Thiamin pyrimidine biosynthesis in Candida albicans : a remarkable reaction between histidine and pyridoxal phosphate

In Saccharomyces cerevisiae , thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest that His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.     

Three-dimensional metal-organic framework with highly polar pore surface: H2 and CO2 storage characteristics

A three-dimensional (3D) pillared-layer metal-organic framework, [Cd(bipy)(0.5)(Himdc)](DMF)](n) (1), (bipy =4,4'-bipyridine and Himdc = 4,5-imidazoledicarboxylate) has been synthesized and structurally characterized. The highly rigid and stable framework contains a 3D channel structure with highly polar pore surfaces decorated with pendant oxygen atoms of the Himdc linkers. The desolvated framework [Cd(bipy)(0.5)(Himdc)](n) (1') is found to exhibit permanent porosity with high H(2) and CO(2) storage capacities. Two H(2) molecules occluded per unit formula of 1' and the corresponding heat of H(2) adsorption (ΔH(H2)) is about ～9.0 kJ/mol. The high value of ΔH(H2) stems from the preferential electrostatic interaction of H(2) with the pendent oxygen atoms of Himdc and aromatic bipy linkers as determined from first-principles density functional theory (DFT) based calculations. Similarly, DFT studies indicate CO(2) to preferentially interact electrostatically (C(δ+)···O(δ-)) with the uncoordinated pendent oxygen of Himdc. It also interacts with bipy through C-H···O bonding, thus rationalizing the high heat (ΔH(CO2) ～ 35.4 kJ/mol) of CO(2) uptake. Our work unveiled that better H(2) or CO(2) storage materials can be developed through the immobilization of reactive hetero atoms (O, N) at the pore surfaces in a metal-organic framework.     

Some results on series and parallel systems of randomized components

We study the system (series/parallel) where the components are randomly chosen from two different batches. We assume that one batch is more reliable than the other in some stochastic sense. In the case of series systems we show that, under certain conditions, lifetime of one system dominates that of the other in different stochastic orders viz. hazard rate, down shifted hazard rate and likelihood ratio orders. Further, we show that the same principle holds for the reversed hazard rate and the likelihood ratio orders in the case of parallel systems.     

2,4‐Dimethyl‐1,3‐thiazole‐5‐carboxylic acid: an X‐ray structural study at 100 K and Hirshfeld surface analysis

The crystal structure of the title thiazolecarboxylic acid derivative, C₆H₇NO₂S, (I), has been determined from single‐crystal X‐ray analysis at 100 K. In the crystal packing, an interplay of O—H...N and C—H...O hydrogen bonds connects the molecules to form C(6)R₂²(8) polymeric chains, which are further linked via weak C—H...O hydrogen bonds into a two‐dimensional supramolecular framework. The relative contributions of different interactions to the Hirshfeld surface in (I) and a few related thiazolecarboxylic acid derivatives indicate that the H...H, N...H and O...H contacts can account for about 50–70% of the total Hirshfeld surface area in this class of compound.     

Super-resolution by pupil plane phase filtering

Resolution capability of any optical imaging system is limited by residual aberrations as well as diffraction effects. Overcoming this fundamental limit is called super-resolution. Several new paradigms for super-resolution in optical systems use ‘a posteriori’ digital image processing. In these ventures the three-dimensional point spread function (PSF) of the lens plays a key role in image acquisition. A straightforward tailoring of the PSF can be performed by appropriate pupil plane filtering. With a brief review of the state-of-art in this research area, this paper dwells upon the inverse problem of global optimization of the pupil function by phase filtering in accordance with the desired PSF.     

Chemistry of andrographolide: formation of novel di-spiropyrrolidino and di-spiropyrrolizidino-oxindole adducts via one-pot three-component [3+2] azomethine ylide cycloaddition

A facile synthesis of novel di-spiro compounds has been achieved via 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to the conjugated double bond of andrographolide. When the amino acid was changed from sarcosine to l-proline, the product formation took a different course as determined by 2D NMR and X-ray crystallographic analysis.     

Morphology and structure of gold-lithium niobate thin film: A laboratory source X-ray scattering study

Laboratory source X-ray scattering set-up has been used to determine the complete morphology and structure of an optically important composite thin film. Analysis of grazing incidence small angle X-ray scattering, X-ray reflectivity and powder diffraction data of Au/LiNbO₃ thin film prepared by sequential deposition of gold and lithium niobate on float glass substrate suggest that the Au-nanocrystallites are dispersed in amorphous medium, which although have average separation but do not have any long range periodicity other than growth or z-direction. The morphology of the nanocomposite thin film determined through X-ray scattering measurements agrees well with the measured optical absorption.     

Synthesis of Axially Chiral Biaryls through Sulfoxide‐Directed Asymmetric Mild C?H Activation and Dynamic Kinetic Resolution

A mild and robust direct C H functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non‐prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated.     

A Novel Thermal Knoevenacel Condensation via A Thermal Michael Reaction

In connection with the total synthesis of natural products by retro-mass spectral approach,^1–3 the thermal reaction between 6,7-dimethoxy-3-isochromanone 1 and benzalmalononitrile 3 was studied. The Knoevenagel condensation product⁴ was obtained over and above the expected Diels-Alder adduct. The scope, limitation and mechanism of the aforesaid unusual thermal Knoevenagel condensation through a thermal Michael reaction is described.     

Modulation of Photophysics and pKa Shift of the Anti‐cancer Drug Camptothecin in the Nanocavities of Supramolecular Hosts

This article reports the pK_a shift of an anti‐cancer drug, 20(S)‐camptothecin (CPT), upon encapsulation into the nanocavity of a cucurbit[7]uril (CB7) macrocycle. Steady‐state, time‐resolved fluorescence and electrospray ionisation mass spectrometry (ESI‐MS) studies provide evidence for the formation of both 1:1 and 2:1 (CB7 ? CPT) stoichiometries. Astonishingly, we have found that protonation of CPT takes place at a higher concentration of macrocycle (≥50 μM ) when the 2:1 stoichiometric complex develops. However, we did not find any proof for protonation of CPT when it is encased by a β‐cyclodextrin cavity, which has a cavity size almost the same as that of CB7. Hence, we conclude that electron‐rich carbonyl portals of CB7 have an important role in protonation of the drug in the 2:1 inclusion complex. Docking and semi‐empirical quantum chemical calculations have been employed to gain an insight into the molecular picture of orientation of CPT in the inclusion complexes. It is clearly seen from the optimised structure of the 2:1 (CB7 ? CPT) inclusion complex that the quinoline nitrogen of CPT does not reside within either of the CB7 cavities, rather it is almost sandwiched between two CB7 rings, and therefore, it experiences huge electron density exerted by both carbonyl portals of the macrocycles. As a result, the pK_a of CPT shifts from 1.2 to 6.2. Finally, controlled release of the drug has been achieved through the introduction of NaCl, which is rich in cells, as an external stimulus. We hope this recognition‐mediated binding and release mechanism can be useful for activation of the drug and controlled release of the drug in therapeutic uses.