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Recent years have seen an increase in the development of computational proteins, including symmetric ones. A ninefold-symmetric β-propeller protein named Cake has recently been developed. Here, attempts were made to further engineer this protein into a threefold-symmetric nine-bladed propeller using computational design. Two nine-bladed propeller proteins were designed, named Scone-E and Scone-R. Crystallography, however, revealed the structure of both designs to adopt an eightfold conformation with distorted termini, leading to a pseudo-symmetric protein. One of the proteins could only be crystallized upon the addition of a polyoxometalate, highlighting the usefulness of these molecules as crystallization additives. keywords: protein design, polyoxometalates, [beta]-propeller, symmetry, Scone ispartof: ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY vol:77 issue:Pt 7 pages:933-942 ispartof: location:United States status: published

The controlled formation of protein supramolecular assemblies is challenging, but it could provide an important route for the development of hybrid biomaterials. In this work, we demonstrate the fo...

Paramagnetic Lanthanide ions incorporated into nano- architectures are emerging as a versatile platform for Magnetic Resonance Imaging (MRI) contrast agents due to their strong contrast enhancement effects combined with the platform capability to include multiple imaging modalities. This short review examines the application of lanthanide based nanoarchitectures (nanoparticles and nano- assemblies) in the development of multifunctional probes for single and multimodal imaging involving high field MRI as one imaging modality. ispartof: CURRENT MEDICINAL CHEMISTRY vol:27 issue:3 pages:352-361 ispartof: location:United Arab Emirates status: published

Structural parameters influencing the reactivity of metal-organic frameworks (MOF) are challenging to establish. However, understanding their effect is crucial to further develop their catalytic potential. Here, we uncovered a correlation between reaction kinetics and the morphological structure of MOF-nanozymes using the hydrolysis of a dipeptide under physiological pH as model reaction. Comparison of the activation parameters in the presence of NU-1000 with those observed with MOF-808 revealed the reaction outcome is largely governed by the Zr6 cluster. Additionally, its structural environment completely changes the energy profile of the hydrolysis step, resulting in a higher energy barrier ΔG ‡ for NU-1000 due to a much larger ΔS ‡ term. The reactivity of NU-1000 towards a hen egg white lysozyme protein under physiological pH was also evaluated, and the results pointed to a selective cleavage at only 3 peptide bonds. This showcases the potential of Zr-MOFs to be developed into heterogeneous catalysts for non-enzymatic but selective transformation of biomolecules, which are crucial for many modern applications in biotechnology and proteomics. ispartof: CHEMICAL SCIENCE vol:11 issue:26 pages:6662-6669 ispartof: location:England status: published

The ability of soluble metal-oxo clusters to specifically interact with protein surfaces makes them attractive as potential inorganic drugs and as artificial enzymes. In particular, metal-substituted polyoxometalates (MS-POMs) are remarkably selective in hydrolyzing a range of different proteins. However, the influence of MS-POMs' redox chemistry on their proteolytic activity remains virtually unexplored. Herein we report a highly site-selective hydrolysis of hemoglobin (Hb), a large tetrameric globular protein, by a Ce(iv)-substituted Keggin polyoxometalate (CeIVK), and evaluate the effect of CeIVK's redox chemistry on its reactivity and selectivity as an artificial protease. At pH 5.0, incubation of Hb with CeIVK resulted in strictly selective protein hydrolysis at six Asp-X bonds, two of which were located in the α-chain (α(Asp75-Leu76) and α(Asp94-Pro95)) and five at the β-chain (β(Asp51-Ala52), β(Asp68-Ser69), β(Asp78-Asp79), β(Asp98-Pro99) and β(Asp128-Phe129)). However, increasing the pH of the reaction mixture to 7.4 decreased the CeIVK hydrolytic reactivity towards Hb, resulting in the cleavage of only one peptide bond (β(Asp128-Phe129)). Combination of UV-Vis, circular dichroism and Trp fluorescence spectroscopy indicated similar interactions between Hb and CeIVK at both pH conditions; however, 31P NMR spectroscopy showed faster reduction of CeIVK into the hydrolytically inactive CeIIIK form in the presence of protein at pH 7.4. In agreement with these results, careful mapping of all hydrolyzed Asp-X bonds on the protein structure revealed that the lower reactivity toward the α-chain was consistent with the presence of more redox-active amino acids (Tyr and His) in this subunit in comparison with the β-chain. This points towards a link between the presence of the redox-active sites on the protein surface and efficiency and selectivity of redox-active MS-POMs as artificial proteases. More importantly, the study provides a way to tune the redox and hydrolytic reactivity of MS-POMs towards proteins through adjustment of reaction parameters like temperature and pH., The redox chemistry of CeIV-polyoxometalates towards proteins is linked to the redox-active residues on protein surface. It can be tuned by adjusting reaction parameters, directly impacting its efficiency and selectivity as an artificial protease.

Materials with enzyme-like activities and proteolytic potential are emerging as a robust and effective alternative to natural enzymes. Herein, a Hf6O8-based NU-1000 metal organic framework (Hf-MOF) is shown to act as a heterogeneous catalyst for the hydrolysis of peptide bonds under mild conditions. In the presence of Hf-MOF, a glycylglycine model dipeptide was hydrolysed with a rate constant of kobs = 8.33 × 10-7 s-1 (half-life (t1/2) of 231 h) at 60 °C and pD 7.4, which is significantly faster than the uncatalyzed reaction. Other Gly-X peptides (X = Ser, Asp, Ile, Ala, and His) were also smoothly hydrolysed under the same conditions with similar rates, except for the faster reactions observed for Gly-His and Gly-Ser. Moreover, the Hf6O8-based NU-1000 MOF also exhibits a high selectivity in the cleavage of a protein substrate, hen egg white lysozyme (HEWL). Our results suggest that embedding Hf6O8 oxo-clusters is an efficient strategy to conserve the hydrolytic activity while smoothing the strong substrate adsorption previously observed for a discrete Hf oxo-cluster that hindered further development of its proteolytic potential. Furthermore, comparison with isostructural Zr-NU-1000 shows that although the Hf variant afforded the same cleavage pattern towards HEWL but slightly slower reaction rates, it exhibited a larger stability window and a better recyclability profile. The results suggest that these differences originate from the intrinsic differences between HfIV and ZrIV centers, and from the lower surface area of Hf-NU-1000 in comparison to Zr-NU-1000. ispartof: NANOSCALE vol:13 issue:28 pages:12298-12305 ispartof: location:England status: published

Single-type, 6-fold symmetrically grooved, and commercially accessible interlocking disks (ILDs) have been used for modeling of sp2 hybridized carbon-based nanoarchitectures and complex polyhedral and reticular material models. In the case of the carbon-based nanoarchitectures, we showcase that the primary ILDs can be directly used for representing individual atoms and bonds. Further on, the spatial connectivity of the primary ILDs can be extended by assembly of symmetrical secondary building units (SBUs). The constructed (deci)meter scale models are robust, light, scalable, and suitable for classroom demonstrations. The ILD technique is also suitable for use in workshops for facile discovery-based learning of nanomolecular structure, showing promise for wider use in the chemistry curriculum.

