A New Oxygen Containing Pyclen-Type Ligand as a Manganese(II) Binder for MRI and 52Mn PET Applications: Equilibrium, Kinetic, Relaxometric, Structural and Radiochemical Studies

A new pyclen-3,9-diacetate derivative ligand (H23,9-OPC2A) was synthesized possessing an etheric O-atom opposite to the pyridine ring, to improve the dissociation kinetics of its Mn(II) complex (pyclen = 3,6,9,15-tetraazabicyclo(9.3.1)pentadeca-1(15),11,13-triene). The new ligand is less basic than the N-containing analogue (H23,9-PC2A) due to the non-protonable O-atom. In spite of its lower basicity, the conditional stability of the [Mn(3,9-OPC2A)] (pMn = −log(Mn(II)), cL = cMn(II) = 0.01 mM. pH = 7.4) remains unaffected (pMn = 8.69), compared to the [Mn(3,9-PC2A)] (pMn = 8.64). The [Mn(3,9-OPC2A)] possesses one water molecule, having a lower exchange rate with bulk solvents (kex298 = 5.3 ± 0.4 ´ 107 s−1) than [Mn(3,9-PC2A)] (kex298 = 1.26´108 s−1). These mild differences are rationalized by density-functional theory (DFT) calculations. The acid assisted dissociation of [Mn(3,9-OPC2A)] is considerably slower (k1 = 2.81 ± 0.07 M−1 s−1) than that of the complexes of diacetates or bisamides of various 12-membered macrocycles and the parent H23,9-PC2A. The [Mn(3,9-OPC2A)] is inert in rat/human serum as confirmed by 52Mn labeling (nM range), as well as by relaxometry (mM range). However, a 600-fold excess of EDTA (pH = 7.4) or a mixture of essential metal ions, propagated some transchelation/transmetalation in 7 days. The H23,9-OPC2A is labeled efficiently with 52Mn at elevated temperatures, yet at 37 °C the parent H23,9-PC2A performs slightly better. Ultimately, the H23,9-OPC2A shows advantageous features for further ligand designs for bifunctional chelators.

Effect of Solvent Conditions in Process of Extraction of Pectin from Banana Peels for the Adsorption of Fe Metal in Groundwater at UPN Veteran Yogyakarta

Iron (Fe) is one of the compounds contained in heavy metals which is very dangerous for the survival of living things when in the environment around the residence that has exceeded the threshold. Fe ions can cause turbidity, corrosion, and other impacts. Iron (Fe) is a transition metal and has the atomic number 26. The oxidation numbers of Fe are +3 and +2. Fe is an essential metal for the body which in high doses is toxic. Given the various dangers caused by exposure to Fe metal, it is necessary to treat Fe metal contained in groundwater. One of the most widely used heavy metal processing methods is the adsorption process. In previous studies, many adsorption processes used activated carbon from various materials as adsorbents. In this study, pectin was extracted from banana peels with hydrochloric acid as a solvent at various temperatures and concentrations. The optimum conditions were at 80oC and a concentration of 0.35 N. The pectin obtained was 2.3171 grams.

An Appraisal of the Field of Metallomics and the Roles of Metal Ions in Biochemistry and Cell Signaling

Humans require about 20 chemical elements. Half of them are essential metal ions. Many additional, non-essential metal ions are present in our bodies through environmental exposures, including in our diet, with functional consequences. Their accumulation is accelerated due to the increasing pollution of soil, air, water and manufacturing processes that employ chemical elements to which we have not been exposed in our evolutionary history. Yet other metal ions are essential for other forms of life, which calls on life scientists to consider the interactions of life processes with most of the chemical elements in the periodic table. Only in this century have attempts been made to integrate specialty disciplines into a science of bioelements called metallomics. Metallomics forms a fifth group when added to the traditional four building blocks of living cells and their areas of investigations, i.e., sugars (glycomics), fats (lipidomics), proteins (proteomics) and nucleic acids (genomics). Neither an understanding of all the essential metals and their interactions nor the functional impacts of the non-essential metals for life, except established toxic elements such as lead, are widely perceived as important in the basic science communities and in the applied sciences such as medicine and engineering. It is a remarkable oversight that this article attempts to address with representative examples.

