Metal Ion Dependence Research Articles

Unveiling the GT114 family: Structural characterization of A075L, a glycosyltransferase from Paramecium bursaria chlorella virus-1 (PBCV-1).

Protein A075L is a β-xylosyltransferase that participates in producing the core of the N-glycans found in VP54, the major viral capsid protein of Paramecium bursaria chlorella virus-1 (PBCV-1). In this study, we present an X-ray crystallographic analysis of the apo form of A075L, along with its complexes with the sugar donor and with a trisaccharide acceptor. The protein structure shows a typical GT-B folding, with two Rossmann-like fold domains, in which the acceptor substrate binds to the N-terminal region, and the nucleotide-sugar donor binds to the C-terminal region. We propose that the catalytic mechanism follows a direct displacement SN2-like reaction, where Asp73 serves as a catalytic base that deprotonates the incoming nucleophile of the acceptor, facilitating direct displacement of the UDP with the inversion of the anomeric configuration of the acceptor without metal ion dependence, while the interactions with side chains of Arg158 and Arg208 stabilize the developing negative charge. Using isothermal titration calorimetry, nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, and molecular dynamics simulations, the catalytic activity and specificity of this enzyme have been unraveled.

Structural and functional characterization of mycobacterial PhoH2 and identification of potential inhibitor of its enzymatic activity.

Mycobacterium tuberculosis is composed of a cumbersome signaling and protein network which partakes in bacterial survival and augments its pathogenesis. Mycobacterial PhoH2 (Mt-PhoH2) is a signaling element and a predictive phosphate starvation protein that works in an ATP-dependent manner. Here, we elaborated the characterization of Mt-PhoH2 through biophysical, biochemical, and computational methods. In addition to its intrinsic ATPase activity, the biochemical experiments revealed itsGTPase activity and both activities are metal iondependent. Magnesium, manganese, copper, iron, nickel, zinc, cesium, calcium, and lithium were examined for their effect on activity, and the optimum activity was found with 10 mM of Mg2+ ions. The kinetic parameters of 3 µM Mt-PhoH2 were observed as Km 4.873 ± 0.44 µM, Vmax 12.3817 ± 0.084 µM/min/mg, Kcat 0.0075 ± 0.00005 s-1, and Kcat/Km 0.0015 ± 0.000001 µM-1 s-1 with GTP. In the case of GTP as a substrate, a 20% decrease in enzymatic activity and a 50% increase in binding affinity of Mt-PhoH2 were observed. The substrates ADP and GDP inhibit the ATPase and GTPase activity of Mt-PhoH2. CD spectroscopy showed the dominance of alpha helix in the secondary structure of Mt-PhoH2, and this structural pattern was altered upon addition of ATP and GTP. In silico inhibitor screening revealed ML141 and NAV_2729 as two potential inhibitorsof the catalytic activity of Mt-PhoH2. Mt-PhoH2 is essential for mycobacterial growth as its knockdown strain showed a decreased growth effect. Overall, the present article emphasizes the factors essential for the proper functioning of Mt-PhoH2 which is a participant in the toxin-antitoxin machinery and may also play an important role in phosphate starvation.

Transition-Metal Isocorroles as Singlet Oxygen Sensitizers.

Building on a highly efficient synthesis of pyrrole-appended isocorroles, we have worked out conditions for manganese, palladium, and platinum insertion into free-base 5/10-(2-pyrrolyl)-5,10,15-tris(4-methylphenyl)isocorrole, H2[5/10-(2-py)TpMePiC]. Platinum insertion proved exceedingly challenging but was finally accomplished with cis-Pt(PhCN)2Cl2. All the complexes proved weakly phosphorescent in the near-infrared under ambient conditions, with a maximum phosphorescence quantum yield of 0.1% observed for Pd[5-(2-py)TpMePiC]. The emission maximum was found to exhibit a strong metal ion dependence for the 5-regioisomeric complexes but not for the 10-regioisomers. Despite the low phosphorescence quantum yields, all the complexes were found to sensitize singlet oxygen formation with moderate to good efficiency, with singlet oxygen quantum yields ranging over 21-52%. With significant absorption in the near-infrared and good singlet oxygen-sensitizing ability, metalloisocorroles deserve examination as photosensitizers in the photodynamic therapy of cancer and other diseases.