A simple, safe and inexpensive amide bond formation directly from non-activated carboxylic acids and free amines is presented in this work. Readily available Zr(IV)- and Hf(IV)-substituted polyoxometalates (POM) are shown to be excellent catalysts for the amide bond formation reaction under mild conditions, low catalyst loading, and without the use of water scavengers, dry solvents, additives for facilitating the amine attack, or specialized experimental setups commonly employed to remove water. Detailed mechanistic investigations revealed the key role of polyoxometalate scaffolds which act as inorganic ligands to protect Zr(IV) and Hf(IV) Lewis acidic metals against hydrolysis, and preserve their catalytic activity in amide bond formation reactions. The new catalysts are compatible with a range of functional groups and heterocycles useful for medicinal, agrochemical and material chemists. The robustness of the Lewis acid-polyoxometalate complexes is further supported by the catalyst reuse without loss of activity. This prolific combination of Zr(IV)/Hf(IV) and polyoxometalates inaugurates a powerful class of catalysts for the amide bond formation, which overcomes key limitations of previously established Zr(IV)/Hf(IV) salts and boron based catalysts. ispartof: Acs Catalysis vol:9 issue:11 pages:10245-10252 status: published

Contrast agents for magnetic resonance imaging have historically been based on paramagnetic metal complexes, particularly Gd3+ chelates, which tend to lose their contrast enhancement ability with increasing magnetic field strength. Emerging high-field MRI applications require the development of novel contrast agents that exhibit high relaxation enhancement as a function of magnetic field strength. Paramagnetic ions such as Dy3+ , Tb3+ or Ho3+ incorporated into supramolecular or inorganic nano-architectures represent promising platforms for the development of high field MRI contrast agents. Furthermore, such platforms allow facile inclusion of multiple imaging modalities, therapeutic loading, and targeting vectors. This Minireview examines the application of contrast agents for high-field MRI, which range from single molecules to nanoparticles. Approaches to create multimodal agents by combining high-field MRI contrast properties with another imaging modality are also discussed. ispartof: CHEMISTRY-A EUROPEAN JOURNAL vol:25 issue:61 pages:13838-13847 ispartof: location:Germany status: published

Mixed micelles based on amphiphilic gadolinium(III)-DOTA and europium(III)-DTPA complexes were synthesized and evaluated for their paramagnetic and optical properties as potential bimodal contrast agents. Amphiphilic folate molecule for targeting the folate receptor protein, which is commonly expressed on the surface of many human cancer cells, was used in the self-assembly process in order to create nanoaggregates with targeting properties. Both targeted and nontargeted nanoaggregates formed monodisperse micelles having distribution maxima of 10 nm. The micelles show characteristic europium(III) emission with quantum yields of 2% and 1.1% for the nontargeted and targeted micelles, respectively. Fluorescence microscopy using excitation at 405 nm and emission at 575-675 nm was employed to visualize the nanoaggregates in cultured HeLa cells. The uptake of folate-targeted and nontargeted micelles is already visible after 5 h of incubation and was characterized with the europium(III) emission, which is clearly observable in the cytoplasm of the cells. The very fast longitudinal relaxivity r

Materials which synergistically combine Lewis and Bronsted acid properties hold potential for applications as efficient heterogeneous catalysts for preparation of biofuels and biolubricants. Herein we report new heterogeneous catalysts based on grafting the intact Lewis metal (ZrIV) substituted Keggin polyoxometalate (POM) on mesoporous silica support. A new approach for immobilization of the POM in MCM-41 silica was developed by co-condensation of Si source (tetraethyl orthosilicate, TEOS) with POM salt in the presence of a template molecule as an alternative to the commonly used acidic POM form and impregnation procedure for catalyst preparation. The proposed synthesis method in combination with extraction of the template proceeded with preservation of the intact POM structure and resulted in hybrid catalysts with in situ generated Bronsted acid sites in addition to the Lewis acidity provided by the metal centers. Textural properties of the catalysts were characterized by X-ray diffraction, N2 physisorption and transmission electron microscopy (TEM). Insight into POM stability and structural transformations during synthesis, template removal and impregnation was provided by solid state 31P and 29Si NMR spectroscopy. Catalytic activity was studied in esterification reactions of levulinic acid with ethanol or octanol to value-added esters. The directly synthesized POM-functionalized hybrid catalysts exceeded the post synthesis impregnated ones, demonstrating significantly higher catalytic activity, recyclability and resistance against leaching. The proposed approach for immobilization of Lewis metal POMs in MCM-41 silica framework with in situ generation of the active Bronsted acid sites opens prospects for the development of efficient hybrid catalysts for esterification reaction, which overcomes the main limitations of common POM based catalysts such as low stability of the acid sites during the synthesis and the catalytic reaction, low surface area, agglomeration of the catalytically active phase and low stability of the Lewis metal center in presence of water.

Efficient and selective hydrolysis of inert peptide bonds is of paramount importance. MOF-808, a metal-organic framework based on Zr6 nodes, can hydrolyze peptide bonds efficiently under biologically relevant conditions. However, the details of the catalyst structure and of the underlying catalytic reaction mechanism are challenging to establish. By means of DFT calculations we first investigate the speciation of the Zr6 nodes and identify the nature of ligands that bind to the Zr6O8H4-x core in aqueous conditions. The core is predicted to strongly prefer a Zr6O8H4 protonation state and to be predominantly decorated by bridging formate ligands, giving Zr6(μ3-O)4(μ3-OH)4(BTC)2(HCOO)6 and Zr6(μ3-O)4(μ3-OH)4(BTC)2(HCOO)5(OH)(H2O) as the most favorable structures at physiological pH. The GlyGly peptide can bind MOF in several different ways, with the preferred structure involving coordination through the terminal carboxylate analogously to the binding mode of formate ligand. The pre-reactive binding mode in which the amide carbonyl oxygen coordinates the metal core lies 7 kcal higher in free energy. The preferred reaction pathway is predicted to have two close-lying transition states, either of which could be the rate-determining step: nucleophilic attack on the amide carbon atom and C-N bond breaking, with calculated relative free energies of 31 and 32 kcal mol-1, respectively. Replacement of formate by water and hydroxide at the Zr6 node is predicted to be possible, but does not appear to play a role in the hydrolysis mechanism. ispartof: PHYSICAL CHEMISTRY CHEMICAL PHYSICS vol:22 issue:43 pages:25136-25145 ispartof: location:England status: published

The development of artificial proteases is challenging, but important for many applications in modern proteomics and biotechnology. The hydrolysis of hydrophobic or unstructured proteins is particularly difficult due to their poor solubility, which often requires the presence of surfactants. Herein, it is shown that a zirconium(IV)-substituted Keggin polyoxometalate (POM), (Et2 NH2 )10 [Zr(α-PW11 O39 )2 ] (1), is able to selectively hydrolyze β-casein, which is an intrinsically unstructured protein at pH 7.4 and 60 °C. Four surfactants (sodium dodecyl sulfate (SDS), N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (ZW3-12), 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), and polyethylene glycol tert-octylphenyl ether (TX-100)), which differ in the nature of their polar groups, were investigated for their role in influencing the selectivity and efficiency of protein hydrolysis. Under experimental conditions, β-casein forms micellar structures in which the hydrophilic part of the protein is water accessible and able to interact with 1. Identical fragmentation patterns of β-casein in the presence of 1 were observed through SDS poly(acrylamide) gel electrophoresis both in the presence and absence of surfactants, but the rate of hydrolysis varied, depending on the nature of surfactant. Whereas TX-100 surfactant, which has a neutral polar head, caused only a slight decrease in the hydrolysis rate, stronger inhibition was observed in the presence surfactants with charges in their polar heads (CHAPS, ZW3-12, SDS). These results were consistent with those of tryptophan fluorescencequenching studies, which showed that the binding between β-casein and 1 decreased with increasing repulsion between the POM and the polar heads of the surfactants. In all cases, the micellar structure of β-casein was not significantly affected by the presence of POM or surfactants, as indicated by circular dichroism spectroscopy. ispartof: CHEMISTRY-A EUROPEAN JOURNAL vol:26 issue:49 pages:11170-11179 ispartof: location:Germany status: published

