Temperature dependence of kinetics of triplet formation in phenazine: analysis by analogue computer

The temperature dependence of kinetic parameters of triplet phenazine have been determined by analysis of transient response to photoexcitation. The analogue computer used in the analysis is described.     

Theoretical analysis and computer simulation of fluorescence lifetime measurements. I. Kinetic regimes and experimental time scales

The configuration-controlled regime and the diffusion-controlled regime of conformation-modulated fluorescence emission are systematically studied for Markovian and non-Markovian dynamics of the reaction coordinate. A path integral simulation is used to model fluorescence quenching processes on a semiflexible chain. First-order inhomogeneous cumulant expansion in the configuration-controlled regime defines a lower bound for the survival probability, while the Wilemski-Fixman approximation in the diffusion-controlled regime defines an upper bound. Inclusion of the experimental time window of the fluorescence measurement adds another dimension to the two kinetic regimes and provides a unified perspective for theoretical analysis and experimental investigation. We derive a rigorous generalization of the Wilemski-Fixman approximation [G. Wilemski and M. Fixman, J. Chem. Phys. 60, 866 (1974)] and recover the 1/D expansion of the average lifetime derived by Weiss [G. H. Weiss, J. Chem. Phys. 80, 2880 (1984)].     

Simulation techniques in analytical chemistry. Microcomputer-controlled simulation of the chromatographie process with an analogue computer

An analogue/digital hybrid interface is presented that allows the support of simulations on an analogue computer EAI 380 by a microcomputer PDP 11/34. On this simulation system the peak spreading process of a Chromatographie column was implemented as an example for a simulation of a dynamic process in analytical chemistry. To implement the Chromatographie mass balance equations on the analogue part of the simulation system, only one hardwired stage of a cascade of reactors is necessary. The output values of one analogue simulation step were stored by the microcomputer as intermediate results and were given back as input values during the next analogue simulation step. The simulation process can be seen on a screen and is easily modified by online variation of the simulation parameters.     

Kinetic analysis of the cross reaction between dithioester and alkoxyamine by a Monte Carlo simulation

A model reaction of dithioester and alkoxyamine is proposed to probe the reversible addition–fragmentation chain transfer (RAFT) process. The kinetics of the model reaction is analyzed and compared with that of pure alkoxyamine homolysis with a Monte Carlo simulation. Although the pure alkoxyamine obeys the law of persistent radical effect, the model reaction results in higher concentration of the persistent radical during the main period of the reaction. However, for a very fast RAFT process or a very low addition rate constant, the time dependence of the persistent radical concentration is quite close to that of pure alkoxyamine. Furthermore, the cross termination between the intermediate and alkyl radicals causes a retardation effect for the model reaction when the intermediate is relatively long‐lived. The Monte Carlo simulation indicates that it is feasible to measure the individual rate constants of the RAFT process, such as the rate constant of addition, with a large excess of alkoxyamine. In addition, the special feature of the system with different leaving groups in the alkoxyamine and dithioester is also discussed. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 374–387, 2007     

Kinetic study of dipivaloylmethane by ozawa method

The lanthanidic complexes of general formula Ln(C₁₁H₁₉O₂)₃ were synthesized and characterized by elementary analysis, infrared absorption espectroscopy, thermogravimetry (TG) and differential scanning calorimetry (DSC). The reaction of thermal decomposition of complexes has been studied by non-isothermal and isothermal TG. The thermal decomposition reaction of complexes began in the solid phase for Tb(thd)₃, Tm(thd)₃ and Yb(thd)₃ and in the liquid phase for Er(thd)₃ and Lu(thd)₃, as it was observed by TG/DTG/DSC superimposed curves. The kinetic model that best adjusted the experimental isothermal thermogravimetric data was the R1 model. Through the Ozawa method it was possible to find coherent results in the kinetic parameters and according to the activation energy the following stability order was obtained: Tb(thd)₃>Lu(thd)₃>Yb(thd)₃>Tm(thd)₃>Er(thd)₃ This revised version was published online in August 2006 with corrections to the Cover Date.     