Ion Mobility and Fourier Transform Ion Cyclotron Resonance Collision Cross Section Techniques Yield Long-Range and Hard-Sphere Results, Respectively.

We determined collision cross section (CCS) values for singly and doubly charged cucurbit[n]uril (n = 5-7), decamethylcucurbit[5]uril, and cyclohexanocucurbit[5]uril complexes of alkali metal cations (Li+-Cs+). These hosts are relatively rigid. CCS values calculated using the projection approximation (PA) for computationally modeled structures of a given host are nearly identical for +1 and +2 complexes, with weak metal ion dependence, whereas trajectory method (TM) calculations of CCS for the same structures consistently yield values 7-10% larger for the +2 complexes than for the corresponding +1 complexes and little metal ion dependence. Experimentally, we measured relative CCS values in SF6 for pairs of +1 and +2 complexes of the cucurbituril hosts using the cross-sectional areas by Fourier transform ion cyclotron resonance ("CRAFTI") method. At center-of-mass collision energies <∼30 eV, CRAFTI CCS values are sensitive to the relative binding energies in the +1 and +2 complexes, but at collision energies >∼40 eV (sufficient that ion decoherence occurs on essentially every collision) that dependence is not evident. Consistent with the PA calculations, these experiments found that the +2 complex ions have CCS values ranging between 94 and 105% of those of their +1 counterparts (increasing with metal ion size). In contrast, but consistent with the TM CCS calculations, ion mobility measurements of the same complexes at close to thermal energies in much less polarizable N2 find the CCS of +2 complexes to be in all cases 9-12% larger than those of the corresponding +1 complexes, with little metal ion dependence.

Folic acid-modified disulfiram/Zn-IRMOF3 nanoparticles for oral cancer therapy by inhibiting ALDH1A1+ cancer stem cells

The repurposing of old drugs can reduce the cost of drug development and speed up the availability of drugs for clinical use. Disulfiram (DSF) is an approved drug for alcohol abuse. In recent years, it has been established that DSF exerts an antitumor effect via targeted inhibition of ALDH1+ cancer stem cells (CSCs). However, due to its metal ion dependence, easy hydrolysis and low availability, the clinical application of DSF is limited. Previous studies have also shown that Zn2+ can inhibit CSCs. Accordingly, we developed a novel metal organic framework (IRMOF3)-Zn2+, and DSF was incorporated in the IRMOF3. Folic acid (FA) was subsequently loaded on the surface yielding IRMOF3 (IRMOF3-DSF-FA) for targeted therapy of tumors. The nanoscale IRMOF3-DSF-FA exhibited a high loading capacity, good biocompatibility and strong cell uptake capacity, which could provide metal ions, target tumor tissues and inhibit ALDH1+ CSCs. In vivo experiments showed that IRMOF3-DSF-FA could significantly inhibit the growth of CSCs and tumors, with no significant vital organ damage during treatment. Accordingly, IRMOF3-DSF-FA has great prospects for application as a DSF carrier, opening new horizons for targeted therapy of oral cancer.

