Podcasts about 1h nmr

How do we decide which fats and oils to consume? Ideally we want to minimize the omega 6 Linoleic Acid consumption as much as possible Let's take a closer look at the fatty acid concentrations of the most common fats in our diet.   – Links For This Episode:  Linoleic acid concentrations in fats and oils http://www.distributionkatrina.com/english/comparison-of-dietary-fats.html   Increase in Adipose Tissue Linoleic Acid of US Adults in the Last Half Century https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4642429   Composition of adipose tissue and marrow fat in humans by 1H NMR at 7 Tesla https://www.sciencedirect.com/science/article/pii/S0022227520346733   Chia seed oil composition https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627181   Sesame oil composition https://www.mdpi.com/2073-4395/9/12/801/htm   Connect with Zane: ReLyte Electrolytes by Redmond Real Salt: https://shop.redmond.life?afmc=Zane Follow me on Instagram: https://www.instagram.com/zanegriggsfitness Follow me on YouTube: https://www.youtube.com/c/ZaneGriggs   QUICK EPISODE SUMMARY Let's talk about fat The different types of fat we store in our body What we can learn from cultures that don't eat a modern diet The risk of the different types of oil A look into what makes up the good oils Where PUFAs could be hiding in other oils  Why you shouldn't trust the packaging How to minimize your exposure to PUFAs

The discussion over what aspect of our diet has been driving the escalation of metabolic disease over the last 100 years has been a confusing one full of contradictory information. It would be logical to look for a change in our diet associated with such a dramatic change in the health of a population There are both correlated evidence and dietary trials to support the theory that the increase in linoleic acid, provided by the introduction of PUFA processed oils into our diet, is the driver. In this episode of Hunger Hunt Feast, I want to share a collection of them to help clarify some of the confusion. -- Episode Specific Links:  Linoleic acid concentrations in fats and oils http://www.distributionkatrina.com/english/comparison-of-dietary-fats.html Increase in Adipose Tissue Linoleic Acid of US Adults in the Last Half-Century https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4642429/ Composition of adipose tissue and marrow fat in humans by 1H NMR at 7 Tesla https://www.sciencedirect.com/science/article/pii/S0022227520346733 Diets could prevent many diseases https://www.researchgate.net/publication/10673140_Diets_could_prevent_many_diseases Corn Oil in Treatment of Ischemic Heart Disease https://ncbi.nlm.nih.gov/pmc/articles/PMC2166702/ Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse https://pubmed.ncbi.nlm.nih.gov/27886622/#:~:text=the%20male%20mouse-,Linoleic%20acid%20causes%20greater%20weight%20gain%20than%20saturated%20fat%20without,doi%3A%2010.1016%2Fj Effects of fatty acids on mitochondria: implications for cell death https://pubmed.ncbi.nlm.nih.gov/12206909/ Can linoleic acid contribute to coronary artery disease? https://pubmed.ncbi.nlm.nih.gov/8192728/ Effects of linoleate-enriched and oleate-enriched diets in combination with alpha-tocopherol on the susceptibility of LDL and LDL subfractions to oxidative modification in humans https://pubmed.ncbi.nlm.nih.gov/8148354/ Acrolein is a product of lipid peroxidation reaction https://www.jbc.org/article/S0021-9258(18)80708-6/fulltext#seccestitle90 The role of dietary oxidized cholesterol and oxidized fatty acids in the development of atherosclerosis https://pubmed.ncbi.nlm.nih.gov/16270280/ Rapeseed oil and sunflower oil diets enhance platelet in vitro aggregation and thromboxane production in healthy men when compared with milk fat or habitual diets https://pubmed.ncbi.nlm.nih.gov/1641826/ Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects https://link.springer.com/article/10.2119/molmed.2010.00078 Circulating levels of linoleic acid and HDL-cholesterol are major determinants of 4-hydroxynonenal protein adducts in patients with heart failure https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909262/ Circulating levels of linoleic acid and HDL-cholesterol are major determinants of 4-hydroxynonenal protein adducts in patients with heart failure https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909262/ Role of Physiological Levels of 4-Hydroxynonenal on Adipocyte Biology: Implications for Obesity and Metabolic Syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038367/ “The Hateful Eight: Enemy Fats That Destroy Your Health - Dr. Cate.” Dr. Cate, 22 May 2020,  https://drcate.com/the-hateful-eight-enemy-fats-that-destroy-your-health/ Effects of diets enriched in linoleic acid and its peroxidation products on brain fatty acids, oxylipins, and aldehydes in mice https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6180905/ Strong increase in hydroxy fatty acids derived from linoleic acid in human low-density lipoproteins of atherosclerotic patients https://pubmed.ncbi.nlm.nih.gov/9488997/ Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA https://journals.physiology.org/doi/full/10.1152/ajpheart.00480.2004?