Synthesis,spectroscopic, and biological characterization of the palladium(II) oxalato complexes with heterocyclic ligands

Palladium(II) oxalato complexes with heterocyclic ligands have been prepared and characterized by spectroscopic and biological studies. The compounds are of the general formula Pd(ox)(L)_n where ox = oxalato For n = 1, the ligand is isoxazole, 3,5-dimethylisoxazole, 2-methyl-benzoxazole, 2,5-dimethylbenzoxazole, and ethylenediamine, for n = 2, the ligand is N methylimidazole, N-ethylimidazole, N-propylimidazole, 3-amino, 5-methylisoxazole, and 5-amino 3,4 dimethylisoxazole. The Pd(ox)(L)₂ soluble in water are monomeric square-planar; the Pd(ox)(L) that are little soluble in water are dimeric square-planar with the ligand bridging bidentate except to the chelate ethylenediamine. All the compounds exhibit a certain inhibitorial effect with the exception of the Pd(ox)(en) derivative.     

Transesterification of oxo-osmium(VI) ligand complexes of thymine derivatives

We have measured the rate of transesterification reactions between glycols (L_O′) and oxo-osmium(VI) esters formed from thymine derivatives and a variety of nitrogen-containing ligands, L_OML_N, according to the equation: L_OML_N + L_O′

L_O′ML_N + L_O. We have also measured the rates of transesterification for this system with the addition of external nitrogen-containing ligands, L_N′. The order of effectiveness of the nitrogen-containing ligands in slowing the rate of transesterification is different depending on whether the ligand is present in the ester (L_N) or whether it is added externally (L_N′). Bathophenanthroline disulfonic acid is the most effective ligand when present in the ester. It forms exceptionally inert complexes. N,N,N′,N′-Tetramethylethylenediamine is the most effective ligand when added externally. The order of effectiveness of the nitrogen-containing ligand does not depend on the nature of either L_O or L_O′ but the nature of the glycol affects both the rate and the equilibria. We present mechanistic proposals, with limiting assumptions, to account for our findings.     

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.     

Interaction of cobalt(II) bovine carbonic anhydrase with pyridine-2,6-dicarboxylate ion and other chelating ligands

The removal of cobalt from cobalt(II) bovine carbonic anhydrase by pyridine-2-carboxylate, pyridine-2,6-dicarboxylate and 5-methyl-1,10-phenanthroline occurs via formation of an intermediate. This is presumed to be a ternary adduct of cobalt(II) enzyme with the ligand. In this, metal-protein bonds are loosened, probably via distortion of the normal geometry, resulting in accelerated breakdown of the adduct to apoprotein, compared with the behavior of the cobalt(II) enzyme alone. With 2-carboxy-1,10-phenanthroline, removal of metal is very rapid but no adduct is observed. Values of stability constants of the adducts and rate constants for their decomposition to apoprotein and their formation from apoprotein and cobalt(II) complex were measured at pH 5.5 and 25°C. Formation and dissociation rate constants for the adduct of cobalt carbonic anhydrase with pyridine-2,6-dicarboxylate could be measured from pH 5 to 7 and 10° to 25°C by stopped flow. Values of thermodynamic parameters for the various reactions agreed well with those estimated from the kinetic data.     

nmr and infrared spectroscopic investigations of the Al(III), Ga(III), and Be(II) complexes of ATP

The interaction of Al(III) with ATP has been examined by ³¹P and ¹H nmr and infrared spectroscopy. At pH 6.2, Al(III) forms a long-lived complex with ATP, in which chemical exchange between free and complexed ATP is slow on the nmr time scale. Infrared spectra of the Al(III)-ATP complex exhibit large perturbations in the band corresponding to the -PO₃^2? antisymmetric stretching mode. At higher pH values, equilibria involving Al(III) and OH^? become favored with the result that Al(III) no longer influences the spectroscopic properties of ATP. Similar spectroscopic results are obtained for the Ga(III) and Be(II) complexes of ATP.     

Investigation of the system cobalt(II) bovine carbonic anhydrase B-trichloroacetaldehyde.

The interactions between hydrated trichloroacetaldehyde and cobalt(II)bovine carbonic anhydrase B have been investigated as a function of pH by means of electronic spectroscopy of FT nmr spectroscopy. The hydrated aldehyde is bound to the metal ion and its apparent affinity constant is pH dependent with a bell-shaped profile. The kinetic parameters of the dissociation process have also been determined.     

Ligational behavior of a novel biologically active donor toward Cu(II) and Ni(II) ions and potentiation of its antibacterial activity by chelation with metal ions

The chelating behavior of a new multidentate ligand with tuberculostatic activity toward Cu(II) and Ni(II) ions has been studied. This ligand 3-(2-carboxyhydrazine)phenylimino-2-oximobutane(H2C POB) is found to chelate the above metal ions in both its keto and enol forms. The probable structures of all the complexes and the location of the bonding sites have been established through magnetic and spectroscopic (infrared, electronic) studies. The Cu(II) complex of the enol form exhibits subnormal magnetic moment at room temperature, indicating the probable existence of some sort of super exchange phenomenon in the system. The ligand itself and a few of its Cu(II) complexes have been found to exert powerful in vitro antibacterial activity toward some tuberculosis mycobacteria, such as Mycobacterium flae, Mycobacterium smegmatis, and Mycobacterium H37Rv.     

