A mechanochemical approach was utilized for the synthesis of naloxone covalently linked poly(lactic acid) and nanoparticles. This preparation was achieved using lactide as a monomer in anionic ring opening polymerization, naloxone as a drug initiator, and CHCl3 to perform liquid-assisted grinding. This process resulted in the direct preparation of a naloxone nanoparticle with a drug loading of similar to 8.3% w/w and nanoparticles around 600 nm. These findings underscore the promise of mechanochemistry in developing drug delivery systems.

Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningitis in >152,000 immunocompromised individuals annually, leading to 112,000 yearly deaths. The four classes of existing antifungal agents target plasma membrane sterols (ergosterol), nucleic acid synthesis, and cell wall synthesis. Existing drugs are not highly effective against Cryptococcus, and antifungal drug resistance is an increasing problem. A novel antimicrobial compound, a eumelanin-inspired indoylenepheyleneethynylene, EIPE-1, was synthesized and has antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MSRA), but not towards Gram-negative organisms. Based on EIPE-1’s antibacterial activity, we hypothesized that EIPE-1 could have antifungal activity. For these studies, we tested EIPE-1 against C. neoformans strain H99 and 6 additional cryptococcal clinical isolates. We examined antifungal activity, cytotoxicity, effects on fungal gene expression, and mechanism of action of EIPE-1. Results showed that EIPE-1 has fungicidal effects on seven cryptococcal strains with MICs ranging from 1.56 to 3.125 μg/mL depending on the strain, and it is non-toxic to mammalian cells. We conducted scanning and transmission electron microscopy on the exposed cells to examine structural changes to the organism following EIPE-1 treatment. Cells exposed displayed structural changes to their cell wall and membranes, with internal contents leaking out of the cells. To understand the effect of EIPE-1 on fungal gene expression, RNA sequencing was conducted. Results showed that EIPE-1 affects several processes involved stress response, ergosterol biosynthesis, capsule biosynthesis, and cell wall attachment and remodeling. Therefore, our studies demonstrate that EIPE-1 has antifungal activity against C. neoformans, which affects both cellular structure and gene expression of multiple fungal pathways involved in cell membrane stability and viability.

Due to their notable antimicrobial activity and optical properties, Schiff base ligands, along with their lanthanide and transition metal complexes, have seen extensive use in various applications. However, despite their potential, a comprehensive investigation into lanthanide and transition metal complexes using the same Schiff base ligand has not been reported to date. In this study, coordination compounds of lanthanide and transition metal ions were synthesized from the Schiff base ligand salicylaldehyde‐dipropylenetriamine. These complexes were characterized by elemental analysis, 1H and 13C NMR, mass spectroscopy, Fourier‐transform infrared spectroscopy ultraviolet–visible spectroscopy (UV–Vis), fluorescence spectroscopy, molar conductivity measurements, and thermogravimetric studies. Furthermore, the molecular structure of the Co (II) complex was determined by means of X‐ray crystallography. Thermogravimetric studies illustrated endothermic and non‐spontaneous degradation pathways of the complexes. UV–Vis spectra showed a new absorption band attributed to the ligand‐to‐metal charge transfer peak supporting the complexation between the ligand and metals. The lanthanide complexes exhibited distinctive luminescence emissions in the Sm (III), Tb (III), and Eu (III) complexes. This observation suggests that the ligand possesses the capability to absorb and efficiently transfer energy to the metal center of these lanthanide ions, thereby resulting in their characteristic luminescent properties. Additionally, antimicrobial investigations revealed that transition metal complexes generally exhibited antimicrobial activity against both gram‐positive and gram‐negative bacterial strains compared to lanthanide metal complexes, in most cases. However, it is noteworthy that the Dy (III) complex displayed the lowest minimum inhibitory concentration and minimum biocidal concentration values of 16 μg/ml against Staphylococcus epidermidis, indicating its potential as a candidate for the treatment of this pathogenic bacterium. The main purpose of this article is to investigate the variations in the synthesis and characterization of lanthanide and transition metal complexes utilizing the same Schiff base ligand suitable for applications in the pharmaceutical industry and optical material sciences.

