Stability of metal ion complexes formed with methyl phosphate and hydrogen phosphate

 The acidity constants of methyl phosphoric acid, CH₃OPO(OH)₂, and orthophosphoric acid, HOPO(OH)₂, and the stability constants of the 1 : 1 complexes formed between Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, or Cd²⁺ and methyl phosphate, CH₃OPO₃ ^2–, or hydrogen phosphate, HOPO₃ ^2–, were determined by potentiometric pH titration in aqueous solution (25  °C;I = 0.1 M, NaNO₃). On the basis of previously established log K versus pK _a straight-line plots for the complexes of simple phosphate monoesters and phosphonate derivatives, R-PO₃ ^2–, where R is a noncoordinating residue, it is shown that the stability of the M(CH₃OPO₃) complexes is solely determined (as one might expect) by the basicity of the –PO₃ ^2– residue. It is emphasized that the mentioned reference lines may also be used to reveal increased complex stabilities, for example, for certain complexes formed with 8-quinolyl phosphate the occurrence of 7-membered chelates can be proven in this way; the same procedure is also applicable to complexes of nucleotides, etc. The M(HOPO₃) complexes are slightly more stable (on average by 0.08 log unit) than it is expected from the basicity of HPO₄ ^2–; this observation is attributed to a more effective solvation, including hydrogen bonding, than is possible with CH₃OPO₃ ^2– species. Received: 9 November 1995 / Accepted: 5 February 1996     

Conformational isomerization of lactate dehydrogenase complexes formed by pyruvate and coenzyme analogs]

The kinetics of LDH-catalyzed reduction of pyruvate involving APADH were studied. It was shown that under conditions of a single turnover reaction the first order rate constant is equal to 37+/-4 sec-1. The reaction rate (vo) did not change when a deutero-coenzyme was used. The relationship between vo and pyruvate concentration is hyperbolic. It is concluded that isomerization of the ternary LDH-APADH-pyruvate complex limits the reaction rate. The spectral properties and the kinetics of formation and dissociation of abortive LDH complexes with pyruvate and NAD analogs (APAD and PAAD) were studied. The participation of the carboxamide group of NAD in conformational isomerization of the LDH-NADH-pyruvate and LDH-NAD-pyruvate complexes was studied.     

Catalytic hydrolysis of DNA by metal ions and complexes

Biomimetic hydrolysis of DNA or RNA is of increasing importance in biotechnology and medicine. Most natural nuclease enzymes that mediate such reactions utilize metal ion cofactors. Recent progress in the design of synthetic metallonucleases has included complexes of antibiotics, peptides, nucleic acids, and other organic ligands. In this article, we review a number of synthetic catalyst systems that have been developed to achieve efficient DNA hydrolysis. Methods to evaluate their catalytic efficiencies are critically discussed, and a prognosis for future work in this area is presented.     

Modulation of biomolecular phase behavior by metal ions

Liquid–liquid phase separation (LLPS) appears to be a newly appreciated aspect of the cellular organization of biomolecules that leads to the formation of membraneless organelles (MLOs). MLOs generate distinct microenvironments where particular biomolecules are highly concentrated compared to those in the surrounding environment. Their thermodynamically driven formation is reversible, and their liquid nature allows them to fuse with each other. Dysfunctional biomolecular condensation is associated with human diseases. Pathological states of MLOs may originate from the mutation of proteins or may be induced by other factors. In most aberrant MLOs, transient interactions are replaced by stronger and more rigid interactions, preventing their dissolution, and causing their uncontrolled growth and dysfunction. For these reasons, there is great interest in identifying factors that modulate LLPS. In this review, we discuss an enigmatic and mostly unexplored aspect of this process, namely, the regulatory effects of metal ions on the phase behavior of biomolecules.     

