Facile construction of polyoxometalate-polymer hybrid nanoparticles with pH/redox dual-responsiveness.

Responsive nanomaterials have emerged as promising candidates for advanced drug delivery systems (DDSs), offering the potential to precisely target disease sites and enhance treatment efficacy. To fulfil their potential, such materials need to be engineered to respond to specific variations in biological conditions. In this work, we present a series of pH/redox dual-responsive hybrid nanoparticles featuring an amphiphilic shell polymer and a pH-responsive core polymer.

Highly selective organo-gallium hydroxamate mediated inhibition of antibiotic resistant .

Five complexes of gallium derived from hydroxamic acids have been synthesised, characterised, and their anti-bacterial activity and mammalian cell toxicity established. These are three metal-organic complexes; [Ga(BPHA)] 1, [Ga(BHA-)] 2, [Ga(SHA-)(SHA-)] 3, and two heteroleptic organometallic complexes [GaMe(BPHA)] 4, and [GaMe(BHA-)] 5, along with the iron complex [Fe(BPHA)] 6 (BPHA-H = -benzoyl--phenylhydroxamic acid, BHA-H = phenylhydroxamic acid, and SHA-H = salicylhydroxamic acid). Solid-state structures of 1, 4-6 were identified by single-crystal X-ray crystallography.

Tri-aryl antimony(V) hydroximato and hydroxamato complexes: Combining lipophilic Sb(III/V) and hydroxamic acids in combating Leishmania.

Six novel tri-aryl antimony(V) hydroximato complexes (3-8) with composition [SbAr(ONCR)] (3: Ar = Ph, R = o-(OH)Ph, 4: Ar = Ph, R = Me, 5: Ar = Ph, R = Ph; 6: Ar = Mes, R = Me, 7: Ar = Mes, R = Ph, 8: Ar = Mes, R = o-(OH)Ph (where Ph = phenyl, Me = methyl, Mes = mesityl)), were synthesised and evaluated for anti-parasitic activity towards Leishmania major (L. major) promastigotes and amastigotes. Complexes of the form [SbAr(ONCR)], with the dianionic hydroximato ligand binding O,O'-bidentate to the Sb(V) centre, exist in the solid-state for the mesityl-derived complexes.

Neutral rhenium(I) tricarbonyl complexes with sulfur-donor ligands: anti-proliferative activity and cellular localization.

Rhenium(I) tricarbonyl complexes are widely studied for their cell imaging properties and anti-cancer and anti-microbial activities, but the complexes with S-donor ligands remain relatively unexplored. A series of six -[Re(NN)(CO)(SR)] complexes, where (NN) is 2,2'-bipyridyl (bipy) or 1,10-phenanthroline (phen), and RSH is a series of thiocarboxylic acid methyl esters, have been synthesized and characterized. Cellular uptake and anti-proliferative activities of these complexes in human breast cancer cell lines (MDA-MB-231 and MCF-7) were generally lower than those of the previously described -[Re(NN)(CO)(OH)] complexes; however, one of the complexes, -[Re(CO)(phen)(SC(Ph)CHC(O)OMe)] (3b), was active (IC ∼ 10 μM at 72 h treatment) in thiol-depleted MDA-MB-231 cells.

Fusing Bismuth and Mercaptocarboranes: Design and Biological Evaluation of Low-Toxicity Antimicrobial Thiolato Complexes.

This study proposes an innovative strategy to enhance the pharmacophore model of antimicrobial bismuth thiolato complex drugs by substituting hydrocarbon ligand structures with boron clusters, particularly icosahedral closo-dicarbadodecaborane (CBH, carboranes). The hetero- and homoleptic mercaptocarborane complexes BiPhL (1) and BiL (2) (L=9-S-1,2-CBH) were prepared from 9-mercaptocarborane (HL) and triphenylbismuth. Comprehensive characterization using NMR, IR, MS, and XRD techniques confirmed their successful synthesis.