Functional Characterisation of Two Novel Deacetylases from Streptococcus pyogenes

Streptococcus pyogenes (Group A Streptococcus, GAS) is an exclusively human pathogen that causes a wide range of diseases. We have identified two novel proteins, Spy1094 and Spy1370, which show sequence similarity with peptidoglycan deacetylases (PGDAs) from other streptococcal species like S. pneumoniae and S. iniae, that represent important virulence factors. Recombinant Spy1094 and Spy1370 were active at a wide pH range (pH 4.0–9.0) and showed metal ion-dependence, with the highest activities observed in the presence of Mn2+, Mg2+and Zn2+. The enzymes showed typical Michaelis–Menten saturation kinetics with the pseudo-substrate GlcNAc3. Binding affinities for rSpy1094 and rSpy1370 were high (Km = 2.2 ± 0.9 μM and 3.1 ± 1.1 μM, respectively), but substrate turnover was low (Kcat = 0.0075/s and 0.0089/s, respectively) suggesting that peptidoglycan might not be the preferred target for deacetylation. Both enzymes were expressed during bacterial growth.

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.

Metal(II) Ion Dependence of the Structures and Properties of Square-Grid Coordination Polymers of Tetrabromobenzenedicarboxylate and Pyrazine as Bridging Ligands

Abstract In this study, we report the synthesis and crystal structures of coordination polymers employing tetrabromobenzenedicarboxylate (Br4bdc2−) and pyrazine (pyz). Uncoordinated pyz molecules are stabilized between the layers by both hydrogen H-bonding and π–π stacking interactions in [M(Br4bdc)(pyz)(H2O)2](pyz), where M = Co(II) and Zn(II). In addition, water molecules are incorporated between the layers in [Cu(Br4bdc)(pyz)(H2O)2](H2O) owing to Jahn–Teller distortion of the Cu(II) ions, which prevents π–π stacking interactions between the pyz and Br4bdc2−. Depending on the metal(II) centers, structural changes that occur during the heating and hydration processes exhibit different behavior. Co(II) compound slowly changes structure by heating and rapidly recovers the crystalline state in air. Conversely, Zn(II) compound assumes the amorphous phase by heating and slowly yields the crystalline phase in ambient conditions. Although the Cu(II) compound also shows structural changes by heating, the dehydrated phase exhibits hydrophobic characteristics. Ion conductivity measurements of the as-synthesized forms show conductivities of 1.9 × 10−6 Scm−1, 4.6 × 10−7 Scm−1, and 1.3 × 10−6 Scm−1, for the Co(II), Zn(II), and Cu(II) complexes at 90 °C and 95% relative humidity (RH), respectively. The relatively low values of the as-synthesized Co(II) and Zn(II) compounds are attributed to the H-bonding interaction and π–π stacking of pyz molecules, which prevent the dynamics of the pyz molecules needed for proton conduction.

A new Pb2+-specific DNAzyme by revisiting the catalytic core of 10–23 DNAzyme

10–23 DNAzyme is a catalytic DNA molecule from in vitro selection, the 15-mer catalytic core was investigated for more DNAzyme variants by block deletions. DNAzyme DZM01 was selected with metal ion dependence of Pb2+ ≫ Mn2+, with no activity in the presence of Mg2+ (20 mM), Ca2+ (20 mM), Zn2+ (20 mM, pH 6). The unique binding properties of Pb2+ with nucleic acids might be responsible for the formation of the catalytic core, which is different from that of other divalent metal ions. More DNAzyme variants are expected to be derived for specific metal ion dependence by various nucleobase sequences and modifications.

Natural Catalytic IgGs Hydrolyzing Histones in Schizophrenia: Are They the Link between Humoral Immunity and Inflammation?

