Current trends and challenges in the analysis of marine environmental contaminants by isotope ratio mass spectrometry.

An increasing number of organic and inorganic pollutants are being detected in the marine environment, posing a severe threat to the ecosystem and human health, even in trace concentrations. Isotope ratio mass spectrometry (IRMS) is one of the critical methods for determining the origin and fate of environmental pollutants and characterising their transformation processes. It has been used for a relatively long time for ecological monitoring of some well-studied industrial hydrocarbons at contaminated sites. However, the method still faces many analytical challenges. This review provides a comprehensive overview of recent technical advances concerning IRMS analysis of various contaminants and discusses typical pitfalls encountered in marine environment analysis. Particular attention is given to the study of sampling techniques and sample preparation for examination, often the keys to successful research given the complexity of marine matrices and the diverse and numerous nature of contaminants. Prospects for developing IRMS to monitor pollution sources and pollutant transformation in the marine environment are outlined.

Mass Spectrometry Insight for Assessing the Destiny of Plastics in Seawater.

Plastic pollution has become an increasingly serious environmental issue that requires using reliable analytical tools to unravel the transformations of primary plastics exposed to the marine environment. Here, we evaluated the performance of the isotope ratio mass spectrometry (IRMS) technique for identifying the origin of polymer material contaminating seawater and monitoring the compositional alterations due to its chemical degradation. Of twenty-six plastic specimens available as consumer products or collected from the Mediterranean Sea, five plastics were shown to originate from biobased polymeric materials. Natural abundance carbon and hydrogen isotope measurements revealed that biopolymers incline to substantial chemical transformation upon a prolonged exposure to seawater and sunlight irradiation. To assess the seawater-mediated aging that leads to the release of micro/nano fragments from plastic products, we propose to use microfiltration. Using this non-destructive separation technique as a front end to IRMS, the fragmentation of plastics (at the level of up to 0.5% of the total mass for plant-derived polymers) was recorded after a 3-month exposure and the rate and extent of disintegration were found to be substantially different for the different classes of polymers. Another potential impact of plastics on the environment is that toxic metals are adsorbed on their surface from the seashore water. We addressed this issue by using inductively coupled mass spectrometry after nitric acid leaching and found that several metals occur in the range of 0.1-90 µg per g on naturally aged plastics and accumulate at even higher levels (up to 10 mg g-1) on pristine plastics laboratory-aged in contaminated seawater. This study measured the degradation degree of different polymer types in seawater, filling in the gaps in our knowledge about plastic pollution and providing a useful methodology and important reference data for future research.

Analysis of Engineered Nanoparticles in Seawater Using ICP-MS-Based Technology: From Negative to Positive Samples.

A growing global emission of engineered nanoparticles (ENPs) into the aquatic environment has become an emerging safety concern that requires methods capable of identifying the occurrence and possibly determining the amounts of ENPs. In this study, we employed sector-field inductively coupled mass spectrometry to assess the presence of ENPs in coastal seawater samples collected from the Black Sea in regions suffering different anthropogenic impacts. Ultrafiltration through commercial 3 kDa membrane filters was shown to be feasible to separate the ENPs from the bulk seawater, and the subsequent ultrasound-mediated acidic dissolution makes the metals constituting the ENPs amenable to analysis. This procedure allowed the ENPs bearing Cu, Zn, V, Mo, and Sn to be for the first time quantitated in seashore surface water, their concentration ranging from 0.1 to 1.0 µg L-1 (as metal) and related to the presence of industry and/or urban stress. While these levels are decreased by natural dilution and possible sedimentation, the monitored ENPs remain measurable at a distance of 2 km from the coast. This can be attributed not only to local emission sources but also to some natural backgrounds.

Seawater analysis of engineered nanoparticles using ICP-MS-based technology: Addressing challenges with the development of reliable monitoring strategy.

