scholarly journals Ternary Copper(II) Complexes in Solution[1,2] Formed With 8-Aza Derivatives of the Antiviral Nucleotide Analogue 9-[2-(Phosphonomethoxy)Ethyl]Adenine (PMEA)

2000 ◽  
Vol 7 (6) ◽  
pp. 313-324 ◽  
Author(s):  
Raquel B. Gómez-Coca ◽  
Larisa E. Kapinos ◽  
Antonín Holý ◽  
Rosario A. Vilaplana ◽  
Francisco González-Vílchez ◽  
...  
Keyword(s):  
Metal Ion ◽  
Biological Properties ◽  
Mixed Ligand ◽  
Aromatic Rings ◽  
Group 14 ◽  
Phosphonate Group ◽  
Nucleotide Analogue ◽  
Ether Oxygen ◽  
The Stability ◽  
Derivatives Of

The stability constants of the mixed-ligand complexes formed between Cu(Arm)2+, where Arm= 2,2'-bipyridine (Bpy) or 1,10-phenanthroline (Phen), and the dianions of 9-[2-(phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA) and 8-[2-(phosphonomethoxy)ethyl]-8-azaadenine (8,8aPMEA) (both also abbreviated as PA2-) were determined by potentiometric pH titrations in aqueous solution (25 °C; I = 0.1 M, NaNO3). All four ternary Cu(Arm)(PA) complexes are considerably more stable than corresponding Cu(Arm)(R-PO3) species, where R-PO32− represents a phosph(on)ate ligand with a group R that is unable to participate in any kind of interaction within the complexes. The increased stability is attributed to intramolecular stack formation in the Cu(Arm)(PA) complexes and also to the formation of 5-membered chelates involving the ether oxygen present in the -CH2-O-CH2-PO32− residue of the azaPMEAs. A quantitative analysis of the intramolecular equilibria involving three structurally different Cu(Arm)(PA) species is carried out. For example, about 5% of the Cu(Bpy)(8,8aPMEA) system exist with the metal ion solely coordinated to the phosphonate group, 14% as a 5-membered chelate involving the -CH2-O-CH2-PO32−residue, and 81% with an intramolecular stack between the 8-azapurine moiety and the aromatic rings of Bpy. The results for the other systems are similar though with Phen a formation degree of about 90% for the intramolecular stack is reached. The existence of the stacked species is also proven by spectrophotometric measurements. In addition, the Cu(Arm)(PA) complexes may be protonated, leading to Cu(Arm)(H;PA)+ species for which it is concluded that the proton is located at the phosphonate group and that the complexes are mainly formed by a stacking adduct between Cu(Arm)2+ and H(PA)-. Conclusions regarding the biological properties of these azaPMEAs are shortly indicated.

Solution properties of metal ion complexes formed with the antiviral and cytostatic nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]-2-amino-6-dimethylaminopurine (PME2A6DMAP)

2014 ◽  
Vol 92 (8) ◽  
pp. 771-780 ◽  
Author(s):  
Raquel B. Gómez-Coca ◽  
Astrid Sigel ◽  
Bert P. Operschall ◽  
Antonín Holý ◽  
Helmut Sigel
Keyword(s):  
Aqueous Solution ◽  
Stability Constants ◽  
Metal Ion ◽  
Present System ◽  
Therapeutic Effects ◽  
Solution Properties ◽  
Acidity Constants ◽  
Nucleotide Analogue ◽  
Ether Oxygen ◽  
The Stability