Schizophrenia is known to be accompanied not only with an imbalance in the neurotransmitter systems but also with immune system dysregulation and chronic low-grade inflammation. Extracellular histones and nucleosomes as damage-associated molecular patterns (DAMPs) trigger systemic inflammatory and toxic reactions by activating Toll-like receptors. In this work, we obtained the first evidence that polyclonal IgGs of patients with schizophrenia effectively hydrolyze five histones (H1, H2a, H2b, H3, and H4). Several strict criteria were used to demonstrate that histone-hydrolyzing activity is a property of the analyzed IgGs. The IgGs histone-hydrolyzing activity level, depending on the type of histone (H1–H4), was statistically significantly 6.1–20.2 times higher than that of conditionally healthy donors. The investigated biochemical properties (pH and metal ion dependences, kinetic characteristics) of these natural catalytic IgGs differed markedly from canonical proteases. It was previously established that the generation of natural catalytic antibodies is an early and clear sign of impaired humoral immunity. One cannot, however, exclude that histone-hydrolyzing antibodies may play a positive role in schizophrenia pathogenesis because histone removal from circulation or the inflamed area minimizes the inflammatory responses. Thus, it can be assumed that histone-hydrolyzing antibodies are a link between humoral immunity and inflammatory responses in schizophrenia.

Different Inhibitors of Aβ42-Induced Toxicity Have Distinct Metal-Ion Dependency.

Oligomers of amyloid β-protein (Aβ) are thought to be the proximal toxic agents initiating the neuropathologic process in Alzheimer's disease (AD). Therefore, targeting the self-assembly and oligomerization of Aβ has been an important strategy for designing AD therapeutics. In parallel, research into the metallobiology of AD has shown that Zn2+ can strongly modulate the aggregation of Aβ in vitro and both promote and inhibit the neurotoxicity of Aβ, depending on the experimental conditions. Thus, successful inhibitors of Aβ self-assembly may have to inhibit the toxicity not only of Aβ oligomers themselves but also of Aβ-Zn2+ complexes. However, there has been relatively little research investigating the effects of Aβ self-assembly and toxicity inhibitors in the presence of Zn2+. Our group has characterized previously a series of Aβ42 C-terminal fragments (CTFs), some of which have been shown to inhibit Aβ oligomerization and neurotoxicity. Here, we asked whether three CTFs shown to be potent inhibitors of Aβ42 toxicity maintained their activity in the presence of Zn2+. Biophysical analysis showed that the CTFs had different effects on oligomer, β-sheet, and fibril formation by Aβ42-Zn2+ complexes. However, cell viability experiments in differentiated PC-12 cells incubated with Aβ42-Zn2+ complexes in the absence or presence of these CTFs showed that the CTFs completely lost their inhibitory activity in the presence of Zn2+ even when applied at 10-fold excess relative to Aβ42. In light of these results, we tested another inhibitor, the molecular tweezer CLR01, which coincidentally had been shown to have a high affinity for Zn2+, suggesting that it could disrupt both Aβ42 oligomerization and Aβ42-Zn2+ complexation. Indeed, we found that CLR01 effectively inhibited the toxicity of Aβ42-Zn2+ complexes. Moreover, it did so at a lower concentration than needed for inhibiting the toxicity of Aβ42 alone. In agreement with these results, CLR01 inhibited β-sheet and fibril formation in Aβ42-Zn2+ complexes. Our data suggest that, for the development of efficient therapeutic agents, inhibitors of Aβ self-assembly and toxicity should be examined in the presence of relevant metal ions and that molecular tweezers may be particularly attractive candidates for therapy development.

Functionalization of 8-17 DNAzymes modulates catalytic efficiency and divalent metal ion preference.

8-17 and 17E DNAzyme are being explored as biosensors for metal ions and RNA motifs of interest, more sensitive and efficient DNAzymes are required to meet the practical applications. Their similarity in the catalytic cores and differences in catalytic efficiency and metal ion dependence initiated great interest about the contribution of the catalytic residues. Functionalization of four adenine residues in the catalytic cores of 8-17 DNAzyme and 17E was conducted with amino, guanidinium, and imidazolyl groups. In the bulge loops of 8-17 and 17E, N6-(3-aminopropyl)-2'-deoxyadenosine (residue 1) at A15 led to new DNAzymes 8-17DZ-A15-1 and 17E-A15-1, with much more efficient cleavage ability in the Ca2+-mediated reaction and the greater preference for Ca2+ over Mg2+ than 8-17 DNAzyme and 17E, respectively, especially with a concentration-dependent increase of the selectivity, which is different from most DNAzymes with the similar dependence on both Mg2+ and Ca2+. With this kind of post-selection modification on 8-17 DNAzymes, for the first time, the catalytic efficiency and metal ion selectivity could be positively modulated. It is also helpful for the catalyic mechanistic studies of these DNAzymes, especially, the role of the unconserved A15 should be emphasized.