Sulfoproteomics Workflow with Precursor Ion Accurate Mass Shift Analysis Reveals Novel Tyrosine Sulfoproteins in the Golgi.

Tyrosine sulfation in the Golgi of secreted and membrane proteins is an important post-translational modification (PTM). However, its labile nature has limited analysis by mass spectrometry (MS), a major reason why no sulfoproteome studies have been previously reported. Here, we show that a phosphoproteomics experimental workflow, which includes serial enrichment followed by high resolution, high mass accuracy MS, and tandem MS (MS/MS) analysis, enables sulfopeptide coenrichment and identification via accurate precursor ion mass shift open MSFragger database search.

Structure-activity effects in the anti-leishmanial activity of di-alkyl gallium quinolin-8-olates.

Six (G1-G6) novel organogallium complexes of the general formula [Ga(R)quin] (where R = Et, Pr, Bu, Bu, Bu and hexyl; quin = quinolin-8-olate, CHNO) have been synthesised and fully characterised. Single crystal X-ray diffraction shows the complexes adopt a five-coordinate geometry through dimerisation. Complexes G1-G5 were analytically pure and could undergo further biological analysis.

Enhanced antibacterial activity of dimethyl gallium quinolinolates toward drug-resistant Klebsiella pneumoniae in low iron environments.

A series of dimethylgallium quinolinolate [GaMeL] (L = 5-chloroquinolinolate, 5, 7-dichloroquinolinolate, 5, 7-dibromoquinolinolate or 5, 7-doiodoquinolinolate) complexes, shown previously to be active toward the Leishmania parasite, have been studied for their antibacterial activity toward a reference and drug resistant strain of Klebsiella pneumoniae (KP). The assays were conducted in standard iron-rich LB media and in the iron depleted RPMI and RPMI-HS media to better understand the effect of Fe concentration on the activity of the Ga complexes. In LB broth the parent quinolinols and the gallium complexes were inactive up to the highest concentration tested, 100 μM.

Gallium reactivates first and second generation quinolone antibiotics towards drug-resistant .

Herein, we report on a series of homoleptic [GaL] and heteroleptic organometallic [GaMeL] complexes of inactive quinolone antibiotics; nalidixic acid, oxolinic acid and norfloxacin with their antibacterial activity (MIC 0.024-0.781 μM) towards four multi-drug resistant strains of through complexation to gallium.

Synthesis and the photophysical and biological properties of tricarbonyl Re(I) diimine complexes bound to thiotetrazolato ligands.

Twelve Re(I) tricarbonyl diimine (2,2'-bipyridine and 1,10-phenanthroline) complexes with thiotetrazolato ligands have been synthesised and fully characterised. Structural characterisation revealed the capacity of the tetrazolato ligand to bind to the Re(I) centre through either the S atom or the N atom with crystallography revealing most complexes being bound to the N atom. However, an example where the Re(I) centre is linked the S atom has been identified.

Synchrotron-Infrared Microspectroscopy of Live Infected Macrophages and Isolated Promastigotes and Amastigotes.

The prevalence of neglected tropical diseases (NTDs) is advancing at an alarming rate. The NTD leishmaniasis is now endemic in over 90 tropical and sub-tropical low socioeconomic countries. Current diagnosis for this disease involves serological assessment of infected tissue by either light microscopy, antibody tests, or culturing with in vitro or in vivo animal inoculation.

Aryl bismuth phosphinates [BiAr(O(O)PRR')]: structure-activity relationships for antibacterial activity and cytotoxicity.