The reactivity of a range of Keggin and Wells-Dawson type heteropolyacids (HPAs): H3 PW12 O40 H4 SiW12 O40 , H3 PMo12 O40 , K6 P2 W18 O62 , and NaH2 W12 O4 , towards the heavily glycosylated α-1-acid glycoprotein (AGP) is reported. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) show that after incubation of the protein with HPAs at 80 °C and pH 2.8 complete hydrolysis of terminal glycosidic bond has been achieved, resulting in the removal of sialic acids with no observed destruction of the protein core or the residual glycan chains. The 1 H NMR spectroscopy confirmed that the released sialic acids preserve intact structure upon their excision from the protein, which makes the reported method suitable for the analysis of sialic acid modifications which play an important role in numerous biological processes. The presence of other sugars was not detected by 1 H NMR and HPAEC-PAD, suggesting that HPAs hydrolyze only the terminal glycosidic bond in the glycoprotein, resulting in the selective release of sialic acid from AGP. The kinetic results have shown that under equal temperature and pH conditions, the hydrolysis of the terminal glucosidic bond occurred faster in the presence of HPAs compared to conventional mineral acids. The observed rate constants were in the range 6,7×10-2 -11,9×10-2 min-1 and the complete and selective excision of sialic acids could be achieved within 60 min of incubation. The Trp fluorescence and CD spectroscopy show that non-covalent interaction between HPA and protein takes place in solution which could lead to stabilization of the sialosyl cation that is formed during the glycosidic bond hydrolysis by anionic HPA cluster.

Redox reactions between polyoxometalates (POMs) and biologically relevant molecules have been virtually unexplored but are important, considering the growing interest in the biological applications of POMs. In this work we give a detailed account on the redox behavior of CeIV-substituted polyoxometalates (CeIV-POMs) toward a range of amino acids and peptides. CeIV-POMs have been shown to act as artificial proteases that promote the selective hydrolysis of peptide bonds. In presence of a protein, a concomitant reduction of CeIV to CeIII ion is frequently observed, leading us to examine the origins of this redox reaction by first using amino acid building blocks as simple models. Among all of the examined amino acids, cysteine (Cys) showed the highest activity in reducing CeIV-POMs to CeIII-POMs, followed by the aromatic amino acids tryptophan (Trp), tyrosine (Tyr), histidine (His), and phenylalanine (Phe). While the redox reaction with Cys afforded the well-defined product cystine, no oxidation products were detected for the Trp, His, Tyr, and Phe amino acids after their reaction with CeIV-POMs, suggesting a radical pathway in which the solvent likely regenerates the amino acid. In general, the rate of redox reactions increased upon increasing the pD, temperature, and ionic strength of the reaction. Moreover, the redox reaction is highly sensitive to the type of polyoxometalate scaffold, as complexation of CeIV to a Keggin (K) or Wells-Dawson (WD) polyoxotungstate anion resulted in a large difference in the rate of redox reaction for both Cys and aromatic amino acids. The reduction of CeIVK was at least 1 order of magnitude faster in comparison to CeIVWD, in accordance with the higher redox potential of CeIVK in comparison to CeIVWD. The reaction of CeIVPOMs with a range of peptides containing redox-active amino acids revealed that the redox reaction is influenced by their coordination mode with CeIV ion, but in all examined peptides the redox reaction is favored in comparison to the hydrolytic cleavage of the peptide bond. ispartof: INORGANIC CHEMISTRY vol:59 issue:15 pages:10569-10577 ispartof: location:United States status: published

The selective hydrolysis of proteins by non‐enzymatic catalysis is difficult to achieve, yet it is crucial for applications in biotechnology and proteomics. Herein, we report that discrete hafnium metal‐oxo cluster [Hf18O10(OH)26(SO4)13⋅(H2O)33] (Hf18), which is centred by the same hexamer motif found in many MOFs, acts as a heterogeneous catalyst for the efficient hydrolysis of horse heart myoglobin (HHM) in low buffer concentrations. Among 154 amino acids present in the sequence of HHM, strictly selective cleavage at only 6 solvent accessible aspartate residues was observed. Mechanistic experiments suggest that the hydrolytic activity is likely derived from the actuation of HfIV Lewis acidic sites and the Brønsted acidic surface of Hf18. X‐ray scattering and ESI‐MS revealed that Hf18 is completely insoluble in these conditions, confirming the HHM hydrolysis is caused by a heterogeneous reaction of the solid Hf18 cluster, and not from smaller, soluble Hf species that could leach into solution. This is the peer-reviewed version of the following article: Moons, J.; de Azambuja, F.; Mihailović, J.; Kozma, K.; Smiljanić, K.; Amiri, M.; Ćirković-Veličković, T.; Nyman, M.; Parac-Vogt, T. Discrete Hf18 Metal‐oxo Cluster as a Heterogeneous Nanozyme for Site‐Specific Proteolysis. Angewandte Chemie (International Edition) 2020, 59 (17), 1–9. [https://doi.org/10.1002/anie.202001036]. Supplementary material: [https://cherry.chem.bg.ac.rs/handle/123456789/4851]

The development of modular platforms that can undergo postfunctionalization reactions permits coupling of inorganic clusters with different organic functionalities, thereby expanding the range of key physicochemical properties that are relevant for applications in different areas of science. In this work, a novel hybrid Wells-Dawson polyoxometalate (POM) platform was developed and successfully used for postfunctionalization via a nucleophilic substitution reaction. Two new halogen-functionalized bis-organosilyl Wells-Dawson POMs TBA6[α2-P2W17O61{O(SiC3H6-X)2}] (X = Cl or I) were synthesized, and their coupling with amine substrates was explored in a one-step postfunctionalization reaction. The iodide form of the POM has proven to be much more reactive, and its reaction with a range of primary and secondary amines resulted in a series of new bis-substituted Wells-Dawson POMs with the general formula TBA6[α2-P2W17O61{O(SiC3H6-NR1R2)2}]. Coupling of 18 amines with R1 and R2 groups, which exhibited a wide variety in terms of both chemical nature and bulkiness, was achieved under mild conditions via a catalyst-free approach. Using Na2CO3 as a base in acetonitrile solutions at 55 °C resulted in hybrid products that were obtained in high purity and good yields, after a simple isolation and purification procedure. ispartof: INORGANIC CHEMISTRY vol:59 issue:14 pages:10146-10152 ispartof: location:United States status: published

MOF-808, a Zr(IV)-based metal-organic framework, has been proven to be a very effective heterogeneous catalyst for the hydrolysis of the peptide bond in a wide range of peptides and in hen egg white lysozyme protein. The kinetic experiments with a series of Gly-X dipeptides with varying nature of amino acid side chain have shown that MOF-808 exhibits selectivity depending on the size and chemical nature of the X side chain. Dipeptides with smaller or hydrophilic residues were hydrolyzed faster than those with bulky and hydrophobic residues that lack electron rich functionalities which could engage in favorable intermolecular interactions with the btc linkers. Detailed kinetic studies performed by 1H NMR spectroscopy revealed that the rate of glycylglycine (Gly-Gly) hydrolysis at pD 7.4 and 60 °C was 2.69 × 10-4 s-1 ( t1/2 = 0.72 h), which is more than 4 orders of magnitude faster compared to the uncatalyzed reaction. Importantly, MOF-808 can be recycled several times without significantly compromising the catalytic activity. A detailed quantum-chemical study combined with experimental data allowed to unravel the role of the {Zr6O8} core of MOF-808 in accelerating Gly-Gly hydrolysis. A mechanism for the hydrolysis of Gly-Gly by MOF-808 is proposed in which Gly-Gly binds to two Zr(IV) centers of the {Zr6O8} core via the oxygen atom of the amide group and the N-terminus. The activity of MOF-808 was also demonstrated toward the hydrolysis of hen egg white lysozyme, a protein consisting of 129 amino acids. Selective fragmentation of the protein was observed with 55% yield after 25 h under physiological pH.

