Photoinduced Energy and Electron Transfer in a 'Two-Point' Bound Panchromatic, Near-Infrared-Absorbing Bis-styrylBODIPY(Zinc Porphyrin)2 - Fullerene Self-Assembled Supramolecular Conjugate.

Structurally well-defined self-assembled supramolecular multi-modular donor-acceptor conjugates play a significant role in furthering our understanding of photoinduced energy and electron transfer events occurring in nature, e. g., in the antenna-reaction centers of photosynthesis and their applications in light energy harvesting. However, building such multi-modular systems capable of mimicking the early events of photosynthesis has been synthetically challenging, causing a major hurdle for its growth. Often, multi-modularity is brought in by combining both covalent and noncovalent approaches. In the present study, we have developed such an approach wherein a π-extended conjugated molecular cleft, two zinc(II)porphyrin bearing bisstyrylBODIPY (dyad, 1), has been synthesized. The binding of 1 via a 'two-point' metal-ligand coordination of a bis-pyridyl fulleropyrrolidine (2), forming a stable self-assembled supramolecular complex (1 : 2), has been established. The self-assembled supramolecular complex has been fully characterized by a suite of physico-chemical methods, including TD-DFT studies. From the established energy diagram, both energy and electron transfer events were envisioned. In dyad 1, selective excitation of zinc(II)porphyrin leads to efficient singlet-singlet excitation transfer to (bisstyrly)BODIPY with an energy transfer rate constant, kEnT of 2.56×1012 s-1. In complex 1 : 2, photoexcitation of zinc(II)porphyrin results in ultrafast photoinduced electron transfer with a charge separation rate constant, kCS of 2.83×1011 s-1, and a charge recombination rate constant, kCR of 2.51×109 s-1. For excitation at 730 nm corresponding to bisstyrylBODIPY, similar results are obtained, where a biexponential decay yielded estimated values of kCS 3.44×1011 s-1 and 2.97×1010 s-1, and a kCR value of 2.10×1010 s-1. The newly built self-assembled supramolecular complex has been shown to successfully mimic the early events of the photosynthetic antenna-reaction center events.

Correction: Paper spray mass spectrometry utilizing Teslin® substrate for rapid detection of lipid metabolite changes during COVID-19 infection.

Correction for 'Paper spray mass spectrometry utilizing Teslin® substrate for rapid detection of lipid metabolite changes during COVID-19 infection' by Imesha W. De Silva et al., Analyst, 2020, 145, 5725-5732, DOI: 10.1039/D0AN01074J.

Inhalation exposure to silver nanoparticles induces hepatic inflammation and oxidative stress, associated with altered renin-angiotensin system signaling, in Wistar rats.

Silver nanoparticles (AgNPs) have become increasingly popular in the biomedical field over the last few decades due to its proven antibacterial property. Previous scientific studies have reported that one of the major organs responsible for detoxification of AgNPs is the liver. The liver is also the primary organ responsible for secretion of angiotensinogen (AGT), a key signaling molecule involved in the renin-angiotensin system (RAS), which plays an important role in maintaining cardiac output and vascular pressure. The aim of this study was to assess any potential changes in the RAS-associated gene signaling, inflammatory response, and hepatocellular toxicity resulting from AgNP exposure. To do this, 6-week-old, male Wistar rats were exposed to a subacute inhalation exposure of AgNP (200 ppb/days over 4 h/days exposure, for 5 d) and their livers were analyzed for alterations in RAS components, inflammation, and oxidative stress. Real time qPCR analysis showed that AgNP-exposure resulted in a significant increase in hepatic AGT, angiotensin converting enzyme (ACE)-1, and ACE-2 mRNA expression. Expression of inflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were also upregulated with AgNP-exposure, compared to controls. Furthermore AgNP-exposure mediated a significant increase in hepatic expression of catalase, and superoxide dismutase, and oxidative stress, as assessed via 8-Oxo-2'-deoxyguanosine staining. Increased oxidative stress was associated with increased monocyte/macrophage-2 staining in the liver of AgNP-exposed rats. Such findings indicate that subacute inhalation exposure to AgNPs mediate increased hepatic RAS signaling, associated with inflammation, macrophage infiltration, and oxidative stress.

