Effects of root-derived organic acids on sorption of pharmaceutically active compounds in sandy topsoil.

The presence and fate of pharmaceutically active compounds (PhACs) in agricultural fields are rarely investigated. The present study highlights that root-derived low-molecular-weight organic acids (LMWOAs) affect the mobility of PhACs in cultivated humic Arenosol. Sorption experiments are conducted using three PhACs characterised by different physicochemical properties: carbamazepine (CBZ), 17α-ethinylestradiol (EE2), and diclofenac-sodium (DFC). The results suggest that the adsorption of EE2 is more intense than the other two PhACs, whereas DFC and CBZ are primarily dominated by desorption. LMWOAs mainly provide additional low-energy adsorption sites for the PhACs, and slight pH changes do not significantly affect the sorption mechanism. During competitive adsorption, the high-energy sites of the adsorbents are initially occupied by EE2 owing to its high adsorption energy (∼15 kJ/mol). The new low-energy binding sites enhance the adsorption of DFC (from 8.5 % to 72.0 %) and CBZ (from 31.0 % to 70.0 %) during multicomponent adsorption. LMWOAs not only affect adsorption by modifying the pH but also provide additional binding sites that allow the PhACs to remain in the root environment for a longer period. As the concentration of LMWOAs temporarily changes, so does the availability of PhACs in the root zone. Environmental changes in the humic horizon enhance the mobility of the adsorbed PhACs, which renders them continuously available for uptake by plants, thus increasing the possibility of PhACs entering the human food chain.

Pharmaceuticals in water and sediment of small streams under the pressure of urbanization: Concentrations, interactions, and risks.

Small streams are crucial but vulnerable elements of ecological networks. To better understand the occurrence of pharmaceutically active compounds (PhACs) in streams, this study focused on the occurrence, distribution, and environmental risk of 111 PhACs and 7 trace elements based on a total of 141 water and sediment samples from small streams located in the urbanizing region of Budapest, Hungary. Eighty-one PhACs were detected in the aqueous phase, whereas sixty-two compounds were detected in the sediment. Carbamazepine (CBZ) was the most frequently identified PhAC in water, and was found in 91.5% of all samples. However, the highest concentrations were measured for lamotrigine (344.8 µg·L-1) and caffeine (221.4 µg·L-1). Lidocaine was the most frequently occurring PhAC in sediment (73.8%), but the maximum concentrations were detected for CBZ (395.9 ng·g-1) and tiapride (187.7 ng·g-1). In both water and sediment, more PhACs were found downstream of the wastewater treatment plants (WWTPs) than in the samples not affected by treated wastewater, even though no relationship was observed between the total amount of treated wastewater and the number of detected PhACs. The PhAC concentrations were also independent of the distance from the WWTP effluents. PhAC-polluted samples were detected upstream of the WWTPs, thereby suggesting the relevance of diffuse emissions in addition to WWTP outlets. The most frequently detected PhACs in the sediment were usually also present in the water samples collected at the same place and time. The varying concentrations of PhACs and the fluctuating water-sediment properties resulted in a lack of correlation between the general chemical properties and the concentrations of PhACs, which makes it difficult to predict PhAC contamination and risks in urbanized small streams. The environmental risk assessment indicated that diclofenac had the highest risk in the sampling area.

Evaluation of the effect of the intrinsic chemical properties of pharmaceutically active compounds (PhACs) on sorption behaviour in soils and goethite.

The role of the chemical properties of Pharmaceutically Active Compounds (PhACs) in their sorption behaviour and consequently in their fate and mobility is of major environmental interest, but a comprehensive evaluation is still lacking. The sorption of nine PhAC molecules with distinct physico-chemical properties on soils and goethite was described using linear, Freundlich and Langmuir models and the relationship between the chemical structures of the compounds and the parameters of the adsorption was evaluated using redundancy analysis (RDA). The latter showed that the sorption of the pharmaceuticals was determined by the intrinsic chemical characteristics of the molecules, as shown by the 35% value of constrained variability. For the hydrophobic estrogens, E1, E2 and EE2, the logD value and the number of hydrogen bond sites were found to be the main controlling factors for adsorption, indicating that hydrophobic interaction and hydrogen bonding are the dominant sorption mechanisms. The π energy of the molecules also proved a very important parameter, governing the retention of PhACs in soils, especially in the case of carbamazepine, oxazepam and lamotrigine. The main controlling factor for ionic compounds, such as diclofenac sodium, tramadol or lidocaine, is the fraction of PhACs present as charged species, revealing the importance of Coulomb forces. The results of this study will allow semi-quantitative predictions to be made on how the molecular structure governs the sorption of PhACs and which sorption mechanism could be involved.

