In Vitro and In Vivo Studies on a Mononuclear Ruthenium Complex Reveals It is a Highly Effective, Fast-Acting, Broad-Spectrum Antimicrobial in Physiologically Relevant Conditions.

The crystal structure of a previously reported antimicrobial Ru complex that targets bacterial DNA is presented. Studies utilizing clinical isolates of Gram-negative bacteria that cause catheter-associated urinary tract infection, (CA)UTI, in media that model urine and plasma reveal that good antimicrobial activity is maintained in all conditions tested. Experiments with a series of clinical isolates show that, unlike the majority of previously reported Ru-based antimicrobial leads, the compound retains its potent activity even in MRSA strains.

Cohort scheduling of freshman exercise physiology majors improves social integration and perceptions of faculty but not academic performance.

Cohort scheduling intentionally places students in the same sections of several classes (e.g., biology, algebra, and writing) with a consistent peer group and is typically done for small groups (<30 students) to enable better interaction among students.

Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy.

Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles.

2,2':4,4'':4',4'''-Quaterpyridine: synthesis, crystal-structure description, and Hirshfeld surface analysis.

The title compound, 2,2':4,4'':4',4'''-quaterpyridine (Qtpy), CHN, crystallizes in the triclinic space group and has half of the mol-ecule in the asymmetric unit, corresponding to 4,4'-bi-pyridine (4,4'-bpy) that serves as the building block for the mol-ecule. C-N-C and/or N-C-C bond-angle parameters show that the 4,4'-bpy ligands are highly rigid, displaying values lower than the linear bond angle of 180°. In the crystal, the 4,4'-bpy units are seen to be facing each other in relatively close proximity.

From Chemotherapy to Phototherapy - Changing the Therapeutic Action of a Metallo-Intercalating Ru -Re Luminescent System by Switching its Sub-Cellular Location.

The synthesis of a new heterodinuclear Re Ru metallointercalator containing Ru (dppz) and Re (dppn) moieties is reported. Cell-free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in-cell properties to its parent.

Selectively inhibiting malignant melanoma migration and invasion in an engineered skin model using actin-targeting dinuclear Ru-complexes.

Due to the poor prognosis of metastatic cancers, there is a clinical need for agents with anti-metastatic activity. Here we report on the anti-metastatic effect of a previously reported Ru(ii) complex [{(phen)Ru}(tpphz)], 1, that has recently been shown to disrupt actin fiber assembly. In this study, we investigated the anti-migratory effect of 1 and a close structural analogue, 2, on two highly invasive, metastatic human melanoma cell lines.

Health Maintenance and Preventative Care in Inflammatory Bowel Disease: A Systematic Review of the Overall Quality of Societal Recommendations.

Background Aims: Preventative care plays an important role in maintaining health in patients with inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on preventative care in IBD.

Methods: A systematic literature search was performed in multiple databases to identify all guidelines pertaining to preventative care in IBD in April 2021.

The role and timing of endoscopic retrograde cholangiopancreatography in acute biliary pancreatitis without cholangitis: A nationwide analysis.

Background/purpose: The role and optimal timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis without cholangitis (ABPwoC) remains unclear. Using a large national database, we aimed to examine hospitalization outcomes of patients with ABPwoC as a function of the performance and timing of ERCP.

Methods: This was a retrospective study of adult patients with ABPwoC utilizing the National Inpatient Sample from 2016-2017.

Clearing an ESKAPE Pathogen in a Model Organism; A Polypyridyl Ruthenium(II) Complex Theranostic that Treats a Resistant Acinetobacter baumannii Infection in Galleria mellonella.

In previous studies we have described the therapeutic action of luminescent dinuclear ruthenium(II) complexes based on the tetrapyridylphenazine, tpphz, bridging ligand on pathogenic strains of Escherichia coli and Enterococcus faecalis. Herein, the antimicrobial activity of the complex against pernicious Gram-negative ESKAPE pathogenic strains of Acinetobacter baumannii (AB12, AB16, AB184 and AB210) and Pseudomonas aeruginosa (PA2017, PA_ 007_ IMP and PA_ 004_ CRCN) are reported. Estimated minimum inhibitory concentrations and minimum bactericidal concentrations for the complexes revealed the complex shows potent activity against all A.

Nanoparticles for super-resolution microscopy: intracellular delivery and molecular targeting.

Following an overview of the approaches and techniques used to acheive super-resolution microscopy, this review presents the advantages supplied by nanoparticle based probes for these applications. The various clases of nanoparticles that have been developed toward these goals are then critically described and these discussions are illustrated with a variety of examples from the recent literature.

A Ruthenium(II) Polypyridyl Complex Disrupts Actin Cytoskeleton Assembly and Blocks Cytokinesis.

The dinuclear Ru complex [(Ru(phen))(tpphz)] (phen=1,10-phenanthroline, tpphz=tetrapyridophenazine) "RuRuPhen" blocks the transformation of G-actin monomers to F-actin filaments with no disassembly of pre-formed F-actin. Molecular docking studies indicate multiple RuRuPhen molecules bind to the surface of G-actin but not the binding pockets of established actin polymerisation inhibitors. In cells, addition of RuRuPhen causes rapid disruption to actin stress fibre organisation, compromising actomyosin contractility and cell motility; due to this effect RuRuPhen interferes with late-stage cytokinesis.

A Ruthenium(II) Polypyridyl Complex Disrupts Actin Cytoskeleton Assembly and Blocks Cytokinesis.

