Inorg Chem Research Articles

Molecular Structures and Electrochemical Activity of Oversaturated Electrolytes

In applications ranging from biochemistry to electrochemistry, the solvation structures and agglomeration forms of ions are a focus of basic scientific study. Prior research has found that the concentration level and preparation conditions of these ionic electrolytes can affect the hydrated structure (e.g., tetrahedral or octahedral) and aggregate framework (e.g., intermolecular connection like ion cluster or network, or intramolecular connection like dissociation or undissociation).1–3 Our recent studies on vanadium (IV) sulfate (VOSO4), a transition metal salt used in redox flow batteries, show that in addition to the electrochemically active ions that can readily convert to V2+, V3+, and V5+ oxidation state, inactive molecules with different solvation structures and agglomerates also form in the electrolyte, and some of the inactive molecules can be converted to active ions while others cannot. The order of the preparation, such as dissolving the metal salt in water first and then adding the acid or vice versa, seems to have an impact on the ratio of the active ions and inactive molecules in the electrolyte. Furthermore, the closer the vanadium salt concentration is to its solubility limit, the higher the fraction of the inactive non-convertible molecule is. Finally, the inactive molecules in these electrolytes can be converted to active molecules by heating the electrolyte to a higher temperature (e.g., >50oC) and then cooling it down to room temperature. Similar electrochemical behavior was also observed in oversaturated FeCl3 solution, indicating that the coexistence of electrochemically active and inactive species above the solubility may be common for transition metal salt solutions.Oversaturated electrolyte solutions are unstable and have been of little interest because they have been deemed to have no applications. However, for applications where the oversaturation state is only needed within its duration of stability, they provide many benefits such as higher concentrations that could translate to higher current density or power output in power source applications and higher energy density in a long-duration energy storage applications. Our presentation will discuss the stabilities, electrochemical performances, and possible solvation structures of VOSO4 and FeCl3 solutions with different concentrations and preparation methods. References S. Kim, H. Kim, J.-H. Choi, and M. Cho, J Chem Phys, 141, 124510 (2014).I. Persson, J Solution Chem, 47, 797–805 (2018).D. L. Wertz and M. L. Steele, Inorg Chem, 19, 1652–1656 (1980).

DFT Calculations for Mössbauer Properties on Dinuclear Center Models of the Resting Oxidized Cytochrome c Oxidase.

Mössbauer isomer shift and quadrupole splitting properties have been calculated using the OLYP‐D3(BJ) density functional method on previously obtained (W.‐G. Han Du, et al., Inorg Chem. 2020, 59, 8906–8915) geometry optimized Fea3 3+−H2O−CuB 2+ dinuclear center (DNC) clusters of the resting oxidized (O state) “as‐isolated” cytochrome c oxidase (CcO). The calculated results are highly consistent with the available experimental observations. The calculations have also shown that the structural heterogeneities of the O state DNCs implicated by the Mössbauer experiments are likely consequences of various factors, particularly the variable positions of the central H2O molecule between the Fea3 3+ and CuB 2+ sites in different DNCs, whether or not this central H2O molecule has H‐bonding interaction with another H2O molecule, the different spin states having similar energies for the Fea3 3+ sites, and whether the Fea3 3+ and CuB 2+ sites are ferromagnetically or antiferromagnetically spin‐coupled.

Insulator-to-half metal transition and enhancement of structural distortions in text {Lu}_2 text {NiIrO}_6 double perovskite oxide via hole-doping

Using density functional theory calculations, we found that recently high-pressure synthesized double perovskite oxide text {Lu}_2 text {NiIrO}_6 exhibits ferrimagnetic (FiM) Mott-insulating state having an energy band gap of 0.20 eV which confirms the experimental observations (Feng et al. in Inorg Chem 58:397–404, 2019). Strong antiferromagnetic superexchange interactions between high-energy half-filled text {Ni}^{+2}-e_g^2uparrow and low-energy partially filled text {Ir}^{+4},t_{2g}^3uparrow t_{2g}^2downarrow orbitals, results in a FiM spin ordering. Besides, the effect of 3d transition metal (TM = Cr, Mn, and Fe) doping with 50% concentration at Ni sites on its electronic and magnetic properties is explored. It is established that smaller size cation-doping at the B site enhances the structural distortion, which further gives strength to the FiM ordering temperature. Interestingly, our results revealed that all TM-doped structures exhibit an electronic transition from Mott-insulating to a half-metallic state with effective integral spin moments. The admixture of Ir 5d orbitals in the spin-majority channel are mainly responsible for conductivity, while the spin minority channel remains an insulator. Surprisingly, a substantial reduction and enhancement of spin moment are found on non-equivalent Ir and oxygen ions, respectively. This leads the Ir ion in a mixed-valence state of +4 and +5 in all doped systems having configurations of 5d^5 (t_{2g}^3uparrow t_{2g}^2downarrow) and 5d^4 (t_{2g}^2uparrow t_{2g}^2downarrow), respectively. Hence, the present work proposes that doping engineering with suitable impurity elements could be an effective way to tailor the physical properties of the materials for their technological potential utilization in advanced spin devices.