With an increasing production and use of engineered nanoparticles (ENPs), inevitably grows their release into the environment. This makes it important to determine in what quantitates they occur in aquatic systems like seawater. However, even when using the most sensitive ICP-MS technique, quantification of very low seawater concentrations of ENPs is still concept rather than the fact. To approach this goal, a unified protocol for the preparation of seawater samples for ICP-MS analysis has been developed in this study using a selection of silver, titanium dioxide and zinc oxide nanoparticles. In order to minimize the risk of particle loss, the effect of sample pH was examined and it was found out that a moderate in-field acidification (to pH 7.5) ensures particle stability prior to analysis. Ultrafiltration through commercial 3 kDa membrane filters was shown feasible to separate the ENPs from the bulk seawater sample provided that the filter unit is pre-conditioned with 0.1 M copper nitrate to avoid ionic metal adsorption. The following ultrasound-mediated dissolution in 30% HNO3 directly in the filer unit and ultrafiltration makes the metals constituting the ENPs amenable to analysis. The latter was for the first time performed using high-resolution ICP-MS method validated according to the common EU standards. The limits of detection attained here were as low as 0.06, 0.09, and 17.5 µg L-1 for Ag, TiO2, and ZnO nanoparticles, respectively. Accuracy of the method was tested with uncontaminated open-sea water spiked with ENPs and recoveries were acceptable ranging from 85 to 110%.

Marine sediment analysis - A review of advanced approaches and practices focused on contaminants.

This review is aimed at critical analysis of current and emerging capabilities of analytical methods as employed for marine sediment analysis. An emphasis is given to the most reliable experimental strategies used to quantifying the various classes of contaminants and thus to acquiring analytical information that is relevant to assess the quality of sediments with regard to possible pollution of marine ecosystems. Advanced analytical methodology in use basically relies on the application of mass spectrometry to enable identification and quantification of hazardous chemical species, directly or after separation using the principles of gas and liquid chromatography. Also addressed are sample preparation techniques which - given the complexity of sediment matrices and the diverse and multiple nature of contaminants - are often a key for successful analysis. Among the trends in marine sediment analysis is an inclination to chemicals that are only recently recognized as emerging pollutants of very high concern, such as microplastics, pharmaceuticals and their metabolites.

Magnetic nanoparticles for highly robust, facile and efficient loading of metal-based drugs.

Direct interaction between iron oxide nanoparticles (IONs), modified with polyethylene glycol and an ionic liquid, and activated cisplatin drug resulted in a fast and high drug loading (up to 0.17 mol of platinum per gram of iron), and the payload does not strongly affect the magnetic properties of IONs and resists protein adsorption in human serum environment. For another, developmental metal-based drug, tris(8-quinolinolato)gallium(III), binding to the IONs allowed for overcoming the disadvantages of low solubility and incompatibility with intravenous administration. The potential of IONs as a magnetic nanoformulation for smart drug delivery has been confirmed by the release of both metallodrugs under conditions relevant to cancer cytosol.

Metal-Specific Response of High-Resolution ICP-MS for Proteins Binding to Gold Nanoparticles in Human Serum.

Metalloproteins have many different functions such as storage and transport of proteins, enzymes, signal transduction proteins, etc. Herein, for a selection of gold nanoparticles differing in shape, size, charge, and surface modification, the binding behavior in human serum was assessed with respect to metal-containing proteins. Our results based on sector-field ICP-MS measurements and a simple calculation algorithm indicate the possible involvement of proteins, incorporating Cu and Fe, in the formation of the biomolecular layer around the particle surface. Given that such binding encompasses a substantial amount of copper and iron within the serum proteome (>50%) at a calculated nanoparticle dose, it may result in depleting their biological functions and should be taken into account when selecting lead candidates with an improved biocompatibility.

How Feasible is Direct Determination of Rare Earth Elements in Seawater by ICP-MS?

With the increasingly wide industrial use of rare earth elements (REEs), their release into marine systems makes it important to understand in what quantities they occur and to what geochemical processes they contribute, preferably using direct analytical methodology. In this study, analytical performance of high-resolution ICP-MS was assessed with regard to quantification of REEs in seawater without matrix separation and analyte preconcentration. With optimized sample dilution, precise and interference-free quantifications of most of the REEs in samples taken from Kara Sea were obtained, with an accuracy of 3 to 9% (against the independently asserted values), repeatability of 3 to 5%, and intermediate precision and reproducibility, averaging 4 and 11%, respectively. The method was further validated by using a certified reference material for nearshore seawater. However, the limits of detection obtained (0.04 - 0.38 ng L-1), while not significantly inferior to those obtained after sample enrichment, appear to be not low enough to analyze high salinity sea samples (over 30 parts per thousand) or open-ocean water samples, which require higher dilution factors or contain (much) lower REE concentrations, respectively. Therefore, it was concluded that the direct determination of REEs is only possible from samples with moderate salinity such as estuarine or shallow-sea water. In the latter case, the longitudinal REE profiling assayed by ICP-MS allowed us to assume that the export of the contaminated material from land areas into estuaries and then to the sea by rivers may substantially contribute to the seawater pool of REEs.

