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In the crystalline sponge method, the crucial step for ordering the absorbed guest is soaking of the guest into the pores of the crystalline sponge. Here, we find that the choice of solvent is particularly important for smooth guest soaking and ordering. Moderately polar solvents, such as ketones and esters, which we have previously avoided for the guest-soaking process, efficiently promote diffusion and guest ordering by filling the gaps in the pores through co-crystallization with the guests. Using this modified protocol, we successfully demonstrate the structural analysis of various steroids.

We attempted to maximize the transmittance of 2D NiTe2 thin film using the liquid-phase exfoliation (LPE) process to confirm the applicability of NiTe2 as a transparent electrode. The LPE process, using a co-solvent of organic solvent and water, is a stable and efficient method of increasing transmittance at low cost. In this report, the effect of 12 different co-solvents, mixtures of acetone, ethanol, isopropyl alcohol, and water, on exfoliation rate was studied. NiTe2 thin film with a thickness of 6.3 nm prepared by sputtering, and exhibited a highest transmittance of 68% and a lowest resistivity of 291 μΩ·cm after 12 hrs sonication in ethanol/water co-solvent (ethanol : water = 60 : 40 vol. %). Three physical properties, polarization and dispersion ratio (p/d ratio), boiling point, and water contents, were compared to determine which property was the main control factor for the LPE process. Unlike previous LPE processes for powders of 2D materials, it was revealed that the improvement in the transmittance of the NiTe2 thin film was more strongly dependent on both of vol.% of water and boiling point of the solvents. This was because the transmittance improved after removing the NiTe2 thin film from the substrate, rather than layer by layer exfoliation. We believe that NiTe2 thin film prepared by sputtering followed by exfoliation process can be one of the potential candidates for transparent electrode.

The purpose of this study was twofold: to investigate leucine crystallization kinetics in co-solvent spray drying for a deeper understanding of the morphology and formation process of spray-dried c...

A Prussian blue (PB)-based sodium-ion battery (SIB) is a promising candidate in large-scale electric energy storage. However, its development is hindered by the poor cyclability of the PB cathode a...

This study optimized a co-solvent free electrochemical method for biodiesel synthesis using graphite electrode and waste concrete heterogeneous catalyst. Various parameters were evaluated, including: applied voltage (9.6, 14.4, 19.2 V), catalyst particle size uniformity (unfiltered and filtered with 150 mesh), and reaction time (15, 30, 120, 240 min). The results obtained 100% FAME content and 78.51% of biodiesel yield that were achieved at 14.4 V within 30 min using filtered catalyst and cooking oil feedstock. However, a slight decline was observed with the use of waste cooking oil. This optimized method offers a reliable and simple condition for mass biodiesel production. Copyright © 2021 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

An improvement of ecological conscience currently has increased the consciousness of researchers in reducing the processing time and cost of solvent for the dissolution of cellulose. Latterly, ionic liquids have been employed to process cellulose as they are recyclable and nonvolatile. Besides that, biopolymers such as chitosan, chitin, starch, protein, and cellulose acetate can also be processed by using ionic liquids for diverse applications. In this short review, examples of imidazolium-based ionic liquids that are commonly used for the dissolution of cellulose are implied. Furthermore, examples of organic liquids that are utilized as co-solvents for ionic liquids were revealed. In addition, examples of imidazolium-based ionic liquid/co-solvent mixtures utilized in the dissolution of cellulose and other biopolymers are also demonstrated. The properties and applications of cellulose and its blends regenerated from different types of cellulose/imidazolium-based ionic liquid/co-solvent solutions are also shortly reviewed. The information acquired from this review gives a better understanding of the changes in the properties of regenerated cellulose and regenerated cellulose blends. In addition, this short review serves as a model basis for the creation of novel applications of regenerated cellulose and regenerated cellulose blends by utilizing imidazolium-based ionic liquid/co-solvent mixtures.

