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The present study investigates deep eutectic solvents (DESs) as potential media for enzymatic hydrolysis. A series of ternary ammonium and phosphonium-based DESs were prepared at different molar ratios by mixing with aqueous glycerol (85%). The physicochemical properties including surface tension, conductivity, density, and viscosity were measured at a temperature range of 298.15 K – 363.15 K. The eutectic points were highly influenced by the variation of temperature. The eutectic point of the choline chloride: glycerol: water (ratio of 1: 2.55: 2.28) and methyltriphenylphosphonium bromide:glycerol:water (ratio of 1: 4.25: 3.75) is 213.4 K and 255.8 K, respectively. The stability of the lipase enzyme isolated from porcine pancreas (PPL) and Rhizopus niveus (RNL) toward hydrolysis in ternary DESs medium was investigated. The PPL showed higher activity compared to the RNL in DESs. Molecular docking simulation of the selected DES with the substrate (p-nitrophenyl palmitate) toward PPL was also reported. It is worth noting that ternary DES systems would be viable lipase activators in hydrolysis reactions.

The work was aimed at using Geant4-DNA software to simulate ultra-low-energy particle irradiation of DNA to understand relevant effects and fundamentals on DNA strand breaks. Light particle species of electron, hydrogen, proton, helium (He), He+ and He2+ with energy ranged in 10 – 1000 eV and fluence varied from 5 × 103 to 1 × 105 particles/cm2 irradiated DNA models, poly-AT, poly-CG and pGFP. The irradiation effect on DNA single strand breaks (SSBs) and double strand breaks (DSBs), particularly the latter, was focused. Results showed that the ratios between the numbers of SSBs and DSBs were nearly the same, independent of the particle energy and fluence. DSBs increased with increasing of ion energy, but not depended on the fluence. Discrepancies between the simulation and experiments were discussed, attributed to the simulation code overlooking the direct interaction of elastic collision between the particle and the DNA atom to cause atomic displacement.

Organic semiconductors generally display significant conformational flexibility which results in significant energetic disorder. In this research, ultraviolet photoelectron spectra are compared with the Gaussian density of states obtained from the density functional theory on assembly of molecules optimized using molecular dynamic simulations. It was found out that spin-coated organic semiconductor, tris(4-carbazoyl-9-ylphenyl)amine (TcTa), displays significant conformational distortion from its minimum geometry with significant Gaussian broadening. Adding poly(vinylcarbazole) (PVK) into TcTa results in increased face to face stacking of carbazole moieties from PVK as evident from increased red-shifted of absorption of PVK. Despite reduction of energy barrier upon addition of TcTa into PVK, the current efficiency of the extra warm white organic light emitting diodes showed limited improvement probably from the increased triplet quenchers from the carbazole dimers.

Scaffold known as designed ankyrin repeat proteins (DARPins) have been utilized by scientists extensively in protein binding, as they acquire remarkable binding properties. Trimodular ankyrin repeat protein (Ank1D4) is a potential macromolecular and antiviral intracellular inhibitor that aims the N-terminal domain capsid protein (NTDCA) of viral Human Immunodeficiency Virus type-1 (HIV-1) at the virus assembly and budding machinery process. The protein-protein interaction between Ank1D4 and the viral capsid CA alpha helixes H1 and H7 have been studied in depth and point mutation strategy at the S451D4 key residue position was conducted to further improve the binding interaction and efficacy on the wildtype Ank1D4 structure with NTDCA. A computational approach via molecular dynamics (MD) simulation has been fully utilized in this study to simulate both the wildtype and potential novel complexes. Free energy contributions on the modified Ank1D4-NTDCA (H1, H7) complexes were acquired by using vigorous scoring functions of implicit solvent models; Molecular Mechanics/Poisson-Boltzmann surface area (MM-PBSA) and Molecular Mechanics/Generalized Born surface area (MM-GBSA), respectively. The wildtype structure of Ank1D4-NTDCA H7 has been proven to possess better binding stability than the H1 complex. From there, two mutants of H7 complex were generated and the computed ∆Gbind values based on both models have revealed that S45Y-H7 has the lowest binding free energy compared to both S45W-H7 and S45-H7 (Wildtype). The binding strength predictions given by both MM-PBSA and MM-GBSA in the following ranking order for the three systems in terms of the value of ∆Gbind: S45Y-H7 > S45 W-H7 > S45-H7. These findings provide a good basis in directing us a step further to discover better novel treatment modalities to treat millions of HIV-1 patients.

