Infections caused by drug-resistant pathogens are rapidly increasing in incidence and pose an urgent global health concern. New treatments are needed to address this critical situation while ...preventing further resistance acquired by the pathogens. One promising approach is antimicrobial photodynamic therapy (PDT), a technique that selectively damages pathogenic cells through reactive oxygen species (ROS) that have been deliberately produced by light-activated chemical reactions via a photosensitiser. There are currently some limitations to its wider deployment, including aggregation, hydrophobicity, and sub-optimal penetration capabilities of the photosensitiser, all of which decrease the production of ROS and lead to reduced therapeutic performance. In combination with nanoparticles, however, these challenges may be overcome. Their small size, functionalisable structure, and large contact surface allow a high degree of internalization by cellular membranes and tissue barriers. In this review, we first summarise the mechanism of PDT action and the interaction between nanoparticles and the cell membrane. We then introduce the categorisation of nanoparticles in PDT, acting as nanocarriers, photosensitising molecules, and transducers, in which we highlight their use against a range of bacterial and fungal pathogens. We also compare the antimicrobial efficiency of nanoparticles to unbound photosensitisers and examine the relevant safety considerations. Finally, we discuss the use of nanoparticulate drug delivery systems in clinical applications of antimicrobial PDT.
Fire-derived organic matter, often referred to as pyrogenic organic matter (PyOM), is present in the Earth's soil, sediment, atmosphere, and water. We investigated interactions of PyOM with ammonia ...(NH
) gas, which makes up much of the Earth's reactive nitrogen (N) pool. Here we show that PyOM's NH
retention capacity under ambient conditions can exceed 180 mg N g
PyOM-carbon, resulting in a material with a higher N content than any unprocessed plant material and most animal manures. As PyOM is weathered, NH
retention increases sixfold, with more than half of the N retained through chemisorption rather than physisorption. Near-edge X-ray absorption fine structure and nuclear magnetic resonance spectroscopy reveal that a variety of covalent bonds form between NH
-N and PyOM, more than 10% of which contained heterocyclic structures. We estimate that through these mechanisms soil PyOM stocks could retain more than 600-fold annual NH
emissions from agriculture, exerting an important control on global N cycling.
RAFT mesoporous silica nanoparticles (MSNs) have been synthesized for the first time via co-condensation of an organoalkoxysilane RAFT agent, 1-phenylethyl(3-(triethoxysilyl)propyl)carbonotrithioate, ...with tetraethoxysilane (TEOS) in aqueous basic cetyltrimethylammonium bromide. The stability of the organoalkoxysilane RAFT agent during the synthesis of MSNs was established using solution NMR and UV–visible spectroscopies. The RAFT-MSNs were then used for elaboration with N-isopropylacrylamide (NIPAM) via controlled surface-initiated RAFT polymerization. The success of the incorporation of the organoalkoxysilane RAFT agent into the silica network, and polymerization of PNIPAM was confirmed with TGA, FT-IR, UV–visible spectroscopy, 13C and 29Si solid state NMR spectroscopy. The effect of the organoalkoxysilane based RAFT agent and PNIPAM grafting on the morphology, size and surface area of the resulting MSNs was investigated using SEM, TEM, XRD, DLS and BET analysis. The appearance of carbon signals in 13C solid state NMR, T signals in 29Si solid state NMR and CH stretching signals in FT-IR establishes that we have successfully obtained organic-inorganic hybrid materials. The pore area calculated using Barrett-Joyner-Halenda (BJH) analysis was 87.8 m2 g−1 for control-MSNs, 91.1 m2 g−1 for RAFT-MSNs and 132.9 m2 g−1 for PNIPAM-MSNs. The thermoresponsive behaviour of PNIPAM grafted inside the pores of MSNs was studied by dye as well as drug loading experiments at variable temperatures, followed by characterization using confocal laser scanning microscopy. The green and red fluorescence corresponding to fluorescein and doxorubicin respectively was strongly retained in the PNIPAM-MSNs after 24 h of incubation at 25 °C while lack of fluorescence after 24 h incubation at 35 °C, demonstrates the thermoresponsive behaviour of the polymer being grafted inside the pores of mesoporous silica nanoparticles.
