Characterization of Three Tetrabromobisphenol-S Derivatives in Mollusks from Chinese Bohai Sea: A Strategy for Novel Brominated Contaminants Identification.

Identification of novel brominated contaminants in the environment, especially the derivatives and byproducts of brominated flame retardants (BFRs), has become a wide concern because of their adverse effects on human health. Herein, we qualitatively and quantitatively identified three byproducts of tetrabromobisphenol-S bis(2,3-dibromopropyl ether) (TBBPS-BDBPE), including TBBPS mono(allyl ether) (TBBPS-MAE), TBBPS mono(2-bromoallyl ether) (TBBPS-MBAE) and TBBPS mono(2,3-dibromopropyl ether) (TBBPS-MDBPE) as novel brominated contaminants. Meanwhile, the mass spectra and analytical method for determination of TBBPS-BDBPE byproducts were presented for the first time. The detectable concentrations (dry weight) of TBBPS-MAE, TBBPS-MBAE and TBBPS-MDBPE were in the ranges 28-394 µg/g in technical TBBPS-BDBPE and 0.1-4.1 ng/g in mollusks collected from the Chinese Bohai Sea. The detection frequencies in mollusk samples were 5%, 39%, 95% for TBBPS-MAE, TBBPS-MBAE and TBBPS-MDBPE, respectively, indicating their prevailing in the environment. The results showed that they could be co-produced and leaked into the environment with production process, and might be more bioaccumulative and toxic than TBBPS-BDBPE. Therefore, the production and use of TBBPS derivatives lead to unexpected contamination to the surrounding environment. This study also provided an effective approach for identification of novel contaminants in the environment with synthesized standards and Orbitrap high resolution mass spectrometry.

Bioactive secondary metabolites from the Red Sea marine Verongid sponge Suberea species.

In a continuation of our efforts to identify bioactive compounds from Red Sea Verongid sponges, the organic extract of the sponge Suberea species afforded seven compounds including two new dibrominated alkaloids, subereamollines C and D (1 and 2), together with the known compounds aerothionin (3), homoaerothionin (4), aeroplysinin-1 (5), aeroplysinin-2 (6) and a revised subereaphenol C (7) as ethyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate. The structures of the isolated compounds were assigned by different spectral data including optical rotations, 1D (1H and 13C) and 2D (COSY, multiplicity-edited HSQC, and HMBC) NMR and high-resolution mass spectroscopy. Aerothionin (3) and subereaphenol C (7) displayed potent cytotoxic activity against HeLa cell line with IC50 values of 29 and 13.3 µM, respectively. In addition, aeroplysinin-2 (6) showed potent antimigratory activity against the human breast cancer cell line MDA-MB-231 with IC50 of 18 µM. Subereamollines C and D are new congeners of the previously reported compounds subereamollines A and B with methyl ester functionalities on the side chain. These findings provide further insight into the biosynthetic capabilities of members of the genus Suberea and the chemical diversity as well as the biological activity of these compounds.

Antifouling compounds from the sub-arctic ascidian Synoicum pulmonaria: synoxazolidinones A and C, pulmonarins A and B, and synthetic analogues.

The current study describes the antifouling properties of four members belonging to the recently discovered synoxazolidinone and pulmonarin families, isolated from the sub-Arctic sessile ascidian Synoicum pulmonaria collected off the Norwegian coast. Four simplified synthetic analogues were also prepared and included in the study. Several of the studied compounds displayed MIC values in the micro-nanomolar range against 16 relevant marine species involved in both the micro- and macrofouling process. Settlement studies on Balanus improvisus cyprids indicated a deterrent effect and a low toxicity for selected compounds. The two synoxazolidinones displayed broad activity and are shown to be among the most active natural antifouling bromotyrosine derivatives described. Synoxazolidinone C displayed selected antifouling properties comparable to the commercial antifouling product Sea-Nine-211. The pulmonarins prevented the growth of several bacterial strains at nanomolar concentrations but displayed a lower activity toward microalgae and no effect on barnacles. The linear and cyclic synthetic peptidic mimics also displayed potent antifouling activities mainly directed against bacterial adhesion and growth.

Isolation and synthesis of pulmonarins A and B, acetylcholinesterase inhibitors from the colonial ascidian Synoicum pulmonaria.

Pulmonarins A and B are two new dibrominated marine acetylcholinesterase inhibitors that were isolated and characterized from the sub-Arctic ascidian Synoicum pulmonaria collected off the Norwegian coast. The structures of natural pulmonarins A and B were tentatively elucidated by spectroscopic methods and later verified by comparison with synthetically prepared material. Both pulmonarins A and B displayed reversible, noncompetitive acetylcholinesterase inhibition comparable to several known natural acetylcholinesterase inhibitiors. Pulmonarin B was the strongest inhibitor, with an inhibition constant (Ki) of 20 µM. In addition to reversible, noncompetitive acetylcholinesterase inhibition, the compounds displayed weak antibacterial activity but no cytotoxicity or other investigated bioactivities.

Cytotoxic psammaplysin analogues from a Suberea sp. marine sponge and the role of the spirooxepinisoxazoline in their activity.

Seventeen bromotyrosine-derived metabolites, including eight new compounds, were isolated from a Micronesian sponge of the genus Suberea. Four of the new compounds were psammaplysin derivatives (10-13), and the other four were ceratinamine derivatives (14-17). Of the compounds obtained, the psammaplysins exhibited cytotoxicity against human cancer cell lines (GI50 values down to 0.8 µM), while the ceratinamine and moloka'iamine analogues showed almost no activity. These results suggest that the spirooxepinisoxazoline ring system is a requirement for cytotoxicity and, therefore, may serve as an attractive molecular scaffold for the development of a potent anticancer agent.

