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The fate of platinum(II) and platinum(IV) anti-cancer agents in cancer cells and tumours.

SRIXE mapping has been used to gain insight into the fate of platinum(II) and platinum(IV) complexes in cells and tumours treated with anticancer active complexes to facilitate the development of improved drugs. SRIXE maps were collected of thin sections of human ovarian (A2780) cancer cells treated with bromine containing platinum complexes, cis-[PtCl(2)(3-Brpyr)(NH(3))] (3-Brpyr=3-bromopyridine) and cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] (OAcBr=bromoacetate), or a platinum complex with an intercalator attached cis-[PtCl(2)(2-[(3-aminopropyl)amino]-9,10-anthracenedione)(NH(3))]. After 24h the complexes appear to be localised in the cell nucleus with a lower concentration in the surrounding cytoplasm. In cells treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] the concentration of bromine was substantially higher than in control cells and the bromine was co-localised with the platinum consistent with the 3-bromopyridine ligand remaining bound to the platinum. The cells treated with cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] also showed an increased level of bromine, but to a much lesser extent than for those treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] suggestive of substantial reduction of the platinum(IV) complex. Maps were also collected from thin sections of a 4T1.2 neo 1 mammary tumour xenograft removed from a mouse 3h after treatment with cis,trans,cis-[PtCl(2)(OH)(2)(NH(3))(2)] and revealed selective uptake of platinum by one cell.

Animals↗

Formation of haloacetic acids during monochloramination.

Factors that affect the formation of haloacetic acids (HAAs) during monochloramination, such as monochloramine application techniques, the initial chlorine (Cl) to ammonia-N (N) ratios, the bromide concentrations, and the wastewater quality, were studied. Aqueous humic acid solutions and undisinfected wastewater effluent samples obtained from two Hong Kong Sewage Treatment Works (STWs) were monochloraminated under various conditions. HAA formation was strongly affected by the monochloramine application techniques. The formation of trichloroacetic acid (TCAA) and total HAAs was reduced by adding preformed monochloramine. A higher initial Cl:N ratio indicated a higher chlorine demand and consequently led to higher HAA yields. Increasing the bromide concentration shifted HAAs from chlorinated species to brominated species and increased the yields of total HAAs, concurrent with decreases in the yields of dichloroacetic acid (DCAA) and TCAA but with increases in those of the other HAAs measured. Variations in the patterns of HAA formation were observed in monochloraminated wastewater effluent samples. The variations cannot be simply explained by the chlorine chemistry involving ammonia and/or bromide but are likely attributable to the combining effects of the water quality and the characteristics of the organics in the wastewater.

Acetates↗

Distribution and levels of brominated flame retardants in sewage sludge.

One hundred and sixteen sewage sludge samples from 22 municipal wastewater treatment plants in Sweden were analysed for brominated flame retardants. Polybrominated diphenyl ethers (PBDEs) were in the range n.d.-450 ng/g wet weight, tetrabromobisphenol A (TBBPA) varied between n.d. and 220 ng/g wet weight, 2,4,6-tribromophenol was in the range n.d.-0.9 ng/g wet weight and polybrominated biphenyls were not detected (except for a possible analytical interference). There was a significant variation in the samples among plants. Influence from industries and other local sources can therefore be assumed. The correlation pattern indicated contribution from three different types of technical products; composed of either low-brominated PBDEs, decaBDE or TBBPA.

Bromine Compounds↗

Prediction of the retentions of polybrominated dibenzo-p-dioxins (PBDDs) by using the retentions of polychlorinated dibenzo-p-dioxins (PCDDs).

The retention equations In k' = A + B/T of 49 polychlorinated dibenzo-p-dioxins (PCDDs) and 4 polybrominated dibenzo-p-dioxins (PBDDs) in gas chromatography (GC) have been investigated to evaluate the properties of regression coefficients A and B. The quantitative relationships between A and B values of PCDDs and those of PBDDs are found. The regression equations derived have correlation coefficients greater than 0.997. The A, B values of any PBDD can be predicted by using the A, B values of the PCDD according to these relationships. Using these predicted A and B values, the retention times of all PBDDs can be predicted at any temperature program. It is very useful to identify the peak position of any PBDD because at present there are only a few standards of PBDDs available.

Bromine Compounds↗

Effect of NOM characteristics on brominated organics formation by ozonation.

In this study, organic fractions, namely, humic acid, fulvic acid, hydrophobic base and neutral, and hydrophilic acid, base, and -neutral, were extracted from source water. First, the characteristics of the organic fractions, such as carboxylic acidity, phenolic acidity, ultraviolet absorbance, and aromatic content, were analyzed. Further, a systematic study was carried out to the by-products obtained when organic fractions, to which various amounts of bromide had been added, were oxidized with ozone. Samples after ozonation were analyzed for several brominated organics. The results indicate that the characteristics of the aquatic organic matter, including carboxylic/phenolic acidity, aromatic/aliphatic content, and ultraviolet absorbance, appear to affect the formation of halogenated organics. In general, hydrophobic organics having higher phenolic acidity, aromatic content, and ultraviolet absorbance have higher ozone consumption and produce higher concentrations of brominated organics than hydrophilic organics. It was also found that humic acid demonstrated the highest bromoform (CHBr(3)), dibromoacetic acid (DBAA), and 2,4-dibromophenol (2,4-DBP) formation, whereas hydrophilic neutral produced less CHBr(3) and 2,4-DBP than the rest of the organic fractions but produced the highest amount of dibromoacetone (DBAC) and dibromoacetonitrile (DBAN).

Benzopyrans↗

A brominated-fluorene insect neuropeptide analog exhibits pyrokinin/PBAN-specific toxicity for adult females of the tobacco budworm moth.

An analog of the insect pyrokinin/PBAN class of neuropeptides, which features a 2-amino7-bromofluorene attached to the carboxy-terminal bioactive core of the insect pyrokinin/PBAN class of neuropeptides (Phe-Thr-Pro-Arg-Leu-NH(2)), via a succinnic acid linker, was tested in adult H. virescens moths. This analog was found to induce pheromone production when injected into or applied topically to moths. Topical application of as much as 1 nmol of the analog to moths induced production of significant amounts of pheromone for only 1-2 h, whereas injection of 500 pmol induced pheromone production for up to 20 h. All insects died within 24 h after injection of 500 pmol of the analog. Mortality studies indicated that the LD(50) for the analog was 0.7 pmol when injected. A non-pyrokinin/PBAN peptide analog formed by attachment of 2-amino-7-bromofluorene to Ala-Ala-Arg-Ala-Ala-NH(2) (via the succinnic acid linker) did not induce mortality when injected at 1 nmol. Similarly no mortality was found when up to 2 nmol of an analog containing a non-brominated fluorene ring, formed by attachment of 9-fluoreneacetic acid to Phe-Thr-Pro-Arg-Leu-NH(2,) was injected into moths. The data indicated that both the bromine and active core of the pyrokinin neuropeptides (Phe-Thr-Pro-Arg-Leu-NH(2)) were critical for a specific toxic action and suggested that the brominated analog poisoned the moths by interacting with pyrokinin receptors.

Animals↗