DNA complexes, formed on aqueous phase surfaces: new planar polymeric and composite nanostructures

The formation of DNA complexes with Langmuir monolayers of the cationic lipid octadecylamine (ODA) and the new amphiphilic polycation poly-4-vinylpyridine with 16% of cetylpyridinium groups (PVP-16) on the surface of an aqueous solution of native DNA of low ionic strength was studied. Topographic images of Langmuir-Blodgett films of DNA/ODA and DNA/PVP-16 complexes applied to micaceous substrates were investigated by the method of atomic force microscopy. It was found that films of the amphiphilic polycation have an ordered planar polycrystalline structure. The morphology of planar DNA complexes with the amphiphilic cation substantially depended on the incubation time and the phase state of the monolayer on the surface of the aqueous DNA solution. Complex structures and individual DNA molecules were observed on the surface of the amphiphilic monolayer. Along with quasi-linear individual bound DNA molecules, characteristic extended net-like structures and quasi-circular toroidal condensed conformations of planar DNA complexes were detected. Mono- and multilayer films of DNA/PVP-16 complexes were used as templates and nanoreactors for the synthesis of inorganic nanostructures via the binding of metal cations from the solution and subsequent generation of the inorganic phase. As a result, ultrathin polymeric composite films with integrated DNA building blocks and quasi-linear arrays of inorganic semiconductor (CdS) and iron oxide nanoparticles and nanowires were obtained. The nanostructures obtained were characterized by scanning probe microscopy and transmission electron microscopy techniques. The methods developed are promising for investigating the mechanisms of structural organization and transformation in DNA and polyelectrolyte complexes at the gas-liquid interface and for the design of new extremely thin highly ordered planar polymeric and composite materials, films, and coatings with controlled ultrastructure for applications in nanoelectronics and nanobiotechnology.     

DNA structural transitions induced by divalent metal ions in aqueous solutions

Using methods of IR spectroscopy, light scattering, gel-electrophoresis DNA structural transitions are studied under the action of Cu2+, Zn2+, Mn2+, Ca2+ and Mg2+ ions in aqueous solution. Cu2+, Zn2+, Mn2+ and Ca2+ ions bind both to DNA phosphate groups and bases while Mg2+ ions-only to phosphate groups of DNA. Upon interaction with divalent metal ions studied (except for Mg2+ ions) DNA undergoes structural transition into a compact form. DNA compaction is characterized by a drastic decrease in the volume occupied by DNA molecules with reversible formation of DNA dense particles of well-defined finite size and ordered morphology. The DNA secondary structure in condensed particles corresponds to the B-form family. The mechanism of DNA compaction under Mt2+ ion action is not dominated by electrostatics. The effectiveness of the divalent metal ions studied to induce DNA compaction correlates with the affinity of these ions for DNA nucleic bases: Cu2+>Zn2+>Mn2+>Ca2+>Mg2+. Mt2+ ion interaction with DNA bases (or Mt2+ chelation with a base and an oxygen of a phosphate group) may be responsible for DNA compaction. Mt2+ ion interaction with DNA bases can destabilize DNA causing bends and reducing its persistent length that will facilitate DNA compaction.     

Inhibition of vitamin K-dependent carboxylase by metal ions and metal complexes: a reassessment

The vitamin K-dependent enzymatic carboxylation of glutamyl residues in blood protein precursors and in synthetic peptides is inhibited in vitro by transition metal complexes. Some authors suggested it is a result of metal ions interaction with intermediary oxygenated species. Using an oxygraph we have observed increases in the rate of oxygen utilization in the carboxylating system containing reduced vitamin K after addition of some transition metal ions and complexes. Kinetic studies indicate that, although oxygen utilization is increased by the addition of Cu2+, Fe3+, and hematin, the initial rate of carboxylation is not affected. The rate of carboxylation rapidly decreases at oxygen concentrations below 50 microM and reaches zero when oxygen is depleted. UV spectroscopy revealed simultaneous acceleration of the conversion of vitamin K hydroquinone into the parent quinone. The magnitude of these effects, as well as carboxylation inhibition, depends on the oxidation potential of the complexed ion and its lipophilicity. Addition of stable Mn parallel ion, which has no inhibitory effect on carboxylation, does not increase the rate of oxygen utilization nor the hydroquinone oxidation. The results suggest that inhibition of carboxylation by transition metals is mainly due to depletion of the necessary components (oxygen, vitamin K hydroquinone) of the carboxylating system rather than quenching of activated, oxygen-containing intermediates.     

