Decoding the Structure of Non-Proteinogenic Amino Acids: The Rotational Spectrum of Jet-Cooled Laser-Ablated Thioproline

The broadband rotational spectrum of jet-cooled laser-ablated thioproline was recorded. Two conformers of this system were observed and identified with the help of DFT and ab initio computations by comparison of the observed and calculated rotational constants and 14N quadrupole coupling constants as well as the predicted energies compared to the observed relative populations. These conformers showed a mixed bent/twisted arrangement of the five-membered ring similar to that of the related compound thiazolidine with the N–H bond in axial configuration. The most stable form had the COOH group in an equatorial position on the same side of the ring as N-H. The arrangement of the C=O group close to the N-H bond led to a weak interaction between them (classified as type I) characterized by a noncovalent interaction analysis. The second form had a trans-COOH arrangement showing a type II O–H···N hydrogen bond. In thioproline, the stability of conformers of type I and type II was reversed with respect to proline. We show how the conformation of the ring depends on the function associated with the endocyclic N atom when comparing the structures of isolated thioproline with its zwitterion observed in condensed phases and with peptide forms.

Methodology development for the synthesis of iminosugars

<p>This thesis investigated the development and application of methodology for the synthesis of iminosugars. The first portion of this thesis (Chapters 2 and 3) explored the scope of previously established protecting-group-free Vasella-reductive-amination and I2-mediated carbamate annulation methodology initially developed within the Stocker-Timmer group for the synthesis of pyrrolidines and piperidines from aldose sugars. In this thesis, the Vasella-reductive-amination methodology was extended to include the use of ketose sugars as starting materials, thereby allowing for the synthesis of primary amines directly from in situ formed ketones under protecting-group-free conditions. The scope of the carbamate annulation was then explored, whereby it was determined that both steric and electronic effects appear to affect transition state energies during the annulation reaction. Here, formation of pyrrolidines with the 2,5-trans and 3,4-cis relationships are favoured, however, in circumstances were conflicting electronic- and steric-effects are present, steric-effects dominate thereby favouring the formation of the 2,5-trans product. Using a combination of this Vasella-reductive-amination and carbamate annulation methodology, 2,5-dideoxy-2,5-imino-L-iditol was thus synthesised in 6 steps and 18% overall yield from D-fructose. Next, the same methodology was applied to the synthesis of the promising molecular chaperone 2,5-dideoxy-2,5-imino-D-altritol. Thus, 2,5-dideoxy-2,5-imino-D-altritol was synthesised over 7 steps and in 22% yield from D-tagatose, which is the most efficient synthesis of this iminosugar to date. The second part of this thesis (Chapters 4 and 5) focused on the optimisation and development of synthetic methodology that would allow for the highly efficient synthesis of a variety of iminosugars including piperidines and azepanes. To this end, modifications to existing synthetic methodology allowed for the rapid synthesis of a variety of iodoglycosides, which are important synthons. Next, reductive amination/cyclisation methodology that allowed for the direct transformation of methyl iodoglycosides or isopropylidene-protected iodoglycosides into iminosugars was developed. As such, the piperidines 1-Deoxynojirimycin, 1-Deoxymannojirimycin (DMJ), L-1-Deoxygalactojirimycin (L-DGJ), and (3R,4r,5S)-piperidine-3,4,5-triol were prepared in 4 steps and good overall yields (44%, 62%, 67%, and 53%, respectively). In the case of DMJ and (3R,4r,5S)-piperidine-3,4,5-triol, these are the most efficient syntheses of these materials to date. Factors influencing the stereochemical outcome of the reductive amination reaction were also explored, and evidence suggests that the reduction occurs from the least sterically hindered face of an intermediate cyclic imine, whereby the preferred conformation of the imine is the one which places the largest number of substituents in the pseudo-equatorial position. Using analogous methodology, the azepane (3S,4R,5S,6R)-azepane-3,4,5,6-tetraol was also prepared in 4 steps and good yield (53%).</p>