A non-conventional method of polymer PAL spectrum analysis by the LT computer program

A new version of computer program (LT v.10) offers a new concept of polymer spectrum analysis. The theoretical model takes into account a few processes in which positron is involved: the process of slow formation and localization of positronium (Ps), delay formation of positronium from shallow trapped electrons and positron trapping in irradiation-induced centers. The model was applied to two series of spectra for LDPE and HDPE collected at constant temperature (much below the glass temperature) as a function of measurement time. The Ps internal relaxation time and time of localization of Ps in a free-volume center were determined. The results show that the trapping rate of positron is strictly correlated with the amount of the shallow trapped electrons. That suggests a coupling between the positron and electron-trapping centers.     

Testing experimental analysis techniques for liquid crystals using computer simulation

Computer simulation has been used widely over the last two decades to investigate the phase behaviour and physical properties of liquid crystal systems. Here we review studies in which simulations have been used to calculate information on the physical properties of liquid crystals in a pseudo-experimental way. We concentrate on the calculation of 'experimental data' from computer simulations, from which we can extract information on the structure and dynamics of the nematic and smectic A phases. Where relevant, these are compared with both existing theoretical and experimental results. In particular, routes between the raw experimental data and physical parameters such as the orientational order parameter are highlighted and their effectiveness investigated.     

Kinetic determination of phenols by a fixed-time method

The fixed-time kinetic method is used for the determination of 15 phenols in methanol and acetic acid by measurement of the yellow products from the oxidation of the phenols with sodium metaperiodate. An increase in acid and metaperiodate concentrations enhances the rate of reaction, whereas the use of 2-propanol as the solvent decreases it.     

Applicability of Kissinger model in nonisothermal crystallization assessed using a computer simulation method

The Kissinger method is one of the most popular approaches for determining kinetic parameters from the nonisothermal processes. The applicability of the Kissinger model in describing the nonisothermal crystallization was verified using the data of the simulated experiments with the given crystallization mechanism. The results show that the data of the Monte Carlo experiments for nonisothermal crystallization can be used to evaluate the nonisothermal crystallization model. The Kissinger model can be used to estimate the parameter of the activation energy of the nonisothermal crystallization from the DSC curves with the different heating rates, but unsuitable to obtain the parameter from the DSC curves with the different cooling rates.     

Analysis of electric conductivity of binary solid-state catalysts by computer simulation

Experimental and model studies of concentration dependencies of electric conductivity have been performed for a number of binary mechanical mixtures. The physical origins of various peculiarities are discussed with Fe₃O₄+MgO, Fe₃O₄+NiO, and Ni+ZrO₂ systems considered as examples. The degree of friability of the systems and the degree of homogeneity of the component distribution are estimated. A considerable mutual influence of the phases is observed, which is, however, not a chemical interaction.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1874–1877, November, 1993.     

A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

Signal proteins are able to adapt their response to a change in the environment, governing in this way a broad variety of important cellular processes in living systems. While conventional molecular-dynamics (MD) techniques can be used to explore the early signaling pathway of these protein systems at atomistic resolution, the high computational costs limit their usefulness for the elucidation of the multiscale transduction dynamics of most signaling processes, occurring on experimental timescales. To cope with the problem, we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility of cancer cells through light stimulus. More specifically, we show that their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding. These applications demonstrate that our approach reliably reproduces the signaling pathways of complex signal proteins, ranging from nanoseconds up to seconds at affordable computational costs.     

A computer simulation of trapping electrophoresis

The gel electrophoretic migration of streptavidin-DNA complexes is severely altered by the phenomenon known as “trapping electrophoresis.” We present a first computer simulation study of this process. Our simulations use the very efficient biased reptation algorithm. The steady state is characterized by a large increase in band broadening and interband separation. However, we also find that for a narrow range of molecular sizes, the separation power of gel electrophoresis is greatly increased. We discuss the implications of our findings for the possible improvement of DNA sequencing technologies. © 1992 John Wiley & Sons, Inc.     

