Mechanism of Action of Oxazoline-Based Antimicrobial Polymers Against Staphylococcus aureus: In Vivo Antimicrobial Activity Evaluation.

Antimicrobial-resistant pathogens have reached alarming levels, becoming one of the most pressing global health issues. Hence, new treatments are necessary for the fight against antimicrobial resistance. Synthetic nanoengineered antimicrobial polymers (SNAPs) have emerged as a promising alternative to antimicrobial peptides, overcoming some of their limitations while keeping their key features.

Bottlebrush copolymers for gene delivery: influence of architecture, charge density, and backbone length on transfection efficiency.

The influence of polymer architecture of polycations on their ability to transfect mammalian cells is probed. Polymer bottle brushes with grafts made from partially hydrolysed poly(2-ethyl-2-oxazoline) are used while varying the length of the polymer backbone as well as the degree of hydrolysis (cationic charge content). Polyplex formation is investigated gel electrophoresis, dye-displacement and dynamic light scattering.

Effect of cysteine thiols on the catalytic and anticancer activity of Ru(II) sulfonyl-ethylenediamine complexes.

We have synthesized a series of novel substituted sulfonyl ethylenediamine (en) Ru arene complexes 1-8 of [(η-arene)Ru(R-SO-EnBz)X], where the arene is benzene, HO(CH)O-phenyl or biphenyl (biph), X = Cl or I, and R is phenyl, 4-Me-phenyl, 4-NO-phenyl or dansyl. The 'piano-stool' structure of complex 3, [(η-biph)Ru(4-Me-phenyl-SO-EnBz)I], was confirmed by X-ray crystallography. The values of their aqua adducts were determined to be high (9.

Aggregation-Induced Emission Featured Supramolecular Tubisomes for Imaging-Guided Drug Delivery.

Polymeric cylinders, a fascinating type of nanostructures with high surface area, internal volume and rigidity, have been exploited as novel drug delivery vehicles over the past decade. However, it's still an open challenge to afford cylindrical nanostructures using polymeric building blocks via traditional self-assembly processes. Herein, we report a hierarchical self-assembly strategy of preparing cylindrical aggregates (tubisomes) from an amphiphilic supramolecular bottlebrush polymer in which a cyclic peptide nanotube is employed as the noncovalent backbone.

Ligand-centred redox activation of inert organoiridium anticancer catalysts.

Organometallic complexes with novel activation mechanisms are attractive anticancer drug candidates. Here, we show that half-sandwich iodido cyclopentadienyl iridium(iii) azopyridine complexes exhibit potent antiproliferative activity towards cancer cells, in most cases more potent than cisplatin. Despite their inertness towards aquation, these iodido complexes can undergo redox activation by attack of the abundant intracellular tripeptide glutathione (GSH) on the chelated azopyridine ligand to generate paramagnetic intermediates, and hydroxyl radicals, together with thiolate-bridged dinuclear iridium complexes, and liberate reduced hydrazopyridine ligand.

Comparative Study of the Cellular Uptake and Intracellular Behavior of a Library of Cyclic Peptide-Polymer Nanotubes with Different Self-Assembling Properties.

Particle shape has been described as a key factor in improving cell internalization and biodistribution among the different properties investigated for drug-delivery systems. In particular, tubular structures have been identified as promising candidates for improving drug delivery. Here, we investigate the influence of different design elements of cyclic peptide-polymer nanotubes (CPNTs) on cellular uptake including the nature and length of the polymer and the cyclic peptide building block.

Hierarchical Self-Assembled Photo-Responsive Tubisomes from a Cyclic Peptide-Bridged Amphiphilic Block Copolymer.

Typically, the morphologies of the self-assembled nanostructures from block copolymers are limited to spherical micelles, wormlike micelles and vesicles. Now, a new generation of materials with unique shape and structures, cylindrical soft matter particles (tubisomes), are obtained from the hierarchical self-assembly of cyclic peptide-bridged amphiphilic diblock copolymers. The capacity of obtained photo-responsive tubisomes as potential drug carriers is evaluated.

Kinetic analysis of the accumulation of a half-sandwich organo-osmium pro-drug in cancer cells.

The organo-osmium half-sandwich complex [(η6-p-cymene)Os(Ph-azopyridine-NMe2)I]+ (FY26) exhibits potent antiproliferative activity towards cancer cells and is active in vivo. The complex is relatively inert, but rapidly activated in cells by displacement of coordinated iodide. Here, we study time-dependent accumulation of FY26 in A2780 human ovarian cancer cells at various temperatures in comparison with the chlorido metabolite [(η6-p-cymene)Os(Ph-azopyridine-NMe2)Cl]+ (FY25).

Photoactivatable Cell-Selective Dinuclear trans-Diazidoplatinum(IV) Anticancer Prodrugs.