The binding affinity and dynamics profiles of non-phosphorylated extracellular regulated kinase 2 (ERK2), in complex with DARPins (designed ankyrin repeat proteins) as a phosphorylation inhibitor, has been investigated using molecular dynamics simulations (MDs) and elastic network model (ENM). The study investigates the effect of ERK2 loop dynamics on its specificity, upon binding with DARPins. From experiments, DARPin E40 has been found as a specific binder (E40/ERK2) with higher binding affinity while DARPin pE59 has lower binding affinity towards ERK2 (pE59/ERK2). Theoretical binding affinities along the 100 ns molecular dynamics simulations between DARPins and ERK2 were analyzed and found in good agreement with the experiments, where BFE (binding free energy) of E40/ERK was found to be much lower (more favorable) as compared to that of pE59/ERK2 with the contribution of activation loop and αG loops. Moreover, elastic network model (ENM) studies successfully delineate the dynamics of four loops of ERK2 (activation, αG, MAPK and L16) along the trajectories. Slow eigenvectors from global mode shapes and dynamic cross correlation indicate the responsible regions for the binding. The specificity of DARPins can be discriminated by the binding free energy of the activation and αG loop, which indicated the stronger interaction of these region in E40/ERK2. Robustness of the average properties (mean-square fluctuations, eigenvectors from global mode shapes, dynamic cross-correlations) controlled by the low frequency motions, which are reproduced in both MDs and ENM suggested that GNM based on a coarsegrained single-site-per-residue model can be used as a complimentary and fast analytical approach to investigate the structural dynamics.

Post-combustion Carbon dioxide (CO2) capture (PCC) via amine absorption-stripping is an evolving technology towards mitigation of CO2 emissions. One of the major challenges in the technology development is the suitability of the solvent. Under the process operating conditions, irreversible reactions occur, thereby degrading the amine. The consequences of amine degradation are inevitable. The degradation products are harmful to the environment, increase the corrosion in the process equipment, cause fouling and ultimately make the process inefficient, hazardous and expensive. Monoethanolamine (MEA) is the benchmark solvent used and tested at industrial level for CO2 capture because of its high absorption rate and capacity to capture CO2 as well as medium to high resistance against oxidative and thermal degradation. This review reports degradation of MEA under process operating conditions, which includes up-to-dated list of degradation products, degradation kinetics and degradation pathways. Furthermore, degradation inhibition, computational studies, corrosivity as well as environmental concerns regarding the emissions of amine degradation products are critically reviewed. The objective of study is to provide researchers with a comprehensive knowledge on degradation of MEA, ways to reduce degradation, corrosion inhibition and understanding of environmental concerns for development of models for better understanding of behaviour of MEA and knowledge gaps.

The interaction of a hydrophilic drug, paracetamol with the cationic surfactant cetyltrimethylammonium bromide (CTAB) in an aqueous media has been investigated by using conductometric, tensiometric and spectroscopic methods. The critical micelle concentration (CMC) values have been determined by two different methods and both the methods yielded identical CMC values. The experimental data of conductance and surface tension have been correlated against temperature and concentration using standard relations. The pseudophase separation model has been adopted for calculation of various thermodynamic parameters such as standard free energy Δ G m 0 , enthalpy, Δ H m i c 0 , and entropy, Δ S m i c 0 , of micelle formation. The increase in the micellization with rising temperature is attributed towards the prevailing hydrophobic-hydrophobic increased interactions between the surfactant-drug aqueous mixtures. From the surface tension data the interfacial parameters such as the maximum surface excess concentration, Γmax, standard Gibbs free energy of adsorption at the air/solvent interface, Δ G a d 0 , and the minimum surface area pre molecule, Amin, were evaluated. Moreover, fourier transform infrared analysis (FTIR) was carried out to estimate the possible interactions prevailing in the miceller systems.

The silver nanoparticles (AgNPs) complexed with curcumin (CUR) extracted from turmeric (TMR) were synthesized and applied for a simple and rapid colorimetric technique for Pb2+ detection. The results reveal that our low-cost and rapid AgNPs-CUR sensor is highly selective for Pb2+ ions with the detection limit of 13.6 µM (2.8 mg.L−1) and can be applied for real water samples. Not only the observed absorption spectrum and the solution color can reveal the contamination of Pb2+ in the sample, but also an orange floccules precipitate can be clearly observed by naked-eye within 20 min. In addition, the results obtained from DFT calculation agree well with the experiments. Density functional theory (DFT), at the M06 level with mixed basis set of 6-31G(d) and def2-tzvp, was applied to propose the binding mechanism of AgNPs with CUR and AgNPs-CUR with Pb2+. Calculated binding energies of the compound of AgNPs with CUR and the AgNPs-CUR with Pb2+ are −145.8 and −361.4 kcal mol−1, respectively, indicating that the AgNPs-CUR is strongly interact with Pb2+ ions through formation of highly stable Pb2+AgNPs-CUR complexes indicating the stable aggregative phenomena which agrees well with FTIR spectrum.

A new chemosensor 1 was synthesized by reacting rhodamine B hydrazide and 2,3,4-trihydroxybenzaldehyde, which was then characterized by spectroscopic techniques and single crystal X-ray crystallography. Sensor 1 has the ability to sense Co2+/Cu2+ ions by “naked-eye” with an apparent colour change from colourless to pink in different solvent system, MeCN and DMF respectively. Furthermore, it can selectively detect Co2+/Cu2+ among wide range of different metal ions, and it exhibits low detection limit of 4.425 × 10−8 M and 1.398 × 10−7 M respectively. Binding mode of the two complexes were determined to be 1:1 stoichiometry for Co2+ complex and 1:2 stoichiometry for Cu2+ complex through Job’s plot, IR spectroscopy, mass spectrometry and 1H NMR spectroscopy. Moreover, reversibility of the sensor 1 as copper (II) ion detector was determined by using EDTA and the results showed that sensor 1 can be reused for at least 6 cycles. Other than that, a low cost chemosensor test strips were fabricated for the convenient “naked-eye” detection of Co2+ and Cu2+ in pure aqueous media. The MTT assay was conducted in order to determine the cytotoxicity of sensor 1 towards human cell lines.

