Fe(II), Mn(II), and Zn(II) Binding to the C-Terminal Region of FeoB Protein: An Insight into the Coordination Chemistry and Specificity of the Escherichia coli Fe(II) Transporter.

The interactions between two peptide ligands [Ac763CCAASTTGDCH773 (P1) and Ac743RRARSRVDIELLATRKSVSSCCAASTTGDCH773 (P2)] derived from the cytoplasmic C-terminal region of Eschericha coli FeoB protein and Fe(II), Mn(II), and Zn(II) ions were investigated. The Feo system is regarded as the most important bacterial Fe(II) acquisition system, being one of the key virulence factors, especially in anaerobic conditions. Located in the inner membrane of Gram-negative bacteria, FeoB protein transports Fe(II) from the periplasm to the cytoplasm. Despite its crucial role in bacterial pathogenicity, the mechanism in which the metal ion is trafficked through the membrane is not yet elucidated. In the gammaproteobacteria class, the cytoplasmic C-terminal part of FeoB contains conserved cysteine, histidine, and glutamic and aspartic acid residues, which could play a vital role in Fe(II) binding in the cytoplasm, receiving the metal ion from the transmembrane helices. In this work, we characterized the complexes formed between the whole cytosolic C-terminal sequence of E. coli FeoB (P2) and its key polycysteine region (P1) with Fe(II), Mn(II), and Zn(II) ions, exploring the specificity of the C-terminal region of FeoB. With the help of a variety of potentiometric, spectroscopic (electron paramagnetic resonance and NMR), and spectrometric (electrospray ionization mass spectrometry) techniques and molecular dynamics, we propose the metal-binding modes of the ligands, compare their affinities toward the metal ions, and discuss the possible physiological role of the C-terminal region of E. coli FeoB.

A family of kojic acid derivatives aimed to remediation of Pb2+ and Cd2.

The present work analyzes the complex formation ability towards Pb2+ and Cd2+ of a series of kojic acid derivatives that join the chelating properties of the pyrone molecules and those of polyamines, with the aim of evaluating how the different effects of oxygen and nitrogen coordinating groups act on the stability of metal complexes. Experimental research is carried out using potentiometric and spectrophotometric techniques supported by 1H and 13C NMR spectroscopy and DFT calculations. Actually, a different coordination mechanism toward Pb2+ and Cd2+ was proved: in the case of Pb2+, coordination takes place exclusively via the oxygen atoms, while the contribute of the nitrogen atoms appears relevant in the case of Cd2+. Lead complexes of all the studied ligands are characterized by significantly stronger stability than those of cadmium. Finally, on the basis of the measured complex formation stabilities, some of the proposed molecules seems promising effective ligands for lead and cadmium ion decorporation from polluted soils or waste waters.

Zn2+ and Cu2+ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein.

The spike protein (S) of SARS-CoV-2 is able to bind to the human angiotensin-converting enzyme 2 (ACE2) receptor with a much higher affinity compared to other coronaviruses. The binding interface between the ACE2 receptor and the spike protein plays a critical role in the entry mechanism of the SARS-CoV-2 virus. There are specific amino acids involved in the interaction between the S protein and the ACE2 receptor. This specificity is critical for the virus to establish a systemic infection and cause COVID-19 disease. In the ACE2 receptor, the largest number of amino acids playing a crucial role in the mechanism of interaction and recognition with the S protein is located in the C-terminal part, which represents the main binding region between ACE2 and S. This fragment is abundant in coordination residues such as aspartates, glutamates, and histidine that could be targeted by metal ions. Zn2+ ions bind to the ACE2 receptor in its catalytic site and modulate its activity, but it could also contribute to the structural stability of the entire protein. The ability of the human ACE2 receptor to coordinate metal ions, such as Zn2+, in the same region where it binds to the S protein could have a crucial impact on the mechanism of recognition and interaction of ACE2-S, with consequences on their binding affinity that deserve to be investigated. To test this possibility, this study aims to characterize the coordination ability of Zn2+, and also Cu2+ for comparison, with selected peptide models of the ACE2 binding interface using spectroscopic and potentiometric techniques.

