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The enzyme catechol-O-methyltransferase (COMT) has water soluble (S-COMT) and membrane associated (MB-COMT), bitopic, isoforms. Of these MB-COMT is a drug target in relation to the treatment of Parkinson's disease. Using a combination of computational and experimental protocols, we have determined the substrate selection mechanism specific to MB-COMT. We show: (1) substrates with preferred affinity for MB-COMT over S-COMT orient in the membrane in a fashion conducive to catalysis from the membrane surface and (2) binding of COMT to its cofactor ADOMET induces conformational change that drives the catalytic surface of the protein to the membrane surface, where the substrates and Mg2+ ions, required for catalysis, are found. Bioinformatics analysis reveals evidence of this mechanism in other proteins, including several existing drug targets. The development of new COMT inhibitors with preferential affinity for MB-COMT over S-COMT is now possible and insight of broader relevance, into the function of bitopic enzymes, is provided.

In this paper, we present the effect of ferrite percentage content and electric current intensity passing through the electromagnet coil on magnetic properties (saturation induction, residual induction, and coercive field) of magnetic staple yarns. Also, we present a method for obtaining magnetic yarns by direct coating with magnetic powder (barium ferrite). The aim of the study is to determine the optimal processing factors that can affect the performance of magnetic characteristics using an experimental design for second-order model. The results show that an increase in ferrite percentage content is influencing the saturation and residual induction more than an increase in applied current intensity. The increase in saturation and residual induction is due to the higher content of ferrite powder from the magnetic solution that adheres on the yarn surface. The higher is the value of coercive field, the larger is the force needed to completely demagnetize the magnetic yarn.

The interplay between electrostatic and van der Waals (vdW) interactions in porphyrin-C60 dyads is still under debate despite its importance in influencing the structural characteristics of such complexes considered for various applications in molecular photovoltaics. In this article, we sample the conformational space of a porphyrin-C60 dyad using Car–Parrinello molecular dynamics simulations with and without empirical vdW corrections. Long-range vdW interactions, which are poorly described by the commonly used density functional theory functionals, prove to be essential for a proper dynamics of the dyad moieties. Inclusion of vdW corrections brings porphyrin and C60 close together in an orientation that is in agreement with experimental observations. The structural differences arising from the vdW corrections are shown to be significant for several properties and potentially less important for others. Additionally, our Mulliken population analysis reveals that contrary to the common belief, porphyrin is not the primary electron donating moiety for C60. In the considered dyad, fullerene's affinity for electrons is primarily satisfied by charge transfer from the amide group of the linker. However, we show that in the absence of another suitable bound donor, C60 can withdraw electrons from porphyrin if it is sufficiently close. © 2015 Wiley Periodicals, Inc.

Ambient Assistive Living (AAL) applications allow elderly people to maintain a healthy life style and live longer in their homes. In this paper we describe a platform that combine physical exercises, health monitoring with a reminder component implemented as a multimodal interface adapted to elderly needs for maintaining a healthy lifestyle for elderly people.

In this study, we present the effect of the needling density and needle gauge on the functional characteristics (fabric weight, fabric thickness and thermal conductivity) of nonwovens used as agrotextiles for the frost protection of crops. The aim is to determine the optimal processing parameters that can affect the performance characteristics using a central composite design, experimental design, for second-order model. Our results show that an increase in needling density is influencing the fabric weight more than an increase in needle gauge. For the same needle gauge, an increase in needling density also increases the thermal conductivity. At the same time, needling density and needle gauge have opposite effects on fabric thickness.

In order to increase the control on the fiber diameter we propose in this paper a methodology to determine stability domains of the process in which the electrospun fiber diameter can be predetermined and also controlled by means of the polymer solution flow and the applied voltage. To define these stability domains we employ a combination of analytical expressions depending on the location along the traveling jet. In the vicinity of the nozzle we employ the expression which links the fiber diameter with the kinematic viscosity of the polymer solution, nozzle-collector distance, solution density, liquid flow, electric current and intensity of the electrostatic field. At larger distances from the nozzle, the fiber diameter can be expressed as a function of solution density, liquid flow, intensity of the applied electrostatic field and distance from the nozzle. Close to the collector the fiber diameter can be expressed with respect to the superficial tension of the polymer solution, dielectric permittivity, liquid flow and intensity of the electric current. Under specific constrains, the superposition of the plots obtained from these mathematical expressions will be used to determine the stability domain for the fiber diameter in which the diameter can be controlled by two process parameters, namely applied voltage and polymer solution flow. Through this approach the present paper can contribute to increased control of the electrospinning process and thus enhanced applicability.

