properly designed, a channel is created with tight walls that do not allow the penetration of small molecules. In contrast to macrocycles that are held together by strong intermolecular forces, such as hydrogen bonds in cyclopeptides or cyclosaccharides, the increased mobility in the liquid-crystalline (LC) phase allows for self-healing and orientation of the channels by external forces (shear, electromagnetic fields, surface properties, etc.). When the channels are appropriately functionalized, the inclusion and manipulation of nano-objects becomes feasible. Columnar mesophases have indeed been found in macrocyclic polyamines. However, because of their flexibility, the macrocyclic rings assume a folded conformation and stable phases with large open voids have not been reported to date. This problem might be overcome by using shapepersistent macrocycles, and columnar liquid-crystalline compounds based on cyclic phenylene and phenylene–ethynylene oligomers with inner diameters of up to 1 nm, as deduced from X-ray diffraction studies (XRD), have been reported (Figure 1a). Powder XRD cannot provide details about the packing of the macrocycles on the molecular level, 12c] whereas solid-state NMR spectroscopy can provide this information with the help of quantum-chemical calculations. In contrast to diffraction techniques, NMR spectroscopy does not require strict periodicity and is therefore particularly suited to probe the local structure in LC phases. Moreover, NMR spectroscopy can be used to reveal the presence of guest molecules inside the channels, including back-folded side chains. Herein, we describe two phenylene–ethynylene–butydiynylene macrocycles 1a and 1b (Figure 1b), each of which contains two benzo[1,2-b:4,3-b’]dithiophene units that include a nanoscale interior with a diameter as large as approximately 1.3 nm (Figure 1a). At the expense of symmetry, we have introduced groups with different electron affinities. Both macrocycles 1a and 1 b were obtained by the statistical oxidative Glaser coupling of the appropriate “half-rings” under Pd/Cu catalysis, and were obtained in yields of 33% (1a) and 50% (1 b) after purification by recycling gel-permeation chromatography (recGPC) using THF as eluent, and subsequent precipitation from methanol and drying under vacuum. The compounds were obtained as slightly yellow powders that do not contain residual solvents as shown by NMR spectroscopy of solutions in dichloromethane (see the Supporting Information). Upon heating above room temperature, the compounds become waxy materials that are birefringent under optical microscopy (crossed polarizers). Differential scanning calorimetry (DSC) investigations (2nd heating; 10 8C min ) showed reversible endothermic transitions for both compounds, thus indicating different LC phases over a broad temperature range (1a : 22 8C (138.9 kJ mol ), 109 8C (85.2 kJmol ), 151 8C (2.8 kJ mol ); 1b : 33 8C (116.6 kJmol ), 160 8C (2.6 kJ mol )). The type of LC phases formed and the lattice parameters were determined by XRD. Upon cooling from the isotropic [*] Dr. M. Fritzsche, Dr. G. Richardt, Prof. Dr. S. H ger Kekul -Institut f r Organische Chemie und Biochemie Rheinische Friedrich-Wilhelms-Universit t Bonn Gerhard-Domagk-Str. 1, 53121 Bonn (Germany) Fax: (+ 49)228-73 5662 E-mail: hoeger@uni-bonn.de

Probing the Relation Between Charge Transport and Supramolecular Organization Down to Ångström Resolution in a Benzothiadiazole‐Cyclopentadithiophene Copolymer

Molecular modeling shows that longitudinal displacement of the backbones by a couple of ångströms has a profound impact on the electronic coupling mediating charge transport in a conjugated copolymer. These changes can be probed by monitoring the calculated X-ray scattering patterns and NMR chemical shifts as a function of sliding of the polymer chains and comparing them to experiment.

Unraveling unprecedented charge carrier mobility through structure property relationship of four isomers of didodecyl[1]benzothieno[3,2-b][1]benzothiophene

The structural and electronic properties of four isomers of didodecyl[1]-benzothieno[3,2-b][1]benzothiophene (C12-BTBT) have been investigated. Results show the strong impact of the molecular packing on charge carrier transport and electronic polarization properties. Field-induced time-resolved microwave conductivity measurements unravel an unprecedented high average interfacial mobility of 170 cm(2) V(-1) s(-1) for the 2,7-isomer, holding great promise for the field of organic electronics.

The impact of the amide connectivity on the assembly and dynamics of benzene-1,3,5-tricarboxamides in the solid state

Solid-state NMR experiments as well as extensive Car–Parrinello Molecular Dynamics simulations are used to study the dependence of supramolecular self-organization of benzene-1,3,5-tricarboxamides (BTA) on the local orientation of the amide functionality. Unlike the known symmetric co-planar helical arrangement of CO-centered BTAs found in supramolecular architectures like supramolecular polymers in gels, N-centered BTAs adopt an asymmetric helical arrangement in the solid-state. The resulting tilt angle between the aromatic cores of neighboring BTA molecules leads to a breaking of the three-fold molecular symmetry and thus causes a splitting of 1H MAS NMR signals. At elevated temperatures, motional averaging of the split 1H MAS NMR signals is observed, which can be attributed to certain dynamics on the ms time scale of individual BTA molecules in the columnar packing arrangement.

