Interaction of D-glucose with alkaline-earth metal ions. Synthesis, spectroscopic, and structural characterization of Mg(II)- and Ca(II)-D-glucose adducts and the effect of metal-ion binding on anomeric configuration of the sugar

The interaction of D-glucose with the hydrated alkaline-earth metal halides has been studied in solution, and adducts of the type Mg(D-glucose)X2.4 H2O, Ca(D-glucose)X2.4 H2O, and Ca(D-glucose)2X2.4 H2O, where X = Cl- and Br-, have been isolated, and characterized by means of F.t.-i.r. and 1H-n.m.r. spectroscopy, X-ray powder diffraction, and molar conductivity measurements. Spectroscopic and other evidence suggested that the Mg(II) ion in the Mg(D-glucose)X2.4 H2O adducts six-coordinate, binding to a D-glucose molecule (possibly via O-1 and O-2 atoms) and to four H2O molecules, whereas, in the corresponding 1:1 Ca-D-glucose adduct, the Ca(II) ion is possibly seven-coordinate, binding to a sugar moiety (through the O-1, O-2, and other sugar donor atoms) and to four H2O molecules. In 1:2 Ca(D-glucose)2X2.4 H2O, the calcium ion may be eight-coordinate, binding to two D-glucose molecules (possibly via the O-1 and O-2 atoms of each sugar moiety) and to four H2O molecules. The strong, sugar H-bonding network is rearranged upon D-glucose adduct-formation, and the alpha-anomeric configuration is favored by these metal cation coordinations.     

X-Ray crystallographic, NMR and antimicrobial activity studies of magnesium complexes of fluoroquinolones - racemic ofloxacin and its S-form, levofloxacin

The magnesium complexes of racemic ofloxacin (oflo) and its pure S-form levofloxacin (S-oflo) have been studied by X-ray crystallography and NMR spectroscopy. Two compounds, [Mg(R-oflo)(S-oflo)(H(2)O)(2)].2H(2)O (1) and [Mg(S-oflo)(2)(H(2)O)(2)].2H(2)O (2), respectively, have been prepared by hydrothermal reactions and their crystal structures have been determined. In both structures the anionic fluoroquinolone ligands are coordinated through the keto and carboxylate oxygens forming 1:2 Mg:oflo complexes. The two structures are practically identical except for the orientation of one of the oxazine methyl groups at the chiral center of 2 which was found in equatorial position, the other oxazine methyl groups in 1 and 2 being axial. This difference affects the stacking pattern of quinolone molecules in the cell. (1)H NMR chemical shift data and Mn(II) paramagnetic line broadening measurements on the free ofloxacin suggest that the coordination of the ligands in solution involves the keto and carboxylate oxygens. However, it is not possible to decide whether the complexes in aqueous solution have 1:1 or 1:2 stoichiometry. The methylated piperazine nitrogen does not interact with the metal ion. Magnesium-quinolone interaction is discussed in relation to the biological activity of quinolones. The antimicrobial activity of the complexes against various microorganisms was tested and it was established that their activity is similar to that of free quinolone drugs.     

FT-IR spectroscopic study of the poly(amino2dA-dT) duplex in Mg(2+)-containing solution and in films.

The alternative structures of the synthetic poly(amino2dA-dT) duplex have been studied using infrared spectroscopy in films and in solution (D2O and H2O) in the presence and in the absence of magnesium salt. In solution without magnesium salt, the polynucleotide exists in a B genus conformation with some of the sugar puckers possibly in the C3'-endo/anti geometry. In magnesium-containing solution (66 mM MgCl2), however, we report infrared spectra of Mg(2+)-poly(amino2dA-dT) which have characteristic marker bands of the A form. Film samples in 70% relative humidity (RH) give similar infrared spectra to those of the polynucleotide obtained using Mg2+. Thus, when analyzed in comparison with previously reported infrared spectra of other oligo and polynucleotides, our data show that double helical poly(amino2dA-dT) goes into the same (or very closely related) conformation in dehydrated films as in solutions containing Mg2+.     

