Biocatalysis from a chemical point of view : case studies of technical and laboratory scale syntheses

Die Biochemie ist ein vergleichsweise junger Zweig der Chemie, obwohl sie schon seit Jahrtausenden vom Menschen im täglichen Gebrauch eingesetzt wird. Möchte man die Werkzeuge der Biochemie auf aktuelle chemische Fragestellungen anwenden wird die Dominanz der biologischen Sichtweise auf diesem Gebiet deutlich. In dieser Arbeit wurden biochemische Projekte mit Verbesserungspotential durch organisch chemische Herangehensweise optimiert. Werden bei einer Synthese die sekundären Parameter, z.B. die Nachhaltigkeit oder Reaktionssicherheit, auf Kosten der primären Parameter wie Ausbeute oder Reaktionsdauer verbessert oder leidet die generelle Effektivität einer Reaktion, besteht Handlungsbedarf. Da die biochemische Rifamycin S-Synthese durch die Verwendung eines aufwendigen Oxidationsmittels, der Meerrettichperoxidase, zwar nachhaltig aber nicht mehr effizient von statten ging, wurden Alternativen dazu aufgezeigt und optimiert. Die vorgestellte Oxidation von Rifamycin B zu Rifamycin O und dessen direkte Hydrolyse büßte nichts an Effektivität gegenüber dem bestehenden Prozesses ein und gewann dennoch ein hohes Maß an Nachhaltigkeit dazu. In einem weiteren Projekt wurde die biochemische Reduktion aktivierter C=C-Doppelbindungen vom organisch-chemischen Standpunkt aus betrachtet. Für diese Reaktion, basierend auf der Reduktion des Enzym-Flavins durch NADH-Cofaktoren, wurden NADH analoge Cofaktoren synthetisiert. Die von Hammett beschriebenen Substituenten-Effekte konnten hierbei für das elektrochemische Potential der synthetischen Cofaktoren gezeigt werden. Darüber hinaus konnte ein Cofaktor entwickelt werden mit dem die enzymatische Reduktion zehn Mal schneller als mit dem natürlichen Cofaktor möglich war. Eine weitere Anwendung fand diese Sichtweise bei der Betrachtung enzymatisch katalysierter Carbenreaktionen. Für die NH-Insertion konnte das Substratspektrum deutlich erweitert, sowie gänzlich neue Stoffklassen zur Reaktion gebracht werden. Dabei wurde ein Set neuer E.coli-eigener Proteine, die zur Katalyse von Carbenreaktionen geeignet sind, entdeckt. Die wohl bedeutendste Entdeckung dieser Arbeit ist die Protein-unterstütze Carbonyl-Olefinierung mit Carbenen. Die Durchführbarkeit dieser Reaktion mit E.coli Proteinen könnte die Grundlage zu einer biologischen und nachhaltigen Anwendung der Wittig-artigen Carbonyl Olefinierung sein. Im Rahmen dieser Arbeit konnte gezeigt werden, dass eine chemisch inspirierte Biologie ebenso interessant ist wie der umgekehrte häufiger angewandte Fall. Für das Feld der synthetischen Biologie ist dies ein wichtiger Fingerzeig für zukünftigeOptimierungsansätze.The biochemistry is a comparatively young area in chemistry although it has been used by mankind since centuries. When the tools of biochemistry are applied to current chemical questions the dominant biological view becomes apparent. In this work three case studies of chemical optimisation of biochemical reactions have been made. If a synthesis is made ecologically sustainable but therefore lacks efficiency due to low yield and selectivity, actions have to been taken. An example is the biochemical production of rifamycin S from rifamycin B. The enzymatic reaction was performed with the enzyme horseradish peroxidase to substitute the non-sustainable industrial reaction with hydrochloric acid in chlorinated solvents. This enzymatic reaction, however, is economically and therefore also ecologically inefficient and therefore not competitive with the current industrial process. Cheaper and readily available oxidation reagents than enzymes have been tested in a process thereby avoiding chlorinated solvents. Within this work I was able to show the oxidation of rifamycin B with ammonia persulfate to rifamycin O and the subsequent hydrolysis to rifamycin S in methanol without the loss of efficiency relative to the currently employed industrial process. In another case study the enzymatic reduction of activated C=C double bonds have been investigated from a chemists point of view. This reaction is based on the reduction of a prosthetic flavin in the active site of the ene-reductase enzyme via the nicotinamide cofactor NADH. The reaction optimisation was realised by the synthesis of several synthetic nicotinamide cofactors to vary the electrochemical potential of these derivatives. It was demonstrated that the substituent effects described by Hammett correlated to the electrochemical potential of the synthetic cofactors. With this strategy a novel cofactor with a tenfold accelerated reaction speed relative to NADH was identified. A third application of the chemical approach was shown for enzyme catalysed carbene reactions. The carbene insertion into NH bonds was limited to aromatic amines using the haem containing enzyme P450. By employing haem-containing proteins from E.coli the substrate scope was broadened for aliphatic NH-insertions as well as O-H-insertions. The probably most significant discovery in this work is the protein supported carbonyl olefination with carbenes. The feasibility of this reaction with E.coli proteins could be the foundation for a biological and sustainable application of the wittig-type carbonyl olefination. Within the scope of this work it was shown that a chemically inspired biology is an useful approach for the optimisation of processes in for the industrial and lab scale as well as the development of new reactions. For the field of synthetic biology the consideration from this chemical angle could be an important point for future optimisations