Toxicological alterations induced by subacute exposure of silver nanoparticles in Wistar rats.

Silver nanoparticles (AgNPs) have become crucial players in the field of medicine and various other industries. AgNPs have a wide array of applications, which includes production of electronic goods, cosmetics, synthesis of dyes, and printing inks, as well as targeted delivery of drugs to specialized cells inside the body. Even though humans readily come in contact with these particles, the organ-specific accumulation and resulting mechanisms of toxicity induced by inhaled AgNPs are still under investigation. The goal of this study was to determine the organ distribution of inhaled AgNPs and investigate the resulting systemic toxicity. To do this, male Wistar rats were exposed by inhalation to AgNPs for 4 hr/day (200 parts per billion/day) for five consecutive days. The nanoparticles were generated using a laser ablation technique using a soft-landing ion mobility (SLIM) instrument. Inductively coupled plasma mass spectrometric (ICP-MS) analysis showed organ-specific accumulation of the nanoparticles, with the highest concentration present in the lungs, followed by the liver and kidneys. Nanoparticle distribution was characterized in the organs using scanning electron microscopy (SEM) and matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) imaging. Bone marrow cytotoxicity assay of the cells from the femur of rats showed micronuclei formation and signs of cellular cytotoxicity. Moreover, rats displayed increased levels of circulating lactate and glutathione disulphide (GSSG), as determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Collectively, our observations suggest that inhaled subacute exposure to AgNP results in accumulation of AgNPs in the lungs, liver, and kidneys, preferentially, as well as mediates induced systemic toxicity.

Paper spray mass spectrometry utilizing Teslin® substrate for rapid detection of lipid metabolite changes during COVID-19 infection.

The SARS-CoV-2 virus is known as the causal agent for the current COVID-19 global pandemic. The majority of COVID-19 patients develop acute respiratory distress syndrome (ARDS), while some experience a cytokine storm effect, which is considered as one of the leading causes of patient mortality. Lipids are known to be involved in the various stages of the lifecycle of a virus functioning as receptors or co-receptors that controls viral propagation inside the host cell. Therefore, lipid-related metabolomics aims to provide insight into the immune response of the novel coronavirus. Our study has focused on determination of the potential metabolomic biomarkers utilizing a Teslin® Substrate in paper spray mass spectrometry (PS-MS) for the development of a rapid detection test within 60 seconds of analysis time. In this study, results were correlated with PCR tests to reflect that the systemic responses of the cells were affected by the COVID-19 virus.

