The use of oxidoreductases (EC1) in non‐conventional reaction media has been increasingly explored. In particular, deep eutectic solvents (DESs) have emerged as a novel class of solvents. Herein, an in‐depth study of bioreduction with an alcohol dehydrogenase (ADH) in the DES glyceline is presented. The activity and stability of ADH in mixtures of glyceline/water with varying water contents were measured. Furthermore, the thermodynamic water activity and viscosity of mixtures of glyceline/water have been determined. For a better understanding of the observations, molecular dynamics simulations were performed to quantify the molecular flexibility, hydration layer, and intraprotein hydrogen bonds of ADH. The behavior of the enzyme in DESs follows the classic dependence of water activity (aW) in non‐conventional media. At low aW values (<0.2), ADH does not show any activity; at higher aW values, the activity was still lower than that in pure water due to the high viscosities of the DES. These findings could be further explained by increased enzyme flexibility with increasing water content.

Deep eutectic solvents (DESs) have gained attention in recent years as attractive alternatives to traditional solvents. There is a growing number of publications dealing with the thermodynamic modeling of DESs highlighting the importance of modeling the solutions' properties. In this review, we summarize the state-of-the-art in DES modeling as well as its current challenges. We also summarize the various modeling approaches to phase equilibria and properties of DESs with g E -models, equations of state (EOS), and molecular dynamics (MD) simulations. Most of the current g E -model and EOS-based approaches handle DESs as pseudocomponents in order to simplify the parametrizations and calculation strategies. However, for the models to become more transferable and predictive, it would be preferable to model the individual DES constituents instead of modeling it as pseudocomponent. This implies that validation with more detailed experimental data that includes the distribution of the DES components is also required. MD simulations, in contrast to g E -models and EOS, are capable of providing information about the liquid structure and can predict dynamic properties, although the latter quantities still show some imprecisions. Therefore, insights into the liquid structure of DES systems from MD could also aid in improving present modeling strategies in addition to allowing a better understanding. Finally, the latest developments for DES force fields are discussed as the quality of the applied force fields determines the results of the MD simulations.

For a knowledge-based design of enzyme catalysis in deep eutectic solvents (DESs), the influence of the DESs properties (e.g., water activity, viscosity), and the impact of DESs and their individual...

The use of oxidoreductases in organic–aqueous biphasic systems is advantageous (effective solvation of reactants, minimization of substrate/product-induced inhibition, improved volumetric productivity, and straightforward downstream processing). This paper explores the effects of organic solvents on horse liver alcohol dehydrogenase (HLADH) by combining experimental and computational studies. Various organic solvents displaying a broad range of hydrophobicity and functionalities are used, namely, ethyl acetate, 2-methyltetrahydrofuran, methyl tert-butyl ether, cyclopentyl methyl ether, toluene, cyclohexane, heptane, and dodecane. The catalytic performance of model enzyme horse liver alcohol dehydrogenase concerning its activity, stability, and selectivity is experimentally evaluated. The results are interpreted with molecular dynamics simulations by assessing the (i) protein location in biphasic media, (ii) organic solvent distribution, and (iii) enzyme conformation. Herein, the stability states the robustness of the enzyme while storing it in biphasic media without catalysis taking place. Overall, different toxicities of the solvent to the enzyme can be pinpointed: “molecular toxicity”, related to the solvent functional groups, and “interfacial toxicity”, related to the position of the enzyme at the interface. Likewise, some solvents are more prone to be located close to the active site of the enzyme, triggering other effects on the enzymatic performance. Thus, methyl tert-butyl ether resulted as an optimal option for the enzyme, whereas other solvents like toluene and 2-methyltetrahydrofuran were detrimental. The combined forces of experiments and simulations have been shown to be useful tools to study the effects of reaction media, thus guiding solvent selection.

Deep eutectic solvents (DESs) have become popular as environmental-friendly solvents for biocatalysis. Molecular dynamics (MD) simulations offer an in-depth analysis of enzymes in DESs, but their performance depends on the force field chosen. Here, we present a comprehensive validation of three biomolecular force fields (CHARMM, Amber, and OPLS) for simulations of alcohol dehydrogenase (ADH) in DESs composed of choline chloride and glycerol/ethylene glycol with varying water contents. Different properties (e.g., protein structure and flexibility, solvation layer, and H-bonds) were used for validation. For two properties (viscosity and water activity) also experiments were performed. The viscosity was calculated with the periodic perturbation method, whereby its parameter dependency is disclosed. A modification of Amber was identified as the best-performing model for low water contents, whereas CHARMM outperforms the other models at larger water concentrations. An analysis of ADH’s structure and interactions with the DESs revealed similar predictions for Amber and CHARMM.

We present the strategic development of a synthetic onepot two-step process for the manufacture of acetyl-protected hydroxystyrenes from phenolic acid substrates using environmentally benign (bio)catalysts in an eco-friendly solvent.

Current best practices for the evaluation of search engines do not take into account duplicate documents. Dependent on their prevalence, not discounting duplicates during evaluation artificially inflates performance scores, and, it penalizes those whose search systems diligently filter them. Although these negative effects have already been demonstrated a long time ago by Bernstein and Zobel [4], we find that this has failed to move the community. In this paper, we reproduce the aforementioned study and extend it to incorporate all TREC Terabyte, Web, and Core tracks. The worst-case penalty of having filtered duplicates in any of these tracks were losses between 8 and 53 ranks.

Sugar (fatty acid) esters are industrially relevant compounds, with a cumbersome production process due to the solubility issues of the substrates, which forces the use of environmentally unfriendly reaction media. Herein, deep eutectic solvents (DESs) are considered as a promising solution: several literature examples use glucose and different acyl donors to illustrate the efficient synthesis of sugar esters in classic DESs like choline chloride/urea (ChCl/U). However, this paper discloses that when sugars like lactose or other disaccharides are used, enzymes cannot efficiently perform (trans)esterifications in DESs, while the same reaction can proceed in mixtures like pyridine/ tetrahydrofuran (Py/THF). This could be explained by computational solubility studies and molecular dynamics simulations of both reaction media, showing two effects: (i) on the one hand, large acyl donors (more than C10) display poor solubility in DESs and (ii) on the other hand, disaccharides interact with DES components. Thus, the DES affects the conformation of lactose (compared to the conformation observed in the Py/THF mixture), in such a way that the enzymatic reaction results impaired. Despite that classic DESs (e.g., ChCl/U) may not be useful for generalizing their use in saccharide ester syntheses, the achieved theoretical understanding of the reaction may enable the design of future DESs that can combine enzyme compatibility with ecofriendliness and efficiency in sugar chemistry.