Enantioselectivity in ecotoxicity of pharmaceuticals, illicit drugs, and industrial persistent pollutants in aquatic and terrestrial environments: A review.

At present, there is a serious concern about the alarming number of recalcitrant contaminants that can negatively affect biodiversity threatening the ecological status of marine, estuarine, freshwater, and terrestrial ecosystems (e.g., agricultural soils and forests). Contaminants of emerging concern (CEC) such as pharmaceuticals (PHAR), illicit drugs (ID), industrial persistent pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and chiral ionic solvents are globally spread and potentially toxic to non-target organisms. More than half of these contaminants are chiral and have been measured at different enantiomeric proportions in diverse ecosystems. Enantiomers can exhibit different toxicodynamics and toxicokinetics, and thus, can cause different toxic effects. Therefore, the enantiomeric distribution in occurrence cannot be neglected as the toxicity and other adverse biological effects are expected to be enantioselective. Hence, this review aims to reinforce the recognition of the stereochemistry in environmental risk assessment (ERA) of chiral CEC and gather up-to-date information about the current knowledge regarding the enantioselectivity in ecotoxicity of PHAR, ID, persistent pollutants (PCBs and PBDEs) and chiral ionic solvents present in freshwater and agricultural soil ecosystems. We performed an online literature search to obtain state-of-the-art research about enantioselective studies available for assessing the impact of these classes of CEC. Ecotoxicity assays have been carried out using organisms belonging to different trophic levels such as microorganisms, plants, invertebrates, and vertebrates, and considering ecologically relevant aquatic and terrestrial species or models organisms recommended by regulatory entities. A battery of ecotoxicity assays was also reported encompassing standard acute toxicity to sub-chronic and chronic assays and different endpoints as biomarkers of toxicity (e.g., biochemical, morphological alterations, reproduction, behavior, etc.). Nevertheless, we call attention to the lack of knowledge about the potential enantioselective toxicity of many PHAR, ID, and several classes of industrial compounds. Additionally, several questions regarding key species, selection of most appropriate toxicological assays and ERA of chiral CEC are addressed and critically discussed.

Erythrocyte-derived liposomes for the treatment of inflammatory diseases.

Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory activity. The EDLs were prepared using lipids extracted from erythrocyte membranes, which are rich in omega-3 fatty acids with several health benefits. Diclofenac, a widely used anti-inflammatory drug, was incorporated into EDLs in relevant therapeutic concentrations. The EDLs were also functionalised with folic acid to allow their active targeting of M1 macrophages, which are key players in inflammatory processes. In the presence of lipopolysaccharide (LPS)-stimulated macrophages, empty EDLs and EDLs incorporating diclofenac were able to reduce the levels of important pro-inflammatory cytokines, namely interleukin-6 (IL-6; ≈85% and 77%, respectively) and tumour necrosis factor-alpha (TNF-α; ≈64% and 72%, respectively). Strikingly, cytocompatible concentrations of EDLs presented similar effects to dexamethasone, a potent anti-inflammatory drug, in reducing IL-6 and TNF-α concentrations, demonstrating the EDLs potential to be used as bioactive carriers in the treatment of inflammatory diseases.

Separation of Enantiomers Using Gas Chromatography: Application in Forensic Toxicology, Food and Environmental Analysis.

Analytical methodologies to accurate quantify enantiomers are nowadays imperative in different areas such as pharmaceutical, agrochemicals, forensic toxicology, food and environmental analysis, among others. This review aims to discuss the use of gas chromatography (GC) methods as a tool for enantiomeric separations. The separation of enantiomers by GC methodologies has been performed using both direct and indirect methods, nevertheless, the selected methodology depends not only on the physical chemical properties of the target compounds but also on the field of application. Indeed, enantiomeric separation by GC in the forensic toxicology field was frequently performed using indirect methods for pharmaceuticals and illicit drugs, while direct methods have been reported as the preferable choice for pesticides and polychlorinated biphenyl compounds. Concerning food analysis chiral separation have been mainly carried out by direct methods while for environmental analysis, both direct and indirect methods have been reported, depending on the class of compounds studied. This manuscript compiles analytical methods of enantioseparation by GC, both direct and indirect methods, and its applicability in forensic toxicology, food and environmental analysis.

