A rhodamine based fluorescent and colorimetric chemosensor for the detection of Cr3+ ions and its utility in a molecular logic gate.

A new rhodamine based fluorescent and colorimetric chemosensor S1 was synthesized for the selective recognition of Cr3+, a trivalent metal ion. The interaction of S1 toward different metal ions has been studied via fluorescence and UV-visible spectroscopy. The studies revealed that the fluorescence and colorimetric changes of chemosensor S1 are prominent for Cr3+ over other competitive metal ions. Moreover, the chemosensor S1 exhibits 1 : 1 complex formation with Cr3+ as apparent from the Job's plot and the Benesi-Hildebrand (B-H) plot. Density functional theory (DFT) studies also revealed that the Cr3+ ion is coordinated to three atoms of S1, which validates the formation of a complex between S1 and Cr3+. The limit of detection (LOD) of chemosensor S1 for Cr3+ was 0.21 µM. Furthermore, to explore the recyclability of S1, ethylenediaminetetraacetic acid (EDTA) was added to the S1-Cr3+ solution. On the addition of EDTA to the solution of S1-Cr3+, the reversibility of the complex was observed, and a colorimetric variation was also observed on the addition of Cr3+ and EDTA to S1 which mimics the "INHIBIT "molecular logic gate. Chemosensor S1 also demonstrated practical utility through detection of Cr3+ in the solid state.

In silico studies of the interaction of the minor groove binder Hoechst 33258 with B-DNA.

Interaction of the minor groove binder, Hoechst 33258, with the Dickerson-Drew DNA dodecamer sequence has been investigated using docking, MM/QM, MM/GBSA and molecular dynamics computations to study the modes of binding and the interactions responsible for the binding. Besides the original Hoechst 33258 ligand (HT), a total of 12 ionization and stereochemical states for the ligand are obtained at the physiological pH and have been docked into B-DNA. These states have one or the other or both benzimidazole rings in protonated states, apart from the piperazine nitrogen, which has a quaternary nitrogen in all the states. Most of these states are found to exhibit good docking scores and free energy of binding with B-DNA. The best docked state has been taken further for molecular dynamics simulations and compared with the original HT. This state is protonated at both benzimidazole rings besides the piperazine ring and hence has very highly negative coulombic interaction energy. In both cases, there are strong coulombic interactions, but these are offset by the almost equally unfavorable solvation energies. Thus, the nonpolar forces, particularly van der Waals contacts, dominate the interaction, and the polar interactions highlight subtle changes in the binding energies, leading to more highly protonated states having more negative binding energies.Communicated by Ramaswamy H. Sarma.

A combination strategy of structure-based virtual screening, MM-GBSA, cross docking, molecular dynamics and metadynamics simulations used to investigate natural compounds as potent and specific inhibitors of tumor linked human carbonic anhydrase IX.

Cancer remains a serious health concern representing one of the leading causes of deaths worldwide. The enzyme human carbonic anhydrase IX (hCA IX) is found to be over-expressed in many cancer types and its selective inhibition over its cytosolic off-target isoform, human carbonic anhydrase II (hCA II), represents a potential area of research in the development of novel anticancer compounds. This work is concerned with the use of various in silico tools for the identification of natural product based molecules that can selectively inhibit hCA IX over hCA II. MM-GBSA assisted structure-based virtual screening against hCA IX was performed for nearly 225,000 natural products imported from the ZINC15 database. The obtained hits were checked for their potency by considering acetazolamide, the bound inhibitor of hCA IX, as the reference molecule, and 121 molecules were identified as potent hCA IX inhibitors. After ensuring their potency, cross-docking, followed by MM-GBSA calculations of the hits with hCA II, was performed, and their selectivity was assessed by considering the hCA IX selective compound SLC-0111 as the reference molecule, and 50 natural products were identified as potent as well as selective hCA IX inhibitors. Molecules with the quinoline scaffold showed the highest selectivity, and their selectivity was attributed to the strong electrostatic interactions of the zinc binding group (ZBG) with the active site Zn(II) ion. Furthermore, the stability of the binding modes of the top hCA IX selective hits was ensured by performing molecular dynamics (MD) simulations, which clearly proved that one of the short-listed molecules is truly selective, as it does not interact with the active site Zn(II) ion of hCA II, but interacts strongly with this ion in hCA IX. Bonding pose metadynamics studies revealed that the ligand moves to a more stable binding site from the one predicted by the docking studies and shows stronger interaction with the protein and Zn(II) at this binding site. The ligand is not likely to have issues with bioavailability. As a result, this ligand can be taken for bioassay testing and subsequently used as a feasible therapeutic treatment for a variety of cancer types. Communicated by Ramaswamy H. Sarma.