To study and evaluate the structure-activity relationships in di-aryl bismuth phosphinates on antibacterial activity and cytotoxicity a series of complexes containing -methoxyphenyl, -methoxyphenyl, -tolyl and -tolyl aryl groups; [Bi(-MeOPh)(O(O)P(H)Ph)]1, [Bi(-MeOPh)(O(O)PPh)]2, [Bi(-MeOPh)(O(O)P(-MeOPh))]3, [Bi(-MeOPh)(O(O)P(H)Ph)]4, [Bi(-MeOPh)(O(O)PPh)]5, [Bi(-MeOPh)(O(O)P(-MeOPh))]6, [Bi(-tol)(O(O)P(H)Ph)]7, [Bi(-tol)(O(O)PPh)]8, [Bi(-tol)(O(O)P(-MeOPh))]9, [Bi(-tol)(O(O)P(H)Ph)]10, [Bi(-tol)(O(O)PPh)]11 and [Bi(-tol)(O(O)P(-MeOPh))]12, were synthesised and characterised. Complexes 4, 7, 8, 10 and 11 were structurally authenticated by X-ray crystallography. Evaluation of their antibacterial activity towards methicillin-resistant (MRSA), vancomycin-resistant (VRE), () and () showed that the bismuth bound aryl group has a profound influence on activity, with the -MeOPh complexes 1-3 showing very little activity while the -MeOPh complexes have the greatest activity towards MRSA and VRE in the range of 0.

Modulating aryl substitution: Does it play a role in the anti-leishmanial activity of a series of tetra-aryl Sb(V) fluorinated carboxylates?

Eight tetra-arylantimony carboxylates of the general formula ArSbOC(O)R with Ar = Ph (a), p-Tol (b), R = CF (1), CHCF (2), CFBr (3), CFCFCF (4) have been synthesised and characterised. Two of them (2b, 3b) are structurally novel. All structures were analytically characterised by FT-IR, H, C NMR spectroscopy.

Medicinal chemistry and biomedical applications of bismuth-based compounds and nanoparticles.

Bismuth as a relatively non-toxic and inexpensive metal with exceptional properties has numerous biomedical applications. Bismuth-based compounds are used extensively as medicines for the treatment of gastrointestinal disorders including dyspepsia, gastric ulcers and infections. Recently, its medicinal application was further extended to potential treatments of viral infection, multidrug resistant microbial infections, cancer and also imaging, drug delivery and biosensing.

Structures of rhodopsin in complex with G-protein-coupled receptor kinase 1.

G-protein-coupled receptor (GPCR) kinases (GRKs) selectively phosphorylate activated GPCRs, thereby priming them for desensitization. Although it is unclear how GRKs recognize these receptors, a conserved region at the GRK N terminus is essential for this process. Here we report a series of cryo-electron microscopy single-particle reconstructions of light-activated rhodopsin (Rho*) bound to rhodopsin kinase (GRK1), wherein the N terminus of GRK1 forms a helix that docks into the open cytoplasmic cleft of Rho*.

The thiol-based reduction of Bi(V) and Sb(V) anti-leishmanial complexes.

Low molecular weight thiols including trypanothione and glutathione play an important function in the cellular growth, maintenance and reduction of oxidative stress in Leishmania species. In particular, parasite specific trypanothione has been established as a prime target for new anti-leishmania drugs. Previous studies into the interaction of the front-line Sb(V) based anti-leishmanial drug meglumine antimoniate with glutathione, have demonstrated that a reduction pathway may be responsible for its effective and selective nature.

Development of new combination anti-leishmanial complexes: Triphenyl Sb(V) mono-hydroxy mono-quinolinolates.

In seeking to develop single entity combination anti-Leishmanial complexes six heteropletic organometallic Sb(V) hydroxido quinolinolate complexes of general formula [SbPh(CHNORR')(OH)] have been synthesised and characterised, derived from a series of halide substituted quinolinols (8-hydroxyquinolines). Single crystal X-ray diffraction on all the complexes show a common distorted six-coordinate octahedral environment at the Sb(V) centre, with the aryl groups and nitrogen atom of quinolinolate ligand bonding in the equatorial planes, with the two oxygen atoms (hydroxyl and quinolinolate) occupying the axial plane in an almost linear configuration. Each complex was tested for their anti-promastigote activity and mammalian cytotoxicity and a selectivity indices established.

