Molecular Modeling Calculations Research Articles

Capacitive Detection of Morphine via Cathodically Electropolymerized, Molecularly Imprinted Poly(p‐aminostyrene) Films

Highly sensitive and selective detection of morphine is exhibited using a capacitive transducer coated with cathodically electropolymerized and molecularly imprinted poly(p aminostyrene). Through molecular imprinting, morphine‐specific recognition sites have been fabricated throughout the film, which shows exceptional binding activity toward morphine based from electrochemical capacitance measurements. The thin film sensor has a linear response to morphine solutions with 20–40 × 10−6 m concentrations and a detection limit of 5.95 × 10−6 m. It demonstrates high selectivity toward morphine as compared to other analog molecules including nicotine and cholesterol. The formation of the polymer film is facilitated and monitored using electrochemical‐quartz crystal microbalance and characterized by X‐ray photoelectron spectroscopy. Infrared spectroscopy confirms the loading and removal of the analyte from the film. Based on molecular modeling calculations, strong hydrogen‐bonding interactions between the monomer, cross‐linker, and analyte form a stable pre‐polymerization complex, which is critical in successfully imprinting morphine into the film and effective sensing of the analyte. image

Synthesis and Characterization of Cu(I)-Folic Acid Complex A Theoretical and Experimental Study

Copper (I) complex containing folic acid ligand was prepared and characterized on the basis of metal analyses, UV-VIS, FTIR spectroscopies and magnetic susceptibility. The density functional theory (DFT) as molecular modeling calculations was used to determine the donor atoms of folic acid ligand which appear clearly at oxygen atoms binding to hydrogen. Detection of donation sights is supported by theoretical parameters such as geometry, mulliken population, mulliken charge and HOMO-LUMO gap obtained by DFT calculations.

Optically Active Porphyrin and Phthalocyanine Systems.

This review highlights and summarizes various optically active porphyrin and phthalocyanine molecules prepared using a wide range of structural modification methods to improve the design of novel structures and their applications. The induced chirality of some illustrative achiral bis-porphyrins with a chiral guest molecule is introduced because these systems are ideal for the identification and separation of chiral biologically active substrates. In addition, the relationship between CD signal and the absolute configuration of the molecule is analyzed through an analysis of the results of molecular modeling calculations. Possible future research directions are also discussed.

Protein Structural Analysis of Calbindin D28k Function and Dysregulation: Potential Competition Between Ca2+ and Zn2+

Calcium homeostasis is an essential physiological process requiring tight control in the normal cell. The dysregulation of calcium homeostasis may play a key role in the onset of Alzheimer's disease (AD) and other disorders, whether through the loss of calcium binding or calcium sensing capacity. Calbindin D28k (CB-D28k), a calcium binding protein composed of six EF-hands, four of which can bind Ca(2+), has been implicated in AD-related calcium dysregulation. In this study, docking and molecular dynamics calculations were employed to refine the protein data base model in order to understand the underlying structural variations between functional and non-functional EF-hands. Molecular modeling calculations improved the modelled protein structure: helix-loop-helix sequences were formed in all hands and most canonical interactions were formed in the four functional hands. The protein can also bind Zn(2+), potentially altering the Ca(2+) binding capability. Analysis of calculated structures of Zn(2+) bound protein showed that only half of the correct EF-hand canonical interactions of Ca(2+) were formed with loop residues. These results have important implications for the understanding of calcium dysregulation as well as for the development of novel therapeutic strategies in AD and other central nervous system disease processes, or in conditions of brain injury where calcium homeostasis is compromised.

Di- and Tri-valent Metal Ions Interactions with Four Biodegradable Hydroxamate and Cataecholate Siderophores: New Insights into Their Complexation Equilibria

The interaction of a number of divalent and trivalent metal ions [iron(III), chromium(III) copper(II), cobalt(II) and nickel(II)] with four isolated and purified microbial catecholate and hydroxamate siderophores was studied using the pH-potentiometric technique to investigate the complexation behavior of these systems as these systems could mimic many biological interactions of the siderophore chelating agent. The protonation constants of these new siderophore analogues as well their binary complex species stability constants were determined using the Hyperquad 2008 estimation model program. From the determined stability constants of the metal complex species, the concentration distribution of the various metal ion complex species involving isolated siderophore analogues in solutions was estimated using the HySS 2009 modeling program. The complex species distribution diagrams were plotted and discussed. Additionally, the Gibbs energies and the molecular structures of the formed complex species were evaluated and predicted using Gaussian 09 software for molecular modeling and density functional theory calculations.

