Identity Of Metal Ion Research Articles

Influence of the Weak Nuclear Force on Metal-Promoted Autocatalytic Strecker Synthesis of Amino Acids: Formation of a Chiral Pool of Precursors for Prebiotic Peptide and Protein Synthesis.

Natural chiral amino acids typically adopt an L structural configuration. While a preference for specific molecular chiralities is observed throughout biology and cellular chemistry, the origins of this preference are unclear. In a previous report the origin of enantiomeric selectivity was analyzed in terms of an "RNA World" model, and a pathway to a chiral preference for d-ribose was proposed based on the autocatalytic transformation of glyceraldehyde as a precursor to the formation of sugars. Metal-ion-promoted catalysis allows the parity non-conserving (PNC) weak nuclear interaction to influence the chirality of a nascent chiral carbon center. Since the PNC effect is the only natural property with an inherent handedness, it is an obvious candidate to influence enantiomeric preference from a catalytic reaction performed over geologically relevant time scales. The PNC influence requires and emphasizes the important role of catalytic metal ions in primordial chemistry. In this study, the impact of geologically available divalent calcium and higher Z alkaline earth elements are examined as mediators of chiral preference. Detailed calculations of the magnitude of the effect are presented, including the influence of time, temperature, pH, and metal ion identity. It is concluded that metal ions can direct chiral preference for amino acid synthesis via a metal-promoted autocatalytic Strecker reaction within a relatively short geological timeframe, thereby providing a pool of l-amino acids for catalytic chemistry evolving either from an RNA-world model of molecular evolution or alternative pathways to protein synthesis.

Exploring the hygroscopicity and chemical composition evolution in organic-inorganic aerosols: A study on internally mixed malonic acid-metal (Na+, Ca2+, Mg2+) nitrates

Chemical transformations in mixed aerosols alter the particulate physical properties. Nitrates and water soluble dicarboxylic acids, such as malonic acid (MA), are major components of ambient aerosol particles. Various metal ions such as, Na+, Ca2+, Mg2+ also become part of these complex aerosol systems during their atmospheric lifetime. Interactions among the co-existing ionic and molecular species govern the chemical changes in the aerosol particles. In this work, we provide a comparative account of the effect of metal ion identity (Na+, Ca2+, Mg2+) on such chemical changes arising from ion-molecular interactions in NaNO3-MA, Ca(NO3)2-MA and Mg(NO3)2-MA mixed inorganic-organic aerosols. In-situ micro-Raman spectroscopy has enabled us to gain molecular level insight on formation of organic salt and simultaneously estimate nitrate depletion in these mixed aerosols during different stages of their hygroscopic cycle. In addition to the nitrate depletion often reported during the drying phase, this study has brought to light an intriguing observation: depletion of nitrate in the humidification phase as well, a phenomenon that has hitherto remained undocumented. For the mixed systems studied here, the extent of nitrate depletion follows the order Mg-MA (58%) > Ca-MA (43%) > Na-MA (15%). The comparatively huge forward shift in the acid displacement reaction equilibrium for the systems, Ca-MA and Mg-MA is driven by complexation. Our results highlight the profound effect of ion-molecular interactions on the acid displacement reaction equilibria in aerosols.

Comparison of metal ions recovered during DNA analysis of brass ammunition and effects of copper and zinc ions on DNA profiling

Analyzing DNA from brass surfaces poses unique challenges that may result from DNA damage and/or PCR inhibition. To examine the relationship between the metal ions present in brass ammunition and the success of Short Tandem Repeat (STR) profiling, six recovery methods were tested to determine the identity and quantity of metal ions co-recovered during DNA sampling. In addition, DNA and metal ion solutions were created at varying concentrations to determine the threshold at which deleterious effects occur. The results of this study show that copper and zinc are recovered in the highest concentrations from both fired and unfired ammunition, but at substantially lower levels than previously published. Furthermore, most metal ions co-recovered with DNA were removed during DNA purification and complete STR profiles were generated when the concentrations of copper and zinc ions were less than 0.1 M and 0.03 M, respectively.

