Bioinorganic chemistry最新文献

Nine new organoplatinum (Pt) compounds, cyclophosphamide (CY), and 5-fluorouracil (FU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 × DBA/2 hybrid mice. In each experiment the Pt + CY dual combination was minimally supra-additive at the doses chosen. However, eight of the nine Pt + CY + FU combination regimens enhanced markedly the increased life span of treated mice as compared with the corresponding dual Pt + CY combination. Collectively, the cure rate (>60-day survival) was less than 6% with the various Pt + CY combinations, and was increased to over 63% upon inclusion of FU in the regimens.

Reduction potentials for a series of free-base porphyrins of widely differing basicity have been measured in DMF (dimethylformamide) solution using phase-selective fundamental harmonic and second harmonic ac polarography. The potentials show a good linear correlation with porphyrin properties, such as electrophilic substitution rates and reduction potentials for the corresponding manganese(III) and iron(III) metalloporphyrins, regardless of the nature of the porphyrin substituent or its position on the porphyrin periphery. Examples provided show that the reduction potentials, which are rapidly and accurately obtained, are a reasonable measure of porphyrin electron density, which can be useful in structure-reactivity correlations.

The copper complex of the antituberculous drug, isonicotinic acid hydrazide (INH), inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus and inactivates its ability to malignantly transform chick embryo cells. The INH-copper complex binds to the 70S genome RNA of Rous sarcoma virus (RSV), which may account for its ability to inhibit the RNA-dependent DNA polymerase. The complex binds RNA more effectively than DNA in contrast to M-IBT-copper complexes, which bind both types of nucleic acids equally. The homopolymers, poly rA and poly rU, are bound by the INH-copper complex to a greater extent than poly rC. Isonicotinic acid hydrazide alone and CuSO₄ alone bind neither DNA, RNA, poly (rA), poly (rU), nor poly (rC). However, CuSO₄ alone binds poly (rI); INH alone does not.

In addition to viral DNA synthesis, chick-embryo cell DNA synthesis is inhibited by the INH-copper complex. The extent of inhibition of cellular DNA synthesis is greater than that of cellular RNA and protein synthesis. No selective inhibition of transformation in cells previously infected with Rous sarcoma virus is observed.

Esr and electronic spectra of complexes of the general composition VO(AA)₂ and VO(ox)(AA) have been characterized; AA = gly, his, cys, pro, val, met, asp amino acids. Spectra of the formulation VO(ox)(LL) (with LL = imidazole plus monodentate oxalate, histamine plus monodentate oxalate, histidine, cysteine, 4-imidazolepropionic acid, mercaptopropionic acid, ethylenediamine and ethanolamine) have been used to deduce a self-consistent assignment of A_L, a ligand donor additivity constant contribution to the observed hyperfine splitting, A_iso. Values of A_L are sensitive to inductive effects in the ligand structure. The solution structures and likely coordination geometries of VO(his)₂, VO(gly)₂, and VO(cys)₂²⁻ are discussed. The role of the imidazole moiety as a σ donor and sulfhydryl sulfur as a π acceptor is observed in VO(AA)₂ and VO(ox)(AA) complexes.

In a study of the biochemical mechanism of renal toxicity of certain antitumor platinum compounds, particularly cis-dichlorodiammineplatinum(II) (NSC-119875), qualitative and quantitative studies of the soluble nonspecific kidney esterases were carried out using (C57BL/6 x DBA/2) mice. There was a major suppression of the testosterone-dependent esterases of treated male mice; these levels dropped to levels below those found in untreated females within 72 h after certain of the drugs were administered. This effect appeared to be in inverse relationship to the numerical value of the LD₅₀ values of the compounds investigated.

Rats were subjected for 2 weeks to separate and combined exposures to mercuric chloride and sodium selenite at doses of 0.5 mg Hg/kg and 0.5 mg Se/kg. The content of mercury, selenium and protein as well as the activities of glutamate dehydrogenas (GLDH) and malate dehydrogenase (MDH) were determined in homogenates, mitochondria and intramitochondrial structures of the exposed animals. It was found that both separate and combined exposures of rats to mercuric chloride and sodium selenite inhibited GLDH activity and did not affect MDH activity in the examined organs. Mercury-selenium interaction brought about a decrease in the content of mercury in the intramitochondrial structures of kidneys and an increased accumulation of both elements in the outer and inner membranes of liver mitochondria. The biochemical mechanism of mercury-selenium interaction is discussed.

The volume changes, ΔV, produced by the formation of two types of 1:1 Cu(II):dipeptide complexes were determined dilatometrically. A volume increase of about 11 ml/mole results from the formation of one category of complex in which the Cu(II) is chelated to the terminal amino and carbonyl oxygen of the peptide. A ΔV of about 20 ml/mole results when a tridentated chelate is formed by the coordination of Cu(II) to the terminal amine, the peptide nitrogen and the carboxylate oxygen of the dipeptide; during this process a proton is expelled from the peptide backbone. These volume parameters exhibit a small dependence on the type and location of nonpolar radicals incorporated in the dipeptide. The values for the protonation of the amine radical or of dipeptides exhibited a small dependence on structure, −3.2

The tryptophan fluorescence maximum for holoprotocatechuate 3,4-dioxygenase(holo PCD) is blue-shifted slightly (3 nm) from that of the apoenzyme. In the preparation of apoenzyme, increases in tryptophan fluorescence intensity coincided with decreases in enzyme activity and decreases in iron content. The tryptophan emission intensity of reconstituted enzyme having full enzyme activity was about 90% of that of the holoenzyme. Although apo PCD has similar molecular weight, amino acid content and essentially the same gross quaternary conformation as holo PCD, the absence of iron in apo PCD causes the changes in emission intensity of tryptophan. Findings indicate that some tryptophan residues may be (or may be near) the iron-binding ligands in the catalytic site of protocatechuate 3,4-dioxygenase.

Inbred female C₃H/St mice exhibit the normal incidence of spontaneous mammary adenocarcinoma of 80~100% if they are maintained on a standard commercial laboratory diet containing 0.15 ppm of selenium with meat and dried skimmed milk as major sources of protein. The tumor incidence drops to 42% if animals of the same strain are kept on a diet containing 0.45 ppm of selenium, with fishmeal as the main source of protein. The tumor incidence declines further to 25, 19 and 10% if the animals in addition receive 0.1, 0.5, and 1.0 ppm of selenium in the drinking water. Selenium supplementation at these levels has no noticable adverse effects on weight-gains and survival of the mice. Selenium supplemented groups of animals also remained tumor-free for

Resonance Raman spectra of tetraphenylporphin in the solid state, tetraphenylporphin dication (with trifluoroacetate as counterion) in the solid state and in chloroform solution, and copper(II) tetraphenylporphin in the solid state were compared with resonance Raman spectra of the corresponding tetra(perdeuteriophenyl)porphin derivatives. The isotopic shift of a band at ~1233 cm⁻¹ in undeuterated compounds to ~1183 cm⁻¹ in phenylperdeuterated compounds demonstrates the existence of phenylporphyrin resonance interactions in the compounds described.