An energy-efficient intensification protocol for biodiesel (fatty acid ethyl ester (FAEE)) production from the mustard de-oiled cake (MDC) and sunflower de-oiled cake (SDC) through concurrent esterification-transesterification reactions has been disclosed employing near-infrared radiation retrofitted batch reactor. The triglycerides and free fatty acids of the de-oiled cake were converted to FAEE through a one-pot synthesis in the presence of ethanol and one of the co-solvents viz. acetone, dimethyl sulfoxide (DMSO), and n-hexane. The optimal condition (75:1 (w/w) ethanol to de-oiled cake ratio, 70°C infrared radiation temperature, 2.5 wt. % H2SO4 catalyst concentration, and 1000 rpm stirrer speed) for maximum FAEE yield was evaluated deploying Taguchi L9 orthogonal method. Higher FAEE yield was achieved under infrared radiation for both MDC (82.4 ± 0.01%) and SDC (81.7 ± 0.02%), in comparison with the conventionally heated reactor (MDC: 56.1 ± 0.02%; SDC: 54 ± 0.02%) employing identical process condition. This enlightened the energy-efficacy of the infrared radiation in accelerating the FAEE yield within a much shorter reaction time. The FAEE composition was assessed by FTIR and GC-MS analyses. The fuel properties of the product biodiesel conformed to EN standards. Thus, a feasible and efficient protocol for the conversion of de-oiled cakes to biodiesel could be explored.

This present study looks at the engine characteristics of beef tallow biodiesel (tallow methyl ethyl ester) produced using methanol–ethanol-based co-solvent transesterification. Unblended samples o...

Areca nut extract provides a variety of pharmacological effects that are beneficial for skincare applications. A nanoemulsion of areca nut extract was developed to mask the intense color and to improve the water solubility of the extract. This work studied the impact of a co-solvent on the characteristics and stability of the nanoemulsion. Our former optimized nanoemulsion was modified by adding a common co-solvent, propylene glycol or polyethylene glycol 400 (PEG400), to the formula. Phase separation, particle characteristics, antioxidant activity, in vitro cytotoxicity, and stability of the modified nanoemulsion were evaluated. This work has shown the successful encapsulation of areca nut extract with a great improvement of stability, well-maintained antioxidant activity and low toxicity on normal human skin fibroblast.

The main challenge of utilizing ethanol in diesel engines in blending mode is the phase separation issue. Therefore, an attempt has been performed to enhance the stability feature of ethanol/Jatrop...

Microalgae have been considered as a potential candidate for biodiesel feedstock. Single-stage simultaneous extraction–transesterification process is proposed for simpler and more effective biodiesel conversion. In this study, the experiment of biodiesel production from microalgae Spirulina sp. was performed in a batch-stirred reactor using palm oil as a co-solvent of methanol and catalyzed by potassium hydroxide at a percentage of 1 wt% (w/w of palm oil). The effects of methanol–palm oil molar ratio, palm oil–microalgae weight ratio, and temperature on biodiesel yield were investigated. The results showed that the best biodiesel yield was 85.28% (99.01% of partial biodiesel yield from palm oil and 16.69% of partial biodiesel yield from dry microalgae), obtained at a methanol–palm oil molar ratio of 10:1, a palm oil–microalgae weight ratio of 5:1, and at a temperature of 60°C. Upon comparison, the overall yield increased by 34.59% (37.73% of partial biodiesel yield from palm oil and 13.00% of partial biodiesel yield from dry microalgae) than that of the two-stage (conventional) method. Single-stage simultaneous extraction–transesterification process also reduced the number of unsaturated fatty acid components in biodiesel that will lower the biodiesel quality.

