Organometallic Pillarplexes That Bind DNA 4-Way Holliday Junctions and Forks.

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination, and repair) and are dynamic structures that adopt either open or closed conformations, the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core, an ideal structure to interact with open DNA junction cavities. Combining experimental studies and MD simulations, we show that an Au pillarplex can bind DNA 4-way (Holliday) junctions in their open form, a binding mode not accessed by synthetic agents before. Pillarplexes can bind 3-way junctions too, but their large size leads them to open up and expand that junction, disrupting the base pairing, which manifests in an increased hydrodynamic size and lower junction thermal stability. At high loading, they rearrange both 4-way and 3-way junctions into Y-shaped forks to increase the available junction-like binding sites. Isostructural Ag pillarplexes show similar DNA junction binding behavior but lower solution stability. This pillarplex binding contrasts with (but complements) that of metallo-supramolecular cylinders, which prefer 3-way junctions and can rearrange 4-way junctions into 3-way junction structures. The pillarplexes' ability to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures. In human cells, the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher-order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction binders into organometallic chemistry.

Investigation of Solvatomorphism and Its Photophysical Implications for Archetypal Trinuclear Au3(1-Methylimidazolate)3.

A new solvatomorph of [Au3(1-Methylimidazolate)3] (Au3(MeIm)3)-the simplest congener of imidazolate-based Au(I) cyclic trinuclear complexes (CTCs)-has been identified and structurally characterized. Single-crystal X-ray diffraction revealed a dichloromethane solvate exhibiting remarkably short intermolecular Au⋯Au distances (3.2190(7) Å). This goes along with a dimer formation in the solid state, which is not observed in a previously reported solvent-free crystal structure. Hirshfeld analysis, in combination with density functional theory (DFT) calculations, indicates that the dimerization is generally driven by attractive aurophilic interactions, which are commonly associated with the luminescence properties of CTCs. Since Au3(MeIm)3 has previously been reported to be emissive in the solid-state, we conducted a thorough photophysical study combined with phase analysis by means of powder X-ray diffraction (PXRD), to correctly attribute the photophysically active phase of the bulk material. Interestingly, all investigated powder samples accessed via different preparation methods can be assigned to the pristine solvent-free crystal structure, showing no aurophilic interactions. Finally, the observed strong thermochromism of the solid-state material was investigated by means of variable-temperature PXRD, ruling out a significant phase transition being responsible for the drastic change of the emission properties (hypsochromic shift from 710 nm to 510 nm) when lowering the temperature down to 77 K.

Antimicrobial Activity and Cytotoxicity of Ag(I) and Au(I) Pillarplexes.

The biological activity of four pillarplex compounds featuring different metals and anions was investigated. The toxicity of the compounds against four bacterial strains [Bacillus subtilis (ATCC6633), Staphylococcus aureus (ATCC6538), Escherichia coli (UVI isolate), Pseudomonas aeruginosa], one fungus (Candida albicans), and a human cell line (HepG2) was determined. Additionally, a UV-Vis titration study of the pillarplexes was carried out to check for stability depending on pH- and chloride concentration changes and evaluate the applicability in physiological media. All compounds are bioactive: the silver compounds showed higher activity against bacteria and fungi, and the corresponding gold pillarplexes were less toxic against human cells.

Thymosin ß4 enhances the healing of medial collateral ligament injury in rat.

The role played by thymosin ß4 (Tß4) in the process of wound healing was reported in several organs. However, there have been no reports that investigated the role of Tß4 in the repair process after ligament injury. The purpose of this study was to determine whether administration of Tß4 would improve ligament repair following injury. The medial collateral ligament (MCL) was sharply transected on the day of surgery. Then, the treatment group received 100 µL of fibrin sealant containing 1 µg of Tß4 placed in the ligament gap. Healing tissues were evaluated by hematoxylin and eosin stain, transmission electron microscopy, and biomechanical test at 4 weeks after surgery. Histologically, healing tissues in Tß4-treated group exhibited uniform and evenly spaced fiber bundles. However, the collagen fibers were not evenly spaced in control rats. Moreover, diameters of collagen fibrils within granulation tissue from the Tß4-treated rats were significantly increased. In Tß4-treated MCLs, the mechanical properties of these healing tissues were significantly higher at 4 weeks after surgery. In terms of the mechanical properties of the healing femur-medial collateral ligament-tibia complexes, the Tß4-treated group had significantly better biomechanical properties than the control group at 4 weeks after surgery. Local administration of Tß4 promotes the healing process of MCL, both histologically and mechanically, in a rat model. These findings provide a basis for potential clinical use of Tß4 in repairing ligaments.

Treatment of pediatric Ogilvie's syndrome with low-dose erythromycin: a case report.

Acute colonic pseudo-obstruction is a poorly understood syndrome, characterized by the signs, symptoms and radiological pattern of a large bowel obstruction without evidence for a mechanical obstruction. We report a case of a 2-year old boy who presented with progressive abdominal distention, vomiting and abdominal pain on postoperative d 3. Plain abdominal z-ray showed markedly dilated large bowel. Mechanical colonic obstruction was ruled out with hypaque enema. Ogilvie's syndrome was suspected. The patient received treatment with oral erythromycin which had an immediate beneficial effect. During the 6 mo follow-up, no recurrences of symptoms were observed. We provide a safe and effective therapy for Ogilvie's syndrome in pediatric individuals.