Coordination chemistry of vitamin C. Part I. Interaction of L-ascorbic acid with alkaline earth metal ions in the crystalline solid and aqueous solution

The interaction of L-ascorbic acid with alkaline earth metal ions has been investigated in aqueous solution at pH 6-7. The solid salts of the type Mg(L-ascorbate)2.4H2O, Ca(L-ascorbate)2.2H2O, Sr(L-ascorbate)2.2H2O and Ba(L-ascorbate)2.2H2O were isolated and characterized by means of 13C NMR and FT-IR spectroscopy. Spectroscopic and other evidence suggested that in aqueous solution, the binding of the alkaline earth metal ions is through the O-3 atom of the ascorbate anion, while in the solid state the binding of the Mg(II) is different from those of the other alkaline earth metal ion salts. The Mg(II) ion binds to the O-3, O-1 atom of the two ascorbate anions and to two H2O molecules, while the eight-coordination around the Ca(II), Sr(II), and Ba(II) ions would be completed by the coordination of three acid anions, through O-5, O-6 of the first, O-3, O-5, O-6 of the second and O-1 of the third anion as well as to two H2O molecules. The structural properties of the alkaline earth metal-ascorbate salts are different in the solid and aqueous solution.     

Sucrose interaction with alkaline earth metal ions. Synthesis,spectroscopic and structural characterization of sucrose adducts with the Mg(II) and Ca(

Crystalline sucrose interacts with hydrous alkaline earth metal ions to give adducts of the type Mg(sucrose)Cl₂.4H₂O, Mg(sucrose)₂Br₂.4H₂O, Ca(sucrose)Cl₂.2H₂O, and Ca(sucrose)₂Br₂.2H₂O. These adducts are characterized by means of elemental analysis, FT-IR spectroscopy. X-ray powder diffraction, and molar conductivity measurements.Due to the marked spectral similarities with those of the structurally known Na(sucrose)Br.2H₂O and other Na-sucrose adducts in the 1:1 metal sugar compounds, the Mg(II) ion is possibly six-coordinate, binding to two sucrose molecules via O(4), O(6) of the first sugar and O(6') of the second molecule and to three H₂O, whereas in the 1:2 metal-sugar adducts, magnesium ion binds to two sugar molecules through O(4), O(6) and to two H₂O, resulting in a six-coordination geometry around the Mg(II) ion. The Ca(II) ion is possibly seven-coordinate in the 1:1 metal-sugar compound, binding to two sucrose molecules through O(4), O(6) of the first and O(6') of the second sugar and to two H₂O molecules as well as to two halide anions, while in the 1:2 metal-sugar adduct it could be bonded to four sugar molecules via O(4), O(6) of the two and O(6') of the other two molecules and to two H₂O, resulting in an eight-coordination geometry around the Ca(II) ion. Upon metal adduct formation, the strong sugar hydrogen bonding network is rearranged to that of the sucrose-OH ... H₂O ... halide ... OH-sucrose system.     

Mg spin determines adenosinetriphosphate energetics

The molecular dynamics method DFT:B3LYP (6-31G** basis set, T = 310 K) was used to study interactions between adenosinetriphosphate (ATP), ATP subsystem, and magnesium cofactor [Mg(H2O)6]2+, Mg subsystem, in water environment modeled with 78 water molecules in singlet (S) and triplet (T) states. The lowest in energy singlet (S) and triplet (T) potential energy surfaces, PESs, are remarkably separated in space and direct the Mg cofactor towards the gamma-beta-phosphate oxygens (O1-O2), S path, or towards the beta-alpha-phosphate oxygens (O2-O3), T path. Chelation of the gamma-beta-phosphates and beta2-alpha-phosphates ends, respectively, in the formation of stable, low-energy, ([Mg(H2O)4-(O1-O2)ATP]2-) and metastable, high-energy, ([Mg(H2O)2-(O2-O3)ATP]2-) chelates, differing in the number of water molecules around the Mg. Intersection between the two T PESs produces an unstable state, a result of spin redistribution between the Mg and ATP subsystems. This state, which is sensitive to a hyperfine interaction with the Mg nuclear spin, 25Mg, reveals an unpaired electron spin and initiates the ATP cleavage along the ion-radical path, yielding a highly reactive adenosinemonophosphate ion-radical, *AMP-, earlier observed in the CIDNP (Chemically Induced Dynamic Nuclear Polarization) experiment (A.A. Tulub, 2006). Biological consequences of the findings are discussed.     

