A generalization of the charge equilibration method for nonmetallic materials

Assigning effective atomic charges that properly reproduce the electrostatic fields of molecules is a crucial step in the construction of accurate interatomic potentials. We propose a new approach to calculate these charges, which as previous approaches are, is based on the idea of charge equilibration. However, we only allow charge to flow between covalently bonded neighbors by using the concept of so-called split charges. The semiempirical fit parameters in our approach do not only reflect atomic properties (electronegativity and atomic hardness) but also bond-dependent properties. The new method contains two popular but hitherto disjunct approaches as limiting cases. We apply our methodology to a set of molecules containing the elements silicon, carbon, oxygen, and hydrogen. Effective charges derived from electrostatic potential surfaces can be predicted more than twice as accurately as with previous works, at the expense of one additional fit parameter per bond type controlling the polarizability between two bonded atoms. Additional bond-type parameters can be introduced, but barely improve the results. An increase in accuracy of only 30% over existing techniques is achieved when predicting Mulliken charges. However, this could be improved with additional bond-type parameters.     

Superoxidation of retinoic acid

Atmospheric pressure chemical ionization mass spectroscopy (APCI-MS) was used to examine the light-induced oxidation products of retinoic acid under conditions that favor and preclude its aggregation. We observed that in conditions that favor aggregation, i.e. in aqueous solutions, retinoic acid undergoes superoxidation to yield highly oxidized species. Oxidation is limited, however, in the absence of such communication, i.e. when the polyene is fully solvated. From a comparison of the measured MS with that obtained from chemical oxidation of retinoic acid under conditions that promote radical oxidation and singlet oxygen-mediated oxidation, we conclude that superoxidation is mediated by reactive oxygen species other than singlet oxygen.     

A comparative mechanistic analysis of the stereoselectivity trends observed in the oxidation of chiral oxazolidinone-functionalized enecarbamates by singlet oxygen, ozone, and triazolinedione

The stereoselectivity in the reactions of the E/Z enecarbamates 1, equipped with the oxazolidinone chiral auxiliary, has been examined for singlet oxygen (¹O₂), ozone (O₃), and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) in a variety of solvents as a function of temperature. The oxidative cleavage of the alkenyl functionality by ¹O₂ and O₃ releases the enantiomerically enriched methyldesoxybenzoin (MDB) product. The extent (% ee) as well as the sense (R vs S) of the stereoselectivity in the MDB formation depends on the electronic nature of the oxidant. A high stereoselectivity, substantially dependent on solvent and temperature, is displayed for the reactions with ¹O₂, whereas the ground-state reactants O₃ and PTAD are rather unaffected by solvent and temperature variations. The present comparative analysis clearly substantiates our hypothesis of stereoselective vibrational quenching of the attacking ¹O₂, whereas O₃ and PTAD are only subject to steric impositions. The electronically excited ¹O₂ is sensitive to all three stereochemically relevant structural characteristics embodied in the chiral enecarbamates, namely the R/S configuration at the C₄ position of the oxazolidinone chiral auxiliary, the Z/E geometry of the ‘alkene’ functionality, and R/S configuration at the C_3′ position of the enecarbamate side chain.     

Submicrometer structure of surface-chemical gradients prepared by a two-step immersion method

Lateral force microscopy and microdroplet density measurements have been used to examine the microstructure of surface-chemical gradients of thiols on gold, prepared by a two-step immersion method. A single-component coverage gradient, generated by gradual immersion of a gold surface into a solution of a single thiol, yielded islands of approximately 25 nm in diameter at the end that had only been briefly immersed, whereas an increasingly continuous film was formed along the gradient. After saturation with a second thiol with a different end group, the structure generated during the initial immersion step was found to persist.     

Recurrences in rotational dynamics and experimental measurement of superfluidity in doped helium clusters

We present the first experimental evidence of recurrences in the rotational dynamics of doped helium clusters. Using the dopant molecule as an experimental microscopic probe of superfluidity, we show that in small He(N)-N2O complexes, superfluidity builds up in stages correlated with the filling and completion of a solvation shell.     