II-VI core/shell quantum dots and doping with transition metal ions as a means of tuning the magnetoelectronic properties of CdS/ZnS core/shell QDs: A DFT study.

This paper examines the alterations in the properties of II-VI Quantum Dots (QDs) when these are coated with a shell made of another material of the same family and investigates the structural, electronic and magnetic properties of doped CdS/ZnS core/shell QDs. The core/shell QDs have been constructed by building the shell over the bare core QD and it is found that this construction of a shell over the bare QD can bring about dramatic changes in its optical properties. On changing the shell by varying either the cation or the anion, substantial variations are brought about in the band gap and electrophilicity. The trend of Fermi energies is more negative for core/shell QDs than for the QDs without a shell, and the value is almost the same for core/shell QDs with the same core. Swapping of the core and the shell materials brings greater stability in the case of shells of the wider band gap materials. Binding energy data demonstrates that the CdS/ZnS, CdSe/ZnSe, CdSe/CdS core/shell systems are more stable than ZnS/CdS, ZnSe/CdSe, CdS/CdSe core/shell systems, respectively. An augmentation in the properties is found on doping the QD with transition metal ions. The binding energies are found to be functions of the kind of dopant as well as the spin multiplicity and account for the stability of one spin state over the other at a specific site of the QD. The most fascinating property that plays a decisive role in the extant work is the introduction of magnetism in core/shell QDs as a result of the entry of unpaired electrons within the CdS/ZnS QDs on doping with transition metal ions. The deviation of the observed magnetic moments from the expected values increases as the dopant is varied from Mn2+ to Fe2+ to Co2+ to Ni2+ to Cu2+. Hirshfeld charge analysis shows that the doped ion accepts negative charge from the sulfide ions in the core, with the smallest charge transfer seen in the case of Hg2+ ions. As we move from Mn2+ to Hg2+, the trend followed for the Hirshfeld charges indicates that the overall charge on the core is lower and that on the shell is higher for all the doped cases in comparison to the undoped CdS/ZnS core/shell QD. The band gap values reveal that the Fe2+ doped CdS/ZnS core/shell structures have the smallest band gaps. Hence, we expect that this paper will help researchers to develop a strategy to produce QDs of the anticipated properties for various applications, and transition metal ions can be successfully employed for modification of various magnetoelectronic properties of the host semiconductor for future applications in nanotechnology.

Identification of potent human carbonic anhydrase IX inhibitors: a combination of pharmacophore modeling, 3D-QSAR, virtual screening and molecular dynamics simulations.

Human carbonic anhydrase IX (hCA IX) is a promising target for the development of potential anticancer agents. In the current study, pharmacophore and 3D-QSAR models have been developed using SLC-0111 derivatives. The developed models have been further utilized for the virtual screening process to develop potent hCA IX inhibitors. Thirteen different models have been developed by employing various combinations of training and test set molecules. Based on this, a model, AADDR.135, comprising two H-bond acceptors, two H-bond donors and one aromatic ring, has been found as the best QSAR model. The proposed model exhibits high robustness (R2 = 0.9789), with good predictive ability (Q2 = 0.6872). An external library of drug-like compounds (∼10000 molecules) imported from the ZINC15 database has been screened over the model AADDR.135. In total, 1601 compounds were obtained as hits. Molecular docking studies and molecular dynamics simulations have been performed on the obtained hits and, based on these computations, two unique molecules have been identified as potential hCA IX inhibitors. These show higher binding energies compared to the parent molecule and its most potent analogue.Communicated by Ramaswamy H. Sarma.

A comparative study of different docking methodologies to assess the protein-ligand interaction for the E. coli MurB enzyme.

We have investigated the active site of E. coli MurB using the Quantum Mechanics/Molecular Mechanics (QM/MM) methodology. The docking of three novel series of 4-thiazolidinone derivatives has been performed using two methods: rigid docking and flexible docking (Induced Fit Docking: IFD). The results have been compared to understand the conformational aspects of the enzyme. The docking results from rigid docking show that the ligands with highly negative ΔGbind have poor docking scores. In addition, the value of the regression coefficient (R) obtained on correlating the ΔGbind and the experimental pMIC values is insignificant. On keeping the protein flexible, there is a remarkable improvement in both the docking score and ΔGbind, along with a good value of R (0.64). Two important residues, Tyr254 and Try190 are found to be highly displaced during the flexible docking and hence their role in effective ligand binding has been confirmed. Thus, comparing the two methodologies, IFD has emerged as the more appropriate one for studying the E. coli MurB enzyme. To further substantiate the findings, MD studies over a time period of 20 ns have been performed on the IFD-LIII j and Rigid/XP-LIII j complexes and the results shows the former complex to be more stable, with lower average RMSD and higher average ΔGbind.Communicated by Ramaswamy H. Sarma.