Applications of Designed Alpha‐Helical Metallopeptides

A variety of strategies have been employed to generate alpha‐helical peptides to mimic native protein‐protein interactions. Here, we present applications of a method that induces secondary structure in short peptides using engineered metal‐binding sites. We propose that the incorporation of metal ions to create helical peptides provides additional benefits that the more widely utilized covalent crosslinking methods lack. We have created a peptide system designed to bind ribose 5‐phosphate isomerase B (RpiB), a protein target in developing treatments for Chagas disease caused by Trypanosoma cruzi. In this system, we have compared peptide structure and stability when using our metal‐crosslinking system to hydrocarbon, lactam, and thioether staples across 1‐ or 2‐turns of an alpha‐helix. We have also measured the ability of each of these peptide constructs to bind RpiB and prevent homodimerization, which is required for parasitic activity. Further, we have studied whether metal‐bound peptides are better able to cross cellular membranes and enter the cytoplasm of mammalian cells compared to metal‐free peptides, as has been previously suggested in the literature, and deduced the impact of metal ion charge, identity, and secondary structure in enhanced permeability.

Redox- and metal-directed structural diversification in designed metalloprotein assemblies.

Herein we describe a designed protein building block whose self-assembly behaviour is dually gated by the redox state of disulphide bonds and the identity of exogenous metal ions. This protein construct is shown - through extensive structural and biophysical characterization - to access five distinct oligomeric states, exemplifying how the complex interplay between hydrophobic, metal-ligand, and reversible covalent interactions could be harnessed to obtain multiple, responsive protein architectures from a single building block.

Metal Ion-Dependent Interfacial Organization and Dynamics of Metal-Phosphonate Monolayers.

Self-assembled monolayers have been studied extensively due to their relative ease of synthesis and the broad range of applications for this class of materials. Monolayer-support interactions can range in strength from physisorption through covalent bond formation, with consequent variability in the robustness and fluidity of the monolayer. Monolayer-support bonding by metal ion complexation is especially attractive because of the ability to adjust the strength of interaction through metal ion identity. For such systems, both the exchange kinetics and thermodynamics of metal ion-complex formation contribute to the observed properties of the monolayer. We have synthesized metal-phosphate/phosphonate monolayers using Zr4+ and In3+ and have evaluated the metal ion dependence of monolayer dynamics for free and bound chromophores. Our findings reveal significant metal ion-dependent variations in monolayer dynamics and organization.

Simultaneous cell lysis and DNA extraction from whole blood using magnetic ionic liquids.

Conventional DNA sample preparation methods involve tedious sample handling steps that require numerous inhibitors of the polymerase chain reaction (PCR) and instrumentation to implement. These disadvantages limit the applicability of conventional cell lysis and DNA extraction methods in high-throughput applications, particularly in forensics and clinical laboratories. To overcome these drawbacks, a series of nine hydrophobic magnetic ionic liquids (MILs) previously shown to preconcentrate DNA were explored as cell lysis reagents. The MILs were found to lyse white blood cells from whole blood, 2-fold diluted blood, and dry blood samples while simultaneously extracting human genomic DNA. The identity of metal ion incorporated within the MIL appears to cause hemolysis while the cationic component further reduces the cell's integrity. Over 500pg of human genomic DNA was isolated from 50μL of whole blood using the trioctylbenzylammonium tris(hexafluoroacetylaceto)nickelate(II) ([N8,8,8,Bz+][Ni(hfacac)3-]) MIL, and 800pg DNA was isolated from a dry blood samples using the trihexyl(tetradecyl)phosphonium tris(phenyltrifluoroacetylaceto)nickelate(II) ([P6,6,6,14+][Ni(Phfacac)3-]) MIL following a 1-min vortex step. A rapid, one-step cell lysis and DNA extraction from blood is ideal for settings that seek high-throughput analysis while minimizing the potential for contamination.Graphical abstract.

