During the current corona pandemic, new therapeutic options against this viral disease are urgently desired. Due to the rapid spread and immense number of affected individuals worldwide, ...cost-effective, globally available, and safe options with minimal side effects and simple application are extremely warranted. This review will therefore discuss the potential of zinc as preventive and therapeutic agent alone or in combination with other strategies, as zinc meets all the above described criteria. While a variety of data on the association of the individual zinc status with viral and respiratory tract infections are available, study evidence regarding COVID-19 is so far missing but can be assumed as was indicated by others and is detailed in this perspective, focusing on re-balancing of the immune response by zinc supplementation. Especially, the role of zinc in viral-induced vascular complications has barely been discussed, so far. Interestingly, most of the risk groups described for COVID-19 are at the same time groups that were associated with zinc deficiency. As zinc is essential to preserve natural tissue barriers such as the respiratory epithelium, preventing pathogen entry, for a balanced function of the immune system and the redox system, zinc deficiency can probably be added to the factors predisposing individuals to infection and detrimental progression of COVID-19. Finally, due to its direct antiviral properties, it can be assumed that zinc administration is beneficial for most of the population, especially those with suboptimal zinc status.
The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: Zn(II). Its coordination environment in ...proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the “mobile” zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide (ZnO). In most investigations, reference is made to zinc or Zn2+ without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn2+ differs from s-block cations such as Ca2+ with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is important in zinc biochemistry and for biological recognition as a variety of low molecular weight zinc complexes have already been implicated in biological processes, e.g. with ATP, glutathione, citrate, ethylenediaminedisuccinic acid, nicotianamine, or bacillithiol.
•Zinc ions not bound to proteins have critical roles in cell biology.•Zinc has a unique coordination chemistry, poorly appreciated in the biosciences.•Its coordination chemistry is significantly different from that of calcium ions.•Specific conditions apply for buffering cellular zinc ions.•Investigations with zinc need to consider solution chemistry and metal buffering.
The role of zinc and its compounds in leukemia Orlov, Alexey P.; Orlova, Marina A.; Trofimova, Tatiana P. ...
Journal of biological inorganic chemistry,
05/2018, Letnik:
23, Številka:
3
Journal Article
Recenzirano
Zinc is one of the most important microelements necessary for normal body functioning. Zinc is marked in numerous diseases and, hence, its properties and behavior in the body have long been a subject ...of extensive study. This review considers trends in the assessment of the role of zinc and its compounds in the past decade. It becomes evident that redox-inactive zinc is the main supervisor in the conformation of the most important molecules in all body organs and tissues. We placed emphasis on the variety of zinc-binding sites and the role of zinc in the genesis and progress of different forms of leukemia. The importance of some families of transcription factors in the development and prognosis of treatment of various leukemia forms is examined; new directions of these studies are shown.
Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we ...provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.
This methods paper details dietary approaches to alter zinc homeostasis in rodents and qualitative and quantitative methods to ensure the zinc status of experimental animals. The outlined accessible and cost-effective protocol will elevate scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of a multitude of health conditions and diseases.
In a pilot study to determine if zinc (Zn) from zinc oxide nanoparticles in sunscreen can penetrate human skin in vivo, nanoparticles (~30nm) of a stable isotope (52% 68Zn enrichment) were ...incorporated into an essentially phytochemical-based formulation and applied to the backs of 3 human subjects twice daily for 5days during the Southern Hemisphere winter. Blood and urine were collected prior to application and at regular intervals and up to 50days. As observed in a larger outdoor trial following this pilot study but with a different formulation and with UV exposure: values of 68Zn in blood continued to increase beyond the 5day application phase with the highest measurement at 14days after the first application; variable amounts of the 68Zn tracer were observed in urine; and the amounts of extra Zn added to blood were small and indicate very low levels of absorption (minimal estimate <0.01% of the applied dose) through the skin. Reasons for differences in absorption detected in the stable isotope trials and previous investigations include: the sensitivity of the stable isotope method; the duration of the investigations; the number of applications of sunscreen formulation; in vitro methods with excised skin; lack of measurement of blood and urine; no skin flexing; and lack of UV exposure.
► A pilot study to test feasibility of using stable Zn isotopes in sunscreens. ► Three volunteers tested over 5days with minimal UV exposure. ► Small amount of 68Zn from ZnO absorbed through skin. ► Results consistent with larger outdoor trial.
H2 evolution is the reason for poor reversibility and limited cycle stability with Zn‐metal anodes, and impedes practical application in aqueous zinc‐ion batteries (AZIBs). Here, using a combined gas ...chromatography experiment and computation, it is demonstrated that H2 evolution primarily originates from solvated water, rather than free water without interaction with Zn2+. Using linear sweep voltammetry (LSV) in salt electrolytes, H2 evolution is evidenced to occur at a more negative potential than zinc reduction because of the high overpotential against H2 evolution on Zn metal. The hypothesis is tested and, using a glycine additive to reduce solvated water, it is confirmed that H2 evolution and “parasitic” side reactions are suppressed on the Zn anode. This electrolyte additive is evidenced to suppress H2 evolution, reduce corrosion, and give a uniform Zn deposition in Zn|Zn and Zn|Cu cells. It is demonstrated that Zn|PANI (highly conductive polyaniline) full cells exhibit boosted electrochemical performance in 1 M ZnSO4–3 M glycine electrolyte. It is concluded that this new understanding of electrochemistry of H2 evolution can be used for design of relatively low‐cost and safe AZIBs for practical large‐scale energy storage.
