Epimerization of trans-Cycloalkenes with the X–C=C–SeR*-Unit – The Steric Demand of X = H, F, Cl, Br, I, Me, Et and CF3

Trans-cycloalkenes with the X–C=C–SeR*-unit and ring sizes from 9 to 20 have been synthesized. Bond the selenium atom is the chiral (S)-o-(1-Methoxypropyl)phenyl-residue R*, and X = H, F, Cl, Br, I, Me, Et and CF3. The planar-chiral trans-cycloalkenes in combination with the chiral residue R* exist as two diastereomers. These can be distinguished in principle by NMR spectroscopy. We have studied the epimerization of the trans-cycloalkenes, i.e., the 180° rotation of the X–C=C-unit through the cavity of the ring. The measurements were done with variable temperature 13C NMR spectroscopy in the range from –110 to 140°C. The obtained values of the Gibbs energy of activation ΔG‡C depend strongly on the ring size. Furthermore, the ΔG‡C values show dramatic steric effects due to the groups X. The steric requirement of X increases in the series H << F << Cl < Me < Br < I < Et < CF3. Here, F is significantly larger than H, and CF3 is larger than Et. The corresponding iPr-compounds could not be synthesized. The transition state structures of the ring inversion for ring sizes 8–20 were calculated at the DFT level of theory

Regularization of the big bang singularity with random perturbations

We show how to regularize the big bang singularity in the presence of random perturbations modeled by Brownian motion using stochastic methods. We prove that the physical variables in a contracting universe dominated by a scalar field can be continuously and uniquely extended through the big bang as a function of time to an expanding universe only for a discrete set of values of the equation of state satisfying special co-prime number conditions. This result significantly generalizes a previous result \cite{Xue:2014} that did not model random perturbations. This result implies that the extension from a contracting to an expanding universe for the discrete set of co-prime equation of state is robust, which is a surprising result. Implications for a purely expanding universe are discussed, such as a non-smooth, randomly varying scale factor near the big bang.Comment: 21 pages, 4 figure

Hydration effects turn a highly stretched polymer from an entropic into an energetic spring

Polyethylene glycol (PEG) is a structurally simple and nontoxic water-soluble polymer that is widely used in medical and pharmaceutical applications as molecular linker and spacer. In such applications, PEG’s elastic response against conformational deformations is key to its function. According to text-book knowledge, a polymer reacts to the stretching of its end-to-end separation by a decrease in entropy that is due to the reduction of available conformations, which is why polymers are commonly called entropic springs. By a combination of single-molecule force spectroscopy experiments with molecular dynamics simulations in explicit water, we show that entropic hydration effects almost exactly compensate the chain conformational entropy loss at high stretching. Our simulations reveal that this entropic compensation is due to the stretching-induced release of water molecules that in the relaxed state form double hydrogen bonds with PEG. As a consequence, the stretching response of PEG is predominantly of energetic, not of entropic, origin at high forces and caused by hydration effects, while PEG backbone deformations only play a minor role. These findings demonstrate the importance of hydration for the mechanics of macromolecules and constitute a case example that sheds light on the antagonistic interplay of conformational and hydration degrees of freedom

Samarium Diiodide Acting on Acetone - Modeling Single Electron Transfer Energetics in Solution

Samarium diiodide is a versatile single electron transfer (SET) agent with various applications in organic chemistry. Lewis structures regularly insinuate the existence of a ketyl radical when samarium diiodide binds a carbonyl group. The study presented here investigates this electron transfer by the means of computational chemistry. All electron CASPT2 calculations with the inclusion of scalar relativistic effects predict an endotherm electron transfer from samarium diiodide to acetone. Energies calculated with the PBE0-D3(BJ) functional and a small core pseudopotential are in good agreement with CASPT2. The calculations confirm the experimentally measured increase of the samarium diiodide reduction potential through the addition of hexamethylphosphoramide also known as HMPA

One‐Pot Covalent Functionalization of 2D Black Phosphorus by Anionic Ring Opening Polymerization

In this work, a one‐pot approach for the covalent functionalization of few‐layer black phosphorus (BP) by anionic ring opening polymerization of glycidol to obtain multifunctional BP‐polyglycerol (BP‐PG) with high amphiphilicity for near‐infrared‐responsive drug delivery and biocompatibility is reported. Straightforward synthesis in combination with exceptional biological and physicochemical properties designates functionalized BP‐PG as a promising candidate for a broad range of biomedical applications