Antimicrobial activities of the bromophenols from the red alga Odonthalia corymbifera and some synthetic derivatives.

A series of bromophenols was obtained by isolation from red alga Odonthalia corymbifera and by reactions of bis(hydroxyphenyl)methanes with bromine. New bromophenols including 3,3',5,5'-tetrabromo-2,2',4,4'-tetrahydroxydiphenylmethane (10), a regioisomer of the potent antimicrobial natural product, together with known derivatives were synthesized in high yield. All of the isolated and synthesized compounds were tested for antimicrobial activity against gram-negative, gram-positive bacteria and fungi. The preliminary structure-activity relationship, to elucidate the essential structure requirements for antimicrobial activity, has been described. Among the isolated natural products 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (4) was found to be the most active derivative against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, and Trichophyton mentagrophytes. The synthetic bromophenols 3,3'-dibromo-6,6'-dihydroxydiphenylmethane (13) and 3,3',5,5'-tetrabromo-6,6'-dihydroxydiphenylmethane (14) showed potent antibacterial effect against Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Proteus vulgaris, and Salmonella typhimurium.

Novel flame retardants, 1,2-bis(2,4,6-tribromophenoxy)ethane and 2,3,4,5,6-pentabromoethylbenzene, in United States' environmental samples.

Two brominated flame retardants, 1,2-bis(2,4,6-tribromophenoxy)ethane (TBE) and 2,3,4,5,6-pentabromoethylbenzene (PEB), were detected and identified in ambient air samples from various sites in the United States. The identifications were confirmed by comparing the gas chromatographic retention times and mass spectra of the compounds found in the environment with those of authentic materials. Generally, the TBE concentrations in air were comparable to those of tetra- through hexabrominated diphenyl ethers (PBDEs) and often higher than those of decabromodiphenyl ether (BDE-209). The atmospheric TBE concentrations at locations in the southern United States were higher than those in the northern United States. TBE was also found in a sediment core from Lake Michigan; the concentrations of TBE increased with time, were lower than those of BDE-209, but were approximately 10 times higher than the sum of BDE-47, -99, and -100. The maximum PEB concentration in Chicago air was 550 pg/ m3, which was 10 times higherthan the concentration of total PBDEs in this sample. In general, the concentrations of PEB in air samples were low but detectable and were less than those of PBDEs. PEB was not found in the sediment core from Lake Michigan. These occurrences of relatively high concentrations of TBE and PEB in environmental samples may reflect the increasing usage of these compounds as flame retardants.

Purealidin S and purpuramine J, bromotyrosine alkaloids from the Fijian marine sponge Druinella sp.

Two bromotyrosine alkaloids, purealidin S (2) and purpuramine J (5), were isolated from the Fijian marine sponge Druinella sp. Eight known bromotyrosine compounds were also isolated. This is the first report of a bromotyrosine N-oxide containing alkaloid. These two compounds were found to have moderate cytotoxic activity. In addition, bioassay data for the eight known bromotyrosine metabolites are reported.

The impact of particulates on the aqueous sonication of bromobenzene.

Sonodegradation of bromobenzene, bromophenolate ion, and 2,4,5-trichlorobiphenyl was studied in the presence of various types of solid particles suspended in water. Three particle diameters (10 nm, 15 microm, and 35 microm) and two particle types (silica particles and organic resin) were investigated over a range of particle concentrations (0.05-10 g l(-1)). The sonochemical decomposition rate constant for bromobenzene (k = 0.044 +/- 7.50 x 10(-4) min(-1) at 20 kHz) was not significantly impacted by very fine silica particles (10 nm). The presence of 15 microm silica decreased sonication rates slightly (<7%) even at a concentration of 10 g l(-1). Organic resin particles demonstrated a more significant impact, particularly at higher concentration and with very hydrophobic compounds. These findings are significant for the application of ultrasound to treatment streams containing solid particles.

Isolation and biological evaluation of filiformin, plakortide F, and plakortone G from the Caribbean sponge Plakortis sp.

The bioassay- and spectroscopic-guided fractionation of the antimalarial extract from a Jamaican sponge, Plakortis sp., resulted in the isolation of three metabolites. The previously reported bromoaromatic filiformin (1) was obtained from our sample of Plakortis sp., and the potential origins of this compound are discussed. The peroxide-containing metabolite, plakortide F (2), is a more typical Plakortis metabolite and was shown to exhibit significant activity against Plasmodium falciparum in vitro. The isolation, structure, and bioactivity of a new lactone, plakortone G (3), are also reported.

Determination of ebrotidine metabolites in overlapping peaks from capillary zone electrophoresis using chemometric methods.

This paper illustrates the possibilities of chemometric methods in the resolution and quantification of various compounds in overlapping peaks from capillary electrophoresis. Ebrotidine and most of its metabolites were efficiently separated by capillary zone electrophoresis (CZE) in a fused-silica capillary. However, the procedure was not suitable for the physical separation of the three less ionizable metabolites, which comigrated and overlapped with the electroosmotic flow signal. Multivariate curve resolution based on an alternating least squares procedure was used for their mathematical resolution. For such a purpose, data obtained in the CZE system with a diode array detector, which consisted of UV spectra registered over time, were analyzed. The ebrotidine metabolites were successfully resolved and quantified in synthetic mixtures and urine samples.