X‐ray Crystal Structure of Agmatinase from Escherichia coli

Agmatinase acts upon the cellular metabolite agmatine to produce putrescine, an important precursor for higher‐order polyamines that are required for cell proliferation, differentiation, and migration. The activity of agmatinase and the role of agmatine have garnered attention due to the importance of agmatine in various medical contexts including: neurological disorders, a possible role for agmatine as a neurotransmitter/neuromodulator, treatment of depression, and even the proposal that the family of metallohydrolases that include agmatinase may find novel biotechnological applications. Here we report the crystal structure of Escherichia coli agmatinase. The structure of E. coli agmatinase exhibits global fold and active site architecture typical of the metal‐dependent ureohydrolase protein superfamily. Moreover, the arrangement of conserved metal ligands and electron density at the active site indicate the presence of two metal ions, which is consistent with reported literature finding E. coli agmatinase to require two Mn2+ ions. Comparisons with the structures of related proteins will be described, along with functional characterization of agmatinase in terms of both enzymatic activity, as well as the requirement and identity of metal ions.

Computational Study of 3d Metals and Their Influence on the Acidity of Methane C-H Bonds.

CCSD(T) methods in conjunction with correlation consistent basis sets are used to predict the pKa for the deprotonation of methane in a 3d metal ion adduct, [M···CH4]+ (M = Sc–Cu), in dimethyl sulfoxide solvent, which is modeled by the SMD continuum solvent model. Results show that the coordination of methane to different M+ ions has a substantial difference of ∼27 pKa units, from most to least acidic, and increases the acidity of the methane C–H bond from ∼8 to 36 pKa units. Furthermore, even with the omission of the more expensive quadruple and quintuple zeta basis sets in the prediction process, similar trends in pKa(C–H) as a function of 3d metal ions are exhibited. This research serves to illustrate the substantial effect that metal ion identity has on the acidity of a coordinated hydrocarbon and the utility that correlation consistent basis sets have in lowering the computational cost of modeling larger systems.

Finding the right match

Bacteria sense metal ions using proteins whose interactions with DNA are sensitive to metal ion availability and identity. Less competitive metal ions trigger protein–DNA binding only at high concentrations.

322 - Radical consequences of redox active metals on α-synuclein assemblies

Histopathological hallmarks of Parkinson’s disease (PD) include the development of granular inclusions known as Lewy bodies that are enriched with aggregates of the protein α-synuclein (αS). Historically, αS has been considered a natively unfolded protein prone to amyloidogenic behavior. A molecular understanding of how the structurally dynamic nature of this protein contributes to PD symptoms is still lacking, but metal dyshomeostasis has long been linked to PD. Thus, a deeper understanding of biometal-influenced dynamics and metal-mediated redox chemistry associated with each of the various conformational states of αS may shed light on PD pathways associated with cerebral metal miscompartmentalization. Work in our lab is dedicated to the overarching goal of elucidating the mechanistic roles of cerebral biometals, specifically iron and copper, as either protagonistic cofactors or antagonistic toxins. My lab has recently demonstrated the biophysical consequences of metal binding that influence αS structure and aggregation, including an FeII/O2-dependent self-association of αS to a PD-relevant oligomer-locked A11+ species with a high degree of right-twisted anti-parallel b-sheet structure. In this work, we further elaborate the downstream effects of metal-αS interactions, including how aerobically aggregated FeII-bound αS, in particular, promotes protein-protein interactions. Secondary structural deconvolution and identification of proteins with homologous structures have implicated protein partners for αS with significance to PD and other neurodegenerative diseases, and we have verified these interactions through immunological analyses and chemical cross-linking. We have also established the metal-induced generation of protein-based radicals that are distinct to the metal ion identity and that contribute to the structural heterogeneity of αS assemblies. Presentation of this work will offer a unique perspective on both the beneficial and consequential role of prevalent transition metals in the brain.