Effect of Isotacticity of Linear Poly(N-isopropylacrylamide) on its Gelation in Benzyl Alcohol

Thermoreversible gelation of three different isotactic linear poly(N-isopropylacrylamide) (PNIPAM)s having meso dyad (m) values 62, 68 and 81% has been observed in benzyl alcohol. All the gels were transparent in nature. SEM image of the dried gels showed fibrillar network morphology. Melting temperature of the gels gradually increased with the increase in the concentration. XRD data of dry polymers and their corresponding dry gels showed shifting in the peak positions. Rheological study showed that stronger gels were formed with increasing isotacticity of PNIPAM while lower isotactic sample exhibited typical polymer melt rheology. The formation of a plunge in the storage modulus as well as in the viscosity plot at the same frequency range indicates the reversible nature of the structure breaking/reformation under frequency sweep. Moreover, the mechanical strength of the gel decreased with increase in temperature. UV-Vis kinetic study also indicated the change in the conformation and aggregation of PNIPAM chains during gelation. Molecular modelling calculation showed that the number of solvent molecules involved in forming gel (polymer-solvent compound) decreased with the increase in the isotacticity of the polymer. Gelation rate of these gels was studied as a function of temperature, concentration and isotacticity using test-tube tilting method. It increased with the increase in the concentration and isoacticity of the polymer, and with the decrease in the temperature. Critical gelation concentration of the gel gradually increased with the decrease in the isotacticity and with the increase in the temperature. All these experimental results indicated that gelation occurs presumably through polymer-solvent compound formation. Thermoreversible gelation of different isotactic [meso diad (m) = 62, 68 and 81%] linear poly(N-isopropylacrylamide) (PNIPAM)s has been observed in benzyl alcohol. Gelation rate depends on temperature, concentration, and isotacticity of PNIPAM. SEM, XRD, rheology and UV-Vis studies, and molecular modelling support its formation presumably via polymer-solvent compound formation.

Electrospun formulations of acyclovir, ciprofloxacin and cyanocobalamin for ocular drug delivery

Two series of fibers containing the active ingredients acyclovir, ciprofloxacin and cyanocobalamin, and combinations of these drugs, were prepared by electrospinning. One set used the hydrophilic poly(vinylpyrrolidone) (PVP) as the filament-forming polymer, while the other used the slow-dissolving poly(ε-caprolactone) (PCL). The fibers were found to have cylindrical morphologies, although there was evidence for solvent occlusion with the PVP systems and for some drug particles in the PCL materials. The active ingredients were generally present in the amorphous physical form in the case of PVP, but evidence of crystallinity was observed with PCL. The existence of intermolecular interactions between the drugs and polymers was proven using simple molecular modeling calculations. Drug release from the various fibers was tested in a validated in vitro outflow model of the eye, and the fiber formulations found to be capable of extending drug release. We thus conclude that electrospun matrices such as those prepared in this work have potential for use as intravitreal implants.

Indicator displacement assay for cholesterol electrochemical sensing using a calix[6]arene functionalized graphene-modified electrode.

A novel electrochemical method has been developed towards cholesterol detection based on competitive host-guest interaction by selecting methylene blue (MB) and calix[6]arene functionalized graphene (CX6-Gra) as the "reporter pair". In the presence of cholesterol, the MB molecules are displaced by cholesterol in the CX6-Gra.MB complex, leading to a "switch off" electrochemical response. A linear response range of 0.50 to 50.00 μM for cholesterol with a low detection limit of 0.20 μM (S/N = 3) was obtained by using the proposed method. This method could be successfully utilized to detect cholesterol in serum samples, and may be expanded to the analysis of other non-electroactive species. Besides, the host-guest interaction between cholesterol and CX6 was studied by molecular modeling calculations, which revealed that the complexation could reduce the energy of the system and the complex of a 1 : 1 host-guest stoichiometry had the lowest binding free energy of -8.01 kcal mol(-1). In addition, the constructed electrochemical sensing platform is important as it does not use any enzyme or antibody for the detection of cholesterol efficiently and selectively over common interfering species.