Effects of pharmaceutically active compounds (PhACs) on fish body and scale shape in natural waters.

BACKGROUND: In recent years, there are growing concerns about pharmaceutically active compounds (PhACs) in natural ecosystems. These compounds have been found in natural waters and in fish tissues worldwide. Regarding their growing distribution and abundance, it is becoming clear that traditionally used risk assessment methodologies and ecotoxicological studies have limitations in several respects. In our study a new, combined approach of environmental impact assesment of PhACs has been used. METHODS: In this study, the constant watercourses of the suburban region of the Hungarian capital (Budapest) were sampled, and the body shape and scale shape of three fish species (roach Rutilus rutilus, chub Squalius cephalus, gibel carp Carassius gibelio) found in these waters were analyzed, based on landmark-based geometric morphometric methods. Possible connections were made between the differences in body shape and scale shape, and abiotic environmental variables (local- and landscape-scale) and measured PhACs. RESULTS: Significant connections were found between shape and PhACs concentrations in several cases. Despite the relatively large number of compounds (54) detected, citalopram, propranolol, codeine and trimetazidine significantly affected only fish body and scale shape, based on their concentrations. These four PhACs were shown to be high (citalopram), medium (propranolol and codeine), and low (trimetazidine) risk levels during the environmental risk assessment, which were based on Risk Quotient calculation. Furthermore, seven PhACs (diclofenac, Estrone (E1), tramadol, caffeine 17α-Ethinylestradiol (EE2), 17α-Estradiol (aE2), Estriol (E3)) were also categorized with a high risk level. However, our morphological studies indicated that only citalopram was found to affect fish phenotype amongst the PhACs posing high risk. Therefore, our results revealed that the output of (traditional) environmental/ecological risk assessment based on ecotoxicological data of different aquatic organisms not necessarily show consistency with a "real-life" situation; furthermore, the morphological investigations may also be a good sub-lethal endpoint in ecotoxicological assessments.

Dataset of pharmaceuticals in the Danube and related drinking water wells in the Budapest region.

The present dataset provides data on the pharmaceutically active compounds (PhACs) concentrations measured in the Danube and the drinking water abstraction wells (DWAW) in the Budapest region. Grab samples were collected during five periods. One hundred and seven water samples from the Danube and ninety water samples from the relevant DWAWs were analyzed to quantify physical-chemical parameters, trace element concentrations, and one hundred and eleven PhACs, including pharmaceutical derivatives, illicit drugs, and alkaloids. The ion concentrations were measured using dual channel ion chromatography, spectrophotometric and titrimetric methods, and inductively coupled plasma mass spectrometry. PhACs concentrations were measured after solid-phase extraction applying supercritical fluid chromatography coupled with tandem mass spectrometry. Fifty-two PhACs were quantified in the Danube, and ten PhACs were present in >80% of the samples. Whereas thirty-two PhACs were quantified in the DWAWs. The present dataset is useful for further comparisons and meta-analyses.

Occurrence of pharmaceuticals in the Danube and drinking water wells: Efficiency of riverbank filtration.

Surface waters are becoming increasingly contaminated by pharmaceutically active compounds (PhACs), which is a potential risk factor for drinking water quality owing to incomplete riverbank filtration. This study examined the efficiency of riverbank filtration with regard to 111 PhACs in a highly urbanized section of the river Danube. One hundred seven samples from the Danube were compared to 90 water samples from relevant drinking water abstraction wells (DWAW) during five sampling periods. The presence of 52 PhACs was detected in the Danube, the quantification of 19 agents in this section of the river was without any precedent, and 10 PhACs were present in >80% of the samples. The most frequent PhACs showed higher concentrations in winter than in summer. In the DWAWs, 32 PhACs were quantified. For the majority of PhACs, the bank filtration efficiency was >95%, and not influenced by concentrations measured in the river. For carbamazepine lidocaine, tramadol, and lamotrigine, low (<50%) filtration efficiency was observed; however, no correlations were observed between the concentrations detected in the Danube and in the wells. These frequently occurring PhACs in surface waters have a relatively even distribution, and their sporadic appearance in wells is a function of both space and time, which may be caused by the constantly changing environment and micro-biological parameters, the dynamic operating schedule of abstraction wells, and the resulting sudden changes in flow rates. Due to the changes in the efficiency of riverbank filtration in space and time, predicting the occurrence and concentrations of these four PhACs poses a further challenge to ensuring a safe drinking water supply.

Investigation of the sorption of 17α-ethynylestradiol (EE2) on soils formed under aerobic and anaerobic conditions.

