Coordination property of poly(1-vinyl-2-methylimidazole)-heme complexes

Poly(1-vinyl-2-methylimidazole) and poly(1-vinyl-2-methylimidazole-co-1-vinylpyrrolidone) predominantly form five-coordinate heme complexes in aqueous solution. The apparent formation constants (K) of the heme complexes were estimated spectroscopically. The K values of the polymer-heme complexes were about 10² to 10³ times those of the corresponding monomeric ones. These large K values were canceled by adding poly(1-vinylpyrrolidone), alcohol, or dimethylformamide. The viscometric measurement of the polymer-heme solution showed that the polymer complex took a compact shape. These results indicate a hydrophobic interaction of heme with the polymer-ligand. Poly(1-vinyl-2-methylimidazole) could form the five-coordinate heme complex, even in the presence of a large amount of imidazole.     

Enzymatic reduction of synthetic polymer-bound hemin derivatives: efficient method to prepare a heme-oxygen adduct in cooled aqueous medium

Synthetic polymer-bound hemin (iron(III) protoporphyrin IX) derivatives were effectively reduced by ferredoxin and ferredoxin-NADP reductase system. The resultant polymer-bound heme (iron(II) protoporphyrin IX) derivatives formed oxygen adducts with a lifetime of ca. 1 hr in aqueous solution at -30 degrees C. The reduction rate is discussed in terms of the structure of the hemin derivatives.     

Raman and infrared spectroscopy of the oxo-bridged iron(III) complex, [Cl3Fe-O-FeCl3]-2 as a spectroscopic model for the oxo bridge in hemerythrin and ribonucleotide reductase

Vibrational spectroscopic data were collected on the salt [C5H6N]2[Cl3FeOFeCl3] . C5H5N, which has previously been structurally characterized by X-ray crystallography. The modes associated with the oxo bridge were identified by experiments on the 18O-containing species. Spectra for the mu-16O complex contain Raman bands at 870, 458, and 203 cm-1 that shift to 826, 440, and 198 cm-1 in the mu-18O complex. These are respectively assigned to the asymmetric, symmetric, and angle deformations of the bent Fe-O-Fe moiety. A normal mode vibration analysis based on a simple valence force field for the Fe-O-Fe portion of the molecule provides surprisingly good agreement with these experimental frequencies and their assignments. The vibrational data for this simple inorganic complex confirm the assignment of a resonance Raman band around 500 cm-1 in the oxygen-carrying protein hemerythrin and enzyme ribonucleotide reductase as the symmetric stretch of an oxo bridge between two iron(III) centers.     

Studies of the reaction products of adenosine with [Pt(NH3)3Cl]Cl and cis-Pt(NH3)2Cl2 by high performance liquid chromatography

The reaction products of adenosine with [Pt(NH₃)₃Cl]Cl or cis-Pt(NH₃)₂Cl₂ have been studied using high performance liquid chromatography and uv spectroscopy. The reaction of [Pt(NH₃)₃Cl]Cl with adenosine (pH = 7.0, Pt/base = 0.5) gives four products. Two of them, mononuclear complexes in which platinum is bound to adenosine through N(7) or N(1), comprise more than 90% of all the products. The N(1) and N(7) sites on adenosine indicate almost equal binding affinity for [Pt(NH₃)₃Cl]Cl. The reaction of cis-Pt(NH₃)₂Cl₂ with adenosine has been studied in the presence of a large excess of adenosine (Pt/base ? 0.05). The reaction gives four products. One is the monomeric 2:1 complex with cis-Pt(NH₃)₂²⁺ bound to two adenosine molecules through the N(7) site and the N(1) site, and another is the monomeric 2:1 complex with cis-Pt(NH₃)₂²⁺ bound to two adenosine molecules through the N(7) sites. cis-Pt(NH₃)₂Cl₂ is stronger affinity to the N(7) site than of adenosine to the N(1) site.     