Here, we investigate the effects of both tuning the range-separation parameter of long-range corrected (LRC) density functionals and including dispersion corrections on describing the local optoelectronic properties of polymer–fullerene interfaces that are critical to the performance of polymer solar cells (PSCs). Focusing on recently studied (Chen, et al., Chem. Mater., 2012, 24, 4766–4772) PSC active layers derived from poly(benzodithiophene-co-quinoxaline) and substituted fullerene PC71BM, we compare the performance of global hybrid functionals (B3LYP and B3LYP-D) alongside two LRC functionals (ωB97X and ωB97X-D) and their optimally tuned (OT) analogs (OT-ωB97X and OT-ωB97X-D). Our results confirm that OT-LRC functionals generally improve the description of the optical properties of the individual materials with respect to experiment. For electron-donor (eD)–electron-acceptor (eA) complexes used to describe the local optoelectronic properties of the material interface, PC71BM is found to preferentially settle near the quinoxaline acceptor units on the copolymer backbone, regardless of the functional, though dispersion corrections have a strong influence on the intermolecular distances and, in turn, the nature of the excited states. All functionals yield very similar descriptions of the transition maxima for the complexes, i.e. predominant local excitations on the copolymer. Importantly, tuning the range-separation parameter of the LRC functional is shown to have a profound effect, as the OT functionals allow for the description of the charge transfer states of the eD–eA complexes, while the non-tuned LRC functionals predict only local intramolecular excitations. These results hold considerable importance for deriving the appropriate physical understanding of the interfacial structure–property–function relationships of PSCs.

Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.

Conjugated donor-acceptor (D-A) copolymers show tremendous promise as active components in thin-film organic bulk heterojunction solar cells and transistors, as appropriate combinations of D-A units enable regulation of the intrinsic electronic and optical properties of the polymer. Here, the structural, electronic, and optical properties of two D-A copolymers that make use of thieno[3,4-c]pyrrole-4,6-dione as the acceptor and differ by their donor unit-benzo[1,2-b:4,5-b']dithiophene (BDT) vs the ladder-type heptacyclic benzodi(cyclopentadithiophene)-are compared using density functional theory methods. Our calculations predict some general similarities, although the differences in the donor structures lead also to clear differences. The extended conjugation of the stiff ladder-type donor destabilizes both the highest occupied and lowest unoccupied molecular orbital energies of the ladder copolymer and results in smaller gap energies compared to its smaller counterpart. However, more significant charge transfer nature is predicted for the smaller BDT-based copolymer by natural transition orbitals than for the ladder copolymer. That is, the influence of the acceptor on the copolymer properties is "diluted" to some extent by the already extended conjugation of the ladder-type donor. Thus, the use of stronger acceptor units with the ladder-type donors would benefit the future design of new D-A copolymers.

The increasing ageing population worldwide imposes some new challenges to the society like the provision of dependable support while facing a shortage in the numbers of caregivers, increased health ...

The effect of a strong electric field generated by molecular dipoles on the ground state electronic structure and the Q and B states as well as the lowest charge transfer (CT) excited state of porphine-2,5-dimethyl-1,4-benzoquinone (PQ) complex has been investigated theoretically. Density functional theory DFT and time-dependent DFT (TDDFT) with the BHHLYP hybrid functional have been applied in these calculations. The molecular dipole effect was generated by imposing one or two helical homopeptides consisting of eight α-aminoisobutyric acid residues (Aib(8)) close to the PQ complex. The molecular dipoles in a close proximity to the PQ complex expose it to an electric field of the order of magnitude of 10(9) V/m. The presence of the ambient molecular dipoles affects mainly the energy of the lowest CT state and barely the energies of the Q and B states. The molecular dipoles affect the energies of the excited states in a similar way as an external electrostatic field. Hence, the electric field induced by the molecular dipoles of the helical peptides could be used analogously to the external electrostatic field to control electron transfer (ET) in the PQ complex.

Adsorption of benzene on oxygen rich and reduced SnO 2 surfaces is studied by employing density functional theory calculations, slab model and linear combination of atomic orbitals approach. Rather than preferential adsorption sites, it is found that the adsorption potential energy surface is flat at both surfaces. The bridging oxygen atoms on the stoichiometric surface induce both covalent and ionic bonding leading to weak chemisorptions, whereas bonding on the reduce surface is closer to physisorption. Deformation of the benzene adsorbate due to adsorption is negligible and only small opposite charge transfer is found explaining the differences between the two surfaces.

Electronic absorption, luminescence, IR and Raman spectra of polymorphous forms of fluoroquinolones were investigated. Assignment of the band maxima due to π→π* and n→π* electronic transitions were done. The structural changes are responsible for the absorption band modifications. One-electron transitions in the long wavelength region, excitation wavelengths, oscillator strengths and involved molecular orbitals for the zwitter-ionic and cationic protonated forms for different fluoroquinolones were calculated with quantum-chemical and molecular dynamic methods. The electron density redistributions on the FQs separate fragments during the photoexcitation to the S(1)*-state were carry out by Mulliken calculations. It was shown that the degree of neutral and zwitter-ion FQs penetration through the bacterium membrane is different.

The potential energy curves (PECs) of the Q, B, and the lowest charge transfer (CT) states of a porphine–2,5-dimethyl-1,4-benzoquinone (PQ) complex have been studied by using the time-dependent density functional theory (TDDFT) with the CAM-B3LYP functional without and with the presence of an external electrostatic field. The PECs calculated using CAM-B3LYP with the original parameters α = 0.19, β = 0.65, and μ = 0.33 a 0 - 1 are practically identical with those obtained using BH&HLYP. Applying of CAM-B3LYP with parameters α = 0.19, β = 0.81, and μ = 0.25 a 0 - 1 yields PECs of the excited states that agree well with the PECs calculated previously using the CC2 method.