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org Changes in Dietary Fat Intake Alter Plasma Levels of Oxidized Low-Density Lipoprotein and Lipoprotein(a) https://pubmed.ncbi.nlm.nih.gov/9844997/ “Dr. Knobbe Presents, ‘Macular Degeneration - Preventable & Treatable - With an Ancestral Diet?' at Weston A. Price Foundation's Annual Conference - Wise Traditions - 2017 - Cure AMD Foundation.” Cure AMD Foundation, https://www.cureamd.org/dr-knobbe-presents-macular-degeneration-preventable-treatable-with-an-ancestral-diet-at-weston-a-price-foundations-annual-conference-wise-traditions-2017/ Unsaturated fatty acids and their oxidation products stimulate CD36 expression in human macrophages https://www.researchgate.net/publication/11260045_Unsaturated_fatty_acids_and_their_oxidation_products_stimulate_CD36_expression_in_human_macrophages Lowering dietary linoleic acid (LA) reduces bioactive oxidized linoleic acid metabolites in humans https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3467319/ Can linoleic acid contribute to coronary artery disease? https://www.researchgate.net/publication/15005994_Can_linoleic_acid_contribute_to_coronary_artery_disease A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans https://pubmed.ncbi.nlm.nih.gov/9844997/ Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2012.38 Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis https://www.bmj.com/content/346/bmj.e8707 Connect with Zane: ReLyte Electrolytes by Redmond Real Salt: https://shop.redmond.life?afmc=Zane Follow me on Instagram: https://www.instagram.com/zanegriggsfitness Follow me on YouTube: https://www.youtube.com/c/ZaneGriggs QUICK EPISODE SUMMARY What causes modern disease The hateful eight oils The correlation between vegetable oils and obesity The oxidation effects of LDL The truth about the dairy data How much cholesterol is in your brain  Where you can find a copy of today's mentioned study What we know about Linoleic acid

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.08.331090v1?rss=1 Authors: Lefort, G., Liaubet, L., Marty-Gasset, N., Canlet, C., Vialaneix, N., Servien, R. Abstract: Metabolomics is a promising approach to characterize phenotypes or to identify biomarkers. It is also easily accessible through NMR, which can provide a comprehensive understanding of the metabolome of any living organisms. However, the analysis of 1H NMR spectrum remains difficult, mainly due to the different problems encountered to perform automatic identification and quantification of metabolites in a reproducible way. In addition, methods that perform automatic identification and quantification of metabolites often do it for one given complex mixture spectrum. Hence, when a set of complex mixture spectra coming from the same experiment has to be processed, the approach is simply repeated independently for every spectrum, despite their resemblance. Here, we present a new method that is the first to identify and quantify metabolites by integrating information coming from several complex spectra of the same experiment. The performances of this new method are then evaluated on both simulated and real datasets. The results show an improvement in the metabolite identification and in the accuracy of metabolite quantifications, especially when the concentration is low. This joint procedure is available in version 2.0 of ASICS package. Copy rights belong to original authors. Visit the link for more info

Bond cleavage and formation are key steps in chemistry and biochemistry. The present work investigates the generation of diphenylmethyl cations (Ph2CH+) via photoinduced bond cleavage of diphenylmethyl derivatives with a cationic or neutral leaving group. The resulting Ph2CH+ cations and its numerous derivatives serve as reference electrophiles for one of the most extensive reactivity scales covering 40 orders of magnitude. In chapter 1, the focus is on the initial bond cleavage of diphenylmethyltriphenylphosphonium ions (Ph2CH−PPh3+) exhibiting a cationic leaving group. With the help of state-of-the-art quantum chemical and quantum dynamical methods, the reaction mechanism of the bond cleavage is revealed. Using a reduced model system, the potential energy surfaces can be calculated at the ONIOM level of theory along specially designed reactive coordinates. Two competing reaction channels emerge: a homolytic one in the S1 state and a heterolytic one in the ground state. They are connected via an energetically accessible conical intersection which makes an efficient generation of the observed Ph2CH+ cations feasible. In contradiction with the experiment in polar or moderately polar solvents, quantum dynamical calculations for the isolated molecule reveal the formation of Ph2CH• radicals. While electrostatic solvent effects are negligible in this system, dynamic solvent effects emerge as being essential to explain the molecular mechanism. Two methods with increasing complexity to describe the dynamic impact of the solvent environment are developed. The first approach, the dynamic continuum ansatz, treats the environment implicitly. It uses Stokes’ law and the dynamic viscosity of the solvent in combination with quantum chemically and dynamically evaluated quantities to obtain the decelerating force exerted on the dissociating fragments. The ansatz does not require any fitting of parameters. The second method, the QD/MD approach, is based on an explicit treatment of the solvent surrounding. It combines molecular dynamics (MD) simulations of the reactant in a box of solvent molecules with quantum dynamics (QD) calculations of the reactant’s dynamics. In this way, a more detailed microscopic picture