The binding of copper(II) and zinc(II) to oxidized glutathione

1H and 13C NMR studies of Zn(II) binding to oxidized glutathione (GSSG) in aqueous solution over the pH range 4-11 show that it forms a complex with a 1:1 Zn:GSSG stoichiometry. At pH values between 6 and 11 the metal ligands are the COO- and NH2 groups of the glutamate residues. Below pH 5 the glycine end of the molecule also binds to the metal ions. EPR and visible absorption spectra of Cu(II) GSSG solutions suggest that similar complexes are formed with Cu(II). The solid products obtained from these solutions are shown by analysis and EPR to be primarily binuclear with Cu2GSSG stoichiometry, although the structures depend on the pH and stoichiometry of the solution from which they were obtained.     

The Reaction of Pt-Antitumor Drugs with Selected Nucleophiles.: II. Preparation and Characterization of Coordination Compounds of Pt(II) andl-Histidine

Various His-Pt(II) coordination compounds were prepared by reaction of K₂PtCl₄ or cis-[Pt(NH₃)₂Cl₂](cis-DDP) with His and analyzed by ¹H and ¹³C NMR spectroscopy, electrophoresis, and ion-exchange chromatography. His may be coordinated to Pt by the imidazol iminogroup and/or the α-aminogroup; the carboxy group remains always free. Both bidentate as well as monodentate ligands were identified. Cis-DDP reacts with His to give a mixture of compounds where all these possibilities are present: cis-diamine-(histidine-N,N-)Pt(II) and three different types of cis-diammine-bis(histidine). HCl trans cleavage of compounds with bidentate His ligands leads to a mixture of two compounds having His ligated to Pt by an amino or imin group. The methods applied are suitable for analyzing reactions of His with cis-DDP under model conditions similar to physiological conditions.     

Preparation and crystal structure of [NEt4]3[Fe6W2S8(SEt)9]; structural and electrochemical comparisons with its molybdenum analogue

[NEt₄]₃[Fe₆M₂S₈(SEt)₉] (M = Mo or W) compounds are isomorphous and contain molybdenum and tungsten atoms in an essentially identical environment. These complexes undergo an irreversible one-electron oxidation at −0.46 V (Mo) and −0.51 V (W) and two one-electron reductions at −1.56 and −1.76 V (Mo) and −1.52 and −1.84 V (W), in DMSO solution versus (0.1 M). The only distinction between the behavior of these molybdenum and tungsten complexes identified thus far is that, for the former the reductions are reversible whereas for the latter they are irreversible. This difference may be relevant to the low activity found for nitrogenases reconstituted with tungsten in place of molybdenum.     

Coordination chemistry of 7,9-disubstituted 6-oxopurine metal compounds. 4. Platinum(II) coordination at N(1). Molecular and crystal structure of [(ethylenediamine)bis(7,9-dimethylhypoxanthine)platinum(II)] hexafluorophosphate

The preparation and molecular and crystal structure of the complex [(ethylenediamine)bis(7,9,-dimethylhypoxanthine)platinum(II)] hexafluorophosphate, [Pt(C₂H₈N₂)(C₇H₈N₄O)₂] (PF₆)₂, are reported. The complex crystallizes in the monoclinic system, space group C2/c, with a = 12.334(2)Å, b = 10.256(2)Å, c = 22.339(3)Å, β = 101.31(1)°, V = 2771.0ų, Z = 4, D_measd = 2.087(3) g cm^?3, D_calc = 2.094 g cm^?3. Intensities for 3992 symmetry-averaged reflections were collected in the θ-2o scan mode on an automated diffractometer employing graphite-monochromatized MoKα radiation. The structure was solved by standard heavy-atom Patterson and Fourier methods. Full matrix least-squares refinement led to a final R value of 0.051. Both the ethylenediamine chelate and the PF₆^? anion are disordered. The primary coordination sphere about the Pt(II) center is approximately square planar with the bidentate ethylenediamine ligand and the N(1) atoms [Pt(II) ? N(1) = 2.020(5)Å] of two 7,9-dimethylhypoxanthine bases (related by a crystallographic twofold axis of symmetry) occupying the four coordination sites. The exocyclic O(6) carbonyl oxygen atoms of the two 7,9-dimethylhypoxanthine ligands participate in intracomplex hydrogen bonding with the amino groups of the ethylenediamine chelate [N(ethylenediamine) ? O(6) = 2.89( )Å]. The observed Pt ? O(6) intramolecular distances of 3.074(6)Å are similar to those found in other Pt(II) N(1)-bound 6-oxopurine complexes and in several Pt(II) N(3)-bound cytosine systems.     