A study was conducted on the sorption of 17α-ethynylestradiol (EE2) on five soils formed under different redox conditions: an Arenosol (A_20) with fully aerobic conditions, two Gleysol samples (G_20 and G_40) with suboxic and anoxic conditions and two Histosols (H_20 and H_80) with mostly anoxic conditions. The soils were characterized on the basis of total organic carbon (TOC), specific surface area (SSA) and the Fourier transform infrared spectra of the humic acid and humin fractions (the soil remaining after alkali extraction) of the soil. The maximum adsorption capacity of the soils (Qmax) ranged from 10.7 to 83.6 mg/g in the order G_20 > H_20 > G_40 > A_20 > H_80, which reflected the organic matter content of the soils. The sorption isotherms were found to be nonlinear for all the soil samples, with Freundlich n values of 0.45-0.68. The strong nonlinearity found in the adsorption of the H_80 samples could be attributed to their high hard carbon content, which was confirmed by the high aromaticity of the humin fraction. The maximum sorption capacity (Qmax) of the soils did not increase indefinitely as the organic carbon content of the soils rose. There could be two reasons for this: (i) the large amount of organic matter may reduce the number of binding sites on the surface, and (ii) the decrease in SSA with increasing soil OC content may limit the ability to adsorb EE2 molecules. In anaerobic soil samples, where organic matter accumulation is pronounced, the amount of aromatic and phenolic compounds was higher than in better aerated soil profiles. Strong correlations were found between the amount of aromatic and phenolic compounds in the organic matter and the adsorption of EE2 molecules, indicating that π-π interaction and H-bonding are the dominant sorption mechanisms.

Thermal baths as sources of pharmaceutical and illicit drug contamination.

Despite the fact that there are tens of thousands of thermal baths in existence, knowledge about the occurrence of pharmaceutically active compounds (PhACs) in untreated thermal wastewater is very limited. Because used thermal water is typically legally discharged into surface waters without any treatment, the effluent poses environmental risks for the receiving water bodies. The aim of this study was to show the occurrence patterns and spatiotemporal characteristics of 111 PhACs in thermal wastewater. Six thermal water outflows of different thermal baths were tested in different seasons in the Budapest metropolitan region (Hungary), and diurnal analysis was performed. After solid-phase extraction, the samples were analysed and quantified by coupling supercritical fluid chromatography and mass spectrometry to perform simultaneous multi-residue drug analysis. The results confirm that water discharge pipes directly transport pharmaceuticals into surface water bodies; 34 PhACs were measured to be over the limit of quantification at least once, and 21 of them were found in more than one water sample. The local anaesthetic drug lidocaine, antiepileptic carbamazepine, analgesic derivative tramadol and illicit drug cocaine were detected in more than half of the samples. Caffeine, metoprolol and bisoprolol (cardiovascular drugs), benzoylecgonine (cocaine metabolite), diclofenac (NSAID), citalopram (antidepressant) and certain types of hormones also have a significant frequency of 30-50%. However, the occurrence and concentrations of PhACs vary according to the season and number/types of visitors. As demonstrated by the diurnal fluctuation, drug contamination of thermal waters can significantly vary, even for similar types of baths; furthermore, the quantity and types of some pollutants rapidly change in the discharged thermal wastewater.

Iterative Coupling of Two Different Enones by Nitromethane Using Bifunctional Thiourea Organocatalysts. Stereocontrolled Assembly of Cyclic and Acyclic Structures.

An organocatalytic iterative assembly line has been developed in which nitromethane was sequentially coupled with two different enones using a combination of pseudoenantiomeric cinchona-based thiourea catalysts. Application of unsaturated aldehydes and ketones in the second step of the iterative sequence allows the construction of cyclic syn-ketols and acyclic compounds with multiple contiguous stereocenters. The combination of the multifunctional substrates and ambident electrophiles rendered some organocatalytic transformations possible that have not yet been realized in bifunctional noncovalent organocatalysis.

(Thio)urea organocatalyst equilibrium acidities in DMSO.

Bordwell's method of overlapping indicators was used to determine the pK(a) values of some of the most popular (thio)urea organocatalysts via UV spectrophotometric titrations. The incremental effect of CF(3) groups on acidic strength was also investigated. The pK(a)'s are in the range of 8.5-19.6. The results may lead to a better understanding of noncovalent organocatalysis and may aid in future catalyst development.

Double diastereocontrol in bifunctional thiourea organocatalysis: iterative Michael-Michael-Henry sequence regulated by the configuration of chiral catalysts.

The importance and reactivity consequences of the double diastereocontrol in noncovalent bifunctional organocatalysis were studied. The results suggest that the bifunctional thioureas can have synthetic limitations in multicomponent domino or autotandem catalysis. Nevertheless, we provided a means to exploit this behavior and used the configuration of the chiral catalyst as a control element in organo-sequential reactions.