EFFECTS OF MOLAR RATIO, FREQUENCY, WATER CONTENT AND TEMPERATURE ON DIELECTRIC PROPERTIES OF DEEP EUTECTIC SOLVENTS

In this study, deep eutectic solvents (DESs) were prepared using choline-chloride as the hydrogen-bond acceptor and glycerol, formic acid and acetic acid as the hydrogen-bond donor. The effect of different process parameters such as molar ratio (1:2, 1:3 and 1:4), water content (15%, 30% and 45%), temperature (25, 50 and 75 °C) and frequency on dielectric properties of the DESs were examined. In conclusion, the highest dielectric constant value was detected at 25 °C for all DESs. Moreover, for all DESs, it was found that a decrease in water content resulted in a decrease in both dielectric constant and loss factor values. This can be explained by the absence of free water molecules which are responsible from dipole rotation mechanism. In light of the results, if DES will be used in microwave extraction, formic or acetic acid containing DESs might give more successful results compared to the one with glycerol.

Strengthening Cellulose Nanopaper via Deep Eutectic Solvent and Ultrasound-Induced Surface Disordering of Nanofibers

The route for the preparation of cellulose nanofiber dispersions from bacterial cellulose using ethylene glycol- or glycerol-based deep eutectic solvents (DES) is demonstrated. Choline chloride was used as a hydrogen bond acceptor and the effect of the combined influence of DES treatment and ultrasound on the thermal and mechanical properties of bacterial cellulose nanofibers (BC-NFs) is demonstrated. It was found that the maximal Young’s modulus (9.2 GPa) is achieved for samples prepared using a combination of ethylene glycol-based DES and ultrasound treatment. Samples prepared with glycerol-based DES combined with ultrasound exhibit the maximal strength (132 MPa). Results on the mechanical properties are discussed based on the structural investigations that were performed using FTIR, Raman, WAXD, SEM and AFM measurements, as well as the determination of the degree of polymerization and the density of BC-NF packing during drying with the formation of paper. We propose that the disordering of the BC-NF surface structure along with the preservation of high crystallinity bulk are the key factors leading to the improved mechanical and thermal characteristics of prepared BC-NF-based papers.

A Pragmatic Pharmacophore Informatics Strategy to Discover New Potent Inhibitors Against Pim-3

Pim-3 (proviral integration site moloney murine leukemia virus-3) is an oncogene which encodes proteins belonging to serine/threonine kinase family, and PIM subfamily. It is generally over expressed in epithelial and hematological tumors. It is known to involve in numerous cellular functions such as cell growth, differentiation, survival, tumorigenesis and apoptosis. It also plays a crucial role in regulation of signal transduction cascades. Therefore it emerged as a hopefultherapeutic target for cancer treatment. In current study, indole derivatives having potent inhibitory activity against Pim 3 were taken and pharmacophore based virtual screening was carried out. A five point pharmacophore hypothesis with one hydrogen bond acceptor, one hydrogen bond donor and three aromatic rings i.e., ADRRR was developed with acceptable R2and Q2 values of 0.913 and 0.748 respectively. It was employed as a query and screening was conducted against Asinex and Otava lead library databases to screen out potent drug like candidates. The obtained compounds were subjected to SP, XP docking using 3D model of pim-3 which was constructed through comparative homology modelling and finally binding free energies were calculated for top hits. The docking and binding free energy studies revealed that six hit molecules showed higher binding energy in comparison to the best active molecule. Finally, MD simulations of the top hit with highest binding energy was carried out which indicated that the obtained hit N1 formed a stable complex with pim-3. We believe that these combined protocols will be helpful and cooperative to discover and design more potent pim-3 inhibitors in near future.