Methodology development for the synthesis of iminosugars

<p>This thesis investigated the development and application of methodology for the synthesis of iminosugars. The first portion of this thesis (Chapters 2 and 3) explored the scope of previously established protecting-group-free Vasella-reductive-amination and I2-mediated carbamate annulation methodology initially developed within the Stocker-Timmer group for the synthesis of pyrrolidines and piperidines from aldose sugars. In this thesis, the Vasella-reductive-amination methodology was extended to include the use of ketose sugars as starting materials, thereby allowing for the synthesis of primary amines directly from in situ formed ketones under protecting-group-free conditions. The scope of the carbamate annulation was then explored, whereby it was determined that both steric and electronic effects appear to affect transition state energies during the annulation reaction. Here, formation of pyrrolidines with the 2,5-trans and 3,4-cis relationships are favoured, however, in circumstances were conflicting electronic- and steric-effects are present, steric-effects dominate thereby favouring the formation of the 2,5-trans product. Using a combination of this Vasella-reductive-amination and carbamate annulation methodology, 2,5-dideoxy-2,5-imino-L-iditol was thus synthesised in 6 steps and 18% overall yield from D-fructose. Next, the same methodology was applied to the synthesis of the promising molecular chaperone 2,5-dideoxy-2,5-imino-D-altritol. Thus, 2,5-dideoxy-2,5-imino-D-altritol was synthesised over 7 steps and in 22% yield from D-tagatose, which is the most efficient synthesis of this iminosugar to date. The second part of this thesis (Chapters 4 and 5) focused on the optimisation and development of synthetic methodology that would allow for the highly efficient synthesis of a variety of iminosugars including piperidines and azepanes. To this end, modifications to existing synthetic methodology allowed for the rapid synthesis of a variety of iodoglycosides, which are important synthons. Next, reductive amination/cyclisation methodology that allowed for the direct transformation of methyl iodoglycosides or isopropylidene-protected iodoglycosides into iminosugars was developed. As such, the piperidines 1-Deoxynojirimycin, 1-Deoxymannojirimycin (DMJ), L-1-Deoxygalactojirimycin (L-DGJ), and (3R,4r,5S)-piperidine-3,4,5-triol were prepared in 4 steps and good overall yields (44%, 62%, 67%, and 53%, respectively). In the case of DMJ and (3R,4r,5S)-piperidine-3,4,5-triol, these are the most efficient syntheses of these materials to date. Factors influencing the stereochemical outcome of the reductive amination reaction were also explored, and evidence suggests that the reduction occurs from the least sterically hindered face of an intermediate cyclic imine, whereby the preferred conformation of the imine is the one which places the largest number of substituents in the pseudo-equatorial position. Using analogous methodology, the azepane (3S,4R,5S,6R)-azepane-3,4,5,6-tetraol was also prepared in 4 steps and good yield (53%).</p>

Polymeric coordination complex of lithium(I) with aqua and cyanurate ligands

The polymeric title complex, poly[hexa-μ-aqua-diaquatetra-μ-cyanurato-tetralithium] [Li4(C3H2N3O3)4(H2O)7] n , synthesized at room temperature from an aqueous solution of lithium hydroxide and cyanuric chloride, crystallizes in the triclinic space group P\overline{1}. There are two distinct Li+ cations in the asymmetric unit, one of which, Li1, has distorted trigonal–bipyramidal geometry and is coordinated via oxygen to two cyanurate anions occupying equatorial positions, and three water molecules, two in the axial positions and the third in an equatorial position. One of the axial water ligands and the equatorial water ligand are involved in bridging to a crystallographically equivalent Li1 cation. A centre of inversion lies between the two Li1 cations and the Li1...Li1 distance is 3.037 (5) Å. The remaining axial water ligand bridges to the second Li cation, Li2, which is disordered over two crystallographic sites with approximately equal occupancy, and has an Li1...Li2 distance of 3.438 (7) Å. The terminal Li2 cation is coordinated to three water molecules and an oxygen atom from a cyanuric anion and has a distorted tetrahedral geometry. A three-dimensional network of intermolecular hydrogen bonds involving N—H...O, O—H...O and O—H...N interactions serves to hold the structure together, as confirmed by a Hirshfeld surface analysis. The title compound was further characterized using IR and UV–vis spectroscopy and TG–DTA analysis.

A novel method to improve the critical damage parameter of powder metallurgical components during the cold upsetting

In the metal forming process, the understanding of metal flows and the fracture strains are most significant to the failure/damage of the components. Usually, in metalworking, damage occurs because of nucleation, growth and coalescence of the void into a small fracture. These small fractures increased in the circumferential path due to the existence of stresses and the pores which leads to failure at the equatorial position during the upsetting of porous samples. Hence, the fracture of the workpieces strongly depends on the stresses and the pores. Such form of stresses and pores if relieved will give a better damage limit of the material. Therefore, in this research, a novel scheme of localised heating is adopted at the equatorial position of the compressed samples to enhance the critical damage parameter. The powder metallurgy route was used to prepare the required compacts with different relative densities (80%–90%) and 1 aspect ratio by applying suitable powder forming pressures. The upsetting test was performed on the obtained porous samples for various weight percentages of titanium (2%–6%) in the aluminium at the stable strain rate (0.1 s−1) and the damage location was noticed for various components. After the identification of damage position, various temperatures (100 °C–250 °C) of localised heating were attempted on the failure site of the specimens after some incremental stages of upsetting tests. The experimental results were analysed using various damage criteria and it was found that the initiation of failure is delayed and increased the critical damage value by selectively heating the samples because of relieving the stresses, reduction in porosity and changes in microstructure.