QM/MM analysis of effect of divalent metal ions on OPRT action

The role of Mg2+ cofactor in orotate phosphoribosyltransferase (OPRT) catalyzed synthesis of orotidine monophosphate (OMP) from phosphoribosyl pyrophosphate (PRPP) and orotate (OA) in substrate binding and the influence of the identity of the divalent metal ion on the reaction mechanism were addressed in this study using quantum mechanics/molecular mechanics framework. Energetics of migration and binding of different substrate complexes in the active site cavity was established. A quantitative analysis of various processes indicated the reaction pathway to consist of complexation of Mg2+ with PRPP, migration of Mg2+-PRPP and OA towards the active site, binding of OA to OPRT, and binding of Mg2+-PRPP complex to OA-OPRT complex. The mechanism of the reaction was unaltered by the change in the identity of divalent metal ion. Experimentally reported inhibiting character of Co2+ was explained on the basis of large Co2+-PRPP binding and migration energies. Mg2+, Ca2+, Mn2+, Co2+ and Zn2+ ions were screened computationally to assess their inhibiting/activating characteristics. Trends obtained by our computational investigations were in correspondence with experimentally reported trends.

Active Site Metal Identity Alters Histone Deacetylase 8 Substrate Selectivity: A Potential Novel Regulatory Mechanism.

Histone deacetylase 8 (HDAC8) is a well-characterized member of the class I acetyl-lysine deacetylase (HDAC) family. Previous work has shown that the efficiency of HDAC8-catalyzed deacetylation of a methylcoumarin peptide varies depending on the identity of the divalent metal ion in the HDAC8 active site. Here we demonstrate that both HDAC8 activity and substrate selectivity for a diverse range of peptide substrates depend on the identity of the active site metal ion. Varied deacetylase activities of Fe(II)- and Zn(II)-HDAC8 toward an array of peptide substrates were identified using self-assembled monolayers for matrix-assisted laser desorption ionization (SAMDI) mass spectrometry. Subsequently, the metal dependence of deacetylation of peptides of biological interest was measured using an in vitro peptide assay. While Fe(II)-HDAC8 is generally more active than Zn(II)-HDAC8, the Fe(II)/Zn(II) HDAC8 activity ratio varies widely (from 2 to 150) among the peptides tested. These data provide support for the hypothesis that HDAC8 may undergo metal switching in vivo that, in turn, may regulate its activity. However, future studies are needed to explore the identity of the metal ion bound to HDAC8 in cells under varied conditions.

Electronic, Magnetic, and Redox Properties and O2 Reactivity of Iron(II) and Nickel(II) o-Semiquinonate Complexes of a Tris(thioether) Ligand: Uncovering the Intradiol Cleaving Reactivity of an Iron(II) o-Semiquinonate Complex.