The study was designed to develop and characterize structured vehicles for effective delivery of glipizide (GPZ) through excised stratum corneum (SC). Several mixed binary systems of ethanol or propylene glycol (PG) were prepared by homogeneous mixing with double distilled water. Different microemulsions were prepared by titration method and their physicochemical properties determined. Transdermal permeation of GPZ was studied in-vitro using modified Franz diffusion cells. Apart from the slight difference in their pH values, there was no significant difference in the physicochemical properties of the drug-loaded coconut oil-based microemulsions and their blank counterparts. Transdermal flux was highest in binary mixtures of 9:1 (v/v) aqueous ethanol (Jss 30.25 ± 5.75 μg/cm2h) and PG (Jss 6.34 ± 1.29 μg/cm2h) compared to their lower strengths. Transdermal GPZ flux, Jss, μg/cm2h was higher in o/w (121.2 ± 9.98) compared to w/o (3.89 ± 0.19) microemulsions with enhanced permeation of ≥ 23 fold using patch size of 10.45 cm2. Biophysical analysis of untreated and treated SC showed that GPZ permeation could depend on the extent of disruption of lipid and protein bilayers of SC by the vehicles. Cremophor RH 40/ethanol/coconut oil-based o/w microemulsion and 9:1 v/v mixed binary systems of ethanol or PG are promising vehicles for delivery of GPZ transdermally. Dhaka Univ. J. Pharm. Sci. 19(1): 29-35, 2020 (June)

An accurate and suitable semi-empirical model is crucial to determine the solubility of plant extracts in supercritical carbon dioxide (SC-CO2) assisted by ethanol as a co-solvent. In this paper, a...

The solvent-protein interactions are important for protein biological functions, especially for a coupled folding and binding system as insulin. By monitoring the conformational change of insulin dimers during dissociation with temperature jump (T-jump) IR spectroscopy, we show that co-solvents can significantly destabilize the dimers by perturbing their hydrophobic center. Transition from native to intermediate dimer state is observed as the buried residues exposed to solvents at the presence of 10% DMSO and with α–helices unfolding when ethanol is present, which reduces the dissociation time dramatically to 20% and 50% of the value in the D(2)O solution, respectively. We propose a self-consistent analysis using complementary methods for resolving this coupled folding and binding process is resolved with, and obtain a much larger rate of monomer association than the intermediate folding. Our results demonstrate that the conformational changes are critical in the dimer formation and are highly affected by co-solvents.

Dalam berat kering biji pepaya mengandung minyak hingga 30% sehingga berpotensi untuk digunakan sebagai bahan baku biodiesel. Transesterifikasi in situ merupakan langkah sederhana dalam menghasilkan biodiesel yaitu dengan cara mengeliminasi proses ekstraksi dan pemurnian minyak sehingga dapat menghemat biaya produksi dan memberikan hasil yang memuaskan. Reaksi satu fase dapat dibentuk dengan menambahkan co-solvent yang dapat meningkatkan kelarutan minyak. N-heksana merupakan co-solvent yang paling baik karena murah, tidak reaktif dan bertitik didih rendah (68 o C) sehingga dapat dipisahkan secara co-distilasi bersama-sama dengan metanol. Gelombang mikro dapat merambat melewati cairan sehingga proses pemanasan akan berlangsung lebih efektif dan proses pembuatan biodiesel dapat dilakukan lebih singkat. Pada penelitian ini variasi daya yang digunakan adalah 30%, 50% dan 70% dari 399 watt serta waktu reaksi yaitu 2, 4, 6, 8 dan 10 menit. Hasil kemudian dianalisa menggunakan GC (Gas Chromatography). Didapatkan yield optimum sebesar 89,25% pada daya sebesar 70% dan waktu reaksi 8 menit. Yield optimum memiliki densitas sebesar 0,86 g/cm 3 dan memiliki angka asam 0,28 mg KOH/g sampel. Hasil tersebut telah memenuhi SNI 7182:2015. In the dry weight of papaya seed oil contains up to 30%, so the potential to be used as raw material for biodiesel. Transesterification in situ is a simple step to produce biodiesel that is by eliminating extraction process and refining of oil so it can save on production costs and give satisfactory results. The reaction of one phase can be formed by adding a co-solvent to increase the solubility of oils. N-hexane is a co-solvent that is best because it is inexpensive, non-reactive and low boiling point (68°C) so that it can be separated by co-distillation with methanol. Microwave can propagate passed through the liquid so that the heating process will take place more effectively and the process of making biodiesel can be made shorter. In this study the variation of power used is 30%, 50% and 70% of 399 watts and the reaction time is 2,4,6,8 and 10 minutes. Results were analyzed by GC (Gas Chromatography). The optimum yield was 89.25% at 70% power and reaction time 8 minutes. The optimum yield has a density of 0.86 g / cm 3 and has an acid number of 0.28 mg KOH/g sample. These results have met the SNI 7182:2015.