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.     

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):

     

A potentiometric and spectroscopic study of the proton and copper(II) complexes of methionine enkephalin and some related ligands

The results are reported of a potentiometric and spectrophotometric study of the proton and copper(II) complexes of methionine enkephalin and four related pentapeptides which all show greater biological activity than their parent enkephalin. Measurements were carried out at 25 degrees C and I = 0.10 mol dm-3 (KNO3). All the ligands studied form stable copper(II) complexes comparable to those formed by pentaglycine, with the peptide chain locked in a folded conformation by NNN or NNNN coordination to the metal ion. There is no indication of bonding through the tyrosine-phenolate oxygen atoms or the methionine sulfurs.     

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.     

Thermal behavior of bone and synthetic hydroxyapatites submitted to magnesium interaction in aqueous medium

The thermal behavior of the products obtained from magnesium interaction with powdered femoral bone and carbonate containing synthetic hydroxyapatite under conditions of pH fluctuation in aqueous medium has been investigated. The products, heat treated at different temperatures from 100 to 1300 degrees C, have been characterized by infrared spectroscopy and X-ray diffraction technique. The results show that the interaction with magnesium ion destabilizes the apatitic structure and favours its thermal conversion into beta-tricalcium phosphate (beta-TCP). The replacement of magnesium with calcium in the beta-TCP crystal lattice hinders its subsequent thermal conversion into the alpha form. The influence of magnesium on the thermal stability is much more evident for carbonate-containing synthetic hydroxyapatite than for bone apatite.     

Structural and electronic mimics of the active site of cobalt(II)-substituted zinc metalloenzymes

Complexes of cobalt(II) and zinc(II) which involve monodentate coordination of two alkyl carboxylate and two imidazole ligands in a slightly distorted tetrahedral fashion have visible and magnetic circular dichroism spectra remarkably similar to the cobalt(II)-substituted proteolytic enzymes thermolysin and carboxypeptidase A. Single crystal x-ray structure determinations on [Co(C₂H₅COO)₂Im₂], Im = imidazole, and its zinc counterpart reveal only minor structural differences between the cobalt and zinc species. Electron paramagnetic resonance spectra of cobalt(II) doped into zinc(II) complexes with known structures demonstrate the extreme sensitivity of the g-values to minor structural differences.     

Vanadyl(IV) conalbumin. II. Mixed metal and anion binding studies

Electron paramagnetic resonance (epr) studies demonstrate that at low levels of conalbumin (CA) saturation with Fe³⁺ or VO²⁺, a ph-dependent preference of the metal exists for different protein binding-site configurations,A, B, and C. The vanadyl ion epr spectra of mixed VO²⁺, Fe³⁺-conalbumin in which Fe³⁺ is preferentially bound to the N- or C-terminal binding site are consistent with all three configurations being formed at both metal sites. At high pH the spectra suggest interaction between binding sites. In the absence of HCO₃^?, VO²⁺ is bound almost exclusively in B configuration; a full binding capacity of 2 VO²⁺ per CA is retained. Stoichiometric amounts of HCO₃^? convert the epr spectrum from B to an A, B, C type. Addition of oxalate to bicarbonate-free preparations converts the B spectrum to an A′, B, C′ type where the B resonances have lost intensity to the A′ and C′ resonances but have not changed position. The data suggest that configuration B is anion independent and that only one equivalent of binding sites at pH 9 responds to the presence of HCO₃^1? or oxalate by changing configuration but not metal binding capability. The form of the bound anion may be HCO₃^? rather than CO₃^2?. The formation rate of the colored ferric conalbumin complex by oxidizing Fe²⁺ to Fe³⁺ in limited HCO₃^? at pH 9 is also consistent with one equivalent of sites having different anion requirements than the remaining sites. Increased NaCl or NaClO₄ concentration or substitution of D₂O for water as solvent affect the environment of bound VO²⁺, but the mechanisms of action are unknown.     

Different iron(II) complexes of bleomycin A2

By 13C-nmr on iron-bleomycin preparations, an iron-bleomycin-CO complex is found that loses its CO upon standing, as demonstrated using 14CO. Iron-bleomycin, prepared without rigorous exclusion of oxygen, reacts with CO to a stable diamagnetic iron-bleomycin-CO complex.     

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.     

Ternary complexes between adenosine 5′-triphosphoric acid, 2, 2′-bipyridyl and the divalent metal ions manganese(II), cobalt(II), copper(II), and zinc(II). Preparation and physicochemical properties

A series of ternary complexes between adenosine 5′-triphosphoric acid (ATP), 2, 2′-bipyridyl, and the transition metal ions manganese(II), cobalt(II), copper(II), and zinc(II) in the ratio 1:1:1 have been prepared. The solid compounds are crystalline and can be formulated as [M(II)-H₂ATP-2, 2′-Bipyridyl]₂·4H₂O (MATPbipy).X-ray powder patterns show them to be all isomorphous. Potentiometric titrations in aqueous solutions are in agreement with the presence of two ionizable protons. Ultraviolet and visible spectra, epr, and magnetic susceptibility measurements suggest that the metal ions have a high-spin distorted octahedral coordination. From infrared spectra it can be deduced that ATP coordinates to the metal only through the oxygen atoms of the phosphate groups.These compounds, which are particularly stable towards hydrolysis, form possible models for ATP transport in biological fluids.     

