New Insight Regarding the Relationship Between Enantioselective Toxicity Difference and Enantiomeric Toxicity Interaction from Chiral Ionic Liquids

Chirality is an important property of molecules. The study of biological activity and toxicity of chiral molecules has important theoretical and practical significance for toxicology, pharmacology, and environmental science. The toxicological significance of chiral ionic liquids (ILs) has not been well revealed. In the present study, the enantiomeric joint toxicities of four pairs of chiral ILs 1-alkyl-3-methylimidazolium lactate to Allivibrio fischeri were systematically investigated by using a comprehensive approach including the co-toxicity coefficient (CTC) integrated with confidence interval (CI) method (CTCICI), concentration-response curve (CRC), and isobole analysis. The direct equipartition ray (EquRay) design was used to design five binary mixtures of enantiomers according to molar ratios of 1:5, 2:4, 3:3, 4:2, and 5:1. The toxicities of chiral ILs and their mixtures were determined using the microplate toxicity analysis (MTA) method. Concentration addition (CA) and independent action (IA) were used as the additive reference models to construct the predicted CRC and isobole of mixtures. On the whole, there was an enantioselective toxicity difference between [BMIM]D-Lac and [BMIM]L-Lac, and [HMIM]D-Lac and [HMIM]L-Lac, while no enantioselective toxicity difference was observed for [EMIM]D-Lac and [EMIM]L-Lac, and [OMIM]D-Lac and [OMIM]L-Lac. Thereinto, the enantiomer mixtures of [BMIM]D-Lac and [BMIM]L-Lac, and [HMIM]D-Lac and [HMIM]L-Lac presented antagonistic action, and the enantiomer mixtures of [EMIM]D-Lac and [EMIM]L-Lac, and [OMIM]D-Lac and [OMIM]L-Lac overall presented additive action. Moreover, the greatest antagonistic toxicity interaction occurred at the equimolar ratio of enantiomers. Based on these results, we proposed two hypotheses, (1) chiral molecules with enantioselective toxicity difference tended to produce toxicity interactions, (2) the highest or lowest toxicity was usually at the equimolar ratio and its adjacent ratio for the enantiomer mixture. These hypotheses will need to be further validated by other enantiomer mixtures.

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Novel Segmented Concentration Addition Method to Predict Mixture Hormesis of Chlortetracycline Hydrochloride and Oxytetracycline Hydrochloride to Aliivibrio fischeri

International Journal of Molecular Sciences ◽

10.3390/ijms21020481 ◽

2020 ◽

Vol 21 (2) ◽

pp. 481 ◽

Cited By ~ 6

Author(s):

Huilin Ge ◽

Min Zhou ◽

Daizhu Lv ◽

Mingyue Wang ◽

Defang Xie ◽

...

Keyword(s):

Mixture Toxicity ◽

Practical Significance ◽

Concentration Addition ◽

High Concentration ◽

Cross Point ◽

Antagonistic Action ◽

Interval Method ◽

Molar Ratios ◽

Ca Model ◽

Aliivibrio Fischeri

Hormesis is a concentration-response phenomenon characterized by low-concentration stimulation and high-concentration inhibition, which typically has a nonmonotonic J-shaped concentration-response curve (J-CRC). The concentration addition (CA) model is the gold standard for studying mixture toxicity. However, the CA model had the predictive blind zone (PBZ) for mixture J-CRC. To solve the PBZ problem, we proposed a segmented concentration addition (SCA) method to predict mixture J-CRC, which was achieved through fitting the left and right segments of component J-CRC and performing CA prediction subsequently. We selected two model compounds including chlortetracycline hydrochloride (CTCC) and oxytetracycline hydrochloride (OTCC), both of which presented J-CRC to Aliivibrio fischeri (AVF). The seven binary mixtures (M1–M7) of CTCC and OTCC were designed according to their molar ratios of 12:1, 10:3, 8:5, 1:1, 5:8, 3:10, and 1:12 referring to the direct equipartition ray design. These seven mixtures all presented J-CRC to AVF. Based on the SCA method, we obtained mixture maximum stimulatory effect concentration (ECm) and maximum stimulatory effect (Em) predicted by SCA, both of which were not available for the CA model. The toxicity interactions of these mixtures were systematically evaluated by using a comprehensive approach, including the co-toxicity coefficient integrated with confidence interval method (CTCICI), CRC, and isobole analysis. The results showed that the interaction types were additive and antagonistic action, without synergistic action. In addition, we proposed the cross point (CP) hypothesis for toxic interactive mixtures presenting J-CRC, that there was generally a CP between mixture observed J-CRC and CA predicted J-CRC; the relative positions of observed and predicted CRCs on either side of the CP would exchange, but the toxic interaction type of mixtures remained unchanged. The CP hypothesis needs to be verified by more mixtures, especially those with synergism. In conclusion, the SCA method is expected to have important theoretical and practical significance for mixture hormesis.