Severe E-Cigarette, or Vaping, Product Use Associated Lung Injury Requiring Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To report a severe case of e-cigarette or vaping product use-associated lung injury with complex course requiring venovenous extracorporeal membrane oxygenation. DESIGN: Case report. SETTING: PICU in an academic medical center. PATIENTS: A 16-year-old girl presenting with gastrointestinal and respiratory symptoms was admitted to our PICU after having progressive respiratory failure and bilateral pulmonary ground-glass opacities on chest CT. INTERVENTIONS: Venovenous extracorporeal membrane oxygenation MEASUREMENTS AND MAIN RESULTS:: After extensive infectious workup was unrevealing, she reported a history of vaping e-cigarette containing either nicotine or delta-9-tetrahydrocannabinol oil prior to symptom onset. She was given a presumptive diagnosis of e-cigarette or vaping product use-associated lung injury. The PICU team in consultation with pulmonology and medical toxicology started high-dose IV methylprednisolone 1 mg/kg bid. Despite initial improvements, she continued to require positive pressure ventilation and developed pneumomediastinum with progression to tension pneumothoraces and a persistent air leak. Unable to maintain her oxygenation, she was placed on venovenous extracorporeal membrane oxygenation for a prolonged course and had a tracheostomy placement. The clinical course, severity, and range of interventions in affected patients around the country have varied widely. Respiratory symptoms have been the most severe, but the constellation of symptoms in e-cigarette or vaping product use-associated lung injury include constitutional symptoms (fevers, weight-loss) and gastrointestinal symptoms (nausea, vomiting, diarrhea). In many cases, steroid use led to rapid clinical improvements. However, other cases with severe illness, like our patient, necessitated high-dose IV steroids, intubation, and venovenous extracorporeal membrane oxygenation. The underlying etiology and pathophysiology of e-cigarette or vaping product use-associated lung injury remains unknown. The Centers for Disease Control and Prevention in conjunction with state/local health departments and the Food and Drug Administration is actively investigating the outbreak. CONCLUSIONS: Clinicians need to be aware of the current outbreak of e-cigarette or vaping product use-associated lung injury and ask about vaping in patients presenting with gastrointestinal and respiratory symptoms. Treatment options are anecdotal and necessitate a multidisciplinary approach.

Nanoextraction Coupled to Liquid Chromatography Mass Spectrometry Delivers Improved Spatially Resolved Analysis.

Direct analyte-probed nanoextraction (DAPNe) is a technique that allows extraction of drug and endogenous compounds from a discrete location on a tissue sample using a nano capillary filled with solvent. Samples can be extracted from spot diameters as low as 6 µm. Studies previously undertaken by our group have shown that the technique can provide good precision (5%) for analyzing drug molecules in 150 µm diameter areas of homogenized tissue, provided an internal standard is sprayed on to the tissue prior to analysis. However, without an isotopically labeled standard, the repeatability is poor, even after normalization to the spot area or matrix compounds. By application to tissue homogenates spiked with drug compounds, we can demonstrate that it is possible to significantly improve the repeatability of the technique by incorporating a liquid chromatography separation step. Liquid chromatography is a technique for separating compounds prior to mass spectrometry (LC-MS) which enables separation of isomeric compounds that cannot be discriminated using mass spectrometry alone, as well as reducing matrix interferences. Conventionally, LC-MS is carried out on bulk or homogenized samples, which means analysis is essentially an average of the sample and does not take into account discrete areas. This work opens a new opportunity for spatially resolved liquid chromatography mass spectrometry with precision better than 20%.

True one cell chemical analysis: a review.

The constantly growing field of True One Cell (TOC) analysis has provided important information on the direct chemical composition of various cells and cellular components. Since the heterogeneity of individual cells has been established, more researchers are interested in the chemical differences between individual cells; TOC is the only form of analysis that can provide this information. This has resulted in the constant development of new technologies and methods. This review highlights the common techniques for micro- and nanomanipulation, Raman spectroscopy, microscopy, and mass spectrometric imaging as they pertain to TOC chemical analysis.

Application of Various Normalization Methods for Microscale Analysis of Tissues Using Direct Analyte Probed Nanoextraction.

Direct analyte probed nanoextraction (DAPNe) is a method of extracting material from a microscale region of a sample and provides the opportunity for detailed mass spectrometry analysis of extracted analytes from a small area. The technique has been shown to provide enhanced sensitivity compared with bulk analysis by selectively removing analytes from their matrix and has been applied for selective analysis of single cells and even single organelles. However, the quantitative capabilities of the technique are yet to be fully evaluated. In this study, various normalization techniques were investigated in order to improve the quantitative capabilities of the technique. Two methods of internal standard incorporation were applied to test substrates, which were designed to replicate biological sample matrices. Additionally, normalization to the extraction spot area and matrix compounds were investigated for suitability in situations when an internal standard is not available. The variability observed can be significantly reduced by using a sprayed internal standard and, in some cases, by normalizing to the extracted area.