Schizophrenia is a neuropsychiatric disorder characterised by positive symptoms, negative symptoms, and cognitive impairment. Dopamine system dysfunction is strongly implicated in the aetiology of schizophrenia, where the hyperactivity in striatal dopamine and hypoactivity in cortical dopamine is considered the key feature of this serious mental disorder. Recent research has been directed toward finding new therapeutic agents to potentiate the D1-receptor signalling and inhibit the D2-receptor signalling. Two enzymes in the phosphodiesterase (PDE) family, PDE1B and PDE10A, have become desirable drug targets for psychiatric disorders in general and schizophrenia in particular due to their high expression in brain regions involved in schizophrenia. The PDE1B enzyme represents the major inactivation mechanism of D1-receptors; therefore, the inhibition of PDE1B activity will potentiate the D1-receptor signalling and mitigate the negative symptoms and cognitive impairments. Whereas the inhibition of PDE10A activity has generated much excitement as a potentially novel mechanism to treat the positive symptoms of schizophrenia, which are attributed to the increased dopamine D2-receptor signalling. In which the inhibition of PDE10A activity will block the D2-receptor signalling and improve the positive symptoms. Therefore, in the quest of searching for a new treatment for schizophrenia, we report here the identification of a novel inhibitor with dual action on PDE1B and PDE10A. A sequential pharmacophore-based virtual screening, molecular docking and molecular dynamic simulations; were combined to identify the new inhibitor. After a detailed analysis of the results, two ligands were selected for the biological evaluation, in which one of the two ligands showed significant inhibitory activity against both PDE1B and PDE10A. The newly identified inhibitor can be explored for further optimisation and evaluated in vivo for its antipsychotic-like effects.

A series of Schiff base metal complexes with the formulations [Ni(L1)PPh3]Cl (1), [Ni(L2)PPh3]Cl (2), [Ni(L3)PPh3] (3), and [Ni(L4)PPh3] (4) (where L1 = 2,3,4-trihydroxybenzaldehyde-4-methyl-3-thiosemicarbazone, L2 = 2,3,4-trihydroxybenzaldehyde-4-ethyl-3-thiosemicarbazone, L3 = 2,3,4-trihydroxybenzaldehyde-4-phenyl-3-thiosemicarbazone, and L4 = 2,3,4-trihydroxybenzaldehyde-4-(4-ethylphenyl)-3-thiosemicarbazone) were synthesised. All compounds were characterised using FT-IR, 1H NMR, and 13C NMR. The complexes were further characterised with single crystal X-ray diffraction. The complexes are four-coordinated and adopt a square planar geometry, in which the Schiff base ligands bind to the metal centre via their tridentate O,N,S atoms. Ligand L2 and complex 1 showed a higher cytotoxic activity than cisplatin with IC50 5.75 ± 0.49 and 4.26 ± 0.29 μM, respectively when tested against human colorectal carcinoma HCT 116. Besides, complex 3 was found to show a stronger cytotoxic activity with an IC50 7.07 ± 0.61 μM than its ligand (L3 IC50 9.82 ± 1.85 µM) when tested against HCT 116. On the other hand, complexes 2 and 3 showed moderate in vitro antimalarial activity with IC50 9.88 ± 0.23 and 1.06 ± 0.01 μM, respectively. Remarkably, the antimalarial activity increases as the hydrophobicity of the substituent group attached at the N(3) position increases. Through molecular docking simulation, complexes 2 and 3 are predicted to be a minor groove binder with an appreciable DNA binding affinity, suggesting that 2 and 3 exerted their cytotoxicity and antiplasmodial activity probably via their benzaldehyde, triphenylphosphine, aliphatic chain and phenyl moieties interaction with DNA base pairs.

This study attempts to bring about a facile approach to selectively adsorb 2,4-dinitrophenol (2,4-DNP) from an aqueous system using sporopollenin supported ionic liquid (SpIL) biosorbent, namely sporopollenin supported methylimidazolium (Sp-MIM). Sporopollenin acts as the host with the accessible chamber, while methylimidazolium acts as the active site that binds 2,4-DNP from the aqueous system. Methylimidazolium, being chemically immobilized onto sporopollenin, simultaneously ensures that the ionic liquid does not leach into the aqueous environment while providing increased affinity and selectivity towards 2,4-DNP. The solid samples were characterized using conventional solid-state testing techniques such as FTIR, 13C CP/MAS solid-state NMR, FESEM-EDX spectroscopy, TGA, and BET/BJH analysis. While UV-Visible spectroscopy was used to study the adsorption parameters. Based on the study, methylimidazolium's immobilization onto sporopollenin increased pore size distinctly from 5.06 nm to 44.94 nm, thereby reporting definitive mesoporous structure with a pronounced affinity towards 2,4-DNP, determined via a series of analyte screening. Adsorption parameter exploration revealed 15 mg of Sp-MIM was able to adsorb 84% of 2,4-DNP from 20 ppm concentrated aqueous solution within 15 min of contact under acidic condition (pH 4) and could be reused up to 5 cycles without any loss to adsorption percentage. The affinity of Sp-MIM towards 2,4-DNP was further explored employing computational calculations using molecular docking and quantum mechanics, both of which support the presence of π-π interaction and hydrogen bonding between Sp-MIM and 2,4-DNP.