Gynura procumbens also recognized as Sambung Nyawa is a type of the herbs found in Malaysia, Indonesia and Thailand. It has been consumed as ‘ulam’ by whom that aware of its potential as medicinal remedy and some even drink it as tea for theuraphatic effect. Supercritical fluid extraction is a fast technique to extract valuable compounds from plant parts especially from leaves and seeds. A preliminary study on the effect of solvent water ratio towards yield of Gynura procumbens is conducted at pressure of 20 MPa, temperature of 70 °C, static time of 15 minutes, ethanol as the co solvent and flow rate of 4 ml/min. The time of extraction is 60 minutes. The solvent water ratio was set as follows: 100% ethanol, 75% ethanol and 50% ethanol. The yield obtained are 1.8267%, 0.5933% and 0.9733% for 100%, 75% and 50% ethanol respectively. The extract is then further analysed using high pressure liquid chromatography to determine valuable compounds extracted within the stipulated time at different solvent water ratio. Reversed phase high performance liquid chromatography separation was done using 0.1% phosphoric acid: acetonitirile as eluent in mobile phase to determine flavonoid compounds.

A complex study of sodium and potassium halides as catalysts of the addition of CO2 to epoxides to yield organic carbonates was carried out. The activity of these metal iodides was investigated. The conditions allowing achievement of a quantitative conversion of epoxides into carbonates were found by varying the temperature, carbon dioxide pressure, and available co-solvents.

Small amphiphilic molecules dissolved in alcohol–water mixtures have been seen to have a tendency to aggregate. Here we present a thorough neutron diffraction experiment, aided by H/D isotopic subs...

We report an industrially viable promising approach to produce micrometer-sized multilayer graphene nanoplatelet powder (MGNP) in a scalable quantity via microwave-assisted exfoliation of graphite (MEG) and fragmented into MGNP through liquid-phase exfoliation in the co-solvent mixture by kitchen mixer (KM). KM allows rapid delaminating MEG into MGNP by shear force dominated exfoliation. Majority of MGNPs are with a diameter of few micrometers and thickness is in nanometers. MGNP are crystalline with very limited defects was confirmed by Raman measurements and transmission electron microscopy. This process transforms, more than 86% of graphite flakes into MGNP. This advanced approach opens a new pathway to produce MGNP in bulk quantity as it is feasible, rapid, and cost-effective.