The antioxidant potential of retrochalcones isolated from liquorice root: A comparative DFT study.

Polyphenolic compounds are known to exhibit potent antioxidant properties owing to the presence of various phenolic groups. The present study reports the antioxidant potentials of six retrochalcones, namely echinatin, and licochalcone A, B, C, D and E, isolated from the root of the Glycyrrhiza species, toward various reactive oxygen and nitrogen species. Different mechanistic pathways, viz. hydrogen atom transfer (HAT), single electron transfer (SET), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), have been considered. In addition, two other pathways, i.e. sequential double proton loss electron transfer (SdPLET) and sequential proton loss hydrogen atom transfer (SPLHAT), which are significant for the scavenging of reactive species by the mono-deprotonated forms of retrochalcones, have also been considered. All the calculations were performed using density functional theory at the B3LYP/6-311++G** level in the gas phase and in aqueous solution. The results suggest the predominance of the HAT mechanism in the gas phase, while in aqueous solution, the SPLET mechanism is thermodynamically favored. The possibility of SdPLET increases at higher pH.

Exploring structural requirements of isoform selective histone deacetylase inhibitors: a comparative in silico study.

Histone deacetylases (HDACs) are a widely popular class of epigenetic regulators, second only in importance to DNA methyltransferases. They are responsible for deacetylating the lysine residues of a wide range of proteins, both nuclear and cytoplasmic. Therefore, deregulated HDAC activity is implicated in disruption of important biological functions leading to cancerous, neuropathological, infectious and inflammatory diseased states. The current therapeutic strategies aimed at combating HDAC related pathologies consist of pan HDAC inhibitors that target multiple HDAC isoforms. Many side-effects of such therapeutics have been reported due to off-target effects. Hence, efforts need to be focused towards developing therapeutics targeting single isoforms. This work aims at recognizing structural features, both of receptors and inhibitors, that would help achieve selective inhibition of HDAC isoforms. Protein alignment studies have been carried out to define the receptor structure differences that can be exploited for this purpose. Binding modes of highly isoform selective inhibitors have been established through molecular docking studies to characterize the receptor-ligand interactions responsible for selective inhibition. This information is represented with the help of pharmacophore models.

Structure-based virtual screening, free energy of binding and molecular dynamics simulations to propose novel inhibitors of Mtb-MurB oxidoreductase enzyme.

Currently, the growing incidence of drug resistance toward tuberculosis intensified the need for discovery of novel targets and their inhibitors. The enzyme MurB which is involved in one of the steps for peptidoglycan biosynthesis is an effective target that can produce drugs having lesser side-effects. Recently the only crystal structure of Mycobacterium Tuberculosis MurB has been deposited and, therefore, in the present study, we have used this as a target for virtual screening of drug-like molecules from the ZINC Database. We have also designed a complete workflow for the process which resulted in 12 hit compounds that have good docking scores, ΔGbind, and Glide energy. The hits obtained have also been found to share structural features with some known antibiotics such as Amoxicillin. Furthermore, MD simulations on the top most hit L1 displayed its stable binding with the enzyme. Thus, this study has proved helpful in proposing novel inhibitors for MurB enzyme that can be tested against various TB strains.

The effect of solvent polarity on the antioxidant potential of echinatin, a retrochalcone, towards various ROS: a DFT thermodynamic study.

The antioxidant properties of echinatin (Ech), isolated from liquorice, have recently been reported. It is well known that the free radical species can be deactivated by phenolic antioxidants via different mechanistic pathways. In this work, the scavenging of eighteen different reactive oxygen species (ROS) has been considered, focussing on three main working mechanisms, namely hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). The investigations have been performed in different dielectric media, viz. gas phase, benzene, methanol and aqueous solution, using density functional theory (DFT) calculations at the M05-2X/6-311++G** level. Various molecular descriptors have been elucidated for Ech as well as the ROS and compared with the reference antioxidant molecule, trolox. In addition, the redox potentials and the equilibrium constants have been calculated to discuss the feasibility of the overall scavenging process. The results demonstrate that the 4-OH group is the first site for H-atom donation, followed by 4'-OH. Further, it has been found that HAT would be the most favourable mechanism in the gas phase. The SPLET mechanism is thermodynamically favoured in polar media like water and methanol, while in the case of non-polar solvents like benzene, the two mechanisms are observed to be competitive.

