Histidine Complexes Research Articles

One His, two His…the emerging roles of histidine in cellular nickel trafficking

Biological environments present a complex array of metal-binding ligands. Metal-binding proteins have been the overwhelming focus of study because of their important and well-defined biological roles. Consequently, the presence of functional low molecular weight (LMW) metal-ligand complexes has been overlooked in terms of their roles in metallobiochemistry, particularly within cells. Recent studies in microbial systems have illuminated the different roles of L-histidine in nickel uptake, gene expression, and metalloenzyme maturation. In this focused critical review, these roles are surveyed in the context of the coordination chemistry of Ni(II) ions and the amino acid histidine, and the physico-chemical properties of nickel complexes of histidine. These complexes are fundamentally important to cellular metal homeostasis and further work is needed to fully define their contributions.

Influence of Cu L-Histidinate Schiff Base Derivatives on Structural Features of Irradiated Rat's DNA.

A study of rats liver DNA damages under the influence of X-ray radiation at a dose of 6.5 Gy(LD60) was carried out. The radioprotective properties of newly synthesized Cu(II) L-Schiff Histidinate complexes were also studied. The survival of rats was determined over a 30-day period after exposure to X-rays without pretreatment and also after preadministration of Cu(II) L-Histidinate-Schiff base complexes. The structural defects of rat's liver DNA were detected at 3, 7, 14, and 30 days post-irradiation extracted. The results obtained revealed that irradiation with a 6.5Gy dose in the control group degraded the characteristics of rat liver DNA in comparison to healthy DNA. On all investigated experimental days, a decrease in the melting temperature (Tm), a widening of the melting interval (ΔT), and a decrease in hypochromicity (Δh) were observed in the DNA samples of irradiated animals compared to the norm. The rat's pretreatment by Cu(II) L-Histidinate complexes 1 or 24 hours prior to irradiation improved DNA characteristics. Electrophoretic studies of DNA were in good agreement with the melting data. Based on the study results, it can be concluded that Cu(II) L-Histidinate complexes exhibit radioprotective properties under the studied conditions and can protect DNA from damage.

Photosensitive polyimide enabled simple, reversible and environmentally friendly selective metallization on diverse substrates

For breaking through the limitation of metal patterning in constructing conductive pathways of electronic devices, which is proposed to be an upgrade of traditional etching technique, a photo-reversible, transparent and soluble polyimide carrying spiropyran side chains is synthesized. The merocyanine isomers produced from the spiropyran moieties under digitalized ultraviolet irradiation bind the silver−histidine complexes in water, while the absorbed silver ions are in-situ reduced into metal silver seeds by the photo-generated radicals from histidine molecules, catalyzing copper deposition and yielding the desired copper patterns. Accordingly, the conventional time-consuming steps (like surface modification, immobilization of catalytic ions and (photo)chemical reduction) are simplified to a single one, and the environmentally unfriendly solvent and costly/toxic palladium reagent are excluded. The Cu patterns deposited on the polyimide show high resolution, electrical conductivity (1.785 × 10−6 Ω‧cm), adhesion strength (18.14 MPa) and fatigue resistance (> 2.6 million cycles of bending). Due to the absence of invasive surface treatments (e.g., surface hydrolysis and laser direct structuring), extremely low surface roughness of 7.83 nm is achieved. Besides, the developed strategy can be easily expanded to stretchable elastomer and other organic/inorganic substrates with irregular surfaces, showing promising application prospects. The solubility of the polyimide and ultraviolet/visible light triggered reversibility of the included spiropyran groups further enable repeated recycling, erasing and re-patterning.

Cyclodextrin Polymers Functionalized with Histidine and Carcinine as Chelating Therapeutics for Copper Dyshomeostasis.