The acidity constants of protonated 9-[2-(phosphonomethoxy)ethyl]-2-amino-6-dimethylaminopurine (H3(PME2A6DMAP)+) are considered, and the stability constants of the M(H;PME2A6DMAP)+ and M(PME2A6DMAP) complexes (M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+) were measured by potentiometric pH titrations in aqueous solution (25 °C; I = 0.1 mol/L, NaNO3). In the M(H;PME2A6DMAP)+ species, H+ and M2+ (mainly outersphere) are at the phosphonate group; this is relevant for phosphoryl-diester bridges in nucleic acids because, in the present system, there is no indication for a M2+–purine binding. This contrasts, for example, with the complexes formed by 9-[2-(phosphonomethoxy)ethyl]adenine, M(H;PMEA)+, where M2+ is mainly situated at the adenine residue. Application of log [Formula: see text] vs. [Formula: see text] plots for simple phosph(on)ate ligands, R–PO32− (R being a residue that does not affect M2+ binding), proves that all M(PME2A6DMAP) complexes have larger stabilities than what would be expected for a M2+–phosphonate coordination. Comparisons with M(PME–R) complexes, where R is a noncoordinating residue of the (phosphonomethoxy)ethane chain, allow one to conclude that the increased stability is due to the formation of five-membered chelates involving the ether–oxygen of the –CH2–O–CH2–PO32− residue: the percentages of formation of these M(PME2A6DMAP)cl/O chelates, which occur in intramolecular equilibria, vary between 20% (Sr2+, Ba2+) and 50% (Zn2+, Cd2+), up to a maximum of 67% (Cu2+). Any M2+ interaction with N3 or N7 of the purine moiety, as in the parent M(PMEA) complexes, is suppressed by the (C2)NH2 and (C6)N(CH3)2 substituents. This observation, together with the previously determined stacking properties, offers an explanation why PME2A6DMAP2– has remarkable therapeutic effects.

Metal Ion-Binding Properties of the Nucleotide Analogue 1-[2-(Phosphonomethoxy)ethyl]cytosine (PMEC) in Aqueous Solution

1999 ◽  
Vol 64 (4) ◽  
pp. 613-632 ◽  
Author(s):  
Claudia A. Blindauer ◽  
Antonín Holý ◽  
Helmut Sigel
Keyword(s):  
Aqueous Solution ◽  
Metal Ions ◽  
Metal Ion ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
Binding Properties ◽  
Nucleotide Analogue ◽  
Ether Oxygen ◽  
The Stability ◽  
Isomeric Equilibria

The acidity constants of the twofold protonated nucleotide analogue 1-[2-(phosphonomethoxy)ethyl]cytosine, H2(PMEC)±, as well as the stability constants of the M(H;PMEC)+ and M(PMEC) complexes with the metal ions M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ have been determined by potentiometric pH titrations in aqueous solution at I = 0.1 M (NaNO3) and 25 °C. Comparison with previous results for the nucleobase-free compound (phosphonomethoxy)ethane, PME, and the parent nucleotides cytidine 5'-monophosphate (CMP2-) and 2'-deoxycytidine 5'-monophosphate (dCMP2-) shows that the metal ion-binding properties of PMEC2- resemble closely those of PME2-: This means, the primary binding site is the phosphonate group and with all of the metal ions studied, 5-membered chelates involving the ether oxygen of the -CH2-O-CH2-PO32- chain are formed. The position of the isomeric equilibria between these chelates and the "open" complexes, -PO32-/M2+ is calculated; the degree of formation of the chelates is identical within the error limits for the M(PME) and M(PMEC) systems. Hence, like in M(CMP) and M(dCMP) no interaction occurs with the cytosine residue in the M(PMEC) complexes. However, the monoprotonated M(H;PMEC)+ as well as the M(H;CMP)+ and M(dCMP)+ species carry the metal ion predominantly at the nucleobase, while the proton is at the phosph(on)ate group. The coordinating properties of PMEC2- and CMP2- or dCMP2- differ thus only with respect to the possible formation of the 5-membered chelates involving the ether oxygen in M(PMEC) species, a possibility which does not exist in the complexes of the parent nucleotides. Possible reasons why PMEC is devoid of a significant antiviral activity are shortly discussed.

Ternary Complexes in Solution+ with Phosphonates as Ligands. Intramolecular Equilibria in the Mixed Ligand Cu2+ Complexes Formed by 2,2′-Bipyridyl or 1,10-Phenanthroline and the Dianion of Phosphonylmethoxyethane in Water-Dioxane Mixtures

1993 ◽  
Vol 48 (9) ◽  
pp. 1279-1287 ◽  
Author(s):  
Matthias Bastian ◽  
Dong Chen ◽  
Fridrich Gregáň ◽  
Guogang Liang ◽  
Helmut Sigel
Keyword(s):  
Equilibrium Constants ◽  
Parent Compound ◽  
Mixed Ligand ◽  
Mixed Ligand Complexes ◽  
Straight Line ◽  
Water As Solvent ◽  
Phosphate Monoesters ◽  
Ether Oxygen ◽  
The Stability ◽  
Straight Lines

