Nano- and microplastics: a comprehensive review on their exposure routes, translocation, and fate in humans.

Contamination of the environment with nano-and microplastic particles (NMPs) and its putative adverse effects on organisms, ecosystems, and human health is gaining increasing scientific and public attention. Various studies show that NMPs occur abundantly within the environment, leading to a high likelihood of human exposure to NMPs. Here, different exposure scenarios can occur. The most notable exposure routes of NMPs into the human body are via the airways and gastrointestinal tract (GIT) through inhalation or ingestion, but also via the skin due to the use of personal care products (PCPs) containing NMPs. Once NMPs have entered the human body, it is possible that they are translocated from the exposed organ to other body compartments. In our review article, we combine the current knowledge on the (1) exposure routes of NMPs to humans with the basic understanding of the potential (2) translocation mechanisms into human tissues and, consequently, their (3) fate within the human body. Regarding the (1) exposure routes, we reviewed the current knowledge on the occurrence of NMPs in food, beverages, personal care products and the air (focusing on indoors and workplaces) and found that the studies suggest an abundant presence of MPs within the exposure scenarios. The overall abundance of MPs in exposure matrices relevant to humans highlights the importance of understanding whether NMPs have the potential for tissue translocation. Therefore, we describe the current knowledge on the potential (2) translocation pathways of NMPs from the skin, GIT and respiratory systems to other body compartments. Here, particular attention was paid to how likely NMPs can translocate from the primary exposed organs to secondary organs due to naturally occurring defence mechanisms against tissue translocation. Based on the current understanding, we conclude that a dermal translocation of NMPs is rather unlikely. In contrast, small MPs and NPs can generally translocate from the GIT and respiratory system to other tissues. Thus, we reviewed the existing literature on the (3) fate of NMPs within the human body. Based on the current knowledge of the contamination of human exposure routes and the potential translocation mechanisms, we critically discuss the size of the detected particles reported in the fate studies. In some cases, the particles detected in human tissue samples exceed the size of a particle to overcome biological barriers allowing particle translocation into tissues. Therefore, we emphasize the importance of critically reading and discussing the presented results of NMP in human tissue samples.

Chances and challenges of long-distance electron transfer for cellular redox reactions.

Biological redox reactions often use a set-up in which final redox partners are localized in different compartments and electron transfer (ET) among them is mediated by redox-active molecules. In enzymes, these ET processes occur over nm distances, whereas multi-protein filaments bridge µm ranges. Electrons are transported over cm ranges in cable bacteria, which are formed by thousands of cells. In this review, we describe molecular mechanisms that explain how respiration in a compartmentalized set-up ensures redox homeostasis. We highlight mechanistic studies on ET through metal-free peptides and proteins demonstrating that long-distance ET is possible because amino acids Tyr, Trp, Phe, and Met can act as relay stations. This cuts one long ET into several short reaction steps. The chances and challenges of long-distance ET for cellular redox reactions are then discussed.

Reduction Kinetic of Water Soluble Metal Salts by Geobacter sulfurreducens: Fe2+/Hemes Stabilize and Regulate Electron Flux Rates.

Geobacter sulfurreducens is a widely applied microorganism for the reduction of toxic metal salts, as an electron source for bioelectrochemical devices, and as a reagent for the synthesis of nanoparticles. In order to understand the influence of metal salts, and of electron transporting, multiheme c-cytochromes on the electron flux during respiration of G. sulfurreducens, the reduction kinetic of Fe3+, Co3+, V5+, Cr6+, and Mn7+ containing complexes were measured. Starting from the resting phase, each G. sulfurreducens cell produced an electron flux of 3.7 × 105 electrons per second during the respiration process. Reduction rates were within ± 30% the same for the 6 different metal salts, and reaction kinetics were of zero order. Decrease of c-cytochrome concentrations by downregulation and mutation demonstrated that c-cytochromes stabilized respiration rates by variation of their redox states. Increasing Fe2+/heme levels increased electron flux rates, and induced respiration flexibility. The kinetic effects parallel electrochemical results of G. sulfurreducens biofilms on electrodes, and might help to optimize bioelectrochemical devices.

Insect allies-Assessment of a viral approach to plant genome editing.

The Insect Allies program of the Defense Advanced Research Projects Agency has already sparked scientific debate concerning technology assessment-related issues, among which the most prevalent is that of dual use. Apart from the issues concerning peaceful applications, the technology also provides the blueprint for a potential bioweapon. However, the combination of a virus-induced genetic modification of crop plants in the field using genetically modified insect vectors poses a greater risk than the hitherto existing use of genetically modified organisms. The technology's great depth of intervention allows a number of sources for hazard and a tendency towards high exposure, but it is also encumbered with notable deficits in knowledge. These issues call for a thorough technology assessment. This article aims to provide an initial characterization from a technology assessment perspective, focusing on potential sources of risk for this novel invasive environmental biotechnology at an early stage of research and development. Integr Environ Assess Manag 2022;18:1488-1499. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

The viral era: New biotechnologies give humans an unprecedented control over Nature and require appropriate safeguards.