Characterization of a single molecule DNA switch in free solution

We have studied a donor-acceptor fluorophore-labeled DNA switch where the acceptor is Alexa-647, a carbocyanine dye, in solution at the single molecule level to elucidate the fluorescence switching mechanism. The acceptor, which is in an initial high fluorescence trans state, undergoes a photoisomerization reaction resulting in two additional states during its sub-millisecond transit across the probe volume. These two states are assigned to a nonfluorescent triplet trans state that strongly quenches the donor emission and a singlet cis state that blocks the fluorescence resonance energy transfer (FRET) pathway and gives rise to donor-only fluorescence. The formation of these states is faster than the transit time, so that all three states are approximately equally populated under our experimental conditions. The acceptor dye can stick to the DNA in all these states, with the rate of unsticking determining the rate of isomerization into the other states. Measurement of the rate of change of the FRET signal therefore provides information about the fluorophore-DNA intramolecular dynamics. These results explain the large zero peak in the proximity ratio, often seen in single molecule FRET experiments, and suggest that photoinduced effects may be important in single molecule FRET experiments using carbocyanine dyes. They also suggest that for fast photoinduced switching the interactions of the acceptor dye with the DNA and other surfaces should be prevented.     

Relaxation dynamics of highly vibrationally excited picoline isomers (E(vib) = 38 300 cm(-1)) with CO2: the role of state density in impulsive collisions

Strong collisions of highly vibrationally excited picoline isomers and CO2 (00(0)0) were investigated using high resolution transient IR absorption probing to investigate the role of donor state density. Vibrationally excited 3-picoline and 4-picoline (3-methylpyridine and 4 methylpyridine) with E(vib) = 38300 cm(-1) were prepared by 266 nm excitation followed by rapid internal conversion. Transient IR probe measurements of the nascent rotational and translational energy gain in CO2 (00(0)0) show that large DeltaE collisions for 3- and 4-picoline are similar to those for excited 2-picoline. The probability distributions for the large DeltaE energy transfer of the three isomers have similar dependence on DeltaE. The results are compared with other earlier results demonstrating that the shape of the large DeltaE probability distribution correlates with the DeltaE dependence of the donor vibrational state density. The results are discussed in terms of the GRETCHEN model for collisional relaxation.     

Carboxylic acid to amide hydrogen bonding. 10-Oxo-semirubins

Using their amide (and pyrrole) groups, dipyrrinones act as hydrogen bonding receptors for carboxylic acids, as found in a large number of 10-oxo-semirubins (1-6). The latter can be synthesized readily by Friedel-Crafts coupling of 9-H dipyrrinones with half-ester acid chlorides or diacid dichlorides of α,ω-dicarboxylic acids, ranging from C₂ to C₁₀. With ω-oxo-alkanoic acid chains of C₅ or ≥C₅, intramolecular hydrogen bonding is observed. With acid chains <C₅ hydrogen bonding is not observed. Uncharacteristically (for dipyrrinones), 10-oxo-dipyrrinone acids (1-6) and their corresponding esters (1e-6e) remain monomeric in hydrogen bond promoting solvents.     

Structure determination of protein-ligand complexes by transferred paramagnetic shifts

Rational drug design depends on the knowledge of the three-dimensional (3D) structure of complexes between proteins and lead compounds of low molecular weight. A novel nuclear magnetic resonance (NMR) spectroscopy strategy based on the paramagnetic effects from lanthanide ions allows the rapid determination of the 3D structure of a small ligand molecule bound to its protein target in solution and, simultaneously, its location and orientation with respect to the protein. The method relies on the presence of a lanthanide ion in the protein target and on fast exchange between bound and free ligand. The binding affinity of the ligand and the paramagnetic effects experienced in the bound state are derived from concentration-dependent (1)H and (13)C spectra of the ligand at natural isotopic abundance. Combined with prior knowledge of the crystal or solution structure of the protein and of the magnetic susceptibility tensor of the lanthanide ion, the paramagnetic data define the location and orientation of the bound ligand molecule with respect to the protein from simple 1D NMR spectra. The method was verified with the ternary 30 kDa complex between the lanthanide-labeled N-terminal domain of the epsilon exonuclease subunit from the Escherichia coli DNA polymerase III, the subunit theta, and thymidine. The binding mode of thymidine was found to be very similar to that of thymidine monophosphate present in the crystal structure.     

Software news and updates. Carma: a molecular dynamics analysis program

A computer program has been developed to aid the analysis of molecular dynamics trajectories. The program is tuned for macromolecular large-scale problems and supports features such as removal of global translations-rotations of the solute, calculation of average distance maps and their corresponding standard deviations, calculation of the variance-covariance and cross-correlation matrices, and principal component analysis of trajectories with the added ability to create artificial trajectories based on selected eigenvectors. Limited graphics (trajectory viewing) capabilities are also available.