Dissecting molecular details and functional effects of the high-affinity copper binding site in plasminogen activator Inhibitor-1.

Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor for plasminogen activators, tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). As a unique member in the serine protease inhibitor (serpin) family, PAI-1 is metastable and converts to an inactive, latent structure with a half-life of 1-2 hr under physiological conditions. Unusual effects of metals on the rate of the latency conversion are incompletely understood. Previous work has identified two residues near the N-terminus, H2 and H3, which reside in a high-affinity copper-binding site in PAI-1 [Bucci JC, McClintock CS, Chu Y, Ware GL, McConnell KD, Emerson JP, Peterson CB (2017) J Biol Inorg Chem 22:1123-1,135]. In this study, neighboring residues, H10, E81, and H364, were tested as possible sites that participate in Cu(II) coordination at the high-affinity site. Kinetic methods, gel sensitivity assays, and isothermal titration calorimetry (ITC) revealed that E81 and H364 have different roles in coordinating metal and mediating the stability of PAI-1. H364 provides a third histidine in the metal-coordination sphere with H2 and H3. In contrast, E81 does not appear to be required for metal ligation along with histidines; contacts made by the side-chain carboxylate upon metal binding are perturbed and, in turn, influence dynamic fluctuations within the region encompassing helices D, E, and F and the W86 loop that are important in the pathway for the PAI-1 latency conversion. This investigation underscores a prominent role of protein dynamics, noncovalent bonding networks and ligand binding in controlling the stability of the active form of PAI-1.

Selective, Catalytic Oxidations of C–H Bonds in Polyethylenes Produce Functional Materials with Enhanced Adhesion

Summary The synthesis of functional and processable polyethylenes from simple vinyl monomers with controlled molecular weights and architectures has been a grand challenge of polymer chemistry. Post-polymerization modification of the homopolymers of ethylene is attractive for this purpose but has been hampered by the lack of efficient methods for the selective functionalization of C–H bonds in polyolefins. We report the selective, catalytic oxidation of C–H bonds in commodity polyethylenes with varying molecular weights and architectures. Remarkably, the functionalized materials, even at low levels of functionalization, exhibit physical properties that are absent in unmodified polyolefins, such as strong adhesion and the ability to be painted with common waterborne latex paint. Such observations indicate that selectively modified polyethylenes as described here may help to transform existing commodity plastics into more valuable and potentially more sustainable materials.

Discharge Reactions of γ-MnO2 and Mo6S8 Tracked in the Electrode Bulk of Sealed Devices By Energy Dispersive X-Ray Diffraction (EDXRD)

