Polyanion Complexes Research Articles

Oxygenation by ruthenium monosubstituted polyoxotungstates in aqueous solution: experimental and computational dissection of a Ru(III)-Ru(V) catalytic cycle.

Molecular polyoxometalates with one embedded ruthenium center, with general formula [Ru(II/III)(DMSO)XW11O39](n-) (X = P, Si; n = 4-6), are readily synthesized in gram scale under microwave irradiation by a flash hydrothermal protocol. These nanodimensional and polyanionic complexes enable aerobic oxygenation in water. Catalytic oxygen transfer to dimethylsulfoxide (DMSO) yielding the corresponding sulfone (DMSO2 ) has been investigated with a combined kinetic, spectroscopic and computational approach addressing: (i ) the Ru(III) catalyst resting state; (ii ) the bimolecular event dictating its transformation in the rate-determining step; (iii ) its aerobic evolution to a high-valent ruthenium oxene species; (iv ) the terminal fate to diamagnetic dimers. This pathway is reminiscent of natural heme systems and of bioinspired artificial porphyrins. The in silico characterization of a key bis-Ru(IV)-μ-peroxo-POM dimeric intermediate has been accessed by density functional theory. This observation indicates a new landmark for tracing POM-based manifolds for multiredox oxygen reduction/activation, where metal-centered oxygenated species play a pivotal role.

Characterization of Self-Assembled Polyelectrolyte Complex Nanoparticles Formed from Chitosan and Pectin

Chronic wounds continue to be a global healthcare concern. Thus, the development of new nanoparticle-based therapies that treat multiple symptoms of these "non-healing" wounds without encouraging antibiotic resistance is imperative. One potential solution is to use chitosan, a naturally antimicrobial polycation, which can spontaneously form polyelectrolyte complexes when mixed with a polyanion in appropriate aqueous conditions. The requirement of at least two different polymers opens up the opportunity for us to form chitosan complexes with an additional functional polyanion. In this study, chitosan:pectin (CS:Pec) nanoparticles were synthesized using an aqueous spontaneous ionic gelation method. Systematically, a number of parameters, polymer concentration, addition order, mass ratio, and solution pH, were explored and their effect on nanoparticle formation was determined. The size and surface charge of the particles were characterized, as well as their morphology using transmission electron microscopy. The effect of polymer concentration and addition order on the nanoparticles was found to be similar to that of other chitosan:polyanion complexes. The mass ratio was tuned to create nanoparticles with a chitosan shell and a controllable positive zeta potential. The particles were stable in a pH range from 3.5 to 6.0 and lost stability after 14 days of storage in aqueous media. Due to the high positive surface charge of the particles, the innate properties of the polysaccharides used, and the harmless disassociation of the polyelectrolytes, we suggest that the development of these CS:Pec nanoparticles offers great promise as a chronic wound healing platform.

Nanoparticle-induced tight-junction opening for the transport of an anti-angiogenic sulfated polysaccharide across Caco-2 cell monolayers

Fucoidan has the ability to inhibit angiogenesis by human umbilical vein endothelial cells (HUVECs). However, a major clinical limitation is its poor oral availability because fucoidan is a hydrophilic macromolecule. In this study, an oversulfation reaction of fucoidan has been performed to enhance its anti-angiogenic activities. The synthesized, oversulfated fucoidan (OFD) was characterized by Fourier transform infrared spectroscopy. The oversulfate content of OFD was estimated to be 41.7% by using a BaCl2 gelatin method. Nanoparticles (NPs) composed of chitosan (CS) and OFD were prepared by a polycation–polyanion complex method. The mean particle sizes of prepared CS/OFD NPs were in the range of 172–265nm with a negative or positive surface charge, depending on the relative concentrations of CS to OFD used. The self-assembled NPs with pH-sensitive characteristics could be used as a pH-switched nanocarrier for oral delivery of the antiangiogenic macromolecule, OFD, in response to simulated gastrointestinal (GI) tract media. Evaluation of test NPs in enhancing the intestinal paracellular transport of OFD suggested that the NPs with a positive surface charge could transiently open the tight junctions between Caco-2 cells and thus increase the paracellular permeability. Tight-junction opening and restoration were examined by monitoring the redistribution of ZO-1 tight-junction proteins using confocal laser scanning microscopy (CLSM). The transported OFD significantly inhibits the tube formation of HUVECs via competitive binding of OFD and basic fibroblast growth factor (bFGF) to bFGF receptors (bFGFRs).