Coexistence of helical morphologies in columnar stacks of star-shaped discotic hydrazones.

Discotic hydrazone molecules are of particular interest as they form discotic phases where the discs are rigidified by intramolecular hydrogen bonds. Here, we investigate the thermotropic behavior and solid-state organizations of three discotic hydrazone derivatives with dendritic groups attached to their outer peripheries, containing six, eight, and ten carbons of linear alkoxy chains. On the basis of two-dimensional wide angle X-ray scattering (2DWAXS), the elevated temperature liquid crystalline (LC) phases were assigned to a hexagonal columnar (Colh) organization with nontilted hydrazone discs for all three compounds. With WAXS, advanced solid-state nuclear magnetic resonance (SSNMR) techniques, and ab initio computations, the compounds with six and ten carbons of achiral alkoxy side chains were further subjected to studies at 25 °C, revealing complex crystalline phases with rigid columns and flexible side chains. This combined approach led to models of coexisting helical columnar stacking morphologies for both systems with two different tilt/pitch angles between successive hydrazone molecules. The differences in tilt/pitch angles between the two compounds illustrate that the columns with short alkoxy chains (six carbons) are more influenced by the presence of other stacks in their vicinity, while those with long side chains are less tilted due to a larger alkoxy (ten carbons) buffer zone. The formation of different packing morphologies in the crystalline phase of a columnar LC has rarely been reported so far, which suggests the possibility of complex stacking structures of similar organic LC systems, utilizing small molecules as potential materials for applications in organic electronics.

Ammonia as a case study for the spontaneous ionization of a simple hydrogen-bonded compound

Modern ab initio calculations predict ionic and superionic states in highly compressed water and ammonia. The prediction apparently contradicts state-of-the-art experimentally established phase diagrams overwhelmingly dominated by molecular phases. Here we present experimental evidence that the threshold pressure of ~120 GPa induces in molecular ammonia the process of autoionization to yet experimentally unknown ionic compound--ammonium amide. Our supplementary theoretical simulations provide valuable insight into the mechanism of autoionization showing no hydrogen bond symmetrization along the transformation path, a remarkably small energy barrier between competing phases and the impact of structural rearrangement contribution on the overall conversion rate. This discovery is bridging theory and experiment thus opening new possibilities for studying molecular interactions in hydrogen-bonded systems. Experimental knowledge on this novel ionic phase of ammonia also provides strong motivation for reconsideration of the theory of molecular ice layers formation and dynamics in giant gas planets.

Towards sugar-derived polyamides as environmentally friendly materials

As part of our ongoing study investigating isohexide-based polyamides, we have synthesized isosorbide(bis(propan-1-amine)) (DAPIS) and studied its reactivity in the polymerization towards fully biobased polyamides. Polycondensation of nylon salts with various contributions of DAPIS afforded a family of homo- and copolyamides, which were characterized using complementary spectroscopic techniques. The chemical structure of the materials was determined by FT-IR, 1D and 2D liquid-state NMR spectroscopy, whilst the supramolecular arrangement, conformational changes upon heating, and molecular mobility of the polymers were investigated by solid-state 13C{1H} Cross-Polarization/Magic-Angle Spinning (CP/MAS) NMR and 13C{1H} Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) experiments. The abundance of the different DAPIS conformers was determined by DFT-D computational methods. The thermal properties of the polyamides were tested for polymers with different amounts of isohexide units in the backbone by DSC and TGA, demonstrating that the increasing amounts of isohexide diamines efficiently decrease their melting points and slightly decrease their thermal stability. The relaxation processes of the isohexide-derived polyamides were studied by DMTA.

Emulating Natural Product Conformation by Cooperative, Non‐Covalent Fluorine Interactions

Pervasive in Nature, the propane unit is an essential component of numerous bioactive molecules. These range from acyclic systems, such as the neurotransmitter γ-aminobutyric acid, through to the bicyclic nuclei of various chromanes and dihydrobenzofurans. In the latter case, cyclisation via cyclic ether formation ensures a highly pre-organised structure, whilst linear scaffolds display more dynamic conformational behaviour resulting from rotation about the two internal C(sp3 )-C(sp3 ) bonds. In this study, the replacement of -[CH2 ]- units by -[CHF]- centres is evaluated as a strategy to achieve acyclic conformational control by hindering these internal rotations. Reinforcing, non-covalent fluorine interactions are validated as powerful design features that result in programmable conformational behaviours: These are encoded by the relative configuration of each centre. By exploiting cooperative neighbouring stereoelectronic effects in a multi-vicinal fluoroalkane it is possible to emulate the overall conformation of the dihydrobenzofuran scaffold found in a variety of natural products with an acyclic mimic. This is described as a function of two bond vectors at the chain termini and validated by combined theoretical, crystallographic and spectroscopic analyses. In view of the favourable physicochemical properties associated with fluorine introduction, this approach to bioactive scaffold design may prove to be expansive.