Energy dispersive X-ray diffraction (EDXRD) from a high energy source allows the evolution of materials to be tracked from deep within large specimens, due to (a) the use of highly penetrating X-rays and (b) the ability to define a well-controlled diffraction gauge volume in space.1,2 This non-destructive characterization tool lends itself to the study of batteries, whose electrodes are generally composites of compressed particles, with electrolyte filling the pore space, and a sealed containment surrounding the cell designed to be as compact as possible. The fundamental electrochemistry of the active material can be known from laboratory experiments, but reaction inhomogeneity that is a consequence of the system itself is best observed in an in situ fashion without disassembly, or in an operando fashion within the battery as it cycles. EDXRD allows tomographic-like observation of the bulk interior of electrodes and critical locations such as the electrode-separator interfaces.3,4 This talk will illustrate the technique for understanding complex electrochemical reactions in three diverse systems: (1) proton insertion into γ-MnO2 in alkaline electrolyte, (2) Al3+ intercalation into Mo6S8 chevrel in chloroaluminate electrolyte, and (3) Zn2+ intercalation into Mo6S8 in aqueous ZnSO4. Deeply cycling MnO2 (617 mAh/g-MnO2) has the potential to provide battery storage of high safety, high energy density, and low cost, for applications such as intermittent renewable generation backup at the scale of the power grid.5 Figure 1a shows the γ-MnO2 discharge curve, in which reduction to one electron equivalent per Mn (x = 1) proceeds through proton insertion. Reaction beyond this point involves new phase formation at relatively constant potential. Operando EDXRD data in Figure 1b reveals that the nominal discharge product Mn(OH)2 was found only in a relatively small region clustered at the Ni current collector, while a propagating front of Mn3O4 traversed the electrode (panel iii). Figure 1c correlates the spatial locations of the various crystalline phases with the potential data in 1a. This shows that the final potential plateau at x = 1.8 corresponded to sudden Mn(OH)2 formation throughout the electrode, a phenomenon not previously reported.6 Dopant strategies to provoke earlier Mn(OH)2 formation and suppress Mn3O4 hold the key to MnO2 rechargeability.7 EDXRD is also useful in situations when electrode discharge products are prone to damage or alteration by cell disassembly, casting doubt on material structures observed by ex situ analysis. The chevrel phase Mo6S8 has been shown to intercalate divalent and trivalent ions, making it an important material of study. It is known that two second order phase transitions are expected during intercalation of a guest ion A into the host chevrel: Mo6S8 → AMo6S8 → A2Mo6S8.8 However, a recent ex situ study of Zn2+ intercalation suggested that conversion to Zn2Mo6S8 may be incomplete.9 We demonstrate this was a consequence of material oxidation during cell disassembly, and that when observed by EDXRD conversion to Zn2Mo6S8 is complete. The corresponding Al3+ intercalation will be compared to show there is only one phase transition in this case. References M. Croft, V. Shukla, E. K. Akdogan, N. Jisrawi, Z. Zhong, R. Sadangi, A. Ignatov, L. Balarinni, K. Horvath and T. Tsakalakos, J Appl Phys, 105 (2009).M. Croft, V. Shukla, N. M. Jisrawi, Z. Zhong, R. K. Sadangi, R. L. Holtz, P. S. Pao, K. Horvath, K. Sadananda, A. Ignatov, J. Skaritka and T. Tsakalakos, Int J Fatigue, 31, 1669 (2009).E. S. Takeuchi, A. C. Marschilok, K. J. Takeuchi, A. Ignatov, Z. Zhong and M. Croft, Energ Environ Sci, 6, 1465 (2013).J. W. Gallaway, C. K. Erdonmez, Z. Zhong, M. Croft, L. A. Sviridov, T. Z. Sholklapper, D. E. Turney, S. Banerjee and D. A. Steingart, Journal of Materials Chemistry A, 2, 2757 (2014).N. D. Ingale, J. W. Gallaway, M. Nyce, A. Couzis and S. Banerjee, J Power Sources, 276, 7 (2015).J. W. Gallaway, G. G. Yadav, D. E. Turney, M. Nyce, J. Huang, Y.-c. K. Chen-Wiegart, G. Williams, J. Thieme, J. S. Okasinski and X. Wei, J Electrochem Soc, 165, A2935 (2018).G. G. Yadav, J. W. Gallaway, D. E. Turney, M. Nyce, J. C. Huang, X. Wei and S. Banerjee, Nature Communications, 8 (2017).E. Levi, E. Lancry, A. Mitelman, D. Aurbach, G. Ceder, D. Morgan and O. Isnard, Chem Mater, 18, 5492 (2006).M. S. Chae, J. W. Heo, S.-C. Lim and S.-T. Hong, Inorg Chem, 55, 3294 (2016). Figure 1

Augmentation of cytochrome P450 monooxygenase catalysis on its interaction with NADPH-cytochrome P450 reductase FMN domain from Trichoderma brevicompactum.

Cytochrome P450s are involved in a variety of monooxygenation reactions that require electron transfer from one redox partner to the other. We have recently shown the catalytic mechanism of a cytochrome P450 monooxygenase like protein (encoded by tri11 gene) that catalyzes the hydroxylation of 12,13-epoxytrichothec-9-ene (EPT) to produce trichodermol in the trichothecene biosynthetic pathway of trichodermin and harzianum A in Trichoderma brevicompactum [J Biol Inorg Chem. 22(8):1197-1209. doi: https://doi.org/10.1007/s00775-017-1496-6]. In the present work we have analyzed the effects of interaction of CPR FMN domain, a redox partner of tri11 protein, on its catalysis. The analysis of protein-protein complex interface showed various important contacts between the two protein partners that may aid in the process of electron transfer. The redox partner binding with tri11 protein on proximal side elicited catalytically important changes on the oppositely situated distal side that may help in stabilizing the active site and may play positive roles during the catalysis.

The Irving-Williams series and the 2-His-1-carboxylate facial triad: a thermodynamic study of Mn2+, Fe2+, and Co2+ binding to taurine/α-ketoglutarate dioxygenase (TauD).