Combined Pharmacophore and Grid-Independent Molecular Descriptors (GRIND) Analysis to Probe 3D Features of Inositol 1,4,5-Trisphosphate Receptor (IP3R) Inhibitors in Cancer

Inositol 1, 4, 5-trisphosphate receptor (IP3R)-mediated Ca2+ signaling plays a pivotal role in different cellular processes, including cell proliferation and cell death. Remodeling Ca2+ signals by targeting the downstream effectors is considered an important hallmark in cancer progression. Despite recent structural analyses, no binding hypothesis for antagonists within the IP3-binding core (IBC) has been proposed yet. Therefore, to elucidate the 3D structural features of IP3R modulators, we used combined pharmacoinformatic approaches, including ligand-based pharmacophore models and grid-independent molecular descriptor (GRIND)-based models. Our pharmacophore model illuminates the existence of two hydrogen-bond acceptors (2.62 Å and 4.79 Å) and two hydrogen-bond donors (5.56 Å and 7.68 Å), respectively, from a hydrophobic group within the chemical scaffold, which may enhance the liability (IC50) of a compound for IP3R inhibition. Moreover, our GRIND model (PLS: Q2 = 0.70 and R2 = 0.72) further strengthens the identified pharmacophore features of IP3R modulators by probing the presence of complementary hydrogen-bond donor and hydrogen-bond acceptor hotspots at a distance of 7.6–8.0 Å and 6.8–7.2 Å, respectively, from a hydrophobic hotspot at the virtual receptor site (VRS). The identified 3D structural features of IP3R modulators were used to screen (virtual screening) 735,735 compounds from the ChemBridge database, 265,242 compounds from the National Cancer Institute (NCI) database, and 885 natural compounds from the ZINC database. After the application of filters, four compounds from ChemBridge, one compound from ZINC, and three compounds from NCI were shortlisted as potential hits (antagonists) against IP3R. The identified hits could further assist in the design and optimization of lead structures for the targeting and remodeling of Ca2+ signals in cancer.

Integration of Choline Chloride-Based Natural Deep Eutectic Solvents and Macroporous Resin for Green Production of Enriched Oil Palm Flavonoids as Natural Wound Healing Agents

Huge quantities of oil palm (Elaeis guineensis Jacq.) leaves (OPL) are generated as agricultural biomass from oil palm plantations. OPL are known to contain significant amounts of flavonoids. For maximal exploitation of these valuable antioxidant compounds, an innovative and sustainable extraction method employing natural deep eutectic solvents (NaDES) combined with ultrasonic assisted extraction was developed. Various NaDES composed of choline chloride as the hydrogen bond donor (HBD) and 1,2 propanediol (PD), 1,4 butanediol (BD), glycerol (GLY), glucose (GLU), maltose (MAL), and lactic acid (LA) as the hydrogen bond acceptor (HBA) were synthesized. The influence of these compositions, the methods of their synthesis, molar ratios, and water contents on their capacity to extract flavonoids from OPL was evaluated. Based on the results, it was found that methods which incorporate a heating step produced NaDES with the best capacity to extract OPL flavonoids. These thermal methods combined with molar ratios of 1:3 or 1:4 and water contents of 17 to 50% were found to be the optimal conditions for preparing NaDES, specifically when applied to the PD, BD, and GLY NaDES. Subsequently, UHPLC-UV/PDA-MS/MS analysis revealed NaDES extracts recovered by macroporous adsorption resin XAD7HP were able to optimally extract at least twelve luteolin and apigenin derivatives in OPL NaDES extracts prepared from glycerol and 1,4-butanediol demonstrated better and comparable efficiency as aqueous methanol in extracting flavonoids from OPL. The in vitro studies of antioxidant and wound healing properties supported these findings by exhibiting good free radical scavenging, cell proliferation, and migration activities. Additionally, the NaDES extracts also showed non-cytotoxicity effects at 1000 µg/mL and below on 3T3 fibroblast cells. Results of the study showed that NaDES could be a promising eco-friendly green solvent to extract bioactive OPL flavonoids that have great potential for applications as wound healing agents.