The Congo basin: an example of failed rift

&lt;p&gt;The Congo basin (CB), considered as a typical intracratonic basin, due its slow and long-lived subsidence history and the largely unknown formation mechanisms, occupies a large part of the Congo craton, derived from the amalgamation of different cratonic pieces. It recorded the history of deposition of up to one billion years of sediments, one of the longest geological records on Earth above a metamorphic basement. The CB initiated very probably as a failed rift in late Mesoproterozoic and evolved during the Neoproterozoic and Phanerozoic under the influence of far-field compressional tectonic events, global climate fluctuation between icehouse and greenhouse conditions and drifting of Central Africa through the South Pole then towards its present-day equatorial position. Since Cretaceous, the CB has been subjected to an intraplate compressional setting due to ridge-push forces related to the spreading of the South Atlantic Ocean, where most of sediments are being eroded and accumulated only in the center of the basin.&lt;/p&gt;&lt;p&gt;In this study, we first reconstructed the stratigraphy, the depths of the main seismic horizons, and the tectonic history of the CB, using geological and exploration geophysical data. In particular, we interpreted about 2600 km of seismic reflection profiles and well log data located inside the central area of the CB (Cuvette Centrale). We used the obtained results to constrain the gravity field data that we analyzed, in order to reconstruct the depth of the basement and investigate the shallow crustal structure of the basin. To this purpose, we used a gravity inversion method with two different density contrasts between the surface sediments and crystalline rocks.&lt;/p&gt;&lt;p&gt;The results evidence NW-SE trending structures, also revealed by magnetic and seismic data, corresponding to the alternation of highs and sediments filled topographic depressions, related to rift structures, characterizing the first stage of evolution of the CB. They also show a general good consistency between the seismic and gravity basement along the seismic profiles and evidence the presence of possible high-density bodies in the shallow to deep crust. The identified structures are prevalently the product of an extensional tectonics, which likely acted in more than one direction.&lt;/p&gt;&lt;p&gt;Therefore, we performed 3D numerical simulations to test the hypothesis of the formation of the CB as multi-extensional rift in a cratonic area, using the thermomechanical I3ELVIS code, based on a combination of a &amp;#64257;nite di&amp;#64256;erence method applied on a uniformly spaced Eulerian staggered grid with the marker-in-cell technique. To this purpose, the numerical tests have been conducted considering a sub-circular weak zone in the central part of the cratonic lithosphere and applying a velocity of 2.5 cm/yr in two orthogonal directions (N-S and E-W). We repeated these numerical tests by increasing the size of the weak zone and varying its lithospheric thickness. The results show the formation of a circular basin in the central part of the cratonic lithosphere, characterized by a series of highs and depressions, consistent with those obtained from geophysical/geological reconstructions.&lt;/p&gt;