Taurine/α-ketoglutarate (αKG) dioxygenase (TauD) is an E. coli nonheme Fe2+- and αKG-dependent metalloenzyme that catalyzes the hydroxylation of taurine, leading to the production of sulfite. The metal-dependent active site in TauD is formed by two histidine and one aspartate that coordinating to one face of an octahedral coordination geometry, known as the 2-His-1-carboxylate facial triad. This motif is found in many nonheme Fe2+ proteins, but there is limited information on the thermodynamic parameters that govern metal-ion binding to this site. Here, we report data from calorimetry and related biophysical techniques to generate complete thermodynamic profiles of Mn2+ and Co2+ binding to TauD, and these values are compared to the Fe2+ data reported earlier Henderson et al. (Inorg Chem 54: 2278-2283, 2015). The buffer-independent binding constants (K) were measured to be 1.6 × 106, 2.4 × 107, and 1.7 × 109, for Mn2+, Fe2+, and Co2+, respectively. The corresponding ΔG° values were calculated to be -8.4, -10.1, and -12.5kcal/mol, respectively. The metal-binding enthalpy changes (ΔH) for these binding events are -11.1 (± 0.1), -12.2 (± 0.1), and -16.0 (± 0.6) kcal/mol, respectively. These data are fully consistent with the Irving-Williams series, which show an increasing affinity for transition metal ions across the periodic table. It appears that the periodic increase in affinity, however, is a result of a complicated summation of enthalpy terms (including favorable metal-ion coordination processes and unfavorable ionization events) and related entropy terms.

Completely Unexpected Coordination Selectivity of Copper Iodide for Thioether Over Ethynyl

The reactivity of the tetradentate ligand bis(p-thiomethylphenylacetylene) (MeSC6H4C≡C–C≡CC6H4SMe; L2) towards the CuI salt is compared to that for the known organometallic analogue trans-bis(p-thiomethylethynylbenzene)bis(trimethyl-phosphine)platinum(II) (trans-Pt(PMe3)2(C≡CC6H4SMe)2; L1). While L1 with CuI form a highly luminescent porous 2D coordination polymer (CP) of general formula ([Cu4I4]L1 · EtCN)n (CP1; Juvenal et al. in Inorg Chem 55:11096–11109, 2016) exhibiting both Cu(η2–C≡C) and Cu–S bonds, L2 reacts with CuI to produce a luminescent non-porous 2D CP exhibiting the general formula ([Cu4I4]{L2}3)n, CP2, which does not use the highly expected Cu(η2–C≡C) linkage, relying strictly upon Cu–S coordination. An examination of the X-ray structures for both L2 and CP2 indicates that CP2 network is built upon an expansion of the L2 lattice (plane sliding and slight L2–L2 distance separation) resembling to a sort of template effect. CP2 has been characterized by TGA, UV–Vis, emission spectroscopy, and photophysics, which are accompanied by DFT and TDDFT computations.

Kinetic characterization of the inhibition of protein tyrosine phosphatase-1B by Vanadyl (VO2+) chelates.

Protein tyrosine phosphatases (PTPases) are a prominent focus of drug design studies because of their roles in homeostasis and disorders of metabolism. These studies have met with little success because (1) virtually all inhibitors hitherto exhibit only competitive behavior and (2) a consensus sequence H/V-C-X5-R-S/T characterizes the active sites of PTPases, leading to low specificity of active site directed inhibitors. With protein tyrosine phosphatase-1B (PTP1B) identifed as the target enzyme of the vanadyl (VO2+) chelate bis(acetylacetonato)oxidovanadium(IV) [VO(acac)2] in 3T3-L1 adipocytes [Ou et al. J Biol Inorg Chem 10: 874-886, 2005], we compared the inhibition of PTP1B by VO(acac)2 with other VO2+-chelates, namely, bis(2-ethyl-maltolato)oxidovanadium(IV) [VO(Et-malto)2] and bis(3-hydroxy-2-methyl-4(1H)pyridinonato)oxidovanadium(IV) [VO(mpp)2] under steady-state conditions, using the soluble portion of the recombinant human enzyme (residues 1-321). Our results differed from those of previous investigations because we compared inhibition in the presence of the nonspecific substrate p-nitrophenylphosphate and the phosphotyrosine-containing undecapeptide DADEpYLIPQQG mimicking residues 988-998 of the epidermal growth factor receptor, a relevant, natural substrate. While VO(Et-malto)2 acts only as a noncompetitive inhibitor in the presence of either subtrate, VO(acac)2 exhibits classical uncompetitive inhibition in the presence of DADEpYLIPQQG but only apparent competitive inhibition with p-nitrophenylphosphate as substrate. Because uncompetitive inhibitors are more potent pharmacologically than competitive inhibitors, structural characterization of the site of uncompetitive binding of VO(acac)2 may provide a new direction for design of inhibitors for therapeutic purposes. Our results suggest also that the true behavior of other inhibitors may have been masked when assayed with only p-nitrophenylphosphate as substrate.