PynA is a pyrimidine 5'-nucleotidase that functions as an antimutator protein in Streptococcuspneumoniae.

Streptococcuspneumoniae is a Gram-positive bacterium that is a major agent of community-acquired bacterial pneumonia, meningitis and sepsis. Although the mismatch repair function of S.pneumoniae has been assigned to the hexA-hexB gene products, an enzyme capable of the direct elimination of noncanonical nucleotides from the cytoplasm has not been described for this bacterium. Our results show that Spr1057, a protein with previously unknown function, is involved in the inactivation of mutagenic pyrimidine nucleotides and was accordingly designated PynA (pyrimidine nucleotidase A). Biochemical assays confirmed the phosphatase activity of the recombinant enzyme and revealed its metal ion dependence for optimal enzyme activity. We demonstrated that PynA forms a homodimer with higher invitro activity towards noncanonical 5-fluoro-2'-deoxyuridine monophosphate than towards canonical thymidine monophosphate. Furthermore, we showed via invivo assays that PynA protects cells against noncanonical pyrimidine derivatives such as 5-fluoro-2'-deoxyuridine and prevents the incorporation of the potentially mutagenic 5-bromo-2'-deoxyuridine (5-BrdU) into DNA. Fluctuation analysis performed under S.pneumoniae exposure to 5-BrdU revealed that the pynA null strain accumulates random mutations with high frequency, resulting in a 30-fold increase in the mutation rate. The data support a model in which PynA, a protein conserved in other Gram-positive bacteria, functions as a house-cleaning enzyme by selectively eliminating noncanonical nucleotides and maintaining the purity of dNTP pools, similar to the YjjG protein described for Escherichiacoli.

Ppn2 endopolyphosphatase overexpressed in Saccharomyces cerevisiae: Comparison with Ppn1, Ppx1, and Ddp1 polyphosphatases

Saccharomyces cerevisiae has high level of inorganic polyphosphate and a multicomponent system of its metabolism, including polyphosphatases Ppx1, Ppn1, Ddp1, and Ppn2.The aim of the study was to construct the yeast strain overexpressing Ppn2 and to compare the properties of Ppn2, Ppx1, Ppn1, and Ddp1 purified from overexpressing strains of S. cerevisiae. We overexpressed Ppn2 in S. cerevisiae under a strong constitutive promoter of the yeast glyceraldehyde-3-phosphate dehydrogenase-encoding gene and suggested biochemical criteria for distinguishing among yeast polyphosphatases, which is important for their identification and understanding of their functions. Ppn2, Ppn1, and Ddp1 had endopolyphosphatase activities, whereas Ppx1 did not. Ppx1 and Ppn1 exhibited high and Ddp1 and Ppn2 low exopolyphosphatase activity: 240, 500, 0.05 and 0.1 U/mg protein, respectively. The enzymes had distinct patterns of exopolyphosphatase activities stimulation by divalent metal ions. Ppn2, Ppn1 and Ddp1 displayed endopolyphosphatase activity in the presence of 1 mM Mg2+. The endopolyphosphatase activities of Ppn2 and Ppn1 were induced by 0.01 mM of Co2+ or Zn2+, whereas that of Ddp1 required 0.1 mM of these cations. The endopolyphosphatase activity of Ppn1 was inhibited by 0.01 mg mL−1 of heparin, while endopolphosphatase activity of Ppn2 was weakly sensitive to 0.25 mg mL−1 of heparin. The Ppx1 and Ppn1 activity with guanosine tetraphosphate was nearly 80% of activity with long-chain polyphosphates. The Ppn1 hydrolyzed dATP, while Ppx1 did not. The differences in the mode of polyphosphate hydrolysis, substrate specificity, metal ion dependence and cell localization suggest distinct roles of these enzymes in yeast.

