vmdICE: a plug-in for rapid evaluation of molecular dynamics simulations using VMD

Molecular dynamics (MD) is a powerful in silico method to investigate the interactions between biomolecules. It solves Newton's equations of motion for atoms over a specified period of time and yields a trajectory file, containing the different spatial arrangements of atoms during the simulation. The movements and energies of each single atom are recorded. For evaluating of these simulation trajectories with regard to biomedical implications, several methods are available. Three well-known ones are the root mean square deviation (RMSD), the root mean square fluctuation (RMSF) and solvent accessible surface area (SASA). Herein, we present a novel plug-in for the software "visual molecular dynamics" (VMD) that allows an interactive 3D representation of RMSD, RMSF, and SASA, directly on the molecule. On the one hand, our plug-in is easy to handle for inexperienced users, and on the other hand, it provides a fast and flexible graphical impression of the spatial dynamics of a system for experts in the field.     

Catalytic Ammonia Synthesis Mediated by Molybdenum Complexes with PN3P Pincer Ligands: Influence of P/N Substituents and Molecular Mechanism

Three molybdenum trihalogenido complexes supported by different PN³P pincer ligands were synthesized and investigated regarding their activity towards catalytic N₂-to-NH₃ conversion. The highest yields were obtained with the H-PN³P^tBu ligand. The corresponding Mo(V)-nitrido complex also shows good catalytic activity. Experiments regarding the formation of the analogous Mo(IV)-nitrido complex lead to the conclusion that the mechanism of catalytic ammonia formation mediated by the title systems does not involve N-N cleavage of a dinuclear Mo-dinitrogen complex, but follows the classic Chatt cycle.     

Evaluation of In Vitro Cytotoxic Potential of Avarol towards Human Cancer Cell Lines and In Vivo Antitumor Activity in Solid Tumor Models

The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the Dysidea avara sponge from the south Adriatic Sea, against different cancer cell lines and two types of mouse carcinoma. To investigate the in vitro cytotoxicity, a human cervix adenocarcinoma cell line (HeLa), human colon adenocarcinoma (LS174), human non-small-cell lung carcinoma (A549), and a normal human fetal lung fibroblast cell line (MRC-5) were used. The in vivo antitumor activity was investigated against two transplantable mouse tumors, the Ehrlich carcinoma (EC) and cervical cancer (CC-5). The effect of avarol on cancer cell survival, which was determined by the microculture tetrazolium test, confirmed a significant in vitro potency of avarol against the investigated cell lines, without selectivity towards MRC-5. The highest cytotoxicity was exhibited against HeLa cancer cells (10.22 ± 0.28 μg/mL). Moreover, potent antitumor activity against two tumor models was determined, as the intraperitoneal administration of avarol at a dose of 50 mg/kg resulted in a significant inhibition of tumor growth in mice. After three administrations of avarol, a 29% inhibition of the EC growth was achieved, while in the case of CC-5, a 36% inhibition of the tumor growth was achieved after the second administration of avarol. Therefore, the results indicate that this marine sesquiterpenoid hydroquinone could be a promising bioactive compound in the development of new anticancer medicine.     

Molecular Engineering To Enhance Reactivity and Selectivity in an Ultrafast Photoclick Reaction

Light-induced 9,10-phenanthrenequinone-electron-rich alkene ( PQ-ERA ) photocycloadditions are an attractive new type of photoclick reaction, featuring fast conversions and high biocompatibility. However, the tunability of the reaction was hardly investigated up to now. To this end, we explored the influence of substituents on both reaction partners and the reaction rate between the PQs and ERAs . We identified new handles for functionalization and discovered that using enamines as ERAs leads to drastically enhanced rates (>5400 times faster), high photoreaction quantum yields ( Φ_P , up to 65 %), and multicolor emission output as well as a high fluorescence quantum yield of the adducts ( Φ_F , up to 97 %). Further investigation of the photophysical and photochemical properties provided insights to design orthogonal reaction systems both in solution and on nanoparticle surfaces for ultrafast chemoselective functionalization by photoclick reactions.     

Controlled Grafting Expansion Microscopy

Expansion microscopy (ExM) is a recently developed technique that allows for the resolution of structures below the diffraction limit by physically enlarging a hydrogel-embedded facsimile of the biological sample. The target structure is labeled and this label must be retained in a relative position true to the original, smaller state before expansion by linking it into the gel. However, gel formation and digestion lead to a significant loss in target-delivered label, resulting in weak signal. To overcome this problem, we have here developed an agent combining targeting, fluorescent labeling and gel linkage in a single small molecule. Similar approaches in the past have still suffered from significant loss of label. Here we show that this loss is due to insufficient surface grafting of fluorophores into the hydrogel and develop a solution by increasing the amount of target-bound monomers. Overall, we obtain a significant improvement in fluorescence signal retention and our new dye allows the resolution of nuclear pores as ring-like structures, similar to STED microscopy. We furthermore provide mechanistic insight into dye retention in ExM.