Siloxane is a favorable candidate as an anchor group that can be used to bind organic molecules to SnO2 surfaces, with a wide range of practical applications. Therefore, adsorption geometries and energies of siloxane coupler on the SnO2 (110) surface have been investigated in this study using quantum-chemical periodic density functional theory (DFT) calculations. We present a comparative study of different siloxane adsorption arrangements on pristine and fluorine doped SnO2 surface. According to the calculations, the surface doping with fluorine leads to stabilization of the siloxane network at the stannic oxide surface. The trend is analyzed in terms of additional charge provided by F impurities to the chemisorbed oxygen atoms thus increasing the ionicity of their bonding. Implications of the current findings for the design of organic-metal oxide interface with better thermo-stability and improved electronic properties are discussed.

Ground state properties and the UV – Vis absorption spectra of three recently synthesized pyridylindolizine derivatives have been studied by using density functional theory (DFT) and its time-dependent counterpart TDDFT. Performances of the two widely used hybrid functionals, B3LYP and PBE0, and of four different basis sets have been compared. The two functionals yield absorption spectra which have very similar shapes and characteristics but the excitations calculated with PBE0 are obtained at slightly shorter wavelengths. Basis sets affect the appearances of the calculated absorption spectra only little. Independent of the solvent polarity, simulation of the solvent effects by COSMO induces only slight changes into the ground state properties compared to those calculated in the gas-phase and into the absorption spectra.

Adsorption of three small hydrocarbons molecules (acetylene, ethylene and ethane) on two SnO2(1 1 0) surfaces is studied by employing density functional theory calculations, slab model and linear combination of atomic orbitals (LCAO) approach. Acetylene and ethylene adsorb preferentially on top of a 5-fold tin atom, while ethane aligns itself with the rows of bridging oxygens and settles between two surface tin atoms. Adsorption energies and changes occurring in the structural characteristics and electronic structure of both the hydrocarbons and SnO2 surface indicate chemisorption of unsaturated hydrocarbons and physisorption of ethane on reduced surfaces. In all cases of chemisorption there are two contributing mechanisms: charge transfer creating ionic bonding (down-shift of levels) and covalent bonding (broadening of levels).

Five new pyrrolo[1,2-b]pyridazine derivatives: 5,6-dicarbomethoxy-2,7-dimethylpyrrolo[1,2-b]pyridazine ( I ), 5,6-dicarbomethoxy-7-methyl-2-phenylpyrrolo[1,2-b]pyridazine ( II ), 5,6-dicarbomethoxy-7-ethyl-2-phenylpyrrolo[1,2-b]pyridazine ( III ), 5-carboethoxy-7-methyl-2-phenylpyrrolo[1,2-b]pyridazine ( IV ) and 7-ethyl-2-phenylpyrrolo[1,2-b]pyridazine ( V ), with aryl or methyl substituents in pyridazinic ring and with alkyl, aryl and/or carbometoxy in the pyrrolic ring have been investigated by spectroscopic methods and electronic structure calculations. UV–vis absorption together with steady-state and time-resolved fluorescence measurements have been conducted in cyclohexane, n -hexane (as inert solvents), and in solid state to evidence comparatively the effect of the structure of the compounds on the absorption and fluorescence properties. All five compounds have an intense fluorescence with high quantum yields. The intense fluorescence is evidenced also in solid state. The electronic structure calculations have been performed in the framework of density functional theory (DFT) and time dependent DFT (TD-DFT) in order to elucidate the differences observed in absorption spectra as an effect of the substituents.

The effects of a static external electric field on the ground state electronic structure of a porphine-quinone (PQ) complex have been studied by using density functional theory (DFT). The energies of the excited states have been calculated with time-dependent density functional theory (TDDFT) and with the approximate coupled cluster singles and doubles (CC2) method. The geometries of porphine and quinone have been optimized with B3LYP. The influence of the external electric field on the PQ complex has been studied at six different intermolecular distances between 2.5 and 5.0 Å with the BHHLYP functional. An external electric field clearly affects the orbitals localized mostly on quinone but not the orbitals localized on porphine. Additionally, the effect of the external field increases with the increasing intermolecular distance. The optical absorption spectrum of porphine obtained by using the BHHLYP functional is consistent with the Gouterman model and with the spectrum previously calculated with CAM-B3LYP. The potential energy curves of the Q and B states and the lowest charge transfer (CT) states of the PQ complex calculated by using the BHHLYP with TDDFT functional have also been compared with those obtained with the CC2 method. Both methods show that the lowest CT state is clearly above the Q states when no external field is applied. Therefore, when the Q states of a porphine-quinone system are excited, the conical intersection is not possible and cannot thus provide a path for electron transfer (ET). The calculations show that the Q and B states are affected by the field much less than the lowest CT state. Consequently, the calculations show that the CT state crosses the Q and B states at certain field strengths. Thus, it is possible that the external electric field triggers ET in porphine-quinone systems via conical intersection.

