On the quantum mechanical scattering statistics of many particles

The probability of a quantum particle being detected in a given solid angle is determined by the S-matrix. The explanation of this fact in time-dependent scattering theory is often linked to the quantum flux, since the quantum flux integrated against a (detector-) surface and over a time interval can be viewed as the probability that the particle crosses this surface within the given time interval. Regarding many particle scattering, however, this argument is no longer valid, as each particle arrives at the detector at its own random time. While various treatments of this problem can be envisaged, here we present a straightforward Bohmian analysis of many particle potential scattering from which the S-matrix probability emerges in the limit of large distances.

Molecular dynamics simulations of proteins: can the explicit water model be varied?

In molecular mechanics simulations of biological systems, the solvation water is typically represented by a default water model which is an integral part of the force field. Indeed, protein nonbonding parameters are chosen in order to obtain a balance between water-water and protein-water interactions and hence a reliable description of protein solvation. However, less attention has been paid to the question of whether the water model provides a reliable description of the water properties under the chosen simulation conditions, for which more accurate water models often exist. Here we consider the case of the CHARMM protein force field, which was parametrized for use with a modified TIP3P model. Using quantum mechanical and molecular mechanical calculations, we investigate whether the CHARMM force field can be used with other water models: TIP4P and TIP5P. Solvation properties of N-methylacetamide (NMA), other small solute molecules, and a small protein are examined. The results indicate differences in binding energies and minimum energy geometries, especially for TIP5P, but the overall description of solvation is found to be similar for all models tested. The results provide an indication that molecular mechanics simulations with the CHARMM force field can be performed with water models other than TIP3P, thus enabling an improved description of the solvent water properties.

Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine

Resistant strains of Plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in vivo (oral ID50 of 25 mu mol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17 mu M). Metaquine shows strong affinity for the putative antimalarial receptor, heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum mechanical calculations (HF/6-31+G*) reveal important regions of protonation and bonding thought to persist at parasitic vacuolar pH concordant with our receptor model. Formation of drug-heme adduct in solution was confirmed using high-resolution positive ion electrospray mass spectrometry. Metaquine showed strong binding with the receptor in a 1: 1 ratio (log K = 5.7 +/- 0.1) that was predicted by molecular mechanics calculations. This study illustrates a rational multidisciplinary approach for the development of new 4-aminoquinoline antimalarials, with efficacy superior to chloroquine, based on the use of a pharmacophore model.

Modelling the propagation of terahertz radiation through a tissue simulating phantom

Terahertz (THz) frequency radiation, 0.1 THz to 20 THz, is being investigated for biomedical imaging applications following the introduction of pulsed THz sources that produce picosecond pulses and function at room temperature. Owing to the broadband nature of the radiation, spectral and temporal information is available from radiation that has interacted with a sample; this information is exploited in the development of biomedical imaging tools and sensors. In this work, models to aid interpretation of broadband THz spectra were developed and evaluated. THz radiation lies on the boundary between regions best considered using a deterministic electromagnetic approach and those better analysed using a stochastic approach incorporating quantum mechanical effects, so two computational models to simulate the propagation of THz radiation in an absorbing medium were compared. The first was a thin film analysis and the second a stochastic Monte Carlo model. The Cole–Cole model was used to predict the variation with frequency of the physical properties of the sample and scattering was neglected. The two models were compared with measurements from a highly absorbing water-based phantom. The Monte Carlo model gave a prediction closer to experiment over 0.1 to 3 THz. Knowledge of the frequency-dependent physical properties, including the scattering characteristics, of the absorbing media is necessary. The thin film model is computationally simple to implement but is restricted by the geometry of the sample it can describe. The Monte Carlo framework, despite being initially more complex, provides greater flexibility to investigate more complicated sample geometries.

Conformational polymorphism of the molecular complex of 3-fluorobenzoic acid with 4-acetylpyridine

Two polymorphs of the molecular complex formed between 3-fluorobenzoic acid with 4-acetylpyridine are described and found to be based upon the same dimeric supramolecular construct. The conformational freedom around the hydrogen bond results in a 180 degrees rotation about this intermolecular link, distinguishing the polymorphs and affecting the packing of the dimeric units. The two polymorphs are fully characterised by single crystal X-ray and neutron diffraction and quantum mechanical calculations. There is evidence of structured crystal growth defects in both polymorphic crystals via observation of diffuse scattering and a disorder model for the average structure of Form I, which can be interpreted as a mixing of the two dimer conformations. The similarity of energy of the distinct dimeric units, supporting their likely co-existence, has been verified by periodic quantum chemical calculations.