Bis(L-cysteinato)gold(I): chemical characterization and identification in renal cortical cytoplasm.

L-Cysteinatogold(I) was prepared by the reaction of L-cysteine with KAuBr4 in acidic media and its solubility determined from pH 4 to 10. The solubility at pH 7.4 and 37 degrees C is 1 microM. In the presence of excess cysteine, the solubility increases because of formation of bis(L-cysteinato)gold(I). The equilibrium-constant for formation of the bis complex is 2.1 +/- 0.4 X 10(-3), which at pH 7.4 CORRESPONDs to an apparant formation constant of 4.4 X10(4). The formation of the bis adduct was confirmed by chromatographic separation of the products of the reaction between [35S]-L-cysteine and Na2AuTM. This complex elutes with Kav = 1.15 which allows it to be distinguished from other gold thiolates that might form in vivo. The bis(cysteinato)gold(I) complex is shown to be present in kidney cytosol isolated from rats given Na2AuTM in vivo. When additional cysteine is added to the cytosol in vitro, the peak at 1.15 is increased, but if glutathione is added, the low molecular weight gold elutes at Kav = 1.00, which is taken as evidence for the existence of bis(cysteinato)gold(I) in the cytosol preparation. The amount of gold present as bis(cysteinato)gold(I) after 4 different dose schedules has been measured and found to increase with the total cytosol gold concentration. L-Cysteinatogold(I) does not dissolve in the presence of bovine serum albumin to form an adduct.     

Vanadyl(IV) conalbumin. I. Metal binding site configurations

Electron paramagnetic resonance (epr) and ultraviolet difference spectroscopy of vanadyl conalbumin indicate a binding capacity of two vanadyl ions, VO²⁺, per protein molecule in the pH 8–11 range; the binding capacity drops in the pH 6–8 range with an apparent pK_a′ = 6.6. Iron-saturated conalbumin does not bind vanadyl ions, which suggests common binding sites for iron and vanadium. Ultraviolet difference spectroscopy indicates 2–3 tyrosines are involved in the binding of each metal ion; pH titrations show that three protons are released per vanadyl ion bound by conalbumin. Room and liquid nitrogen temperature X-band (ca. 9.2–9.5 gHz) epr spectra show that the vanadyl ion binds in three magnetically distinct environments (A, B, and C) that arise from interconvertible metal site configurations. These configurations are probably examples of conformational substrates of the protein. Q-band (ca 34 gHz) epr spectra resolve the spectral features more clearly and show that two configurations (A and B) have axially symmetric epr parameters but angles of noncoincidence of 12° and 8°, respectively, between the z components of the g and nuclear hyperfine tensors. The third (C) configuration has rhombic magnetic symmetry and a 6° angle of noncoincidence. These observations demonstrate that the metal sites are of low symmetry and are flexible in their geometry about the metal.The isotropic g and nuclear hyperfine tensor values and the line widths used in computer-simulated epr spectra are consistent with four oxygen or three oxygen and one nitrogen donor atoms binding equatorially to the VO²⁺ group. The apparent stability constant indicates that vanadyl ion binds to conalbumin approximately twelve orders of magnitude more weakly than iron to human serotransferrin but still sufficiently strongly to overcome hydrolysis.     

A Mössbauer study of gold(I) and gold(III) dithiolate complexes related to anti-arthritic drugs

The sensitivity of the ¹⁹⁷Au Mössbauer isomer shift and quadrupole splitting to gold oxidation state has enabled characterization of new stable, water—soluble Au(I) and Au(III) complexes of dimercaptosuccinic acid. The Au(I) complex exhibits a curious asymmetric line—broadening effect. Comparisons are also made with dimercaptopropanol and dithiocarbamate complexes. Relationships to existing and potential gold drugs are discussed.     