The catalytic mechanism of peptidylglycine alpha-hydroxylating monooxygenase investigated by computer simulation

The molecular basis of the hydroxylation reaction of the Calpha of a C-terminal glycine catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM) was investigated using hybrid quantum-classical (QM-MM) computational techniques. We have identified the most reactive oxygenated species and presented new insights into the hydrogen abstraction (H-abstraction) mechanism operative in PHM. Our results suggest that O(2) binds to Cu(B) to generate Cu(B)(II)-O(2)(.-) followed by electron transfer (ET) from Cu(A) to form Cu(B)(I)-O(2)(.-). The computed potential energy profiles for the H-abstraction reaction for Cu(B)(II)-O(2)(.-), Cu(B)(I)-O(2)(.-), and [Cu(B)(II)-OOH](+) species indicate that none of these species can be responsible for abstraction. However, the latter species can spontaneously form [Cu(B)O](+2) (which consists of a two-unpaired-electrons [Cu(B)O](+) moiety ferromagnetically coupled with a radical cation located over the three Cu(B) ligands, in the quartet spin ground state) by abstracting a proton from the surrounding solvent. Both this monooxygenated species and the one obtained by reduction with ascorbate, [Cu(B)O](+), were found to be capable of carrying out the H-abstraction; however, whereas the former abstracts the hydrogen atom concertedly with almost no activation energy, the later forms an intermediate that continues the reaction by a rebinding step. We propose that the active species in H-abstraction in PHM is probably [Cu(B)O](+2) because it is formed exothermically and can concertedly abstract the substrate HA atom with the lower overall activation energy. Interestingly, this species resembles the active oxidant in cytochrome P450 enzymes, Compound I, suggesting that both PHM and cytochrome P450 enzymes may carry out substrate hydroxylation by using a similar mechanism.     

Arrest of fluid demixing by nanoparticles: a computer simulation study

We use lattice Boltzmann simulations to investigate the formation of arrested structures upon demixing of a binary solvent containing neutrally wetting colloidal particles. Previous simulations for symmetric fluid quenches pointed to the formation of "bijels": bicontinuous interfacially jammed emulsion gels. These should be created when a glassy monolayer of particles forms at the fluid-fluid interface, arresting further demixing and rigidifying the structure. Experimental work has broadly confirmed this scenario, but it shows that bijels can also be formed in volumetrically asymmetric quenches. Here, we present new simulation results for such quenches, compare these to the symmetric case, and find a crossover to an arrested droplet phase at strong asymmetry. We then make extensive new analyses of the postarrest dynamics in our simulated bijel and droplet structures, on time scales comparable to the Brownian time for colloid motion. Our results suggest that, on these intermediate time scales, the effective activation barrier to ejection of particles from the fluid-fluid interface is smaller by at least 2 orders of magnitude than the corresponding barrier for an isolated particle on a flat interface.     

Morphology of bile salt micelles as studied by computer simulation methods

The relative arrangement of the neighboring bile ions and the shape of the hydrophobic and hydrogen-bonded primary micelles as well of the large secondary micelles formed by these ions are analyzed in detail on the basis of molecular dynamics computer simulations of 30 and 300 mM sodium cholate and sodium deoxycholate solutions. In the lower concentration considered, the systems only contain primary micelles, whereas in both of the 300 mM systems secondary micelles are also present. The simulations performed were long enough that the systems reached thermodynamic equilibrium. It is found that the neighboring cholate ions prefer alignments in which their quasi-planar tetracyclic ring systems are parallel with each other, whereas for deoxycholate an opening of the angle between these planes is observed. The shape of the micelles is characterized by the ratio of their three principal moments of inertia. The primary deoxycholate micelles are found to be rather spherical, whereas in the case of cholate somewhat flattened, disklike or oblate shaped ellipsoidal primary micelles are found, irrespective of whether these micelles are kept together by hydrogen bonds or are of hydrophobic origin. Finally, the secondary micelles are found to exhibit a large variety of shapes, ranging from flattened oblates to rodlike objects through various different irregular shapes, characterized by markedly different values of the three principal moments of inertia. The observed preferences of the relative arrangement of the neighboring ions and of the aggregate shapes as well as the differences observed in the behavior of the two bile ions studied in these respects are traced back to the molecular structure of these ions.     