Calculating the geometry and Raman spectrum of physiological bis(L-histidinato)copper(II): an assessment of DFT functionals for aqueous and isolated systems.

Reliable density functional theory (DFT) calculations can be performed in conjuction with spectroscopic measurements to elucidate the structural properties of physiologically important bis(amino acidato)copper(II) compounds in solutions. They can provide insight into the influence of intermolecular interactions on the molecular geometry in the crystal lattice or solution when compared with a DFT gas-phase minimum. Our previous paper [Marković et al. (2014) Eur J Inorg Chem 198] reported the DFT-determined geometries and Raman spectra for different conformers of physiological bis(L-histidinato)copper(II) with 20 explicit water molecules, as calculated using the B3LYP functional. The present study examined the reliability of those B3LYP results by applying the M06 functional instead, as it should better account for noncovalent interactions. The water molecules were positioned more compactly around the complex by M06 than by B3LYP. The accuracies of the two functionals when compared to relevant experimental data showed that M06 was better at reproducing in-plane Cu-N bond lengths but B3LYP gave more accurate axial Cu-O distances. Both functionals reproduced the experimental Raman spectrum at pH8 to similar levels of accuracy and provided precise information on the Cu(II) coordination mode and conformation in aqueous solution. Additionally, we assessed several DFT and DFT-D functionals (BP86, B3LYP, B3LYP-D, M06, M06L, wB97XD, mPW2PLYPD) by using them to model the geometries of experimental bis(L-histidinato)copper(II) crystalline conformationsas isolated systems, and then benchmarking the results against those from high-level second-order pertubation Møller-Plesset (MP2) calculations. Although this assessment resulted in an equivocal conclusion because the MP2 results for the isolated complex were inconsistent with the corresponding DFT outcomes, it does provide new information on future benchmark options.

Mechanisms of the Water–Gas Shift Reaction Catalyzed by Carbonyl Complexes Mo(CO)6 and Mo2(CO)10: A Density Functional Theory Study

Four different mechanistic pathways for Mo(CO)6 and a reaction mechanism for the binuclear species Mo2(CO)10 catalyzed water–gas shift reaction (WGSR) have been analyzed using density functional method. It turned out that the binuclear catalyst provides more facile transformations through lower barriers in comparison to the mononuclear catalyst, which is explained by the metal–metal cooperativity between the two Mo centers. The energy span model indicates that the higher the TOF calculated, the faster the catalytic rate and the higher the catalytic efficiency. The bimetallic catalyst (Mo2(CO)10) with the highest value of the calculated TOF (2.60 × 10−15 s−1), which is higher than that of Fe2(CO)9 (8.96 × 10−20 s−1) (see Kuriakose et al. in Inorg Chem 51: 377, 2012). The later prove the WGSR catalyst with high performance. Our conclusions will be useful for the design of improved WGSR catalysts in the future.

Theoretical insights into [NiFe]-hydrogenases oxidation resulting in a slowly reactivating inactive state.

[NiFe]-hydrogenases catalyse the relevant H2→2H++2e- reaction. Aerobic oxidation or anaerobic oxidation of this enzyme yields two inactive states called Ni-A and Ni-B. These states differ for the reactivation kinetics which are slower for Ni-A than Ni-B. While there is a general consensus on the structure of Ni-B, the nature of Ni-A is still controversial. Indeed, several crystallographic structures assigned to the Ni-A state have been proposed, which, however, differ for the nature of the bridging ligand and for the presence of modified cysteine residues. The spectroscopic characterization of Ni-A has been of little help due to small differences of calculated spectroscopic parameters, which does not allow to discriminate among the various forms proposed for Ni-A. Here, we report a DFT investigation on the nature of the Ni-A state, based on systematic explorations of conformational and configurational space relying on accurate energy calculations, and on comparisons of theoretical geometries with the X-ray structures currently available. The results presented in this work show that, among all plausible isomers featuring various protonation patterns and oxygenic ligands, the one corresponding to the crystallographic structure recently reported by Volbeda et al. (J Biol Inorg Chem 20:11-22, 19)-featuring a bridging hydroxide ligand and the sulphur atom of Cys64 oxidized to bridging sulfenate-is the most stable. However, isomers with cysteine residues oxidized to terminal sulfenate are very close in energy, and modifications in the network of H-bond with neighbouring residues may alter the stability order of such species.