Streamlining the Exploration of Chemical Space for Aqueous Molecular Metal Oxides as Thin Film Precursors

Metal oxide thin films based on V, Mo, W, Nb and/or Ta are relevant for a wide range of applications such as high-k dielectric materials or diffusion barriers. Recent advances in manufacturing techniques allowed their production through the spin coating of molecular metal oxide in aqueous solution. This is more environmentally friendly and cost-effectively than the traditional non-aqueous methods, however it is key to understand their speciation and the influence of the experimental conditions such as temperature, pH and/or concentration. Density functional theory calculations were used to construct a complex speciation network up to the formation of hexanuclear molecular metal oxides. These results were used to map the potential energy surface through a normal mode sampling into a neural network potential capable to reproduce the quantum mechanics energetics at a fraction of the cost. The neural network potential can be subsequently used to expand the chemical space and the formation of the nanometric molecular metal oxides which are beyond the reach of quantum mechanics

Theoretische Untersuchungen multivalenter Reaktionen

A strong but easily reversible connection is important on the molecular level in biological recognition, adhesion, and signaling processes but also for drug design or supramolecular complexes. This connection can be achieved by using multivalency: the connection is formed with a large number of weak interactions instead of only one strong interaction. Multivalency and the underlying cooperative effects are not yet fully understood. Small multivalent crown ether/ammonium assemblies are used in this thesis as model system for multivalent interactions and as building blocks for functionalized supramolecular host-guest complexes. For analysis, a theoretical multilevel approach to determine the Gibbs energy of association in solution of these assemblies in silico has been developed. Dispersion corrected density functional theory is used to obtain the association energies in the gas phase. The effects of translation, rotation and vibration are taken into account by a rigid-rotor-harmonic-oscillator approximation with a free-rotor approximation for low-lying vibrations. The solvation is included by the implicit solvent models COSMO-RS and D-COSMO-RS. Addionally counterions have to be included explicitly for a good agreement with the experiments. The average deviation from the experimental results was about 5 kJ/mol, which is state-of-the-art. In collaboration with specialists for supramolecular chemistry and for molecular dynamic simulations new insights into the bond formation of crown ether/ammonium assemblies and multivalency were gained. Attractive spacer- spacer interactions yield a strong positive chelate cooperativity. The results were summarized to a general guideline to create multivalent molecular assemblies with high binding affinity. Most important is a high complementarity of host and guest. A mix of preoganisation and adaptability is preferred over maximizing the preoganisation by lowering the adaptability. Additionally this thesis includes the investigation of two functionlized supramolecular complexes: a photoswitch and a donor-acceptor complex. The theoretical multilevel approach to determine was then applied in a mechanistic investigation of the samarium diiodide mediated reductive coupling of the N-oxoalkylsubstituted methyl indole-3-carboxylates. It was found that the high diastereoselectivity in the cyclization step is caused by the formation of an energetically highly favorable chelate complex. Finally the stretching of polyethylene glycol in water was investigated in collaboration with experts for atomic force microscope experiments and molecular dynamic simulations. Surprisingly the stretching of polyethylene glycol in water is enthalpically unfavorable and not entropically unfavorable. This indicates that a multivalent host or guest in water with a flexible polyethylene glycol spacer suffers from an enthalpic penalty and not from an entropic penalty in complex formation. Together with the results of the crown ether/ammonium assemblies, this challenges the notion that flexible spacers cause in general an entropic penalty in complex formations. Spacer length, intramolecular interactions, solvent and counterions can affect the conformational space of both the flexible spacer and the whole system or have strong enthalpic effects. The in silico methods presented in this thesis are powerful tools to identify the important effects in chemical reactions and to comprehend the experimental findings.Feste, jedoch leicht