Chemical Sniffing Instrumentation for Security Applications.

Border control for homeland security faces major challenges worldwide due to chemical threats from national and/or international terrorism as well as organized crime. A wide range of technologies and systems with threat detection and monitoring capabilities has emerged to identify the chemical footprint associated with these illegal activities. This review paper investigates artificial sniffing technologies used as chemical sensors for point-of-use chemical analysis, especially during border security applications. This article presents an overview of (a) the existing available technologies reported in the scientific literature for threat screening, (b) commercially available, portable (hand-held and stand-off) chemical detection systems, and (c) their underlying functional and operational principles. Emphasis is given to technologies that have been developed for in-field security operations, but laboratory developed techniques are also summarized as emerging technologies. The chemical analytes of interest in this review are (a) volatile organic compounds (VOCs) associated with security applications (e.g., illegal, hazardous, and terrorist events), (b) chemical "signatures" associated with human presence, and

Laser ablation coupled with DAPNe-NSI-MS applied to redacted documents.

Laser ablation has been applied to redacted documents, where the text has been concealed by other ink. This technique strips the redacting ink revealing the text that was once redacted. Once removed, a nanomanipulation technique is used to extract the ink of the underlying text where mass spectrometry is then implemented to analyze its ink chemistry. In order to facilitate microscopy with direct analyte-probed nanoextraction coupled to nanospray ionization mass spectrometry (DAPNe-NSI-MS), laser ablation must be executed prior to ink extraction. Laser ablation has a nondestructive approach of stripping the ink used to redact the document. Not only does this reveal the text, it clears an area for DAPNe to directly extract ink, in miniscule amounts, from the document without inducing destruction. The redacting ink was concluded to affect the aging process of the concealed handwritten ink more than the printed text. The redacted handwritten sample obtained higher relative peak area (%) values than the control samples (text that was not redacted) and the control for the printed text produced higher amounts of low molecular weight products than the sample. Implementing laser ablation on these samples could also affect the chemical properties of the underlying ink due to the additional UV radiation and plasma heating. Results indicate by using laser ablation to remove the redacting ink, the relative peak area of the underlying ink deviates by 1.25%. The thermal degradation of binding agents such as polymethylene, polyethylene glycol, and diethylene glycol was monitored by calculating the relative peak area for five days which, in turn, tracks the oxidation process. The relative peak area values were also used to determine the chemical kinetics of polyethylene glycol, where degradation and polymerization occur.

Vehicle-Mounted Portable Mass Spectrometry System for the Covert Detection via Spatial Analysis of Clandestine Methamphetamine Laboratories.

The ability to detect atmospheric effluent from clandestine methamphetamine manufacture is a useful tool for law enforcement. A membrane inlet mass spectrometer is mounted onto an all-electric drive capable hybrid vehicle that samples the atmosphere while in motion. Attributing a latitude and longitude to each spectrum collected, unique chemical fingerprints from clandestine manufacture are then mapped. This location-based mass spectrum data provides a localization to an area of interest. The synthesis of methamphetamine precursors was performed, and the impurities from such reactions were observed. A mock manufacture was setup, and the impurities were introduced into the atmosphere via heating. The detection of products and impurities using this mobile platform has shown the effectiveness of locating and localizing the manufacture of methamphetamine.

Hydrogen as a GC/MS carrier and buffer gas for use in forensic laboratories.

A custom set of ion volumes was manufactured in order to investigate the gain and byproducts using hydrogen as a buffer gas following electron ionization in a quadrupole ion trap mass spectrometer as compared with helium. Analyses of illicit drugs such as cocaine, codeine, and oxycodone, and explosives such as TNT, RDX, and HMTD with ion volume exit orifices of 1mm, 2mm, 4mm, 6mm, 8mm and 10mm were performed using GC/MS. Strong similarities between hydrogen and helium spectra of illicit drugs and explosives provide evidence that hydrogen can be used effectively as a buffer gas in an ion trap mass spectrometer.