Metal ion-biomolecule interactions. XII. 1H and 13C NMR evidence for the preferred reaction of thymidine over guanosine in exchange and competition reactions with Mercury(II) and Methylmercury(II)

Mercury(II) bridge complexes of the type [Nuc-Hg-Nuc] (Nuc = thymidine or guanosine), and methylmercury(II) complexes of thymidine and guanosine of the type [CH₃Hg(Nuc)], have been prepared under appropriate conditions of pH and reactant's stochiometry in acqueous soluton. The various complexes have been characterized by ¹H and ¹³C NMR and used as probes, in competition and exchange studies, to establish the relative affinities of Hg(II) and CH₃Hg(II) towards the nucleosides guanosine and thymidine. These studies have confirmed that Hg(II) and CH₃Hg(II) bind to N₃ of thymidine in preference to N₁ of guanosine. The studies further show that reactions of mercury(II) with the nucleosides are thermodynamically controlled; the preperential binding reflects the relative stabilities of the respective complexes.     

Specific heavy metal labeling of the 3-'terminus of phosphorothioate modified yeast tRNAPhe.

Yeast tRNAPhe containing a phosphorothioate modified -CS-CS-A terminus binds two moles of chloroterpyridineplatinum(II). This result was determined by titrating the tRNA with [3H](terpy)PtCl] Cl, removing excess platinum by cation exchange chromatography, and determining the amount of bound platinum by radiocounting techniques. It has thus been established that adjacent phosphorothioate modified nucleotides can be labeled with an electron dense stain, a necessary requirement for electronmicroscopic sequencing of polynucleotides to become practical.     

Complexes of vitamin B6, V interaction of pyridoxal with pyridoxamine in the presence of copper(II)

The interaction of pyridoxal (PL) with pyridoxamine (PM) in the presence or absence of CU(II) has been studied in acidic aqueous solutions. We conclude that a ternary complex is formed prior to the interaction of pyridoxal with pyridoxamine in the presence of Cu(II) ions. Although the rate of interaction of excess PL with the Cu(II)-PM system of composition 1:1 followed pseudo-first-order kinetics, this was not so with composition ratios of PM to Cu(II), greater than unity. The observed rate constant (k_obs) has the following form for Cu(II):PM:PL in the ratio 1:1:10 (or more):

     

Equilibrium and structural studies of silicon(IV) and aluminium(III) in aqueous solution. 12. A potentiometric and 29Si-NMR study of silicon tropolonates

Complexation in the H⁺-Si(OH)₄-tropolone (HL) system was studied in 0.6 M (Na)Cl medium at 25° C. Speciation and formation constants were determined from potentiometric (glass electrode) and ²⁹Si-NMR data. Experimental data cover the ranges 1.5 ? - log[H⁺] ? 8.4, 0.002 ? B ? 0.012 M, and 0 ? C ? 0.060 M (B and C stand for the total concentration of Si and tropolone, respectively). In acid solutions (-log[H⁺] ? 3) a hexacoordinated cationic complex, SiL₃⁺, is formed with log K(Si(OH)₄ + 3HL + H⁺ XXX SiL₃⁺ + 4H₂O) = 7.08 ± 0.03. Furthermore, the formation of a disilicic acid was established from ²⁹Si-NMR data. The dimerization constant of Si(OH)₄ was found to be 10 exp (1.2 ± 0.1). In model calculations the solubility of quartz and amorphous SiO₂ in the presence of tropolone is demonstrated. Data were analyzed using the least-squares computer program LETAGROPVRID.     