Design of a New Molecularly Imprinted Polymer Selective for Hydrochlorothiazide Based on Theoretical Predictions Using Gibbs Free Energy

A molecularly imprinted polymer (MIP) for the diuretic drug hydrochlorothiazide (HCTZ) based on theoretical predictions was developed. Molecular modeling calculations were performed to study the intermolecular interactions in the pre-polymerization mixture and to select a suitable functional monomer and a porogenic solvent for the synthesis of the MIP. To confirm the results of the theoretical predictions, three MIPs were synthesized and evaluated using the equilibrium batch rebinding method. A water-compatible MIP was prepared using HCTZ as the template and acrylamide as the functional monomer (FM) with ethylene glycol dimethacrylate as the cross-linker and tetrahydrofuran as the porogen. An imprinting factor of 8.24 was obtained. The polymer was characterized by Fourier transform infrared (FTIR), solid-state nuclear magnetic resonance, scanning electron microscopy, thermogravimetric analysis and nitrogen sorption porosimetry. In addition to HCTZ, six structurally related compounds were tested to evaluate the selectivity of the HCTZ-MIP, and cross-selectivity of the MIP was verified.

Synthesis and Characterization of Cu(I)-Folic Acid Complex A Theoretical and Experimental Study

Copper (I) complex containing folic acid ligand was prepared and characterized on the basis of metal analyses, UV-VIS, FTIR spectroscopies and magnetic susceptibility. The density functional theory (DFT) as molecular modeling calculations was used to determine the donor atoms of folic acid ligand which appear clearly at oxygen atoms binding to hydrogen. Detection of donation sights is supported by theoretical parameters such as geometry, mulliken population, mulliken charge and HOMO-LUMO gap obtained by DFT calculations.

Brazoides A-D, New Alkaloids from Justicia gendarussa Burm. F. Species

Four new alkaloids, Brazoides A-D, together with three known compounds squalene, β-sitosterol and lupeol, were isolated from leaves of Justicia gendarussa. These structures were established by spectrometric techniques, mainly high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR), including comparative analysis with literature values. Structural determination of the compounds, Brazoides A-D, was strengthened by molecular modeling and density functional theory (DFT) calculations to predict the NMR data and compare with the experimental NMR values of these natural products. The new compounds were tested against three human cancer cell lines (glioblastoma, prostate and colon), but none exhibited activity.

Molecular modeling and docking calculations of 4-acyloxy-biphenyl-4′-N-butylcarbamates as potential inhibitors of human butyrylcholinesterase

The kinetic studies and drug designs of butyrylcholinesterase play an important role in the development of Alzheimer’s disease therapeutics. In this research, automated docking studies were performed to provide useful insights into butyrylcholinesterase inhibition binding modes with designed 4-acyloxy-biphenyl-4′-N-butylcarbamates (compounds 1–8). Moreover, several significant linear correlations between experimental and calculated docking results are observed. Among compounds 1–7, compound 3, which exhibits the strongest hydrophobicity and has four carbonyl hydrogen bindings, shows the highest binding affinity (Ki = 1.4 μmol/L) with a binding energy of −7.99 kcal/mol. The observed linear correlation of experimental and calculated inhibition constants (Ki) indicates that the molecular docking results are reliable. Moreover, a good linear correlation is observed between calculated binding energies and experimental pKi. The experimental Hansch hydrophobicity constants (π values) are also correlated with the docked binding energy. This study reveals important correlations between butyrylcholinesterase experimental and docking results that contribute to the kinetic based identification of antagonists for the treatment of Alzheimer’s disease. Furthermore, these docked models provide important insights into a potential series of 4,4′-biphenol-based inhibitors of butyrylcholinesterase.

Assignment of the absolute configuration at stereogenic phosphorus atoms in P-diastereomers of dithymidyl-(N3′→P5′)-phosphoramidothioate

P-diastereomers of dithymidyl-(N3′→P5′)-phosphoramidothioate (TNPST) were synthesized by condensation of chromatographically separated P-diastereomers of 5′-O-DMT-2′,3′-dideoxythymidine-3′-N-(2-thio-4,4-dimethyl-1,3,2-oxathiaphospholanes) (OTP derivatives, assigned as fast and slow-eluting diastereoisomers) with 3′-O-acetylthymidine. The resulting (TNPST) dimers were transformed into S-methyl derivatives by a standard treatment with methyl iodide in a pyridine/acetonitrile solution. The absolute configuration at phosphorus atoms of each S-methylated diastereoisomer was assigned by the analysis of the 2D NMR ROESY cross-peaks, analogously to the approach already published for 2′-deoxyribonucleoside methylphosphonamidates NNPMeN. To the TNPST dimers originating from the fast- and slow-OTP substrate the SP and RP absolute configurations were assigned, respectively. The obtained NMR results are well supported by molecular modeling calculations.