of the molecular process can be derived taking into account individual arrangements of the solvent. Both methods unveil the crucial impact of the solvent cage on the bond cleavage mechanism. It hinders the free dissociation in the S1 state and guides the molecular system to the conical intersection. QD simulations including the non-adiabatic coupling around the conical intersection show the formation of Ph2CH+ within ∼400 fs which compares well with the initial rise of the cation absorption in the experiment. Chapter 2 deals with the position of the counterion X– in the ion pairs Ph2CH−PPh3+ X–, PhCH2−PPh3+ X–, and (p-CF3-C6H4)CH2−PPh3+ X– in solution with X– being Cl–, Br–, BF4–, and SbF6–. These structures are essential to clarify the role of oxidizable counterions like e.g. Cl– during the initial bond cleavage in dichloromethane. The structures determined quantum chemically in dichloromethane show a similar counterion position than in the crystal. They are confirmed by the good accordance of the calculated and measured 1H NMR shifts. The C(α)–H···X– hydrogen bonds account for the pronounced counterion-dependent 1H NMR shifts of the C(α)–H in CD2Cl2. The strong downfield shift of the signals increases according to SbF6– < BF4–

In this episode, we review proton NMR and take a trip to a Japanese wesite with lots of spectral data.

This video is part of a 28-lecture graduate-level course titled "Organic Spectroscopy" taught at UC Irvine by Professor James S. Nowick. The course covers infrared (IR) spectroscopy, mass spectrometry, and nuclear magnetic resonance (NMR) spectroscopy, the latter of which is the main focus. Topics covered in the NMR spectroscopy part of the course include chemical shifts, spin-spin coupling, dynamic effects in NMR spectroscopy, and 2D NMR spectroscopy (COSY, HMQC, HMBC, TOCSY, NOESY, ROESY).

NMR absorptions; chemical shift; 13C NMR; 1H NMR; integration; spin-spin splitting

Phycobilins are light harvesting pigments of cyanobacteria and red algae. In cyanobacteria, four phycobiliproteins are organized in phycobilisomes: phycocyanin (PC), allophycocyanin (APC), and often also phycoerythrocyanin (PEC) or phycoerythrin (PE). Their phycobilin chromophores, linear tetrapyrroles, are generally bound to the apoprotein at conserved positions by cysteinyl thioether linkages. A final step in phycobiliprotein biosynthesis is the post-translational phycobilin addition to the various biliproteins. In vivo, the correct attachment of most chromophores is catalyzed by binding-site and chromophore-specific lyases. Only two such lyases, which both belong to the E/F-type were known at the beginning of this work. Two additional types, S/(U)-type and T-type lyase, have been characterized during this work. In addition, the correct structures of the products from all three lyase types have been verified, and evidence was obtained for the reaction mechanisms. This characterization relied on two methodological advances. The first is the use of a multi-plasmidic expression system for reconstitution of phycobiliproteins in E. coli. After cloning of apophycobiliprotein genes, phycobilin biosynthesis genes and (putative) lyase genes from several cyanobacteria, various phycobiliproteins could be biosynthesized in the heterologous E. coli system using dual plasmids containing the respective genes. This heterologous system produces higher yields than the in vitro reconstitution, it is nearly devoid of spontaneous binding, better reproducible, and more easily controlled. The second methodological advance is the consequent use of a combination of chromatographic, electrophoretic and spectroscopic tools that allowed a full characterization of the structure and binding sites of attached chromophores. This included, besides optical spectroscopy, in particular mass and magnetic resonance (1H-NMR) spectroscopy. Using the unmodified genes coding for both subunits of PEC, as well as their cystein mutants, three lyases were identified for the three binding site. Besides the already known isomerizing lyase, PecE/PecF, for Cys-84 of α-PEC, these are the two new lyases, CpcT (all5339) for Cys-153 of β-PEC, and CpcS (alr0617) for Cys-82 of β-PEC. The spectroscopic analysis proved that the chromophores (PCB and PVB)are correctly attached to these three binding sites. Similarly, three lyases were identified for the three binding sites of CPC. The well known heterodimeric lyase (CpcE/CpcF) catalyzes the covalent attachment of PCB to αC84 of CPC, CpcS catalyses the site-selective attachment of PCB to cysteine-β84 in CpcB; and CpcT for cysteine-β155 of CpcB. CpcE/F is specific for CpcA, while CpcS and CpcT can react with both CpcB and PecB. We also tested the lyase activity of the deoxyhyposyl-hydroxylase (DOHH) from the malaria parasite, Plasmodium falciparum. This enzyme has Heat-like repeats that are characteristic for the E/F-type lyases, but it had not chromophore-attaching activity. The substrate specificity of the new lyase, CpcS (coded by alr0617), was further tested with APC subunits; It is very unspecific with regard to the acceptor protein and attaches PCB to ApcA1, ApcB, ApcD ApcF, as well as to the product of an additional gene, apcA2; of unknown function that is highly homologous to apcA1 coding for the APC α-subunit. Obviously, this lyase has a much broader substrate specificity than the E/F-type lyases, but it has high site-specificity, attaching the chromophore exclusively to the Cys-84 (consensus sequence) binding site of the APC subunits. CpcS from Anabaena PCC7120 is a relatively simple system, it acts as a monomer, and does not require any cofactors. CpcS binds PCB rapidly (