Extraction of Phenolic Compound using Natural Deep Eutectic Solvent from Biomass Waste

Phenolic compounds are aromatic compounds known for their bioactive substances which can be found in plants. It has been widely used in various applications due to its antibiotics, anti-inflammatory, anti-allergic, and other benefits. There are various methods to extract the phenolic compounds from plants including ionic liquid, liquid-liquid extraction as well as supercritical extraction. However, all of these methods requires energy extensive, laborious processes, advanced technology, and generate toxic waste. Therefore, there is a growing need to find an alternative green extraction method to reduce the environmental impact while improving the efficiency of the extraction process. Thus, natural deep eutectic solvents (NADES), a combination of two or more components that comes from primary metabolites like organic acids, choline chloride, or sugar, are able to form liquids upon mixing with lower melting point of individual constituents due to hydrogen bond interactions were proposed as alternatives to conventional extraction methods. Therefore, this research determined the suitable combination of NADES solvents (hydrogen bond acceptor/donor ratio) for extraction of phenolic compounds from biomass waste which included young and mature coconut shells and coconut husk, banana peel, empty fruit bunch, and palm oil fruit husk. The extracted compound was analysed using fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) to identify the functional groups and type of phenolic compounds present. The best biomass waste was coconut shell and the best NADES combination was choline chloride and ascorbic acid at 1:2 molar ratio. The FTIR analysis of coconut shell extracted by NADES showed peaks at 3404 cm−1 and 3523 cm−1 indicating OH stretching followed by 2915 cm−1, 1388 cm−1 to 1473 cm−1, and 1674 cm−1 showing C-H stretching, sp3 C-H band and C=C stretch respectively. As for GC-MS analysis, 26 compounds were detected and four phenolic compounds were identified at peaks 2, 13, 22, and 25. The research was successful in determining the best biomass waste and NADES combination for highest total phenol. The use of NADES was able to extract more phenolic compound from coconut shell than water due to the hydrogen bond between the choline chloride and ascorbic acid.

Prediction of solvation properties of low transition temperature mixtures (LTTMs) using COSMO-RS and NMR approach

The concept of sustainable and green solvent has always highlighted in the field of energy and environmental science. The synthesis and application of natural-based Low Transition Temperature Mixture (LTTM) as a novel and green solvent for the lignocellulose biomass pre-treatment such as delignification of Oil-Palm Empty Fruit Bunch (EFB) have been greatly emphasized. In this present work, the investigation of LTTM efficiency as green solvent in delignification process was conducted using both theoretical and experimental studies. Initially, screening of solvation properties of different types of hydrogen bond acceptor (HBA) and predicted hydrogen bond donor (HBD) for synthesis of LTTMs was conducted using conductor-like screening model (COSMO-RS) software and formation of hydrogen bonding was evidenced using NMR spectroscopy analysis. Three types of HBA namely sucrose, choline chloride and monosodium glutamate were mixed with malic acids as HBD and their charge density distribution on the surface was determined through sigma profile (σ). The COSMO-RS results determined the σ profile of pure component malic acid to be 11.42, sucrose to be 25.37 and the total value of σ profile for mixtures is 14.19 as the best combination of LTTM composition compared to LTTM from choline chloride and monosodium glutamate (MSG). The reliability of the COSMO-RS predictions data was correlated with Nuclear Magnetic Resonance (NMR) analysis through determination of peaks with chemical shifts hydrogen bonding that suggested existence of potential interaction between malic acids and sucrose has occurred.