In recent years, cyclodextrin polymeric nanoparticles have been designed to introduce new properties and extend their medical applications. Based on the features of cyclodextrins, we derivatized cross-linked cyclodextrin polymers with histidine or carcinine moieties. We found that amylases do not hydrolyze cyclodextrin polymers. The new polymers can form copper(II) complexes and may act as nanochelators to counteract copper(II) dyshomeostasis-related diseases. Furthermore, the copper(II) complexes show superoxide dismutase activity, similar to free carcinine and histidine complexes. The antioxidant biological activity of the copper(II) complex formed in situ may protect cells from oxidative damage related to copper dyshomeostasis.

Nanobiomineralization of Carbon Dioxide by Molecularly Engineered Metal–Histidine Complex Nanozymes

Next-generation carbon capture, utilization, and storage (CCUS) technologies will be indispensable elements of global decarbonization efforts. In this context, permanent and rapid sequestration of carbon dioxide (CO2) at high capacities will impact their utility broadly. CO2 mineralization into solid inorganic carbonates is an appealing CCUS approach, which requires fast CO2 hydration for effective implementation. The carbonic anhydrases (CAs) have, thus, gained considerable attention as rate promoters for CO2 hydration. Nevertheless, the poor stability and high cost of CAs limit their practical application prospects. Here, we demonstrate that the molecular size control of histidine-based bolaamphiphiles (HisBolas) is a viable strategy for forming robust nanoarchitectures with unusual CA-like catalytic activity. HisBola molecules self-assemble into nanoparticles (∼40 nm) that fuse into globules in water, and the metal coordination of these supramolecular nanoassemblies results in nanozymes. The developed bioinspired nanozymes boost the CO2 hydration kinetics, thus efficiently catalyzing the mineralization process. Systematically studying the alkyl chain length of HisBolas (HisBola5, 7, and 10), we optimized the catalytic activity of the nanozymes. The nanozyme with the optimum structure, zinc-coordinated HisBola5, showed the highest esterase activity [kcat/Km of ∼33.44 M–1·s–1 and Michaelis constant (Km) of ∼0.29 mM] and CO2 hydration kinetics (kcat.hyd/Km.hyd of ∼30,300 M–1·s–1 and Km.hyd of ∼14 mM) among all metal-coordinated HisBolas screened. Overall, low-molecular-weight HisBolas offer a promising platform for designing metal-coordinated nanozymes with high catalytic activity, outstanding thermal stability, and rapid catalytic CO2 hydration ability for CO2 mineralization. We argue that the alkyl unit-controlled performance manipulation of produced nanozymes offers a new path for engineering supramolecular CA mimics, which share a common trait with proteinaceous enzymes, that is, the supporting role of noncatalytic units in catalytic activity.

Evaluation of hydrophilic interaction chromatography versus reversed-phase chromatography for fast aqueous species distribution analysis of Nickel(II)-Histidine complex species

Nickel (Ni) is a trace heavy metal of importance in biological and environmental systems, with well documented allergy and carcinogenic effects in humans. With Ni(II) as the dominant oxidation state, the elucidation of the coordination mechanisms and labile complex species responsible for its transportation, toxicity, allergy, and bioavailability is key to understanding its biological effects and location in living systems. Histidine (His) is an essential amino acid that contributes to protein structure and activity and in the coordination of Cu(II) and Ni(II) ions. The aqueous low molecular weight Ni(II)-Histidine complex consists primarily of two stepwise complex species Ni(II)(His)1 and Ni(II)(His)2 in the pH range of 4 to 12. Four chromatographic columns, including the superficially porous Poro-shell EC-C18, Halo RP-amide and Poro-shell bare silica-HILIC columns, alongside a Zic-cHILIC fully porous column, were evaluated for the fast separation of the individual Ni(II)-Histidine species. Of these the Zic-cHILIC exhibited high efficiency and selectivity to distinguish between the two stepwise species Ni(II)His1 and Ni(II)His2 as well as free Histidine, with a fast separation within 120 s at a flow rate of 1 ml/min. This HILIC method utilizing the Zic-cHILIC column was initially optimized for the simultaneous analysis of Ni(II)-His-species using UV detection with a mobile phase consisting of 70% ACN and sodium acetate buffer at wwpH 6. Furthermore, the aqueous metal complex species distribution analysis for the low molecular weight Ni(II)-histidine system was chromatographically determined at various metal-ligand ratios and as a function of pH. The identities of Ni(II)His1 and Ni(II)-His2 species were confirmed using HILIC electrospray ionization- mass spectrometry (HILIC-ESI-MS) at negative mode.