A DFT-D2 study on the adsorption of phosgene derivatives and chloromethyl chloroformate on pristine and Fe4-decorated graphene.

Phosgene derivatives and chloromethyl chloroformate are chlorinated organic compounds, which are toxic in nature and are used as chemical warfare agents and for the synthesis of other organic compounds. In this work, the different modes of adsorption of these toxic molecules on pristine graphene and Fe4-decorated graphene have been studied. It has been found that physisorption of these adsorbates occurs on pristine graphene, but when graphene is decorated with a Fe4-cluster, dissociative adsorption takes place and the adsorption energy and charge transfer increase. After Fe4-cluster decoration, the surface exhibits magnetic character and its band gap decreases. The magnetic properties of the surface, before and after adsorption, have been studied using density of states (DOS)/partial density of states (PDOS) and electron density difference plots and it is found that the band gap increases after adsorption of the adsorbates.

A comparative study of the binding modes of SLC-0111 and its analogues in the hCA II and hCA IX active sites using QM/MM, molecular docking, MM-GBSA and MD approaches.

Human carbonic anhydrase IX (hCA IX) is over-expressed in many tumor types and serves as an important target for the discovery of novel anticancer agents. However, development of compounds that can selectively inhibit hCA IX over its widespread cytosolic isoform human carbonic anhydrase II (hCA II) is a major challenge. This work focuses on recognizing the structural features of the hCA IX receptor that could help in achieving its selective inhibition. Tools such as protein structure alignment, rigid as well as flexible docking, QM/MM calculations and molecular dynamics simulations on SLC-0111, a selective hCA IX inhibitor, in complexation with each receptor, have been used to differentiate the receptor-ligand interactions in the two complexes. It is found that the ligand shows better binding to hCA IX due to stronger coordination to the Zn (II) ion. The ligand provides bidentate coordination through its negatively charged nitrogen and an oxygen of the sulfonamide zinc binding group. Binding energy calculations show that the potency of this ligand is due to the hydrophobic contacts, whereas the selectivity is due to the electrostatic interactions. Molecular docking and binding energy calculations for three different series of SLC-0111 analogs have identified a few molecules that show high potency and selectivity toward hCA IX. It is found that both hydrophobic and polar contacts contribute to the potency and selectivity of the ligands.

Pharmacophore-enabled virtual screening, molecular docking and molecular dynamics studies for identification of potent and selective histone deacetylase 8 inhibitors.

Histone deacetylases (HDACs) play important roles in various biological processes, but are also notorious for their over-expression in numerous cancers and neurological disorders. Therefore, the development of isoform selective HDAC inhibitors is crucial in order to prevent any side effects of pan inhibition. This work focuses on identifying novel inhibitors for the selective inhibition of HDAC8, an isoform implicated in fatal diseases like T-cell lymphoma, colon cancer and childhood neuroblastoma. Virtual screening of the 'In-trials' subset of ZINC database has been carried out with the help of two pharmacophore models signifying potent and selective HDAC8 inhibition. A detailed molecular docking strategy, followed by molecular dynamics simulations and post-scoring with MM-GBSA calculations, has led to the identification of six promising molecules that have excellent binding with the HDAC8 active site. In order to establish the selectivity profile of these molecules, their binding to off-target HDAC isoforms has also been evaluated. Substitution analyses of the proposed inhibitors suggest that aromatic substituents that access the adjacent hydrophobic pocket of the HDAC8 active site have the potential to further enhance the HDAC8 selectivity.

An insight into selective and potent inhibition of histone deacetylase 8 through induced-fit docking, pharmacophore modeling and QSAR studies.