One of the important transformations of alcohols to esters is the reaction with acetic anhydride catalysed by 4-(dimethylamino)pyridine (DMAP) in the presence of an auxiliary base like triethyl amine. Although this is a widely used reaction, several questions left unaddressed until now: the reaction mechanism of the latter transformation was not completely conceived. Since Steglich and Litvenencko found DMAP in 1969 independently as nucleophilic catalyst, there was hardly any effort to search for new nucleophilic catalysts of higher catalytic efficiency than DMAP or 4-(pyrrolidinyl)pyridine (PPY). All chiral nucleophilic catalysts are based on these structural motifs and due to their lack of catalytic efficiency, there are hitherto no examples for kinetic resolution experiments of tertiary alcohols described. In this dissertation, the following goals were achieved: With computational methods, the reaction pathway of tert-butanol with acetic anhydride in the presence of DMAP was explored. Based on these results a fast computational tool was developed to screen for more efficient nucleophilic catalysts. The best candidates were synthesised, the catalytic efficiency quantified and the best catalysts applied in the synthesis of esters. The reaction mechanism of the acetylation of tert-alcohols was explored by calculating the nucleophilic and base catalysed reaction pathway of tert-butanol with acetic anhydride in the presence of DMAP at B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level of theory. In the course of this study, a nucleophilic and base catalysed reaction pathway with DMAP as catalyst was found. The energetically lowest transition state of the base catalysed reaction pathway is 37.9 kJ mol-1 higher in energy then the energetically lowest transition state in the rate-determining step of the nucleophilic reaction path. The combination of kinetic measurements with the calculation of the nucleophilic reaction path reveals that no triethyl amine is involved in the rate-determining step of nucleophilic reaction pathway. This shows clearly that nucleophilic catalysis is the preferred and that the acetate anion is deprotonating the alcohol in the rate-determining step. Furthermore, the results of the recalculation of the nucleophilic reaction path with a different catalyst show that a higher stabilisation of the transient acylpyridinium cation has a pivotal influence on the overall reaction rate of the ester formation. Therefore, relative acetylation enthalpies (ΔH298) were calculated at B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level of theory by using an isodesmic reaction approach. In this way a large number of new nucleophilic catalysts were screened and numerous promising candidates were synthesised which have a larger negative ΔH298 value then DMAP (-82.1 kJ mol 1). The catalytic effiency of the new nucleophilic catalysts was quantified by a test reaction using 1 equiv. of 1-ethynylcyclohexanol, 2 equiv. of acetic or isobutyric anhydride and 3 equiv. triethyl amine. The conversion of 1-ethynylcyclohexyl acetate or -isobutyrate was monitored by 1H NMR spectroscopy. Pyrido[3,4-b]pyrazine- and pyrido[3,4 b]quinoxaline-derivatives show the best catalytic effiency. Especially (rac) 5,10-diethyl-5,5a,6,7,8,9a,10-octahydropyrido[3,4 b]-quinoxaline (DOPQ) shows equal to better catalytic efficiency then 6,6-tricyloaminopyridine (TCAP), which was hitherto the best nucleophilic catalyst. DOPQ can be synthesised very efficiently in a four step protocol starting from commercially available 3,4-diaminopyridine and cyclohexane-1,2-dione with an overall yield of 45 % while TCAP is only available in a five step synthesis with an overall yield of 8-13 %. The synthesis of DOPQ starts with the Schiff-base formation of 3,4-diaminopyridine and cyclohexane-1,2-dione. Reduction with LiAlH4 yields the cis-configured octahydro[3,4-b]quinoxaline, which can be alkylated without the use of any protecting group in the presence of acetic anhydride in pyridine and subsequent reduction with LiAlH4/AlCl3 to yield DOPQ. The structure of the latter compound was confirmed by X ray single crystal structure. The new catalysts were applied to an enhanced Gooßen esterification to transform sterically hindered acids to their tert-butyl esters. The reaction mechanism was explored by monitoring the substrate, intermediate and product conversions with 1H NMR spectroscopy. With this enhanced reaction protocol, it was possible to transform 1-phenylcyclohexane carboxylic acid into the tert-butyl ester under high concentration conditions at room temperature in the presence of 5 mol% DOPQ within 270 min while with the standard DCC/DMAP protocol only the anhydride of the carboxylic acid is formed. With this very mild method, it was possible to convert a variety of substrates into their tert-butyl- and benzyl esters, which are not accessible with any other method starting from the free carboxylic acid. In the case of chiral substrates no lose of stereochemical information was detected. Combination of high concentration conditions and new catalysts provide attractive reaction times of a few minutes instead of several hours with the Gooßen protocol.