Peptide Cross-Linking Using Tyrosine Residues Facilitated by an Exogenous Nickel-Histidine Complex: A Facile Approach for Enhancing Vaccine-Specific Immunogenicity.

An improved method for the generation of peptide vaccines using di-tyrosine cross-linking is described. The conserved ion channel peptide, M2e, of influenza A virus was modified with the addition of small tyrosine-rich regions (GYGY-) at both the N- and C-termini and extensively cross-linked via tyrosine-tyrosine linkages to form peptide nanoclusters. The cross-linking was catalyzed using exogenous nickel(II) ions complexed to an exogenous glycine-glycine-histidine peptide in the presence of an oxidizer. Mice that were intranasally or intramuscularly immunized with the M2e-vaccine nanoclusters induced comparable levels of M2e-specific serum antibodies. Vaccination via the intranasal or intramuscular route protected mice from subsequent lethal challenge with an influenza A virus. In comparison to our previous approach, where a histidine-rich tag was added into the peptide structure, the use of exogenous histidine reduced irrelevant off-target immune response. Additionally, the purity of the resulting nanoclusters is an attractive feature, making this approach appealing for vaccine development.

Structure of Zinc and Nickel Histidine Complexes in Solution Revealed by Molecular Dynamics and Raman Optical Activity.

The histidine residue has an exceptional affinity for metals, but solution structure of its complexes are difficult to study. For zinc and nickel complexes, Raman and Raman optical activity (ROA) spectroscopy methods to investigate the link between spectral shapes and the geometry were used. The spectra were recorded and interpreted on the basis of ionic equilibria, molecular dynamics, ab initio molecular dynamics, and density functional theory. For zwitterionic histidine the dominant tautomer was determined by the decomposition of experimental spectra into calculated subspectra. An octahedral structure was found to prevail for the ZnHis2 complex in solution, in contrast to a tetrahedral arrangement in the crystal phase. The solution geometry of NiHis2 is more similar to the octahedral structure found by X-ray. The Raman and ROA structural determinations of metal complexes are dependent on extensive computations, but reveal unique information about the studied systems.

Synthesis, IR characterization and antioxidant capacity of Cu(II) complexes with amino acids and melatonin

In this paper, the reactions of anhydrous copper(II) chloride in methanolic solution with alanine, glycine, histidine, L-tryptophan, and melatonin were investigated and the resulting products were characterized by FTIR spectroscopy. Based on FTIR characterization, it was shown that these reaction conditions result in the formation of Cu(II) complexes with glycine and alanine, which are more complex structures than bis(glycinato) - and bis(alaninato) copper(II) complexes. Analysis of the FTIR spectrum of the histidine complex shows the participation of several groups in coordination at the Cu(II) center. The complex prepared with melatonin shows unusual changes in the spectral region of the amidic nitrogen bonds. The latter observation is very significant for very few known metal complexes of melatonin, while the synthesis of most of them is an experimentally demanding process with simultaneous control of several parameters. The antioxidant capacity of the synthesized complexes was examined, with the CEAC range from 121.6 to 734.4 µM. The lowest values of antioxidant capacity were recorded for the copper complex with tryptophan, while the highest values were recorded for the copper complex with alanine. A high antioxidant capacity of the copper complex with melatonin (673.8 µM) was also observed.