New biotechnologies such as gene drives and engineered viruses herald a viral era that would give humans exceptional power over any organism at the level of the genotype.

Rolf Huisgen (1920-2020).

Rolf Huisgen would have celebrated his 100th birthday this year. Three of his academic progeny look back on Huisgen as a person, teacher, and scientist. They underline his leading role in rebuilding the chemistry department in Munich after the Second World War and the enduring importance of the 1,3-dipolar cycloaddition (Huisgen reaction).

Kinetics and Mechanism of Mineral Respiration: How Iron Hemes Synchronize Electron Transfer Rates.

Anaerobic microorganisms of the Geobacter genus are effective electron sources for the synthesis of nanoparticles, for bioremediation of polluted water, and for the production of electricity in fuel cells. In multistep reactions, electrons are transferred via iron/heme cofactors of c-type cytochromes from the inner cell membrane to extracellular metal ions, which are bound to outer membrane cytochromes. We measured electron production and electron flux rates to 5×105  e s-1 per G. sulfurreducens. Remarkably, these rates are independent of the oxidants, and follow zero order kinetics. It turned out that the microorganisms regulate electron flux rates by increasing their Fe2+ /Fe3+ ratios in the multiheme cytochromes whenever the activity of the extracellular metal oxidants is diminished. By this mechanism the respiration remains constant even when oxidizing conditions are changing. This homeostasis is a vital condition for living systems, and makes G. sulfurreducens a versatile electron source.

Gene drives as a new quality in GMO releases-a comparative technology characterization.

Compared to previous releases of genetically modified organisms (GMOs) which were primarily plants, gene drives represent a paradigm shift in the handling of GMOs: Current regulation of the release of GMOs assumes that for specific periods of time a certain amount of GMOs will be released in a particular region. However, now a type of genetic technology arises whose innermost principle lies in exceeding these limits-the transformation or even eradication of wild populations. The invasive character of gene drives demands a thorough analysis of their functionalities, reliability and potential impact. But such investigations are hindered by the fact that an experimental field test would hardly be reversible. Therefore, an appropriate prospective assessment is of utmost importance for an estimation of the risk potential associated with the application of gene drives. This work is meant to support the inevitable characterization of gene drives by a comparative approach of prospective technology assessment with a focus on potential sources of risk. Therein, the hazard and exposure potential as well as uncertainties with regard to the performance of synthetic gene drives are addressed. Moreover, a quantitative analysis of their invasiveness should enable a differentiated evaluation of their power to transform wild populations.

Amide Neighbouring-Group Effects in Peptides: Phenylalanine as Relay Amino Acid in Long-Distance Electron Transfer.

In nature, proteins serve as media for long-distance electron transfer (ET) to carry out redox reactions in distant compartments. This ET occurs either by a single-step superexchange or through a multi-step charge hopping process, which uses side chains of amino acids as stepping stones. In this study we demonstrate that Phe can act as a relay amino acid for long-distance electron hole transfer through peptides. The considerably increased susceptibility of the aromatic ring to oxidation is caused by the lone pairs of neighbouring amide carbonyl groups, which stabilise the Phe radical cation. This neighbouring-amide-group effect helps improve understanding of the mechanism of extracellular electron transfer through conductive protein filaments (pili) of anaerobic bacteria during mineral respiration.

Risks, Release and Concentrations of Engineered Nanomaterial in the Environment.

For frequently used engineered nanomaterials (ENMs) CeO2-, SiO2-, and Ag, past, current, and future use and environmental release are investigated. Considering an extended period (1950 to 2050), we assess ENMs released through commercial activity as well as found in natural and technical settings. Temporal dynamics, including shifts in release due to ENM product application, stock (delayed use), and subsequent end-of-life product treatment were taken into account. We distinguish predicted concentrations originating in ENM use phase and those originating from end-of-life release. Furthermore, we compare Ag- and CeO2-ENM predictions with existing measurements. The correlations and limitations of the model, and the analytic validity of our approach are discussed in the context of massive use of assumptive model data and high uncertainty on the colloidal material captured by the measurements. Predictions for freshwater CeO2-ENMs range from 1 pg/l (2017) to a few hundred ng/l (2050). Relative to CeO2, the SiO2-ENMs estimates are approximately 1,000 times higher, and those for Ag-ENMs 10 times lower. For most environmental compartments, ENM pose relatively low risk; however, organisms residing near ENM 'point sources' (e.g., production plant outfalls and waste treatment plants), which are not considered in the present work, may be at increased risk.

5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology.

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclinical characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations. No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound's safety profile, identifies 1 as a clinical candidate with a broad application range in oncology, including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clinical trials for advanced solid tumors and refractory lymphoma.

Formation of Silver Nanoparticles by Electron Transfer in Peptides and c-Cytochromes.