A rhodamine-based colorimetric sensor, RBOV has been synthesized and modified for selective detection of Cu2+, Ni2+ and Co2+ ions simultaneously in aqueous medium. The difference in color change upon binding with these three cations makes it an interesting multianalyte sensor. Furthermore, the detection limits of RBOV for Cu2+, Ni2+ and Co2+ are down to 4.0 × 10−2 µM, 3.2 × 10−1 µM and 4.8 × 10−1 µM respectively. The possible sensing mechanism analyzed from Benesi-Hildebrand plot, Job's plot, FTIR and DFT studies showed a 1:1 stoichiometry of sensor-metal complex for all three analytes. Practical application of sensor was conducted in real time using test strips and MTT assay was conducted to determine its cytotoxicity.

Effective novel peptide inhibitors which targeted the domain III of the dengue envelope (E) protein by blocking dengue virus (DENV) entry into target cells, were identified. The binding affinities of these peptides towards E-protein were evaluated by using a combination of docking and explicit solvent molecular dynamics (MD) simulation methods. The interactions of these complexes were further investigated by using the Molecular Mechanics-Poisson Boltzmann Surface Area (MMPBSA) and Molecular Mechanics Generalized Born Surface Area (MMGBSA) methods. Free energy calculations of the peptides interacting with the E-protein demonstrated that van der Waals (vdW) and electrostatic interactions were the main driving forces stabilizing the complexes. Interestingly, calculated binding free energies showed good agreement with the experimental dissociation constant (Kd) values. Our results also demonstrated that specific residues might play a crucial role in the effective binding interactions. Thus, this study has demonstrated that a combination of docking and molecular dynamics simulations can accelerate the identification process of peptides as potential inhibitors of dengue virus entry into host cells.

In order to understand the phase equilibrium behavior of aqueous ionic liquids (ILs) guanidinium triflate [gua][OTf] solution (binary solvent) at 7 different molar fractions of water ranged from 0.1 to 0.7 at 440.15 K classical molecular dynamic simulations were performed. The simulations measured changes in different properties such as density, structural, bonding properties (radial distribution function, water clustering and hydrogen bonding) and dynamic property (diffusion coefficient). The analysis of radial distribution and spatial distribution functions revealed a significant long-range structural correlation between IL and water. Water molecules intercalated in the coordination shell of both ions, thus weakening their electrostatic interaction. It was observed that, water molecules started to connect with each other and formed a large hydrogen bond network throughout the system with the increasing water molar fraction. Thus, improved both translational and rotational motions of [gua]+ and [OTf]− ions significantly. As the results, [OTf]− ions diffused faster than [gua]+ ions and improved both translational and rotation motions of the ions mentioned significantly. The application of aqueous [gua][OTf] at high temperature has a promising potential particularly in the carbon dioxide removal area for natural gas industry.

Naturally occurring proteins are emerging as novel therapeutics in the protein-based biopharmaceutical industry for the treatment of diabetes and obesity. However, proteins are not suitable for oral delivery due to short half-life, reduced physical and chemical stability and low permeability across the membrane. Chemical modification has been identified as a formulation strategy to enhance the stability and bioavailability of protein drugs. The present study aims to study the effect of charge-specific modification of basic amino acids (Lys, Arg) and guanidination on the interaction of insulin with its receptor using molecular modelling. Our investigation revealed that the guanidination of insulin (Lys-NHC = NHNH2) enhanced and exerted stronger binding of the protein to its receptor through electrostatic interaction than native insulin (Lys-NH3+). Point mutations of Lys and Arg (R22, K29; R22K, K29; R22, K29R; R22K, K29R) were attempted and the effects on the interaction and stability between insulin/modified insulins and insulin receptor were also analyzed in this study. The findings from the study are expected to provide a better understanding of the possible mechanism of action of the modified protein at a molecular level before advancing to real experiments.

Cationic (Malachite Green) and anionic dyes (Indigo carmine) removal by cross-linked chitosan (CSglu) beads has been investigated using experimental and computational approaches. The experimental investigations of the adsorption isotherm, kinetics, and thermodynamics information correlated well with computational studies in term of structures and binding energies (ΔEB). Cross-linked chitosan adsorb Malachite Green better than Indigo carmine using Langmuir adsorption isotherm. The CSglu beads in frozen dried form showed highly adsorption capacity (714.29 mg.g−1) for malachite green (MG) but they are not favorable for indigo carmine (IND). In order to probe the atomistic-level detail between these two dyes and CSglu, molecular dynamics simulations (MDs) have been applied to determine detailed analysis of binding site of the complexes. MG is more preferable to bind with CSglu than IND due to its complementary of the molecular electrostatic potential (MEP) to the CSglu surface. The quantum calculations using density functional theory (DFT) with different levels and basis set super position error (BSSE) were used to calculate ΔEB and to effectively predict the adsorption capabilities of cationic and anionic dyes by cross-linked chitosan.