Synthesis, IR characterization and antioxidant capacity of Cu(II) complexes with amino acids and melatonin

In this paper, the reactions of anhydrous copper(II) chloride in methanolic solution with alanine, glycine, histidine, L-tryptophan, and melatonin were investigated and the resulting products were characterized by FTIR spectroscopy. Based on FTIR characterization, it was shown that these reaction conditions result in the formation of Cu(II) complexes with glycine and alanine, which are more complex structures than bis(glycinato) - and bis(alaninato) copper(II) complexes. Analysis of the FTIR spectrum of the histidine complex shows the participation of several groups in coordination at the Cu(II) center. The complex prepared with melatonin shows unusual changes in the spectral region of the amidic nitrogen bonds. The latter observation is very significant for very few known metal complexes of melatonin, while the synthesis of most of them is an experimentally demanding process with simultaneous control of several parameters. The antioxidant capacity of the synthesized complexes was examined, with the CEAC range from 121.6 to 734.4 µM. The lowest values of antioxidant capacity were recorded for the copper complex with tryptophan, while the highest values were recorded for the copper complex with alanine. A high antioxidant capacity of the copper complex with melatonin (673.8 µM) was also observed.

Rare Silver-Histidine Cluster Complex and Its Single-Crystal-to-Single-Crystal Phase-Transition Behavior.

Silver complexes with proteinogenic amino acid ligands are of interest for biomedical and antimicrobial applications. In this work, we obtained {[Ag7(l-his)4](NO3)3·3H2O}0.2{[Ag8(l-his)4(H2O)2](NO3)4·3H2O}0.8 (1) and {[Ag7(d-his)4](NO3)3·3H2O}0.2{[Ag8(d-his)4(H2O)2](NO3)4·3H2O}0.8 (2), which represent the first example of any Ag-exclusive complex featuring a cluster-type core motif and with only proteinogenic amino acid ligands. Upon immersion into acetonitrile, an interesting single-crystal-to-single-crystal transformation occurred to produce a new cluster complex of the formula [Ag8(l-his)4(NO3)(H2O)](NO3)3 (3). Using a racemic mixture of histidine, the reaction under otherwise identical conditions led to the production of the second example of a three-dimensional (3D) network structured Ag-exclusive complex with only a proteinogenic amino acid ligand. Compared with other Ag–histidine complexes in the literature, the significance of reaction conditions, particularly the Ag/histidine ratio and pH of the reaction mixture, is revealed. Temperature-dependent emission of 1 and 2 at 440 nm characteristic of silver–philophilic interactions was also observed.

Global analysis for pD-variation NMR titration of organic electrolyte complexes

ABSTRACT This is an addendum to our preceding article, ‘NMR pD-variation method to determine the proper stabilities of organic electrolyte complexes: case of histidine complexes with a cyclophane acid’ Supramolecular Chemistry https://doi.org/10.1080/10610278.2022.2134017, which proposes that the species distribution of complexes between organic electrolytes is determined by observing the pD dependence of NMR signals for a mixture of the reactants; the species distribution can be replotted in a pH scale. This addendum demonstrates that the process of data analysis is simplified even more reliably by employing a global fitting method in place of a local, successive method used previously; comparative evaluation was made using Excel® spreadsheets appended. The straightforward global analysis will facilitate the practice of pD-variation NMR titration. The application range is potentially extendable by the use of 13C NMR, which overcomes some weak points of the 1H NMR method.

NMR pD-variation method to determine the proper stabilities of organic electrolyte complexes: case of histidine complexes with a cyclophane acid

ABSTRACT The complexation of organic electrolytes, like carboxylic acids and amines, is studied usually by spectrometric titration at a constant pH. Obtained stability constants are, however, conditional and dependent on the pH selected, differing from the proper constants. In nuclear magnetic resonance (NMR) titration in D2O, a stability constant determined at a given pD is not directly correlated to other properties observed at a pH in H2O because of difference between acid dissociations in the solvents. To overcome these problems, this report proposes pD-variable NMR spectrometry, which monitors NMR signals of a mixture of the reactants with the variation of pD. This method identifies complexes formed in different pD ranges, and determines the proper stability constants, to yield the species distribution, which can be replotted in pH scale. The usefulness and limitation are examined by simulation of titration curves. An experimental example is presented for complexation of histidine with a cyclophane acid. Excel® files for calculations are available in Supplementary material.

