Molecular Analogues Research Articles

High-valent states in cobalt and nickel oxygen-evolving catalysts and their role in O—O bond formation

The solar-to-fuels conversion is a promising alternative to traditional energy sources such as fossil fuels, and the overall efficiency relies heavily on catalysts of the oxygen evolution half-reaction (i.e., 2H_2O → O_2 + 4H^+ + 4e^–). This four-electron, four-proton coupled reaction ultimately provides the reducing equivalents for solar fuels synthesis. Earth-abundant first-row transition metal oxides of cobalt, nickel, and their mixed-metal forms can drive this half-reaction at relatively low overpotentials. This presentation will discuss recent studies utilizing a combination of in situ and ex situ optical and X-ray spectroscopies, including resonant inelastic X-ray scattering, on oxygen-evolving thin films and their molecular and heterogeneous inorganic analogs. Experiment coupled with density functional theory calculations has provided insights into the electronic structures of the high-valent states involved in the mechanism of O–O bond formation.

Selective Electrochemical Oxidation of Lactic Acid Using Iridium-Based Catalysts

Catalysts that allow for selective oxidation of organic compounds in solution are useful tools in chemical synthesis, waste remediation, and renewable energy storage schemes. Of these, iridium oxide and iridium-based molecular compounds are frequently employed as catalysts to oxidize substrates ranging from small organic molecules to water. Here, we study the mechanism and evaluate the potential of iridium-based catalysts for small molecule oxidation in wastewater treatment, using lactic acid as a substrate. By investigating the reaction products, kinetic isotope effects, and electrochemical properties of iridium oxide and a molecular analogue on a high surface area antimony-doped tin oxide (ATO) support, we find evidence for a new iridium-catalyzed pathway for lactic acid oxidation. Applying this at concentrations representative of effluent from dairy production processes, we show that iridium oxide can selectively remove small amounts of lactic acid from water by oxidizing it to CO2 with concomitant cat...

Effect of the embedded atom on the electronic, optical properties and kinetic stability of [3,6]silaprismane

Using ab initio calculations it is found that endohedral complexes C@Si18H12, Si@Si18H12 and Ge@Si18H12 are less kinetically stable than pure [3,6]silaprismane Si18H12. Moreover, kinetic stability of Si18H12 is higher than the stability of its carbon molecular analogue C18H12. The height of the minimum energy barrier preventing the Si18H12 isomerization is found to be 1.09eV and its lifetime at room temperature will reach several hours that is acceptable not only for its immediate experimental observation but for the laboratory synthesis without using the extreme temperature conditions as well. It is also found that embedded atoms can significantly change the electronic properties of Si18H12 cage that is directly affect the optical characteristics of the systems considered. Thus, the doped Si18H12s can be experimentally divided from each other due to the changes in their optical spectra.

Perylene Diimide as a Precise Graphene-like Superoxide Dismutase Mimetic.

Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG–HCCs), will afford important insights into the highly efficient activity of PEG–HCCs and their graphitic analogues. PEGylated perylene diimides (PEGn–PDI) serve as well-defined molecular analogues of PEG–HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied. PEGn–PDIs have two reversible reduction peaks, which are more positive than the oxidation peak of superoxide (O2•–). This is similar to the reduction peak of the HCCs. Thus, as with PEG–HCCs, PEGn–PDIs are also strong single-electron oxidants of O2•–. Furthermore, reduced PEGn–PDI, PEGn–PDI•–, in the presence of protons, was shown to reduce O2•– to H2O2 to complete the catalytic cycle in this SOD analogue. The kinetics of the conversion of O2•– to O2 and H2O2 by PEG8–PDI was measured using freeze-trap EPR experiments to provide a turnover number of 133 s–1; the similarity in kinetics further supports that PEG8–PDI is a true SOD mimetic. Finally, PDIs can be used as catalysts in the electrochemical oxygen reduction reaction in water, which proceeds by a two-electron process with the production of H2O2, mimicking graphene oxide nanoparticles that are otherwise difficult to study spectroscopically.

Endogenous lysophosphatidic acid (LPA1 ) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts.

Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11 , Gi/o and G12/13 proteins. This promiscuity of coupling raises the possibility that some of the LPA analogues may bias the LPA1 receptor towards one signalling pathway over another. Here, we have explored the signalling profiles of a range of LPA analogues in HLF that endogenously express the LPA1 receptor. HLF were treated with LPA analogues and receptor activation monitored via calcium mobilization and ERK phosphorylation. These analyses demonstrated that the 16:0, 17:0, 18:2 and C18:1 LPA analogues appear to exhibit ligand bias between ERK phosphorylation and calcium mobilization when compared with 18:1 LPA, one of the most abundant forms of LPA that has been found in human plasma. The importance of LPA as a key signalling molecule is shown by its widespread occurrence in biological fluids and its association with disease conditions such as fibrosis and cancer. These findings have important, as yet unexplored, implications for the (patho-) physiological signalling of the LPA1 receptor, as it may be influenced not only by the concentration of endogenous ligand but the isoform as well.

Dicyanoaurate-based heterobimetallic uranyl coordination polymers.

The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers and molecular complexes has been synthesized. Reactions of [A][Au(CN)2] (A = [nBu4N]+ or [(Ph3P)2N]+ ([PPN])) and uranyl nitrate in alcoholic solvents in ambient light led to [A]2[(UO2)2(μ-η2:η2-O2)(NO3)2(μ-Au(CN)2)2], which incorporates peroxo ligands into a one-dimensional ladder topology with alternating aurophilic and peroxo rungs. Conducting the reaction with non-alcoholic solvents formed two polymorphs of a one-dimensional chain, [PPN][UO2(NO3)2Au(CN)2], from acetone, and a molecular analogue, [PPN]2[UO2(NO3)2(Au(CN)2)2], from acetonitrile, none of which exhibited aurophilic interactions. The addition of 2,2'-bipyridine to the initial reaction resulted in [UO2(bipy)(MeO)(MeOH)]2[(μ-Au(CN)2)(Au(CN)2)], a one-dimensional structure which propagates via a series of linear aurophilic bonds with pendant uranyl complexes; methanol and methoxy ligands provide additional connections through hydrogen bonding. The addition of 5,5'-dimethyl-2,2'-bipyridine using solvothermal conditions resulted in the one-dimensional ladder [UO2(Me2bipy)Au(CN)2]2[(μ-OH)2], generated through aurophilic bonds and hydroxide ligands. The incorporation of 2,2':6',2''-terpyridine (terpy) using solvothermal conditions resulted in [[UO2(terpy)]2(μ-NO3)(μ-O)][Au(CN)2], a molecular salt with no aurophilic interactions. Emission spectra attributable to aurophilic interactions are observed in [nBu4N]2[(UO2)2(μ-η2:η2-O2)(NO3)2(μ-Au(CN)2)2], while all others only show emission typical of the uranyl cation.

The Dynamics of Water in Porous Two-Dimensional Crystals

Porous two-dimensional crystals offer many promises for water desalination applications. For computer simulation to play a predictive role in this area, however, one needs to have reliable methods for simulating an atomistic system with hydrodynamic currents and interpretative tools to relate microscopic interactions to emergent macroscopic dynamical quantities, such as friction, slip length, and permeability. In this article, we use Gaussian dynamics, a nonequilibrium molecular dynamics method that provides microscopic insights into the interactions that control the flows of both simple liquids and liquid water through atomically small channels. In simulations of aqueous transport, we mimic the effect of changing the membrane chemical composition by adjusting the attractive strength of the van der Waals interactions between the membrane atoms and water. We find that the wetting contact angle, a common measure of a membrane's hydrophobicity, does not predict the permeability of a membrane. Instead, the hydrophobic effect is subtle, with both static and dynamic effects that can both help and hinder water transport through these materials. The competition between the static and dynamical hydrophobicity balances an atomic membrane's tendency to wet against hydrodynamic friction, and determines an optimal contact angle for water passage through nonpolar membranes. To a reasonable approximation, the optimal contact angle depends only on the aspect ratio of the pore. We also find that water molecules pass through the most hydrophobic membranes in a punctuated series of bursts that are separated by long pauses. A continuous-time Markov model of these data provides evidence of a molecular analogue to the clogging transition, a phenomenon observed in driven granular flows.