Accidental falls and reduced mobility are major risk factors in later life. Changes in a person’s mobility patterns can be related with personal well-being and with the frequency of memory lapses and can be used as risk detectors of incipient neuro-degenerative diseases. Thus, developing technologies for fall detection and indoor localization and novel methods for mobility pattern analysis is of utmost importance in e-health. Choosing the right technology is not only a matter of cost and performance, but also a matter of user acceptability and the perceived ease-of-use by the end user. In this paper, we employ an Analytic Hierarchy Process (AHP) to assess the best fit-to-purpose technology for fall detection and user mobility estimation. Our multi-criteria decision making process is based on the survey results collected from 153 elderly volunteers from 5 EU countries and on 10 emerging e-health technologies for fall detection and indoor mobility pattern estimation. Our analysis points out towards a Bluetooth Low Energy wearable solution as the most suitable solution.

A doubly linked porphyrin–fullerene dyad is studied by molecular dynamics (MD) simulations in polar and non-polar solvent, as well as in vacuum. Two conformations representing the most probable vacuum structures are optimised with semi-empirical and density functional methods (DFT) and the structural differences are assessed. The distances between the centres of the porphyrin and fullerene appear very similar in MD simulations regardless of the environment. Optimization with DFT calculations produces centre-to-centre distances that are within 0.07–5% of the corresponding MD values of realistic environments. The results validate the electronic structure calculations relevant to describing photoinduced electron-transfer and related properties in the dyad.

In the present work density functional theory (DFT) is applied to calculate geometries and electronic structures of 3,4-dimethyl- N -{2-[10,15,20-tris-(3,5-di- tert -butyl-phenyl)-porphyrin-5-yl]-phenyl}benzamide (H 2 P–O34) and its zinc complex (ZnP–O34). The influences of the substituents in the porphyrin ring on the energies of frontier molecular orbitals are evaluated. This is done by gradually increasing the amount of substituents in the investigated porphine and zinc porphine rings. The DFT framework used in this work is found to correctly describe the differences in electronic structures, which arise from differences in the location, number, and electronic effects of the substituents at the meso -positions of the porphyrin ring. In addition, the applicability of the ground state DFT method for evaluating the one-electron transition energies, which correspond to the near UV–Vis optical absorptions of porphyrin molecules, is investigated. The transition energies and the orbitals involved in electronic transitions are well reproduced by this method, as shown by comparing the results to our time dependent density functional calculations.

Polyaniline is a conductive polymer (organic metal) with multiple uses as a sensor for mineral acids, ammonia, VOCs etc. The yield of the electrochemical reactions being proportional to the surface area, it is expected that polyaniline nanofibers to provide great opportunities for applications in electronic nanodevices. This article reviews electrospinning configurations (classic, coaxial, with 2 collectors, with rotary collector, with liquid collector etc.) used to obtain 3D structures of electrospun polyaniline, alone or mixed with other polymers, which are used in sensors. publishedVersion

We report parametrization of dipalmitoyl-phosphatidylcholine (DPPC) in the framework of the Optimized Parameters for Liquid Simulations all-atom (OPLS-AA) force field. We chose DPPC as it is one of the most studied phospholipid species and thus has plenty of experimental data necessary for model validation, and it is also one of the highly important and abundant lipid types, e.g., in lung surfactant. Overall, PCs have not been previously parametrized in the OPLS-AA force field; thus, there is a need to derive its bonding and nonbonding parameters for both the polar and nonpolar parts of the molecule. In the present study, we determined the parameters for torsion angles in the phosphatidylcholine and glycerol moieties and in the acyl chains, as well the partial atomic charges. In these calculations, we used three methods: (1) Hartree-Fock (HF), (2) second order Moller-Plesset perturbation theory (MP2), and (3) density functional theory (DFT). We also tested the effect of the polar environment by using the polarizable continuum model (PCM), and for acyl chains the van der Waals parameters were also adjusted. In effect, six parameter sets were generated and tested on a DPPC bilayer. Out of these six sets, only one was found to be able to satisfactorily reproduce experimental data for the lipid bilayer. The successful DPPC model was obtained from MP2 calculations in an implicit polar environment (PCM).

