Bioinorganic chemistry最新文献

The rates of formation of a number of metallocarboxypeptidases from metal ions and bovine apocarboxypeptidase A (CPA) have been measured directly and by a competitive method. Rates were determined within pH = 6–8 by utilising the pH change attending metal-ion incorporation, employing indicator and stopped-flow. Second-order rate constants (k_f, M⁻¹ s⁻¹ at 25°C, I = 1 M NaCl, pH = 7, Tris = 25 μM) were 1.7 × 10⁵ (Mn²⁺), 3 × 10⁴ (Co²⁺), 5 × 10³ (Ni²⁺), 7 × 10⁵ (Zn²⁺), and 9 × 10⁵ (Cd²⁺). Relative incorporation rate constants were determined at 25°, pH = 7.0, Tris = 0.1 M, by competing two metal ions for a deficiency of apoprotein and analyzing the products by differential enzyme activity. Agreement between the two methods was reasonable. Rate constants for dissociation of CoCPA, NiCPA, and ZnCPA were measured by loss of enzyme activity on addition of the metal ion scavenger EDTA. Values of k_d at 25°, I = 1.0 M NaCl, pH = 7.0 were 8 × 10⁻³, 3 × 10⁻⁵, and 4 × 10⁻⁴ s⁻¹, respectively, Values of K obtained kinetically (k_f/k_d) were in good agreement with those determined by activity measurements of equilibrated solutions. Results are compared with those of bovine apocarbonic anhydrase, where generally significantly slower rates are encountered.

The study of the (L Lysine)_n-Cu(II) (I:I) system with n = 4 and n = 25 using circular dischroism (CD) data has provided evidence indicating the formation of two complexes in a two-atep process. In the first of these complexes, obtained at pH 6.6 the α-amino terminal group and the adjacent deprotonated amide nitrogen are bound to the metal. In the second, additional amino nitrogens of side chains lie at the other two corners of the coordination square.A comprehensive investigation of changes occuring in special patterns when coordination takes place enables the assignment of three bands that are characteristic to each type of nitrogen coordination.

N-Methyl isatin β-thiosemicarbazone-copper complex inhibits the RNA-dependent DNA polymerase activity of Rous sarcoma virus (RSV), but not its ribonuclease H. activity. In addition, bovine pancreatic RNase and DNase are not inhibited by the complex.

Vitamin B_12s effects the reductive dechlorination of mirex (dechlorane) in protic solvent systems, under both catalytic and stoichiometric conditions, mainly to yield compounds of composition C₁₀Cl_12-nH_n, with n = 1–8, in which the basic dihomocubane cage structure is retained; the formation of cage-opened, reductively dehalogenated derivatives of 4,7-methanoindene occurs only to a very minor extent.

The corresponding reactions of kepone (chlordecone), in contrast, occur with predominant formation of indene derivatives C₉Cl_8-nH (with n = 3–5), presumably via 4,7-methanoinden-8-one derivatives. Under certain mild conditions, vitamin B_12s induces a fragmentation of kepone leading to the destruction of the dihomocubane moiety and the formation of an isolable organocobalamin having a C₃Cl₃H₂ residue attached to the cobalt atom. In strongly alkaline media, the reaction of kepone with vitamin B_12s may in addition yield high-molecular-weight condensation products of unknown constitution. Reactions of this type are of interest as prototypes of soil-decontamination processes.