reversible Verbindungen auf molekularer Ebene sind essentiell für biologische Prozesse und werden mittlerweile auch in der medizinischen Wirkstoffforschung und für supramolekulare Komplexe genutzt. Diese Art von Verbindung kann mittels Multivalenz erreicht werden, das heißt die Verbindung wird mit einer Vielzahl schwacher Wechselwirkungen geformt anstatt einer einzigen sehr starken. Multivalenz und die zugrundeliegenden kooperativen Effekte sind allerdings bis heute noch nicht vollständig verstanden. In der vorliegenden Dissertation werden kleine multivalente Kronenether/Ammonium Aggregate als Modellsystem für multivalente Wechselwirkungen und als Bausteine für funktionalisierte supramolekulare Wirt- Gast-Komplexe verwendet. Zur Analyse wurde eine theoretische Mehrstufen- Methode zur in silico Berechnung der Gibbs-Energie der Assoziation solcher Aggregate im Lösungsmittel entwickelt. In dieser wird die Assoziationsenergie der Partner in der Gasphase mit Hilfe von dispersionskorrigierter Dichtefunktionaltheorie bestimmt. Die Effekte der Translation, Rotation und Vibration werden mittels einer Starrer-Rotator-Harmonischer-Oszillator- Näherung mit Freier-Rotator-Näherung für niedrig liegende Vibrationen berücksichtigt. Die Solvatisierung wird mittels der Lösungsmittelmodelle COSMO-RS und D-COSMO-RS einbezogen. Zusätzlich müssen Gegenionen explizit mit berücksichtigt werden, um eine gute Übereinstimmung mit dem Experiment zu erhalten. Die durchschnittliche Abweichung zu den experimentellen Ergebnissen lag bei circa 5 kJ/mol. Dies entspricht dem derzeitigen Stand der Technik. In Kooperation mit Spezialisten für supramolekuare Chemie und für Moleküldynamik- Simulationen konnten neue Erkenntnisse über die Bildung von Kronenether/Ammonium Aggregaten und über die Multivalenz erhalten werden. Die Ergebnisse lassen sich zu einer allgemeinen Leitlinie für die Herstellung multivalenter molekularer Aggregate mit hoher Assoziationskonstante zusammenfassen. Am wichtigsten ist ein hoher Grad an Komplementarität von Wirt und Gast. In dieser Dissertation wurden darüber hinaus zwei funktionalisierte Wirt-Gast-Komplexe untersucht, ein Photoschalter und ein Elektronen-Donor- Akzeptor-Komplex. Die theoretische Mehrstufen-Methode zur Berechnung, wurde ebenfalls in einer mechanistischen Untersuchung einer Samariumdiiodid vermittelten reduktiven Kupplung angewendet. Es hat sich gezeigt, dass die hohe Diastereoselektivität im Zyklisierungsschritt durch die Bildung eines energetisch sehr vorteilhaften Chelatkomplexes hervorrufen wird. Des weiteren wurde mit Experten für Rasterkraftmikroskopie und Moleküldynamik-Simulationen die Dehnung von Polyethylenglycol in Wasser untersucht. Die Dehnung von Polyethylenglycol in Wasser war enthalpisch und nicht entropisch ungünstig. Das bedeutet, dass ein multivalenter Wirt oder Gast mit einem flexiblen Polyethylenglycol-Spacer bei der Komplexbildung enthalpisch und nicht entropisch benachteiligt ist. Zusammen mit dem Ergebnissen für die Kronenether/Ammonium Aggregate widerspricht dies der Auffassung, dass flexible Spacer im allgemeinen entropisch ungünstig sind. Die in silico Methoden, die in dieser Dissertation vorgestellt werden, stellen wirkungsvolle Werkzeuge dar, um die wichtigen Effekte in chemischen Reaktionen zu identifizieren und experimentelle Ergebnisse nachzuvollziehen

First principle investigation of the linker length effects on the thermodynamics of divalent pseudorotaxanes

The Gibbs energies of association (Gibbs free (binding) energies) for divalent crown-8/ammonium pseudorotaxanes are determined by investigating the influence of different linkers onto the binding. Calculations are performed with density functional theory including dispersion corrections. The translational, rotational and vibrational contributions are taken into account and solvation effects including counter ions are investigated by applying the COSMO-RS method, which is based on a continuum solvation model. The calculated energies agree well with the experimentally determined ones. The shortest investigated linker shows an enhanced binding strength due to electronic effects, namely the dispersion interaction between the linkers from the guest and the host. For the longer linkers this ideal packing is not possible due to steric hindrance

Gating the photochromism of an azobenzene by strong host–guest interactions in a divalent pseudo[2]rotaxane

The ability of an E-configured azobenzene guest to undergo photoisomerisation is controlled by the presence of a complementary host. Addition of base/acid allowed for a weakening/strengthening of the interactions in the divalent pseudo[2]rotaxane complex and hence could switch on/off photochromic activity.Peer Reviewe