Lanthanides, holmium(iii), dysprosium(iii), and terbium(iii), were coordinated to an amphiphilic DOTA bis-coumarin derivative and then further assembled with an amphiphilic europium(iii) DTPA bis-coumarin derivative into mono-disperse micelles. The self-assembled micelles were characterized and assessed for their potential as bimodal contrast agents for high field magnetic resonance and optical imaging applications. All micelles showed a high transverse relaxation (r2) of 46, 34, and 30 s-1 mM-1 at 500 MHz and 37 °C for Dy(iii), Ho(iii) and Tb(iii), respectively, which is a result of the high magnetic moment of these lanthanides and the long rotational correlation time of the micelles. The quantum yield in aqueous solution ranged from 1.8% for Tb/Eu to 1.4% for Dy/Eu and 1.0% for the Ho/Eu micelles. Multi-photon excited emission spectroscopy has shown that due to the two-photon absorption of the coumarin chromophore the characteristic Eu(iii) emission could be observed upon excitation at 800 nm, demonstrating the usefulness of the system for in vivo fluorescence imaging applications. To the best of our knowledge, this is the first example reporting the potential of a holmium(iii) chelate as a negative MRI contrast agent. ispartof: DALTON TRANSACTIONS vol:47 issue:31 pages:10646-10653 ispartof: location:England status: published

A novel, reversible redox-active MRI probe, GdNR1, has been developed for the study of redox changes associated with diseased states. This system exhibits switching in relaxivity upon reduction and oxidation of the appended nicotinimidium. Relaxivity studies and cyclic voltammetry confirmed the impressive reversibility of this system, at a biologically-relevant reduction potential. A 2.5-fold increase in relaxivity was observed upon reduction of the complex, which corresponds to a change in the number of inner-sphere water molecules, as confirmed by luminescence lifetimes of the Eu(iii) analogue and NMRD studies. This is the first example of a redox-responsive MRI probe utilising the biologically-inspired nicotinimidium redox switch. In the future this strategy could enable the non-invasive identification of hypoxic tissue and related cardiovascular disease. ispartof: CHEMICAL COMMUNICATIONS vol:54 issue:92 pages:12986-12989 ispartof: location:England status: published

Group (IV) metal oxo clusters are a diverse class of compounds with rapidly growing applications in catalysis, materials chemistry, electronics and optics. They possess unique structural stability, reactivity and electronic properties; however, their potential remains underexplored due to the gaps in fundamental understanding about their structure, intrinsic features, and nuances in their synthesis that overall would allow for great tunability of their properties. In this context, here we review the chemistry of discrete zirconium, hafnium, and titanium metal oxo clusters reported in the literature in order to provide a critical overview of the structural features, properties and reactivity disclosed to date. While a comprehensive summary of Zr and Hf clusters is presented, only the most recent Ti oxo clusters are discussed in addition to some key compounds that have been revised elsewhere. Envisioning the growing relevance group (IV) metal oxo clusters for the synthesis of nanostructure materials and in catalysis, we also summarize key principles of their surface chemistry, and the photoactivity of Ti oxo clusters, given the paramount importance of these properties for the development of future applications.

This study represents the first example of protein hydrolysis at pH = 7.4 and 60 °C by a metal-substituted polyoxometalate (POM) in the presence of a zwitterionic surfactant. Edman degradation results show that in the presence of 0.5% w/v 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) detergent, a Zr(IV)-substituted Wells-Dawson-type POM, K15H[Zr(α2-P2W17O61)2]·25H2O (Zr1-WD2), selectively hydrolyzes human serum albumin exclusively at peptide bonds involving Asp or Glu residues, which contain carboxyl groups in their side chains. The selectivity and extent of protein cleavage are tuned by the CHAPS surfactant by an unfolding mechanism that provides POM access to the hydrolyzed peptide bonds. ispartof: ACS Omega vol:2 issue:5 pages:2026-2033 ispartof: location:United States status: published

Na/K-ATPase is emerging as an important target for a variety of anticancer metal-based drugs. The interactions of Na/K-ATPase (in its E1 state) with three representative and structurally related cytotoxic gold(III) complexes, i.e. [Au(bipy)(OH)(2)][PF6], bipy = 2,2'-bipyridine; [Au(py(dmb)-H)(CH3COO)(2)], py(dmb)-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine and [Au(bipy(dmb)-H)(OH)][PF6], bipy(c)-H = deprotonated 6-(1,1-dimethylbenzyl)-2,20-bipyridine, are investigated here in depth using a variety of spectroscopic methods, in combination with docking studies. Detailed information is gained on the conformational and structural changes experienced by the enzyme upon binding of these gold(III) complexes. The quenching constants of intrinsic enzyme fluorescence, the fraction of Trp residues accessible to gold(III) complexes and the reaction stoichiometries were determined in various cases. Specific hypotheses are made concerning the binding mode of these gold(III) complexes to the enzyme and the likely binding sites. Differences in their binding behaviour toward Na/K-ATPase are explained on the ground of their distinctive structural features. The present results offer further support to the view that Na/K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest and may thus be involved in their overall mode of action.

A mild post-functionalization method, based on a copper(i) catalyzed azide-alkyne cycloaddition, was developed for the fragile [P2W15V3]9- (PWV). PWV was functionalized with an azide and used as a platform to attach various alkyne functionalized compounds.

A highly negatively charged binuclear ZrIV-substituted Keggin polyoxometalate [{α-PW11O39Zr(μ-OH)(H2O)}2]8- (ZrK 2 : 2) has been shown to promote the hydrolytic cleavage of phosphoester bonds in the supercoiled plasmid pUC19 DNA under physiological pH and temperature, giving relaxed and linear forms of pUC19 as hydrolysis products. The interaction between ZrK 2 : 2 and DNA was experimentally proven by circular dichroism (CD) spectroscopy and 31P diffusion ordered NMR spectroscopy. crosscheck: This document is CrossCheck deposited related_data: Supplementary Information identifier: T. N. Parac-Vogt (ORCID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal history: Received 24 October 2016; Accepted 9 December 2016; Accepted Manuscript published 9 December 2016; Advance Article published 16 December 2016; Version of Record published 3 January 2017 ispartof: Chemical Communications vol:53 issue:3 pages:617-620 ispartof: location:England status: published