Using a combined gas chromatography experiment and computation, it is demonstrated that H2 evolution primarily originates from solvated water, rather than free water without interaction with Zn2+. Using linear sweep voltammetry in salt electrolytes, H2 evolution is evidenced to occur at a more negative potential than zinc reduction because of the high overpotential against H2 evolution on Zn metal. The hypothesis is tested and using glycine additive to reduce solvated water, and it is confirmed that H2 evolution and “parasitic” side reactions are suppressed on the Zn anode.
Serum zinc concentration is used to assess the zinc status of populations. Cutoffs for serum zinc were developed on the basis of data from the second NHANES (1976–1980).
The objective of this study ...was to evaluate serum zinc concentrations in the US population and to determine factors affecting serum zinc with the use of NHANES 2011–2014.
Serum zinc was determined in males and females aged ≥6 y with the use of NHANES 2011–2014 (n = 4347). Dietary zinc intake was determined, and factors affecting serum zinc were identified with the use of regression models adjusting for sex, age, fasting status, and time of blood draw. ORs were calculated to identify factors associated with the risk of being below the serum zinc cutoff, and the prevalence of low serum zinc in the US was calculated. P < 0.01 was considered significant.
Mean ± SE serum zinc concentrations in males and females were 84.9 ± 0.8 and 80.6 ± 0.6 μg/dL, respectively (P < 0.0001). Regression models with serum zinc as the dependent variable indicated that afternoon and evening blood draws (β = –9.7 and –15.3; P < 0.0001) were negatively associated with serum zinc concentrations and serum albumin (β = 16.1; P < 0.0001) and hemoglobin (β = 1.0; P = 0.0048) were positively associated with serum zinc concentrations. Hypoalbuminemia (OR = 11.2; 99% CI: 3.4, 37.3), anemia in females (OR: 3.4; 99% CI: 1.7, 6.9), and pregnancy (OR: 9.6; 99% CI: 2.9, 31.9) increased the odds of being below the serum zinc cutoff (P < 0.0001 for all). Zinc from diet or supplements did not affect serum zinc (P > 0.01). Approximately 3.8% of children (<10 y), 8.6% of males (≥10 y), and 8.2% of females (≥10 y) were below the serum zinc cutoff.
Factors such as sex, age, and time of blood draw should be considered when using serum zinc concentration to determine the zinc status of a population. Caution is advised when interpreting serum zinc concentration in populations with a high prevalence of hypoalbuminemia or anemia. This trial was registered at http://www.isrctn.com as ISRCTN96013840.
Metallic zinc is an ideal anode for aqueous energy storage; however, Zn anodes suffer from nonhomogeneous deposition, low reversibility, and dendrite formation; these lead to an overprovision of zinc ...metal in full cells. Herein, oriented‐attachment‐regulated Zn stacking initiated through a trapping‐then‐planting process with a high zinc utilization rate (ZUR) is reported. Due to the isometric topology features of cubic‐type Prussian blue analog (PBA), the initial Zn plating occurs at specific sites with equal spacing of ≈5 Å in the direction perpendicular to the substrate; the trace amount of zinc ions trapped in tunnel matrix provides nuclei for the oriented attachment of Zn (002) deposits. As a result, the PBA‐decorated substrate delivers high reversibility of dendrite‐free zinc plating/stripping for more than 6600 cycles (1320 h) and achieves an average Coulombic efficiency (CE) of 99.5% at 5 mA cm−2 with 100% ZUR. Moreover, the anode‐limited full cell with a low negative–positive electrode ratio (N/P) of 1.2 can be operated stably for 360 cycles, displaying an energy density of 214 Wh kg−1; this greatly exceeds commercial aqueous batteries. This work provides a proof of concept design of metal anodes with a high utilization ratio and a practical method for developing high‐energy‐density batteries.
A strategy of “trapping‐then‐planting” oriented‐attached deposition is demonstrated toward high‐performance zinc‐metal anode battery. Stable zinc plating/stripping for 6600 cycles (1320 h) at 5 mA cm−2 and a Coulombic efficiency of 99.5% with a rigorous 100% ZUR (zinc utilization ratio) protocol are realized. Moreover, an anode‐limited pouch cell with a low N/P of 1.2 that displays an energy density of 214 Wh kg−1 is constructed; this greatly exceeds commercial aqueous batteries.
The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. ...Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years.
N-(tert-Butylsulfinyl)-alpha-(aminomethyl)acrylates with tethered silylated alkynes undergo a tandem 1,4-addition/carbozincation reaction upon exposure to dialkylzinc compounds in the presence of ...air. The process follows a zinc-radical-transfer mechanism and provides vinylzinc adducts that can react subsequently with electrophiles. High levels of chiral induction (dr > 90:10) from the tert-butylsulfinyl directing group are achieved during the radical 5-exo-dig cyclization by adding samarium(III) triflate. The sequence overall provides straightforward modular access to enantiopure (E)-4-alkylidene-beta-prolines from tert-butanesulfinamide.
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