Triplet state properties of the methylmercury(II)-tyrosine complex

CH₃Hg(II)OH forms complexes at pH 8 with tyrosine and with tyrosine ethyl ester (TEE) that are detected by ultraviolet difference absorption spectra. With K_f defined by CH₃HgOH + HB

CH₃HgB + H₂O, we find log K_f = 3.61 (tyrosine) and 3.36 (TEE). A heavy-atom effect is observed in frozen glasses of the complexes; this indicates a close interaction between Hg and the chromophore. No UV difference spectrum or heavy-atom effect is observed with N-acetyl tyrosine ethyl ester, indicating that complexing at the phenol O does not occur, and suggesting that binding occurs at the amine N. Zero field optically detected magnetic resonance (ODMR) measurements of the CH₃Hg(II)-tyrosine triplet state give (D, E) = (0.129, 0.047) or (0.134, 0.041) cm^?1 depending upon assignment of transitions. D of tyrosine is relatively unaffected, but E is reduced by CH₃Hg(II) complexing. Low-temperature kinetic measurements show that the shortest lived sublevel of the complex is T_z, where z lies along the phenol long axis in tyrosine. A dominant 11.6-msec component in the 77 K decay of the phosphorescence is consistent with the individual sublevel lifetimes obtained by ODMR.     

The reaction of Pt-antitumor drugs with selected nucleophiles. II. Preparation and characterization of coordination compounds of Pt(II) and L-histidine

Various His-Pt(II) coordination compounds were prepared by reaction of K2PtCl4 or cis-[Pt(NH3)2Cl2](cis-DDP) with His and analyzed by 1H and 13C NMR spectroscopy, electrophoresis, and ion-exchange chromatography. His may be coordinated to Pt by the imidazol iminogroup and/or the alpha-aminogroup; the carboxygroup remains always free. Both bidentate as well as monodentate ligands were identified. Cis-DDP reacts with His to give a mixture of compounds where all these possibilities are present: cis-diamine-(histidine-N,N-)Pt(II) and three different types of cis-diammine-bis(histidine). HCl trans cleavage of compounds with bidentate His ligands leads to a mixture of two compounds having His ligated to Pt by an amino or imin group. The methods applied are suitable for analyzing reactions of His with cis-DDP under model conditions similar to physiological conditions.     

Investigation of the binding of inorganic complexes to blue copper proteins by 1H nmr spectroscopy,I. The interaction between the [Cr(phen)3]3+ and [Cr(CN)6]3− ions and the copper(I) form of parsley plastocyanin

The effects of the addition of [Cr(phen)₃](ClO₄)₃ and K₃[Cr(CN)₆] on the ¹H nmr spectrum of the copper(I) form of parsley plastocyanin are described. It is concluded that the ions [Cr(phen)₃]³⁺ and [Cr(CN)₆]^3? bind to different parts of the protein.     

Kinetics of Ni(II) and Co(II) monocomplex formation with O-phospho-dl-serine

The complexation reactions of O-phospho-DL-serine with Ni(II) or Co(II) were studied at 25°C and ionic strength 0.2 M (KNO₃) by temperature-jump. The observed rate constants for formation of the Ni²⁺ and Co⁺² monocomplexes were (1.32 ± 0.09) × 10⁵ and (1.73 ± 0.33) × 10⁷ M^?1 sec^?1, respectively. Complexation is postulated to involve formation of a monocoordinated steady state intermediate followed by rate-determining chelate ring closure.     

(2R*, 3S*)-1-[18F]fluoro-2,3-bis(4-hydroxyphenyl)pentane [( 18F]fluoronor-hexestrol), a positron-emitting estrogen that shows highly-selective, receptor-mediated uptake by target tissues in vivo

The positron-emitting, non-steroidal estrogen (2R*, 3S*)-1-[18F]fluoro-2,3-bis(4-hydroxyphenyl)pentane [( 18F]-fluoronor-hexestrol), has been prepared by fluoride ion displacement on a labile trifluoromethanesulfonate (triflate) derivative of a suitably protected precursor, followed by removal of the aryl triflate groups with lithium aluminum hydride and purification by HPLC. In immature female rats, this compound is taken up selectively by the uterus and is retained for prolonged periods, due to its binding to the estrogen receptor. This compound and related 18F-labeled estrogens thus appear to be promising agents for imaging estrogen receptor-positive breast tumors in humans.