Creating efficient and residue-directed artificial proteases is a challenging task due to the extreme inertness of the peptide bond, combined with the difficulty of achieving specific interactions between the catalysts and the protein side chains. Herein we report strictly site-selective hydrolysis of a multi-subunit globular protein, hemoglobin (Hb) from bovine blood, by a range of ZrIV -substituted polyoxometalates (Zr-POMs) in mildly acidic and physiological pH solutions. Among 570 peptide bonds in Hb, selective cleavage was observed at only eleven sites, each occurring at Asp-X peptide bonds located in the positive patches on the protein surface. The molecular origins of the observed Asp-X selectivity were rationalized by means of molecular docking, DFT-based binding, and mechanistic studies on model peptides. The proposed mechanism of hydrolysis involves coordination of the amide oxygen to ZrIV followed by a direct nucleophilic attack of the side chain carboxylate group on the C-terminal amide carbon atom with formation of a cyclic anhydride, which is further hydrolyzed to give the reaction products. The activation energy for the cleavage of the structurally related Glu-X sequence compared to Asp-X was calculated to be higher by 1.4 kcal mol-1 , which corresponds to a difference of about one order of magnitude in the rates of hydrolysis. The higher activation energy is attributed to the higher strain present in the six-membered ring of glutaric anhydride (Glu-X), as compared to the five-membered ring of the succinic anhydride (Asp-X) intermediate. Similarly, the cleavage at X-Asp and X-Glu bonds are predicted to be kinetically less likely as the corresponding activation energies were 6 kcal mol-1 higher, explaining the experimentally observed selectivity. The synergy between the negatively charged polyoxometalate cluster, which binds at positive patches on protein surfaces, and selective activation of Asp-X peptide bonds located in these regions by ZrIV ions, results in a novel class of artificial proteases with aspartate-directed reactivity, which is very rare among naturally occurring proteases. ispartof: CHEMISTRY-A EUROPEAN JOURNAL vol:25 issue:63 pages:14370-14381 ispartof: location:Germany status: published

Hydrolysis of Transferin (Tf), a glycoprotein consisting of 679 amino acids and three glycan chains, has been examined in the presence of Ce(IV)-substituted Keggin polyoxometalate [CeIV(α-PW11O39)2]10− (Ce-K POM). Incubation at pH = 7.4 and at 37 °C resulted in selective fragmentation of the Tf after 24 h, which was followed by sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE). After 5 days of incubation nearly 90% of Tf was hydrolyzed, giving 9 fragments with molecular weight (Mw) in the range between 13.7 and 69.5 kDa. Under the same conditions, the sample of Tf which did not contain the Ce-K POM, showed only 7% of background hydrolysis. The interactions between Ce-K and Tf were studied by tryptophan fluorescence, circular dichroism (CD) and 31P Nuclear magnetic resonance (NMR) spectroscopy. The association constant (Ka) for the interaction was calculated to be 3.2 × 104 M−1 from tryptophan quenching studies. CD spectroscopy revealed that binding of Ce-K to Tf resulted in significant secondary structure changes, mainly affecting the alpha-helical content of the protein. 31P NMR spectroscopy showed that in the presence of the Tf partial reduction of Ce(IV) to Ce(III) occurred, which did not affect the overall structure of the Keggin POM. ispartof: Polyhedron vol:170 pages:570-575 status: published

ispartof: FRONTIERS IN CHEMISTRY vol:7 ispartof: location:Switzerland status: published

© 2019 American Chemical Society and Division of Chemical Education, Inc. Single-type, 8-fold-grooved, commercially accessible interlocking disks (ILDs) have been used for modeling of complex polyhedral and reticular topologies with relevance to inorganic and hybrid materials. The assembly of complex topologies relies on the preparation of secondary building units (SBUs), which exhibit different connectivity than that of the primary ILDs. All ILD-based models are light, scalable, programmable, and suitable for discovery-based learning and classroom demonstrations of stereochemistry and complex chemical concepts. ispartof: Journal Of Chemical Education vol:96 issue:3 pages:601-605 status: published

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Four Wells–Dawson type metal-substituted polyoxometalates (MSPs), 1:2 ZrIV-Wells–Dawson [ZrIV(α2-P2W17O61)]8– (1), 1:1 CoII-Wells–Dawson [CoII(α2-P2W17O61)]10– (2), 1:1 NiII-Wells–Dawson [NiII(α2-P2W17O61)]10– (3) and 1:1 CuII-Wells–Dawson [CuII(α2-P2W17O61)]10– (4), which differ in the nature of the imbedded metal ion, were examined in co-crystallization experiments with a protein Hen Egg White Lysozyme (HEWL). Single crystal X-ray structures of four noncovalent complexes between POMs and HEWL have been determined, and the influence of the type of substituted metal on the mode of POM binding to a protein was investigated. All crystal structures exhibited a high degree of similarity, suggesting that the interaction is largely independent on the nature of substituted metal within the same polyoxometalate (POM) archetype. The main driving force for the formation of the noncovalent complex is electrostatic attraction between POM and HEWL surface regions. Stabilization is further provided by direct and water mediated hydrogen bonding between terminal oxygen atoms of the POM framework and flexible HEWL residues. ispartof: EUROPEAN JOURNAL OF INORGANIC CHEMISTRY vol:2019 issue:3-4 pages:506-511 status: published

In this study, mechanisms of hydrolysis of all four chemically diverse cleavage sites of human serum albumin (HSA) by [Zr(OH)(PW11 O39 )]4- (ZrK) have been investigated using the hybrid two-layer QM/MM (ONIOM) method. These reactions have been proposed to occur through the following two mechanisms: internal attack (IA) and water assisted (WA). In both mechanisms, the cleavage of the peptide bond in the Cys392-Glu393 site of HSA is predicted to occur in the rate-limiting step of the mechanism. With the barrier of 27.5 kcal/mol for the hydrolysis of this site, the IA mechanism is found to be energetically more favorable than the WA mechanism (barrier = 31.6 kcal/mol). The energetics for the IA mechanism are in line with the experimentally measured values for the cleavage of a wide range of dipeptides. These calculations also suggest an energetic preference (Cys392-Glu393, Ala257-Asp258, Lys313-Asp314, and Arg114-Leu115) for the hydrolysis of all four sites of HSA. © 2018 Wiley Periodicals, Inc. ispartof: JOURNAL OF COMPUTATIONAL CHEMISTRY vol:40 issue:1 pages:51-61 ispartof: location:United States status: published

The hydrolysis of horse heart cytochrome c (cytC) protein by two isostructural Keggin-type polyoxometalates (POMs), (Me2NH2)10[Ce(α-PW11O39)2] (Ce1–K2) and (Et2NH2)10[Zr(PW11O39)2] (Zr1–K2), which differ in the nature of the embedded Lewis acid metal ion, has been investigated. In the presence of Ce1–K2, selective hydrolysis of cytC was observed at the Trp60-Lys61 and Gly78-Thr79 peptide bonds at pH 7.4 and 37 °C. However, the isostructural Zr1–K2 exhibited a lower reactivity and different selectivity, cleaving cytC at the Asp3-Val4, Asp51-Ala52 and Gly78-Thr79 peptide bonds. Different spectroscopic techniques were used to verify the molecular interactions between cytC and each metal-substituted Keggin POM to elucidate the role of the Lewis acid metal ion in directing the selectivity of protein hydrolysis. ispartof: European Journal of Inorganic Chemistry vol:2016 issue:32 pages:5098-5105 status: published

A new prototype consisting of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles decorated with europium(III) ions encapsulated in a DO3A organic scaffold was designed as a platform for further development of bimodal contrast agents for MRI and optical imaging. The USPIO nanoparticles act as negative MRI contrast agents, whereas the europium(III) ion is a luminophore that is suitable for use in optical imaging detection. The functionalized USPIO nanoparticles were characterized by TEM, DLS, XRD, FTIR, and TXRF analysis, and a full investigation of the relaxometric and optical properties was conducted. The typical luminescence emission of europium(III) was observed and the main red emission wavelength was found at 614 nm. The relaxometric study of these ultrasmall nanoparticles showed r2 values of 114.8 mM(-1) Fes(-1) at 60 MHz, which is nearly double the r2 relaxivity of Sinerem(®).

