Scientific facilities generate vast amounts of data, not only large but also diverse and at a fast speed. Additional challenges are posed by the management of users, instruments, report generation, and invoicing. Here we present EMhub, a web platform designed to address these challenges by supporting daily operations of a scientific facility. It allows manipulation of users, instruments, bookings, and project tracking in a simple way. The application was originally inspired by the needs of a CryoEM facility, but it has been general enough that its implementation is extended to other domains. EMhub is implemented in a modular way, allowing the extension of the core functionality. Moreover, different external processes can be connected to the application via a REST API to automate various tasks (e.g. folder creation, user and password generation, etc) and for monitoring on-the-fly data processing independently of the software used. EMhub has been in use in the last few years at the Swedish National CryoEM Facility and more recently also installed in the CryoEM center at the Structural Biology Department at St. Jude Children's Research Hospital. There, a fully automated single particle pipeline has been implemented for on-the-fly data processing and analysis. At St. Jude, the Xray Crystallography Center and the Single-Molecule Imaging Center have already extended the platform to support their data management workflows.

Most scientific facilities produce large amounts of heterogeneous data at a rapid pace. Managing users, instruments, reports and invoices presents additional challenges. To address these challenges, EMhub, a web platform designed to support the daily operations and record-keeping of a scientific facility, has been introduced. EMhub enables the easy management of user information, instruments, bookings and projects. The application was initially developed to meet the needs of a cryoEM facility, but its functionality and adaptability have proven to be broad enough to be extended to other data-generating centers. The expansion of EMHub is enabled by the modular nature of its core functionalities. The application allows external processes to be connected via a REST API, automating tasks such as folder creation, user and password generation, and the execution of real-time data-processing pipelines. EMhub has been used for several years at the Swedish National CryoEM Facility and has been installed in the CryoEM center at the Structural Biology Department at St. Jude Children's Research Hospital. A fully automated single-particle pipeline has been implemented for on-the-fly data processing and analysis. At St. Jude, the X-Ray Crystallography Center and the Single-Molecule Imaging Center have already expanded the platform to support their operational and data-management workflows.

Murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP) are important cell survival proteins in tumor cells. As a dual MDM2/XIAP inhibitor reported previously, compound MX69 has low potency with an IC50 value of 7.5 μM against an acute lymphoblastic leukemia cell line EU-1. Herein, we report the structural optimization based on the MX69 scaffold, leading to the discovery of a 25-fold more potent analogue 14 (IC50 = 0.3 μM against EU-1). We demonstrate that 14 maintains its mode of action by dual targeting of MDM2 and XIAP through inducing MDM2 protein degradation and inhibiting XIAP mRNA translation, respectively, which resulted in cancer cell growth inhibition and cell death. The results strongly suggest that the scaffold based on 14 is promising for further optimization to develop a new therapeutic agent for leukemia and possibly other cancers where MDM2 and XIAP are dysregulated.

Structural modifications of molecular cobalt catalysts have provided important insights into the structure-function relationship for the hydrogen evolution reaction. We have shown that replacement of equatorial pyridines with more basic and conjugate isoquinoline groups of a pentadentate ligand results in lower overpotential and higher catalytic activity for electro- and photolytic H-2 production in aqueous solutions. To fully understand the electronic and steric effects of the axial group that lies trans to the proposed cobalt hydride intermediate, isoquinoline groups were introduced in two new pentadentate ligands, N,N-bis(2-pyridinylmethyl)[3-(2-pyridinyl)isoquinoline)]-1-methanamine (DPA-1-MPI) and N,N-bis(2-pyridinylmethyl)[1-(2-pyridinyl)-isoquinoline)]-3-methanamine (DPA-3-MPI). Despite a slight structural difference of the introduced isoquinoline group, the resulting cobalt complexes display drastic changes in their electro- and photochemical properties. There are positive shifts of 290 and 260 mV, respectively, for the Co-II/Co-I and Co-III-H/Co-II-H couples from [Co(DPA-1-MPI)(H2O)](PF6)(3) to [Co(DPA-3-MPI)(H2O)](PF6)(3), with the former being similar to 32 times as active as the latter in photocatalytic H-2 production. Density functional theory (DFT) calculations show that the protonation of CoI to yield the Co-III-H species is energetically more favorable for [Co(DPA-1-MPI)(H2O)](PF6)(3) than that of [Co(DPA-3-MPI)(H2O)](PF6)(3). Both experimental results and DFT computations suggest that the presence of a planar conjugate bipyridyl unit or its isoquinoline derivative is a key feature for stabilizing low valent CoI species toward proton binding. The incorporation of an electron-donating group trans to the proposed Co-H species also facilitates proton binding and H-H bond formation, which is proposed to occur by the heterolytic coupling of Co-II-H species. The overall catalytic H-2 evolution is presented as the modified electron transfer (E)-proton transfer (C)-electron transfer (E)-proton transfer (C) (mod-ECEC) pathway. This study provides important new insight into the electronic and steric factors controlling catalytic H-2 production by Co complexes with pentadentate ligands.