Microspeciation in the copper(II)-L-histidylglycine system. An ESR study by the two-dimensional computer simulation method

Twelve ESR-active (and one inactive) copper(II) complexes of L-histidylglycine (HL) were characterized via their formation (micro)constants and ESR parameters obtained by two-dimensional ESR spectroscopic evaluation in aqueous solution. In strongly acidic media, the ligand is coordinated through its N-terminal donor groups: the complex [CuLH(2)](3+) involves monodentate imidazole binding, whereas [CuLH](2+) involves bidentate ligation through the amino and imidazole N atoms. This histamine-like bonding mode also predominates in the isomers of [CuL(2)], formed at ligand excess near pH 7: in the major 4N isomer, both ligands occupy two equatorial sites, while in the 3N isomer, the second dipeptide is coordinated equatorially by the amino and axially by the imidazole groups. At above pH 3-4, deprotonation of the peptide group also starts: in approximately 60% of the molecules of [CuL](+), the peptide group is deprotonated, while in the minor isomer histamine-like coordination occurs. At higher pH, the active dimer [Cu(2)L(2)H(-2)], the mixed hydroxo complexes (the inactive [Cu(2)L(2)H(-3)](-) and the active [CuLH(-2)](-)), and the bis complexes [CuL(2)H](+) and [CuL(2)H(-1)](-) all involve tridentate equatorial ligation of the backbone by the amino and deprotonated peptide N and the carboxylate O atoms. In the active dimer, the neutral imidazole groups form bridges between CuLH(-1) units. In [CuL(2)H](+), the second ligand is bound equatorially via its imidazole group; in [CuL(2)H(-1)](-), the L ligand occupies the fourth equatorial site and an axial site through its amino and imidazole N atoms, respectively.     

Kinetic wavelength-pair method as an alternative approach to simultaneous multi-component analysis

The kinetic wavelength-pair method involves adapting a well established principle to the simultaneous kinetic-based determination of two or more compounds with diode-array detection. It relies on measuring the difference in the rate of change of the absorbance with time at two preset wavelength pairs such that the values of these measuring parameters are the result of the contribution of one or two components. The theoretical basis adapted to first-order kinetic-based determinations was established and checked on four systems. The method thus developed was compared with other differential kinetic methods and applied to the resolution of formaldehyde-acrolein mixtures.     

An approximate but efficient method to calculate free energy trends by computer simulation: Application to dihydrofolate reductase-inhibitor complexes

Summary Derivatives of free energy differences have been calculated by molecular dynamics techniques. The systems under study were ternary complexes of Trimethoprim (TMP) with dihydrofolate reductases of E. coli and chicken liver, containing the cofactor NADPH. Derivatives are taken with respect to modification of TMP, with emphasis on altering the 3-, 4- and 5-substituents of the phenyl ring. A linear approximation allows the encompassing of a whole set of modifications in a single simulation, as opposed to a full perturbation calculation, which requires a separate simulation for each modification. In the case considered here, the proposed technique requires a factor of 1000 less computing effort than a full free energy perturbation calculation. For the linear approximation to yield a significant result, one has to find ways of choosing the perturbation evolution, such that the initial trend mirrors the full calculation. The generation of new atoms requires a careful treatment of the singular terms in the non-bonded interaction. The result can be represented by maps of the changed molecule, which indicate whether complex formation is favoured under movement of partial charges and change in atom polarizabilities. Comparison with experimental measurements of inhibition constants reveals fair agreement in the range of values covered. However, detailed comparison fails to show a significant correlation. Possible reasons for the most pronounced deviations are given.     

Investigation of the catalytic mechanism of farnesyl pyrophosphate synthase by computer simulation

Farnesyl pyrophosphate synthase (FPPS) catalyses the formation of a key cellular intermediate in isoprenoid metabolic pathways, farnesyl pyrophosphate, by the sequential head-to-tail condensation of two molecules of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP). Recently, FPPS has been shown to represent an important target for the treatment of parasitic diseases such as Chagas disease and African trypanosomiasis. Bisphosphonates, pyrophosphate analogues in which the oxygen bridge between the two phosphorus atoms has been replaced by a carbon substituted with different side chains, are able to inhibit the FPPS enzyme. Moreover, nitrogen-containing bisphosphonates have been proposed as carbocation transition state analogues of FPPS. On the basis of structural and kinetic data, different catalytic mechanisms have been proposed for FPPS. By analyzing different reaction coordinates we propose that the reaction occurs in one step through a carbocationic transition state and the subsequent transfer of a hydrogen atom from IPP to the pyrophosphate moiety of DMAPP. Moreover, we have analyzed the role of the active site amino acids on the activation barrier and the reaction mechanism. The structure of the active site is well conserved in the isoprenyl diphosphate synthase family; thus, our results are relevant for the understanding of this important class of enzymes and for the design of more potent and specific inhibitors for the treatment of parasitic diseases.