Assessment of Douro and Ave River (Portugal) lower basin water quality focusing on physicochemical and trace element spatiotemporal changes.

Water quality of Douro and Ave lower basin was evaluated regarding physicochemical parameters (pH, conductivity, dissolved oxygen and temperature), nutrient compounds (nitrates, nitrites, ammonium and orthophosphates), chlorophyll a and occurrence of trace elements (Li, Be, Al, Ti, V, Cr, Co, Ni, Cu, Zn, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, Th and U). To study spatiotemporal variations and possible anthropogenic sources, estuarine samples were collected at nine sampling sites in Douro and five in Ave distributed along the estuaries at four sampling campaigns (spring, summer, fall and winter). According to the water quality standards for aquatic life and recreation, Douro and Ave river water quality was found out of safe limits regarding several parameters. Nitrate levels were systematically high (> 50 mg L-1 in a significant number of samples) and mean levels of trace elements were higher than the established values of Canadian Environmental Quality Guidelines for aquatic life protection for Al, Cu, Se, Ag, Cd and Pb in Douro and Ave, and also Zn in Ave. Significant spatial differences were found in Ave river estuary for trace elements with a clear trend for higher values from upstream to downstream found. Seasonal differences were also observed particularly in Douro river estuary with higher levels in spring for most elements.

Distribution and environmental assessment of trace elements contamination of water, sediments and flora from Douro River estuary, Portugal.

The present study evaluated the content and distribution of several trace elements (Li, Be, Al, V, Cr, Co, Ni, Cu, Zn, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, and U) in the Douro River estuary. For that, three matrices were collected (water, sediments and native local flora) to assess the extent of contamination by these elements in this estuarine ecosystem. Results showed their occurrence in estuarine water and sediments, but significant differences were recorded on the concentration levels and pattern of distribution among both matrices and sampling points. Generally, the levels of trace elements were higher in the sediments than in the respective estuarine water. Nonetheless, no correlation among trace elements was determined between water and sediments, except for Cd. Al was the trace element found at highest concentration at both sediments and water followed by Zn. Pollution indices such as geo-accumulation (Igeo), enrichment factor (EF) and contamination factor (CF) were determined to understand the levels and sources of trace elements pollution. Igeo showed strong contamination by anthropogenic activities for Li, Al, V, Cr, Ni, Cu, Zn, Ba and Pb at all sampling points while EF and CF demonstrated severe enrichment and contamination by Se, Sb and Pb. Levels of trace elements were compared to acceptable values for aquatic organisms and Sediment Quality Guidelines. The concentration of some trace elements, namely Al, Pb and Cu, were higher than those considered acceptable, with potential negative impact on local living organisms. Nevertheless, permissible values for all trace elements are still not available, demonstrating that further studies are needed in order to have a complete assessment of environmental risk. Furthermore, the occurrence and possible accumulation of trace elements by local plant species and macroalgae were investigated as well as their potential use as bioindicators of local pollution and for phytoremediation purposes.

Bacterial degradation of moxifloxacin in the presence of acetate as a bulk substrate.

Fluoroquinolones constitute a group of emerging pollutants and their occurrence in different environmental compartments is becoming object of increasing public concern due to their ecotoxicological effects and the potential to develop resistant bacteria. This study aimed to investigate the biodegradation of moxifloxacin (MOX), for which studies in the literature are very scarce. An activated sludge (AS) consortium and three bacterial strains able to degrade fluoroaromatic compounds - strains F11, FP1 and S2 - were tested. Biodegradation studies were conducted using acetate as a bulk carbon source. Strain F11 showed the highest biodegradation capacity, being able to completely consume and dehalogenate 7.5 µM of the target antibiotic when daily co-supplemented with acetate present as a readily degradable organic substrate in wastewaters. MOX could be used by strain F11 as a sole nitrogen source but the presence of an external nitrogen source in the culture medium was essential for complete biodegradation. Strain F11 was capable of completely consuming MOX in a range between 2 and 11 µM, although stoichiometric fluoride release was not obtained for the highest tested concentration. The antibacterial activity of residual MOX and of the metabolic products potentially resultant from the biodegradation process was investigated by agar diffusion tests, demonstrating that MOX biodegradation is associated with the elimination of the antibacterial properties of the target antibiotic and of the produced metabolites, which is an important result, as the activity of antibiotics and/or their metabolites in the environment, even at low levels, may lead to the development of resistant bacterial strains. Overall, the results obtained in this study suggest that strain F11 is a promising microorganism for the treatment of waters contaminated with MOX, where it could be used for bioaugmentation/bioremediation purposes. To the best of our knowledge, this is the first study reporting complete removal and dehalogenation of MOX by a single microorganism.