Carboxylesterases (CEs) are ubiquitous enzymes that are responsible for the metabolism of xenobiotics, including drugs such as irinotecan and oseltamivir. Inhibition of CEs significantly modulates the efficacy of such agents. We report here that β-lapachone is a potent, reversible CE inhibitor with Ki values in the nanomolar range. A series of amino and phenoxy analogues have been synthesized, and although the former are very poor inhibitors, the latter compounds are highly effective in modulating CE activity. Our data demonstrate that tautomerism of the amino derivatives to the imino forms likely accounts for their loss in biological activity. A series of N-methylated amino derivatives, which are unable to undergo such tautomerism, were equal in potency to the phenoxy analogues and demonstrated selectivity for the liver enzyme hCE1. These specific inhibitors, which are active in cell culture models, will be exceptionally useful reagents for reaction profiling of esterified drugs in complex biological samples.

1α,20 S -Dihydroxyvitamin D3 [1,20 S (OH) 2 D 3 ], a natural and bioactive vitamin D3 metabolite, was chemically synthesized for the first time. X-ray crystallography analysis of intermediate 15 confirmed its 1α-OH configuration. 1,20 S (OH) 2 D 3 interacts with the vitamin D receptor (VDR), with similar potency to its native ligand, 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] as illustrated by its ability to stimulate translocation of the VDR to the nucleus, stimulate VDRE-reporter activity, regulate VDR downstream genes ( VDR , CYP24A1 , TRPV6 and CYP27B1 ), and inhibit the production of inflammatory markers (IFNγ and IL1β). However, their co-crystal structures revealed differential molecular interactions of the 20 S -OH moiety and the 25-OH moiety to the VDR, which may explain some differences in their biological activities. Furthermore, this study provides a synthetic route for the synthesis of 1,20 S (OH) 2 D 3 using the intermediate 1α,3β-diacetoxypregn-5-en-20-one (3), and provides a molecular and biological basis for the development of 1,20 S (OH) 2 D 3 and its analogs as potential therapeutic agents.

Software wanting to consume or produce CIF data has several challenges to overcome.On one hand, there is a diversity of both official and unofficial variations on the format itself, culminating in CIF 2.0, that the most flexible CIF consumers will want to support.On the other hand, the volume and complexity of crystallographic data continue to increase, whereas CPU speed has reached a plateau, and focus in some quarters is shifting toward smaller, less powerful devices.These trends make both processing efficiency and memory efficiency ongoing concerns for CIF software.Furthermore, CIF carries the legacy of having been promoted as a human readable and writable format, in the form of a comparative prevalence of malformed instances.These challenges and others were addressed during the design and implementation of the opensource CIF API, a powerful, flexible, and portable C library for reading and writing CIF data in any of its variations.We discuss some of the lessons learned through designing and implementing the CIF API, and we present some of the features it has to offer for supporting robust CIF programs.[1]

Version 2.0 of the CIF format incorporates novel features implemented in STAR 2.0. Among these are an expanded character repertoire, new and more flexible forms for quoted data values, and new compound data types. The CIF 2.0 format is compared with both CIF 1.1 and STAR 2.0, and a formal syntax specification is provided.

The CIF API is an application programming interface and accompanying reference implementation for reading and writing CIFs and manipulating CIF data, with support for all versions of CIF through CIF 2.0. It features full support for Unicode in data block and save frame codes, data names, and data values; flexible character encoding; CIF 2.0 List and Table data types; CIF version auto-detection; event-based parsing; and arbitrary-precision numeric values. The interface and implementation are written in portable C, and they have been successfully built and tested on Linux, OS X and Windows. The CIFAPI is open-source software, available for use under the GNU Lesser General Public License.