Interactions of Non-steroidal Anti-inflammatory Drugs and Their Bismuth Analogues (BiNSAIDs) with Biological Membrane Mimics at Physiological pH.

Previous studies have demonstrated the potential for non-steroidal anti-inflammatory drugs (NSAIDs), in particular aspirin, to be used as chemopreventives for colorectal cancer; however, a range of unwanted gastrointestinal side effects limit their effectiveness. Due to the role of bismuth in the treatment of gastrointestinal disorders, it is hypothesized that bismuth-coordinated NSAIDs (BiNSAIDs) could be used to combat the gastrointestinal side effects of NSAIDs while still maintaining their chemopreventive potential. To further understand the biological activity of these compounds, the present study examined four NSAIDs, namely, tolfenamic acid (tolfH), aspirin (aspH), indomethacin (indoH), and mefenamic acid (mefH) and their analogous homoleptic BiNSAIDs ([Bi(L)]), to determine how these compounds interact with biological membrane mimics composed of 1-palmitoyl-2-oleoyl--glycero-3-phosphocholine (POPC) or a mixture of POPC and cholesterol.

Antimicrobial innovation: a current update and perspective on the antibiotic drug development pipeline.

As bacteria continue to develop resistance to our existing treatment options, antibiotic innovation remains overlooked. If current trends continue, then we could face the stark reality of a postantibiotic era, whereby routine bacterial infections could once again become deadly. In light of a warning signaled by the WHO, a number of new initiatives have been established in the hope of reinvigorating the antibiotic drug development pipeline.

Main Group Metal-Mediated Transformations of Imines.

Main-group-metal-mediated transformations of imines have earned a valued place in the synthetic chemist's toolbox. Their versatility allows the simple preparation of various nitrogen containing compounds. This review will outline the early discoveries including metallation, addition/cyclisation and metathesis pathways, followed by the modern-day use of imines in synthetic methodology.

Impact of structural changes in heteroleptic bismuth phosphinates on their antibacterial activity in Bi-nanocellulose composites.

To study and evaluate the effect of ligand choice and distribution in bismuth phosphinates on toxicity and antibacterial activity, a series of novel diphenyl mono-phosphinato bismuth complexes, [BiPh2(O(O[double bond, length as m-dash])P(H)Ph)] 1, [BiPh2(O(O[double bond, length as m-dash])PPh2)] 2, [BiPh2(O(O[double bond, length as m-dash])PMe2)] 3 and [BiPh2(O(O[double bond, length as m-dash])P(p-MeOPh)2)] 4, were synthesised, characterised and structurally authenticated by X-ray crystallography. Evaluation of their antibacterial activity towards Staphylococcus aureus (S. aureus), methicillin-resistant S.

Isomers of Alkali Metal (Methylbenzyl)allylamides: A Theoretical Perspective.

Recent studies of alkali metal -(α-methylbenzyl)allylamides containing lithium, sodium, and potassium have shown unique rearrangements in NMR experiments. It was found that lithium isomers favored the formation of aza-allyl and aza-enolate complexes that could exist in a solution for a substantial amount of time. As the radius of the metal ion increases going from lithium to potassium, so does the preference for the formation of the imine structure.

Bismuth(III) Flavonolates: The Impact of Structural Diversity on Antibacterial Activity, Mammalian Cell Viability and Cellular Uptake.

A series of homoleptic and heteroleptic bismuth(III) flavonolate complexes derived from six flavonols of varying substitution have been synthesised and structurally characterised. The complexes were evaluated for antibacterial activity towards several problematic Gram-positive (Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE)) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. The cell viability of COS-7 (monkey kidney) cells treated with the bismuth flavonolates was also studied to determine the effect of the complexes on mammalian cells.