Introduction Unique impermeability properties of the gram-negative outer cell envelope typically render these organisms intrinsically resistant to hydrophobic antibacterial compounds. Eumelanin-inspired indoylenephenyleneethynylene (EIPE) compounds possess scaffolding to which functional groups were attached to potentially provide antibacterial properties in the forms of hydrophilic (EIPE-HCl) and hydrophobic (EIPE-1) derivatives. Methods Standardized disk agar diffusion and microbroth dilution bioassays were employed to assess the susceptibility of disparate gram-negative and gram-positive bacterial pathogens to the two compounds. EIPE-1 mechanisms of action and intrinsic resistance were further investigated turbidimetrically in batch cultures with the aid of the gram-negative outer membrane permeabilizer compound 48/80. Results Hydrophobic derivative EIPE-1 exhibited a gram-positive antibacterial spectrum, while hydrophilic derivative EIPE-HCl possessed no antibacterial properties. EIPE-1 exhibited minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values below 2.0 µg/mL against all gram-positive bacteria, including two methicillin-resistant strains. In contrast, MIC/MBC values greater than 128 µg/mL were obtained for all gram-negative bacteria examined. Susceptibility of two strains of the strict anaerobe Clostridioides difficile indicated the EIPE-1 mechanism of action does not require molecular oxygen. Turbidimetric growth curves revealed EIPE-1 induced rapid bacteriolysis of Bacillus subtilis ATCC 6633, thereby suggesting a membrane-directed modality. Lastly, the outer membrane permeabilizer compound 48/80 failed to markedly sensitize any of three phylogenetically disparate gram-negative organisms to EIPE-1. Conclusion These data suggest that the hydrophobic melanin-inspired derivative EIPE-1 inhibits gram-positive bacteria in a cytoplasmic membrane-directed manner independent of oxygen. Moreover, a secondary mechanism may function concomitantly with outer membrane exclusionary properties to underly the intrinsic resistance of gram-negative pathogens.

Due to its biodegradable and biocompatible nature, poly(lactic acid) (PLA) has found widespread use in biomedical applications. Controlled drug delivery using PLA-based nanoparticles (PLA-NPs) is an important tool for tuning the bioavailability of therapeutics. Traditional methods to prepare PLA-NPs require a multistep process that is time-consuming and produces significant aqueous and organic waste streams. This work reports a one-pot mechanochemical synthesis of lactide to PLA-NPs. In this report, we developed and trained an artificial neural network algorithm to optimize PLA and PLA-NP preparation. Our results demonstrate a robust and optimized one-pot method for preparing precisely defined nanoparticles that generates minimal waste.

The mu opioid receptor antagonist naloxone has been a vital, long-standing countermeasure in the ongoing battle against opioid use disorders (OUD) and toxicity. However, due to its distinctive short elimination half-life, naloxone has shown diminished efficacy in cases of synthetic opioid poisoning as larger or repeated doses of the antidote have been required to achieve adequate reversal of severe respiratory depression and prevent episodes of renarcotization. This report describes the synthesis, characterization, and in vivo evaluation of a novel, nanoparticle-based naloxone formulation that provides extended protection against the toxic effects of the powerful synthetic opioid fentanyl. The strategy was predicated on a modified two-step protocol involving the synthesis and subsequent nanoprecipitation of a poly(lactic-co-glycolic acid) polymer scaffold bearing a covalently linked naloxone chain end (drug loading ∼7% w/w). Pharmacokinetic evaluation of the resulting covalently loaded naloxone nanoparticles (cNLX-NP) revealed an elimination half-life that was 34 times longer than high dose free naloxone (10 mg/kg) in male Sprague-Dawley rats. This enhancement was further demonstrated by cNLX-NP in subsequent in vivo studies affording protection against fentanyl-induced respiratory depression and antinociception for up to 48 h following a single intramuscular injection. These discoveries support further investigation of cNLX-NP as a potential therapeutic to reverse overdose and prevent renarcotization from fentanyl and its potent analogs.

This study aims to analyse the heavy metal pollutants in Jeddah, the second largest city in the Gulf Cooperation Council with a population exceeding 3.5 million, and many vehicles. Ninety-eight street dust samples were collected seasonally from the six major roads as well as the Jeddah Beach, and subsequently digested using modified Leeds Public Analyst method. The heavy metals (Fe, Zn, Mn, Cu, Cd, and Pb) were extracted from the ash using methyl isobutyl ketone as solvent extraction and eventually analysed by atomic absorption spectroscopy. Multivariate statistical techniques, principal component analysis (PCA), and hierarchical cluster analysis were applied to these data. Heavy metal concentrations were ranked according to the following descending order: Fe > Zn > Mn > Cu > Pb > Cd. In order to study the pollution and health risk from these heavy metals as well as estimating their effect on the environment, pollution indices, integrated pollution index, enrichment factor, daily dose average, hazard quotient, and hazard index were all analysed. The PCA showed high levels of Zn, Fe, and Cd in Al Kurnish road, while these elements were consistently detected on King Abdulaziz and Al Madina roads. The study indicates that high levels of Zn and Pb pollution were recorded for major roads in Jeddah. Six out of seven roads had high pollution indices. This study is the first step towards further investigations into current health problems in Jeddah, such as anaemia and asthma.