Cardiolipins (CL) are uniquely structured double lipids that are universally found in membranes which couple electron transport and phosphorylation. The proposed roles of CL in these membranes include mainly two aspects: the effects on the structure and dynamics of the membranes' lipid component and the interplay with membrane-associated proteins. In previous work, we have studied both of these aspects by utilizing atomistic molecular dynamics simulations, starting with the general effects of CL on membrane properties and the interplay with ions [1], further moving on to the interactions with the membrane-embedded respiratory complex cyt bc1 [2]. The latter model system that is of greater interest comprises the entire cyt bc1 dimer of the purple photosynthetic bacterium Rhodobacter capsulatus embedded in a lipid bilayer, whose lipid composition mimics that of the inner mitochondrial membrane. Intriguingly CLs were observed to diffuse spontaneously to the dimer interface and to the immediate vicinity of the catalytic Qi-sites [2]. This observation is in agreement with experimental data, as CLs are indeed located close to the Qi-sites in several X-ray crystal structures of the complex. Importantly, our observations support the proposed role of CL in delivering protons for the non-reduced substrate forms in the active site.In ongoing work that we discuss here we focus more specifically on the roles of individual components of the proposed proton uptake pathway (CL, water, and individual protein residues) and on the atom-level reaction mechanism in the binding pocket. To this end, further MD simulations, QM calculations, and cite-directed mutagenesis experiments were employed. We also discuss whether there is a plausible pathway for substrate movement between the active sites through the lipid-filled insides of the complex, and the role of oxidative stress in cyt bc1 behavior.References[1] Poyry et al. J.Phys.Chem.B,113, 15513(2009).[2] Poyry et al. BBA,1827, 769(2013).

In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C-60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C-60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C-60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C-60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C-60 that is slightly less cytotoxic than m-cresol. Hydrophobicity of chemicals correlates with co-effects when secretion of pro-inflammatory cytokines IL-1 beta and TNF-alpha is considered. Complementary atomistic molecular dynamics simulations reveal that C-60 co-aggregates with all chemicals in aqueous environment. Stable aggregates have a fullerene-rich core and a chemical-rich surface layer, and while essentially all C-60 molecules aggregate together, a portion of organic molecules remains in water.

In the present study, a etoxymethylresorcinarene (EMR) is used as a trap for C60 molecules at the air−water interface. The resulting self-assembled EMR:C60 complexes form stable well-ordered monolayers which can be easily transferred to a solid substrate. The interlayer charge transfer between poly(3-hexylthiophene) (PHT) and C60 was studied using the time-resolved Maxwell displacement charge (TRMDC) method. The structural details of the EMR molecule were calculated by means of molecular mechanics, semiempirical and ab initio methods. The computational results predict that there is enough space for the C60 molecule to be placed between the tails of the resorcinarene molecule.

Electron transfer at the adsorbate-surface interface is crucial in many applications but the steps taking place prior to and during the electron transfer are not always thoroughly understood. In this work a model system of 4-(porphyrin-5-yl)benzoic acid adsorbed as a corresponding benzoate on the ZnO wurtzite (101[combining macron]0) surface is studied using density functional theory (DFT) and time-dependent DFT. Emphasis is on the initial photoexcitation of porphyrin and on the strength of coupling between the porphyrin LUMO or LUMO + 1 and the ZnO conduction band that plays a role in the electron transfer. Firstly, ZnO wurtzite bulk is optimized to minimum energy geometry and the properties of the isolated ZnO (101[combining macron]0) surface model and the porphyrin model are discussed to gain insight into the combined system. Secondly, various orientations of the model porphyrin on the ZnO surface are studied: the porphyrin model standing perpendicularly to the surface and gradually brought close to the surface by tilting the linker in a few steps. The porphyrin model approaches the surface either sideways with hydrogen atoms of the porphyrin ring coming down first or twisted in a ca. 45° angle, giving rise to π-interactions of the porphyrin ring with ZnO. Because porphyrins are closely packed and near the surface, emerging van der Waals (vdW) interactions are examined using Grimme's D2 method. While the orientation affects the initial excitation of porphyrin only slightly, the coupling between the LUMO and LUMO + 1 of porphyrin and the conduction band of ZnO increases considerably if porphyrin is close to the surface, especially if the π-electrons are interacting with the surface. Based on the results of coupling studies, not only the distance between porphyrin and the ZnO surface but also the orientation of porphyrin can greatly affect the electron transfer.

Cytochrome (cyt) bc 1 is a multi-subunit membrane protein complex that is a vital component of the respiratory and photosynthetic electron transfer chains both in bacteria and eukaryotes. Although the complex’s dimer structure has been solved using X-ray crystallography, it has not yet been studied in large-scale classical molecular dynamics (MD) simulations. In part, this is due to lack of suitable force field parameters, centered atomic point charges in particular, for the complex’s prosthetic redox centers. Accurate redox center charges are needed to depict realistically the inter-molecular interactions at different redox stages of the cyt bc 1 complex. Accordingly, here we present high-precision atomic point charges for the metal centers of the cyt bc 1 complex of Rhodobacter capsulatus derived from extensive density functional theory calculations, fitted using the restrained electrostatic potential methodology and combined with the CHARMM force field parameters. We also provide the Hartree–Fock charges for all substrate forms (quinol, quinone, and semiquinone) and the inhibitors antimycin and stigmatellin of the bacterial bc 1 complex. The accuracy of the parameterization scheme was verified by running a 200-ns MD simulation encompassing the entire cyt bc 1 complex embedded in a lipid bilayer and solvated with explicit water. The results indicate that these meticulously derived parameters are ready for running extensive MD simulations encompassing all biologically relevant stages of the cyt bc 1 complex reaction cycle.