Divalent copper ion bound amyloid-β(40) and amyloid-β(42) alloforms are less preferred than divalent zinc ion bound amyloid-β(40) and amyloid-β(42) alloforms.

Divalent copper and zinc ions bind to the amyloid-β(40) and amyloid-β(42) alloforms and affect their structural stability as well as their chemical and physical properties. Current literature debates the impact of copper ions on amyloid-β alloforms. Recently, we reported the structural and thermodynamic properties of apo amyloid-β and divalent zinc ion bound amyloid-β alloforms (see, Wise-Scira et al. in J Biol Inorg Chem 17:927-938, 2012 and Coskuner et al. in ACS Chem Neurosci 4: 310-320, 2013). In our search for understanding the impacts of transition metal ions on disordered amyloid-β, we also developed and reported new potential functions using quantum mechanics, which are required for high-quality molecular dynamics simulations of divalent copper ion bound amyloid-β alloforms (see, Wise and Coskuner in J Comput Chem 35:1278-1289, 2014). The structures and thermodynamic properties of the divalent copper ion bound amyloid-β(40) and amyloid-β(42) alloforms in an aqueous medium are studied. The secondary and tertiary structures of divalent copper ion bound amyloid-β(40) and amyloid-β(42) along with their thermodynamic properties including enthalpy, entropy, Gibbs free energy and potential of mean force surface are investigated. Results are compared to those for apo amyloid-β and divalent zinc ion bound amyloid-β alloforms. Results demonstrate that copper binding to Aβ alloforms is thermodynamically less preferred rather than zinc binding. Less compact structures of copper ion bound amyloid-β alloforms possess reduced stability in comparison to zinc ion bound amyloid-β alloforms. Cu(II) binding impacts the thermodynamic properties, secondary and tertiary structural properties of Aβ40 and Aβ42.

Theoretical Study of the Water-Gas Shift Reaction Catalyzed by Tungsten Carbonyls

A density functional theory calculation has been carried out to investigate the mechanism of W(CO)6 and W2(CO)10 catalyzed water-gas-shift reaction (WGSR). The calculations indicate that the bimetallic catalyst (W2(CO)10) would be likely to be more highly active than the mononuclear metal-based catalyst (W(CO)6) due to the possibility of metal–metal cooperativity in reducing the barriers for the WGSR. The energetic span model is a tool to compute catalytic turnover frequencies (TOFs) which is the traditional measure of the efficiency of a catalyst. The one with the highest efficiency usually gives the highest TOF. The bimetallic catalyst (W2(CO)10) exhibits high catalytic activity towards WGSR due to the highest value of the calculated TOF (3.62 × 10−12 s−1, gas phase; 8.74 × 10−15 s−1, solvent phase), which is higher than the value of TOF (8.96 × 10−20 s−1, gas phase; 3.96 × 10−19 s−1, solvent phase) proposed by Kuriakose et al. (Inorg Chem 51:377–385, 2012). Our results will be important for designing a better catalyst for the industrially important reaction.

Theoretical investigation of [Ru(tpy)2]2+, [Ru(tpy)(bpy)(H2O)]2+ and [Ru(tpy)(bpy)(Cl)]+ complexes in acetone revisited: Inclusion of strong spin–orbit couplings to quantum chemistry calculations

In the present paper, we theoretically reinvestigate structural properties, and photo-physical and chemical characteristics and electronic absorption spectra of three kinds of ruthenium polypyridyl complexes [Ru(tpy)[Formula: see text], [Ru(tpy)(bpy)(H2O)][Formula: see text], and [Ru(tpy)(bpy)(Cl)][Formula: see text] complexes in acetone (tpy[Formula: see text]2,2[Formula: see text],2[Formula: see text]-terpyridine and bpy[Formula: see text]2,2[Formula: see text]-bipyridine). In particular, the experimental absorption spectra of these complexes are revisited theoretically in detail and are simulated using the first-order perturbation theory based on time-dependent density functional theory (TD-DFT) where the first-order perturbation term is the spin–orbit (SO) coupling Hamiltonian, and quantum chemistry calculations based on various functionals and basis sets. It was found that in general the theory including SO coupling can reproduce experimental data better than the simple quantum chemistry calculation neglecting SO coupling, which indicates that SO coupling is very important to understand the optical features of these complexes and that therefore the mixing between singlet and triplet states is strong due to the large SO coupling constant of Ru atom involved in these complexes. This suggests the fact that the disagreement between the experimental and calculated absorption spectra was found in TDB3LYP/(SDD with triple-[Formula: see text] for Ru and 6-31G* for others) [Jakubikova EJ et al., Inorg Chem 48:10720, 2009] can be tracked down to the neglect of SO couplings. It was also found that the choice of the DFT functionals and basis sets is crucial for a good theoretical reproduction of experimental data.