The interaction between the 1:2 Zr(IV) :Wells-Dawson complex, K15 H[Zr(α2 -P2 W17 O61 )2] (1), and a range of surfactants was studied in detail with the aim of developing metal-substituted POMs as potential artificial proteases for membrane proteins. The surfactants include the positively charged cetyl(trimethyl)ammonium bromide (CTAB), the negatively charged sodium dodecyl sulfate (SDS), the neutral Triton X-100 (TX-100), and zwitterionic 3-[dodecyl(dimethyl)ammonio]-1-propanesulfonate (Zw3-13) and 3-[dimethyl(3-{[(3α,5β,7α,12α)-3,7,12-trihydroxy-24-oxocholan-24-yl]amino}propyl)ammonio]-1-propanesulfonate (CHAPS). A combination of multinuclear (1)H, (13)C, and (31) P NMR spectroscopy, (1)H diffusion-ordered NMR spectroscopy ((1)H DOSY), and nuclear Overhauser effect spectroscopy (NOESY) was used to examine the interaction between 1 and each surfactant on the molecular level. Cationic surfactant CTAB caused precipitation of 1 due to strong electrostatic interactions, while the anionic SDS and neutral TX-100 surfactants did not exhibit any interaction at neutral pD. (1)H DOSY NMR spectroscopy indicated an interaction between 1 and zwitterionic surfactants Zw3-12 and CHAPS, which occurs via the positively charged ammonium group in the surfactant molecule. In the presence of anionic, neutral, and zwitterionic surfactants, 1 preserves its catalytic activity towards the hydrolysis of the peptide bond in the dipeptide glycyl-l-histidine (GH). The fastest hydrolysis was observed at pD 7.0 and could be rationalized by taking into account pD-dependent speciation of 1 and coordination properties of GH.

Dysprosium(iii) was coordinated to four 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) bisamide derivatives functionalized with amphiphilic p-dodecylaniline and p-tetradecylaniline in a differing cis- and trans-orientation. The complexes were assembled into mono-disperse micelles having size distribution maxima ranging from 10 to 15 nm and the magnetic and optical properties of the micelles were examined in detail. The micelles show characteristic Dy(iii) emission with quantum yields reaching 0.8%. The transverse relaxivity r2 per Dy(iii) ion at 500 MHz and 310 K reaches maximum values of ca. 20 s(-1) mM(-1) which is a large increase when compared to a value of 0.8 s(-1) mM(-1) observed for Dy(III)-DTPA. The micelles were stable in water when incubated at 37 °C for 1 week and showed no relaxivity decrease when measured in the presence of 4% (w/v) human serum albumin. The efficient T2 relaxation, especially at strong magnetic fields, is sustained by the high magnetic moment of the dysprosium(iii) ion, the coordination of water molecules and long rotational correlation times.

Peptide bond hydrolysis of 18 different dipeptides, divided into four groups depending on the nature of the amino acid side chain, by the dimeric Zr(IV)-substituted Keggin type polyoxometalate (POM) (Et2NH2)8[{α-PW11O39Zr-(μ-OH)(H2O)}2]·7H2O (1) was studied by means of kinetic experiments and 1H/13C NMR spectroscopy. The observed rate constants highly depend on the bulkiness and chemical nature of the X amino acid side chain. X-Ser and X-Thr dipeptides showed increased reactivity due to intramolecular nucleophilic attack of the hydroxyl group in the side chain on the amide carbon, resulting in a reactive ester intermediate. A similar effect in which the amino acid side chain acted as an internal nucleophile was observed for the hydrolysis of Gly-Asp. Interestingly, in the presence of 1 deamidation of Gly-Asn and Gly-Gln into Gly-Asp and Gly-Glu was observed. Dipeptides containing positively charged amino acid side chains were hydrolyzed at higher rates due to electrostatic interactions between the negatively charged POM surface and positive amino acid side chains.

The catalytic hydrolysis of a phosphoester bond in the DNA-model substrate 4-nitrophenyl phosphate (NPP) promoted by Zr(iv)-substituted Wells-Dawson Na14[Zr4(P2W16O59)2(μ3-O)2(OH)2(H2O)4]·57H2O polyoxometalate (ZrWD 4 : 2) was followed by means of (1)H and (31)P NMR spectroscopy. The hydrolytic reaction proceeded with a rate constant of 8.44 (±0.36) × 10(-5) s(-1) at pD 6.4 and 50 °C, representing a 300-fold rate enhancement in comparison with the spontaneous hydrolysis of NPP (kobs = 2.81 (±0.25) × 10(-7) s(-1)) under the same reaction conditions. The ZrWD 4 : 2 was also active towards hydrolysis of bis(4-nitrophenyl) phosphate (BNPP) and the RNA model substrate 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP). The pD dependence of kobs shows that the rate constants for NPP hydrolysis decrease significantly when the pD values of the reaction mixtures increase. The formation constant (Kf = 190 M(-1)) and catalytic rate constant (kc = 6.40 × 10(-4) s(-1)) for the NPP-ZrWD 4 : 2 complex, activation energy (Ea) of 110.15 ± 7.06 kJ mol(-1), enthalpy of activation (ΔH(‡)) of 109.03 ± 6.86 kJ mol(-1), entropy of activation (ΔS(‡)) of 15.20 ± 2.49 J mol(-1) K(-1), and Gibbs activation energy (ΔG(‡)) of 104.32 ± 6.09 kJ mol(-1) at 37 °C were calculated from kinetic studies. The recyclability of ZrWD 4 : 2 was examined by adding an extra amount (5.0 mM) of NPP twice to a fully hydrolyzed mixture of 5.0 mM NPP and 1.0 mM ZrWD 4 : 2. The interaction between ZrWD 4 : 2 and the P-O bond of NPP was evidenced by a change in the (31)P chemical shift of the (31)P atom in NPP upon addition of ZrWD 4 : 2. Based on (31)P NMR experiments and the kinetic studies, a mechanism for NPP hydrolysis promoted by ZrWD 4 : 2 has been proposed. ispartof: Dalton Transactions vol:45 issue:30 pages:12174-12180 ispartof: location:England status: published

The catalytic fragmentation of hydrophobic proteins by polyoxometalates (POMs) requires the presence of surfactants in order to increase the solubility of the protein. Depending on the nature of the surfactant, different effects on the kinetics of protein hydrolysis are observed. As the molecular interactions between the POMs and surfactants in solutions have been scarcely explored, in this study, the interaction between the catalytically active Keggin polyoxometalate [Zr(&alpha, PW11O39)2]10&minus, and four different surfactants&mdash, sodium dodecyl sulfate (SDS), dodecyldimethyl(3-sulfopropyl)ammonium (Zw3-12), dodecyldimethyl(3-sulfopropyl) ammonium (CHAPS), and polyethylene glycol tert-octylphenyl ether (TX-100)&mdash, have been studied in aqueous media. The effect of polyoxometalate on the self-assembly of surfactant molecules into micelles and on the critical micellar concentration (CMC) has been examined by fluorescence spectroscopy and diffusion ordered NMR spectroscopy (DOSY).