Histone deacetylase 8 (HDAC8) has emerged as an important therapeutic target due to its involvement in various cancerous and neurodegenerative disease states. Since pan HDAC inhibition has been linked to various side effects, the need of the hour is to develop inhibitors truly selective for one isoform. This work attempts to explore the structural basis of selective HDAC8 inhibition by docking, pharmacophore and 3 D QSAR studies of 53 highly potent and highly selective triazol-based hydroxamic acid inhibitors. The binding modes of these novel inhibitors have been explored via Glide XP (Extra Precision) and induced-fit docking (IFD) strategies. The IFD poses of highly active and selective inhibitors showed conformational changes in active site residues like Trp141, Phe152 and Phe208, which were further verified by molecular dynamics simulations. A new CH-π interaction, which is atypical of HDAC inhibitors, was also observed in case of some highly selective inhibitors. Two pharmacophore models have been proposed; one highlights the structural basis of potency of these inhibitors and the other focuses on the selectivity. The corresponding QSAR models, obtained from alignment of the inhibitors as per the proposed pharmacophore models, are highly statistically significant. These models highlight the importance of size of the hydrophobic and aromatic groups present in the inhibitors and their contribution to activity of the inhibitors. The ADMET properties of the ligand library have also been analyzed and the predicted descriptors have been correlated with activity using principal components analysis to gain insight into the effect of pharmacokinetic properties on the activity.Communicated by Ramaswamy H. Sarma.

Multifunctional mesoporous curcumin encapsulated iron-phenanthroline nanocluster: A new Anti-HIV agent.

A new strategy to encapsulating the drug curcumin into the hydrophobic core of the iron-phenanthroline nanocomplex (NIP) and eventually its release is signified. NIP was prepared via coordinate interaction between Fe2+ and the lone pairs present on the N atoms of the bidentate phenanthroline ligand (spherical morphology, diameter 18.8 nm, mesoporous with pore size 2.443 nm, amorphous). Thereafter, curcumin was successfully encapsulated (NCIP) in NIP, resulting in its enhanced stability (spherical morphology, diameter 46.8 nm). The nanocomplex NIP was used for drug delivery applications. We evaluated the anti-HIV effects of NCIP in vitro on cultures of HIV infected human microglia. The treatment of HIV-1 infected microglia with NCIP significantly decreased the expression of HIV-p24 by 41% and pro-inflammatory mediators TNF-α, IL-8 and NO by 61.2%, 41% and 50.2%, respectively, compared to NIP. Flow cytometry data also support the decrease in TNF-α and IL-8 expression in case of NCIP. NCIP induced antioxidative effects by increasing the gene expression of catalase (CAT) and simulatenously decreasing hemeoxygenase-1 (HMOX-1) gene expression, thereby maintaining homeostasis which reduces neuroinflammation. These results support our premise that NCIP may be a significant adjuvant when used with traditional anti-retroviral regimens and may ameliorate HIV-1 associated neurotoxicity.

Arousing the Reactive Fe Sites in Pyrite (FeS2) via Integration of Electronic Structure Reconfiguration and in Situ Electrochemical Topotactic Transformation for Highly Efficient Oxygen Evolution Reaction.

Despite significant advances in the development of highly efficient and robust oxygen evolution reaction (OER) electrocatalysts to replace noble-metal catalysts, commercializing OER catalysts with high catalytic activity for sustainable development still remains a great challenge. Especially, transition-metal Fe-based OER catalysts, despite their earth-abundant, cost-efficient, and environmentally benign superiorities over Co- and Ni-based materials, have received relatively insufficient attention because of their poor apparent OER activities. Herein, by rational design, we report Ni-modified pyrite (FeS2) spheres with yolk-shell structure that could serve as pre-electrocatalyst precursors to induce a highly active nickel-iron oxyhydroxide via in situ electrochemical topological transformation under the OER process. Notably, as confirmed by the results of X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, and density functional theory (DFT) calculations, Ni doping could effectively regulate the intrinsic electronic structure of FeS2 to realize a semiconductor-to-semimetal transition, which endows FeS2 with dramatically improved conductivity and water adsorption ability, providing prequisites for subsequent topological transformation. Moreover, systematic post-characterizations further reveal that the optimal Ni-FeS2-0.5 sample completely converts to amorphous Ni-doped FeOOH via an in situ electrochemical transformation with yolk-shell structure well-preserved under the OER conditions. The electronic structure modulation combined with electrochemical topotactic transformation strategies well stimulate the reactive Fe sites in Ni-FeS2-0.5, which show impressively low overpotentials of 250 and 326 mV to drive the current densities ( j) of 10 and 100 mA cm-2, respectively, and a Tafel slope as small as 34 mV dec-1 for the OER process. When assembled as a water electrolyzer for the overall water splitting, Ni-FeS2-0.5 can display a low voltage of 1.55 V to drive a current density of 10 mA cm-2, outperforming most of the transition-metal-based bifunctional electrocatalysts to date. This work may provide new insight into the rational design of other high-performance Fe-based OER electrocatalysts and inspire the exploration of cost-effective, ecofriendly electrocatalysts to meet the demand for future sustainable development.