Residual Erythropoiesis Protects Against Cardiac Iron Loading in Transfusion Dependent Thalassaemia (TDT) By Lowering Labile Plasma Iron (LPI) through Transient Apotransferrin Generation

▪IntroductionMyocardial iron loading frequently complicates TDT but factors affecting the highly variable risk are not fully understood and current available predictors do not explain this variability. Chronic blood transfusion in TDT, by correcting anemia, is life saving but also aims to reduce ineffective erythropoiesis (IE) and its complications. Such transfusion will also decrease utilisation of transferrin (Tf) iron by the erythron and increase Tf saturation (TfSat) (Porter et al, Brit J Haematol 2014). Here we examine for the first time, how variable levels of residual erythropoiesis in TDT (marked by soluble transferrin receptors, sTfR), and the consequent presence of ApoTf, affect myocardial iron loading. We then examine how the difference between the transfusional iron loading rate (ILR) and Tf iron utilisation (calculated from sTfR levels) impact on myocardial iron loading. We finally test the hypotheses generated by these findings, using in vitro models of cellular uptake of NTBI and its redox active component LPI, the main conduits of myocardial iron uptake, in the presence and absence of ApoTf.MethodsA cohort of 73 TDT patients on deferasirox (DFX) had cardiac MRI and blood biomarkers measured at baseline and at 1.5 years later, over which time the ILR was calculated. Patients were divided into those with cardiac iron (24 cases, cardiac T2*<20ms, R2* >50s-1) and those without (59 controls, T2*>20ms, R2* <50s-1): biomarkers of iron metabolism and routine biochemical variables were compared in both groups with data shown for the 1.5 year measurements. 48h washout from DFX was ensured prior to blood sampling for which patients gave written informed consent. NTBI, LPI, sTfR, TfSat were performed as in Porter et al 2014, mouse HL-1 cardiomyocytes grown as in Claycomb et al, PNAS 1998, Ferric citrate (Fe-cit) prepared as in Evans et al, J Biol Inorg Chem 2008, and total cellular iron was assayed by ferrozine as in Riemer et al Anal Biochem 2004.Results and DiscussionTf iron utilisation and myocardial iron in TDT. Of all biomarkers analysed, sTfR was most significantly associated with heart iron (p<0.001) being >3x higher in controls than cases. NTBI, LPI, TfSat and ILR were not significantly different in cases and controls, but LIC and ferritin were higher in cases (p=0.003 and 0.002). With sTfR expressed as Tf iron utilisation rate (or erythroid Tf uptake rate, ETUR) after Beguin et al, Blood 1993 and compared to ILR, myocardial iron was present only when the net ILR (ILR-ETUR) exceeded 0.21 mg/kg/d (p<0.001). Above and below this threshold LIC, TfSat and NTBI were similar (9.7 vs 10.1 mg/g dry weight, 96 vs 98%, 3 vs 2.6µM, p=ns), while LPI was 3x higher (0.35 vs 0.1 µM p=0.01). Thus LPI was high only in patients where the net ILR exceeded 0.21 whereas LIC, TfSat, NTBI showed no difference between patients with and without myocardial siderosis, even when adjusted for the net ILR (Figure 1).Effect of ApoTf and Fe:cit ratio on NTBI uptake into cultured cardiomyocytes. ApoTf or TfSat <100% inhibited NTBI uptake into HL-1 cells as well as LPI but did not increase iron release from cells preloaded with iron. Fe-cit, the main NTBI species, is less visible as LPI than NTA iron.Increasing excess of cit:Fe increases the proportion of iron visible to the LPI assay,increases myocardial iron uptake and iron binding to Tf. Previous work (Evans et al J Biol Inorg Chem 2008) showed that Fe:cit ratio does not affect the NTBI assay, by contrast we show it affects the LPI assay. The ratio affects uptake and because uptake may be redox dependent (Oudit et al, Nat Med 2003), it is very likely that a redox facile NTBI, i.e. LPI, is the key species taken up by the heart, further supported by Fe:cit ratios <1:100 (more citrate) accounting for the majority of uptake (EC90=1.09µM, Figure 2)ConclusionTaken together these data suggest that the risk of myocardial siderosis in TDT is critically dependent on the degree of residual erythropoiesis and the net balance between the transfusional iron delivery (ILR) and the iron utilisation rate by the erythron (ETUR). Myocardial siderosis occurs when the net ILR-ETUR exceeds 0.21 mg/kg/day, the same threshold at which LPI is increased. The likely mechanism is that higher ILR-ETUR values decrease TfSat<100% hence allowing transiently formed ApoTf to decrease LPI. This mechanism is supported by the finding that as little as 1µM ApoTf inhibits NTBI uptake into cardiomyocytes in culture while also decreasing LPI. [Display omitted] [Display omitted] DisclosuresPorter:Celgene: Consultancy; Shire: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding.