Density functional theory calculations of the H 2 molecule over the Pt(111), Pt 4 Pd 5 (111), Pt 3 Ir 6 (111), and Pt 8 Ru 1 (111) surfaces were carried out to derive key properties involving interactions and electronic state of each atom. From the calculations, H 2 dissociative adsorption shows the lowest barrier in case of the Pt 3 Ir 6 (111) surface. Pt 4 Pd 5 (111) and Pt 8 Ru 1 (111) surfaces show a small energy barrier, while the Cu(111) surface is the highest energy barrier. The difference in the reactivity of H 2 molecule with the surface is pointed out by the differences in the valence electron configuration of approaching hydrogen which is also verified from the density of state curve. The electronic structure plots illustrate the substituted atoms can interact with molecular H 2 projected on the surface d-orbital.

DNA surface and DNA strand breaks of 12 base pairs of alternating poly-AT double strands of DNA in A form were investigated by Monte Carlo simulations to find the preferential binding sites and Langevin Molecular Dynamics simulations after exposure to 0.2, 20, and 200 eV carbon atoms. Final simulated structures were further optimized using the AMBER force field and details in the surface changes, the interaction between DNA and carbon and the interaction between single-stranded strand and its pair were investigated. The solvent accessible area surface and volume of DNA were determined and significant differences observed under higher energy and temperature conditions. Both simulations concluded that under the low energy irradiation and low temperature, carbon atoms could explore the surface and interact to the preferential sites at phosphate oxygen or nitrogen in base pairing, dominated by the local base pair shift in a stagger and buckle manner, while under higher energy irradiation more severe base pair shift could be caused in combination with propeller and opening manner and several bonds could be elongated to lead to DNA damage.

Modulation of P-glycoprotein (P-gp)’s function may lead to significant changes in the prescription drugs’ pharmacokinetic profiles and increase potential risks in occurring of drug-drug including herb-drug interactions. This computational structured-based study aimed to screen bioflavonoids which play a role in herb-drug interactions as a P-gp inhibitor utilising molecular docking analysis. 25 flavonoids were used as ligands for docking study. The mouse P-gp (code: 4Q9H) was acquired from the Protein Data Bank (PDB). Docking analysis was operated utilising AutoDock 4.2.6. A lowest estimated free energy of binding value in a cluster of each flavonoid against nucleotide-binding domain 1 (NBD1) of P-gp was analysed. The result points out the high correlation between the estimated free energies of binding and percentage of inhibitory efficiency values of flavonoids applied in the molecular modelling that is powerful and capable to predict potential P-gp interactions among flavonoids and its substrates.

A new fluorescent sensor ( FC4 ) based on fluorescein dithia-cyclic skeleton was designed and prepared as a fluoroionophore for the optical and visual-eye detections of Hg 2+ in aqueous buffer solution. FC4 was prepared via Kornblum oxidation, ester hydrolysis, alkylation, imine formation and imine reduction. The sensor provided highly sensitive and selective ON–OFF fluorescence sensing toward Hg 2+ and was shown to discriminate various interfering metal ions, particularly Cu 2+ and Pb 2+ as well as Al 3+ , Ba 2+ , Ca 2+ , Cd 2+ , Fe 3+ , K + , Mg 2+ , Mn 2+ , Na + and Ni 2+ . Sensor FC4 also exhibited chromogenic change upon binding to Hg 2+ , which served as a “visual-eye” indicator which could be observed as a noticeable change of the solution color from yellow to orange. The Hg 2+ detection limit of the sensor was 7.38 × 10 −9 or 1.48 ppb which was lower than a permissible concentration of Hg 2+ in drinking water regulated by the United States Environmental Protection Agency (U.S. EPA).

Toxic metabolites that could promote the formation of tumors are generated with high levels of β-glucuronidase activities. Hence, the inhibition of the β-glucuronidase enzyme is effective in the prevention of colonic carcinogenesis, and other diseases. This study aims to investigate the β-glucuronidase inhibitory effect of compounds that were isolated from Nauclea subdita (Korth.) Steud. and Alpinia pahangensis Ridley, together with their mode of inhibition, and their interactions with the enzyme. Angustine (1) and (E)-labda-8 (17),12-dien-15,16-dial (2) are secondary metabolites which were isolated from Nauclea subdita (Korth.) Steud. and Alpinia pahangensis Ridley, respectively. Both exhibited potent inhibitory activities against the β-glucuronidase enzyme with IC50 values of 5.6 ± 0.70 and 23.61 ± 3.32 μM, respectively. The enzyme kinetic studies suggested that compounds 1 and 2 were non-competitive inhibitors with inhibition constants (Ki) of 8.46 and 22.0 μM, respectively. In silico molecular docking and molecular dynamics simulation studies showed that the amino acid residues that interacted with compounds 1 and 2 were Phe161, Leu361, Phe448, Tyr468, Tyr472, and Leu561. These amino acid residues interacted with compound 1 with lower energy as compared to compound 2. Furthermore, the binding free energy of compound 1 (GBTOT value of −31.69 kcal mol−1) was found to be lower than that of compound 2 (GBTOT value of −22.32 kcal mol−1). Compound 1 was thus predicted to be a more active inhibitor through in silico molecular docking and molecular dynamics simulation studies.