Examining the Potential Formation of Ternary Chromium-Histidine-DNA Complexes and Implications for Their Carcinogenicity.

The mutagenic and carcinogenic properties of chromium(VI) complexes have been ascribed to the formation of ternary Cr(III)-small molecule-DNA complexes. As part of these laboratories efforts to establish the structure and properties of discrete binary and ternary adducts of Cr(III) and DNA at a molecular level, the properties of Cr(III)-histidine-DNA complexes formed from Cr(III) were examined. These studies determined the composition of previously described "prereacted" chromium histidinate and reveal the reaction of "prereacted" chromium histidinate with DNA does not form ternary complexes as previously proposed. The products instead are chromium histidinate complexes weakly bound, probably in the minor groove, to DNA. These weakly bound adducts cannot be responsible for the mutagenic and carcinogenic properties ascribed to ternary Cr(III)-histidine-DNA adducts. The results of biological studies where "ternary adducts" of Cr(III), histidine, and DNA were made from "prereacted" chromium histidinate must, therefore, be interpreted with caution.

Zinc(II) Complexes of Amino Acids as New Active Ingredients for Anti-Acne Dermatological Preparations.

Zinc compounds have a number of beneficial properties for the skin, including antimicrobial, sebostatic and demulcent activities. The aim of the study was to develop new anti-acne preparations containing zinc–amino acid complexes as active ingredients. Firstly, the cytotoxicity of the zinc complexes was evaluated against human skin fibroblasts (1BR.3.N cell line) and human epidermal keratinocyte cell lines, and their antimicrobial activity was determined against Cutibacterium acnes. Then, zinc complexes of glycine and histidine were selected to create original gel formulations. The stability (by measuring pH, density and viscosity), microbiological purity (referring to PN-EN ISO standards) and efficacy of the preservative system (according to Ph. Eur. 10 methodology) for the preparations were evaluated. Skin tolerance was determined in a group of 25 healthy volunteers by the patch test. The preparations containing zinc(II) complexes with glycine and histidine as active substances can be topically used in the treatment of acne skin due to their high antibacterial activity against C. acnes and low cytotoxicity for the skin cells. Dermatological recipes have been appropriately composed; no irritation or allergy was observed, and the preparations showed high microbiological purity and physicochemical stability.

Effects of supplementing different chromium histidinate complexes on glucose and lipid metabolism and related protein expressions in rats fed a high-fat diet

BackgroundThe objective of this study was to investigate the effects of different chromium histidinate (CrHis) complexes added to the diet of rats fed a high-fat diet (HFD) on body weight changes, glucose and lipid metabolism parameters, and changes in biomarkers such as PPAR-γ, IRS-1, GLUTs, and NF-κB proteins. MethodsForty-two Sprague–Dawley rats were divided equally into six groups and fed either a control, an HFD, or an HFD supplemented with either CrHis1, CrHis2, CrHis3, or a combination of the CrHis complexes as CrHisM. ResultsFeeding an HFD to rats increased body weights, HOMA-IR values, fasting serum glucose, insulin, leptin, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and MDA concentrations as well as AST activities, and decreased serum and brain serotonin concentrations compared with rats fed a control diet (P < 0.0001). The levels of the PPAR-γ, IRS-1, and GLUTs in the liver and brain decreased, while NF-κB level increased, with feeding an HFD (P < 0.05). Although all the CrHis supplements reversed the negative effects of feeding an HFD (P < 0.05), the CrHis1 complex was most effective in changing the protein levels, while CrHisM was most effective in influencing certain parameters such as body weight and serum metabolites. ConclusionThe results of the present work suggest that the CrHis1 complex is most potent for alleviating the negative effects of feeding an HFD. The efficacy of CrHisM is likely due to the presence of the CrHis1 complex.