Enantiomeric resolution of kielcorin derivatives by HPLC on polysaccharide stationary phases using multimodal elution.

Analytical HPLC methods using carbamate chiral stationary phases of polysaccharide derivatives were developed for the enantiomeric resolution of five racemic mixtures of xanthonolignoids: rac-trans-kielcorin C, rac-cis-kielcorin C, rac-trans-kielcorin D, rac-trans-isokielcorin D, and rac-trans-kielcorin E. The separations were evaluated with the stationary phases cellulose tris-3,5-dimethylphenylcarbamate, amylose tris-3,5-dimethylphenylcarbamate, amylose tris-(S)-1-phenylethylcarbamate, and amylose tris-3,5-dimethoxyphenylcarbamate under normal, reversed-phase, and polar organic elution conditions. Chiral recognition of those chiral stationary phases, the influence of mobile phases on the enantiomers separation, and the effects of structural features of the solutes on the chiral discrimination observed are discussed. The best performance was achieved on an amylose tris-3,5-dimethylphenylcarbamate phase. Polar organic conditions gave shorter retention factors and better resolutions and were a valuable alternative to the alcohol-hexane or reversed-phase conditions.

Enantiomeric resolution by HPLC of axial chiral amides using amylose tris[(S)-1-phenylethylcarbamate].

The enantiomeric resolution of a series of N-arylamides was examined on amylose tris[(S)-1-phenylethylcarbamate] coated onto aminopropylated 7 microns silica with 500 A diameter pores and on naked silica 5 microns particle size with 500 A diameter pores. The enantiomeric resolution obtained for this series was excellent on both columns. The enantioselectivity of cellulose and amylose tris(3,5-dimethylphenylcarbamate) coated onto APS-Hypersil (120 A pore size, 5 microns particle size) was also investigated for this series of compounds.

Developing gossypol derivatives with enhanced antitumor activity.

Preclinical and clinical studies have pointed to the antitumor potential of the naturally occurring polyphenolic binaphthyl dialdehyde, gossypol, as well as its purified (-,+) enantiomers. To explore further the antitumor properties of this multifunctional agent, we synthesized several reactive derivatives including the (-,+) enantiomers of gossypolone and four different gossypol Schiff's bases (AR1, AR2, AR3, AR4). The biological activities of these new agents were screened by measuring their in vitro antiproliferative activity against malignant (MCF-7, MCF-7/adr) or immortalized (HBL-100) human breast epithelial cell lines. Racemic gossypolone showed relatively uniform antiproliferative activity against all of the breast epithelial cell lines with 3- to 5-fold less activity than (--)-gossypol against MCF-7 and MCF-7/adr cells. Of interest, the relative antitumor potency of purified gossypolone enantiomers was reverse that of gossypol enantiomers, since (+)-gossypolone showed up to 3-fold greater inhibition of MCF-7 culture growth than (--)-gossypolone. Of the Schiff's base derivatives only AR3 with its isopropyl amine substituent demonstrated cytotoxic activity comparable to that of (--)-gossypol; derivatives with ethyl, propyl, or butyl amine substituents (AR1, AR2, AR4) had little growth inhibitory activity at culture concentrations up to 25 microM. AR3 activity was greatest against HBL-100 and MCF-7 cells [MCF-7 IC50 values: AR3 = 0.9 microM, (--)-gossypol = 2.3 microM]; unlike (--)-gossypol, however, AR3 showed substantially reduced activity against the multidrug-resistant subline, MCF-7/adr. These structure-activity comparisons suggest that isolation of (-,+)-enantiomers of AR3 and additional chemical modifications including the synthesis of an isopropyl amine Schiff's base of gossypolone will likely yield a newer generation of gossypol analogues with enhanced anticancer potential.