The iron(II) semiquinonate character within the iron(III) catecholate species has been proposed by numerous studies to account for the O2 reactivity of intradiol catechol dioxygenases, but a well-characterized iron(II) semiquinonate species that exhibits intradiol cleaving reactivity has not yet been reported. In this study, a detailed electronic structure description of the first iron(II) o-semiquinonate complex, [PhTttBu]Fe(phenSQ) [PhTttBu = phenyltris(tert-butylthiomethyl)borate; phenSQ = 9,10-phenanthrenesemiquinonate; Wang et al. Chem. Commun. 2014, 50, 5871-5873], was generated through a combination of electronic and Mössbauer spectroscopies, SQUID magnetometry, and density functional theory (DFT) calculations. [PhTttBu]Fe(phenSQ) reacts with O2 to generate an intradiol cleavage product, diphenic anhydride, in 16% yield. To assess the dependence of the intradiol reactivity on the identity of the metal ion, the nickel analogue, [PhTttBu]Ni(phenSQ), and its derivative, [PhTttBu]Ni(3,5-DBSQ) (3,5-DBSQ = 3,5-di-tert-butyl-1,2-semiquinonate), were prepared and characterized by X-ray crystallography, mass spectrometry, 1H NMR and electronic spectroscopies, and SQUID magnetometry. DFT calculations, evaluated on the basis of the experimental data, support the electronic structure descriptions of [PhTttBu]Ni(phenSQ) and [PhTttBu]Ni(3,5-DBSQ) as high-spin nickel(II) complexes with antiferromagnetically coupled semiquinonate ligands. Unlike its iron counterpart, [PhTttBu]Ni(phenSQ) decomposes slowly in an O2 atmosphere to generate 14% phenanthrenequinone with a negligible amount of diphenic anhydride. [PhTttBu]Ni(3,5-DBSQ) does not react with O2. This dramatic effect of the metal-ion identity supports the hypothesis that a metal(III) alkylperoxo species serves as an intermediate in the intradiol cleaving reactions. The redox properties of all three complexes were probed using cyclic voltammetry and differential pulse voltammetry, which indicate an inner-sphere electron-transfer mechanism for the formation of phenanthrenequinone. The lack of O2 reactivity of [PhTttBu]Ni(3,5-DBSQ) can be rationalized by the high redox potential of the metal-ligated 3,5-DBSQ/3,5-DBQ couple.

Using Diffusion To Characterize Interfacial Heterogeneity

We report on the use of molecular diffusional motion over a range of length scales to characterize compositional heterogeneity in monolayer structures. This work focuses on the diffusional motion of perylene in two types of films supported on functionalized silica surfaces: single-component (stearic acid) and two-component (hydrocarbon/fluorocarbon) films. Langmuir-Blodgett (LB) monolayers were deposited directly on silica or were bound to surface-modified silica by means of metal ion complexation. The LB films were characterized by their π-A isotherms and by Brewster angle microscopy (BAM) during formation and deposition. Chromophore mobility and monolayer structural heterogeneity were evaluated by comparing rotational diffusion data (fluorescence anisotropy decay imaging) and translational diffusion data (fluorescence recovery after photobleaching) on the same LB films. Our results indicate that the mobility of the chromophore depends sensitively on both metal ion identity and film composition.

Dual chemistry catalyzed by human acireductone dioxygenase.

Acireductone dioxygenase (ARD) from the methionine salvage pathway of Klebsiella oxytoca is the only known naturally occurring metalloenzyme that catalyzes different reactions in vivo based solely on the identity of the divalent transition metal ion (Fe2+ or Ni2+) bound in the active site. The iron-containing isozyme catalyzes the cleavage of substrate 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, whereas the nickel-containing isozyme uses the same substrates to catalyze an off-pathway shunt to form methylthiopropionate, carbon monoxide and formate. This dual chemistry was recently demonstrated in vitro by ARD from Mus musculus (MmARD), providing the first example of a mammalian ARD exhibiting metal-dependent catalysis. We now show that human ARD (HsARD) is also capable of metal-dependent dual chemistry. Recombinant HsARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. As with MmARD, the Fe2+-bound HsARD shows the highest activity and catalyzes on-pathway chemistry, whereas Ni2+, Co2+ or Mn2+ forms catalyze off-pathway chemistry. The thermal stability of the HsARD isozymes is a function of the metal ion identity, with Ni2+-bound HsARD being the most stable followed by Co2+ and Fe2+, and Mn2+-bound HsARD being the least stable. As with the bacterial ARD, solution NMR data suggest that HsARD isozymes can have significant structural differences depending upon the metal ion bound.

Metal-Dependent Nucleobase Recognition by Picolinamide.