Study of the histidine complex of uranium(IV): synthesis, spectrophotometric, magnetic and electrochemical properties

We synthesized the novel histidine complex of uranium(IV). A 1:3 mole ratio was found between metal and ligand by the mole ratio method, while –NH2 and –COO– groups of histidine behave as coordinating sites. The IR spectra confirmed the lone pair donating or coordinating sites. The elemental analysis confirmed the stoichiometry. The bathochromic shift with an increase in the optical density in the UV-Visible range indicated that the compound and its central metal ion hold uniform electronic charge distribution. The electrochemical results indicated a quasi-reversible (neither completely reversible nor completely irreversible) oxidation of the complex to its uranium(V) product at the platinum working electrode. The quasi-reversible process shows a comparatively slow electron transfer (ET) rate with the heterogeneous electron transfer rate constant ‘ks’ (3.4 × 10–4 cm s-1) at 50 mV s-1 and 305 ± 0.5 K. The kinetics such as diffusion and charge transfer lead the reaction with an ECE (electrochemical–chemical–electrochemical) mechanism. The thermodynamic parameters of activation such as ΔH*; 4.257 kJ mol–1, ΔS*; -2.519 × 10–3 J mol–1 K–1 and ΔG* 4.26 kJ mol–1 helped to propose an associative mechanism of the electron transfer at the platinum working electrode.&#x0D; &#x0D; KEY WORDS: Uranium, Histidine, Spectroscopy, Electrochemistry, Kinetics&#x0D; &#x0D; Bull. Chem. Soc. Ethiop. 2020, 34(3), 557-569. &#x0D; DOI: https://dx.doi.org/10.4314/bcse.v34i3.11

Fenton-like reaction of the iron(II)-histidine complex generates hydroxyl radicals: implications for oxidative stress and Alzheimer's disease.

The hydroxyl radical (˙OH), generated from Fenton/Fenton-like reactions of iron(II) species in biology, can oxidatively damage biomolecules, inducing oxidative stress and diseases. However, this common understanding has been questioned recently after a carbonate radical was observed from the Fenton-like reaction of the iron(II)-carbonate complex. Herein, we report that the Fenton-like reaction of the iron(II)-histidine complex, one major iron(II) species in blood plasma, can occur at neutral pH to generate ˙OH, not iron(IV). Our findings and critical analyses on relevant studies clarify the above doubt, reveal a new pathway of causing oxidative stress by the iron(II) species, and have implications for Alzheimer's disease.

Dual crosslinked metallopolymers using orthogonal metal complexes as rewritable shape-memory polymers

This study presents shape-memory metallopolymers based on weak histidine and strong terpyridine complexes. The use of two different salts results in seperated activation temperatures, allowing the very good shape-memory process and rewriting.

The use of EQCM for setting the optimum conditions of the determination of Pd2+ ions via its palladium–histidine complex

Electrochemical quartz crystal microbalance (EQCM) was used as a novel approach for the determination of palladium–histidine complex formation on an amalgam film gold based electrode. We have demonstrated the applicability of an amalgam-modified gold QCM substrate to monitor histidine adsorption and palladium ions complexation under electrochemical control. The results of EQCM measurements revealed that adsorption of histidine on amalgam film gold based electrode is dependent on the potential, indicating that the electrosorption occurs which depends on the charge on the gold–mercury surface and the charge of the histidine ions. The interactions of palladium ions with the adsorbed layer of histidine at open circuit potential results in the removal of histidine from mercury surface, indicating stronger bonds between histidine and palladium than between histidine and mercury. On the other hand, by applying the potential of −200 mV upon the introduction of palladium ions it is possible to obtain histidine-palladium complex adsorbed on the mercury surface. This phenomenon was used for the determination of Pd using adsorptive stripping voltammetry (AdSV). Application of the deposition potential indicated by EQCM led to well defined analytical signals increasing with standard addition.