In der vorliegenden Arbeit werden stabile Übergangsmetall-Komplexe der d6-konfigurierten Metalle Rhenium(1), Ruthenium(2), Rhodium(3) und Iridium(3), sowie von Rhodium(1), Iridium(1), Palladium(2) und Platin(2) mit d8-Konfiguration hergestellt. Als Liganden kommen zweizähnige, aromatische N,N'- und N,P-Liganden ohne weitere funktionelle Gruppen zum Einsatz, bei denen die beiden Donor-Atome in einer 1,4-Relation zueinander stehen. Die gebildeten 5-Ring-Metallacyclen weisen entsprechend der beiden unterschiedlichen Donor-Atome zwei verschieden stark gebundene Koordinationsstellen auf. Die aus dieser Konstellation resultierenden Eigenschaften der isolierten Komplexe werden spektroskopisch (IR-, 1H-NMR, 13C-NMR, 31P-NMR) untersucht und die Molekülstrukturen durch Einkristall-Röntgenstrukturanalyse ermittelt. Bei den untersuchten relativ stabilen Systemen kann der Ligandenaustausch so gesteuert werden, dass voll charakterisierbare Spezies erhalten werden. Diese sollen das Verständnis katalytischer Reaktionen in labileren Systemen vertiefen, welche auch durch Modifikation der vorgestellten Liganden zugänglich sind.

Silazanes: Using HMDS and SiCl4 it was possible to synthesize and characterize several new silazanes. This could be done by direct reaction or with further reactive compounds. For the cyclic disilazane 2,2,4,4-tetrachloro-1,3-bis(trimethylsilyl)-[1,3,2,4]-diazadisiletidine it has been possible to proof the centric symmetry of the molecule in the solid state. Since the asymmetric unit was built up by one complete molecule and the tms-groups showed strong rotational disorder, this information was not accessible by X-ray diffraction analysis. A combination of calculations and experiments allowed to take a closer look at the conformation of the latter bis(trimethylsilylamino)­dichlorosilane. Although the molecule possesses only two NH-groups, three signals of different intensities pertaining to that bond were found in the IR-spectra. DFT calculations showed that these signals have to be related to different conformations of the molecule, which were unequivocally present in the solution. The condensation reaction of bis(trimethylsilylamino)dichlorosilane leads to poly-silicondiimide (sol-gel process) and, finally, to Si3N4. X-ray powder diffraction yields the following results: the tetrahedra Si(NH)4 or SiN4, appearing in amorphous poly-silicondiimide and the derived amorphous Si3N4, respectively, turned out to be partially edge-sharing. Si3N4 obtained from bis(trimethylsilylamino)dichlorosilane did not crystallize before reaching its decomposition temperature. Using bis(trimethylsilylamino)dichlorosilane and the corresponding secondary amine it has been possible to synthesize the substitution variants bis(trimethylsilylamino)-dialkylaminochlorosilane (alkyl = Me, Et, iPr) and bis(trimethylsilylamino)-bis(dialkylamino)silane (alkyl = Et). By using the dialkyltrimethylsilylamines, the appearance of precipitates could be suppressed. Further substitution variants of bis(trimethylsilylamino)­dichlorosilane could be obtained by further reaction with HMDS. The separation of the resulting silanes tris(trimethylsilylamino)chlorosilane and tetrakis(trimethylsilylamino)silane was found to be difficult due to the combination of thermal sensitiveness with a high boiling point. Separation from polymeric by-products was only possible using high vacuum. Reactions of metal containing silazanes: While handling the metal chlorides a crystalline oxonium salt could be isolated and its X-ray structure could be determined. In the crystal [Ti2Cl9]- showed up as a weakly coordinating anion. Therefor, the cation could be observed almost undisturbed. It consists of two molecules Et2O solvating a proton between