Soft-landing ion mobility of silver clusters for small-molecule matrix-assisted laser desorption ionization mass spectrometry and imaging of latent fingerprints.

Matrix-assisted laser desorption ionization (MALDI) imaging is gaining popularity, but matrix effects such as mass spectral interference and damage to the sample limit its applications. Replacing traditional matrices with silver particles capable of equivalent or increased photon energy absorption from the incoming laser has proven to be beneficial for low mass analysis. Not only can silver clusters be advantageous for low mass compound detection, but they can be used for imaging as well. Conventional matrix application methods can obstruct samples, such as fingerprints, rendering them useless after mass analysis. The ability to image latent fingerprints without causing damage to the ridge pattern is important as it allows for further characterization of the print. The application of silver clusters by soft-landing ion mobility allows for enhanced MALDI and preservation of fingerprint integrity.

Parallel artificial membrane permeability assay for blood-brain permeability determination of illicit drugs and synthetic analogues.

With the number of designer drugs on the streets rampantly on the rise, it's becoming more and more important to be able to rapidly characterize them in a biologically relevant way. Using a parallel artificial membrane permeability assay (PAMPA) to assess the blood brain barrier permeability has shown to be a high throughput way to compare new drugs with currently controlled substances via their effective permeability values. This combined with direct infusion electrospray ionization-mass spectrometry creates a rapid technique for characterization of new designer drugs. PAMPA has successfully determined the effective permeabilities of cocaine, methamphetamine, heroin, MDMA, and several tryptamine derivatives.

Imidazolium salts with varying anions as charge carriers for detection of neutral bis(triphenylphosphine)palladium(II) dichloride in electrospray ionization mass spectrometry.

RATIONALE: While electrospray ionization is a popular technique for mass analysis, without a charged species it is ineffective. This coupled with solvent restrictions hinders the analysis of organometallic complexes. Detecting neutral species whose solubility is limited to nonconventional solvents is a problem that can be overcome with the right charge carrier, which is described in this study. METHODS: Ionic liquids were synthesized and analyzed by electrospray ionization quadrupole ion trap mass spectrometry. The neutral palladium complex was also analyzed using different imidazolium salts as the charge carrier with the same method and instrumentation. Theoretical complements were also performed using Gaussian 09 at the density functional theory levels, using B3LYP functionals and the 6-31 g (d,p) basis set for geometry optimizations. RESULTS: Low concentration imidazolium salts in methanol showed aggregation behavior of the ionic liquid, where the cation peak and [cation](n+1)[anion]n peaks were observed in positive mode, while the [cation]n[anion](n+1) peaks were seen in negative mode. The unbound anion was observed in all the negative mode spectra except for the salt with the SCN anion when in THF. Solutions of PdCl2(PPh3)2 and a small amount of ionic liquid in THF showed the palladium complex adducted with the imidazolium cation for each of the ionic liquids studied. CONCLUSIONS: A charge carrier for a neutral organometallic complex was found in imidazolium salts, where the cation was observed as the ionizing agent. Differing ion intensities of the complex-adduct peak resulted from the anions ability to dissociate from the cation.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy Sensitivity to the Thermal Decay of Bone Collagen.

The analysis of collagen stability is of interest in forensics, archaeology, and molecular paleontology. Collagen decay rates are often measured by thermal kinetic studies that employ liquid chromatography mass spectrometry (LC-MS) to assay collagen quantities. However, these kinetic studies generally focus on measuring the decreasing levels of collagen instead of an exact molecular concentration of each sample. Thus, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can offer a simpler and less expensive alternative to LC-MS. The application of a new protocol to determine decreasing amounts of bone collagen in artificially decayed porcine and bovine bone was assessed. The protocol uses a forensic application of ATR FT-IR spectroscopy on size-restricted bone powder from three uniformly high temperature conditions. Also, for the first time, collagen-specific second-harmonic generation (SHG) imaging was also applied to artificially aged bone to add an independent, qualitative perspective to parallel FT-IR assessments. SHG images and ATR FT-IR spectra together reveal the same orderly bone collagen decay as found in previous thermal kinetic studies. Resulting Arrhenius plots with r2 values > 0.95 suggest that the ATR FT-IR-based protocol has potential as a precise and simple tool for measuring bone collagen decay rates. The results are significant for applications of thermal kinetic studies, and our protocol can serve as an inexpensive, precise, and pragmatic means of evaluating bone collagen stability within an array of conditions.