Chalcogenide-halides of niobium (V). 1. Gas-phase structures of NbOBr3, NbSBr3, and NbSCl3. 2. Matrix infrared spectra and vibrational force fields of NbOBr3, NbSBr3, NbSCl3, and NbOCl3

The molecular structures of NbOBr3, NbSCl3, and NbSBr3 have been determined by gas-phase electron diffraction (GED) at nozzle-tip temperatures of 250 degreesC, taking into account the possible presence of NbOCl3 as a contaminant in the NbSCl3 sample and NbOBr3 in the NbSBr3 sample. The experimental data are consistent with trigonal-pyramidal molecules having C-3v symmetry. Infrared spectra of molecules trapped in argon or nitrogen matrices were recorded and exhibit the characteristic fundamental stretching modes for C-3v species. Well resolved isotopic fine structure (Cl-35 and Cl-37) was observed for NbSCl3, and for NbOCl3 which occurred as an impurity in the NbSCl3 spectra. Quantum mechanical calculations of the structures and vibrational frequencies of the four YNbX3 molecules (Y = O, S; X = Cl, Br) were carried out at several levels of theory, most importantly B3LYP DFT with either the Stuttgart RSC ECP or Hay-Wadt (n + 1) ECP VDZ basis set for Nb and the 6-311 G* basis set for the nonmetal atoms. Theoretical values for the bond lengths are 0.01-0.04 Angstrom longer than the experimental ones of type r(a), in accord with general experience, but the bond angles with theoretical minus experimental differences of only 1.0-1.5degrees are notably accurate. Symmetrized force fields were also calculated. The experimental bond lengths (r(g)/Angstrom) and angles (angle(alpha)/deg) with estimated 2sigma uncertainties from GED are as follows. NbOBr3: r(Nb=O) = 1.694(7), r(Nb-Br) = 2.429(2), angle(O=Nb-Br) = 107.3(5), angle(Br-Nb-Br) = 111.5(5). NbSBr3: r(Nb=S) = 2.134(10), r(Nb-Br) = 2.408(4), angle(S=Nb-Br) = 106.6(7), angle(Br-Nb-Br) = 112.2(6). NbSCl3: Nb=S) = 2.120(10), r(Nb-Cl) = 2.271(6), angle(S=Nb-Cl) = 107.8(12), angle(Cl-Nb-Cl) = 111.1(11).

Rapid, uncatalyzed ring-opening polymerization of individual macrocyclic poly(arylene thioether ketone)s under dynamic heating conditions

Uncatalyzed, ring-opening polymerization of individual macrocyclic poly(arylene thioether ketone)s (1-4) and mixtures (5) under dynamic heating conditions has been demonstrated for the first time. High-molecular-weight, film-forming products were obtained after heating of the macrocycles up to 480 degreesC, with a heating rate of 10-20 degreesC /min. Depending on the macrocyclic structure and heat treatment conditions, the polymers obtained were amorphous or semicrystalline, soluble or slightly crosslinked. NMR analyses of the soluble polymers revealed their linear, highly regular structure. According to NMR, DSC, and TGA studies, the polymers obtained do not contain any residual macrocycles. The polymers with thio-p-arylene moieties in the main chain were thermally stabile. The catalyzed ring opening polymerization of 5 carried out in diphenyl sulfone solution is also reported for comparison. Using quantum mechanical calculations of the ring opening of macrocycles, a reaction mechanism is suggested. Preparation of nanosized poly(thioether ketone) fibrils by a replication method is described.

Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit

The self-assembly of a peptide based on a sequence from the amyloid beta peptide but incorporating the non-natural amino acid beta-2-thienylalanine (2-Thi) has been investigated in aqueous and methanol solutions. The peptide AAKLVFF was used as a design motif, replacing the phenylalanine residues (F) with 2-Thi units to yield (2-Thi)(2-Thi)VLKAA. The 2-Thi residues are expected to confer interesting electronic properties due to charge delocalization and pi-stacking. The peptide is shown to form beta-sheet-rich amyloid fibrils with a twisted morphology, in both water and methanol solutions at sufficiently high concentration. The formation of a self-assembling hydrogel is observed at high concentration. Detailed molecular modeling using molecular dynamics methods was performed using NOE constraints provided by 2D-NMR experiments. The conformational and charge properties of 2-Thi were modeled using quantum mechanical methods, and found to be similar to those previously reported for the beta-3-thienylalanine analogue. The molecular dynamics simulations reveal well-defined folded structures (turn-like) in dilute aqueous solution, driven by self-assembly of the hydrophobic aromatic units, with charged lysine groups exposed to water.

Structure–activity relations (SARs) for gas-phase reactions of NO3, OH and O3 with alkenes: an update

We present updated structure-activity relations (SARs) for the prediction of rate coefficients for gas-phase reactions with alkenes of the major atmospheric oxidants NO3, OH and O-3. Such SARs provide one way of incorporating essential information about reactivity into atmospheric models. Rate coefficients obtained from correlations relating the logarithms of the rate coefficients to the energies of the highest occupied molecular orbitals (HOMOs) of the alkenes were used to refine the SARs. SARs have an advantage for the user over the direct application of the correlations in that knowledge of the structure of the alkene of interest is sufficient to estimate rate coefficients, and no quantum-mechanical calculations need to be performed. A comparison of the values predicted by the SARs with experimental data where they exist allowed us to assess the reliability of our method.

The power of NMR. Part 1: the beginnings

Nuclear mnagnetic resonance (NMR) spectroscopy involves the excitation of nuclei by electromagnetic radiation in the radio-frequency range of the electromagnetic spectrum. For a nucleus to absorb energy from radiowaves in this way, it must hve the quantum mechanical property of spin. A spinning nucleus, such as that of the hydrogen atom, will dopt one f only two possible states when placed in a magnetic field. (In NMR, the hydrogen nucleus is often referred to as a proton, and is given the abbreviation 1H.) Az the strength of the magnetic field is increased, there is a proportional increase in the energy 'gap' between these two states. We can predic the resonant frequency at which any spinning nucleus will absorb energy from radio-frequency radiation as it jumps from the lower energy state to the upper state.

Modeling the tetraphenylalanine-PEG hybrid amphiphile: from DFT calculations on the peptide to molecular dynamics simulations on the conjugate

The conformational properties of the hybrid amphiphile formed by the conjugation of a hydrophobic peptide with four phenylalanine (Phe) residues and hydrophilic poly(ethylene glycol), have been investigated using quantum mechanical calculations and atomistic molecular dynamics simulations. The intrinsic conformational preferences of the peptide were examined using the building-up search procedure combined with B3LYP/ 6-31G(d) geometry optimizations, which led to the identification of 78, 78, and 92 minimum energy structures for the peptides containing one, two, and four Phe residues. These peptides tend to adopt regular organizations involving turn-like motifs that define ribbon or helicallike arrangements. Furthermore, calculations indicate that backbone ... side chain interactions involving the N-H of the amide groups and the pi clouds of the aromatic rings play a crucial role in Phe-containing peptides. On the other hand,MD simulations on the complete amphiphile in aqueous solution showed that the polymer fragment rapidly unfolds maximizing the contacts with the polar solvent, even though the hydrophobic peptide reduce the number of waters of hydration with respect to an individual polymer chain of equivalent molecular weight. In spite of the small effect of the peptide in the hydrodynamic properties of the polymer, we conclude that the two counterparts of the amphiphile tend to organize as independent modules.

On the time-dependent analysis of Gamow decay

Gamow's explanation of the exponential decay law uses complex 'eigenvalues' and exponentially growing 'eigenfunctions'. This raises the question, how Gamow's description fits into the quantum mechanical description of nature, which is based on real eigenvalues and square integrable wavefunctions. Observing that the time evolution of any wavefunction is given by its expansion in generalized eigenfunctions, we shall answer this question in the most straightforward manner, which at the same time is accessible to graduate students and specialists. Moreover, the presentation can well be used in physics lectures to students.