へパリン起因性血小板減少症における血小板第4因子（PF4）/ポリアニオンを用いた抗PF4/へパリン複合体抗体測定の臨床的意義

へパリン起因性血小板減少症における血小板第4因子（PF4）/ポリアニオンを用いた抗PF4/へパリン複合体抗体測定の臨床的意義

Coarse-Grained Simulation Studies of Effects of Polycation Architecture on Structure of the Polycation and Polycation–Polyanion Complexes

Polycations are a promising class of nonviral DNA delivery agents that bind to negatively charged DNA and transfect the DNA into target cells. The architecture and chemistry of the polycation strongly affect polycation–DNA complexation and in turn the ability of polycations to transfect DNA into cells. Here we develop coarse-grained models and conduct Langevin dynamics simulations to understand how the architecture of lysine-based polycations affects their complexation with DNA-like polyanions. We first characterize the structure of linear polylysine and oligolysines grafted to a polyolefin backbone and then the structure of complexes (termed polyplexes) formed by these polycations with polyanions of varying flexibility. We find that increasing oligolysine graft length and decreasing graft spacing both increase the size and rigidity of the grafted oligolysines, although they remain less rigid than semiflexible linear polylysine. Increasing ionic strength or counterion valency reduces polycation size and m...

How I Diagnose and Manage HIT

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4)/polyanion complexes. Platelet activation assays, such as the serotonin-release assay, are superior to PF4-dependent immunoassays in discerning which heparin-induced antibodies are clinically relevant. When HIT is strongly suspected, standard practice includes substituting heparin with an alternative anticoagulant; the 2 US-approved agents are the direct thrombin inhibitors (DTIs) lepirudin and argatroban, which are "niche" agents used only to manage HIT. However, only ~ 10% of patients who undergo serological investigation for HIT actually have this diagnosis. Indeed, depending on the clinical setting, only 10%-50% of patients with positive PF4-dependent immunoassays have platelet-activating antibodies. Therefore, overdiagnosis of HIT can be minimized by insisting that a positive platelet activation assay be required for definitive diagnosis of HIT. For these reasons, a management strategy that considers the real possibility of non-HIT thrombocytopenia is warranted. One approach that I suggest is to administer an indirect, antithrombin (AT)-dependent factor Xa inhibitor (danaparoid or fondaparinux) based upon the following rationale: (1) effectiveness in treating and preventing HIT-associated thrombosis; (2) effectiveness in treating and preventing thrombosis in diverse non-HIT situations; (3) both prophylactic- and therapeutic-dose protocols exist, permitting dosing appropriate for the clinical situation; (4) body weight-adjusted dosing protocols and availability of specific anti-factor Xa monitoring reduce risk of under- or overdosing (as can occur with partial thromboplastin time [PTT]-adjusted DTI therapy); (5) their long half-lives reduce risk of rebound hypercoagulability; (6) easy coumarin overlap; and (7) relatively low cost.