Isatin and its derivatives: a survey of recent syntheses, reactions, and applications.

Isatin (1H-indole-2,3-dione) and its derivatives represent an important class of heterocyclic compounds that can be used as precursors for drug synthesis. Since its discovery, a lot of research work has been done regarding the synthesis, chemical properties, and biological and industrial applications of isatin. In this review, we have reported several novel methods for the synthesis of N-, C2-, and C3-substituted and spiro derivatives of isatin. The isatin moiety also shows important chemical reactions such as oxidation, ring expansion, Friedel-Crafts reaction and aldol condensation. These reactions, in turn, produce several biologically viable compounds like 2-oxindoles, tryptanthrin, indirubins, and many more. We have also summarized some recently reported biological activities exhibited by isatin derivatives, like anti-cancer, anti-bacterial, anti-diabetic and others. Special attention has been paid to their anti-cancer activity, and various anti-cancer targets such as histone deacetylase, carbonic anhydrase, tyrosine kinase, and tubulin have been discussed in detail. Other applications of isatin derivatives, such as in the dye industry and in corrosion prevention, have also been discussed.

Identification of novel urease inhibitors: pharmacophore modeling, virtual screening and molecular docking studies.

Pharmacophore modeling and atom-based three-dimensional quantitative structure-activity relationship (3D-QSAR) have been developed on N-acylglycino- and hippurohydroxamic acid derivatives, which are known potential inhibitors of urease. This is followed by virtual screening and ADMET (absorption, distribution, metabolism, excretion and toxicity) studies on a large library of known drugs in order to get lead molecules as Helicobacter pylori urease inhibitors. A suitable three-featured pharmacophore model comprising one H-bond acceptor and two H-bond donor features (ADD.10) has been found to be the best QSAR model. An external library of compounds (∼3000 molecules), pre-filtered using Lipinski's rule of five, has been further screened using the pharmacophore model ADD.10. By analyzing the fitness of the hits with respect to the pharmacophore model and their binding interaction inside the urease active site, four molecules have been predicted to be extremely good urease inhibitors. Two of these have significant potential and should be taken up for further drug-designing process.

In Silico study of the active site of Helicobacter pylori urease and its inhibition by hydroxamic acids.

Hydroxamic acids have emerged as the most promising candidates from among the different classes of inhibitors of urease. In order to understand the mechanism of their action, we have studied in detail using quantum mechanics the active site of Helicobacter pylori urease complexed with acetohydroxamic acid. A diverse library of ligands having the hydroxamate moiety has been prepared and docked into the active site of urease using the QM/MM methodology. It is found that hydroxamic acids with hydrophobic groups attached to them are more potent inhibitors of urease because they can easily penetrate the hydrophobic environment surrounding the active site. The -CONHO- moiety of the hydroxamic acid is also found to be absolutely necessary for chelation and inhibition of urease. In order to determine the roles of residues His 221 and Ala 365, which are not part of the active site, but are nevertheless involved in hydrogen bonding with the ligand, we have performed Molecular Dynamics simulations, both on the wild urease and also on its mutated counterpart, with the two residues substituted, respectively, by alanine and glycine.

Nanocrystalline Hierarchical ZSM-5: An Efficient Catalyst for the Alkylation of Phenol with Cyclohexene.

In this paper, authors report the synthesis of nanocrystalline hierarchical zeolite ZSM-5 and its application as a heterogeneous catalyst in the alkylation of phenol with cyclohexene. The catalyst was synthesized by vacuum-concentration coupled hydrothermal technique in the presence of two templates. This synthetic route could successfully introduce pores of higher hierarchy in the zeolite ZSM-5 structure. Hierarchical ZSM-5 could catalyse effectively the industrially important reaction of cyclohexene with phenol. We ascribe the high efficiency of the catalyst to its conducive structural features such as nanoscale size, high surface area, presence of hierarchy of pores and existence of Lewis sites along with Brønsted acid sites. The effect of various reaction parameters like duration, catalyst amount, reactant mole ratio and temperature were assessed. Under optimum reaction conditions, the catalyst showed up to 65% selectivity towards the major product, cyclohexyl phenyl ether. There was no discernible decline in percent conversion or selectivity even when the catalyst was re-used for up to four runs. Kinetic studies were done through regression analysis and a mechanistic route based on LHHW model was suggested.