Rearranged Diterpenes and Norditerpenes from Three Australian Goniobranchus Mollusks.

Three new norditerpenes (1, 6, and 7) and four diterpenes (2-5) with extensively rearranged carbon skeletons have been characterized from Australian nudibranchs. The relative configuration of the cyclopropyl-containing verrielactone (1) from Goniobranchus verrieri was suggested by spectroscopic analysis at 500 MHz informed by a combination of molecular modeling and DFT calculations. The nudibranchs G. splendidus and G. cf. splendidus provided 2-7, for which the structures and stereochemistry were deduced by 2D NMR studies at either 500 or 700 MHz. Each of the seven terpenoids exhibited a carbon skeleton modified from one of the tetrahydroaplysulphurin, spongionellin, or gracilane series of terpenes. A biosynthetic pathway to terpenes 1-7 from spongialactone is proposed.

Structural Correspondence of the Oriented Attachment Growth Mechanism of Crystals of the Pharmaceutical Dirithromycin.

The oriented attachment (OA) mechanism is promising for designing novel nanomaterials, yet an intensive understanding of the relationship between the crystal structure and attachment orientation is still lacking. In this work, we report layered hexagonal crystals of the pharmaceutical dirithromycin (DIR) containing multiple layers fabricated via a solvothermal method for a certain period of time at 40 °C. These elongated hexagonal crystals experience an OA that is preferentially on the face (001) of the initial crystals to assemble the final crystals into layered stacks. Through agreement with molecular modeling calculations, we predicted the final crystal growth morphology and confirmed the favored attachment surface based on the energy change ΔE following an OA event. These simulation results at the molecular level yielded good agreement with the crystal growth experiments. This study demonstrates the critical importance of combining experiments with a computational approach to understand the intrinsic molecular details of the OA growth mechanism of other compounds and to design nanomaterials with a desirable morphology and physical and chemical properties.

Spectral, thermal, molecular modeling and biological studies on mono- and binuclear complexes derived from oxalo bis(2,3-butanedionehydrazone)

BackgroundHydrazones and their metal complexes were heavily studied due to their pharmacological applications such as antimicrobial, anticonvulsant analgesic, anti-inflammatory and anti-cancer agents. This work aims to synthesize and characterize novel complexes of VO2+, Co2+, Ni2+, Cu2+, Zn2+, Zr4+and Pd2+ ions with oxalo bis(2,3-butanedione-hydrazone). Single crystals of the ligand have been grown and analyzed.ResultsOxalo bis(2,3-butanedionehydrazone) [OBH] has a monoclinic crystal with P 1 21/n 1 space group. The VO2+, Co2+, Ni2+, Cu2+, Zn2+, Zr4+ and Pd2+ complexes have the formulas: [VO(OBH–H)2]·H2O, [Co(OBH)2Cl]Cl·½EtOH, [Ni2(OBH)Cl4]·H2O·EtOH, [Cu(OBH)2Cl2]·2H2O, [Zn(OBH–H)2], [Zr(OBH)Cl4]·2H2O, and [Pd2(OBH)(H2O)2Cl4]·2H2O. All complexes are nonelectrolytes except [Co(OBH)2Cl]Cl·½EtOH. OBH ligates as: neutral tetradentate (NNOO) in the Ni2+ and Pd2+ complexes; neutral bidentate (OO) in [Co(OBH)2Cl]Cl·½EtOH, [Zr(OBH)Cl4]·2H2O and [Cu(OBH)2Cl2]·2H2O and monobasic bidentate (OO) in the Zn2+ and VO2+ complexes. The NMR (1H and 13C) spectra support these data. The results proved a tetrahedral for the Zn2+ complex; square-planar for Pd2+; mixed stereochemistry for Ni2+; square-pyramid for Co2+ and VO2+ and octahedral for Cu2+ and Zr4+ complexes. The TGA revealed the outer and inner solvents as well as the residual part. The molecular modeling of [Ni2(OBH)Cl4]·H2O·EtOH and [Co(OBH)2Cl]Cl·½EtOH are drawn and their molecular parameters proved that the presence of two metals stabilized the complex more than the mono metal. The complexes have variable activities against some bacteria and fungi. [Zr(OBH)Cl4]·2H2O has the highest activity. [Co(OBH)2Cl]Cl·½EtOH has more activity against Fusarium.ConclusionOxalo bis(2,3-butanedionehydrazone) structure was proved by X-ray crystallography. It coordinates with some transition metal ions as neutral bidentate; mononegative bidentate and neutral tetradentate. The complexes have tetrahedral, square-planar and/or octahedral structures. The VO2+ and Co2+ complexes have square-pyramid structure. [Cu(OBH)2Cl2]·2H2O and [Ni2(OBH)Cl4]·H2O·EtOH decomposed to their oxides while [VO(OBH–H)2]·H2O to vanadium. The energies obtained from molecular modeling calculation for [Ni2(OBH)Cl4]·H2O·EtOH are less than those for [Co(OBH)2Cl]Cl·½EtOH indicating the two metals stabilized the complex more than mono metal. The Co(II) complex is polar molecule while the Ni(II) is non-polar.Graphical abstractElectronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0135-y) contains supplementary material, which is available to authorized users.