Lipids extraction from wet and unbroken microalgae (Chlorella vulgaris) using subcritical water with aid of co-solvents has been investigated. Lipids extraction from wet and unbroken microalgae has a crucial role in order to eliminate dewatering and drying steps. Subcritical water is able to extract lipids from feedstock with high water content. This work was conducted to study several factors affecting in subcritical water extraction (SWE) from wet and unbroken microalgae. In this study, effect of co-solvent types (without co-solvent, chloroform, methanol, ethanol, ethyl acetate, and n-hexane) under subcritical water (microalgae = 5g (dry weight), moisture content= 94.12%, T= 160°C, P = 80 bar, t= 30 min), extraction time (15 min, 30 min, 1 h, 3 h, and 5 h), and temperature (160o C, 180o C and 200o C) on yield of lipids were investigated orderly. Yield of lipids obtained without co-solvent (water polarity index = 10.2) and with co-solvents of methanol (PI=5.1), ethanol (PI=5.2), chloroform (PI=4.1), ethyl acetate (PI=4.4), and n-hexane (PI=0.1) were 38.73%, 26.47%, 26.12%, 51.93%, 53.40%, and 25.59%, respectively compared to the yield of lipids extracted using Bligh and Dyer method. Ethyl acetate is solvent with moderate PI, therefore can extract more lipids that is also have moderate polarity. Ethyl acetate shows a good performance to extract lipids from wet and unbroken microalgae because ethyl acetate can extract broader range of lipids including neutral and polar lipids. This study also found that increasing of extraction time and temperature to extract lipids in subcritical water condition can increase yield of lipids.

The solubility of lamotrigine in the aqueous mixtures of 1-hexyl-3-methylimidazolium bromide [HMIm][Br] were determined up to 0.8 mass fraction of [HMIm][Br] at several temperatures T= (293.2 to 313.2) K. The λ -h and van’t Hoff models with temperature dependency and Jouyban-Acree-van’t Hoff, e-NRTL, UNIQUAC and Wilson models with temperature and solvent composition dependency were used to correlate the experimental solubility data. The overall %ARD value using the van’t Hoff model is lower than the λ -h equation. Moreover, the obtained %ARDs show that the Jouyban-Acree-van’t Hoff and UNIQUAC models have the best consistency with the experimental solubility data, and the order of %ARDs for these models are UNIQUAC

Solubility of ILs [Bmim][NTf2] and [Emim]Ac in scCO2 with co-solvents, including ethanol, acetone and DMSO were determined respectively at 40 °C, 50 °C, 60 °C and pressure up to 15.0 MPa. The results showed that the addition of co-solvents had a significant effect on solubility of ILs in scCO2. The ability of different co-solvents to enhance solubility of [Emim]Ac in scCO2 followed the order: ethanol > DMSO > acetone. Solubility of [Emim]Ac in scCO2/ethanol or acetone decreased slowly as temperature increased. As for DMSO, temperature lower than 50 °C wouldn't be a remarkable parameter for solubility. However, observable decrease of solubility was caused by temperature higher than 60 °C. Moreover, solubility of ILs increased as pressure increased from 8 to 15 MPa. Three models were used to correlate the 216 solubility data, Modified-Christal equation possessed highest accuracy.

Yinggemajianfeng lignite (YL) was subjected to thermal dissolution (TD) in a co-solvent of an ionic liquid (IL, 1-butyl-3-methyl-imidazolium chloride, 1-butyl-3-methylimidazolium tetrafluoroborate,...

The co-solvent prepared from glycerol and hydrochloric acid (HCl) was used for producing low molecular weight chitin from lobster shell. Different reaction temperature, time and acid concentration were studied. The results suggested that the effect of reaction temperature and acid concentration on molecular weight of chitin is most remarkable. The physicochemical properties of chitins were intact during co-solvent treatment. At least 5% HCl was necessary for demineralization and deproteinization. Low molecular weight chitin could be obtained by increasing reaction temperature, acid concentration and prolonging time. The optimized condition for production low molecular weight chitin was at 120 °C for 2 h with acid concentration of 7% (55 kDa) or at 150 °C for 2 h with acid concentration of 5% (57 kDa). This method provides a fast strategy to obtain low molecular weight chitin with high purity from lobster shell.

Molecular Dynamics (MD) based computational co-solvent mapping methods involve the generation of an ensemble of MD-sampled target protein conformations and using selected small molecule fragments to identify and characterize binding sites on the surface of a target protein. This approach incorporates atomic-level solvation effects and protein mobility. It has shown great promise in the identification of conventional competitive and allosteric binding sites. It is also currently emerging as a useful tool in the early stages of drug discovery. This review summarizes efforts as well as discusses some methodological advances and challenges in binding site identification process through these co-solvent mapping methods.