Purification, Characterization and Degradation Performance of a Novel Dextranase from Penicillium cyclopium CICC-4022.

A novel dextranase was purified from Penicillium cyclopium CICC-4022 by ammonium sulfate fractional precipitation and gel filtration chromatography. The effects of temperature, pH and some metal ions and chemicals on dextranase activity were investigated. Subsequently, the dextranase was used to produce dextran with specific molecular mass. Weight-average molecular mass (Mw) and the ratio of weight-average molecular mass/number-average molecular mass, or polydispersity index (Mw/Mn), of dextran were measured by multiple-angle laser light scattering (MALS) combined with gel permeation chromatography (GPC). The dextranase was purified to 16.09-fold concentration; the recovery rate was 29.17%; and the specific activity reached 350.29 U/mg. Mw of the dextranase was 66 kDa, which is similar to dextranase obtained from other Penicillium species reported previously. The highest activity was observed at 55 °C and a pH of 5.0. This dextranase was identified as an endodextranase, which specifically degraded the α-1,6 glucosidic bonds of dextran. According to metal ion dependency tests, Li+, Na+ and Fe2+ were observed to effectively improve the enzymatic activity. In particular, Li+ could improve the activity to 116.28%. Furthermore, the dextranase was efficient at degrading dextran and the degradation rate can be well controlled by the dextranase activity, substrate concentration and reaction time. Thus, our results demonstrate the high potential of this dextranase from Penicillium cyclopium CICC-4022 as an efficient enzyme to produce specific clinical dextrans.

Insights into Catalytic and tRNA Recognition Mechanism of the Dual-Specific tRNA Methyltransferase from Thermococcus kodakarensis.

The tRNA methyltransferase Trm10, conserved throughout Eukarya and Archaea, catalyzes N1-methylation of purine residues at position 9 using S-adenosyl methionine as the methyl donor. The Trm10 family exhibits diverse target nucleotide specificity, with some homologs that are obligate m1G9 or m1A9-specific enzymes, while others are bifunctional enzymes catalyzing both m1G9 and m1A9. This variability is particularly intriguing given different chemical properties of the target N1 atom of guanine and adenine. Here we performed an extensive kinetic and mutational analysis of the m1G9 and m1A9-catalyzing Trm10 from Thermococcus kodakarensis to gain insight into the active site that facilitates this unique bifunctionality. These results suggest that the rate-determining step for catalysis likely involves a conformational change to correctly position the substrate tRNA in the active site. In this model, kinetic preferences for certain tRNA can be explained by variations in the overall stability of the folded substrate tRNA, consistent with tRNA-specific differences in metal ion dependence. Together, these results provide new insight into the substrate recognition, active site and catalytic mechanism of m1G/m1A catalyzing bifunctional enzymes.

Purification and Characterization of a Biofilm-Degradable Dextranase from a Marine Bacterium.

This study evaluated the ability of a dextranase from a marine bacterium Catenovulum sp. (Cadex) to impede formation of Streptococcus mutans biofilms, a primary pathogen of dental caries, one of the most common human infectious diseases. Cadex was purified 29.6-fold and had a specific activity of 2309 U/mg protein and molecular weight of 75 kDa. Cadex showed maximum activity at pH 8.0 and 40 °C and was stable at temperatures under 30 °C and at pH ranging from 5.0 to 11.0. A metal ion and chemical dependency study showed that Mn2+ and Sr2+ exerted positive effects on Cadex, whereas Cu2+, Fe3+, Zn2+, Cd2+, Ni2+, and Co2+ functioned as inhibitors. Several teeth rinsing product reagents, including carboxybenzene, ethanol, sodium fluoride, and xylitol were found to have no effects on Cadex activity. A substrate specificity study showed that Cadex specifically cleaved the α-1,6 glycosidic bond. Thin layer chromatogram and high-performance liquid chromatography indicated that the main hydrolysis products were isomaltoogligosaccharides. Crystal violet staining and scanning electron microscopy showed that Cadex impeded the formation of S. mutans biofilm to some extent. In conclusion, Cadex from a marine bacterium was shown to be an alkaline and cold-adapted endo-type dextranase suitable for development of a novel marine agent for the treatment of dental caries.