The effect of intermolecular proton transfer on the spectral properties of levofloxacin in the ground and excited electronic states was studied. The preferred direction of possible protolytic reactions induced by UV irradiation in this compound was studied. It was found that the proton transfer processes have a considerable effect on the capability of the compound to emit light and occur on the nanosecond timescale. The photochemical reactions of the tree forms of levofloxacin (pH: 4.0, 7.0, 10.0) were studied by laser flash photolysis and product studies. Irradiation at pH 4 yielded a pulse and transient (λmax = 395, 515, 575 nm) assigned to the protonated triplet. Irradiation at pH 7 yielded a transient species (λmax = 525, 610 nm) assigned to the neutral form. Protonation of the anionic singlet excited state was also observed (λmax = 440, 570, 680 nm).

Molecular dynamics simulation has been used to study the speci fi c interactions between poly(ethylene glycol) (PEG) and three drug molecules for which PEG is used to aid delivery: paclitaxel and piroxicam, where PEG is a carrier agent, and hematoporphyrin, where PEG is covalently attached to form a “ stealth shield ” . Simulating at physiological salt concentration, we found no evidence of any speci fi c interaction between paclitaxel or piroxicam with PEG, but found a strong interaction for the case of hematoporphyrin. This interaction is lipophilic in nature, between the nonpolar (CH 2 ) 2 groups of the PEG and the porphin ring of the hematoporphyrin. This interaction was found to be strong enough that the PEG aggregated to the hematoporphyrin, independent of whether or not it was covalently bound. Interestingly, when the simulation was repeated in absence of salt we found evidence of this interaction being weakened. This led us to hypothesize a previously unforeseen mechanism: interaction with salt cations cause the PEG to coil around the salt ions, each ion binding to many PEG oxygens, increasing the exposure of the nonpolar ethylene groups, thus increasing the e ff ective hydrophobicity of PEG. The Hydrophobic ethylene groups of the PEG chains adhere strongly to the hydrophobic porphin ring. Experiments involving absorption spectra measurements were conducted, and these results also indicated that presence of salt at physiological level increases the e ff ective attractive interaction between PEG and hematoporphyrin. Taken together, our results demonstrate that while PEG, due to its solubility in both polar and nonpolar solvents, may act as a dissolution aid for paclitaxel and piroxicam, of the three drug molecules studied it will only have a protective role for the case of the hematoporphyrin.

Location Based Services (LBS) are nowadays recognized as having one of the most fast-paced developments in the wireless field. The underlying location technology is still mainly based on the Global Navigation Satellite Systems (GNSS), but many complementary technologies, such as cellular-based location, WLAN-based location and other Signal of Opportunity-based location are rapidly trying to close the remaining technology gaps. There is a myriad of potential future applications for LBS, but their perceived value for the user is still not well-studied or understood. The goal of our paper is to better define the user requirements in terms of mobile device features and LBS applications, based on a survey among 47 students at a top technical university in Bucharest, Romania.

Nowadays, location-enabled mobile phones are becoming more and more widespread. Various players in the mobile business forecast that, in the future, a significant part of total wireless revenue will come from Location-Based Services (LBS). An LBS system extracts information about the user’s geographical location and provides services based on the positioning information. A successful LBS service should create value for the end-user, by satisfying some of the users’ needs or wants, and at the same time preserving the key factors of the mobile wireless device, such as low costs, low battery consumption, and small size. From many users’ perspectives, location services and mobile location capabilities are still rather poorly known and poorly understood. The aim of this research is to investigate users’ views on the LBS, their requirements in terms of mobile device characteristics, their concerns in terms of privacy and usability, and their opinion on LBS applications that might increase the social wellbeing in the future wireless world. Our research is based on two surveys performed among 105 students (average student age: 24 years) from two European technical universities. The survey questions were intended to solicit the youngsters’ views on present and future technological trends and on their perceived needs and wishes regarding Location-Based Services, with the aim of obtaining a better understanding of designer constraints when building a location receiver and generating new ideas related to potential future killer LBS applications.

Cytochrome (cyt) bc1 complex has two active sites where energy-sustaining electron/proton transfer reactions occur. To determine the exact transfer steps involving the substrate quinone, the cyt bc1 complex of Rhodobacter capsulatus was studied using atomistic molecular dynamics simulations. The computations give clear-cut ideas how the proton transfer might take place at both of the active sites. The simulations strongly suggest that water-mediated interactions are needed to achieve quinol oxidation and to prevent short-circuit suppression at the Qo-site. In the case of the Qi-site, the simulations emphasize the role of negatively charged cardiolipin in quinone reduction. Together with site-directed mutagenesis this in silico approach provides long-awaited information regarding the structure-function relationship of the cyt bc1 complex.