Self-assembled monolayers (SAMs) of terphenylthiol (TP0) prepared on Au(111) from ethanolic solution at room temperature and subsequently annealed at different temperatures of up to 473 K were investigated using scanning tunneling microscopy and infrared reflection absorption spectroscopy. Upon annealing, the TP0 adlayer formed a series of different structural phases with different molecular arrangements. Our results show that SAMs prepared at RT without annealing and SAMs annealed at 313 K exhibited the formation of a closely packed "alpha" structure where TP0 molecular axes are orientated almost upright. The formation of the alpha-phase was accompanied by the formation of a loosely packed phase (beta-phase). During annealing from 333 to 473 K, the results revealed the formation of different structural phases, namely, gamma, delta, epsilon, sigma, and phi. With the exception of the phi-phase, the phases were found to form loosely packed structures with the molecular axes largely tilted away from surface normal but do not form "flat-lying" phases. Surprisingly, upon annealing at 453 K, the SAMs exhibited a phase transition to a higher dense network of molecular structure (phi-phase) with almost upright standing molecules. An additional annealing at 463 K led to a significant increase in the size of the well-ordered domains of the phi-phase at the expense of their density. At the same time, a partial desorption of the TP0-SAMs was noticed to take place. The formation of a densely packed phase upon annealing and subsequently desorption of TP0 molecules from this state completely contradicts the behavior of n-alkanethiol and other oligophenylthiol SAMs, in which desorption occurs from lying-flat geometry. The phi-phase, which was the only one remaining on the surface, did not cover more than 30% of the gold surface area. A further increase of the annealing temperature to 473 K caused a substantial increase in the number of the desorbed molecules. Therefore, a remarkable reduction in both the size and density of the ordered domains of the phi-phase was observed. On the other hand, the annealing temperature was found to have a significant influence on both the appearance and the shape of the gold islands. Moreover, it has been found that the gold islands, regardless of their shapes, were always covered by standing-up, densely packed, and ordered phases such as the alpha- and phi-phases.

A series of lanthanide complexes with the general formulae [Ln(dmpc)(NO3)2(H2O)2]NO3 (Ln=Pr, Nd, Sm, Eu, Gd, Tb, Dy, and Er) and [La(dmpc)(NO3)2(H2O)2]NO3 were prepared by direct reaction between hydrated lanthanide(III) nitrate and dimethylpyridine-2,6-dicarboxylate (dmpc) in a 1:1 M ratio in ethylacetate–chloroform mixture. The luminescence properties of the dmpc and its Ln(III) complexes were investigated in solid state and in methanol, DMF and DMSO solutions. The Tb–dmpc, Eu–dmpc, Sm–dmpc and Dy–dmpc complexes exhibit characteristic luminescence of Tb(III), Eu(III), Sm(III) and Dy(III) ions indicating energy transfer from the dmpc to the Ln(III) ions. Scavenging activities of the dmpc and its Ln(III) complexes on DPPH• free radical were investigated in DMSO solution at a different concentrations ranges.

In order to investigate the levels of selected heavy metals and propose the causes for the presence of these metals in street and house dust of Al-Qunfudah province (Saudi Arabia), one hundred dust samples were collected, digested and analyzed. All collected samples were digested using Leeds Public Analyst method. The concentrations of heavy metals (Fe, Cu, Mn, Zn, Cd, Co and Pb) were analyzed using atomic absorption spectroscopy. Six heavy metals (Fe, Cu, Mn, Zn, Co and Pb) were measured in all samples; the concentration of Cd was not detected in Al-Qunfudah dust by atomic absorption spectroscopy. Generally, house dust samples have lower concentrations for Fe and Pb compared to the street dust samples. Conversely, Cu, Mn, Co and Zn have higher concentrations in house dust samples compared to the street dust samples. The street heavy metal levels increase according to the following descending order: Fe > Mn > Zn > Cu > Pb > Co. The values of heavy metals in dust samples in this study were compared with values found in other investigations within the country and in various other countries. The correlation coefficients and enrichment factors relative to earth crust abundances of heavy metals were calculated in order to predict the possible sources in dust. Health risk, the hazard index (HI), values for all studied elements were lower than safe limit of 1 indicating that there is no potential health risk due to exposure to heavy metals from outdoor dust in the study area.

A series of lanthanide complexes with a Schiff base ligand, L (N,N′-bis(2-hydroxy-1-naphthylidene)-1,6-hexadiimine) are presented. The ligand and its complexes were synthesized and characterized based on elemental analyses, molar conductance, IR, 1H and 13C NMR, UV–Vis, and TGA studies. These analytical and spectral data reveal that the ligand L coordinates to the central Ln(III) ion by its two imine nitrogen atoms and two phenolic oxygen atoms and the general formula of the complex is [LnL(NO3)2·2H2O]NO3, Ln=[Ln=La(III), Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III) and Er(III)] Under the excitation at 396nm, the luminescence emission properties for Sm, Tb, and Eu complexes are observed. These observations show that the ligand favors energy transfers to the emitting energy level of these lanthanide ions. Furthermore, the antimicrobial activities of all complexes were studied against a number of pathogenic bacteria. The antimicrobial activity results show that most of the synthesized Ln(III) complexes possessed good antibacterial activity and in most cases higher than that of the corresponding ligand L.