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•RAFT mesoporous silica nanoparticles have been synthesized via co-condensation of an organoalkoxysilane RAFT agent and tetraethoxysilane.•The success of incorporation of RAFT agent and polymerization of PNIPAM was confirmed using FT-IR, UV-visible, and solid state NMR spectroscopy.•The effect of RAFT agent and PNIPAM grafting on the morphology, size and surface area was investigated using SEM, TEM, XRD, DLS and BET analysis.•The thermoresponsive behaviour of PNIPAM grafted MSNs was studied by dye as well as drug loading experiments and characterization using CLSM.
Metal‐free polymeric carbon nitrides (PCNs) are promising photocatalysts for solar hydrogen production, but their structure–photoactivity relationship remains elusive. Two PCNs were characterized by ...dynamic‐nuclear‐polarization‐enhanced solid‐state NMR spectroscopy, which circumvented the need for specific labeling with either 13C‐ or 15N‐enriched precursors. Rapid 1D and 2D data acquisition was possible, providing insights into the structural contrasts between the PCNs. Compared to PCN_B with lower performance, PCN_P is a more porous and more active photocatalyst that is richer in terminal N−H bonds not associated with interpolymer chains. It is proposed that terminal N−H groups act as efficient carrier traps and reaction sites.
Generous to a fault: Structural defects in photocatalytic polymeric carbon nitrides are correlated with photocatalyzed hydrogen evolution. An increased number of terminal N−H bonds (▪(blue)) and reduced hydrogen bonding is associated with high performance, whereas polymer containing fewer terminal N−H bonds (•) solicits lower performance.
In nature, self-assembly processes based on amphiphilic molecules play an integral part in the design of structures of higher order such as cells. Among them, amphiphilic glycoproteins or glycolipids ...take on a pivotal role due to their bioactivity. Here we show that sugars, in particular, fructose, are capable of directing the self-assembly of highly insoluble curcumin resulting in the formation of well-defined capsules based on non-covalent forces. Simply by mixing an aqueous solution of fructose and curcumin in an open vessel leads to the generation of capsules with sizes ranging between 100 and 150 nm independent of the initial concentrations used. Our results demonstrate that hydrogen bonding displayed by fructose can induce the self-assembly of hydrophobic molecules such as curcumin into well-ordered structures, and serving as a simple and virtually instantaneous way of making nanoparticles from curcumin in water with the potential for template polymerization and nanocarriers.
Surface modification of natural halloysite clay nanotubes with γ-aminopropyltriethoxysilane (APTES) was investigated. Untreated and modified samples were characterized by nitrogen adsorption, X-ray ...diffraction, elemental analysis, thermogravimetry, transmission electron microscopy, atomic force microscopy, MAS nuclear magnetic resonance (29Si, 13C, 29Al), and Fourier transform infrared spectroscopy. The modification mechanism was found to include not only the direct grafting of APTES onto the hydroxyl groups of the internal walls, edges and external surfaces of the nanotubes but other processes in which oligomerized APTES condensed with the directly grafted APTES to form a cross-linked structure. The thermal and evacuation pretreatment conditions were found to play an important role in controlling the extent and mechanism of the modification. The extent of modification is also strongly affected by the morphological parameters of the original clay samples. This study demonstrates that the surface chemistry of halloysite nanotubes is readily modified, enabling applications in nanocomposites, enzyme immobilization and controlled release.
This study uses 35Cl and 14N solid-state NMR (SSNMR) spectroscopy and dispersion-corrected plane-wave density functional theory (DFT) calculations for the structural characterization of chloride ...salts of nutraceuticals in their bulk and dosage forms. For eight nutraceuticals, we measure the 35Cl EFG tensor parameters of the chloride ions and use plane-wave DFT calculations to elucidate relationships between NMR parameters and molecular-level structure, which provide rapid NMR crystallographic assessments of structural features. We employ both 35Cl direct excitation and 1H→35Cl cross-polarization methods to characterize a dosage form containing α-d-glucosamine HCl, observe possible impurity and/or adulterant phases, and quantify the weight percent of the active ingredient. To complement this, we also investigate 14N SSNMR spectroscopy and DFT calculations to characterize nitrogen atoms in the nutraceuticals. This includes a discussion of targeted acquisition experimental protocols (i.e., acquiring a select region of the overall pattern that features key discontinuities) that allow ultrawideline spectra to be acquired rapidly, even for unreceptive samples (i.e., those with long values of T 1(14N), short values of T 2 eff(14N), or very broad patterns). It is hoped that these experimental and computational protocols will be useful for the characterization of various solid forms of nutraceuticals (i.e., salts, polymorphs, hydrates, solvates, cocrystals, amorphous solid dispersions, etc.), help detect impurity and counterfeit solid phases in dosage forms, and serve as a foundation for future NMR crystallographic studies of nutraceutical solid forms, including studies using ab initio crystal structure prediction algorithms.