The fluorescence properties of three pyridylindolizine derivatives (one tricarbomethoxy-7-pyridyl-pyrrolopyridine and two dicarboethoxy-3-bromobenzoyl-7-pyridyl-pyrrolopyridines) have been investigated by applying density functional theory (DFT) and the time-dependent DFT (TDDFT). Performances of two hybrid-type functionals (BH&HLYP and B3LYP) and one generalized gradient approximation (GGA) functional (PBE) as well as three basis sets (SV(P), DZP, and TZVP) have been assessed. The solvent environment has been modeled with the conductor-like screening model (COSMO). Of the three functionals only BH&HLYP is able to yield reasonable estimates for all the studied indolizine derivatives whereas the success of the PBE and B3LYP functionals is highly dependent on the structure of the studied molecule. The SV(P) basis set provides geometrical changes as well as fluorescence maxima and Stokes shifts that agree with those obtained with DZP and TZVP. When a nonpolar solvent is used, COSMO is able to reproduce the experimental fluorescence maxima and Stokes shifts well. However, the agreement between the calculations and experiments is not as good when a solvent with higher polarity is used.

The authors consider two porphyrin-fullerene dyads with different conformational flexibility. Molecular dynamics has been used to find the 300 K conformations in typical solutions and vacuum. Furthermore, the zero-Kelvin electronic structure calculations have been validated as a good model.

Structure, photoabsorption and excited states of two representative conformations obtained from molecular dynamics (MD) simulations of a doubly-linked porphyrin-fullerene dyad DHD6ee are studied by using both DFT and wavefunction based methods. Charge transfer from the donor (porphyrin) to the acceptor (fullerene) and the relaxation of the excited state are of special interest. The results obtained with LDA, GGA, and hybrid functionals (SVWN, PBE, and B3LYP, respectively) are analyzed with emphasis on the performance of used functionals as well as from the point of view of their comparison with wavefunction based methods (CCS, CIS(D), and CC2). Characteristics of the MD structures are retained in DFT optimization. The relative orientation of porphyrin and fullerene is significantly influencing the MO energies, the charge transfer (CT) in the ground state of the dyad and the excitation of ground state CT complex (g-CTC). At the same time, the excitation to the locally excited state of porphyrin is only little influenced by the orientation or cc distance. TD-DFT underestimates the excitation energy of the CT state, however for some cases (with relatively short donor-acceptor separations), the use of a hybrid functional like B3LYP alleviates the problem. Wavefunction based methods and CC2 in particular appear to overestimate the CT excitation energies but the inclusion of proper solvation models can significantly improve the results.

Structure, photoabsorption, and excited states of a covalently bonded porphyrin-fullerene dyad H(2)P-O34-C(60) are studied using DFT and TD-DFT approaches. Charge transfer from the donor (porphyrin) to the acceptor (fullerene) and the excited-state geometrical relaxation are of special interest. An analysis of differences in the description of these delicate phenomena due to the different exchange-correlation functionals is presented. We compare the results given by LDA, GGA, and hybrid functionals (i.e., SVWN, PBE, B3LYP, and PBE0). The ground-state center-to-center (cc) equilibrium distance between the donor and the acceptor moieties is 6.3, 7.1, and 7.9 Angstrom with SVWN, PBE, and B3LYP, respectively. The associated charge transfer of 0.15, 0.11, and 0.09 electrons is shown to depend on this distance but not directly on the functional itself. The same trend is seen in the HOMO-LUMO difference results, and further, in the lowest excitation energies, except for the hybrid functional calculations that yield the largest HOMO-LUMO gap and the highest energy for the lowest electronic excitation. The hybrid functionals were not found practical for excited-state conformational relaxation with the present computing resources. With LDA, the relaxation increases the cc distance by about 0.2 Angstrom, which is associated with a 0.14 eV decrease in energy. As compared to the ground-state dipole moment of about 4 D, the relaxed excited-state charge-transfer complex dipole moment turns out to become about 20 D. A local excitation of the porphyrin donor is considered, as well, and based on all these results, the nature and interpretation of the photoinduced electron-transfer process is discussed.

Spectroscopic properties of a ground state nonbonded porphine-buckminsterfullerene (H2P...C60) complex are studied in several different relative orientations of C60 with respect to the porphine plane by using the density functional (DFT) and time-dependent density functional (TDDFT) theories. The geometries and electronic structures of the ground states are optimized with the B3LYP and PBE functionals and a SVP basis set. Excitation energies and oscillator strengths are obtained from the TDDFT calculations. The relative orientation of C60 is found to affect the equilibrium distance between H2P and C60 especially in the case of the PBE functional. The excitation energies of different H2P...C60 complexes are found to be practically the same for the same excitations when the B3LYP functional is used but to differ notably when PBE is used in calculations. Existence of the states related to a photoinduced electron transfer within a porphyrin-fullerene dyad is also studied. All calculations predict a formation of an excited charge-transfer complex state, a locally excited donor (porphine) state, as well as a locally excited acceptor (fullerene) state in the investigated H2P...C60 complexes.