Insights into the Gelating Abilities of Ricinelaidic Acid and its Ammonium Salts: How do Stereochemistry, Charge, and Chain Lengths Control Gelation of a Long-Chain Alkenoic Acid?

The gelating abilities of ricinelaidic acid (d-REA), the trans-isomer of ricinoleic acid (d-RA), and a series of its alkylammonium and alkane-α,ω-diammonium salts have been examined in a wide range of organic liquids. The gelation efficiency of the trans acid is much better than that of the cis, although neither is as efficient as is the completely saturated molecular gelator analogue, (R)-12-hydroxystearic acid (d-12HSA). The formation of ammonium salts also improves the gelation ability of d-REA in high polarity liquids. The gelating properties are highly dependent upon the chain length of the alkyl group of the alkylammonium salts, but not very dependent on the chain length of the alkane-α,ω-diammonium salts. Structural insights from Fourier transform infrared spectroscopy and powder X-ray diffraction indicate that the absence or presence of unsaturation, the incorporation of (charged) ammonium centers, and the different chain lengths of the alkylammonium salts lead to different packing arrangements and different strengths of H-bonding interactions within the gel assemblies of the d-REA derivatives. Insights into the relationships among the various systematic structural changes to d-REA and the properties of their aggregated structures, including the gel states, are provided.

C-H Activation on Co,O Sites: Isolated Surface Sites versus Molecular Analogs.

The activation and conversion of hydrocarbons is one of the most important challenges in chemistry. Transition-metal ions (V, Cr, Fe, Co, etc.) isolated on silica surfaces are known to catalyze such processes. The mechanisms of these processes are currently unknown but are thought to involve C-H activation as the rate-determining step. Here, we synthesize well-defined Co(II) ions on a silica surface using a metal siloxide precursor followed by thermal treatment under vacuum at 500 °C. We show that these isolated Co(II) sites are catalysts for a number of hydrocarbon conversion reactions, such as the dehydrogenation of propane, the hydrogenation of propene, and the trimerization of terminal alkynes. We then investigate the mechanisms of these processes using kinetics, kinetic isotope effects, isotopic labeling experiments, parahydrogen induced polarization (PHIP) NMR, and comparison with a molecular analog. The data are consistent with all of these reactions occurring by a common mechanism, involving heterolytic C-H or H-H activation via a 1,2 addition across a Co-O bond.

Reductive Transformations of a Pyrazolate-Based Bioinspired Diiron-Dinitrosyl Complex.

Flavo-diiron nitric oxide reductases (FNORs) are a subclass of nonheme diiron proteins in pathogenic bacteria that reductively transform NO to N2O, thereby abrogating the nitrosative stress exerted by macrophages as part of the immune response. Understanding the mechanism and intermediates in the NO detoxification process might be crucial for the development of a more efficient treatment against these bacteria. However, low molecular weight models are still rare, and only in a few cases have their reductive transformations been thoroughly investigated. Here, we report on the development of two complexes, based on a new dinucleating pyrazolate/triazacyclononane hybrid ligand L-, which serve as model systems for nonheme diiron active sites. Their ferrous nitrile precursors [L{Fe(R'CN)}2(μ-OOCR)](X)2 (1) can be readily converted into the corresponding nitrosyl adducts ([L{Fe(NO)}2(μ-OOCR)](X)2, 2). Spectroscopic characterization shows close resemblance to nitrosylated nonheme diiron sites in proteins as well as previous low molecular weight analogues. Crystallographic characterization reveals an anti orientation of the two {Fe(NO)}7 (Enemark-Feltham notation) units. The nitrosyl adducts 2 can be (electro)chemically reduced by one electron, as shown by cyclic voltammetry and UV/vis spectroscopy, but without the formation of N2O. Instead, various spectroscopic techniques including stopped-flow IR spectroscopy indicated the rapid formation, within few seconds, of two well-defined products upon reduction of 2a (R = Me, X = ClO4). As shown by IR and Mössbauer spectroscopy as well as X-ray crystallographic characterization, the reduction products are a diiron tetranitrosyl complex ([L{Fe(NO)2}2](ClO4), 3a') and a diacetato-bridged ferrous complex [LFe2(μ-OAc)2](ClO4) (3a″). Especially 3a' parallels suggested products in the decay of nitrosylated methane monooxygenase hydroxylase (MMOH), for which N2O release is much less efficient than for FNORs.