Sugar interaction with biologically active cis-PtCl2(NH3)2 (anticancer) and its inactive trans isomer

The interaction of D-glucuronic and D-gluconic acids with cis- and trans-PtCl2(NH3)2 (cisplatin and transplatin) has been investigated in aqueous solution and solid complexes of the type cis-[PtL(NH3)2]L.H2O and trans-[PtL2(NH3)2]L.H2O, where L = D-glucuronate or D-gluconate anions, are isolated and characterized by means of Fourier transform-infrared and 1H-NMR spectroscopy, and molar conductivity and X-ray powder diffraction measurements. Spectroscopic and other evidence indicated that the sugar anions bind monodentately in trans-[PtL2(NH3)2].H2O and bidentately in cis-[PtL(NH3)2]L.H2O complexes through the carboxylate oxygen atoms and other sugar donor groups. The strong sugar intermolecular hydrogen-bonding network is altered to that of the sugar-OH...NH3(H2O)...OH-sugar, upon platinum-ammine interaction. The D-glucuronate anion has the beta-anomer configuration both in the free salt and in these platinum-sugar complexes.     

Sugar adducts with alkaline earth metal ions. Interaction of L-arabinose with Sr(II) and Ba(II) ions and the effects of metal ion binding on the sugar anomeric configurations

The reaction between L-arabinose and hydrated Sr(II) or Ba(II) halide salts has been studied in H2O solution and adducts of the type M(L-arabinose)X(2).4H(2)O, where M = Sr(II) or Ba(II) and X = Cl- or Br- have been isolated and characterized by means of Fourier transform infrared spectroscopy, 1H-NMR spectroscopy, molar conductivity and X-ray powder diffraction measurements. Due to the marked spectral similarities with those of the structurally known Ca(L-arabinose)X2 . 4H2O (X= Cl- or Br-) compounds, the Sr(II) and the BA(II) ions are eight-coordinated, binding to two l-arabinose molecules via O1, O5 of the first and O3, O4 of the second sugar moiety and to four H2O molecules. 1H-NMR spectroscopy indicated that the free L-arabinose has the beta-anomer configuration in aqueous solution, whereas the alpha-anomer isomer is preferred by Mg(II), Ca(II), Sr(II) and Ba(II) ions, on complexation.     

Sugar-metal ion interaction. Synthesis,spectroscopic and structural analysis of Zn(II), Cd(II), and Hg(II) sugar complexes containing l-arabinose

Interaction between l-arabinose and the zinc group metal-ion salts has been studied in aqueous solution and solid complexes of the type M(l-arabinose)X₂·nH₂O, where M = Zn(II), Cd(II), and Hg(II) ions, X = Cl⁻ or Br⁻, and n = 0–2 have been isolated and characterized. On comparison with the structurally known Ca(l-arabinose) Cl₂·4H₂O and the corresponding magnesium compounds, it is concluded that the Zn(II) and Cd(II) ions are six-coordinated, binding to two arabinose moieties via 03, 04 of the first and 01, 05 of the second sugar molecule as well as to two H₂O molecules. The Hg(II) ion binds only to two sugar molecules in a similar fashion to zinc and cadmium ions, resulting in a four coordination around the mercury ion. The strong intermolecular hydrogen bonding network of the free arabinose is rearranged to that of the sugar OH...H₂O...halide system upon metalation. The β-anomer sugar conformation is predominant in the free sugar, while the α-anomer conformation is preferred by the alkaline earth and Zn(II), Cd(II), and Hg(II) cations.     