Electron transfer at the adsorbate–surface interface is crucial in many applications but the steps taking place prior to and during the electron transfer are not always thoroughly understood. In this work a model system of 4-(porphyrin-5-yl)benzoic acid adsorbed as a corresponding benzoate on the ZnO wurtzite (100) surface is studied using density functional theory (DFT) and time-dependent DFT. Emphasis is on the initial photoexcitation of porphyrin and on the strength of coupling between the porphyrin LUMO or LUMO + 1 and the ZnO conduction band that plays a role in the electron transfer. Firstly, ZnO wurtzite bulk is optimized to minimum energy geometry and the properties of the isolated ZnO (100) surface model and the porphyrin model are discussed to gain insight into the combined system. Secondly, various orientations of the model porphyrin on the ZnO surface are studied: the porphyrin model standing perpendicularly to the surface and gradually brought close to the surface by tilting the linker in a few steps. The porphyrin model approaches the surface either sideways with hydrogen atoms of the porphyrin ring coming down first or twisted in a ca. 45° angle, giving rise to π-interactions of the porphyrin ring with ZnO. Because porphyrins are closely packed and near the surface, emerging van der Waals (vdW) interactions are examined using Grimme's D2 method. While the orientation affects the initial excitation of porphyrin only slightly, the coupling between the LUMO and LUMO + 1 of porphyrin and the conduction band of ZnO increases considerably if porphyrin is close to the surface, especially if the π-electrons are interacting with the surface. Based on the results of coupling studies, not only the distance between porphyrin and the ZnO surface but also the orientation of porphyrin can greatly affect the electron transfer.

The reaction mechanism of the cytochrome (cyt) bc 1 complex relies on proton and electron transfer to/from the substrate quinone/quinol, which in turn generate a proton gradient across the mitochondrial membrane. Cardiolipin (CL) have been suggested to play an important role in cyt bc 1 function by both ensuring the structural integrity of the protein complex and also by taking part in the proton uptake. Yet, the atom-scale understanding of these highly charged four-tail lipids in the cyt bc 1 function has remained quite unclear. We consider this issue through atomistic molecular dynamics simulations that are applied to the entire cyt bc 1 dimer of the purple photosynthetic bacterium Rhodobacter capsulatus embedded in a lipid bilayer. We find CLs to spontaneously diffuse to the dimer interface to the immediate vicinity of the higher potential heme b groups of the complex's catalytic Q i-sites. This observation is in full agreement with crystallographic studies of the complex, and supports the view that CLs are key players in the proton uptake. The simulation results also allow us to present a refined picture for the dimer arrangement in the cyt bc 1 complex, the novelty of our work being the description of the role of the surrounding lipid environment: in addition to the specific CL-protein interactions, we observe the protein domains on the positive side of the membrane to settle against the lipids. Altogether, the simulations discussed in this article provide novel views into the dynamics of cyt bc 1 with lipids, complementing previous experimental findings.

Conformational space of a porphyrin–fullerene dyad with the donor and acceptor connected by a relatively flexible linker is studied by molecular dynamics simulations in both non-polar and polar solvents, as well as in vacuum. The most probable conformations obtained from the vacuum MD simulations were optimized with semi-empirical (SE) and density functional theory (DFT) methods and the extent of the structural changes is assessed. The computational results indicate the co-existence of different conformers in both polar and nonpolar solvents showing agreement with experimental results. The most probable vacuum conformations at 300 K are similar to the ones at 0 K, while the structures most often observed in the solvents show less compact conformations. Optimization with SE and DFT calculations leads to structures, which represent relatively well the folded conformations in solvent, which validates the electronic structure calculations relevant to describing photoinduced electron-transfer in H2P–O34–C60.

Classical atom-scale molecular dynamics simulations, constrained free energy calculations, and quantum mechanical (QM) calculations are employed to study the diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is considered here as a representative of the fluoroquinolone antibiotics class. Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being predominant. Simulations reveal that only the neutral form permeates the bilayer, and it does so through a novel mechanism that involves dissolution of concerted stacks of zwitterionic ciprofloxacins. Subsequent QM analysis of the observed molecular stacking shows the important role of partial charge neutralization in the stacks, highlighting how the zwitterionic form of the drug is neutralized for translocation. The findings propose a translocation mechanism in which zwitterionic CPFX molecules approach the membrane in stacks, but they diffuse through the membrane as neutral CPFX monomers due to intermolecular transfer of protons favored by partial solvation loss. The mechanism is expected to be of importance in the permeation and translocation of a variety of ampholitic drugs with stacking tendencies. (C) 2012 Elsevier B.V. All rights reserved.

In the present work, the time-dependent density functional theory (TD-DFT) is applied to study the electronic transitions which give rise to the near-ultraviolet−visible (near-UV−vis) optical absorptions of 3,4-dimethyl-N-{2-[10,15,20-tris-(3,5-di-tert-butyl-phenyl)-porphyrin-5-yl]-phenyl} benzamide (H2P−O34) and its zinc complex ZnP−O34. Optimizations of the molecular structures were performed using the GGA type Perdew−Burke−Ernzerhof exchange-correlation functional. Excitation energies and oscillator strengths were obtained from the TD-DFT calculations. Calculations were also carried out by using the BP and B3LYP functionals. A large number of electronic transitions are responsible for the optical absorptions in the near-UV−vis region. It was also found that distortions induced to the porphyrin ring by the substituents contribute