Catecholase activity, DNA cleavage and cytotoxicity of six Zn(II) complexes synthesized from designed Mannich ligands: higher reactivity of mononuclear over dinuclear.

Six zinc(II) complexes have been synthesized from two designed Mannich-base ligands which consist of three dinuclear complex [Zn2(L(1))2X2] (1-3) and three mononuclear complex [ZnH(L(2))X2] (4-6), respectively, where X=Cl(-) (1,4), Br(-) (2,5), I(-) (3,6), as reported earlier by us (Sanyal et al., Inorg Chem 53:85-96, 2014). The catecholase activity of the complexes has been investigated under completely aerobic conditions in DMF-water medium (9:1) at pH 8.5 against the model substrate 3,5-di-tert-butylcatechol (3,5-DTBC). Saturation kinetic studies show that the order of conversion of substrate to product (quinone) follows the trend 5>4>2>1 while 3 and 6 are inactive. The generation of phenoxyl radicals, confirmed by UV-vis and EPR spectral studies, is supposed to be responsible for the oxidation of 3,5-DTBC. The in vitro evaluation of 1-6 comprises the study of their DNA-cleaving ability using plasmid DNA and the assessment of their cytotoxic activity against Jurkat (T cell lymphoma) cell line by MTT assay. The mechanisms of toxicity appeared to be predominantly by reactive oxygen species (ROS). The comparative analysis helps to arrive at the following facts under experimental conditions: (1) mononuclear species prevail over the dinuclear ones, unlike the behavior in phosphatase activity as reported in Inorganic Chemistry; (2) the halide substituents at the active site control the overall activity in the order: (a) In catecholase activity, Cl(-)<Br(-) (dinuclear) and Cl(-)>Br(-) (mononuclear) and (b) in biological activity, Cl(-)>Br(-)>I(-) regardless of nuclearity.

Paramagnetic properties and molecular structure of coordination saturated inclusive lanthanide complexes with 18-crown-6 using NMR

Earlier NMR spectra of lanthanide complexes [Ln(18-crown-6)(NO3)3] have been analyzed by us (Babailov in Inorg Chem 51(3):1427–1433, 2012), where Ln3+ = La3+ (I), Ce3+ (II), Pr3+ (III) and Nd3+ (IV). The NMR signal assignment and conformational molecular dynamic have been found by 1D NOE and relaxation spectroscopy as well as on 2D NOESY and EXSY experiments at 170 K. In the present paper the 1H NMR method is used to study the features of paramagnetic properties of complexes I–IV and [Eu(18-crown-6)(NO3)3] (V) at ambient temperature. The investigation was carried out by special method based on analysis of Δδ/ on k(Ln)/ (where k(Ln) is Bleaney’s constant, Δδ is paramagnetic contribution to the lanthanide-induced shifts). The obtained results indicate that the structure of the complexes (in CDCl3 and CD2Cl2) are very similar.

SAPP modulates iron efflux from brain microvascular endothelial cells by stabilizing the ferrous iron exporter ferroportin.

A sequence within the E2 domain of soluble amyloid precursor protein (sAPP) stimulates iron efflux. This activity has been attributed to a ferroxidase activity suggested for this motif. We demonstrate that the stimulation of efflux supported by this peptide and by sAPPα is due to their stabilization of the ferrous iron exporter, ferroportin (Fpn), in the plasma membrane of human brain microvascular endothelial cells (hBMVEC). The peptide does not bind ferric iron explaining why it does not and thermodynamically cannot promote ferrous iron autoxidation. This peptide specifically pulls Fpn down from the plasma membrane of hBMVEC; based on these results, FTP, for ferroportin-targeting peptide, correctly identifies the function of this peptide. The data suggest that in stabilizing Fpn via the targeting due to the FTP sequence, sAPP will increase the flux of iron into the cerebral interstitium. This inference correlates with the observation of significant iron deposition in the amyloid plaques characteristic of Alzheimer's disease.