The successful cocrystallization of the noncovalent complex formed between (Et2NH2)8[{α-PW11O39Zr-(μ-OH)(H2O)}2]·7H2O Keggin polyoxometalate (2) and Hen Egg White Lysozyme (HEWL) protein is reported. The resulting structural model revealed interaction between monomeric [Zr(PW11O39)]4−(1), which is a postulated catalytically active species, and the protein in two positions in the asymmetric unit. The first position (occupancy 36%) confirms the previously observed binding sites on the protein surface, whereas the second position (occupancy 14%) provides novel insights into the hydrolytic mechanisms of ZrIV-substituted polyoxometalates. The new interaction site occurs at the Asn65 residue, which is directly next to the Asp66–Gly67 peptide bond that was identified recently as a cleavage site in the polyoxometalate-catalysed hydrolysis of HEWL. Furthermore, in this newly discovered binding site, the monomeric polyoxometalate 1 is observed to bind directly to the side chain of the Asn65 residue. This binding of ZrIV as a Lewis-acid metal to the carbonyl O atom of the Asn65 side chain is very similar to the intermediate state proposed in density functional theory (DFT) studies in which ZrIV activates the peptide bond via interaction with its carbonyl O atom, and can be thus regarded as a model for interaction between ZrIV and a peptide bond.

In this paper we investigate the effect of three different types of surfactants, on the hydrolysis of Cytochrome c (Cyt c), a predominantly α helical protein containing a heme group, promoted by [Ce(α PW11O39)2]10- (CeK) and [Zr(α PW11O39)2]10- (ZrK) polyoxometalates. In the presence of SDS, Zw3 12, or CHAPS surfactants, which are commonly used for solubilizing hydrophobic proteins, the specificity of CeK or ZrK toward hydrolysis of Cyt c does not change. However, the hydrolysis rate of Cyt c by CeK was increased in the presence of SDS, but decreased in the presence of CHAPS, and was nearly inhibited in the presence of Zw3 12. The Circular dichroism and Tryptophan fluorescence spectroscopy have shown that the structural changes in Cyt c caused by surfactants are similar to those caused by POMs, hence the same specificity in the absence or presence of surfactants was observed. The results also indicate that for Cyt c hydrolysis to occur, large unfolding of the protein is needed in order to accommodate the POMs. While SDS readily unfolds Cyt c, the protein remains largely folded in the presence of CHAPS and Zw3 12. Addition of POMs to Cyt c solutions in CHAPS results in unfolding of the structure allowing the interaction with POMs to occur and results in protein hydrolysis. Zw3 12, however, locks Cyt c in a conformation that resists unfolding upon addition of POM, and therefore results in nearly complete inhibition of protein hydrolysis. ispartof: FRONTIERS IN CHEMISTRY vol:6 issue:AUG ispartof: location:Switzerland status: published

Working under the supervisor of William Lawrence Bragg at the University of Manchester and being under the direct personal and scientific influence by Linus Pauling, Dr. James Fargher Keggin some 85 years ago published a highly unique discovery-the structure of phosphotungstic acid (Nature 1933, 131, 908-909). This structure sparked the reports of other related polyanions from Keggin's contemporaries, marking the true beginnings of structural polyoxometalate chemistry. In this perspective article, we unveil some aspects and applications of Keggin's structure and discuss how it has shaped the course of our understanding of polyoxometalate chemistry and nanomolecular metal oxides/hydroxides in general. ispartof: FRONTIERS IN CHEMISTRY vol:6 issue:AUG ispartof: location:Switzerland status: published

In this study, a combined molecular docking (rigid and flexible) and all-atom molecular dynamics simulations technique have been employed to investigate interactions of 1:1 Zr-containing Keggin polyoxometalate (ZrK) with four chemically distinct cleavage sites [Arg114-Leu115 (site 1), Ala257-Asp258 (site 2), Lys313-Asp314 (site 3), and Cys392-Glu393 (site 4)] of human serum albumin (HSA). The ZrK-HSA complexations were analyzed using electrostatic potentials, the chemical nature of amino acid residues, binding free energies, and secondary structures as parameters. They suggested that ZrK binds in a rather distinct manner to different cleavage sites, and its association was dominated by hydrogen bonding, both direct and solvent mediated, and electrostatic interactions, as suggested experimentally. The computed binding free interaction energies (-57.5, -24.2, -50.8, and -91.2 kJ/mol for sites 1, 2, 3, and 4, respectively) predicted the existence of one major binding site (site 4) and three minor binding sites (site 1, site 2, and site 3). The strong exothermicity of the binding was also supported by isothermal calorimetry experiments. Additionally, the binding of ZrK did not alter the overall α-helical secondary structure of HSA, which was in line with experimental observation. Furthermore, hydrolysis of the peptide bonds of the substrate was found to retain its overall structure. These results have provided a deeper understanding of the complex ZrK interactions with proteins, and they will lead to the design of the next generation of catalytically active polyoxometalates with improved hydrolytic activities. ispartof: JOURNAL OF PHYSICAL CHEMISTRY B vol:122 issue:29 pages:7219-7232 ispartof: location:United States status: published

The selective hydrolysis of the glycosidic bond between the terminal sialic acid and the penultimate sugar has been achieved in the alpha-2-HS-glycoprotein (Fetuin-A) in the presence of H3PW12O40, a Keggin type polyoxometalate. A controlled liberation of sialic acid from the glycoprotein could be achieved at pH 3.0 and 37 °C without the destruction of the protein backbone.

A recent study [Angew. Chem. Int. Ed. 2015, 54, 7391-7394] has shown that horse heart myoglobin (HHM) is selectively hydrolyzed by a range of zirconium(IV)-substituted polyoxometalates (POMs) under mild conditions. In this study, the molecular interactions between the Zr-POM catalysts and HHM are investigated by using a range of complementary techniques, including circular dichroism (CD), UV/Vis spectroscopy, tryptophan fluorescence spectroscopy, and 1 H and 31 P NMR spectroscopy. A tryptophan fluorescence quenching study reveals that, among all examined Zr-POMs, the most reactive POM, 2:2 ZrIV -Keggin, exhibits the strongest interaction with HHM. 31 P NMR spectroscopy studies show that this POM dissociates in solution, resulting in the formation of a monomeric 1:1 ZrIV -Keggin structure, which is likely to be a catalytically active species. In the presence of ZrIV -POMs, HHM does not undergo complete denaturation, as evidenced by CD, UV/Vis, tryptophan fluorescence, and 1 H NMR spectroscopy. CD spectroscopy shows a gradual decrease in the α-helical content of HHM upon addition of ZrIV -POMs. The largest effect is observed in the presence of a large ZrIV -Wells-Dawson structure, whereas small ZrIV -Lindqvist POM has the least influence on the decrease in the α-helical content of HHM. In all cases, the Soret band at λ=409 nm is maintained in the presence of all examined Zr-POMs, which indicates that no conformational changes in the protein occur near the heme group. ispartof: ChemPhysChem vol:18 issue:18 pages:1-9 ispartof: location:Germany status: published

A new postfunctionalization method was developed for the Anderson-type POM based on a nucleophilic substitution reaction occurring at an electrophilic sp3 hybridized carbon localized on the hybrid POM. Using this method, several types of different nucleophiles including primary and secondary amines, carboxylates, and thiolates were efficiently coupled to a chloride-functionalized Anderson-type POM in high yields and purity. The heterogeneous acetonitrile-Na2CO3 conditions were found to be superior over other bases and solvents for the coupling of amines and thiolates to the chloride-functionalized POM. Moreover, the addition of 1 equiv of tetrabutylammonium iodide as a catalyst drastically decreased the reaction times to 24 h for the complete coupling of amines and only a couple of hours for thiolates. In the case of carboxylic acids as substrates, using tetrabutylammonium hydroxide as the base for the reaction proved to be beneficial. This is because the resulting tetrabutylammonium carboxylates were fou...