Metal organic frameworks as a catalyst for oxygen reduction: an unexpected outcome of a highly active Mn-MOF-based catalyst incorporated in activated carbon.

Owing to their unique chemistry and physical properties, metal-organic frameworks (MOFs) are an interesting class of materials which can be utilized for a wide array of applications. MOFs have been proposed to be used as catalysts for fuel cells, but their low intrinsic electronic conductivity hampered their utilization as is. In this work, we present the synthesis and application of MOF-based precious-metal-group-free (PGM-free) catalysts for oxygen reduction based on a unique metal-organic framework-carbon composite material. Benzene tricarboxylic acid-based MOFs were synthesized inside activated carbon (AC) with four different, first row transition metals: Mn, Fe, Co, and Cu. The MOFs@AC were analyzed electrochemically to measure their catalytic activity. Further physical and chemical characterization studies are performed to measure the material properties. The MOFs@AC are found to be conductive and active catalysts for the oxygen reduction reaction in an alkaline environment. Surprisingly, the Mn-MOF-based@AC exhibits the best performance with an onset potential of 0.9 V vs. RHE and the almost four-electron mechanism, as opposed to most other known PGM-free catalysts, which show Fe and Co as the most active metals.

Toward separation of hydrogen isotopologues by exploiting zero‐point energy difference at strongly attractive adsorption site models

AbstractRecent reports on hydrogen isotope separation in metal‐organic frameworks are rationalized by the presence of undercoordinated metal sites. In this work, we screen undercoordinated divalent metals for their performance as hydrogen separating agents in common chemical environments (as free dications, as part of M2(HCOO)4 paddlewheels and in metal porphyrins). We calculate heat of adsorption and selectivity using the Langmuir model and the density‐functional‐based potential energy surface. Our calculations show a strong metal ion dependence of the adsorption energy in paddlewheels, but rather small impact of metal choice in stable porphyrins. D2‐over‐H2 selectivities reach top values of 12 for paddlewheels, while only oxidatively unstable porphyrins incorporating Cr2+, V2+, and Ti2+ show high selectivities.

Analysis of plant UDP-arabinopyranose mutase (UAM): Role of divalent metals and structure prediction

UDP-arabinopyranose mutase (UAM) is a plant enzyme which interconverts UDP-arabinopyranose (UDP-Arap; a six-membered sugar) to UDP-arabinofuranose (UDP-Araf; a five-membered sugar). Plant mutases belong to a small gene family called Reversibly Glycosylated Proteins (RGPs). So far, UAM has been identified in Oryza sativa (Rice), Arabidopsis thaliana and Hordeum vulgare (Barley). The enzyme requires divalent metal ions for catalytic activity. Here, the divalent metal ion dependency of UAMs from O. sativa (rice) and A. thaliana have been studied using HPLC-based kinetic assays. It was determined that UAM from these species had the highest relative activity in a range of 40–80μM Mn2+. Excess Mn2+ ion concentration decreased the enzyme activity. This trend was observed when other divalent metal ions were used to test activity. To gain a perspective of the role played by the metal ion in activity, an ab initio structural model was generated based on the UAM amino acid sequence and a potential metal binding region was identified. Based on our results, we propose that the probable role of the metal in UAM is stabilizing the diphosphate of the substrate, UDP-Arap.