Synthetic lung surfactants containing SP-B and SP-C peptides plus novel phospholipase-resistant lipids or glycerophospholipids.

BackgroundThis study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB) DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP)-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl-oleoyl phosphatidylglycerol (POPG), while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight). The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary) for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury.MethodsSurface activity of synthetic lipid/peptide surfactants was assessed in vitro at 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer. In vivo pulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance) in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO2 to <100 mmHg, consistent with clinical acute respiratory distress syndrome (ARDS).ResultsSynthetic surfactants containing 5:3:2 DPPC:POPC:POPG or 9:1 DEPN-8:PG-1 combined with 3% (by wt) of S-MB DATK, 3% SP-Css ion-lock 1, or 1.5% each of both peptides all adsorbed rapidly to low equilibrium surface tensions and also reduced surface tension to ≤1 mN/m under dynamic compression at 37 °C. However, dual-peptide surfactants containing 1.5% S-MB DATK + 1.5% SP-Css ion-lock 1 combined with 9:1 DEPN-8:PG-1 or 5:3:2 DPPC:POPC:POPG had the greatest in vivo activity in improving arterial oxygenation and dynamic lung compliance in ventilated animals with ARDS. Saline dispersions of these dual-peptide synthetic surfactants were also found to have shear viscosities comparable to or below those of current animal-derived surfactant drugs, supporting their potential ease of deliverability by instillation in future clinical applications.DiscussionOur findings support the potential of dual-peptide synthetic lipid/peptide surfactants containing S-MB DATK + SP-Css ion-lock 1 for treating diseases of surfactant deficiency or dysfunction. Moreover, phospholipase-resistant dual-peptide surfactants containing DEPN-8/PG-1 may have particular applications in treating direct forms of ARDS where endogenous phospholipases are present in the lungs.

Discrimination of Axial and Central Stereogenic Elements in Chiral Bis(oxazolines) Based on Atropisomeric 3,3'-Bithiophene Scaffolds Through Chiroptical Spectroscopies.

Two diastereoisomeric pairs of bis-oxazolines, provided with a stereogenic center at carbon 4 and based on the 3,3'-bithiophene atropisomeric scaffold, were synthesized and structurally characterized. They differ in the substituents at positions 2 and 5 of the thiophene rings, which are functionalized with methyl (1) or phenyl (2) groups, respectively. In vibrational circular dichroism (VCD) spectra, recorded in CCl4 solutions, it is possible to distinctly recognize the characteristic features of axial and central stereogenic elements. In tandem with Density Functional Theory (DFT) calculations, the absolute configuration (AC) of the diastereoisomers was safely established. In this case, VCD was shown to be superior to ECD (electronic circular dichroism) in the assignment of AC. The normal modes, evaluated from DFT calculations, show that the VCD signals in correspondence with the stereogenic axis of the bithiophene unit are different for 1 and 2. The VCD spectra of a molecular analog of 1, the (S)-2,2',5,5'-tetramethyl-4,4'-bis-(diphenylphosphino)-3,3'-bithiophene oxide (3), characterized by the same 3,3'-bithiophene scaffold, but devoid of stereogenic centers, exhibits signals similar to those observed in the case of diastereoisomer (aS,R,R)-1a, associated with almost identical normal modes. Chirality 28:686-695, 2016. © 2016 Wiley Periodicals, Inc.

Double differential cross sections for proton induced electron emission from molecular analogues of DNA constituents for energies in the Bragg peak region.