Biological Effects of Human Exposure to Environmental Cadmium.

Cadmium (Cd) is a toxic metal for the human organism and for all ecosystems. Cd is naturally found at low levels; however, higher amounts of Cd in the environment result from human activities as it spreads into the air and water in the form of micropollutants as a consequence of industrial processes, pollution, waste incineration, and electronic waste recycling. The human body has a limited ability to respond to Cd exposure since the metal does not undergo metabolic degradation into less toxic species and is only poorly excreted. The extremely long biological half-life of Cd essentially makes it a cumulative toxin; chronic exposure causes harmful effects from the metal stored in the organs. The present paper considers exposure and potential health concerns due to environmental cadmium. Exposure to Cd compounds is primarily associated with an elevated risk of lung, kidney, prostate, and pancreatic cancer. Cd has also been linked to cancers of the breast, urinary system, and bladder. The multiple mechanisms of Cd-induced carcinogenesis include oxidative stress with the inhibition of antioxidant enzymes, the promotion of lipid peroxidation, and interference with DNA repair systems. Cd2+ can also replace essential metal ions, including redox-active ones. A total of 12 cancer types associated with specific genes coding for the Cd-metalloproteome were identified in this work. In addition, we summarize the proper treatments of Cd poisoning, based on the use of selected Cd detoxifying agents and chelators, and the potential for preventive approaches to counteract its chronic exposure.

An updated overview on metal nanoparticles toxicity.

Although thousands of different nanoparticles (NPs) have been identified and synthesized to date, well-defined, consistent guidelines to control their exposure and evaluate their potential toxicity have yet to be fully established. As potential applications of nanotechnology in numerous fields multiply, there is an increased awareness of the issue of nanomaterials' toxicity among scientists and producers managing them. An updated inventory of customer products containing NPs estimates that they currently number over 5.000; ten years ago, they were one fifth of this. More often than not, products bear no information regarding the presence of NPs in the indicated list of ingredients or components. Consumers are therefore largely unaware of the extent to which nanomaterials have entered our lives, let alone their potential risks. Moreover, the lack of certainties with regard to the safe use of NPs is curbing their applications in the biomedical field, especially in the diagnosis and treatment of cancer, where they are performing outstandingly but are not yet being exploited as much as they could. The production of radical oxygen species is a predominant mechanism leading to metal NPs-driven carcinogenesis. The release of particularly reactive metal ions capable of crossing cell membranes has also been implicated in NPs toxicity. In this review we discuss the origin, behavior and biological toxicity of different metal NPs with the aim of rationalizing related health hazards and calling attention to toxicological concerns involved in their increasingly widespread use.

Environmental barium: potential exposure and health-hazards.

The relatively widespread presence of environmental barium is raising a growing public awareness as it can lead to different health conditions. Its presence in humans may produce several effects, especially among those chronically exposed from low to moderate doses. Barium accumulation can mainly occur by exposure in the workplace or from drinking contaminated water. However, this element is also assumed with the diet, mainly from plant foods. The average amount of barium intake worldwide and its geographical variation is little known due to the lack of research attention. Barium was never considered as an essential nutrient for humans, although it is undoubtedly naturally abundant enough and distinctive in its chemical properties that it might well have some biochemical function, e.g., for regulatory purposes, both in animals and plants. The information on the potential health effects of barium exposure is primarily based on animal studies and reported as comprising kidney diseases, neurological, cardiovascular, mental, and metabolic disorders. The present paper considers exposure and potential health concerns on environmental barium, giving evidence to information that can be used in future epidemiological and experimental studies.

Rh(I) Complexes in Catalysis: A Five-Year Trend.