Templating α-Helical Poly(l-lysine)/Polyanion Complexes by Nanostructured Uniaxially Oriented Ultrathin Polyethylene Films

We report a templating effect of uniaxially oriented melt-drawn polyethylene (MD-PE) films on α-helical poly(L-lysine)/poly(styrenesulfonate) (α-PLL/PSS) complexes deposited by the layer-by-layer (LBL) method. The melt-drawing process induced an MD-PE fiber texture consisting of nanoscale lamellar crystals embedded in amorphous regions on the MD-PE film surface whereby the common crystallographic c axis is the PE molecular chain direction parallel to the uniaxial melt-drawing direction. The MD-PE film and the α-PLL/PSS deposit were analyzed by atomic force microscopy (AFM) and in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) using polarized light as a complementary method. Both methods revealed that α-PLL/PSS complexes adsorbed at the MD-PE surface were anisotropic and preferentially oriented perpendicular to the crystallographic c direction of the MD-PE film. Quantitatively, from AFM image analysis and ATR-FTIR dichroism of the amide II band of the α-PLL, mean cone opening angles of 12-18° for both rodlike α-PLL and the anisotropic α-PLL/PSS complexes with respect to the PE lamellae width direction were obtained. A model for the preferred alignment of α-PLL along the protruding PE lamellae is discussed, which is based on possible hydrophobic driving forces for the minimization of surface free energy at molecular and supermolecular topographic steps of the PE surface followed by electrostatic interactions between the interconnecting PSS and the α-PLL during layer-by-layer adsorption. This study elucidates the requirements and mechanisms involved in orienting biomolecules and may open up a path for designing templates to induce directed protein adsorption and cell growth by oriented polypeptide- or protein-modified PE surfaces.

MMX Chains and Molecular Species Containing Rh 2 n+ ( n = 4, 5, and 6) Units: Electrical Conductivity in Crystal Phase of MMX Polymers

The control of the experimental conditions in the reaction of Rh 2 (O 2 CCH 3 ) 4 with halides allows the isolation of the novel dirhodium complexes K x [Rh 2 X(O 2 CCH 3 ) 4 ] x ·4xH 2 O (X = Br, 1·4H 2 O and I, 2·4H 2 O) [Rh 2 (O 2 CCH 3 ) 4 Cl] x H 2 O (3·H 2 O), [Rh 2 (O 2 CCH 3 )Cl] x ·4xH 2 O (3·4H 2 O), and {Rh 2 (O 2 CCH 3 ) 4 I 2 ]· 4H 2 0 (4·4H 2 O) containing Rh 2 n+ (n = 4, 5 and 6) units. The X-ray structure determination of compounds 1-4 reveals the presence of dirhodium units in different oxidation states. The polyanionic complexes 1·4H 2 O and 2·4H 2 O containing Rh 2 4+ units give zig-zag chains. In contrast, the partially oxidized complexes 3·H 2 O and 3·4H 2 O containing Rh 2 5+ units are linked by chloride ligands forming linear chains. The first tetracarboxylatodirhodium(III) compound 4·4H 2 O is also described. Its structure consists of discrete binuclear [Rh 2 (O 2 CCH 3 ) 4 ] 2+ units with both axial positions occupied by iodide ligands. The very simple synthetic procedures presented here to achieve the partial or complete oxidation of the dirhodium(II) precursors open new perspectives in dirhodium complexes containing different oxidation states and in their potential applications in the construction of molecular devices. The electrical characterization of the polymer chains confirms conductivity in crystal phase. In addition, isolation of 1·4H 2 O and 2·4H 2 O on mica and morphological characterization of individual chains by atomic-force microscopy have been achieved.

An ion crystal based on silver double helicates and Keggin polyanions

An ion crystal [Ag2L2][(n-C4H9)4N][PMo12O40] · H2O · 0.5CH3OH · 0.25 DMF (I) (DMF is N,N-dimethylformamide) has been synthesized by the complexation of metal double helix and Keggin polyanions in a DMF-CH3 OH solution and structurally characterized by elemental analysis, IR spectra, and single-crystal X-ray diffraction. In compound I [PMo12O40]3− anions and [(n-C4H9)4N]+ ions alternately arrange themselves in a special order in consistence with that of [Ag2L2]2+ metal helicates based on π-π stacking interactions, yielding a packing of complex cations and Keggin anions.