For track structure simulations in the Bragg peak region, measured electron emission cross sections of DNA constituents are required as input for developing parameterized model functions representing the scattering probabilities. In the present work, double differential cross sections were measured for the electron emission from vapor-phase pyrimidine, tetrahydrofuran, and trimethyl phosphate that are structural analogues to the base, the sugar, and the phosphate residue of the DNA, respectively. The range of proton energies was from 75 keV to 135 keV, the angles ranged from 15° to 135°, and the electron energies were measured from 10 eV to 200 eV. Single differential and total electron emission cross sections are derived by integration over angle and electron energy and compared to the semi-empirical Hansen-Kocbach-Stolterfoht (HKS) model and a quantum mechanical calculation employing the first Born approximation with corrected boundary conditions (CB1). The CB1 provides the best prediction of double and single differential cross section, while total cross sections can be fitted with semi-empirical models. The cross sections of the three samples are proportional to their total number of valence electrons.

Antimutagenic systems based on chitosan conjugates with plant antioxidants

It was shown using various methods that the radical scavenging and radical scavenging activities of chitosan conjugates with phenolic antioxidants of plant origin significantly exceed the corresponding values of their low molecular weight analogs (gallic and syringic acids, quercetin and dihydroquercetin). Cytogenetic analysis of human peripheral blood lymphocytes demonstrated that the conjugates showed pronounced antimutagenic efficiency when the cells were γ-irradiated in vitro at a dose of 2 Gy.

(Invited) Molecular Hydrogen-Evolution Electrocatalysts for Dye-Sensitized Solar Fuels

Proton reduction is one of the most fundamental and important reactions in nature. MoS2 edges have been identified as the active sites for hydrogen evolution reaction (HER) electrocatalysis. Designing molecular mimics of MoS2 edge sites is an attractive strategy to understand the underlying catalytic mechanism of different edge sites and improve their activities. Herein I will discuss our recent progress in this aspect. The first example is a dimeric molecular analog [Mo2S12]2-, as the smallest unit possessing both the terminal and bridging disulfide ligands. Our electrochemical tests show that [Mo2S12]2- is a superior heterogeneous HER catalyst under acidic conditions. Computations suggest that the bridging disulfide ligand of [Mo2S12]2- exhibits a hydrogen adsorption free energy near zero (-0.05 eV). The second example is a group of compounds with the general formular of MoO(S2)2bpy. By varying substitution on the bpy ligand, we demonstrate the induction effect on the S—S ligand, thereby tuning the rate constants for HER and overpotentials. We have studied homogenous electrocatalytic hydrogen production performance metrics of three catalysts with different bipyridine substitutions. By varying the electron-donating abilities, we present the first demonstration of using the ligand to tune catalytic properties of the S—S bond in molecular MoS2 edge site mimics. These works can shed light on the relationship between structure and electrocatalytic activity of molecular MoS2 catalysts and thus is of broad importance from catalytic hydrogen production to biological enzyme functions. Lastly, I will discuss how to integrate the molecular catalysts into dye-sensitized photoeletrochemical platforms for solar hydrogen production.

Imatinib alters cell viability but not growth factors levels in TM4 Sertoli cells

The anticancer agent imatinib (IM) is a small molecular analog of ATP that inhibits tyrosine kinase activity of platelet derived growth factors (PDGFs) and stem cell factor (SCF) receptor in cancer cells. However these factors have a key role in regulating growth and development of normal Sertoli, Leydig and germ cells. The aim of this study was to determine cell viability, PDGF and SCF levels in mouse normal Sertoli cells exposed to IM. In this experimental study, the mouse TM4 Sertoli cells were treated with 0, 2.5, 5, 10 and 20 μM IM for 2, 4 or 6 days. The cell viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, One-Way ANOVA was performed. IM showed significant decrease in Sertoli cell viability compared to control group (p=0.001). However, IM increased PDGF and SCF level insignificantly (p>0.05). Results suggested that IM treatment induced a dose dependent reduction of cell viability in Sertoli cells. It seems that treatment with this anticancer drug is involved in the fertility process. Further studies are needed to evaluate the role of PDGF and SCF in this cell.

Anion-Controlled Positional Switching of a Phenyl Group about the Dinuclear Core of a AuSb Complex.