them. The existence of the proton could be proven in solution by means of 1H NMR spectroscopy. The spectra of the 47Ti and 49Ti nuclei showed the anion to be persistent in solution. Reactions of the silazanes with TiCl4 in the presence of Et2NH did not yield the wanted titana­silazanes but ended up in the reduction of Ti(IV) and the formation of the salt [Et2NH2]+[(Et2NH)2TiCl4]-, which could be characterized using X-ray diffraction. However, the reaction of bis(trimethylsilylamino)­dichlorosilane with TiCl4 in non-polar or only weakly polar aprotic solvents quantitatively led to the crystalline titanosilazane [µ-ClTiCl2N(SiMe3)SiCl2NH2]2. This compound exhibits a planar Ti-N-Si-N ring as characteristic entity as well as Si, which is surrounded by two N and to Cl. The latter renders the compound a particularly suitable candidate for transformation into ternary silicon nitrides. In addition, while investigating the formation of [µ-ClTiCl2N(SiMe3)SiCl2NH2]2, an intermediate could be observed using NMR spectroscopy. After modification of the disilazane, and reaction of bis(trimethylsilylamino)­chlordiethylaminosilane with TiCl4, the salt [(Me3SiNH)2SiClNHEt2]+ [Et2NClSi(NSiMe3)2TiCl-µ-Cl3TiCl3] – could be isolated almost quantitatively. Because of the additional amino-group of the silazane, a reaction with TiCl4 could take place and the protons liberated during the reaction could be partially neutralized. The substance turned out to be unstable, and decomposed within several days. The products of that decomposition reaction could not be identified as yet. The change of the amino group resulted in a reaction of bis(trimethylsilylamino)­chlordimethylaminosilane with TiCl4. The main product is obtained as a yellow to orange powder and its structure could not be solved yet. However, a by-product of the reaction, the salt [Me2NH2]+ [TiCl6] –, could be characterized by X-ray diffraction. This suggests that the reaction of bis(trimethylsilylamino)­chlor­di­methyl­amino­silane with TiCl4 proceeds similar to the reaction of bis(trimethylsilylamino)­dichlorosilane with TiCl4. The salt [Me2NH2]+ [TiCl6] – was obtained also directly from Me2NH2Cl and TiCl4 as a powder. By elaborating this direct access, it could be seen that it may be possible to obtain further, yet unknown, crystalline phases by the reaction of Me2NH2Cl with TiCl4. Furthermore, reactions of the titanosilazane [µ-ClTiCl2N(SiMe3)SiCl2NH2]2 were a subject of interest. It could be shown that ammonolysis is a simple way to substitute the chlorine atoms bonded to Si. The use of secondary amines as reactants led to amorphous products, considered to be paramagnetic. The use of dialkyamino-trimethylsilylamines led to interesting reactions, and single crystalline products could be obtained. Pyrolysis: It was proven that the titanosilazane [µ-ClTiCl2N(SiMe3)SiCl2NH2]2 could be used to synthesize a nanocomposite consisting of nanocrystalline TiN and amorphous Si3N4. The elemental composition of the products showed a strong dependence on the reaction conditions of the pyrolysis. If using [µ-ClTiCl2N(SiMe3)SiCl2NH2]2, the products have been homogenous down to a few nanometers. A detailed investigation of the pyrolysis using temperature dependent X-ray powder diffraction gave no evidence for further crystalline phases. TG and MS investigations were assessed as a strong indication for a rearrangement of the titanosilazane molecule at about 120 °C. Performing the pyrolysis with ammonolized [µ-ClTiCl2N(SiMe3)SiCl2NH2]2, a less homo­genous distribution of the elements in the product resulted. The data from temperature dependent X-ray powder diffraction studies showed the existence of an additional crystalline phase besides NH4Cl and (NH4)2TiCl6 at about 250 °C.