Columnar lyomesophases formed in hydrocarbon solvents by chiral lipophilic guanosine-alkali metal complexes

The lipophilic guanosine derivative 1 acts as a self-assembled ionophore and, in the presence of alkali metal ions, forms chiral polymeric structures in organic solvents. These polymeric columnar aggregates are comprised of G-quartets held together by alkali metal ions which are located inside the tubular structure; the quartets are surrounded by hydrocarbon chains. In hydrocarbon solvents, these columnar aggregates form lyomesophases of the cholesteric and hexagonal type. Copyright 2000 Wiley-Liss, Inc.     

Superoxide and hydrogen peroxide suppression by metal ions and their EDTA complexes

Redox-active metal ions such as Fe(II)\(III) and Cu(I)\(II) have been proposed to activate reactive oxygen and nitrogen species (RONS) and thus, perpetuate oxidative damage. Here, we show that concentrations of metal ions and EDTA complexes with superoxide-destroying activities equivalent to 1 U SOD are Fe(III) 5.1 microM, Mn(II) 0.77 microM, Cu(II)-EDTA 3.55 microM, Fe(III)-EDTA 2.34 microM, and Mn(II)-EDTA 1.38 microM. The most active being the aquated Cu(II) species which exhibited superoxide-destroying activity equivalent to 2U of SOD at 0.29 microM. Hydrogen peroxide-destroying activities were as follows Fe(III)-EDTA ca. 70 U/mg and aquated Fe(III) 141 U/mg. In contrast, DTPA prevented superoxide-destroying activity and significantly depleted hydrogen peroxide-destroying activity. In conclusion, non-protein bound transition metal ions may have significant anti-oxidant effects in biological systems. Caution should be employed in bioassays when chelating metal ions. Our results demonstrate that DTPA is preferential to EDTA for inactivating redox-active metal ions in bioassays.     

The removal by crab shell of mixed heavy metal ions in aqueous solution

In order to examine the inhibition effect of other heavy metal ions on the removal by crab shell of heavy metal ions in aqueous solutions, three ions (Pb(2+), Cd(2+), Cr(3+)) were used in single, binary and ternary systems. In single heavy metal ion systems, the removals of Cr(3+) and Pb(2+) were much higher than that of Cd(2+). In binary heavy metal ions systems, Cd(2+) did not affect Pb(2+) removal while Cr(3+) had a severe inhibition effect on the removal of Pb(2+). Cd(2+) removal was slightly affected by the presence of Pb(2+); however, it was severely affected by the presence of Cr(3+). The inhibitory effect of Cd(2+) on Cr(3+) was relatively lower than that of Pb(2+).     

Coordinated cations in dipicolinato complexes of divalent metal ions

Several salts of alkali, alkaline earth metal and organic ammonium cations of a complex anion [ML₂]²⁻ {Where L = dipicolinato dianion, M = copper(II), nickel(II) and zinc(II)} are prepared. The coordination effect of [ML₂]²⁻ with the cations such as sodium, potassium, calcium, magnesium, and organic cations namely diammonium cation of 1,5-pentanediamine, diammonium cation of 1,8-octyldiamine, mono ammonium cation of 4-aminobenzylamine are studied by determining their X-ray crystal structures. Depending on the nature of cations, four different types of structures are obtained. When calcium is the cation a polymeric structure with calcium ions bridging the [ML₂]²⁻ is observed. The salts having sodium and potassium cations form polymeric chain like structures by oxo and aqua bridges. In the case of magnesium, the hydrated form of magnesium cations coordinates to [ML₂]²⁻. The organic ammonium salts of [ML₂]²⁻ have the structural features of conventional ionic complexes. These salts easily exchange cations. The organic ammonium salts of [ML₂]²⁻ decomposes to give the corresponding metal oxides at relatively low temperature range 300-450 °C.     