Ein einkerniger Cobalt-Komplex mit einem neuartigen fünfzähnigen Liganden (siehe Bild) katalysiert die Entwicklung von Wasserstoff in ausschließlich wässriger Lösung. Der Komplex könnte als Elektro- sowie als Photokatalysator zur effizienten Bildung von Wasserstoff verwendet werden. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

A highly modular and convergent synthetic route was devised to construct a series of planar pi-conjugated molecules with systematically varied structural dimensions and electronic characteristics. High-yielding triple Schiff base condensation reactions between pi-extended bulky anilines and 1,3,5-triformylphloroglucinol furnished a series of pseudo C-3-symmetric tris(N-salicylideneamine)s displaying intense absorptions at lambda(max) = 445-475 nm and emissions at lambda(max) = 470-504 nm. X-Ray crystallographic studies revealed that intricate hydrogen-bonding networks sustain the planar conjugation of these discotic molecules, the HOMO-LUMO gaps of which decrease with increasing conjugation area. This reduction in excitation energy is accompanied by a nearly 4-fold enhancement in emission quantum yield (Phi(F)). Past a structural threshold, however, increasing conjugation area leads to either (i) decrease in Phi(F) or (ii) development of localized electronic transitions. These findings provide a well-defined structural window for future elaboration of this emerging family of dynamic 2-D conjugation, the luminescence properties of which have already been shown to reversibly change in response to external stimuli.

A covalently triggered fluorescence turn-on detection scheme has been implemented for a tris(N-salicylideneamine)-derived dynamic fluorophore. Selective cleavage of strategically placed Si-O bonds by fluoride ion induces spring-loaded conformational transitions that are tightly coupled to fluorescence enhancement.

A highly modular and convergent synthetic route was devised to construct a series of planar π-conjugated molecules with systematically varied structural dimensions and electronic characteristics. High-yielding triple Schiff base condensation reactions between π-extended bulky anilines and 1,3,5-triformylphloroglucinol furnished a series of pseudo C3-symmetric tris(N-salicylideneamine)s displaying intense absorptions at λmax = 445–475 nm and emissions at λmax = 470–504 nm. X-Ray crystallographic studies revealed that intricate hydrogen-bonding networks sustain the planar conjugation of these discotic molecules, the HOMO–LUMO gaps of which decrease with increasing conjugation area. This reduction in excitation energy is accompanied by a nearly 4-fold enhancement in emission quantum yield (ΦF). Past a structural threshold, however, increasing conjugation area leads to either (i) decrease in ΦF or (ii) development of localized electronic transitions. These findings provide a well-defined structural window for future elaboration of this emerging family of dynamic 2-D conjugation, the luminescence properties of which have already been shown to reversibly change in response to external stimuli.

An expedient tandem deprotonation-trapping protocol was employed to prepare a tris(difluoroboronyl) complex of a triferrocenyl ligand that is geometrically analogous to substituted triphenylenes. A triple Schiff base condensation reaction between 1,3,5-triformylphloroglucinol and aminoferrocene afforded the tris(N-salicylideneamine) adducts 5a + 5b in ca. 1:1 ratio. The keto-enamine tautomeric core of this isomeric mixture could be converted to a common enolate-imine intermediate. Subsequent trapping with BF3.Et2O cleanly afforded the tris(difluoroboronyl) adduct 6 in essentially quantitative yield. The electronic and structural properties of this new class of ferrocene compounds were investigated using various methods including UV-vis, cyclic voltammetry (CV), differential pulse voltammetry (DPV), and X-ray crystallography. In CH2Cl2-CH3CN, 6 displayed a reversible three-electron oxidation process at E1/2ox = +210 mV (vs Fc/Fc+). Despite the sharing of a common [pi,pi]/[n,pi]-conjugated core, no significant electronic communication was observed among the three ferrocenyl units in 6 under either CV or DPV conditions. On the other hand, the broad oxidation wave of 5a + 5b at E1/2ox = +60 mV in CH2Cl2-CH3CN was comprised of at least two major components at +20 and +90 mV, which collapsed to become a single peak in DMF electrolyte, despite that the ratios between the two isomers 5a,b remained essentially invariant to the change in solvent.