Rhodium is one of the most used metals in catalysis both in laboratory reactions and industrial processes. Despite the extensive exploration on "classical" ligands carried out during the past decades in the field of rhodium-catalyzed reactions, such as phosphines, and other common types of ligands including N-heterocyclic carbenes, ferrocenes, cyclopentadienyl anion and pentamethylcyclopentadienyl derivatives, etc., there is still lively research activity on this topic, with considerable efforts being made toward the synthesis of new preformed rhodium catalysts that can be both efficient and selective. Although the "golden age" of homogeneous catalysis might seem over, there is still plenty of room for improvement, especially from the point of view of a more sustainable chemistry. In this review, temporally restricted to the analysis of literature during the past five years (2015-2020), the latest findings and trends in the synthesis and applications of Rh(I) complexes to catalysis will be presented. From the analysis of the most recent literature, it seems clear that rhodium-catalyzed processes still represent a stimulating challenge for the metalloorganic chemist that is far from being over.

Metal Toxicity and Speciation: A Review.

BACKGROUND: Essential metal ions play a specific and fundamental role in human metabolism. Their homeostasis is finely tuned, and any concentration imbalance in the form of deficiency or excess could lead to a progressive reduction and failure of normal biological function, to severe physiological and clinical outcomes, may eventually causing death. Conversely, non-essential metals are not necessary for life, and only noxious effects could arise after their exposure. Large environmental amounts of such chemicals come from both natural and anthropogenic sources, with the latter being predominant because of human activities. The dissipation of toxic metals contaminates water, air, soil, and food, causing a series of chronic and acute syndromes. OBJECTIVE: This review discusses the toxicity of non-essential metals considering their peculiar chemical characteristics, such as different forms, hard-soft character, oxidation states, binding capabilities, and solubility, which can influence their speciation in biological systems, and subsequently, the main cellular targets. Particular focus is given to selected toxic metals, major non-essential metals, or semimetals related to toxicity, such as mercury, lead, cadmium, chromium, nickel, and arsenic. In addition, we provide indications on the possible treatments/interventions for metal poisoning based on chelation therapy. CONCLUSION: Toxic metal ions can exert their peculiar harmful effects in several ways. They strongly coordinate with important biological molecules on the basis of their chemical- physical characteristics (mainly HSAB properties) or replace essential metal ions from their natural locations in proteins, enzymes, or hard structures, such as bones or teeth. Metals with redox properties could be key inducers of reactive oxygen species, leading to oxidative stress and cellular damage. Therapeutic detoxification, through complexation of toxic metal ions by specific chelating agents, appears an efficacious clinical strategy, mainly in acute cases of metal intoxication.

Ni(II) interaction with a peptide model of the human TLR4 ectodomain.

Ni(II) stimulates innate immunity via the direct binding to human Toll Like Receptor 4 (hTLR4), the bacterial lypopolysaccharide receptor. The binding is specific for humans and causes nickel contact allergy. The protein sequence analysis of hTLR4 revealed that the ectodomain, the region supposed to coordinate the metal ions, contains a histidine-rich motif that is not conserved among all organisms. To elucidate the role of each histidine residue on the protein-nickel binding, we examined the formation of Ni(II) complexes with the model peptide NH2-FQHSNRKQMSERSVFRSRRNRIYRDISHTHTR-COO-, which encompasses the sequence 429-460 of hTLR4. The amino acid sequence of the peptide has been modified by the substitution of some selected lipophilic residues (Leu and Phe) with hydrophilic residues (Arg), aiming at increasing the peptide hydro solubility of the protein fragment. Potentiometric, ultraviolet-visible (UV-vis), nuclear magnetic resonance (NMR) and circular dichroism (CD) measurements demonstrate that the non-conserved histidines in the ectodomain cooperate in metal coordination and consequently enable the activation of the molecular mechanism of nickel hypersensitivity reaction.