Polyanion Hydrophobicity and Protein Basicity Affect Protein Stability in Protein−Polyanion Complexes

Stability of four dissimilar basic proteins (chymotrypsinogen A, ribonuclease A, cytochrome c, lysozyme) in the complex with four polyanions (heparin, poly(vinylsulfate), poly(4-styrene-sulfonate), Nafion) has been studied by differential scanning calorimetry. The polyanions were chosen because of their different charge density and hydrophobicity. Relative hydrophobicity of polyanions have been compared by three different parameters: (i) partition coefficient determined in octanol/water system, (ii) electrocapillary curves obtained by the method of controlled convection, and (iii) change in absorbance of small cationic amphiphilic molecule, aminoacridine, due to interaction with polyanion. Our results suggest that stability of proteins in the complex with polyanions negatively correlate with charge-related properties of the proteins such as isoelectric point and surface charge density and hydrophobicity of the polyanions.

The Effect of the Amide Substituent on the Biodistribution and Tolerance of Lanthanide(III) DOTA-Tetraamide Derivatives

Recent advances in the design of MRI contrast agents have rendered the lanthanide complexes of DOTA-tetraamide ligands of considerable interest, both as responsive MR agents and paramagnetic chemical exchange saturation transfer agents. The potential utility of these complexes for in vivo applications is contingent upon them being well tolerated by the body. The purpose of this study was to examine how the nature of the amide substituent, and in particular its charge, affected the fate of these chelates postinjection. Complexes of 6 DOTA-tetraamide ligands were prepared in which the nature of the amide substituent was systematically altered. The 6 ligands formed 3 series: a phosphonate series that included tri-cationic, mono-anionic, and poly-anionic complexes; a carboxylate series made up of a tri-cationic complex and a mono-anionic complex; and lastly, a tri-cationic complex with an aromatic amide substituent. These complexes were labeled with an appropriate radioisotope, either Gd or Lu, and the biodistribution profiles in rats recorded 2 hours postinjection. Biodistribution profiles were initially acquired at low doses to minimize adverse effects. All the complexes studied were found to be excreted primarily through the renal system, with the majority of the dose being found in the urine. None of the complexes exhibited substantial uptake by bone, liver, and spleen, except for a complex with 4 phosphonate groups that exhibited significant bone targeting capabilities. Increasing the dose of each complex to that of a typical MR contrast agent was found to render all 3 tri-cationic complexes studied here acutely toxic. In contrast, no ill effects were observed after administration of similar doses of the corresponding anionic complexes. The absence of uptake by the liver and spleen indicate that irrespective of the ligand structure and charge, these complexes are not prone to dissociation in vivo. This is in agreement with previously published work that indicates high kinetic inertness for this class of compounds. At low doses, all complexes were well tolerated; however, for applications that require higher doses, the structure and charge of the ligand becomes a fundamentally important parameter. The results reported herein demonstrate the importance of incorporating negatively charged groups on amide substituents if a DOTA-tetraamide complex is to be employed at high doses in vivo.

Complexation of single strand telomere and telomerase RNA template polyanions by deoxyribonucleic guanidine (DNG) polycations: Plausible anticancer agents

Cancerous cell immortality is due to relatively high concentrations of telomerase enzyme which maintains telomere sequence during cell division. Deoxyribonucleic guanidine (DNG) is a positively charged DNA analog in which guanidine replaces the phosphordiester linkage of DNA. Mixed sequences of DNG and DNA oligonucleotides are referred to as chimera. Complexation of DNG and chimeric polycations with the complementary negatively charged non-coding telomere single strand d(5′-TTAGGG-3′) n and the 11-base telomeric RNA template (5′-CUAACCCUAAC-3′) in the active site of telomerase has been studied. Calculated by ensemble sampling simulations in GBMV solvent model, we found that binding of complementary DNG hexamer with telomere is favored over that of DNA-telomere by ∼10 6-fold and binding of chimera hexamer is favored by ∼10 4-fold. Binding of complementary DNG with telomeric RNA is favored by 43 kcal/mol over telomere substrate binding with telomeric RNA.