Clarification of proton transfer mechanisms is crucial to the development of proton exchange membrane fuel cells (PEMFCs). Nitrogen-containing heterocyclic compounds ( e.g. , imidazole derivatives) are well known for their potential to assist proton hopping through hydrogen bond networks at high temperatures. Among the many imidazole derivatives reported thus far, 1,3,5-tri(2-benzimidazolyl)benzene (TBIB) is assumed to be one of the most promising imidazole derivatives because of its triple-stranded three-dimensional hydrogen bond network. In fact, TBIB immersed into a polyphosphoric acid matrix was reported to enhance the proton conductivity to 10 −2 –10 −1 S/cm in the high-temperature range up to 170 °C. In the present work, the proton transfer mechanism has been investigated using density functional theory (DFT) with a DNP basis set and the GGA exchange-correlation functional BLYP and molecular dynamics simulations (MD) to provide insight into the cause of the remarkable proton conductivity of TBIB. Transition states in the proton hopping process were obtained using two types of models constructed from the X-ray crystal structure: an isolated two-molecule system (type I) and a periodic three-molecule system (type II). Alterations of charge distribution, molecular conformation and molecular orientation were investigated from these models. Further, the diffusion coefficient of proton transfer has been estimated and the mechanisms along three specific channels that favor efficient proton transfer between the layers have been examined in detail. Additionally, the effect of an electric field perturbation was investigated for these two models. The application of an external electric field was found to affect the proton hopping process remarkably, as evidenced by large changes in the activation energies and proton hopping times. In conclusion, the highly organized hydrogen-bonding network observed for TBIB was found to be a key factor in enhancing the efficiency of proton transfer.

Preparation of the oxabicyclic [3.3.1] cores of morusalbanol A and 441772-64-1 was achieved via the intramolecular cyclization of cis–trans (endo) mulberry Diels–Alder adducts. The latter were derived from a hydrogen bond-assisted regioselective Diels–Alder reaction between a chalcone dienophile and a dehydroprenyl diene. Results from these studies provide important insights into the syntheses of morusalbanol A and related mulberry Diels–Alder adducts.

A chiral organocatalyst derived from (R)-1,1′-bi-2-naphthol (BINOL) was developed for immobilisation onto magnetic iron oxide particle (MIOP). This heterogeneous organocatalyst was characterised using infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA) and scanning electron microscope (SEM). The performance of BINOL-grafted MIOP (BINOL–MIOP) was then evaluated using aldol reaction between benzaldehydes and cyclic ketones. Comparative studies between homogeneous versus heterogeneous aldol reaction revealed the similar reactivity for both reaction systems. The reaction system mediated by BINOL–MIOP was versatile to produce aldol adducts in moderate-to-good yields (45–99%) from different benzaldehydes and cyclic ketones. In addition, more syn adducts were produced in most cases. Up to 35% ee was observed in anti adducts, despite that a higher 50% ee of anti adduct was observed in the homogeneous reaction system. This observation was supported by the results obtained from the molecular modelling, which revealed the reduced selectivity in the heterogeneous system that was possibly caused by the torsional angle distortion of BINOL after immobilisation. In contrast to the free-BINOL, the distorted-BINOL exhibited lower tendency to form a complex with aldehyde, thereby reducing the selectivity that the free-BINOL could deliver. In addition, the reaction system mediated by BINOL–MIOP was exhibiting an excellent reusability for up to 10 cycles of reactions.

Inclusion complex formation of Alizarin Red S (ARS) with β-cyclodextrin was studied by UV–visible, Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), cyclic voltammetry (CV) and molecular modeling methods. FTIR and NMR results had justified that ARS was partly included into the β-CD cavity. The inclusion complex has 1:1 stoichiometry, where the apparent formation constant achieved was 4.137 × 103 L/mol using Benesi–Hildebrand equation. Cyclic voltammetry results shows the peak current decreased as the ARS molecule entered the hydrophobic cavity of β-CD. Molecular modeling results showed that the aromatic ring of the ARS entered into the secondary hydroxyl rim of the CD cavity was more thermodynamically favorable. The lowest stabilization energy, ΔE was −17.80 kcal/mol, and dipole-dipole interaction is was one of the driving forces for the inclusion complex formation.

Through this letter to the editor (Rebuttal), we had given our explanation for the queries raised by Professor Juan J. Melendez commenting on the high substitution energies, the small simulation supercells, and the inconsistence of experimental data and simulation results. We agree with the comment that applying a “chemical potential diagram” is a general way to study defect system. However, there are some experimental concerns on “what the initial materials should be used”, whereas many degrees of freedom become feasible. Therefore, the formation energy equation (with foreign atoms substitution) cannot be trivially answered by the formation energy within a chemical potential diagram framework, unlike substitution energy calculated directly from our suggested chemical equation. We explain in the details on our approach and confirm the validity of our main equation; FeO+Ba 8 Ti 8 O 23 →Ba 8 Ti 7 FeO 23 +TiO 2 for the substitution energy with 2×2×2 supercell size which the results still show some suggestive trends.

