Supramolecular Handshakes: Characterization of Urea-Carboxylate Interactions Within Calixarene Frameworks.

The research of molecular capsules offers high application potential and numerous benefits in various fields. With the aim of forming supramolecular capsules which can be reversibly assembled and dissociated by simple external stimuli, we studied interactions between calixarenes containing urea and carboxylate moieties. To this end two ureido-derivatives of p-tert-butylcalix[4]arene comprising phenylureido-moieties and diacetate-calix[4]arenes were prepared. The binding of acetate by ureido-derivatives of calixarene in acetonitrile was characterized, revealing high affinity of ureido-calixarenes for carboxylates. This suggested high potential for uniting the complementary calix[4]arenes via H-bonds between carboxylic groups and urea moieties. The assembly of calixarenes was examined in detail by means of UV, 1H NMR, ITC, DOSY, MS, and conductometry providing insight in the structure-stability relationship. The tetraureido-calixarene derivative formed the most stable heterodimers with diacetate-calix[4]arenes featuring practically quantitative association upon mixing the two calixarene counterparts. The possibility of controlling the formation of the heterodimer by protonating the carboxylates, thereby hindering the interactions critical for capsule assembly, was investigated. Indeed, the reversibility of breaking and re-forming the heterodimer by addition of an acid and base to the solution containing urea- and carboxylate-derivative calix[4]arene was demonstrated using NMR spectroscopy.

Toxicity of binary mixtures of pesticides and pharmaceuticals toward Vibrio fischeri: Assessment by quantitative structure-activity relationships.

Pollutants in real aquatic systems commonly occur as chemical mixtures. Yet, the corresponding risk assessment is still mostly based on information on single-pollutant toxicity, accepting the assumption that pollutant mixtures exhibit additive toxicity effect which is often not the case. Therefore, it is still better to use the experimental approach. Unfortunately, experimental determination of toxicity for each mixture is practically unfeasible. In this study, quantitative structure-activity relationship (QSAR) models for the prediction of toxicity of binary mixtures towards bioluminescent bacteria Vibrio fischeri were developed at three toxicity levels (EC10, EC30 and EC50). For model development, experimentally determined toxicity values of 14 pollutants (pharmaceuticals and pesticides) were correlated with their structural features, applying multiple linear regression together with genetic algorithm. Statistical analysis, internal validation and external validation of the models were carried out. The toxicity is accurately predicted by all three models. EC30 and EC50 values are mostly influenced by geometrical distances between nitrogen and sulfur atoms. Furthermore, the simultaneous presence of oxygen and chlorine atoms in mixture can induce the increase in toxicity. At lower effect levels (EC10), nitrogen atom bonded to different groups has the highest impact on mixture toxicity. Thus, the analysis of the descriptors involved in the developed models can give insight into toxic mechanisms of the binary systems.

Combined toxicities of binary mixtures of alachlor, chlorfenvinphos, diuron and isoproturon.

Pesticides are the chemicals of increased concern regarding their adverse environmental effects. In particular, the reports on their joint toxicity effects are scarce in the literature. Therefore, this paper describes the experiments on toxicities of four pesticides: alachlor, chlorfenvinphos, diuron, and isoproturon, toward Vibrio fischeri. In particular, the joint toxicity effects for all possible binary combinations of the pesticides were analyzed. The analysis included the application of concentration addition and independent action models at two toxicity levels: EC10 and EC50. The analysis revealed additive behavior between all pesticide pairs. The only exception was isoproturon and chlorfenvinphos whose combination resulted in synergistic toxic activity. The original form of the logistic function was given preference over the linearized form in describing the response-dose relationships of investigated pesticides.

Toxicity of pharmaceuticals in binary mixtures: Assessment by additive and non-additive toxicity models.

Current risk assessment in many countries, including European Union, is still placing focus on single substances rather than their mixtures, although mixtures are commonly found in the environment. To overcome this problem and gain new insights, six pharmaceuticals, namely: azithromycin (AZM), erythromycin (ERM), carbamazepine (CBA), oxytetracycline (OTC), dexamethasone (DXM), and diclofenac (DCF), were selected in order to analyze their combined toxicity in binary mixtures. Overall, 45 binary mixtures were analyzed. Single component toxicities were determined as well, for modelling purpose. Two most common mathematical models for the description of mixture toxicities were applied: concentration addition (CA) and independent action (IA) model. Comparison of the predicted and experimentally obtained toxicities provided information about the modes of toxicity action in the mixtures. OTC-DCF binary mixture indicated synergism with respect to additive behavior (CA model). All other binary combinations containing OTC or DCF were acting very similarly: the synergism with respect to additive behavior was observed for OTC-CBA and DCF-CBA combinations, while OTC-AZM, OTC-ERM, DCF-AZM and DCF-ERM exhibited antagonistic behavior with respect to CA model. All the remaining binary mixtures indicated additive behavior. The applicability of IA model as a proof of independent toxic action of the components was confirmed in cases of DCF-AZM, DCF-ERM, and OTC-AZM mixtures.