DOI: 10.1002/chem.201602263 URL: http://onlinelibrary.wiley.com/doi/10.1002/chem.201602263/abstract;jsessionid=A78A0F5D7DA73B8D67E1019C41603BD2.f02t02?systemMessage=Due+to+essential+maintenance+the+subscribe%2Frenew+pages+will+be+unavailable+on+Wednesday+26+October+between+02%3A00+-+08%3A00+BST%2F+09%3A00+%E2%80%93+15%3A00++SGT%2F+21%3A00-+03%3A00+EDT.+Apologies+for+the+inconvenience. Filiació URV: SI Inclòs a la memòria: SI The molecular interactions between the CeIV-substituted Keggin anion [PW11O39Ce(OH2)4]3− (CeK) and hen egg-white lysozyme (HEWL) were investigated by molecular dynamics simulations. The analysis of CeK was compared with the CeIV-substituted Keggin dimer [(PW11O39)2Ce]10− (CeK2) and the ZrIV-substituted Lindqvist anion [W5O18Zr(OH2)(OH)]3− (ZrL) to understand how POM features such as shape, size, charge, or type of incorporated metal ion influence the POM⋅⋅⋅protein interactions. Simulations revealed two regions of the protein in which the CeK anion interacts strongly: cationic sites formed by Arg21 and by Arg45 and Arg68. The POMs chiefly interact with the side chains of the positively charged (arginines, lysines) and the polar uncharged residues (tyrosines, serines, aspargines) via electrostatic attraction and hydrogen bonding with the oxygen atoms of the POM framework. The CeK anion shows higher protein affinity than the CeK2 and ZrL anions, because it is less hydrophilic and it has the right size and shape for establishing interactions with several residues simultaneously. The larger, more negatively charged CeK2 anion has a high solvent-accessible surface, which is sub-optimal for the interaction, while the smaller ZrL anion is highly hydrophilic and cannot efficiently interact with several residues simultaneously.

Hydrolytic cleavage of 4-nitrophenyl phosphate (NPP), a commonly used DNA model substrate, was examined in the presence of series of lanthanide-substituted Keggin-type polyoxometalates (POMs) [Me2NH2]11[CeIII(PW11O39)2], [Me2NH2]10[CeIV(PW11O39)2] (abbreviated as (CeIV(PW11)2), and K4[EuPW11O39] by means of NMR and luminescence spectroscopies and density functional theory (DFT) calculations. Among the examined complexes, the Ce(IV)-substituted Keggin POM (CeIV(PW11)2) showed the highest reactivity, and its aqueous speciation was fully determined under different conditions of pD, temperature, concentration, and ionic strength by means of 31P and 31P diffusion-ordered NMR spectroscopy. The cleavage of the phosphoester bond of NPP in the presence of (CeIV(PW11)2) proceeded with an observed rate constant kobs = (5.31 ± 0.06) × 10–6 s–1 at pD 6.4 and 50 °C. The pD dependence of NPP hydrolysis exhibits a bell-shaped profile, with the fastest rate observed at pD 6.4. The formation constant (Kf = 127 M–1) and cat...

The gallium(III)-containing heteropolytungstates [Ga4(H2O)10(β-XW9O33)2](6-) (X = As(III), 1; Sb(III), 2) were synthesized in aqueous acidic medium by reaction of Ga(3+) ions with the trilacunary, lone-pair-containing [XW9O33](9-). Polyanions 1 and 2 are isostructural and crystallized as the hydrated sodium salts Na6[Ga4(H2O)10(β-AsW9O33)2]·28H2O (Na-1) and Na6[Ga4(H2O)10(β-SbW9O33)2]·30H2O (Na-2) in the monoclinic space group P21/c, with unit cell parameters a = 16.0218(12) Å, b = 15.2044(10) Å, c = 20.0821(12) Å, and β = 95.82(0)°, as well as a = 16.0912(5) Å, b = 15.2178(5) Å, c = 20.1047(5) Å, and β = 96.2(0)°, respectively. The corresponding tellurium(IV) derivative [Ga4(H2O)10(β-TeW9O33)2](4-) (3) was also prepared, by direct reaction of sodium tungstate, tellurium(IV) oxide, and gallium nitrate. Polyanion 3 crystallized as the mixed rubidium/sodium salt Rb2Na2[Ga4(H2O)10(β-TeW9O33)2]·28H2O (RbNa-3) in the triclinic space group P1̅ with unit cell parameters a = 12.5629(15) Å, b = 13.2208(18) Å, c = 15.474(2) Å, α = 80.52(1)°, β = 84.37(1)°, and γ = 65.83(1)°. All polyanions 1-3 were characterized in the solid state by single-crystal XRD, FT-IR, TGA, and elemental analysis, and polyanion 2 was also characterized in solution by (183)W NMR and UV-vis spectroscopy. Polyanion 2 was used as a homogeneous catalyst toward adenosine triphosphate (ATP) and the DNA model substrate 4-nitrophenylphosphate, monitored by (1)H and (31)P NMR spectroscopy. The encapsulated gallium(III) centers in 2 promote the Lewis acidic synergistic activation of the hydrolysis of ATP and DNA model substrates at a higher rate in near-physiological conditions. A strong interaction of 2 with the P-O bond of ATP was evidenced by changes in chemical shift values and line broadening of the (31)P nucleus in ATP upon addition of the polyanion.

A detailed reaction mechanism is proposed for the hydrolysis of the phosphoanhydride bonds in adenosine triphosphate (ATP) in the presence of the binuclear Zr(IV)-substituted Keggin type polyoxometalate (Et2NH2)8[{α-PW11O39Zr(μ-OH)(H2O)}2]·7H2O (ZrK 2:2). The full reaction mechanism of ATP hydrolysis in the presence of ZrK 2:2 at pD 6.4 was elucidated by a combination of (31)P, (31)P DOSY, and (31)P EXSY NMR spectroscopy, demonstrating the potential of these techniques for the analysis of complex reaction mixtures involving polyoxometalates (POMs). Two possible parallel reaction pathways were proposed on the basis of the observed reaction intermediates and final products. The 1D (31)P and (31)P DOSY spectra of a mixture of 20.0 mM ATP and 3.0 mM ZrK 2:2 at pD 6.4, measured immediately after sample preparation, evidenced the formation of two types of complexes, I1A and I1B, representing different binding modes between ATP and the Zr(IV)-substituted Keggin type polyoxometalate (ZrK). Analysis of the NMR data shows that at pD 6.4 and 50 °C ATP hydrolysis in the presence of ZrK proceeds in a stepwise fashion. During the course of the hydrolytic reaction various products, including adenosine diphosphate (ADP), adenosine monophosphate (AMP), pyrophosphate (PP), and phosphate (P), were detected. In addition, intermediate species representing the complexes ADP/ZrK (I2) and PP/ZrK (I5) were identified and the potential formation of two other intermediates, AMP/ZrK (I3) and P/ZrK (I4), was demonstrated. (31)P EXSY NMR spectra evidenced slow exchange between ATP and I1A, ADP and I2, and PP and I5, thus confirming the proposed reaction pathways. ispartof: Inorganic Chemistry vol:55 issue:10 pages:4864-4873 ispartof: location:United States status: published