Lignin valorization is significantly hindered by the intrinsic heterogeneity of its complex structures and variability of biomass feedstocks. Fractionation of lignin can overcome these challenges by producing functionally distinct lignin cuts that can be further tailored to end products. Herein, lignin was extracted and depolymerized from poplar by the co-solvent enhanced lignocellulosic fractionation method with renewable THF to obtain CELF lignin. Several solvents were screened to separate soluble and insoluble fractions from the parent CELF lignin. The ethanol soluble portion was then fractionated into different molecular weight cuts via sequential precipitation of the lignin by reducing the concentration of THF. The physicochemical structures of different CELF lignin cuts were elucidated by GPC and NMR techniques. These results suggest that CELF lignin cuts with lower molecular weight contain progressively higher phenolic and carboxylic acid OH groups, which can be more suitable as green antioxidants than the parent lignin.

We herein describe a new protocol for copper-mediated trifluoromethylation of α-diazoesters and α-diazoketones, both using readily available fluoroform-derived CuCF3. The synergistic effect of using 1,4-dioxane as a co-solvent and pyridine as a promoter is revealed. Reaction conditions are mild and easy to handle, allowing the synthesis of a range of α-trifluoromethyl esters and ketones in one-step from α-diazo carbonyl compounds. The ultimate CF3 source is the inexpensive, nontoxic, industrial waste fluoroform.

Transesterification of used cooking oil (UCO) using NaN3/modified clay catalyst and investigation of the acetone effect have been done.The modified clay catalyst was synthesized by destructing the Merauke clay with8M HCl solution, then fusion by NaOH pellet, followed by treating with AlCl3.6H2O, CTAB and distilled water.Then the mixture was regulated to pH of 11.5. Next, the mixture was then poured into a reactor for hydrothermal process at 140 oC for 48 h. The results of the dealumination of clay was characterized byX-ray Fluorescence and the synthesized zeolite was characterized using surface area analyzer and X-Ray Diffraction.The synthesized zeolite was impregnated by NaN3 as a precussor produced the NaN3/modified clay catalyst sample.Rasio of catalyst :UCO : methanol was 1.0 : 20.0 : 13.3 and the ratio of aceton to methanol was 2:1. The transesterificationprocess was carried out at 60 and 65oC. The liquid product was analyzed using Gas Chromatography Mass Spectrometer.The resulted showed that themodified clay had surface area of 5.5685 m2/g, pore volume of 0.0126 cm3/g, and pore diameter of 8.871 nm. The results of measurements with XRD produced a different form of chromatogram and type of mineral. The main mineral was gismondine.In this research, The transesterification of UCO using NaN3/MC catalyst at 60 oC resulted methyl esters of 65.3 wt %.Furthermore, after adding acetone to the same treatment, the resulting methyl ester was 82.7 wt%.The transesterification of UCO at 65 ° C using NaN3/MC catalyst and acetone produced the highest content of methyl esters or biodiesel that was equal to 94.4 wt %.

Acid Red 138, as a weak acid azo dye with a long alkyl chain, is widely used for protein fiber dyeing while it cannot dissolve in supercritical carbon dioxide. The objective of this study is to investigate the solubility of Acid Red 138 with water at the temperatures of 353.15, 363.15, 373.15, 393.15 and 413.15 K and over a pressure range of 20 to 26 MPa. The test results revealed that the phase equilibrium of water and Acid Red 138 was affected by the competition between pressure and density of supercritical carbon dioxide. Furthermore, the experimental solubilities were correlated by three types of density-based model. Good agreement with less than 3.36% of average absolute relative deviation between the calculated and the experimental data of water was achieved. In addition, the Chrastil model, Mendez-Santiago–Teja model and Sung–Shim model exhibited excellent correlation results for Acid Red 138 solubilities with the AARD values of 8.58%, 6.06% and 5.19%. Better understanding of the solubility behavior of Acid Red 138 in supercritical carbon dioxide displays potential for developing a microemulsion system for the eco-friendly dyeing of natural fibers.