The stability constants of the mixed ligand complexes formed by Cu2+, 2,2′-bipyridyl or 1,10-phenanthroline (= Arm), and the dianion of phosphonylmethoxyethane (PME2-), ethyl phosphonate (EtP2-), methyl phosphonate (MeP2-), or D-ribose 5′-monophosphate (RibMP2-) (= R–PO32-) were determined by potentiometric pH titrations in water containing 30 or 50% (v/v) 1,4-dioxane (I = 0.1 M, NaNO3; 25°C). The corresponding results regarding water as solvent were taken from our earlier work. Previous measurements with simple phosphate monoesters, together with the present results for RibMP2-, were used to establish log versus straight line plots. With the aid of the equilibrium constants determined for the MeP2- and EtP2- systems it is shown that simple phosphonates, i.e., those without an additional binding site, fit also on the same straight lines. Therefore, it could be demonstrated with these reference lines that the Cu(Arm)(PME) complexes in all solvents have a higher stability than expected for a sole phosphonate Cu2+ coordination. This increased stability is attributed to the formation of 5-membered chelates involving the ether oxygen present in the – CH2– O – CH2–PO32- residue of PME2-. The formation degree of the 5-membered chelates in the Cu(Arm)(PME) systems varies only between about 65 and 85% in the three mentioned solvents, despite the fact that the stabilities of the Cu(Arm)(PME) complexes increase by more than 1.8 log units by going from water to 50% dioxane-water. It is concluded that (i) such 5-membered chelates will also be formed in mixed ligand complexes of other metal ions in solvents with a reduced polarity, and (ii), more importantly, that the same interactions will also occur with the parent compound of PME2-, i.e. the dianion of 9-(2-phosphonylmethoxyethyl)adenine (PMEA2-), a compound which shows antiviral properties and for which the ether oxygen is important.

Ternary Complexes in Solution, XXX Increased Stability Through Intramolecular Stacking in Mixed-Ligand Cu 2+ and Zn 2+ Complexes of 2,2′ -Bipyridyl and Carboxymethyl Aryl Derivatives

1979 ◽  
Vol 34 (2) ◽  
pp. 208-216 ◽  
Author(s):  
Etelka Farkas ◽  
Beda E. Fischer ◽  
Rolf Griesser ◽  
Volker M. Rheinberger ◽  
Helmut Sigel
Keyword(s):  
Metal Ion ◽  
Ternary Systems ◽  
Ternary Complexes ◽  
Mixed Ligand ◽  
Difference Spectra ◽  
Ternary Metal ◽  
The Stability ◽  
Stability Enhancement ◽  
Aryl Sulfide ◽  
Enhanced Stability

Abstract The stability constants of ternary Cu 2+ and Zn 2+ complexes, each of which contains 2,2′-bipyridyl and a carboxymethyl aryl sulfide, were determined in 50% aqueous dioxane. A comparison of the stability of these ternary complexes with those formed with simple carboxylates demonstrates an enhanced stability of the carboxymethyl aryl sulfide containing mixed ligand complexes. This enhanced stability is not due to a thioether-metal ion interaction, but due to an intramolecular aromatic stacking interaction between the aryl moiety of the carboxymethyl aryl sulfide and 2,2′-bipyridyl. Indeed, by UV difference spectra and by PMR measurements it is possible to show that a binary (metal ion-free) stacked adduct between the aromatic moieties of the two mentioned ligands is formed. Furthermore, by studying the binary and ternary systems of Zn 2+ or Cu 2+ , 2,2′-bipyridyl and hydrocinnamate, i.e. 3-phenylpropionate (-S-of carboxymethyl phenyl sulfide is replaced by -CH2-), it becomes obvious that the thioether moiety is not essential for the observation of an enhanced stability of the ternary complexes. PMR shift studies of 2,2′-bipyridyl/Zn 2+ /carboxymethyl aryl sulfide systems confirm the presence of stacking in the corresponding ternary complexes. Depending on the kind of the ternary metal ion complex the stability enhancement, due to the intramolecular stacking between the aromatic parts of the coordinated ligands, is between about 0.2 to 0.5 log unit.