Investigation of the regiospecificity and stereospecificity of proton transfer in the yeast inorganic pyrophosphatase catalyzed reaction

The regiospecificity and stereospecificity of proton transfer in the yeast inorganic pyrophosphatase (PPase) catalyzed hydrolysis of P1,P2-bidentate Mg(H2O)4(PPi)2- were probed with exchange-inert metal complexes of imidodiphosphate (PNP) and thiopyrophosphate (PPS). PPase was unable to catalyze the hydrolysis of Mg(H2O)4PNP and P1,P2-bidentate Co(NH3)4PNP under conditions that resulted in rapid hydrolysis of the corresponding metal-PPi complexes. PPase was found to catalyze the hydrolysis of Mg(H2O)4PPS at 17% the rate of Mg(H2O)4PPi hydrolysis. The Km of Mg(H2O)4PPS was determined to be 300 microM, which is a value 10-fold greater than that observed for Mg(H2O)4PPi. P1,P2-Bidentate Cr(H2O)4PPS and Co(NH3)4PPS (prepared from PPS) were both found to be substrates for PPase. The enzyme specifically catalyzed the hydrolysis of the Rp enantiomers of these complexes and not the Sp enantiomers. These results are accommodated by a reaction mechanism involving enzyme-mediated proton transfer to the pro-R oxygen atom of the incipient phosphoryl leaving group of the bound P1,P2-bidentate Mg(H2O)4PPi2- complex.     

Vitamin C interaction with cobalt-ammine cations. Synthesis, spectroscopic and structural characterization of cobalt-pentammine and cobalt-tetrammine sugar complexes containing L-ascorbate anion

Interaction between [Co(NH3)5Cl]Cl2, [Co(NH3)4Cl2]Cl and L-ascorbic acid has been investigated in aqueous solution and solid complexes of the type [Co(NH3)5 ascorbate]Cl2 X H2O and [Co(NH3)4 ascorbate]Cl2 X H2O have been isolated and characterized by 13C-NMR, FT-IR and electron absorption spectroscopy. Spectroscopic and other evidence suggested that the sugar anion binds monodentately in the [Co(NH3)5 ascorbate]2+ cation via the ionized O3 oxygen atom and bidentately in [Co(NH3)4 ascorbate]2+ through the O1 and O4 oxygen atoms, resulting in a six-coordinate geometry around the Co(III) ion. The intermolecular sugar hydrogen-bonding network is perturbed upon sugar metalation and the sugar moiety shows a similar conformation to that of the sodium ascorbate compound in these series of cobalt-ammine complexes.     

Synthesis,crystal structure,and nuclease activity of planar mono-heterocyclic base copper(II) complexes

A series of mononuclear copper(II) complexes having a 1:1 molar ratio of copper and the planar heterocyclic base like 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) are prepared from a reaction of copper(II) nitrate.trihydrate and the base (L) in ethanol or aqueous ethanol at different temperatures. The complexes [Cu(dpq)(NO(3))(2)] (2), [Cu(dpq)(NO(3))(H(2)O)(2)](NO(3)) (3), [Cu(dpq)(NO(3))(2)(H(2)O)(2)].2H(2)O (4.2H(2)O) and [Cu(dppz)(NO(3))(2)(H(2)O)].H(2)O (5.H(2)O) have been characterized by X-ray crystallography. The crystal structures show the presence of the heterocyclic base in the basal plane. The coordination geometries of the copper(II) centers are axially elongated square-pyramidal (4+1) in 2, 3 and 5, and octahedral (4+2) in 4. The nitrate anion in the coordination sphere displays unidentate and bidentate chelating bonding modes. The axial ligand is either H(2)O or NO(3) in these structures giving a Cu-L(ax) distance of approximately 2.4 A. The one-electron paramagnetic complexes (mu approximately 1.8 mu(B)) exhibit axial EPR spectra in DMF glass at 77 K giving g(parallel)>g( perpendicular ) with an A(parallel) value of approximately 170G indicating a [d(x)2(-y)2](1) ground state. The complexes are redox active and display a quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.0 V vs. SCE giving an order of the E(1/2) values as 5(dppz)>2-4 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). The complexes bind to calf thymus DNA giving an order 5 (dppz)>2 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). An effect of the extended planar ring in dpq and dppz is observed in the DNA binding. The complexes show nuclease activity with pUC19 supercoiled DNA in DMF/Tris-HCl buffer containing NaCl in presence of mercaptopropanoic acid as a reducing agent. The extent of cleavage follows the order: [Cu(phen)(2)(H(2)O)](ClO(4))(2)>5>2 approximately 3 approximately 4>1. The bis-phen complex is a better cleaver of SC DNA than 1-5 having mono-heterocyclic base. Mechanistic investigations using distamycin reveal minor groove biding for the phen, dpq complexes, and a major groove binding for the dppz complex 5. The cleavage reactions are found to be inhibited in the presence of hydroxyl radical scavenger DMSO and the reactions are proposed to proceed via sugar hydrogen abstraction pathway. The ancillary ligand is found to have less effect in DNA binding but are of importance in DNA cleavage reactions.     