Coupling a single electron to a Bose-Einstein condensate

The coupling of electrons to matter is at the heart of our understanding of material properties such as electrical conductivity. One of the most intriguing effects is that electron-phonon coupling can lead to the formation of a Cooper pair out of two repelling electrons, the basis for BCS superconductivity. Here we study the interaction of a single localized electron with a Bose-Einstein condensate (BEC) and show that it can excite phonons and eventually set the whole condensate into a collective oscillation. We find that the coupling is surprisingly strong as compared to ionic impurities due to the more favorable mass ratio. The electron is held in place by a single charged ionic core forming a Rydberg bound state. This Rydberg electron is described by a wavefunction extending to a size comparable to the dimensions of the BEC, namely up to 8 micrometers. In such a state, corresponding to a principal quantum number of n=202, the Rydberg electron is interacting with several tens of thousands of condensed atoms contained within its orbit. We observe surprisingly long lifetimes and finite size effects due to the electron exploring the wings of the BEC. Based on our results we anticipate future experiments on electron wavefunction imaging, investigation of phonon mediated coupling of single electrons, and applications in quantum optics.Comment: 4 pages, 3 figures and supplementary informatio

Ultracold chemical reactions of a single Rydberg atom in a dense gas

Within a dense environment ($\rho \approx 10^{14}\,$atoms/cm$^3$) at ultracold temperatures ($T < 1\,\mu{}\text{K}$), a single atom excited to a Rydberg state acts as a reaction center for surrounding neutral atoms. At these temperatures almost all neutral atoms within the Rydberg orbit are bound to the Rydberg core and interact with the Rydberg atom. We have studied the reaction rate and products for $nS$ $^{87}$Rb Rydberg states and we mainly observe a state change of the Rydberg electron to a high orbital angular momentum $l$, with the released energy being converted into kinetic energy of the Rydberg atom. Unexpectedly, the measurements show a threshold behavior at $n\approx 100$ for the inelastic collision time leading to increased lifetimes of the Rydberg state independent of the densities investigated. Even at very high densities ($\rho\approx4.8\times 10^{14}\,\text{cm}^{-3}$), the lifetime of a Rydberg atom exceeds $10\,\mu\text{s}$ at $n > 140$ compared to $1\,\mu\text{s}$ at $n=90$. In addition, a second observed reaction mechanism, namely Rb$_2^+$ molecule formation, was studied. Both reaction products are equally probable for $n=40$ but the fraction of Rb$_2^+$ created drops to below 10$\,$% for $n\ge90$.Comment: 13 pages, 13 figure

Attitude and Orbit Control of the Grace Satellites at extremely low power

The two GRACE satellites were launched on March 17, 2002 by a Russian Rockot. GRACE not only was the first dual-satellite mission operated by German Space Operations Center (GSOC), but it also was the first formation flying at an altitude below 500 km. The mission was successful from a scientific point of view and the originally envisaged mission duration of five years finally became almost sixteen. A follow-on mission with the same partners started 2018 and JPL projects a new generation of satellites for gravity measurements in the twenties, so there was a strong incentive to prolong the GRACE mission as long as possible in order to minimize the gap. Infirmity comes with age and several components deteriorated towards the end or even were defunct. The scientific goals were still obtained to a very high level until June 2017, four months before decommissioning. The major challenge for operations was posed by the degradation of the NiH2 batteries. These are comprised of twenty cells packaged in the common pressure vessel (CPV) configuration. Three cells had shorted out on Grace 1 and seven on Grace 2 by the middle of 2017. The charge capacity of the operational cells was severely degraded. The longevity and the occurrence of several anomalies due to power problems depleted fuel ever more rapidly