Properties of the Ternary (Dien)Pt(PMEA-N7) Complex Containing Diethylenetriamine (Dien) and the Antiviral 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA). Synthesis, Biological Screening, Acid-Base Behaviour, and Metal Ion-Binding in Aqueous Solution

2000 ◽  
Vol 55 (12) ◽  
pp. 1141-1152 ◽  
Author(s):  
Gunnar Kampf ◽  
Marc Sven Lüth ◽  
Jens Müller ◽  
Antonín Holý ◽  
Bernhard Lippert ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Metal Ions ◽  
Metal Ion ◽  
Ion Binding ◽  
Uv Spectrophotometry ◽  
Metal Ion Binding ◽  
Ph Titration ◽  
Complex Species ◽  
Ether Oxygen ◽  
The Stability

The synthesis of (Dien)Pt(PMEA-N7), where Dien = diethylenetriamine and PMEA2- = dianion of 9-[2-(phosphonomethoxy)ethyl]adenine, is described. No useful biological activity could be discovered for this complex which is in contrast to the known antiviral properties of PMEA itself. The acidity constants of the twofold protonated H2[(Dien)Pt(PMEA-N7)]2+ complex were determined (UV spectrophotometry and potentiometric pH titration): The release of the proton from the -P(O)2(OH)- group is only slightly affected by the N7-coordinated (Dien)Pt2+ unit, whereas the acidity of the (N1)H+ site is strongly enhanced. The stability constants of the M[(Dien)Pt(PMEA-N7)]2+ complexes with the metal ions M2+ = Mg2+, Ca2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ were measured by potentiometric pH titrations in aqueous solution at 25 °C and I = 0.1 M (NaNO3). Application of previously determined straightline plots of log KM(R-PO3)M versus KH(R-PO3)H for simple phosph(on)ate ligands, R-PO32- where R represents a non-inhibiting residue without an affinity for metal ions, proves that the primary binding site of the complex-ligand, (Dien)Pt(PMEA-N7), with all the metal ions studied is the phosphonate group; in most instances the expected stability is actually reduced by about 0.4 log units due to the N7-bound (Dien)Pt2+ unit. Only for the Cu[(Dien)Pt(PMEA-N7)]2+ and the Zn[(Dien)Pt(PMEA-N7)]2+ systems the formation of some 5-membered chelates involving the ether oxygen atom of the -CH2-O-CH2-PO32- residue could be detected; the formation degrees are 52 ± 9% and 32 ± 14%, respectively. The metal ion-binding properties of (Dien)Pt(PMEA-N7) differ considerably from those of PMEA2-, yet they are relatively similar to those of pyrimidine-nucleoside 5'-monophosphates. The structures of the various complex species in solution are discussed and compared.

Binding of calcium and lead ions to carboxystarch prepared by action of nitrogen dioxide on native starch and its 2,3-dialdehyde derivatives

1986 ◽  
Vol 51 (6) ◽  
pp. 1340-1351 ◽  
Author(s):  
Rudolf Kohn ◽  
Karol Tihlárik
Keyword(s):  
Nitrogen Dioxide ◽  
Alkaline Medium ◽  
Binding Capacity ◽  
Lead Ions ◽  
Carbonyl Groups ◽  
Weakly Alkaline ◽  
Exchange Cations ◽  
Counter Ions ◽  
The Stability ◽  
Derivatives Of

The binding of calcium and lead ions to carboxy derivatives of starch prepared by allowing nitrogen dioxide to act on native maize starch (procedure A) and on starch 2,3-dialdehyde derivatives of degrees of oxidation DO(d.a.) ≥ 0.94 (procedure B) was studied. The carboxy group content of the samples in the H+ form was 4.6 - 12.1 mmol g-1. The effect of alkaline medium on the stability of the carboxy derivatives and on their ability to bind and exchange cations was examined. The Ca2+ → 2K+ exchange was evaluated in terms of the decrease in the electrostatic free enthalpy Δ(Gel/N)KCa, determined by alkalimetric potentiometric titrations, and the binding of Pb2+ ions was evaluated in terms of the activity of the Pb2+ counter-ions determined in suspensions of Pb salts of the carboxy derivatives by means of an ion specific electrode. The IR and CD spectra revealed that the carboxystarch preparations obtained by procedure A contained, in addition to free carboxy groups, a considerable amount of carbonyl groups. During the conversion of the latter groups to the former, even in a weakly alkaline medium, the carboxy derivatives undergo an appreciable degradation and lose, to a great extent, their ability to bind and exchange cations. Procedure B, on the other hand, leads to highly selective starch and amylose carboxy derivatives, exhibiting a small amount of carbonyl groups and featuring a relative stability towards alkaline medium; their binding capacity is as high as 12 milliequivalents of cations per g of sample.