Toward a deeper and simpler understanding of serum protein-mediated transformations of magnetic nanoparticles by ICP-MS.

A great variety of magnetic nanomaterials are entering preclinical investigations with the objective to select the most promising candidates for diagnostic and therapeutic applications. For an analytical approach to be used as a high-throughput screening tool, simple and cost-efficient sample preparation protocol is a basiс prerequisite. Here, we demonstrate how the application of continuous magnetic field allows for quantitatively separating iron oxide magnetic nanoparticles from a mixture with human serum to facilitate monitoring of their biomolecular interactions with high-resolution inductively coupled plasma mass spectrometry. By measuring the signals of sulfur and metal isotopes, it is possible to monitor the formation of the protein corona and alterations in the concentrations of relevant metals due to binding of specific metalloproteins, respectively.

Current trends and challenges in analysis and characterization of engineered nanoparticles in seawater.

With the increasingly wide use of engineered nanoparticles (ENPs), their release into the environment makes it important to determine in what quantitates they occur in aquatic systems and to understand their fate therein. In particular, detection and quantification of ENPs in seawater is challenging and often requires analytical methods to perform close to the feasibility confines. This review is aimed at critical analysis of current and emerging capabilities of analytical methods as have been employed for the analysis and characterization of ENPs in seawater in the last decade. An emphasis is given to the most reliable experimental strategies focused on avoiding the high-salt matrix effect and isolation and enrichment of the nanoparticulate fraction prior to analysis. Advanced analytical methodology in use basically relies on the application of elemental mass spectrometry to determine various particle-core metals and its single-particle mode to characterize the seawater-mediated transformation of ENPs, including dissolution, aggregation, etc. On the other hand, common microscopy, light scattering or X-ray based techniques are not sensitive enough to acquire the transformation information from real seawater samples. Finally, attention is pinpointed upon an acute shortcoming of the current research which is in the overwhelming majority of cases restricted to samples spiked with ENPs and often at excessive concentration levels.

An ICP-MS-based assay for characterization of gold nanoparticles with potential biomedical use.

Most of potential diagnostic and therapeutic nanoparticles fail to reach clinical trials because assessment of their 'drug-like' properties is often overlooked during the discovery stage. This compromises the results of cell culture and animal experiments, making them insufficient to evaluate the lead candidates for testing on patients. In this study, we demonstrate the potential of high-resolution inductively coupled plasma mass spectrometry (ICP-MS) as a nanoparticle qualification tool. Using novel gold nanoparticles stabilized by N-heterocyclic carbenes as test nanoparticles, it was shown that important prerequisites for biomedical applications, such as resistance to the action of human serum milieu or reactivity toward serum biomolecules, can be reliably assessed by recording the signals of gold or sulfur isotopes. Implemented during the screening stage, the method would provide benefits in shortening timelines and reducing cost for selection and initial testing of medicinal nanoparticle candidates.

High-resolution ICP-MS approach for characterization of magnetic nanoparticles for biomedical applications.

The potential of iron oxide-based nanoparticles (IONs) as theranostic agents is believed to be in a great part due to non-invasive diagnosis and therapeutic applications. However, there is still a lack of well-recognized methodology to assess bioresistance, hypotoxicity, reactivity toward pertinent biomolecules, as well as an eventual dose of IONs as prerequisites for their clinical use. In this study, we demonstrate how application of high-resolution ICP-MS in combination with conventional ultrafiltration can address these important issues in a simple and high-throughput way. Based upon interference-free and sensitive measurements of iron and sulfur isotopes ensured by sector-field ICP-MS mode, the comparative testing of a series of novel IONs modified by PEG or PEG and an ionic liquid, was performed. Satisfactory stability (less than 1 % of soluble Fe), minor toxicity (by virtue of releasing a free iron) and transit into bioconjugates in human serum, different in speed, proved the prospective of the tested IONs for in-depth preclinical development.

How versatile is the use of ultrafiltration to study biointeractions of therapeutic metallodrugs?

For a representative number of approved or investigational anticancer metallodrugs varying in lipophilicity, unspecific adsorption onto ultracentrifugal filter units was studied. It was found that for fairly hydrophilic compounds, such as cisplatin and oxaliplatin, the binding to filters does not substantially affect their amount measured (by ICP-MS) after ultrafiltration (>95%). In the case of metal complexes with moderate lipophilicity (log P > -0.1), adsorption effects turn out to be substantial. This might impede using ultrafiltration for studying the transformations of such drugs in human serum, unless they are rapidly converted into the protein adducts. The adsorption-suppressing effect of proteins was proved for indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] whose recovery from the filters was 61 and 14% in free and HSA-bound form, respectively.