Specific volume and compressibility of human serum albumin–polyanion complexes

The ultrasound velocimetry, densitometry, and differential scanning calorimetry have been used to study the formation of the complexes between human serum albumin (HSA) and polyanions heparin (HEP) and/or dextran sulfate (DS). The values of the ultrasound velocity and specific volume allowed us to determine the specific adiabatic compressibility, ϕ K/ β 0, which reflects the degree of volume compressibility of the complexes. We showed that in the presence of HEP and DS the adiabatic compressibility of HSA decreases with increasing concentration of polyanions. HEP more strongly interacts with HSA than DS. pH of electrolyte in the range 4.7–8.5 weakly affects the adiabatic compressibility. Changes of compressibility of HSA can be caused by increase of the hydration due to the formation of the HSA–polyanion complexes and due to partial unfolding of HSA. The HSA–polyanion interaction resulted in decrease of phase transition temperature of the protein. This evidences about protein destabilization in the presence of polyanions.

Heavy metal precipitation by polycation–polyanion complex of PEI and its phosphonomethylated derivative

The removal of various heavy metal ions such as Cu 2+, Co 2+, Zn 2+, Ni 2+ and Pb 2+ from aqueous solutions by precipitation with polyelectrolyte complex of PPEI and PEI was conducted. Heavy metal binding with PPEI was initially allowed to occur and then upon equilibration, PEI was added to initiate precipitation of the polyelectrolyte complex together with the heavy metal ion. The PPEI–PEI system was found effective for heavy metal scavenging purposes even in the presence of high concentrations of non-transition metal ions like Na +. Heavy metal concentration may be reduced beyond emission standards for industrial wastewaters. The PPEI–PEI polyelectrolyte complex was found to be more effective than traditional precipitation methods for the treatment of a representative electroless Ni plating waste solution.

Adsorptive Voltammetry of Polyelectrolyte Complex Between 11‐Ferrocenyltrimethylundecylammonium and Polyanions at Carbon Paste Electrode

AbstractFor polyelectrolyte complex between cationic surfactant and polyanion, the adsorptive voltammetry at carbon paste electrode using an electroactive cationic surfactant was examined. The adsorption state of the cationic surfactant in the complexes at CPE was estimated from the half‐height width of the oxidation waves. The half‐height width for poly(styrene sulfonate) was independent of the molecular weight, and was same as that for poly(vinyl sulfate). The half‐height width for heparin was broad and different from that of the vinyl polyanions. According to the analysis by Frumkin isotherm, the interaction between cationic surfactants was attractive in heparin complex at CPE, however, in the vinyl polyanion complexes at CPE the interaction was non‐cooperative as that predicted with the Langmuir isotherm. In spite of the same adsorption state, the concentration dependency of the peak current for poly(styrene sulfonate) was quite different from that for poly(vinyl sulfate). The concentration dependence indicated the reactive property of each polyanion on the association with the cationic surfactant in aqueous solution.

Monte Carlo simulations of flexible polyanions complexing with whey proteins at their isoelectric point.

Electrostatic complexation of flexible polyanions with the whey proteins alpha-lactalbumin and beta-lactoglobulin is studied using Monte Carlo simulations. The proteins are considered at their respective isoelectric points. Discrete charges on the model polyelectrolytes and proteins interact through Debye-Huckel potentials. Protein excluded volume is taken into account through a coarse-grained model of the protein shape. Consistent with experimental results, it is found that alpha-lactalbumin complexes much more strongly than beta-lactoglobulin. For alpha-lactalbumin, strong complexation is due to localized binding to a single large positive "charge patch," whereas for beta-lactoglobulin, weak complexation is due to diffuse binding to multiple smaller charge patches.