A series of dinuclear octahedral Pt complexes trans, trans, trans-[{Pt(N)(py)(OH)(OC(O)CHCHC(O)NH)}R] containing pyridine (py) and bridging dicarboxylate [R = -CHCH- (1), trans-1,2-CH- (2), p-CH- (3), -CHCHCHCH- (4)] ligands have been synthesized and characterized, including the X-ray crystal structures of complexes 1·2MeOH and 4, the first photoactivatable dinuclear Pt complexes with azido ligands. The complexes are highly stable in the dark, but upon photoactivation with blue light (420 nm), they release the bridging ligand and mononuclear photoproducts. Upon irradiation with blue light (465 nm), they generate azidyl and hydroxyl radicals, detected using a 5,5-dimethyl-1-pyrroline N-oxide electron paramagnetic resonance spin trap, accompanied by the disappearance of the ligand-to-metal charge-transfer (N → Pt) band at ca.

In Vivo Selectivity and Localization of Reactive Oxygen Species (ROS) Induction by Osmium Anticancer Complexes That Circumvent Platinum Resistance.

Platinum drugs are widely used for cancer treatment. Other precious metals are promising, but their clinical progress depends on achieving different mechanisms of action to overcome Pt-resistance. Here, we evaluate 13 organo-Os complexes: 16-electron sulfonyl-diamine catalysts [(η-arene)Os( N, N')], and 18-electron phenylazopyridine complexes [(η-arene)Os( N, N')Cl/I] (arene = p-cymene, biphenyl, or terphenyl).

Transfer Hydrogenation and Antiproliferative Activity of Tethered Half-Sandwich Organoruthenium Catalysts.

We report the synthesis and characterization of four neutral organometallic tethered complexes, [Ru(η-Ph(CH)-ethylenediamine--R)Cl], where R = methanesulfonyl (Ms, ), toluenesulfonyl (Ts, ), 4-trifluoromethylbenzenesulfonyl (Tf, ), and 4-nitrobenzenesulfonyl (Nb, ), including their X-ray crystal structures. These complexes exhibit moderate antiproliferative activity toward human ovarian, lung, hepatocellular, and breast cancer cell lines. Complex in particular exhibits a low cross-resistance with cisplatin.

Half-Sandwich Arene Ruthenium(II) and Osmium(II) Thiosemicarbazone Complexes: Solution Behavior and Antiproliferative Activity.

We report the synthesis, characterization, and antiproliferative activity of organo-osmium(II) and organo-ruthenium(II) half-sandwich complexes [(η--cym)Os(L)Cl]Cl ( and ) and [(η--cym)Ru(L)Cl]Cl ( and ), where L = -(2-hydroxy)-3-methoxybenzylidenethiosemicarbazide () or -(2,3-dihydroxybenzylidene)-3-phenylthiosemicarbazide (), respectively. X-ray crystallography showed that all four complexes possess half-sandwich pseudo-octahedral "three-legged piano-stool" structures, with a neutral N,S-chelating thiosemicarbazone ligand and a terminal chloride occupying three coordination positions. In methanol, / isomerization of the coordinated thiosemicarbazone ligand was observed, while in an aprotic solvent like acetone, partial dissociation of the ligand occurs, reaching complete displacement in a more coordinating solvent like DMSO.

Effect of sulfonamidoethylenediamine substituents in Ru arene anticancer catalysts on transfer hydrogenation of coenzyme NAD by formate.

A series of neutral pseudo-octahedral RuII sulfonamidoethylenediamine complexes [(η6-p-cym)Ru(N,N')Cl] where N,N' is N-(2-(R1,R2-amino)ethyl)-4-toluenesulfonamide (TsEn(R1,R2)) R1,R2 = Me,H (1); Me,Me (2); Et,H (3); benzyl,H (Bz, 4); 4-fluorobenzyl,H (4-F-Bz, 5) or naphthalen-2-ylmethyl,H (Naph, 6), were synthesised and characterised including the X-ray crystal structure of 3. These complexes catalyse the reduction of NAD+ regioselectively to 1,4-NADH by using formate as the hydride source. The catalytic efficiency depends markedly on the steric and electronic effects of the N-substitutent, with turnover frequencies (TOFs) increasing in the order: 1 < 2 < 3, 6 < 4, 5, achieving a TOF of 7.

Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes.

Mitochondria generate energy but malfunction in many cancer cells, hence targeting mitochondrial metabolism is a promising approach for cancer therapy. Here we have designed cyclometallated iridium(iii) complexes, containing one TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) spin label [CHNOIr·PF]˙ () and two TEMPO spin labels [CHNOIr·PF]˙ (). Electron paramagnetic resonance (EPR) spectroscopy revealed spin-spin interactions between the TEMPO units in .

Cyclic Peptide-Polymer Nanotubes as Efficient and Highly Potent Drug Delivery Systems for Organometallic Anticancer Complexes.

Functional drug carrier systems have potential for increasing solubility and potency of drugs while reducing side effects. Complex polymeric materials, particularly anisotropic structures, are especially attractive due to their long circulation times. Here, we have conjugated cyclic peptides to the biocompatible polymer poly(2-hydroxypropyl methacrylamide) (pHPMA).

Larger islands house more bacterial taxa.

The power law that describes the relationship between species richness and area size is one of the few generalizations in ecology, but recent studies show that this relationship differs for microbes. We demonstrate that the natural bacterial communities inhabiting small aquatic islands (treeholes) do indeed follow the species-area law. The result requires a re-evaluation of the current understanding of how natural microbial communities operate and implies that analogous processes structure both microbial communities and communities of larger organisms.