A simple assay for probing transformations of superparamagnetic iron oxide nanoparticles in human serum.

A novel approach for monitoring the biomolecular interactions of superparamagnetic nanoparticles was disclosed. Based on ultrafiltration of a human serum-nanoparticle mixture and the mass spectrometric analysis of filtrates, this assay revealed for iron oxide nanoparticles coated with poly(acrylic acid) satisfactory biopersistence and a bimodal binding to sulfur-containing biomolecules, with the formation of the protein corona completed in about 1 h.

RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation.

The RNA polymerase II (RNAPII) C-terminal domain (CTD) heptapeptide repeats (1-YSPTSPS-7) undergo dynamic phosphorylation and dephosphorylation during the transcription cycle to recruit factors that regulate transcription, RNA processing and chromatin modification. We show here that RPRD1A and RPRD1B form homodimers and heterodimers through their coiled-coil domains and interact preferentially via CTD-interaction domains (CIDs) with RNAPII CTD repeats phosphorylated at S2 and S7. Crystal structures of the RPRD1A, RPRD1B and RPRD2 CIDs, alone and in complex with RNAPII CTD phosphoisoforms, elucidate the molecular basis of CTD recognition. In an example of cross-talk between different CTD modifications, our data also indicate that RPRD1A and RPRD1B associate directly with RPAP2 phosphatase and, by interacting with CTD repeats where phospho-S2 and/or phospho-S7 bracket a phospho-S5 residue, serve as CTD scaffolds to coordinate the dephosphorylation of phospho-S5 by RPAP2.

Human snRNA genes use polyadenylation factors to promote efficient transcription termination.

RNA polymerase II transcribes both protein coding and non-coding RNA genes and, in yeast, different mechanisms terminate transcription of the two gene types. Transcription termination of mRNA genes is intricately coupled to cleavage and polyadenylation, whereas transcription of small nucleolar (sno)/small nuclear (sn)RNA genes is terminated by the RNA-binding proteins Nrd1, Nab3 and Sen1. The existence of an Nrd1-like pathway in humans has not yet been demonstrated. Using the U1 and U2 genes as models, we show that human snRNA genes are more similar to mRNA genes than yeast snRNA genes with respect to termination. The Integrator complex substitutes for the mRNA cleavage and polyadenylation specificity factor complex to promote cleavage and couple snRNA 3'-end processing with termination. Moreover, members of the associated with Pta1 (APT) and cleavage factor I/II complexes function as transcription terminators for human snRNA genes with little, if any, role in snRNA 3'-end processing. The gene-specific factor, proximal sequence element-binding transcription factor (PTF), helps clear the U1 and U2 genes of nucleosomes, which provides an easy passage for pol II, and the negative elongation factor facilitates termination at the end of the genes where nucleosome levels increase. Thus, human snRNA genes may use chromatin structure as an additional mechanism to promote efficient transcription termination in vivo.

A safe lithium mimetic for bipolar disorder.

Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, therapeutic target of lithium remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist. Here we report that the antioxidant ebselen inhibits inositol monophosphatase and induces lithium-like effects on mouse behaviour, which are reversed with inositol, consistent with a mechanism involving inhibition of inositol recycling. Ebselen is part of the National Institutes of Health Clinical Collection, a chemical library of bioavailable drugs considered clinically safe but without proven use. Therefore, ebselen represents a lithium mimetic with the potential both to validate inositol monophosphatase inhibition as a treatment for bipolar disorder and to serve as a treatment itself.

NQR parameters of complexes and polarizability effect.

The literature data on substituent influence on the nuclear quadrupole resonance frequencies (ν), quadrupole coupling constants (e(2) Qq ⋅ h(- 1) ), and asymmetry parameters (η) for 36 series of the H-complexes, charge-transfer complexes, transition metal complexes and other donor-acceptor complexes have been considered, using the correlation analysis. Generally the ν, e(2) Qq ⋅ h(- 1) , and η values were first established to depend on the inductive, resonance, polarizability, and steric effects of substituents. The presence or otherwise of certain effects as well as relation between their contributions are determined by the type of series. The polarizability effect owes its existence to the appearance of an excess charge on the indicator centre as a result of the complexation. The contribution of this effect ranges up to 75%.