Cretaceous Black Shales in the Pacific: The Equatorial Position Hypothesis

&lt;p&gt;Although anoxia is rare in modern oceans, the marine stratigraphic record is punctuated by sedimentary and geochemical evidence for episodes of widespread oceanic anoxia. The last time in Earth history that a large volume of the ocean became anoxic was in the middle Cretaceous: black organic-carbon-rich muds were repeatedly preserved on the deep seafloor during oceanic anoxic events (OAEs).&lt;/p&gt;&lt;p&gt;Sedimentary and geochemical evidence for oceanic anoxia during OAEs comes mainly from the Atlantic and Tethys Oceans. Data from the Pacific Ocean, which was the largest ocean basin in the middle Cretaceous, is scarce and equivocal. Based on black shales deposited at depths of about 500&amp;#8211;1500 m on seamounts, Monteiro et al. (2012) have suggested that at least 50 vol% of the ocean was anoxic at the climax of Cretaceous oceanic anoxia during the late Cenomanian. They also included a single black shale at DSDP Site 585 in the Mariana Basin as evidence for anoxia in the deep Pacific. We will show, however, that this is a mud turbidite reworked from shallower water.&lt;/p&gt;&lt;p&gt;For this study, we reviewed all available data and publications from scientific drilling that recovered Cretaceous sediments in the Pacific Ocean. The little available Cretaceous record from the Pacific consists mainly of well-oxidized sediments. The exceptions are black shales that occur at depths of about 500&amp;#8211;1500 m on seamounts. Takashima et al. (2011) have shown that the Asian and North American continental margins of the Pacific were indeed oxic for most of the late Cenomanian OAE.&amp;#160;&lt;/p&gt;&lt;p&gt;We used a new paleomagnetic reconstruction of the Pacific plate back to 150 Ma to show that all investigated Cretaceous organic-carbon-rich sediments in the Pacific Ocean were deposited while the site was located in the Equatorial Divergence Zone (10&amp;#176;S to 10&amp;#176;N). We therefore argue that organic matter deposition in the Pacific Ocean might not have been directly related to OAEs, but rather be associated with the passage of seamounts beneath the equatorial belt of high productivity.&lt;/p&gt;&lt;p&gt;Several authors have challenged suggestions that OAEs were characterized by globally pervasive anoxic deep water and pointed to the difficulty in sustaining whole-ocean anoxia, even in warm oceans. We agree and our results show that oceanic anoxia in the Pacific is a local phenomenon superposed on a global trend of expanded oxygen minima in the ocean.&lt;/p&gt;

From Ru-bda to Ru-bds: a step forward to highly efficient molecular water oxidation electrocatalysts under acidic and neutral conditions

Significant advances during the past decades in the design and studies of Ru complexes with polypyridine ligands have led to the great development of molecular water oxidation catalysts and understanding on the O−O bond formation mechanisms. Here we report a Ru-based molecular water oxidation catalyst [Ru(bds)(pic)2] (Ru-bds; bds2− = 2,2′-bipyridine-6,6′-disulfonate) containing a tetradentate, dianionic sulfonate ligand at the equatorial position and two 4-picoline ligands at the axial positions. This Ru-bds catalyst electrochemically catalyzes water oxidation with turnover frequencies (TOF) of 160 and 12,900 s−1 under acidic and neutral conditions respectively, showing much better performance than the state-of-art Ru-bda catalyst. Density functional theory calculations reveal that (i) under acidic conditions, the high valent Ru intermediate RuV=O featuring the 7-coordination configuration is involved in the O−O bond formation step; (ii) under neutral conditions, the seven-coordinate RuIV=O triggers the O−O bond formation; (iii) in both cases, the I2M (interaction of two M−O units) pathway is dominant over the WNA (water nucleophilic attack) pathway.

The smell of coffee: the carbon atom microwave structure of coffee furanone validated by quantum chemistry

The rotational spectra of coffee furanone (2-methyltetrahydrofuran-3-one) have been measured in the frequency range from 2.0 to 26.5 GHz using a molecular jet Fourier transform microwave spectrometer. Quantum chemical calculations used for the conformational analysis yielded two stable twist conformers, which were described using the Cremer–Pople notation for five-membered rings. The experimental spectrum of the more stable conformer with the methyl group in equatorial position was assigned and fitted using a rigid rotor model with centrifugal distortion corrections. The spectra of all five 13C-isotopologues could be observed in natural abundance. The carbon atom structure was experimentally deduced using Kraitchman’s equations and compared with the structure calculated by quantum chemistry.

1-Ethyl 2-methyl 3,4-bis(acetyloxy)pyrrolidine-1,2-dicarboxylate: crystal structure, Hirshfeld surface analysis and computational chemistry

The title compound, C13H19NO8, is based on a tetra-substituted pyrrolidine ring, which has a twisted conformation about the central C—C bond; the Cm—Ca—Ca—Cme torsion angle is 38.26 (15)° [m = methylcarboxylate, a = acetyloxy and me = methylene]. While the N-bound ethylcarboxylate group occupies an equatorial position, the remaining substituents occupy axial positions. In the crystal, supramolecular double-layers are formed by weak methyl- and methylene-C—H...O(carbonyl) interactions involving all four carbonyl-O atoms. The two-dimensional arrays stack along the c axis without directional interactions between them. The Hirshfeld surface is dominated by H...H (55.7%) and H...C/C...H (37.0%) contacts; H...H contacts are noted in the inter-double-layer region. The interaction energy calculations point to the importance of the dispersion energy term in the stabilization of the crystal.