Interaction of guanylic acid with the Mg(II), Ca(II), Sr(II), and Ba(II) ions in the crystalline solid and aqueous solution: evidence for the ribose C2'-endo/anti and C3'-endo/anti conformational changes.

The interaction of guanosine-5'-monophosphoric acid (H2-GMP) with the alkaline earth metal ions has been studied in aqueous solution at neutral pH. The crystalline salts of the type Mg-GMP.5H2O, Ca-GMP.6H2O, Sr-GMP.7H2O, and Ba-GMP.7H2O were isolated and characterized by Fourier transform ir, 1H-nmr and x-ray powder diffraction measurements. Two types of macrochelate complexes have been identified: (a) The direct metalbase and indirect metal-phosphate bindings (inner and outer sphere interaction) for the Mg(II), Ca(II), and Sr(II), ions; and (b) the indirect metal-base and direct metal-phosphate bindings (outer and inner sphere interaction) for the Ba(II) ion. In aqueous solution, an equilibrium exists between the base-metal-H2O...PO3 and base...H2O-M-PO3 interactions. The ribose moiety shows C3'-endo/anti conformation in the free acid; C2'-endo/anti in the Na2-GMP salt; C3'-endo/anti in the Mg(II)-, Ca(II)-, and Sr(II)-GMP salts; and C2'-endo/anti, in the Ba(II)-GMP salt.     

RNA-ligant interactions. (I) Magnesium binding sites in yeast tRNAPhe.

X-ray crystallagraphic studies studies indicate that there are at least four site-specifically bound hydrated Mg2+ ions, [Mg(H2O)n]2+, in yeast tRNAPhe. The size and the octahedral coordination geometry, rather than the charge, of [Mg(H2O)N]2+ appear to be the primary reasons for the specificity of magnesium ions in site-binding and in the stabilization of the tertiary structure of tRNA.     

Cercospora beticola toxins. Part VI: preliminary studies of protonation and complexation equilibria

The biological activity of Cercospora beticola toxins might be enhanced by the complex formation with magnesium. Therefore, protonation and complexation equilibria of beticolins were studied. Beticolins carry three dissociable functions (H3B) two of which dissociate at a physiological pH. In the presence of magnesium, the neutralisation and protonation curves provide evidence for the formation of complexes. At physiological pH, the uncharged complex, Mg2H2B2, is the predominant form. The nonionised forms of free beticolin-1 and -2 fluoresce in a 50% dioxan-water solution and their emission maxima shift to higher wavelengths in water. The dianion HB(2-) is non-fluorescent both in water and in less polar media. The formation of the Mg2H2B2 complex which strongly fluoresces in nonpolar media is confirmed by a marked increase in fluorescence at 520 nm and by a shift of the excitation maximum.     