Inhibition of cellulase-catalyzed lignocellulosic hydrolysis by iron and oxidative metal ions and complexes

Enzymatic lignocellulose hydrolysis plays a key role in microbially driven carbon cycling and energy conversion and holds promise for bio-based energy and chemical industries. Cellulases (key lignocellulose-active enzymes) are prone to interference from various noncellulosic substances (e.g., metal ions). During natural cellulolysis, these substances may arise from other microbial activities or abiotic events, and during industrial cellulolysis, they may be derived from biomass feedstocks or upstream treatments. Knowledge about cellulolysis-inhibiting reactions is of importance for the microbiology of natural biomass degradation and the development of biomass conversion technology. Different metal ions, including those native to microbial activity or employed for biomass pretreatments, are often tested for enzymatic cellulolysis. Only a few metal ions act as inhibitors of cellulases, which include ferrous and ferric ions as well as cupric ion. In this study, we showed inhibition by ferrous/ferric ions as part of a more general effect from oxidative (or redox-active) metal ions and their complexes. The correlation between inhibition and oxidation potential indicated the oxidative nature of the inhibition, and the dependence on air established the catalytic role that iron ions played in mediating the dioxygen inhibition of cellulolysis. Individual cellulases showed different susceptibilities to inhibition. It is likely that the inhibition exerted its effect more on cellulose than on cellulase. Strong iron ion chelators and polyethylene glycols could mitigate the inhibition. Potential microbiological and industrial implications of the observed effect of redox-active metal ions on enzymatic cellulolysis, as well as the prevention and mitigation of this effect in industrial biomass conversion, are discussed.     

Alpha-glucosidase inhibitory effect of anti-diabetic metal ions and their complexes

We found alpha-glucosidase inhibitory (α-GI) effect of metal ions and their complexes which showed the high blood glucose lowering effect in diabetic model animals. The Cu(II) ion and its complexes showed strong α-GI activity greater than clinically used acarbose in in vitro studies. Furthermore, in in vivo experiments, α-GI action was newly discovered in normal ddy mice. These results suggested that one of action mechanisms of the anti-diabetic metal ions and complexes is related to the α-GI effects.     

Antioxidant properties of complexes of flavonoids with metal ions

The formation of complexes of metal ions with the flavonoids quercetin (L1), rutin (L2), galangin (L3) and catechin (L4) has been investigated by UV-visible spectroscopy. The antioxidant activities of the compounds were evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicalscavenging method. In this work, we have shown that the complexed flavonoids are much more effective free radical scavengers than the free flavonoids. We suggest that the higher antioxidant activity of the complexes is due to the acquisition of additional superoxide dismutating centers. Radical scavenging activities of the compounds were also investigated from an electrochemical point of view. There is a relationship between the logarithm of the antioxidant activity (represented by EC50) and the oxidation potential. The synergic effect of the complexes and ascorbic acid were studied by [13C]-NMR analyses. The results show that ascorbic acid can protect flavonoids from oxidative degradation, and reveal antioxidant synergies between ascorbic acid and the compounds.     

Further structural analysis of GnRH complexes with metal ions

MALDI-TOF mass spectrometry, 1H NMR spectrometry, the continuous variation method and molecular modeling by MM3 calculation confirmed our earlier studies showing that gonadotropin-releasing hormone (GnRH) forms complex with copper(II) ion with the binding ratio 1:1. The copper(II) complex formed at physiological pH has a square planar configuration and GnRH complexes with nickel(II) and cobalt(II) ions are less stable than that of copper(II).     

Stability constants of metal complexes of phosphonoacetic acid

The antiviral drug, phosphonoacetic acid (PAA), forms stable complexes with Mg²⁺, Ca²⁺, Cu²⁺ and Zn²⁺. Stability constants of these complexes were determined in aqueous solution (0.15 M in KNO₃, 37°) by potentiometric titration. Mixed ligand complex formation of Cu²⁺ and Zn²⁺ with PAA and glycinate ion, and with PAA and histidinate ion, was studied. In a theoretical model for blood plasma, PAA affects the distribution of Mg²⁺ and, to a lesser extent, Ca²⁺.