It is well known that biomembranes and subcellular organelles are susceptible to lipid peroxidation. There is a steadily increasing body of evidence indicating that lipid peroxidation is involved in basic deteriorative mechanisms, e.g., membrane damage, enzyme damage, and nucleic acid mutagenicity. The formation of lipid peroxides can be induced by enzymatic or nonenzymatic peroxidation in the presence of oxygen. The mechanisms of formation and removal of reactive oxygen species, lipid peroxides, and free radicals in biological systems are briefly reviewed. In recent years, there has been renewed interest in the role played by lipid peroxidation in many disease states. Xanthine oxidase has been shown to generate reactive oxygen species, superoxide (O2−·), and hydrogen peroxide (H2O2) that are involved in the peroxidative damage to cells that occurs in ischemia-reperfusion injury. During ischemia, this enzyme is induced from xanthine dehydrogenase. We have shown that peroxynitrite (a reactive nitrogen species) has the potential to convert xanthine dehydrogenase to oxidase. The following biological effects of lipid peroxidation were found: a) the lipid peroxidation induced by ascorbic acid and Fe2+ affects the membrane transport in the kidney cortex and the cyclooxygenase activity in the kidney medulla, and b) the hydroperoxy adducts of linoleic acid and eicosapentaenoic acid inhibit the cyclooxygenase activity in platelets. The balance between the formation and removal of lipid peroxides determines the peroxide level in cells. This balance can be disturbed if cellular defenses are decreased or if there is a significant increase in peroxidative reactions. Once lipid peroxidation is initiated, the reactive intermediate formed induces cell damage.
Exploitation of saturated macrocyclic polyamines has led to the discovery of numerous novel functions and new molecules such as 1) unique proton sponge properties; 2) uptake of biological polyanions; 3) peptide-like metal uptake properties; 4) stabilization of unusual oxidation states of metal ions (e.g., CuIII, NiIII); 5) novel uptake and activation of O2 by new NiII-macrocyclic complexes; 6) a new synthetic pathway to functionalize macrocyclic polyamines; 7) the first gold(III) complex that is a new candidate for gold-plating agents; 8) intrinsic zinc(II) properties pertinent to zinc enzymes; 9) selective recognition of thymine by ZnII complexes; and 10) new cage supermolecules. These newly discovered molecules and properties have opened up a new field of supramolecular science.
We developed two methods for solubility screening of drug candidates in drug discovery. The first is a solution-precipitation (SP) method, in which the sample solutions are prepared by adding the drug solution in dimethylsulfoxide (DMSO) to buffers followed by filtering off the precipitate using 96-well filterplate. The second is a powder-dissolution (PD) method, in which the solid samples are dissolved to the buffer in the HPLC vial equipped with the filter membrane in the HPLC autosampler. An HPLC equipped with a photodiode array detector is used to measure the concentration of the sample solutions in both methods. The SP method was used for high throughput screening the solvating process of the candidates in aqueous solutions with lower sample consumption, and the PD method was used for screening both inter-molecular interaction in solid state and solvation in aqueous solution with more sample amount than that of SP method. Therefore, the solubility screening from early to final stage of lead optimization process would be successfully accomplished by using both methods complementarily.
In case of poisoning by herbicide compounded with Propanil (DCPA) and Carbaryl (NAC), we attempted simultaneous solid-phase extractions of DCPA, NAC, and 3,4-dichloroaniline (DCA), a metabolite of DCPA, from the patient's serum, and quantitative analytical method using HPLC-UV detection. With this HPLC method, the quantitative detection limits in the serum are 0.005μg/ml for DCPA and DCA and 0.001μg/ml for NAC, and the UV spectra of all three compounds could easily be obtained using a diode-array detection limit of 0.05μg/ml. When the three compounds were added to serum at concentrations ranging from 0.1—10.0μg/ml, the recovery rates were satisfactory at between 91.1% and 101.9%. On analysis of the serum of patient who had ingested Kusanon A Emulsion, the ingested substance apparently caused an increase in the DCA concentration, which led to the appearance of methemoglobinemia. The possibility that the DCA concentration might be used for prognositic purposes was suggested.
Essential oils on the market were analyzed using GC-MS and the main ingredients of each essential oil were quantified. Analysis of the essential oil of Lavandula officinalis (lavender oil) showed that each sample had a different ratio of the contents of main ingredients, such as linalool, linalyl acetate, and camphor. In addition, some commercial lavender oils were analyzed by GC-MS for comparison with the Lavandula flagrans (lavandin oil) and the reference standard1). As a result of this analysis, although the components of almost all commercial lavender oils were approximately the same as those of the reference standard,1) there were a few products that contained more than 0.5% of the amont of camphor in lavandin oil. This suggests that some lavender oil samples are mixed with lavandin oil to lower the price. Commercial essential oils of Melaleuca alternifolia (teatree oil) and Mentha piperita (peppermint oil) were also analyzed by GC-MS. Each of the peppermint oil samples had a different ratio in the content of its main ingredient. With respect to teatree oils, the amount of terpinens in each sample differed. These results led to concern about the efficacy of essential oils. For achieve the expected efficacy of essential oils, correct information on their ingredients should be available and quality control using instrumental analysis should be introduced.