Hydroxylation and deglycosylation of 2'-deoxyguanosine in the presence of magnesium and nickel

Nickel (Ni), a carcinogenic and genotoxic metal, has been shown to enhance deglycosylation and hydroxylation of 2'-deoxyguanosine (dG) that has been caused by ascorbic acid and H2O2. There is evidence that Mg is a competitive antagonist of the toxicological effects of Ni. A factorial design was used to examine the interactive influence of Mg and Ni on the deglycosylation and hydroxylation of dG under a range of pH conditions in which ascorbate (Ascb) and H2O2 were added. Formation of guanine (Gu) (deglycosylation) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) (hydroxylation) appeared in large amounts in samples in which both H2O2 and Ascb were present. The largest amounts of Gu appeared where both Ni or magnesium (Mg) were present. When Mg alone was present, the amounts of Gu was intermediate between these two. Slightly less 8-OH-dG was formed where only Mg was present. The reaction mixtures were more sensitive to the pH than to the respective presence or absence of metals. At slightly acid or neutral pH (6.2-7.0) large amounts of both Gu and 8-OH-dG were formed. Gu formation decreased dramatically between pH 7.0 and 7.2. There was no 8-OH-dG formed at pH 7.8 and only small amounts at pH 7.6. The formation of 8-OH-dG was generally less where Mg was present. When Ni was absent, 8-OH-dG formation was greater in the pH 6.8 mixtures. The formation of Gu and 8-OH-dG from 2'-deoxyguanosine are directly a function of pH. Slight changes in pH greatly effected the formation of these biomarkers of oxidatively damaged DNA. Additional research is needed to determine if this is a cause or effect, i.e. does pH enhance toxicity conditions, thus permitting formation of 8-OH-dG, or does pH permit the reaction to proceed.     

NMR studies of echinomycin bisintercalation complexes with d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution: sequence-dependent formation of Hoogsteen A1.T4 and Watson--Crick T1.A4 base pairs flanking the bisintercalation site

We report on two-dimensional proton NMR studies of echinomycin complexes with the self-complementary d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution. The exchangeable and nonexchangeable antibiotic and nucleic acid protons in the 1 echinomycin per tetranucleotide duplex complexes have been assigned from analyses of scalar coupling and distance connectivities in two-dimensional data sets recorded in H2O and D2O solution. An analysis of the intermolecular NOE patterns for both complexes combined with large upfield imino proton and large downfield phosphorus complexation chemical shift changes demonstrates that the two quinoxaline chromophores of echinomycin bisintercalate into the minor groove surrounding the dC-dG step of each tetranucleotide duplex. Further, the quinoxaline rings selectively stack between A1 and C2 bases in the d(ACGT) complex and between T1 and C2 bases in the d(TCGA) complex. The intermolecular NOE patterns and the base and sugar proton chemical shifts for residues C2 and G3 are virtually identical for the d(ACGT) and d(TCGA) complexes. A change in sugar pucker from the C2'-endo range to the C3'-endo range is detected at C2 on formation of the d(ACGT) and d(TCGA) complexes. In addition, the sugar ring protons of C2 exhibit upfield shifts and a large 1 ppm separation between the H2' and H2" protons for both complexes. The L-Ala amide protons undergo large downfield complexation shifts consistent with their participation in intermolecular hydrogen bonds for both tetranucleotide complexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigation of the role of the substrate metal ion in the yeast inorganic pyrophosphatase reaction

The substrate activities of a series of tripositive metal ion-pyrophosphate complexes with yeast inorganic pyrophosphatase were examined. While the Michaelis constants for these complexes were shown to be between one and two orders of magnitude greater than that of the natural substrate, [Mg(H2O)4PPi]2-, the turnover numbers were in general comparable to that of [Mg(H2O)4PPi]2-. These data suggest that the nature of the metal ion cofactor effects substrate binding but in most cases not catalysis. Thus, the role of the metal ion in catalysis is probably restricted to that of an electron sink.     

Characterization of bis(isoorotato)diaquamagnesium(II) dihydrate: a potentially useful complex for magnesium supplementation.

The synthesis and crystal structure of a new Mg(II) complex of stoichiometry [Mg(isoor)2(H2O)2].2H2O, where isoor is the monoanion of 5-carboxyuracil (isoorotic acid), are reported. The structure, solved by single-crystal X-ray diffractometry, shows that it crystallizes in the triclinic space group P(-1) with Z = 1. The electronic, IR and Raman spectra of the complex are briefly discussed. Its thermal behavior was also investigated by means of thermal gravimetry (TG) and differential thermal analysis (DTA) measurements in an oxygen atmosphere. Dissolution studies support the usefulness of the compound for magnesium supplementation.