Binding of Phosphate, Pyrophosphate, and Hexacyanoferrate(II) by Fully N-Methyl Substituted Polyammonium Cations in Aqueous Solution

In this study, we determined the stability of some fully N-methyl substituted polycation−inorganic polyanion complexes by potentiometric measurements at t = 25 °C. As for other previously studied similar systems, the stability of ALHr species (A = amine; L = inorganic polyanion; r = 1, 2, ... m, with m ≥ n, n = maximum protonation degree of the amine) is a function of the charges involved in the formation equilibrium. The basicity of the polyanion also plays a fairly significant role. The stability of these species is compared with that of analogous species of unsubstituted amines and with that of polyammonium−carboxylate complexes. Simple predictive stability relationships are given.

Binding of acrylic and sulphonic polyanions by open-chain polyammonium cations

The interactions between some acrylic and sulphonic polyanions and some protonated amines (diamines NH 2-(CH 2) x -NH 2, x=2,…,10; linear tri-, tetra-, penta- and hexa-amines) were studied potentiometrically in aqueous solution, at 25°C. For both types of polyanions AL 2H i (L −, monomer of polyanion, A, amine) species are formed, with i=1,…, n ( n=number of amino groups in the amine). The stability of these species is strictly dependent on the polyammonium cation charge, and fairly independent of the type of amine (in diamine species maximum stability is observed for x=4, 5). Acrylic and sulphonic polyanion complexes are considerably stronger than analogous species formed by low molecular weight anions. Mean stability can be expressed as log K=2.87 ζ 2/3, for polyacrylic anions and log K=2.42 ζ 2/3 for polysulphonic anions ( ζ=absolute value for charge product of reactants).

Structural and electronic properties of liquid alkali–tin alloys

There is a debate about the preservation of tetrahedral polyanions formed in crystalline equiatomic (Na/K/Rb/Cs)–(Sn/Pb) compounds on melting. Diffraction experiments demonstrate the existence of a narrow first diffraction peak in the static structure factor indicative of local ordering. On the other hand reverse Monte-Carlo calculations and classical as well as quantum-mechanical simulations have failed to confirm the existence of polyanionic complexes in a liquid phase. We present ab initio local density functional studies of the structural and electronic properties of crystalline and liquid (Li/Na/K)–Sn alloys. While our calculations demonstrate the existence of tetrahedral complexes in KSn, for NaSn they agree with previous conclusions that the Sn 4 4−-tetrahedra are distorted or even destroyed in the liquid. For the liquid LiSn alloy we demonstrate that, due to the small size of the Li-ion, interactions between the Sn-ions destabilize the polyanionic order.

Binding of polyanions by biogenic amines. II. Formation and stability of protonated putrescine and cadaverine complexes with carboxylic ligands

The formation and stability of protonated diamines–carboxylic ligand complexes was studied potentiometrically (H +-glass electrode). Species formed are ALH r (A=cadaverine, putrescine, L=acetate, malate, tartrate, malonate, citrate, 1,2,3-propanetricarboxylate, 1,2,3,4-butanetetracarboxylate and glutamate; r=1... m+1, where m is the maximum degree of protonation of the carboxylic ligand), and their stability is a function of charges involved in the formation reaction. For the equilibrium H i A i+ +H j L ( j− z) =ALH ( i+ j− z) i+ j the following linear relationships can be written: log K 1 j =−0.25+0.75 | j− z|, log K 2 j =0.50+0.90 | j− z| (by also considering some ethylenediamine and 1,2-diaminopropane complexes). Medium effects were considered. Comparison was made with analogous inorganic polyanion complexes. The simplest relationships −Δ G 0=6.5±0.3 and −Δ G 0=7.9±0.6 kJ mol −1 n −1 ( n=number of possible salt bridges) were found for carboxylic and inorganic anions, respectively.