The ring-opening polymerization (ROP) mechanism of d -lactide using tin (IV) alkoxides, (CH 3 (CH 2 ) 3 ) 3 SnOR, as initiators was theoretically studied. The high level adiabatic mapping B3LYP/LANL2DZ calculations were performed. This work evaluates role of the tin (IV) alkoxide initiators and gives molecular detail of the polymerization mechanism. In order to investigate the effects of the substituent (R) group of initiator on the ROP reaction rate, the R group was modeled to be linear R groups; –CH 2 CH 3 , –(CH 2 ) 3 CH 3 , –(CH 2 ) 5 CH 3 , –(CH 2 ) 7 CH 3 , –(CH 2 ) 9 CH 3 and branch R groups; –CH 2 CH 3 , –CH 2 CH(CH 3 ) 2 , –C(CH 3 ) 3 . The calculations show that the rate limiting step of the ROP reaction mechanism is the first transition state (TS1) of the reaction which corresponds to the steric effect of the initiators. For the initiators with a linear R group, the steric effect on the potential energy barrier of the TS1 is not significant whereas the initiators with branch R groups relatively increase the potential energy barrier. However, the determined potential energies of the TS1 for most initiators studied in the work are in the same range (16.0–20.2 kcal/mol). Therefore, all the initiators except (CH 3 (CH 2 ) 3 ) 3 SnOC(CH 3 ) 3 are suitable for the ROP of the d -lactide.

The site predilection and effects of the impurity in the form of Fe (II) and Fe (III) in the tetragonal barium titanate lattice were systematically determined by density function theory calculations. All electron calculation was carried out in the local density approximation (LDA). It is shown that both Fe (II) and Fe (III) prefer to substitute at the titanium site with oxygen vacancy compensation as a result of lowest substitution energy. Effect of Fe dopant both in form of Fe (II) and Fe (III) at titanium site with oxygen vacancy compensation lead to change in electrical property in terms of energy band structure of the tetragonal barium titanate lattice.

Proton transfer is a governing factor in the proton exchange efficiency in membrane fuel cells (PEMFCs), which are an alternative environmentally friendly resource. To develop the capacity of the PEMFC system, anhydrous membranes containing imidazole groups have garnered much interest. In this research, the relationship between the hydrogen bond networks, including the consequent packing structure, and the proton conductivity of water and imidazole (Im) systems have been systematically studied. The effect of external electrostatic perturbation was investigated in (H 2 O)H + ⋯H 2 O, (Im)H + ⋯Im, bulk water, and imidazole superlattice systems. In all of these cases, the application of an electric field in a direction opposite to that of the overall system dipole significantly reduces the activation barrier for proton transport. In isolated systems, (H 2 O)H + ⋯H 2 O and (Im)H + ⋯Im, the preferred orientation angle between the neighbouring molecules was 90°. From density functional molecular dynamics simulations of the bulk system, the proton diffusion coefficient was found to increase under the perturbation by the applied electric fields in range of 1.29 × 10 7 to 3.86 × 10 7 V cm −1 (0.0025–0.0075 a.u.) for both water and imidazole. To trace the efficient proton transfer, the proton movement trajectory was explicitly analysed in detail. Interestingly, a tilted proton hopping direction was found for imidazole crystal.

Nafion, a polymer electrolyte membrane of a fuel cell, can be modified by low energy Ar + beam bombardment to increase its interfacial area with a catalyst. Recent experiments indicated that the sputtered sulfonate could lead to a decrease of hydrophilicity of Nafion when bombarded by a low energy Ar + beam. To investigate the surface modification at the atomic level, molecular dynamic (MD) simulations and experiment were carried out. The effects of Ar + at 0.5–3.0 keV, and doses in the range of 10 14 –10 15 ions cm − 2 on the damage of the Nafion surface after bombardment were deduced from the simulations. This was assessed through both the chemical and physical changes of the Nafion side chain. The potential dissociation of the C S bond after bombardment was analyzed in terms of the elongated bond population. The percentage of the extended C S bond in the system was calculated to determine the possibility of sulfonate sputtering. Real-time determination of the amount of molecular species defragged under Ar + ion bombardment by quadrupole mass spectroscopy (QMS) was used. The percentage of the amount of potentially broken C S bonds after bombardment derived from MD simulations was found in a correlation with sputtering of SO 3 − fragments obtained from the experiments. The calculated results confirm the thresholds at 2.0 keV as observed in experiment.

Two novel macromolecules based on 2-[3-(2-aminoethylsulfanyl)propylsulfanyl]ethanamine covalently bound to one and two units of rhodamine-B moieties, 1 and 2 , were prepared and utilized as fluoroionophores and chromophores for the optical detection of Hg 2+ ions. The sensors were readily prepared by a conventional two-step synthesis. Especially, sensor 1 exhibits high sensitivity and selective OFF–ON fluorescence enhancement and chromogenic change upon binding to Hg 2+ , which served as a “naked-eye” indicator by a noticeable color change of the solution (from colorless to pink–red color). 1 is shown to discriminate various competing metal ions, particularly Ag + and Cu 2+ , as well as Cd 2+ , Na + , Li + , K + , Ba 2+ , Co 2+ , Ni 2+ , Mg 2+ , Mn 2+ and Al 3+ , with a detection limit of 10 ppb.