The reduction of Ag+ ions to Ag0 atoms is a highly endergonic reaction step, only the aggregation to Agn clusters leads to an exergonic process. These elementary chemical reactions play a decisive role if Ag nanoparticles (AgNPs) are generated by electron transfer (ET) reactions to Ag+ ions. We studied the formation of AgNPs in peptides by photoinduced ET, and in c-cytochromes by ET from their Fe2+ /hemes. Our earlier photoinduced experiments in peptides had demonstrated that histidine prevents AgNP formation. We have now observed that AgNPs can be easily synthesized with less-efficient Ag+ -binding amino acids, and the rate increases in the order lysine

Surface-enhanced Raman spectroscopy (SERS) in food analytics: Detection of vitamins B2 and B12 in cereals.

Food analysis has been gaining interest throughout recent decades for different reasons: the detection of hazardous substances in food and routine investigations of food composition and vitamin/nutrient contents. Regardless of the targeted component, food analysis raises a few challenges regarding the complexity of the matrix and detecting trace amounts of substances. We report herein the results obtained regarding the simultaneous detection of two B vitamins (riboflavin, vitamin B2 and cyanocobalamin, vitamin B12) by means of SERS. SERS provides molecular fingerprint identification and high analytical sensitivity together with a low processing time and cost. All these make SERS a promising tool for the development of food analytical methods.

Electronic structure of hole-conducting states in polyprolines.

Electron transfer over long distances in proteins by a hopping process requires transient relay stations that can harbor charge and spin for a short time span. Certain easily oxidizable or reducible side chains may assume that role, but it has been shown that charge transport in peptides can also take place in the absence of such groups which implies that the peptide backbone provides for hopping stations. We have identified three different types of radical cation states in such peptides that are associated with significantly lower ionization potentials than those of the constituent amino acids, and which may thus serve as relay stations for hole transport. Which of these states is the most stable one depends on the nature and the conformation of the peptide. In contrast to α-helices which, due to their high dipole moments, can only form stable radical cation states that are localized on the C-terminal amino acids, polyprolines are capable of accommodating such states inside the PPII helices and those states may serve as relay stations for hole transfer through polyprolines. Of which type these states are depends often on small conformational changes, and sometimes the most stable states are hybrids of the three types we have identified.

Electron transfer in peptides: on the formation of silver nanoparticles.

Some microorganisms perform anaerobic mineral respiration by reducing metal ions to metal nanoparticles, using peptide aggregates as medium for electron transfer (ET). Such a reaction type is investigated here with model peptides and silver as the metal. Surprisingly, Ag(+) ions bound by peptides with histidine as the Ag(+)-binding amino acid and tyrosine as photoinducible electron donor cannot be reduced to Ag nanoparticles (AgNPs) under ET conditions because the peptide prevents the aggregation of Ag atoms to form AgNPs. Only in the presence of chloride ions, which generate AgCl microcrystals in the peptide matrix, does the synthesis of AgNPs occur. The reaction starts with the formation of 100 nm Ag@AgCl/peptide nanocomposites which are cleaved into 15 nm AgNPs. This defined transformation from large nanoparticles into small ones is in contrast to the usually observed Ostwald ripening processes and can be followed in detail by studying time-resolved UV/Vis spectra which exhibit an isosbestic point.

Fragment orbital based description of charge transfer in peptides including backbone orbitals.

Charge transfer in peptides and proteins can occur on different pathways, depending on the energetic landscape as well as the coupling between the involved orbitals. Since details of the mechanism and pathways are difficult to access experimentally, different modeling strategies have been successfully applied to study these processes in the past. These can be based on a simple empirical pathway model, efficient tight binding type atomic orbital Hamiltonians or ab initio and density functional calculations. An interesting strategy, which allows an efficient calculations of charge transfer parameters, is based on a fragmentation of the system into functional units. While this works well for systems like DNA, where the charge transfer pathway is naturally divided into distinct molecular fragments, this is less obvious for charge transfer along peptide and protein backbones. In this work, we develop and access a strategy for an effective fragmentation approach, which allows one to compute electronic couplings for large systems along nanosecond time scale molecular dynamics trajectories. The new methodology is applied to a solvated peptide, for which charge transfer properties have been studied recently using an empirical pathway model. As could be expected, dynamical effects turn out to be important, which emphasizes the importance of using effective quantum approaches which allow for sufficient sampling. However, the computed rates are orders of magnitude smaller than experimentally determined, which indicates the shortcomings of present modeling approaches.

Radicals in stereoselective synthesis and electron transfer reactions.

This short historical review describes the work of the Giese group on radicals and radical ions that has led to the award of the Paracelsus prize in 2012.

Kinetics of ion transport through supramolecular channels in single crystals.

Single-crystal to single-crystal transformations are possible by ion-exchange and transport reactions through supramolecular channels that are composed of crown ether molecules and use trihalide ions as scaffolds. Kinetic measurements of ion transport at different temperatures provide activation energy data and show that a very fast exchange of K(+) ions with Na(+) ions occurs.