Structure of the complexes of ethylenediphosphinetetraacetic acid in solution

1985 ◽  
Vol 50 (2) ◽  
pp. 445-453 ◽  
Author(s):  
Jana Podlahová ◽  
Josef Šilha ◽  
Jaroslav Podlaha
Keyword(s):  
Metal Ion ◽  
Carboxyl Groups ◽  
Complex Solution ◽  
Square Planar ◽  
Weak Complexes ◽  
Carboxylic Groups ◽  
Uv Visible ◽  
The Stability ◽  
Tetrahedral Complexes ◽  
Free Carboxyl

Ethylenediphosphinetetraacetic acid is bonded to metal ions in aqueous solutions in four ways, depending on the type of metal ion: 1) through an ionic bond of the carboxylic groups to form weak complexes with a metal:ligand ratio of 1 : 1 (Ca(II), Mn(II), Zn(II), Pb(II), La(III)); 2) through type 1) bond with contributions from weak interaction with the phosphorus (Cd(II)); 3) through coordination of the ligand as a monodentate P-donor with the free carboxyl groups with formation of 2 : 1 and 1 : 1 complexes (Cu(I), Ag(I)); 4) through formation of square planar or, for Hg(II), tetrahedral complexes with a ratio of 1 : 2 with the ligand as a bidentate PP-donor with the free carboxyl groups (Fe(II), Co(II), Ni(II), Pd(II), Pt(II)). On acidification of the complex solution, the first two protons are bonded to the carboxyl groups. The behaviour during further protonation depends on the type of complex: in complexes of types 1) and 2) phosphorus is protonated and the complex dissociates; in complexes of types 3) and 4) the free carboxyl groups are protonated and the phosphorus-metal bond remains intact. The results are based on correlation of the stability constants, UV-visible, infrared, 1H and 31P NMR spectra and magnetic susceptibilities of the complexes in aqueous solution.

scholarly journals Antioxidant Network Based on Sulfonated Polyhydroxyalkanoate and Tannic Acid Derivative

2021 ◽  
Vol 8 (1) ◽  
pp. 9
Author(s):  
Laura Brelle ◽  
Estelle Renard ◽  
Valerie Langlois
Keyword(s):  
Gallic Acid ◽  
Tannic Acid ◽  
Water Soluble ◽  
Gel Formation ◽  
Ene Reaction ◽  
Inorganic Cations ◽  
Medium Chain Length ◽  
Physically Crosslinked ◽  
The Stability ◽  
Derivatives Of

A novel generation of gels based on medium chain length poly(3-hydroxyalkanoate)s, mcl-PHAs, were developed by using ionic interactions. First, water soluble mcl-PHAs containing sulfonate groups were obtained by thiol-ene reaction in the presence of sodium-3-mercapto-1-ethanesulfonate. Anionic PHAs were physically crosslinked by divalent inorganic cations Ca2+, Ba2+, Mg2+ or by ammonium derivatives of gallic acid GA-N(CH3)3+ or tannic acid TA-N(CH3)3+. The ammonium derivatives were designed through the chemical modification of gallic acid GA or tannic acid TA with glycidyl trimethyl ammonium chloride (GTMA). The results clearly demonstrated that the formation of the networks depends on the nature of the cations. A low viscoelastic network having an elastic around 40 Pa is formed in the presence of Ca2+. Although the gel formation is not possible in the presence of GA-N(CH3)3+, the mechanical properties increased in the presence of TA-N(CH3)3+ with an elastic modulus G’ around 4200 Pa. The PHOSO3−/TA-N(CH3)3+ gels having antioxidant activity, due to the presence of tannic acid, remained stable for at least 5 months. Thus, the stability of these novel networks based on PHA encourage their use in the development of active biomaterials.

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