A novel fluorometric sensor bearing three dansyl moieties based on tris[2-(2-aminoethylthio)ethyl]amine was prepared by a simple approach using a conventional two-step synthesis. The sensor exhibits highly Hg 2+ -selective ON–OFF fluorescence quenching behavior in aqueous acetonitrile solutions and is shown to discriminate various competing metal ions, particularly Cu 2+ , Ag + , and Pb 2+ as well as Ca 2+ , Cd 2+ , Co 2+ , Fe 3+ , Mn 2+ , Na + , Ni 2+ , and Zn 2+ , with a detection limit of 1.15 × 10 −7 M or 23 ppb.

In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by

A five percent by weight of carboxylic acid terminated perfluoropolyether hybrid with silica (Krytox-Silica) in Nafion composite polymer was used in the modification of a polymer electrolyte fuel cell membrane in order to improve its efficiency at high operating temperatures. Molecular dynamics (MD) simulations were carried out in order to understand the microscopic properties of two systems, Krytox-Silica in Nafion and pure Nafion. A model of five percent Krytox-Silica in a Nafion composite polymer consisting of 15 Nafion side chains, 15 hydronium ions and one of Krytox-Silica was used. In another system, pure Nafion was modeled without Krytox-Silica. Models with various amounts of water molecules and temperatures were simulated to study the water content and temperature effects. The results were in good agreement with the experiments and could be used to describe the application of Krytox-Silica–Nafion composite at high temperatures. The effect of the amount of water molecules on the diffusion coefficient or proton conductivity showed more deviations between 5% wt of Krytox-Silica–Nafion composite and pure Nafion system at lower water content (or higher temperature) than at high water content (or low temperature). According to the diffusion coefficient results, the percentage of water molecules at each temperature corresponded to the known experimental trend. Silica, as the water absorbent in the hybrid polymer membrane, did not have a strong interaction with water molecules or H3O+ ions; thus the proton conductivities will not be highly affected by adding Krytox-Silica to the Nafion.

The present work reports the results of a conformational study performed on three essential non-polar amino acids: valine, leucine and isoleucine. Ab initio calculations were done at the MP2/6–311++G(2d,2p) level in the gas phase. The 6, 8 and 12 conformers served as a basis to represent the shapes of valine, leucine and isoleucine in the gas phase, respectively, with the relative energies ( Δ E Total ) below 1.25 kcal mol−1 compared to the most stable conformer of each amino acid. The Δ E Total values are reported at the MP2/6-311++G(2d,2p) level with corrections for zero-point vibrational energies. The lowest energy conformers of each amino acid contained the intramolecular hydrogen bond (H-bond) interactions between the NH2 and COOH groups which are the N–H…O = C, N–H…O–H and O–H…N–H H-bonds. It is obvious that the H-bond interaction plays an important role in the conformational energy and harmonic vibrational frequencies. From the theoretical vibrational spectra, the O–H out of plane and in-plane bending shift ranged from ∼1100 cm−1 to ∼1360 cm−1 and the O–H stretching shifts from ∼3600 cm−1 to 3400 cm−1 due to the O–H…N–H H-bond interaction. In addition, the side-chain orientations can also affect the conformational stability and diversity, resulting in a large number of low energy conformational minima of amino acid.

Low-pressure plasma has been used to improve the hydrophobicity of Thai silk. In this study, Glycine–Alanine (GA) and Alanine–Glycine (AG) were chosen to represent model compounds of Bombyx mori silk. Single crystals of the simplified model compounds were characterized by polarizing microscopy and X-ray diffraction. The space groups of P212121 and P21 were found for AG and GA, respectively. The initial structures for calculation were obtained from the experimental crystal structures. Density functional theory at the BHandHLYP levels was used to investigate possible mechanisms of fluorine radicals reacting with AG and GA in the SF6 plasma treatment. The results indicate that hydrogen atoms of silk model compounds were most likely to be abstracted from the alanine residue.

Since the emergence of the severe acute respiratory syndrome (SARS) to date, neither an effective antiviral drug nor a vaccine against SARS is available. However, it was found that a mixture of two HIV-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the SARS virus. To understand the fine details of the molecular interactions between these proteinase inhibitors and the SARS virus via complexation, molecular dynamics simulations were carried out for the SARS-CoV 3CL(pro) free enzyme (free SARS) and its complexes with lopinavir (SARS-LPV) and ritonavir (SARS-RTV). The results show that flap closing was clearly observed when the inhibitors bind to the active site of SARS-CoV 3CL(pro). The binding affinities of LPV and RTV to SARS-CoV 3CL(pro) do not show any significant difference. In addition, six hydrogen bonds were detected in the SARS-LPV system, while seven hydrogen bonds were found in SARS-RTV complex.