Intermediate mass fragment emission in 32S + 51V, 109Ag, and 238U collisions at E = 31.6 MeV A

Intermediate mass fragment emission for reactions of $^{32}\text{S} +\,^{51}\text{V},\,^{109}$Ag, and $^{238}\text{U}$ has been studied. Double differential cross sections were analysed in terms of the generalised moving source model yielding charge distributions. Isotope ratios show strong fragment mass dependencies. The data were successfully reproduced by the coalescence model as well as by statistical multifragmentation model calculations. Quantum molecular dynamics model calculations were not so successful.

Studies Of The Interaction Of Bovine Serum Albumin With Pyrimidine-annulated Spiro-dihydrofuran And Its Biological Activities

The interaction between pyrimidine-annulated spiro-dihydrofuran (PSDF) with bovine serum albumin (BSA) was investigated following spectroscopic studies. The results indicate that dynamic quenching contributes to the fluorescence quenching of BSA by PSDF. The binding constant (K) and the number of binding sites (n) were calculated from the recorded spectra. Based on the Forster's non-radiative energy transfer theory, the average binding distance between BSA and PSDF was estimated. The synchronous fluorescence spectra and circular dichroism indicate that the conformation of BSA has been subjected to alteration in presence of PSDF. The thermodynamic parameters namely ΔH, ΔG, ΔS were calculated at different temperatures (20 o C, 30 o C, and 40 o C) and the results indicated van der Waals force and hydrogen bonding were predominantly present. The compound PSDF also found to exhibit antifungal activity against Aspergillus sp. In addition, the results obtained from molecular modeling calculation vividly elucidate the binding mode and the binding sites and results were not well in agreement with the experimental observations. Copyright © 2015 VBRI Press.

Novel water-soluble fisetin/cyclodextrins inclusion complexes: Preparation, characterization, molecular docking and bioavailability

Novel water-soluble inclusion complexes for fisetin (FIT) were developed by introducing β-cyclodextrin (β-CD) and γ-CD. Properties of the obtained complexes, as well as the interactions between each component, were systematically investigated in both solution and solid states by means of ESI-MS, NMR, FT-IR, XRD, DSC, SEM etc. All characterization information demonstrated that FIT/CDs inclusion complexes were formed, and exhibited different spectroscopic features and properties from FIT. A complex with 1:1 stoichiometry of FIT and CDs was confirmed with Job's method. Meanwhile, as supported by molecular modeling calculations, we suggested that phenyl group (C ring) of FIT molecule was included in the CDs cavity from the wide side. Moreover, the water solubility of FIT/CDs was successfully improved from 2.8 mg/mL (in ethanol aqueous solution) to 4.5 mg/mL (FIT/β-CD complex) and 7.8 mg/mL (FIT/γ-CD complex), and higher thermal stability results were shown by thermal analysis for those complexes. Notably, the inclusion complexes displayed almost two times higher cytotoxicity compared to free FIT against Hela and MCF-7 cells. These results suggested that FIT/CDs complexes could be potentially useful in food industry and healthcare area.

Multifragmentation of nearly symmetric and asymmetric reactions within a dynamical model

We make an extensive study of the fragmentation pattern for various asymmetric reactions using isospin-dependent quantum molecular dynamics model and confront our theoretical calculations with the available experimental data. A comparison with various other models is also presented. Our detailed analysis reveals that isospin-dependent quantum molecular dynamics model calculations nicely reproduce the measurements of asymmetric reactions around Fermi energies, whereas deviation can be seen at extreme lower as well as at higher incident energies.