>>Novel bacteriochlorophyll e structures and species-specific variability of pigment composition in green sulfur bacteria>Characterization and in situ carbon metabolism of phototrophic consortia>The significance of organic carbon compounds for in situ metabolism and chemotaxis of phototrophic consortia

GABA transporters GAT-1, GAT-2 and GAT-3 are new targets for drug design. The substitution of the nitrogen atoms in Nicopetic acid (11), Guvacine (12) and cis-4- Hydroxynicopetic acid (13) with appropriate bulky lipophilic groups resulted in very potent GABA uptake inhibitors for GAT-1 as well as for GAT-3. Pyrrolidine-2-acetic acid derivatives with the three N-substituents 24a-c (Scheme 54) also showed a highly potent inhibition at GAT-1 and GAT-3, respectively. My intention was to investigate how the potency of pyrrolindine-2-carboxylic acid derivatives and of pyrrolidine-2-acetic acid derivatives at GAT-1 and GAT-3 is influenced by the introduction of a hydroxy group or both of a hydroxy and a (4-methoxy)phenyl group at C-4. For this study, the N-substituents 24a-d were chosen. Thus, the four series of pyrrolidine derivatives 20-23 shown below were designed as potential GABA uptake inhibitors. L-trans-4-hydroxypyrrolidine [(2S,4R)-25] was chosen as a precursor, from which the four key intermediates (2S,4R)-38, (2R,4R)-38, (2S,4R)-86 and (2R,4R)-64 were synthesized. The known compounds (2S,4R)-38 and (2R,4R)-38 were prepared from (2S,4R)-25 according to literature procedures. N-protection of (2S,4R)-25 with Cbz group gave (2S,4R)-58 (90% yield). After a series of reactions  electrolysis (97% yield), O-silyl protection (85%), nucleophilic addition of 1- ethoxy-1-(trimethylsilyloxy)ethene (cis-71 79%; trans-71 9%) and finally O-deprotection (88%) and N-deprotection (89%)  (2R,4R)-64 was obtained in 46% overall yield [from (2S,4R)-25]. After the reaction conditions for the conversion of 70 into 71 have been optimized, the best stereoselectivity [a ratio of cis/trans 97:3; yield cis-71 74%, trans-(2S,4R)-71 1.7%] and a good yield of 88% (cis 79%, trans 9%) were achieved. BF3⋅Et2O appeared to be slightly better for a higher stereoselectivity than TiCl4. (2S,4R)-83 was obtained in 90% yield by protecting the hydroxy group of (2S,4R)-58. An Arndt-Eistert reaction (64% yield) starting from (2S,4R)-83 followed by a simultaneous N,Odeprotection (90% yield) of (2S,4R)-85 led to (2S,4R)-86 in 47% overall yield [from (2S,4R)- 25]. As illustrated in Scheme 58 and 59, (2S,4R)-38 and (2S,4R)-86, (2R,4R)-38 and (2R,4R)-64 were used as starting materials for the synthesis of the N-substituted target compounds (2S,4R)-40a-b, (2S,4S)-40a-b, (2R,4S)-40a-b, (2R,4R)-40a-b, (2S,4R)-89a-d, (2S,4S)-89a-d, (2R,4R)-89a-d and (2R,4S)-89a-d. N-alkylation of these four starting materials with the halides of 24a-d yielded the corresponding tertiary amines. Mitsunobu reactions gave access to the stereoisomers by inversion of the stereocenter at C-4 of the pyrrolidine ring. Finally upon hydrolysis, all the N-substituted pyrrolidine derivatives with a 2-carboxylic acid side chain or a 2-acetic acid side chain were obtained. In the same manners (scheme 58 and 59), the series 96 also were synthesized and finally their hydrogenolysis over Pd-C provided each of four stereoisomers 97. The N-substituted 4-oxopyrrolidine derivatives (2S)-52a-b and (2S)-100a-c (see Scheme 61) were prepared (81-92% yields) via Swern oxidation, and fortunately, the acid-sensitive Nsubstituent 24b was not affected. The N-Cbz-protected 4-oxopyrrolidine derivatives 60 and 108 (Scheme 61) were prepared in good yield (71-78%) via Jones’ oxidation, but in low yield (10-27%) via Swern oxidation. The addition reactions of the organometallic reagents to the N-substituted pyrrolidine derivatives 52a-b and (2S)-100b-c were carried out in two different ways. Depending on the starting material and the employed organometallic reagent, two different results were obtained: Under condition A [(4-MeOC6H4)MgBr at –78 °C in ether] the cis addition product (cis refers to the ester group) was formed as the major diastereomer and a good diastereoselectivity was achieved (cis/trans addition from 79:21 to 89:11; total yields 45- 65%); Under condition B [(4-MeOC6H4)MgBr/CeCl3 at –78 °C in THF], the trans addition product was obtained as a major diastereomer (cis/trans addition from 30:70 to 17:83; total yields 32-48%). In the case of the N-Cbz-protected pyrrolidine derivative (2S)-60, a single diastereomer (2S,4R)-61 was formed in 56% yield under condition B [(4-MeOC6H4)MgBr/CeCl3 in THF at – 60 °C for 4 h]. However, for the homologous (2S)-108 under the same conditions, (2S,4R)- 109 (25% yield) and a side product (5%) resulting from a simultaneous addition to the ester group were formed. The addition of (4-MeOC6H4)MgBr to (2S)-108 (at –78 °C in ether for 4 h), however, led to (2S,4R)-109 (38% yield) as a single diastereomer. Each of the N-substituted stereoisomers from the reaction above was subjected to a basic hydrolysis, which was followed by hydrogenolysis over Pd-C, where necessary, to afford the free amino acids (70-98% yields). Via the similar synthetic procedures as described above, the rest of the stereoisomers (2R,4R)- 57a-b and (2R,4S)-57a-b, (2R,4R)-104b-c and (2R,4S)-104b-c, (2R,4S)-63 and (2R,4S)-111 were obtained from (2R,4R)-39a-b, (2R,4R)-88b-c, (2R)-60 and (2R,4R)-73. The relative stereochemistry of the products obtained from the addition of the organometallic reagents to the 4-oxopyrrolidine derivatives was determined by chemical correlation and NOE measurements. NOE experiments performed with (2S,4R)-114 revealed that the phenyl group and H-2 are cis to each other. As important signals for the assignment overlapped in the 1H NMR spectrum of (2S,4R)-115, the NOE experiments were performed with (2S,4R)-111, which is the sodium salt of (2S,4R)-115. The NOE measurement revealed that the phenyl group is located cis to H- 2, thus, (2S,4R)-111 and (2S,4R)-115 being of the stereochemistry shown. The N-alkylation of (2S,4R)-114 with the bromide of 24a, and of (2S,4R)-115 with the bromide of 24c led to (2S,4R)-53a and (2S,4R)-102c, respectively. With these compounds as references, also the stereochemistry of all related compounds differing only in side chain on the amino nitrogen could be deduced. The target compounds obtained in this study were evaluated for their biological activities. Membrane fractions from frontal cortex of bovine brain (or porcine brain) were utilized to study the inhibitory potency of the test compounds regarding the GAT-1-mediated GABAuptake. For the determination of the potency as GAT-3 inhibitors, membrane fractions from brain stem of bovine brain (or porcine brain) were used. As compared to the corresponding 4-unsubstituted compounds with (2S) configuration (IC50 2.56 µM at GAT-1) and with (2R) configuration (IC50 18.5 µM), the 40a-b series containing a 4-hydroxy group showed a significant drop in the inhibitory potency at both GAT-1 and GAT-3, only one compound [(2R,4R)-40a] showed a reasonable potency at GAT-1 (IC50 9.4 µM) and no one of them for GAT-3 (IC50 > 100 µM). (2S,4S)-89a (IC50 3.29 µM at GAT-1) and (2S,4S)-89c (5.14 µM), (2S,4R)-89a (4.92 µM) and (2S,4R)-89c (3.15 µM) exhibiting a 4-hydroxypyrrolidine-2-acetic acid skeleton showed an inhibitory potency at GAT-1, which was only one order of magnitude lower than the potency of corresponding compounds with (2S) configuration without the 4-hydroxy group (with Nsubstituent 24a: IC50 0.40 µM and with N-substituent 24c: 0.34 µM). (2R,4S)-89b was the most potent inhibitor at GAT-3 (IC50 19.9 µM) of all the stereoisomers of series 89a-d and showed a much higher potency than its isomer (2R,4R)-89b (126 µM). According to these data a 4-hydroxy group is detrimental to the potency at both GAT-1 and GAT-3, and (2S)-configuration of the pyrrolidine-2-acetic acid unit is crucial for a reasonable potency at GAT-1. As compared to the 40b series, some stereoisomers of the 57b series, the latter exhibiting a (4-methoxy)phenyl group at C-4 of the pyrrolidine ring, showed an increased potency as inhibitors at GAT-1 and GAT-3 [e.g. (2S,4R)-57b: IC50 29.7 µM at GAT-3; (2R,4S)-57b: IC50 of 38.0 µM at GAT-3]. In contrast, the introduction of a (4-methoxy)phenyl group into C-4 of the 89b-c series, resulting in the compounds of 104b-c, gave rise to diverse biological results. As compared with (2R,4S)-89b, (2R,4R)-104b displayed a loss of inhibitory potency at GAT- 3 but some enhancement at GAT-1.