The dinuclear Ru complex [(Ru(phen) ) (tpphz)] (phen=1,10-phenanthroline, tpphz=tetrapyridophenazine) "RuRuPhen" blocks the transformation of G-actin monomers to F-actin filaments with no disassembly of pre-formed F-actin. Molecular docking studies indicate multiple RuRuPhen molecules bind to the surface of G-actin but not the binding pockets of established actin polymerisation inhibitors. In cells, addition of RuRuPhen causes rapid disruption to actin stress fibre organisation, compromising actomyosin contractility and cell motility; due to this effect RuRuPhen interferes with late-stage cytokinesis.

A Dinuclear Osmium(II) Complex Near-Infrared Nanoscopy Probe for Nuclear DNA.

With the aim of developing photostable near-infrared cell imaging probes, a convenient route to the synthesis of heteroleptic Os complexes containing the Os(TAP) fragment is reported. This method was used to synthesize the dinuclear Os complex, [{Os(TAP)}tpphz] (where tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2''-h:2‴,3'''-j]phenazine and TAP = 1,4,5,8- tetraazaphenanthrene). Using a combination of resonance Raman and time-resolved absorption spectroscopy, as well as computational studies, the excited state dynamics of the new complex were dissected.

A Minimal Load-and-Lock Ru Luminescent DNA Probe.

Threading intercalators bind DNA with high affinities. Here, we describe single-molecule studies on a cell-permeant luminescent dinuclear ruthenium(II) complex that has been previously shown to thread only into short, unstable duplex structures. Using optical tweezers and confocal microscopy, we show that this complex threads and locks into force-extended duplex DNA in a two-step mechanism.

Triazole-based osmium(ii) complexes displaying red/near-IR luminescence: antimicrobial activity and super-resolution imaging.

Cellular uptake, luminescence imaging and antimicrobial activity against clinically relevant methicillin-resistant (MRSA) bacteria are reported. The osmium(ii) complexes [Os(^)] (^ = 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole ( ); 1-benzyl-4-(pyrimidin-2-yl)-1,2,3-triazole ( ); 1-benzyl-4-(pyrazin-2-yl)-1,2,3-triazole ( )) were prepared and isolated as the chloride salts of their meridional and facial isomers. The complexes display prominent spin-forbidden ground state to triplet metal-to-ligand charge transfer (MLCT) state absorption bands enabling excitation as low as 600 nm for /- and observation of emission in aqueous solution in the deep-red/near-IR regions of the spectrum.

Mononuclear ruthenium(ii) theranostic complexes that function as broad-spectrum antimicrobials in therapeutically resistant pathogens through interaction with DNA.

Six luminescent, mononuclear ruthenium(ii) complexes based on the tetrapyridophenazine (tpphz) and dipyridophenazine (dppz) ligands are reported. The therapeutic activities of the complexes against Gram-negative bacteria (, , ) and Gram-positive bacteria ( and ) including pathogenic multi- and pan-drug resistant strains were assessed. Estimated minimum inhibitory and bactericidal concentrations show the activity of the lead compound is comparable to ampicillin and oxacillin in therapeutically sensitive strains and this activity was retained in resistant strains.

An In-labelled bis-ruthenium(ii) dipyridophenazine theranostic complex: mismatch DNA binding and selective radiotoxicity towards MMR-deficient cancer cells.

Theranostic radionuclides that emit Auger electrons (AE) can generate highly localised DNA damage and the accompanying gamma ray emission can be used for single-photon emission computed tomography (SPECT) imaging. Mismatched DNA base pairs (mismatches) are DNA lesions that are abundant in cells deficient in MMR (mismatch mediated repair) proteins. This form of genetic instability is prevalent in the MMR-deficient subset of colorectal cancers and is a potential target for AE radiotherapeutics.

Transcriptomic Analysis of the Activity and Mechanism of Action of a Ruthenium(II)-Based Antimicrobial That Induces Minimal Evolution of Pathogen Resistance.

Increasing concern over rising levels of antibiotic resistance among pathogenic bacteria has prompted significant research into developing efficacious alternatives to antibiotic treatment. Previously, we have reported on the therapeutic activity of a dinuclear ruthenium(II) complex against pathogenic, multi-drug-resistant bacterial pathogens. Herein, we report that the solubility properties of this lead are comparable to those exhibited by orally available therapeutics that in comparison to clinically relevant antibiotics it induces very slow evolution of resistance in the uropathogenic, therapeutically resistant, strain EC958, and this resistance was lost when exposure to the compound was temporarily removed.

Mitochondriotropic lanthanide nanorods: implications for multimodal imaging.

Two-photon active mitochondriotropic lanthanide nanorods for high resolution fluorescence imaging. The presence of Gd in the nanorods also enabled us to utilize this material as a T-T dual-mode contrast reagent for recording magnetic resonance images of the mouse brain.

Ruthenium based antimicrobial theranostics - using nanoscopy to identify therapeutic targets and resistance mechanisms in .

In previous studies we reported that specific dinuclear Ru complexes are particularly active against pathogenic Gram-negative bacteria and, unusually for this class of compounds, appeared to display lowered activity against Gram-positive bacteria. With the aim of identifying resistance mechanisms specific to Gram-positive bacteria, the uptake and antimicrobial activity of the lead complex against SH1000 and other isolates, including MRSA was investigated. This revealed differential, strain specific, sensitivity to the complex.