A C-nucleoside featuring picolinamide as the base moiety has been synthesized and incorporated in the middle of a DNA oligonucleotide. The melting temperatures of duplexes formed by this modified oligonucleotide with its unmodified counterparts placing either adenine, cytosine, guanine or thymine opposite to the picolinamide residue were found to be highly dependent on the identity and concentration of transition metal ions in the samples. For example, AgI uniquely promoted pairing with adenine and PdII with guanine. Pairing with cytosine, on the other hand, was retarded by all of the metal ions studied (AgI , CuII , HgII , NiII , PdII and ZnII ).

Metal-Dependent Function of a Mammalian Acireductone Dioxygenase.

The two acireductone dioxygenase (ARD) isozymes from the methionine salvage pathway of Klebsiella oxytoca are the only known pair of naturally occurring metalloenzymes with distinct chemical and physical properties determined solely by the identity of the divalent transition metal ion (Fe(2+) or Ni(2+)) in the active site. We now show that this dual chemistry can also occur in mammals. ARD from Mus musculus (MmARD) was studied to relate the metal ion identity and three-dimensional structure to enzyme function. The iron-containing isozyme catalyzes the cleavage of 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, which is the penultimate step in methionine salvage. The nickel-bound form of ARD catalyzes an off-pathway reaction resulting in formate, carbon monoxide (CO), and 3-(thiomethyl) propionate. Recombinant MmARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. The Fe(2+)-bound protein, which shows about 10-fold higher activity than that of others, catalyzes on-pathway chemistry, whereas the Ni(2+), Co(2+), or Mn(2+) forms exhibit off-pathway chemistry, as has been seen with ARD from Klebsiella. Thermal stability of the isozymes is strongly affected by the metal ion identity, with Ni(2+)-bound MmARD being the most stable, followed by Co(2+) and Fe(2+), and Mn(2+)-bound ARD being the least stable. Ni(2+)- and Co(2+)-bound MmARD were crystallized, and the structures of the two proteins found to be similar. Enzyme-ligand complexes provide insight into substrate binding, metal coordination, and the catalytic mechanism.

Empirical and Theoretical Insights into the Structural Features and Host–Guest Chemistry of M8L4 Tube Architectures

We demonstrate a general method for the construction of M8L4 tubular complexes via subcomponent self-assembly, starting from Cu(I) or Ag(I) precursors together with suitable elongated tetraamine and 2-formylpyridine subcomponents. The tubular architectures were often observed as equilibrium mixtures of diastereomers having two different point symmetries (D2d or D2 ⇄ D4) in solution. The equilibria between diastereomers were influenced through variation in ligand length, substituents, metal ion identity, counteranion, and temperature. In the presence of dicyanoaurate(I) and Au(I), the D4-symmetric hosts were able to bind linear Au(Au(CN)2)2(-) (with two different configurations) as the best-fitting guest. Substitution of dicyanoargentate(I) for dicyanoaurate(I) resulted in the formation of Ag(Au(CN)2)2(-) as the optimal guest through transmetalation. Density functional theory was employed to elucidate the host-guest chemistries of the tubes.

Quantum mechanical investigation of aqueous desferrioxamine B metal complexes: Trends in structure, binding, and infrared spectroscopy

A systematic density functional theory study supported by extended X-ray absorption fine structure (EXAFS) and infrared spectroscopic data was conducted to elucidate how structure and vibrational spectra of aqueous desferrioxamine B (DFOB) metal complexes vary with the metal ion identity. Structural parameters derived from EXAFS analyses and trends in metal binding constants are well reproduced and validated by the applied computational model. Vibrational mode analysis guides determination and recognition of crucial structure- and metal-sensitive infrared marker bands. The key marker bands, CO and CN stretching modes, dominate the infrared spectra in the 1400–1650cm−1 region. The modes are sensitive to the stability and size of the metal core (first coordination shell) and indicative of its deformation from the octahedral symmetry. The results shed light on the fundamental structural and electronic factors that control metal binding by siderophores, and drive their potentially rich and largely unexplored interactions with trace metals.