► We studied the structure of rutin/cyclodextrin complex using 2D ROESY 1H NMR. ► We found that the A ring of rutin inserted into the cavity of cyclodextrins. ► The complexation is an exothermic ...process that occurs spontaneously. ► Formation of the complex protected rutin from thermal and UV degradation. ► Formation of the complex enhanced the antioxidant activity of rutin.
The formation of supramolecular inclusion complexes between rutin and four cyclodextrins, namely β-cyclodextrin (β-CD), (2-hydroxypropyl)-α-cyclodextrin (HP-α-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD), and the effects of the complexation on the stability and antioxidant activity of rutin were investigated. Results from phase-solubility studies showed that rutin formed 1:1 stoichiometric inclusion complexes with HP-α-CD, β-CD, HP-β-CD and HP-γ-CD; the complexes formed with HP-γ-CD and HP-β-CD had the greatest stability constants, followed by β-CD and HP-α-CD. Thermodynamic studies demonstrate that the inclusion of rutin into HP-β-CD was an exothermic process which occurred spontaneously. Two-dimensional rotating-frame nuclear Overhauser effect spectroscopy (2D ROESY) 1H NMR analyses show that the A ring of rutin was the part of the molecule that most likely inserted into the cavity of HP-β-CD, thus forming a supramolecular inclusion complex. Formation of such an inclusion complex conferred moderate degrees of protection to rutin from degradation by heat and UV radiation during storage, and significantly enhanced its antioxidant capacity as determined by three different procedures.
We performed whole-genome sequencing (WGS) of 208 genomes from 53 families affected by simplex autism. For the majority of these families, no copy-number variant (CNV) or candidate de novo ...gene-disruptive single-nucleotide variant (SNV) had been detected by microarray or whole-exome sequencing (WES). We integrated multiple CNV and SNV analyses and extensive experimental validation to identify additional candidate mutations in eight families. We report that compared to control individuals, probands showed a significant (p = 0.03) enrichment of de novo and private disruptive mutations within fetal CNS DNase I hypersensitive sites (i.e., putative regulatory regions). This effect was only observed within 50 kb of genes that have been previously associated with autism risk, including genes where dosage sensitivity has already been established by recurrent disruptive de novo protein-coding mutations (ARID1B, SCN2A, NR3C2, PRKCA, and DSCAM). In addition, we provide evidence of gene-disruptive CNVs (in DISC1, WNT7A, RBFOX1, and MBD5), as well as smaller de novo CNVs and exon-specific SNVs missed by exome sequencing in neurodevelopmental genes (e.g., CANX, SAE1, and PIK3CA). Our results suggest that the detection of smaller, often multiple CNVs affecting putative regulatory elements might help explain additional risk of simplex autism.
Dramatic changes in molecular structure, degradation pathway, and porosity of biochar are observed at pyrolysis temperatures ranging from 250 to 550 °C when bamboo biomass is pretreated by ...iron-sulfate-clay slurries (iron–clay biochar), as compared to untreated bamboo biochar. Electron microscopy analysis of the biochar reveals the infusion of mineral species into the pores of the biochar and the formation of mineral nanostructures. Quantitative 13C nuclear magnetic resonance (NMR) spectroscopy shows that the presence of the iron clay prevents degradation of the cellulosic fraction at pyrolysis temperatures of 250 °C, whereas at higher temperatures (350–550 °C), the clay promotes biomass degradation, resulting in an increase in both the concentrations of condensed aromatic, acidic, and phenolic carbon species. The porosity of the biochar, as measured by NMR cryoporosimetry, is altered by the iron–clay pretreatment. In the presence of the clay, at lower pyrolysis temperatures, the biochar develops a higher pore volume, while at higher temperature, the presence of clay causes a reduction in the biochar pore volume. The most dramatic reduction in pore volume is observed in the kaolinite-infiltrated biochar at 550 °C, which is attributed to the blocking of the mesopores (2–50 nm pore) by the nonporous metakaolinite formed from kaolinite.
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