The synthesis of virtually all the lanthanide octaethylporphyrin complexes have been achieved by heating appropriate anhydrous lanthanide halide and octaethylporphyrin in imidazole melt at 210°C for two hours. The lighter lanthanide porphyrin complexes are very susceptible to hydrolysis, the middle lanthanide porphyrin complexes are moderately stable, and the heavier lanthanide porphyrin complexes are relatively more stable to hydrolysis. Two out of four lanthanide porphyrin complexes studied in detail, namely ytterbium and lutetium octaethylporphyrins, aggregate in benzene and the Soret bands in their absorption spectra are about 6 nm shifted to higher energies upon a hundred-fold increase in their concentrations. The aggregations of these lanthanide porphyrin complexes in non-coordinating solvents have been further verified by ¹H NMR spectral studies. This spectral behavior can be interpreted qualitatively in terms of the model of the molecular exciton interactions with stacking of at least two prophyrins. A dimeric structure of these lanthanide porphyrin complexes has been proposed on the basis of geometrical considerations. On the contrary, the europium and gadolinium octaethylporphyrins associate very weakly in benzen in the concentration range studied. All four lanthanide porphyrin complexes interact with pyridine and piperidine, and the Soret bands in their absorption spectra are about 8 nm shifted to low energies as compared with their values in pure benzene.

The ionization constants and some divalent cation dissociation constants of nalidixic and oxolinic acids, both specific inhibitors of bacterial DNA replication, have been determined. The carboxylic pK_a′ values are 6.1 and 6.9 at 25° for nalidixic and oxolinic acids, respectively. These values indicate that intramolecular hydrogen-bonding stabilizes the un-ionized form of these compounds in aqueous solution. Both compounds bind divalent cations; the divalent cation dissociation constants for oxolinic acid are somewhat smaller that those for nalidixic acid. We suggest that both compounds may act by forming a complex in situ with a divalent cation in a metalloprotein involved in DNA replication. The evidence that both drugs inhibit at the same target site is briefly reviewed.

Equilibria between hemin and imidazole in various organic and aqueous organic solvents have been investigated by uv-visible spectrophotometry at 25°C, and the following types of equilibria have been established:

The twenty-four hour inhibition of m-malate dehydrogenase (E.C. 1.1.1.37)¹ by various complexes of cis-platinum(II) and cis-platinum(IV) was measured as a function of the platinum concentration. It was observed that increased alkylation of the amine groups of Pt(II) and to a lesser degree of Pt(IV) decreased the activity consistently. It was also observed that the Pt(IV) analogues inhibit the enzyme to about an order of magnitude greater than the Pt(II) complexes. These phenomena will be interpreted.

This communication demonstrates further that terbium(III) can be used as a probe for DNA. The stoichiometry of terbium binding to DNA was measured by two new methods. In the first method, calf-thymus DNA was titrated with radioactive terbium-160, which is an isotope of the common terbium-159. The resulting DNA-terbium complex was trapped and measured on millipore filters. In the second method, a peak of UV absorption of terbium was found at 219 nm and was used to measure stoichiometry. By both methods, the stoichiometry of binding was one Tb(III) for each three available phosphate groups in DNA. Finally, a rapid method was developed using terbium-160 to measure the amount of nucleic acid in a solution.

The time courses of induction in rat liver of copper chelatin by copper, cadmium thionein by cadmium, and zinc thionein by copper, cadmium, and zinc were monitored following single intraperitoneal injections of metal salts. Low dosages of inducing metal were used in order to avoid toxic effects, being 5 mg zinc, 0.5 mg copper, and 0.25 mg cadmium per kg body weight. Peak times of induction and half times of decay observed were: copper chelatin (9 h, 8.6 h), cadmium thionein (18 h, 6.80 days), and zinc thionein (zinc rats, 18 h, 10.1 h; copper rats, 9 h, 18.2 h; cadmium rats, 24 h, 4.53 days). Administration of actinomycin D (1 mg per kg body weight) at the peak times of induction of the various proteins had no effect on the concentrations of chelatin or cadmium thionein observed up to 24 hours later, but in the case of zinc thionein, induced by zinc, copper, or cadmium, elevated concentrations were observed up to 23 h after administration of the drug. Such behavior is reminiscent of superinduction previously seen with other proteins and enzymes. We postulate that the intracellular concentration of free zinc in liver is of fundamental importance in the induction of zinc thionein, and this can be disturbed by exogenous copper or cadmium resulting in the induction of synthesis of zinc thionein.