Visualization of lipid droplet composition by direct organelle mass spectrometry.

An expanding appreciation for the varied functions of neutral lipids in cellular organisms relies on a more detailed understanding of the mechanisms of lipid production and packaging into cytosolic lipid droplets (LDs). Conventional lipid profiling procedures involve the analysis of tissue extracts and consequently lack cellular or subcellular resolution. Here, we report an approach that combines the visualization of individual LDs, microphase extraction of lipid components from droplets, and the direct identification of lipid composition by nanospray mass spectrometry, even to the level of a single LD. The triacylglycerol (TAG) composition of LDs from several plant sources (mature cotton (Gossypium hirsutum) embryos, roots of cotton seedlings, and Arabidopsis thaliana seeds and leaves) were examined by direct organelle mass spectrometry and revealed the heterogeneity of LDs derived from different plant tissue sources. The analysis of individual LDs makes possible organellar resolution of molecular compositions and will facilitate new studies of LD biogenesis and functions, especially in combination with analysis of morphological and metabolic mutants. Furthermore, direct organelle mass spectrometry could be applied to the molecular analysis of other subcellular compartments and macromolecules.

The removal of single layers from multi-layer graphene by low-energy electron stimulation.

The removal of single atomic layers from multi-layer graphene using a He plasma is reported. By applying sample biases of -60 and +60 V during He plasma exposure, layer removal is found to be due to electrons instead of He ions or neutrals in the plasma. The rate of layer removal depends on exposure time, sample bias, and pre-annealing treatments. Optical contrast microscopy and atomic force microscopy studies show that the removal of C atoms occurs approximately one layer at a time across the entire multi-layer sample with no observable production of large pits or reduction in lateral dimensions. Layer removal is proposed to arise from the electron-stimulated dissociation of C atoms from the basal plane. This process differs from plasma techniques that use reactive species to etch multi-layer graphene.

On-stage liquid-phase lipid microextraction coupled to nanospray mass spectrometry for detailed, nano-scale lipid analysis.

RATIONALE: Developments in instrumentation aimed at microscopic sampling have led to an emphasis on applications analyzing small volumes and molecular concentrations within biological, chemical, and industrial samples. Simultaneous improvements in the sensitivity and versatility of nanospray mass spectrometers have made it possible to directly couple these sampling and analysis processes. METHODS: We developed a versatile liquid-phase lipid microextraction (LPME) technique for nanoliter to microliter volumes that is amenable to direct nanospray mass spectrometry (NMS). Lipophilic analytes within several types of biological samples were extracted and analyzed by partitioning and concentrating the analytes based on their solubility within two immiscible or partially miscible liquid phases. RESULTS: The utility of LPME-NMS is demonstrated by extracting and analyzing molecules in four different types of applications: (1) visualization of an extracted neutral lipid-specific fluorescent dye from an aqueous solvent; (2) identification of controlled acid-catalyzed hydrolysis of triacylglycerols within nanospray capillaries; (3) reproducible sampling of a fatty acid emulsion; and (4) profiling of diverse lipids in a complex biological matrix of rabbit serum. CONCLUSIONS: The modified instrumentation of a multi-port, on-stage bioworkstation shows considerable versatility by combining nanomanipulation, microextraction and direct NMS for a variety of chemical, biological, industrial, and clinical applications.