A spectroscopic and electrochemical study of the interaction between copper (II) glycylglycyl-L-histidine-N-methylamide and iron (III) tetra-p-sulfophenylporphine

A binuclear complex has been produced by the reaction of an iron porphyrin (sodium tetra-p-sulfophenylporphine iron (III)-FeTPPS) with a copper metallo-tripeptide (copper (II) glycylglycyl-L-histidine-N-methylamide-CuGGH) in aqueous solution. The system has been characterized by electron spin resonance (ESR) spectroscopy, optical absorption spectroscopy, and electrochemical methods. Room-temperature ESR spectra of the copper complex and low-temperature ESR spectra of the iron porphine provide evidence for the formation of a binuclear complex. These findings are supported by absorption spectroscopy and electrochemical studies, and lead to a value of ca. 2 X 10(-3) M-1 (at room temperature) for the equilibrium constant for complex formation. The relevance of this system to the enzymic active site of mammalian cytochrome c oxidase is discussed.     

Activation of yeast enolase by Cd(II)

Activation of yeast enolase by Cd2+ exhibits properties similar to activation by the physiological cofactor Mg2+. The activity is weakly stimulated, then inhibited by increasing ionic strength. The activity increases, then falls with increasing Cd2+ concentration. The effect of pH on activity produced by Cd2+ is very similar to that produced by Mg2+, except that the Cd2+ profile is shifted one pH unit to more alkaline values, and the maximum activity of the Cd2+-enzyme is about 10% of that of the Mg2+-enzyme. The apparent kinetic parameters of Cd2+ activation show little effect of pH except for inhibition by high concentrations of Cd2+: the apparent Ki increases sharply with pH. This is interpreted as the result of Cd2+ being a less effective "catalytic" metal ion, and Cd2+ being more effective in stabilizing the enzyme at alkaline pH's. The similarity of effects of ionic strength, divalent cation, and pH may be due to interaction with the same six sites per mole of enzyme. We also characterized the dependence of what is believed to be the enzyme-catalyzed enolization of a substrate analog, D-tartronate semialdehyde-2-phosphate (TSP) on similar parameters of pH, ionic strength, etc. The putative enolization is dependent on catalytic metal ion, although the TSP binds to the conformational Cd2+-enzyme complex. The reaction is very slow and very pH dependent, increasing with pH with a midpoint of reaction velocity at pH 8.7. There is a strong qualitative correlation between pH dependencies of reaction velocity of substrate conversion and TSP enolization and absorbance of the enzyme-bound TSP enolate, whether with Mg2+ or Cd2+ as cofactor. The slowness of the Cd2+-TSP reaction is not limited by proton release or any reaction involving covalent bonds to hydrogen. The apparent reaction rate constant increases linearly with Cd2+ concentration. Addition of excess ethylenediaminetetraacetic acid reverses the TSP reaction, but again very slowly. The binding of Cd2+ to the catalytic sites is characterized by low association and dissociation rate constants.     

A spectral investigation of the copper(II) complex of the antitumor compound bleomycin

A thorough spectral investigation of the copper(II) complex of the antitumor compound, bleomycin, has been carried out in solution employing optical, difference optical, electron spin resonance, and circular dichroism techniques. The optical spectrum of a pH = 7 solution of the 1:1 complex between copper(II) and bleomycin is characterized by a broad weak band in the visible region (λ_max = 610 nm) that cannot be resolved and intense ultraviolet bands at 317 (? = 2800), 327 (shoulder), 250 (? = 4700), and 257 nm (shoulder). The circular dichroism spectrum in the visible region shows the broad and weak visible absorption band contains at least three components (558, 675, and 880 nm) that are likely to be “d-d” in origin. The electron spin resonance spectrum is characteristic of a tetragonal d⁹ copper(II) system showing no rhombic distoritions at X-band frequencies (g_x = g_y ± 0.002). The spin Hamiltonian parameters for the pH = 7.0 solution corrected for second order effects are A_∥ = 177 × 10^?4 cm^?1, A_⊥ ? 15 × 10^?4 cm^?1, g_∥ = 2.214, g_⊥ = 2.039. Most interesting was the observation of extra hyperfine splitting due to endogenous nitrogen coordination in a 30% glycerol glass (A^N = 12.0 × 10^?4 cm^?1). That pattern is best interpreted as a seven-line sequence associated with three liganded nitrogens. A dramatic change in all spectral properties occurs when the pH of the copper(II)-bleomycin complex is lowered to 2.5. All these data taken together suggest a CuN₃O coordination complex in solution. Details and justifications as well as a discussion of the limitations of the interpretations are presented.