Extracts rich in anthocyanin compounds were obtained from haskap berry pulp paste using supercritical carbon dioxide (scCO2) and water as co-solvent. The extraction conditions including pressure, temperature, and amount of water were further optimized by Box-Behnken design. The highest total anthocyanins (TA) yield of 52.7% was achieved at 45 MPa, 65 °C, 5.4 g water to 3.2 g berry pulp paste, 15 min static and 20 min dynamic time. Different combinations of water and ethanol as co-solvent did not significantly affect the TA yield. Furthermore, similar anthocyanin extraction yields were obtained in the case of the pulp paste and rehydrated freeze-dried berry pulp powder, which indicates that freeze drying pretreatment is not required prior to scCO2 extraction. Compared with conventional extraction, the use of scCO2 and water as co-solvent offered higher anthocyanin extraction efficiency (52.7% versus 38.3%) with improved antioxidant activity (89.8% versus 72.2%).

In this study, ethyl biodiesel (FAEE) from catfish oil was produced by a new method using FAEE as co-solvent. The study results show that due to the short reaction time with very high conversion (> 99%) and there was no need to remove the FAEE co-solvent, the cost of the product was reduced by about 30%. FAEE, a multipurpose product, can be used as an engine fuel itself and its ester-rich fraction of omega-3, -6, -9 acids can also be extracted to produce high added value supplements.

The use of cosolutes and high hydrostatic pressure has been described as an efficient means to modulate the stability of enzymes and their catalytic activity. Cosolvents and pressure can lead to increased reaction rates without compromising the stability of the enzyme. Inspired by the multi-component nature of the crowded cellular milieu of biological cells of piezophiles, we studied the combined effects of macromolecular crowding agents, different types of cosolvents and pressure in concert on a hydrolysis reaction catalyzed by α-chymotrypsin. We have seen that crowding agents and cosolvents can have very diverse effects on enzymatic activity. Addition of the deep-sea osmolyte trimethylamine-N-oxide displays by far the most positive effect on the catalytic efficiency, keff, of the reaction, which is even markedly enhanced at high pressures. Addition of the chaotropic agent urea leads to the reverse effect, and PEG and dextran as two representative crowding agents of a different nature show nearly similar values for keff compared to the pure buffer data. Such information may not only be relevant for understanding life processes in extreme environments, but also for the use of enzymes in industrial processing, which often requires harsh conditions as well., ChemSystemsChem;3(2)

The exchange proteins activated by cAMP (EPAC) are implicated in a large variety of physiological processes and they are considered as promising targets for a wide range of therapeutic applications. Several recent reports provided evidence for the therapeutic effectiveness of the inhibiting EPAC1 activity cardiac diseases. In that context, we recently characterized a selective EPAC1 antagonist named AM-001. This compound was featured by a non-competitive mechanism of action but the localization of its allosteric site to EPAC1 structure has yet to be investigated. Therefore, we performed cosolvent molecular dynamics with the aim to identify a suitable allosteric binding site. Then, the docking and molecular dynamics were used to determine the binding of the AM-001 to the regions highlighted by cosolvent molecular dynamics for EPAC1. These analyses led us to the identification of a suitable allosteric AM-001 binding pocket at EPAC1. As a model validation, we also evaluated the binding poses of the available AM-001 analogues, with a different biological potency. Finally, the complex EPAC1 with AM-001 bound at the putative allosteric site was further refined by molecular dynamics. The principal component analysis led us to identify the protein motion that resulted in an inactive like conformation upon the allosteric inhibitor binding. Electronic supplementary material The online version of this article (10.1007/s10822-020-00332-y) contains supplementary material, which is available to authorized users.