As part of our continuing interest in redox-active, anion-responsive main-group transition-metal platforms, we have investigated the effect of chloride by fluoride anion substitution on the core structure of a dinuclear AuSb platform. Starting from [(o-(iPr2P)C6H4)2Cl2SbPh]AuCl (2) in which the antimony-bound phenyl group is positioned trans to the gold atom, we found that the introduction of fluoride anions, as in [(o-(iPr2P)C6H4)2F2SbPh]AuCl (3) and [(o-(iPr2P)C6H4)2ClFSbPh]AuCl (4), produces structures in which the phenyl group switches to a perpendicular direction with respect to the gold atom. Replacement of the gold-bound chloride anion in 3 by a fluoride anion can be achieved by successive treatment with TlPF6 and [nBu4N][Ph3SiF2]. These reactions, which proceed via the intermediate zwitterionc gold antimonate complex [o-(iPr2P)C6H4)2F3SbPh]Au (6), trigger migration of the phenyl group to gold and afford [(o-(iPr2P)C6H4)2F3Sb]AuPh (7). Because the phenyl group in 7 is orthogonal to that in 3 and opposite to that in 2, the title AuSb platform can be regarded as a molecular analogue of a mechanical three-way switch in which the switching element is a phenyl group. Finally, while all complexes involved retain a Au → Sb interaction, this interaction is no longer present in the zwitterionic derivative 6 because of the neutralization of the Lewis acidity of the antimony center.

Computational Method for the Systematic Identification of Analog Series and Key Compounds Representing Series and Their Biological Activity Profiles.

A computational methodology is introduced for detecting all unique series of analogs in large compound data sets, regardless of chemical relationships between analogs. No prior knowledge of core structures or R-groups is required, which are automatically determined. The approach is based upon the generation of retrosynthetic matched molecular pairs and analog networks from which distinct series are isolated. The methodology was applied to systematically extract more than 17 000 distinct series from the ChEMBL database. For comparison, analog series were also isolated from screening compounds and drugs. Known biological activities were mapped to series from ChEMBL, and in more than 13 000 of these series, key compounds were identified that represented substitution sites of all analogs within a series and its complete activity profile. The analog series, key compounds, and activity profiles are made freely available as a resource for medicinal chemistry applications.

Tuning Gold Nanoparticle Aggregation through the Inhibition of Acid Phosphatase Bioactivity: A Plasmonic Sensor for Light-Up Visual Detection of Arsenate (AsV ).

A plasmonic biosensor for arsenate has been developed which uses gold nanoparticles (AuNPs) as the signal reporter and in which the biocatalytic activity of acid phosphatase (AcP) is modified by the target ion. The enzyme catalyzes the hydrolysis of negatively charged adenosine 5'-monophosphate (AMP) to neutral adenosine, causing appreciable aggregation of AuNPs and then visible color change of the solution from red to blue. The presence of arsenate (AsV ), as a molecular analogue of phosphate, can effectively interfere with the bioactivity of AcP by competitive inhibition, and so the hydrolysis process is slowed down. This is reflected by the change in the solution color from blue to red with increasing concentrations of AsV . In contrast to AuNP-based sensors for arsenic (basically AsIII ) that employ the strong interaction between AsIII -specific molecules and AsIII , this sensor adopts a different sensing principle and is the first visible sensor for specifically AsV specifically using AuNPs. Finally the practical assay of AsV in groundwater and lake water was performed with satisfactory results, suggesting this approach can be used for quantification of AsV levels in real water samples.

Homology model, molecular dynamics simulation and novel pyrazole analogs design of Candida albicans CYP450 lanosterol 14 α-demethylase, a target enzyme for antifungal therapy

Candida albicans infections and their resistance to clinically approved azole drugs are major concerns for human. The azole antifungal drugs inhibit the ergosterol synthesis by targeting lanosterol 14α-demethylase of cytochrome P450 family. The lack of high-resolution structural information of fungal pathogens has been a barrier for the design of modified azole drugs. Thus, a preliminary theoretical molecular dynamic study is carried out to develop and validate a simple homologous model using crystallographic structure of the lanosterol 14α-demethylase of Mycobacterium tuberculosis (PDB ID-1EA1) in which the active site residues are substituted with that of C. albicans (taxid 5476). Further, novel designed pyrazole analogs (SGS1-16) docked on chimeric 1EA1 and revealed that SGS-16 show good binding affinity through non-bonding interaction with the heme, which is different from the leading azole antifungals. The ADME-T results showed these analogs can be further explored in design of more safe and effective antifungal agents.