Role of excretion in manganese homeostasis and neurotoxicity: A historical perspective

The essential metal manganese (Mn) induces incurable neurotoxicity at elevated levels that manifests as parkinsonism in adults and fine motor and executive function deficits in children. Studies on Mn neurotoxicity have largely focused on the role and mechanisms of disease induced by elevated Mn exposure from occupational or environmental sources. In contrast, the critical role of excretion in regulating Mn homeostasis and neurotoxicity has received less attention although (1) studies on Mn excretion date back to 1920s; (2) elegant radiotracer Mn excretion assays in the 1940s-60s established the routes of Mn excretion; and; (3) studies in patients with liver cirrhosis in the 1990s-2000s identified an association between decreased Mn excretion and the risk of developing Mn-induced parkinsonism in the absence of elevated Mn exposure. Notably, the last few years have seen renewed interest in Mn excretion largely driven by the discovery that hereditary Mn neurotoxicity due to mutations in SLC30A10 or SLC39A14 are caused, at least in part, by deficits in Mn excretion. Quite remarkably, some of the recent results on SLC30A10 and SLC39A14 provide explanations for observations made ~40-50 years ago. The goal of the current review is to integrate the historic studies on Mn excretion with more contemporary recent work, and provide a comprehensive state-of-the-art overview of Mn excretion and its role in regulating Mn homeostasis and neurotoxicity. A related goal is to discuss the significance of some of the foundational studies on Mn excretion so that these highly consequential earlier studies remain influential in the field.

Gestational Cd Exposure in the CD-1 Mouse Sex-Specifically Disrupts Essential Metal Ion Homeostasis

In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific hepatic insulin resistance, metabolic disruption, and obesity. To evaluate whether sex differences in cadmium uptake and changes in essential metal concentrations contribute to metabolic outcomes, placental and liver cadmium and essential metal concentrations were quantified in male and female offspring perinatally exposed to 500 ppb CdCl2. Exposure resulted in increased maternal liver Cd+2 concentrations (364 microgram/kg) similar to concentrations found in non-occupationally exposed human liver. At gestational day (GD) 18, placental cadmium and manganese concentrations were significantly increased in exposed males and females, and zinc was significantly decreased in females. Placental efficiency was significantly decreased in GD18 exposed males. Increases in hepatic Cd concentrations and a transient prenatal increase in zinc were observed in exposed female liver. Fetal and adult liver iron concentrations were decreased in both sexes, and decreases in hepatic zinc, iron, and manganese were observed in exposed females. Analysis of GD18 placental and liver metallothionein mRNA expression revealed significant Cd-induced upregulation of placental metallothionein in both sexes, and a significant decrease in fetal hepatic metallothionein in exposed females. In placenta, expression of metal ion transporters responsible for metal ion uptake was increased in exposed females. In liver of exposed adult female offspring, expression of the divalent cation importer (Slc39a14/Zip14) decreased, whereas expression of the primary exporter (Slc30a10) increased. These findings demonstrate that Cd can preferentially cross the female placenta, accumulate in the liver, and cause lifelong dysregulation of metal ion concentrations associated with metabolic disruption.

Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy

An increasing number of pathologies correlates with both toxic and essential metal ions dyshomeostasis. Next to known genetic disorders (e.g., Wilson’s Disease and β-Thalassemia) other pathological states such as neurodegeneration and diabetes are characterized by an imbalance of essential metal ions. Metal ions can enter the human body from the surrounding environment in the form of free metal ions or metal-nanoparticles, and successively translocate to different tissues, where they are accumulated and develop distinct pathologies. There are no characteristic symptoms of metal intoxication, and the exact diagnosis is still difficult. In this review, we present metal-related pathologies with the most common onsets, biomarkers of metal intoxication, and proper techniques of metal qualitative and quantitative analysis. We discuss the possible role of drugs with metal-chelating ability in metal dyshomeostasis, and present recent advances in therapies of metal-related diseases.

The Effects of Essential and Non-Essential Metal Toxicity in the Drosophila melanogaster Insect Model: A Review

The biological effects of environmental metal contamination are important issues in an industrialized, resource-dependent world. Different metals have different roles in biology and can be classified as essential if they are required by a living organism (e.g., as cofactors), or as non-essential metals if they are not. While essential metal ions have been well studied in many eukaryotic species, less is known about the effects of non-essential metals, even though essential and non-essential metals are often chemically similar and can bind to the same biological ligands. Insects are often exposed to a variety of contaminated environments and associated essential and non-essential metal toxicity, but many questions regarding their response to toxicity remain unanswered. Drosophila melanogaster is an excellent insect model species in which to study the effects of toxic metal due to the extensive experimental and genetic resources available for this species. Here, we review the current understanding of the impact of a suite of essential and non-essential metals (Cu, Fe, Zn, Hg, Pb, Cd, and Ni) on the D. melanogaster metal response system, highlighting the knowledge gaps between essential and non-essential metals in D. melanogaster. This review emphasizes the need to use multiple metals, multiple genetic backgrounds, and both sexes in future studies to help guide future research towards better understanding the effects of metal contamination in general.