A Comprehensive Study of CO2 Absorption and Desorption by Choline-Chloride/Levulinic-Acid-Based Deep Eutectic Solvents

Amine absorption (or amine scrubbing) is currently the most established method for CO2 capture; however, it has environmental shortcomings and is energy-intensive. Deep eutectic solvents (DESs) are an interesting alternative to conventional amines. Due to their biodegradability, lower toxicity and lower prices, DESs are considered to be “more benign” absorbents for CO2 capture than ionic liquids. In this work, the CO2 absorption capacity of choline-chloride/levulinic-acid-based (ChCl:LvAc) DESs was measured at different temperatures, pressures and stirring speeds using a vapour–liquid equilibrium rig. DES regeneration was performed using a heat treatment method. The DES compositions studied had ChCl:LvAc molar ratios of 1:2 and 1:3 and water contents of 0, 2.5 and 5 mol%. The experimental results showed that the CO2 absorption capacity of the ChCl:LvAc DESs is strongly affected by the operating pressure and stirring speed, moderately affected by the temperature and minimally affected by the hydrogen bond acceptor (HBA):hydrogen bond donator (HBD) molar ratio as well as water content. Thermodynamic properties for CO2 absorption were calculated from the experimental data. The regeneration of the DESs was performed at different temperatures, with the optimal regeneration temperature estimated to be 80 °C. The DESs exhibited good recyclability and moderate CO2/N2 selectivity.

Integrated computational analysis on some Indolo-quinoline derivatives for the development of novel antiplasmodium agents: CoMFA, Pharmacophore mapping, molecular docking and ADMET studies

Background: The development of multi-resistant strains of the Plasmodium parasite has become a global problem. Therefore, designing of new antimalarial agents is an exclusive solution.: Objective: To improve the activity and identify potentially efficacious new antimalarial agents, integrated computational perspectives such as pharmacophore mapping, 3D-QSAR and docking study have been applied to a series of indolo-quinoline derivatives. Methods: The pharmacophore mapping generated various hypotheses based on key functional features and the best hypothesis ADRRR_1 revealed that indolo-quinoline scaffold is essential for antimalarial activity. 3D-QSAR model was established based on CoMFA and CoMSIA models by using 30 indolo-quinoline analogues as training set and the rest of 19 as test set. Results: The molecular field analysis (MFA) with PLS (partial least-squares) method was used to develop significant CoMFA (q2=0.756, r2=0.996) and CoMSIA (q2=0.703, r2=0.812) models. The CoMFA and CoMSIA models showed good predictive ability with r2pred values of 0.9623 and 0.9214 respectively. Docking studies were performed by using pfLDH to identify structural insight into the active site and results signify that the quinoline nitrogen acts as a hydrogen bond acceptor region to facilitate interaction with Glu122. Finally, designed molecules were screened through the ADMET tool to evaluate the pharmacokinetic and drug-likeness parameters. Conclusion: Thus, these studies suggested that established models have good predictability and would help in the optimization of newly designed molecules that may produce potent antimalarial activity.

Crystalline Forms of Trazodone Dihydrates

In this study, treatment of anhydrous trazodone powder with ammonium carbamate in warm water crystallised two new polymorphs or dihydrates of trazodone after 5 h, whose structures were determined by X-ray single crystal diffraction. Each dihydrate contains infinite zigzag hydrogen-bonded chains of water molecules, which are stabilised by the N4 acceptor atom of the piperazine ring and the pendant carbonyl O1 atom of the triazole ring, as well as other water molecules. The strong dipole moment expected for the O1 atom makes it a good hydrogen bond acceptor for stabilising the chains of water molecules. Each molecule of trazodone has a similar conformation in both hydrates, except for the propyl chains, which adopt different conformations: anti-gauche in the β hydrate (triazole N-C-C-C and C-C-C-piperazine N) and anti-anti in the γ hydrate. Both piperazine rings adopt chair conformations, and the exocyclic N-C bonds are in equatorial orientations. The Hirshfeld surfaces and two-dimensional fingerprint plots for the polymorphs were calculated using CrystalExplorer17, which indicated contacts significantly shorter than the sum of the van der Waals radii in the vicinity of the piperazine N4 and triazole O1 atoms corresponding to the strong hydrogen bonds accepted by these atoms.