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Chiral Ionic Liquids Based on L-Cysteine Derivatives for Asymmetric Aldol Reaction

Catalysts ◽

10.3390/catal12010047 ◽

2022 ◽

Vol 12 (1) ◽

pp. 47

Author(s):

Karolina Zalewska ◽

Małgorzata E. Zakrzewska ◽

Luis C. Branco

Keyword(s):

Ionic Liquids ◽

Aldol Condensation ◽

Aldol Reaction ◽

Reaction Medium ◽

Chiral Molecules ◽

Asymmetric Aldol ◽

Chiral Ionic Liquids ◽

Asymmetric Aldol Reaction ◽

Aldehydes And Ketones ◽

Asymmetric Catalyst

Structure, and consequently properties, of ionic liquids can be easily tailored by changing cation/anion combinations and/or attaching functional groups. By grafting enantiopure moieties to the framework of ionic liquid it is possible to prepare bioinspired chiral molecules that can serve as a reaction medium, additive or even asymmetric catalyst. In this context, new chiral ionic liquids (CILs), based on biomolecules, such as aminoacids (L-cysteine derivatives), have been synthesised and tested in asymmetric aldol condensation of aldehydes and ketones. The best results were obtained for CILs composed of S-methyl-L-cysteine cation and bis(trifluoromethane)sulfonimide anion, in the reaction of 2- or 4-nitrobenzaldehyde with acetone or cyclohexanone, giving the aldol product in moderate yields 70–76% and high ee values (up to 96%).

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Integrative Assessment of Mixture Toxicity of Three Ionic Liquids on Acetylcholinesterase Using a Progressive Approach from 1D Point, 2D Curve, to 3D Surface

International Journal of Molecular Sciences ◽

10.3390/ijms20215330 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5330 ◽

Cited By ~ 2

Author(s):

Huilin Ge ◽

Shanshan Tao ◽

Min Zhou ◽

Bingjun Han ◽

Hongqiu Yuan

Keyword(s):

Ionic Liquids ◽

Reference Model ◽

Mixture Toxicity ◽

Ternary Mixtures ◽

Coefficient Of Determination ◽

Concentration Addition ◽

Weibull Function ◽

Additive Action ◽

Integrative Assessment ◽

Almost All

The joint toxicities of [BMIM]BF4, [BMIM]PF6, and [HMIM]BF4 on acetylcholinesterase (AChE) were systematically investigated by using a progressive approach from 1D single effect point, 2D concentration-response curve (CRC), to 3D equivalent-surface (ES) level. The equipartition equivalent-surface design (EESD) method was used to design 10 ternary mixtures, and the direct equipartition ray (EquRay) design was used to design 15 binary mixtures. The toxicities of ionic liquids (ILs) and their mixtures were determined using the microplate toxicity analysis (MTA) method. The concentration addition (CA), independent action (IA), and co-toxicity coefficient (CTC) were used as the additive reference model to analyze the toxic interaction of these mixtures. The results showed that the Weibull function fitted well the CRCs of the three ILs and their mixtures with the coefficient of determination (R2) greater than 0.99 and root-mean-square error (RMSE) less than 0.04. According to the CTC integrated with confidence interval (CI) method (CTCICI) developed in this study, the 25 mixtures were almost all additive action at 20% and 80% effect point levels. At 50% effect, at least half of the 25 mixtures were slightly synergistic action, and the remaining mixtures were additive action. Furthermore, the ESs and CRCs predicted by CA and IA were all within the CIs of mixture observed ESs and CRCs, respectively. Therefore, the toxic interactions of these 25 mixtures were actually additive action. The joint toxicity of the three ILs can be effectively evaluated by the ES method. We also studied the relationship between the mixture toxicities and component concentration proportions. This study can provide reference data for IL risk assessment of combined pollution.

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Synergistic Effect of Aldicarb on the Toxicity of Ionic Liquid Mixtures to Vibrio qinghaiensis sp.-Q67

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.864-867.413 ◽

2013 ◽

Vol 864-867 ◽

pp. 413-417

Author(s):

Jin Zhang ◽

Shu Shen Liu ◽

Hui Ping Deng ◽

Shu Guang Zhu ◽

Qi Ling

Keyword(s):

Ionic Liquid ◽

Individual Component ◽

Liquid Mixtures ◽

Environmental Safety ◽

Concentration Addition ◽

Ray Method ◽

Equivalent Effect ◽

Additive Action ◽

Toxicity Analysis ◽

Ratio Of Components

Various chemicals emerge in environment and exist as mixtures with different forms and concentrations. Toxicity interaction by mixtures may pose potential hazards and risks to the environmental safety and human health. Recent data show that toxicity interaction within ionic liquid (IL) mixtures related with some certain component. However, how to determine the specific component in a mixture is not an easy work and needs more researches about it. Therefore, we investigated the toxicity of twelve groups of mixtures by using three ILs and one pesticide aldicarb as mixture components. Four binary and eight pseduo-binary mixtures were designed by equivalent effect concentration ratio ray method using EC5and EC50of individual component. The toxicities of single chemicals and these mixtures to a freshwater photobacteriumVibrio qinghaiensissp.-Q67 were determined by using the microplate toxicity analysis method. Toxicity interaction within mixtures were determined based on an additive referrence model, concentration addition (CA). The results showed that three binary IL mixture exhibited additive action and one antagonism. Interstingly, most pusedo-mixtures of aldicab and binary IL mixture exhibited cleary synergism especialy when they were mixed in the ratio of components EC5.

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